Sustainable aggregates production : green applications for aggregate by-products.

DOT National Transportation Integrated Search

2015-06-01

Increased emphasis in the construction industry on sustainability and recycling requires production of : aggregate gradations with lower dust (cleaner aggregates) and smaller maximum sizeshence, increased : amount of quarry by-products (QBs). QBs ...

Functional exploration of extracellular polymeric substances (EPS) in the bioleaching of obsolete electric vehicle LiNixCoyMn1-x-yO2 Li-ion batteries.

PubMed

Wang, Jia; Tian, Bingyang; Bao, Yihui; Qian, Can; Yang, Yiran; Niu, Tianqi; Xin, Baoping

2018-07-15

As a fairly new concept, the recovery of valuable metals from urban mining by using bioleaching has become a hotspot. However, the function of extracellular polymeric substances (EPS) in the bioleaching of urban mining gains little attention. The current study used spent EV LIBs to represent urban mining products and systematically explored the function and role of EPS in the attachment of cells to the cathodes, formation of aggregates (cell-EPS-cathode), variation in the electrical and surface properties of the aggregates, concentration of both Fe 2+ and Fe 3+ surrounding the aggregates, electron transfer inside the aggregates and metals released from the aggregates. The results indicated that a strong adhesion of cells to the cathodes occurs mediated by EPS via both hydrophobic force as a main role and electrostatic force as a minor role. Second, the EPS not only adsorb Fe 3+ but also more strongly adsorb Fe 2+ to concentrate the Fe 2+ /Fe 3+ cycle inside the aggregates, witnessing stronger reductive attack on the high valence state of metals as a contact reductive mechanism. Third, the retention or addition of EPS elevated the electronic potential and reduced the electronic resistance to lift the corrosion electric current, thereby boosting the electron transfer and metal dissolution. Copyright © 2018 Elsevier B.V. All rights reserved.

Method for Producing Non-Neoplastic, Three Dimensional, Mammalian Tissue and Cell Aggregates Under Microgravity Culture Conditions and the Products Produced Therefrom

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor); Prewett, Tracey L. (Inventor)

1996-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural, and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Tangeretin-loaded protein nanoparticles fabricated from zein/β-lactoglobulin: preparation, characterization, and functional performance.

PubMed

Chen, Jingjing; Zheng, Jinkai; McClements, David Julian; Xiao, Hang

2014-09-01

The aim of this study was to design a colloidal delivery system to encapsulate poor water-soluble bioactive flavonoid tangeretin so that it could be utilized in various food products as functional ingredient. Tangeretin-loaded protein nanoparticles were produced by mixing an organic phase containing zein and tangeretin with an aqueous phase containing β-lactoglobulin and then converted into powder by freeze-drying. This powder formed a colloidal suspension when dispersed in water that is relatively stable to particle aggregation and sedimentation. The influence of temperature, ionic strength, and pH on the stability of the protein nanoparticles was tested. Extensive particle aggregation occurred at high ionic strength (>100mM) and intermediate pH (4.5-5.5) due to reduced electrostatic repulsion. Extensive aggregation also occurred at temperatures exceeding 60 °C, which was presumably due to increased hydrophobic attraction. Overall, this study shows that protein-based nanoparticles can be used to encapsulate bioactive tangeretin so that it can be readily dispersed in compatible food products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Complement component 5 promotes lethal thrombosis

PubMed Central

Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

2017-01-01

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

Protein aggregates as depots for the release of biologically active compounds.

PubMed

Artemova, Natalya V; Kasakov, Alexei S; Bumagina, Zoya M; Lyutova, Elena M; Gurvits, Bella Ya

2008-12-12

Protein misfolding and aggregation is one of the most serious problems in cell biology, molecular medicine, and biotechnology. Misfolded proteins interact with each other or with other proteins in non-productive or damaging ways. However, a new paradigm arises that protein aggregation may be exploited by nature to perform specific functions in different biological contexts. From this consideration, acceleration of stress-induced protein aggregation triggered by any factor resulting in the formation of soluble aggregates may have paradoxical positive consequences. Here, we suggest that amorphous aggregates can act as a source for the release of biologically active proteins after removal of stress conditions. To address this concept, we investigated the kinetics of thermal aggregation in vitro of yeast alcohol dehydrogenase (ADH) as a model substrate in the presence of two amphiphilic peptides: Arg-Phe or Ala-Phe-Lys. Using dynamic light scattering (DLS) and turbidimetry, we have demonstrated that under mild stress conditions the concentration-dependent acceleration of ADH aggregation by these peptides results in formation of large but soluble complexes of proteins prone to refolding.

Integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by CHO cells.

PubMed

Johari, Yusuf B; Estes, Scott D; Alves, Christina S; Sinacore, Marty S; James, David C

2015-12-01

Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized process, showing that protein-specific cell/process engineering can provide a solution that exceeds the limits of genetic/functional diversity within heterogeneous host cell populations. . © 2015 Wiley Periodicals, Inc.

Application of Glass Fiber Waste Polypropylene Aggregate in Lightweight Concrete – thermal properties

NASA Astrophysics Data System (ADS)

Citek, D.; Rehacek, S.; Pavlik, Z.; Kolisko, J.; Dobias, D.; Pavlikova, M.

2018-03-01

Actual paper focus on thermal properties of a sustainable lightweight concrete incorporating high volume of waste polypropylene aggregate as partial substitution of natural aggregate. In presented experiments a glass fiber reinforced polypropylene (GFPP) which is a by-product of PP tubes production, partially substituted fine natural silica aggregate in 10, 20, 30, 40 and 50 mass %. Results were compared with a reference concrete mix without plastic waste in order to quantify the effect of GFPP use on concrete properties. Main material physical parameters were studied (bulk density, matrix density without air content, and particle size distribution). Especially a thermal transport and storage properties of GFPP were examined in dependence on compaction time. For the developed lightweight concrete, thermal properties were accessed using transient impulse technique, where the measurement was done in dependence on moisture content (from the fully water saturated state to dry state). It was found that the tested lightweight concrete should be prospective construction material possessing improved thermal insulation function and the reuse of waste plastics in concrete composition was beneficial both from the environmental and financial point of view.

Cationic Conjugated Polymers-Induced Quorum Sensing of Bacteria Cells.

PubMed

Zhang, Pengbo; Lu, Huan; Chen, Hui; Zhang, Jiangyan; Liu, Libing; Lv, Fengting; Wang, Shu

2016-03-15

Bacteria quorum sensing (QS) has attracted significant interest for understanding cell-cell communication and regulating biological functions. In this work, we demonstrate that water-soluble cationic conjugated polymers (PFP-G2) can interact with bacteria to form aggregates through electrostatic interactions. With bacteria coated in the aggregate, PFP-G2 can induce the bacteria QS system and prolong the time duration of QS signal molecules (autoinducer-2 (AI-2)) production. The prolonged AI-2 can bind with specific protein and continuously regulate downstream gene expression. Consequently, the bacteria show a higher survival rate against antibiotics, resulting in decreased antimicrobial susceptibility. Also, AI-2 induced by PFP-G2 can stimulate 55.54 ± 12.03% more biofilm in E. coli. This method can be used to understand cell-cell communication and regulate biological functions, such as the production of signaling molecules, antibiotics, other microbial metabolites, and even virulence.

Thermal properties of light-weight concrete with waste polypropylene aggregate

NASA Astrophysics Data System (ADS)

Záleská, Martina; Pokorný, Jaroslav; Pavlíková, Milena; Pavlík, Zbyšek

2017-07-01

Thermal properties of a sustainable light-weight concrete incorporating high volume of waste polypropylene as partial substitution of natural aggregate were studied in the paper. Glass fiber reinforced polypropylene (GFPP), a by-product of PP tubes production, partially substituted fine natural silica aggregate in 10, 20, 30, 40, and 50 mass%. In order to quantify the effect of GFPP use on concrete properties, a reference concrete mix without plastic waste was studied as well. For the applied GFPP, bulk density, matrix density, and particle size distribution were measured. Specific attention was paid to thermal transport and storage properties of GFPP that were examined in dependence on compaction time. For the developed light-weight concrete, thermal properties were accessed using transient impulse technique, whereas the measurement was done in dependence on moisture content, from the dry state to fully water saturated state. Additionally, the investigated thermal properties were plotted as function of porosity. The tested light-weight concrete was found to be prospective construction material possessing improved thermal insulation function. Moreover, the reuse of waste plastics in concrete composition was beneficial both from the environmental and financial point of view considering plastics low biodegradability and safe disposal.

Prediction of the aggregation propensity of proteins from the primary sequence: aggregation properties of proteomes.

PubMed

Castillo, Virginia; Graña-Montes, Ricardo; Sabate, Raimon; Ventura, Salvador

2011-06-01

In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellulose modulates biofilm formation by counteracting curli-mediated colonization of solid surfaces in Escherichia coli.

PubMed

Gualdi, Luciana; Tagliabue, Letizia; Bertagnoli, Stefano; Ieranò, Teresa; De Castro, Cristina; Landini, Paolo

2008-07-01

In enterobacteria, the CsgD protein activates production of two extracellular structures: thin aggregative fimbriae (curli) and cellulose. While curli fibres promote biofilm formation and cell aggregation, the evidence for a direct role of cellulose as an additional determinant for biofilm formation is not as straightforward. The MG1655 laboratory strain of Escherichia coli only produces limited amounts of curli and cellulose; however, ectopic csgD expression results in strong stimulation of curli and cellulose production. We show that, in a csgD-overexpressing derivative of MG1655, cellulose production negatively affects curli-mediated surface adhesion and cell aggregation, thus acting as a negative determinant for biofilm formation. Consistent with this observation, deletion of the bcsA gene, necessary for cellulose production, resulted in a significant increase in curli-dependent adhesion. We found that cellulose production increased tolerance to desiccation, suggesting that the function of cellulose might be related to resistance to environmental stresses rather than to biofilm formation. Production of the curli/cellulose network in enterobacteria typically takes place at low growth temperature (<32 degrees C), but not at 37 degrees C. We show that CsgD overexpression can overcome temperature-dependent control of the curli-encoding csgBA operon, but not of the cellulose-related adrA gene, suggesting very tight temperature control of cellulose production in E. coli MG1655.

Jack bean (Canavalia ensiformis) urease induces eicosanoid-modulated hemocyte aggregation in the Chagas' disease vector Rhodnius prolixus.

PubMed

Defferrari, M S; da Silva, R; Orchard, I; Carlini, C R

2014-05-01

Ureases are multifunctional proteins that display biological activities independently of their enzymatic function, such as induction of exocytosis and insecticidal effects. Rhodnius prolixus, a major vector of Chagas' disease, is a model for studies on the entomotoxicity of jack bean urease (JBU). We have previously shown that JBU induces the production of eicosanoids in isolated tissues of R. prolixus. In insects, the immune response comprises cellular and humoral reactions, and is centrally modulated by eicosanoids. Cyclooxygenase products signal immunity in insects, mainly cellular reactions, such as hemocyte aggregation. In searching for a link between JBU's toxic effects and immune reactions in insects, we have studied the effects of this toxin on R. prolixus hemocytes. JBU triggers aggregation of hemocytes after injection into the hemocoel and when applied to isolated cells. On in vitro assays, the eicosanoid synthesis inhibitors dexamethasone (phospholipase A2 indirect inhibitor) and indomethacin (cyclooxygenase inhibitor) counteracted JBU's effect, indicating that eicosanoids, more specifically cyclooxygenase products, are likely to mediate the aggregation response. Contrarily, the inhibitors esculetin and baicalein were inactive, suggesting that lipoxygenase products are not involved in JBU's effect. Extracellular calcium was also necessary for JBU's effect, in agreement to other cell models responsive to ureases. A progressive darkening of the medium of JBU-treated hemocytes was observed, suggestive of a humoral response. JBU was immunolocalized in the cultured cells upon treatment along with cytoskeleton damage. The highest concentration of JBU tested on cultured cells also led to nuclei aggregation of adherent hemocytes. This is the first time urease has been shown to affect insect hemocytes, contributing to our understanding of the entomotoxic mechanisms of action of this protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

Discrimination among spawning aggregations of lake herring from Lake Superior using whole-body morphometric characters

USGS Publications Warehouse

Hoff, Michael H.

2004-01-01

The lake herring (Coregonus artedi) was one of the most commercially and ecologically valuable Lake Superior fishes, but declined in the second half of the 20th century as the result of overharvest of putatively discrete stocks. No tools were previously available that described lake herring stock structure and accurately classified lake herring to their spawning stocks. The accuracy of discriminating among spawning aggregations was evaluated using whole-body morphometrics based on a truss network. Lake herring were collected from 11 spawning aggregations in Lake Superior and two inland Wisconsin lakes to evaluate morphometrics as a stock discrimination tool. Discriminant function analysis correctly classified 53% of all fish from all spawning aggregations, and fish from all but one aggregation were classified at greater rates than were possible by chance. Discriminant analysis also correctly classified 66% of fish to nearest neighbor groups, which were groups that accounted for the possibility of mixing among the aggregations. Stepwise discriminant analysis showed that posterior body length and depth measurements were among the best discriminators of spawning aggregations. These findings support other evidence that discrete stocks of lake herring exist in Lake Superior, and fishery managers should consider all but one of the spawning aggregations as discrete stocks. Abundance, annual harvest, total annual mortality rate, and exploitation data should be collected from each stock, and surplus production of each stock should be estimated. Prudent management of stock surplus production and exploitation rates will aid in restoration of stocks and will prevent a repeat of the stock collapses that occurred in the middle of the 20th century, when the species was nearly extirpated from the lake.

Measuring Aggregation of Events about a Mass Using Spatial Point Pattern Methods

PubMed Central

Smith, Michael O.; Ball, Jackson; Holloway, Benjamin B.; Erdelyi, Ferenc; Szabo, Gabor; Stone, Emily; Graham, Jonathan; Lawrence, J. Josh

2017-01-01

We present a methodology that detects event aggregation about a mass surface using 3-dimensional study regions with a point pattern and a mass present. The Aggregation about a Mass function determines aggregation, randomness, or repulsion of events with respect to the mass surface. Our method closely resembles Ripley’s K function but is modified to discern the pattern about the mass surface. We briefly state the definition and derivation of Ripley’s K function and explain how the Aggregation about a Mass function is different. We develop the novel function according to the definition: the Aggregation about a Mass function times the intensity is the expected number of events within a distance h of a mass. Special consideration of edge effects is taken in order to make the function invariant to the location of the mass within the study region. Significance of aggregation or repulsion is determined using simulation envelopes. A simulation study is performed to inform researchers how the Aggregation about a Mass function performs under different types of aggregation. Finally, we apply the Aggregation about a Mass function to neuroscience as a novel analysis tool by examining the spatial pattern of neurotransmitter release sites as events about a neuron. PMID:29046865

Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders.

PubMed

Caughey, Byron; Lansbury, Peter T

2003-01-01

Many neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates.

Nonenzymatic Browning and Protein Aggregation in Royal Jelly during Room-Temperature Storage.

PubMed

Qiao, Jiangtao; Wang, Xueyu; Liu, Liqiang; Zhang, Hongcheng

2018-02-28

Royal jelly possesses numerous functional properties. Improper storage usually causes bioactivity loss, especially queen differentiation activity. To determine changes in royal jelly, we investigated nonenzymatic browning and protein changes in royal jelly during room-temperature storage from 1 to 6 months. Our results indicate that royal jelly experiences nonenzymatic browning and protein aggregation. The products of nonenzymatic browning dramatically increased, especially N ε -carboxymethyl lysine (CML) with growth of approximately 7-fold. We speculate that CML may be recognized as a freshness marker for royal jelly. Our results also demonstrate that the major royal jelly protein 1 (MRJP1) monomer gradually aggregated with MRJP1 oligomers into new oligomers of about 440 and 700 kDa. This suggests that the reduction of MRJP1 monomer may be attributable to aggregation. We provide the novel explanation that the differentiation loss of royal jelly may be due to the aggregation of MRJP1 limiting the honeybees' ability to digest and absorb royal jelly.

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.

PubMed

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

2015-05-20

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

Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

PubMed Central

Frautschy, Sally

2014-01-01

The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell. PMID:25386560

Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates

PubMed Central

Tank, Elizabeth M. H.; True, Heather L.

2009-01-01

Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration. PMID:19214209

Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

PubMed

Hom, Sarah; Chen, Li; Wang, Tony; Ghebrehiwet, Berhane; Yin, Wei; Rubenstein, David A

2016-11-01

Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

Environmental aspects and renewable energy sources in the production of construction aggregate

NASA Astrophysics Data System (ADS)

Skrzypczak, Izabela; Kokoszka, Wanda; Buda-Ożóg, Lidia; Kogut, Janusz; Słowik, Marta

2017-11-01

The main activity of open pit mining of aggregates are aggregates' exploitation of natural mineral deposits and its modification in order to obtain high-quality aggregates. The development of aggregate production is conditioned by a number of factors. The most important are: documented material resources, mining and manufacturing capabilities, the need of environmental protection (environmental aspects), the subordination of the plan of spatial development, formal and legal issues, as well as economic and financial aspects. While identifying and assessing the environmental impacts of manufacturing aggregates one may distinguish those environmental aspects that have or may have the greatest magnitude of the impact on the environment as a result of industrial activities. Manufacturers producing aggregates located in the areas covered by the special environmental protection require extra diligence in the conduct of mining activities for preservation of natural resources. The article discusses some main environmental aspects of the production of construction aggregates on the example of one of the largest producers of this material in Subcarpathian province of Poland. Environmental protection in production of aggregates may refer to four aspects: the use of natural resources, having excluded land from agriculture and forestry, land reclamation after exploitation, and use of energy from renewable energy sources. The economic and environmental impact of production volume of aggregates is evaluated by the index information capacity method and the method of graphs.

Reconciling opposing soil processes in row-crop agroecosystems via soil functional zone management

USDA-ARS?s Scientific Manuscript database

Sustaining soil productivity in agroecosystems presents a fundamental ecological challenge: nutrient provisioning depends upon aggregate turnover and microbial decomposition of organic matter (SOM); yet to prevent soil depletion these processes must be balanced by those that restore nutrients and SO...

Urban scaling and the production function for cities.

PubMed

Lobo, José; Bettencourt, Luís M A; Strumsky, Deborah; West, Geoffrey B

2013-01-01

The factors that account for the differences in the economic productivity of urban areas have remained difficult to measure and identify unambiguously. Here we show that a microscopic derivation of urban scaling relations for economic quantities vs. population, obtained from the consideration of social and infrastructural properties common to all cities, implies an effective model of economic output in the form of a Cobb-Douglas type production function. As a result we derive a new expression for the Total Factor Productivity (TFP) of urban areas, which is the standard measure of economic productivity per unit of aggregate production factors (labor and capital). Using these results we empirically demonstrate that there is a systematic dependence of urban productivity on city population size, resulting from the mismatch between the size dependence of wages and labor, so that in contemporary US cities productivity increases by about 11% with each doubling of their population. Moreover, deviations from the average scale dependence of economic output, capturing the effect of local factors, including history and other local contingencies, also manifest surprising regularities. Although, productivity is maximized by the combination of high wages and low labor input, high productivity cities show invariably high wages and high levels of employment relative to their size expectation. Conversely, low productivity cities show both low wages and employment. These results shed new light on the microscopic processes that underlie urban economic productivity, explain the emergence of effective aggregate urban economic output models in terms of labor and capital inputs and may inform the development of economic theory related to growth.

Urban Scaling and the Production Function for Cities

PubMed Central

Lobo, José; Bettencourt, Luís M. A.; Strumsky, Deborah; West, Geoffrey B.

2013-01-01

The factors that account for the differences in the economic productivity of urban areas have remained difficult to measure and identify unambiguously. Here we show that a microscopic derivation of urban scaling relations for economic quantities vs. population, obtained from the consideration of social and infrastructural properties common to all cities, implies an effective model of economic output in the form of a Cobb-Douglas type production function. As a result we derive a new expression for the Total Factor Productivity (TFP) of urban areas, which is the standard measure of economic productivity per unit of aggregate production factors (labor and capital). Using these results we empirically demonstrate that there is a systematic dependence of urban productivity on city population size, resulting from the mismatch between the size dependence of wages and labor, so that in contemporary US cities productivity increases by about 11% with each doubling of their population. Moreover, deviations from the average scale dependence of economic output, capturing the effect of local factors, including history and other local contingencies, also manifest surprising regularities. Although, productivity is maximized by the combination of high wages and low labor input, high productivity cities show invariably high wages and high levels of employment relative to their size expectation. Conversely, low productivity cities show both low wages and employment. These results shed new light on the microscopic processes that underlie urban economic productivity, explain the emergence of effective aggregate urban economic output models in terms of labor and capital inputs and may inform the development of economic theory related to growth. PMID:23544042

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

Pollesch, N.; Dale, V. H.

In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study ofmore » aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.« less

Applications of aggregation theory to sustainability assessment

DOE PAGES

Pollesch, N.; Dale, V. H.

2015-04-01

In order to aid in transition towards operations that promote sustainability goals, researchers and stakeholders use sustainability assessments. Although assessments take various forms, many utilize diverse sets of indicators that can number anywhere from two to over 2000. Indices, composite indicators, or aggregate values are used to simplify high dimensional and complex data sets and to clarify assessment results. Although the choice of aggregation function is a key component in the development of the assessment, there are few examples to be found in literature to guide appropriate aggregation function selection. This paper develops a connection between the mathematical study ofmore » aggregation functions and sustainability assessment in order to aid in providing criteria for aggregation function selection. Relevant mathematical properties of aggregation functions are presented and interpreted. Lastly, we provide cases of these properties and their relation to previous sustainability assessment research. Examples show that mathematical aggregation properties can be used to address the topics of compensatory behavior and weak versus strong sustainability, aggregation of data under varying units of measurements, multiple site multiple indicator aggregation, and the determination of error bounds in aggregate output for normalized and non-normalized indicator measures.« less

Polypeptide Grafted Hyaluronan: Synthesis and Characterization

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

Wang, Xiaojun; Messman, Jamie M; Mays, Jimmy

2010-01-01

Poly(L-leucine) grafted hyaluronan (HA-g-PLeu) has been synthesized via a Michael addition reaction between primary amine terminated poly(L-leucine) and acrylate-functionalized HA (TBAHA-acrylate). The precursor hyaluronan was first functionalized with acrylate groups by reaction with acryloyl chloride in the presence of triethylamine in N,N-dimethylformamide. 1H NMR analysis of the resulting product indicated that an increase in the concentration of acryloylchoride with respect to hydroxyl groups on HA has only a moderate effect on functionalization efficiency, f. A precise control of stoichiometry was not achieved, which could be attributed to partial solubility of intermolecular aggregates and the hygroscopic nature of HA. Michael additionmore » at high [PLeu- NH2]/[acrylate]TBAHA ratios gave a molar grafting ratio of only 0.20 with respect to the repeat unit of HA, indicating grafting limitation due to insolubility of the grafted HA-g-PLeu. Soluble HA-g-PLeu graft copolymers were obtained for low grafting ratios (<0.039) with <8.6% by mass of PLeu and were characterized thoroughly using light scattering, 1H NMR, FT-IR, and AFM techniques. Light scattering experiments showed a strong hydrophobic interaction between PLeu chains, resulting in aggregates with segregated nongrafted HA segments. This yields local networks of aggregates, as demonstrated by atomic force microscopy. Circular dichroism spectroscopy showed a -sheet conformation for aggregates of poly(L-leucine).« less

Improving reliability of aggregation, numerical simulation and analysis of complex systems by empirical data

NASA Astrophysics Data System (ADS)

Dobronets, Boris S.; Popova, Olga A.

2018-05-01

The paper considers a new approach of regression modeling that uses aggregated data presented in the form of density functions. Approaches to Improving the reliability of aggregation of empirical data are considered: improving accuracy and estimating errors. We discuss the procedures of data aggregation as a preprocessing stage for subsequent to regression modeling. An important feature of study is demonstration of the way how represent the aggregated data. It is proposed to use piecewise polynomial models, including spline aggregate functions. We show that the proposed approach to data aggregation can be interpreted as the frequency distribution. To study its properties density function concept is used. Various types of mathematical models of data aggregation are discussed. For the construction of regression models, it is proposed to use data representation procedures based on piecewise polynomial models. New approaches to modeling functional dependencies based on spline aggregations are proposed.

Ring aggregation pattern of metro passenger trips: A study using smart card data

NASA Astrophysics Data System (ADS)

Wang, Ziyang; Hu, Yuxin; Zhu, Peng; Qin, Yong; Jia, Limin

2018-02-01

With the widespread implementation of smart cards and with more travel details being recorded, travel patterns can be studied more precisely and deeply. Although considerable attention has been paid to travel patterns, the relationship between travel patterns and the functional structure of a city is yet to be well understood. In this research, we study this relationship by analysing metro passenger trip data (in Beijing and Shenzhen in China and London in the United Kingdom), and we present two unprecedented findings. First, through averaging, a linear relationship is found to exist between individual travel distance and the distance between the origin and the city centre. The underlying mechanism is a travel pattern we call "ring aggregation", i.e., the daily movement of city passengers is aggregated into a ring (with approximately equal distances to the city centre). Then, for commuting trips, the daily travel pattern can be regarded as switching between the outer residential ring and the inner work ring. Second, this linear relationship and the ring aggregation pattern seem to be exclusive characteristics of metro systems (and may also fit other moderate- and long-distance transportation modes) but do not apply to short-distance transportation modes, such as bicycles and taxis. This finding implies that the ring aggregation pattern is a product of the relationship between travel patterns and the city functional structure at a large scope.

Biological framework for soil aggregation: Implications for ecological functions.

NASA Astrophysics Data System (ADS)

Ghezzehei, Teamrat; Or, Dani

2016-04-01

Soil aggregation is heuristically understood as agglomeration of primary particles bound together by biotic and abiotic cementing agents. The organization of aggregates is believed to be hierarchical in nature; whereby primary particles bond together to form secondary particles and subsequently merge to form larger aggregates. Soil aggregates are not permanent structures, they continuously change in response to internal and external forces and other drivers, including moisture, capillary pressure, temperature, biological activity, and human disturbances. Soil aggregation processes and the resulting functionality span multiple spatial and temporal scales. The intertwined biological and physical nature of soil aggregation, and the time scales involved precluded a universally applicable and quantifiable framework for characterizing the nature and function of soil aggregation. We introduce a biophysical framework of soil aggregation that considers the various modes and factors of the genesis, maturation and degradation of soil aggregates including wetting/drying cycles, soil mechanical processes, biological activity and the nature of primary soil particles. The framework attempts to disentangle mechanical (compaction and soil fragmentation) from in-situ biophysical aggregation and provides a consistent description of aggregate size, hierarchical organization, and life time. It also enables quantitative description of biotic and abiotic functions of soil aggregates including diffusion and storage of mass and energy as well as role of aggregates as hot spots of nutrient accumulation, biodiversity, and biogeochemical cycles.

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

PubMed

Peluso, Ilaria; Palmery, Maura; Serafini, Mauro

2015-07-01

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

Cellular Strategies for Regulating Functional and Nonfunctional Protein Aggregation

PubMed Central

Gsponer, Jörg; Babu, M. Madan

2012-01-01

Summary Growing evidence suggests that aggregation-prone proteins are both harmful and functional for a cell. How do cellular systems balance the detrimental and beneficial effect of protein aggregation? We reveal that aggregation-prone proteins are subject to differential transcriptional, translational, and degradation control compared to nonaggregation-prone proteins, which leads to their decreased synthesis, low abundance, and high turnover. Genetic modulators that enhance the aggregation phenotype are enriched in genes that influence expression homeostasis. Moreover, genes encoding aggregation-prone proteins are more likely to be harmful when overexpressed. The trends are evolutionarily conserved and suggest a strategy whereby cellular mechanisms specifically modulate the availability of aggregation-prone proteins to (1) keep concentrations below the critical ones required for aggregation and (2) shift the equilibrium between the monomeric and oligomeric/aggregate form, as explained by Le Chatelier’s principle. This strategy may prevent formation of undesirable aggregates and keep functional assemblies/aggregates under control. PMID:23168257

Efficiency and Productivity Analysis of Multidivisional Firms

NASA Astrophysics Data System (ADS)

Gong, Binlei

Multidivisional firms are those who have footprints in multiple segments and hence using multiple technologies to convert inputs to outputs, which makes it difficult to estimate the resource allocations, aggregated production functions, and technical efficiencies of this type of companies. This dissertation aims to explore and reveal such unobserved information by several parametric and semiparametric stochastic frontier analyses and some other structural models. In the empirical study, this dissertation analyzes the productivity and efficiency for firms in the global oilfield market.

Protein A chromatography increases monoclonal antibody aggregation rate during subsequent low pH virus inactivation hold

PubMed Central

Mazzer, Alice R.; Perraud, Xavier; Halley, Jennifer; O’Hara, John; Bracewell, Daniel G.

2015-01-01

Protein A chromatography is a near-ubiquitous method of mAb capture in bioprocesses. The use of low pH buffer for elution from protein A is known to contribute to product aggregation. Yet, a more limited set of evidence suggests that low pH may not be the sole cause of aggregation in protein A chromatography, rather, other facets of the process may contribute significantly. This paper presents a well-defined method for investigating this problem. An IgG4 was incubated in elution buffer after protein A chromatography (typical of the viral inactivation hold) and the quantity of monomer in neutralised samples was determined by size exclusion chromatography; elution buffers of different pH values predetermined to induce aggregation of the IgG4 were used. Rate constants for monomer decay over time were determined by fitting exponential decay functions to the data. Similar experiments were implemented in the absence of a chromatography step, i.e. IgG4 aggregation at low pH. Rate constants for aggregation after protein A chromatography were considerably higher than those from low pH exposure alone; a distinct shift in aggregation rates was apparent across the pH range tested. PMID:26346187

Coherent and incoherent ultrasound backscatter from cell aggregates.

PubMed

de Monchy, Romain; Destrempes, François; Saha, Ratan K; Cloutier, Guy; Franceschini, Emilie

2016-09-01

The effective medium theory (EMT) was recently developed to model the ultrasound backscatter from aggregating red blood cells [Franceschini, Metzger, and Cloutier, IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58, 2668-2679 (2011)]. The EMT assumes that aggregates can be treated as homogeneous effective scatterers, which have effective properties determined by the aggregate compactness and the acoustical characteristics of the cells and the surrounding medium. In this study, the EMT is further developed to decompose the differential backscattering cross section of a single cell aggregate into coherent and incoherent components. The coherent component corresponds to the squared norm of the average scattering amplitude from the effective scatterer, and the incoherent component considers the variance of the scattering amplitude (i.e., the mean squared norm of the fluctuation of the scattering amplitude around its mean) within the effective scatterer. A theoretical expression for the incoherent component based on the structure factor is proposed and compared with another formulation based on the Gaussian direct correlation function. This theoretical improvement is assessed using computer simulations of ultrasound backscatter from aggregating cells. The consideration of the incoherent component based on the structure factor allows us to approximate the simulations satisfactorily for a product of the wavenumber times the aggregate radius kr ag around 2.

Commercial Demonstration of the Manufactured Aggregate Processing Technology Utilizing Spray Dryer Ash

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

Milton Wu; Paul Yuran

2006-12-31

Universal Aggregates LLC (UA) was awarded a cost sharing Co-operative Agreement from the Department of Energy (DOE) through the Power Plant Improvement Initiative Program (PPII) to design, construct and operate a lightweight aggregate manufacturing plant at the Birchwood Power Facility in King George, Virginia in October 2001. The Agreement was signed in November 2002. The installation and start-up expenses for the Birchwood Aggregate Facility are $19.5 million. The DOE share is $7.2 million (37%) and the UA share is $12.3 million (63%). The original project team consists of UA, SynAggs, LLC, CONSOL Energy Inc. and P. J. Dick, Inc. Usingmore » 115,000 ton per year of spray dryer ash (SDA), a dry FGD by-product from the power station, UA will produce 167,000 tons of manufactured lightweight aggregate for use in production of concrete masonry units (CMU). Manufacturing aggregate from FGD by-products can provide an economical high-volume use and substantially expand market for FGD by-products. Most of the FGD by-products are currently disposed of in landfills. Construction of the Birchwood Aggregate Facility was completed in March 2004. Operation startup was begun in April 2004. Plant Integration was initiated in December 2004. Integration includes mixing, extrusion, curing, crushing and screening. Lightweight aggregates with proper size gradation and bulk density were produced from the manufacturing aggregate plant and loaded on a stockpile for shipment. The shipped aggregates were used in a commercial block plant for CMU production. However, most of the production was made at low capacity factors and for a relatively short time in 2005. Several areas were identified as important factors to improve plant capacity and availability. Equipment and process control modifications and curing vessel clean up were made to improve plant operation in the first half of 2006. About 3,000 tons of crushed aggregate was produced in August 2006. UA is continuing to work to improve plant availability and throughput capacity and to produce quality lightweight aggregate for use in commercial applications.« less

Use of wastes derived from earthquakes for the production of concrete masonry partition wall blocks

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

Xiao Zhao; Faculty of Architecture, Civil Engineering and Environment Engineering and Mechanics, Sichuan University; Ling, Tung-Chai

2011-08-15

Highlights: > Solved the scientific and technological challenges impeding use of waste rubble derived from earthquake, by providing an alternative solution of recycling the waste in moulded concrete block products. > Significant requirements for optimum integration on the utilization of the waste aggregates in the production of concrete blocks are investigated. > A thorough understanding of the mechanical properties of concrete blocks made with waste derived from earthquake is reported. - Abstract: Utilization of construction and demolition (C and D) wastes as recycled aggregates in the production of concrete and concrete products have attracted much attention in recent years. However,more » the presence of large quantities of crushed clay brick in some the C and D waste streams (e.g. waste derived collapsed masonry buildings after an earthquake) renders the recycled aggregates unsuitable for high grade use. One possibility is to make use of the low grade recycled aggregates for concrete block production. In this paper, we report the results of a comprehensive study to assess the feasibility of using crushed clay brick as coarse and fine aggregates in concrete masonry block production. The effects of the content of crushed coarse and fine clay brick aggregates (CBA) on the mechanical properties of non-structural concrete block were quantified. From the experimental test results, it was observed that incorporating the crushed clay brick aggregates had a significant influence on the properties of blocks. The hardened density and drying shrinkage of the block specimens decreased with an increase in CBA content. The use of CBA increased the water absorption of block specimens. The results suggested that the amount of crushed clay brick to be used in concrete masonry blocks should be controlled at less than 25% (coarse aggregate) and within 50-75% for fine aggregates.« less

A Consensus Method for the Prediction of ‘Aggregation-Prone’ Peptides in Globular Proteins

PubMed Central

Tsolis, Antonios C.; Papandreou, Nikos C.; Iconomidou, Vassiliki A.; Hamodrakas, Stavros J.

2013-01-01

The purpose of this work was to construct a consensus prediction algorithm of ‘aggregation-prone’ peptides in globular proteins, combining existing tools. This allows comparison of the different algorithms and the production of more objective and accurate results. Eleven (11) individual methods are combined and produce AMYLPRED2, a publicly, freely available web tool to academic users (http://biophysics.biol.uoa.gr/AMYLPRED2), for the consensus prediction of amyloidogenic determinants/‘aggregation-prone’ peptides in proteins, from sequence alone. The performance of AMYLPRED2 indicates that it functions better than individual aggregation-prediction algorithms, as perhaps expected. AMYLPRED2 is a useful tool for identifying amyloid-forming regions in proteins that are associated with several conformational diseases, called amyloidoses, such as Altzheimer's, Parkinson's, prion diseases and type II diabetes. It may also be useful for understanding the properties of protein folding and misfolding and for helping to the control of protein aggregation/solubility in biotechnology (recombinant proteins forming bacterial inclusion bodies) and biotherapeutics (monoclonal antibodies and biopharmaceutical proteins). PMID:23326595

Photophysics of Zinc Porphyrin Aggregates in Dilute Water-Ethanol Solutions.

PubMed

Stevens, Amy L; Joshi, Neeraj K; Paige, Matthew F; Steer, Ronald P

2017-12-14

Dimeric and multimeric aggregates of a model metalloporphyrin, zinc tetraphenylporphyrin (ZnTPP), have been produced in a controlled manner by incrementally increasing the water content of dilute aqueous ethanol solutions. Steady state absorption, fluorescence emission, and fluorescence excitation spectra have been measured to identify the aggregates present as a function of solvent composition. The dynamics of the excited states of the aggregates produced initially by excitation in the Soret region have been measured by ultrafast fluorescence upconversion techniques. Only the monomer produces measurable emission from S 2 with a picosecond lifetime; all Soret-excited aggregates, including the dimer, decay radiationlessly on a femtosecond time scale. The S 1 state is the only significant product of the radiationless decay of the S 2 state of the excited monomer, and the aggregates also produce substantial quantum yields of S 1 fluorescence when initially excited in the Soret region. The resulting fluorescent aggregates all decay on a subnanosecond time scale, likely by a mechanism that involves dissociation of the excited monomer from the excitonic multimer. The ZnTPP dimers excited at their ground state geometries in the Soret region exhibit a dynamic behavior that is quite different from those produced following noncoherent triplet-triplet annihilation under the same conditions. The important implications of these observations in determining the aggregation conditions promoting efficient photon upconversion by excitonic annihilation in a variety of media are thoroughly discussed.

Comparative environmental assessment of natural and recycled aggregate concrete.

PubMed

Marinković, S; Radonjanin, V; Malešev, M; Ignjatović, I

2010-11-01

Constant and rapid increase in construction and demolition (C&D) waste generation and consumption of natural aggregate for concrete production became one of the biggest environmental problems in the construction industry. Recycling of C&D waste represents one way to convert a waste product into a resource but the environment benefits through energy consumption, emissions and fallouts reductions are not certain. The main purpose of this study is to determine the potentials of recycled aggregate concrete (concrete made with recycled concrete aggregate) for structural applications and to compare the environmental impact of the production of two types of ready-mixed concrete: natural aggregate concrete (NAC) made entirely with river aggregate and recycled aggregate concrete (RAC) made with natural fine and recycled coarse aggregate. Based on the analysis of up-to-date experimental evidence, including own tests results, it is concluded that utilization of RAC for low-to-middle strength structural concrete and non-aggressive exposure conditions is technically feasible. The Life Cycle Assessment (LCA) is performed for raw material extraction and material production part of the concrete life cycle including transport. Assessment is based on local LCI data and on typical conditions in Serbia. Results of this specific case study show that impacts of aggregate and cement production phases are slightly larger for RAC than for NAC but the total environmental impacts depend on the natural and recycled aggregates transport distances and on transport types. Limit natural aggregate transport distances above which the environmental impacts of RAC can be equal or even lower than the impacts of NAC are calculated for the specific case study. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Probiotic properties of lactic acid bacteria isolated from water-buffalo mozzarella cheese.

PubMed

Jeronymo-Ceneviva, Ana Beatriz; de Paula, Aline Teodoro; Silva, Luana Faria; Todorov, Svetoslav Dimitrov; Franco, Bernadette Dora G Mello; Penna, Ana Lúcia B

2014-12-01

This study evaluated the probiotic properties (stability at different pH values and bile salt concentration, auto-aggregation and co-aggregation, survival in the presence of antibiotics and commercial drugs, study of β-galactosidase production, evaluation of the presence of genes encoding MapA and Mub adhesion proteins and EF-Tu elongation factor, and the presence of genes encoding virulence factor) of four LAB strains (Lactobacillus casei SJRP35, Leuconostoc citreum SJRP44, Lactobacillus delbrueckii subsp. bulgaricus SJRP57 and Leuconostoc mesenteroides subsp. mesenteroides SJRP58) which produced antimicrobial substances (antimicrobial peptides). The strains survived the simulated GIT modeled in MRS broth, whole and skim milk. In addition, auto-aggregation and the cell surface hydrophobicity of all strains were high, and various degrees of co-aggregation were observed with indicator strains. All strains presented low resistance to several antibiotics and survived in the presence of commercial drugs. Only the strain SJRP44 did not produce the β-galactosidase enzyme. Moreover, the strain SJRP57 did not show the presence of any genes encoding virulence factors; however, the strain SJRP35 presented vancomycin resistance and adhesion of collagen genes, the strain SJRP44 harbored the ornithine decarboxylase gene and the strain SJRP58 generated positive results for aggregation substance and histidine decarboxylase genes. In conclusion, the strain SJRP57 was considered the best candidate as probiotic cultures for further in vivo studies and functional food products development.

Cell culture media impact on drug product solution stability.

PubMed

Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

2016-07-08

To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

Cointegration of output, capital, labor, and energy

NASA Astrophysics Data System (ADS)

Stresing, R.; Lindenberger, D.; Kã¼mmel, R.

2008-11-01

Cointegration analysis is applied to the linear combinations of the time series of (the logarithms of) output, capital, labor, and energy for Germany, Japan, and the USA since 1960. The computed cointegration vectors represent the output elasticities of the aggregate energy-dependent Cobb-Douglas function. The output elasticities give the economic weights of the production factors capital, labor, and energy. We find that they are for labor much smaller and for energy much larger than the cost shares of these factors. In standard economic theory output elasticities equal cost shares. Our heterodox findings support results obtained with LINEX production functions.

Diatom-associated bacteria are required for aggregation of Thalassiosira weissflogii

PubMed Central

Gärdes, Astrid; Iversen, Morten H; Grossart, Hans-Peter; Passow, Uta; Ullrich, Matthias S

2011-01-01

Aggregation of algae, mainly diatoms, is an important process in marine systems leading to the settling of particulate organic carbon predominantly in the form of marine snow. Exudation products of phytoplankton form transparent exopolymer particles (TEP), which acts as the glue for particle aggregation. Heterotrophic bacteria interacting with phytoplankton may influence TEP formation and phytoplankton aggregation. This bacterial impact has not been explored in detail. We hypothesized that bacteria attaching to Thalassiosira weissflogii might interact in a yet-to-be determined manner, which could impact TEP formation and aggregate abundance. The role of individual T. weissflogii-attaching and free-living new bacterial isolates for TEP production and diatom aggregation was investigated in vitro. T. weissflogii did not aggregate in axenic culture, and striking differences in aggregation dynamics and TEP abundance were observed when diatom cultures were inoculated with either diatom-attaching or free-living bacteria. The data indicated that free-living bacteria might not influence aggregation whereas bacteria attaching to diatom cells may increase aggregate formation. Interestingly, photosynthetically inactivated T. weissflogii cells did not aggregate regardless of the presence of bacteria. Comparison of aggregate formation, TEP production, aggregate sinking velocity and solid hydrated density revealed remarkable differences. Both, photosynthetically active T. weissflogii and specific diatom-attaching bacteria were required for aggregation. It was concluded that interactions between heterotrophic bacteria and diatoms increased aggregate formation and particle sinking and thus may enhance the efficiency of the biological pump. PMID:20827289

On defense strategies for system of systems using aggregated correlations

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

Rao, Nageswara S.; Imam, Neena; Ma, Chris Y. T.

2017-04-01

We consider a System of Systems (SoS) wherein each system Si, i = 1; 2; ... ;N, is composed of discrete cyber and physical components which can be attacked and reinforced. We characterize the disruptions using aggregate failure correlation functions given by the conditional failure probability of SoS given the failure of an individual system. We formulate the problem of ensuring the survival of SoS as a game between an attacker and a provider, each with a utility function composed of asurvival probability term and a cost term, both expressed in terms of the number of components attacked and reinforced.more » The survival probabilities of systems satisfy simple product-form, first-order differential conditions, which simplify the Nash Equilibrium (NE) conditions. We derive the sensitivity functions that highlight the dependence of SoS survival probability at NE on cost terms, correlation functions, and individual system survival probabilities.We apply these results to a simplified model of distributed cloud computing infrastructure.« less

Lights, Camera, Reaction! The Influence of Interfacial Chemistry on Nanoparticle Photoreactivity

NASA Astrophysics Data System (ADS)

Farner Budarz, Jeffrey Michael

The ability of photocatalytic nanoparticles (NPs) to produce reactive oxygen species (ROS) has inspired research into several new applications and technologies, including water purification, contaminant remediation, and self-cleaning surface coatings. As a result, NPs continue to be incorporated into a wide variety of increasingly complex products. With the increased use of NPs and nano-enabled products and their subsequent disposal, NPs will make their way into the environment. Currently, many unanswered questions remain concerning how changes to the NP surface chemistry that occur in natural waters will impact reactivity. This work seeks to investigate potential influences on photoreactivity - specifically the impact of functionalization, the influence of anions, and interactions with biological objects - so that ROS generation in natural aquatic environments may be better understood. To this aim, titanium dioxide nanoparticles (TiO2) and fullerene nanoparticles (FNPs) were studied in terms of their reactive endpoints: ROS generation measured through the use of fluorescent or spectroscopic probe compounds, virus and bacterial inactivation, and contaminant degradation. Physical characterization of NPs included light scattering, electron microscopy and electrophoretic mobility. These systematic investigations into the effect of functionalization, sorption, and aggregation on NP aggregate structure, size, and reactivity improve our understanding of trends that impact nanoparticle reactivity. Engineered functionalization of FNPs was shown to impact NP aggregation, ROS generation, and viral affinity. Fullerene cage derivatization can lead to a greater affinity for the aqueous phase, smaller mean aggregate size, and a more open aggregate structure, favoring greater rates of ROS production. At the same time however, fullerene derivatization also decreases the 1O2 quantum yield and may either increase or decrease the affinity for a biological surface. These results suggest that the biological impact of fullerenes will be influenced by changes in the type of surface functionalization and extent of cage derivatization, potentially increasing the ROS generation rate and facilitating closer association with biological targets. Investigations into anion sorption onto the surface of TiO2 indicate that reactivity will be strongly influenced by the waters they are introduced into. The type and concentration of anion impacted both aggregate state and reactivity to varying degrees. Specific interactions due to inner sphere ligand exchange with phosphate and carbonate have been shown to stabilize NPs. As a result, waters containing chloride or nitrate may have little impact on inherent reactivity but will reduce NP transport via aggregation, while waters containing even low levels of phosphate and carbonate may decrease "acute" reactivity but stabilize NPs such that their lifetime in the water column is increased. Finally, ROS delivery in a multicomponent system was studied under the paradigm of pesticide degradation. The presence of bacteria or chlorpyrifos in solution significantly decreased bulk ROS measurements, with almost no •OH detected when both were present. However, the presence of bacteria had no observable impact on the rate of chlorpyrifos degradation, nor chlorpyrifos on bacterial inactivation. These results imply that investigating reactivity in simplified systems may significantly over or underestimate photocatalytic efficiency in realistic environments, depending on the surface affinity of a given target. This dissertation demonstrates that the reactivity of a system is largely determined by NP surface chemistry. Altering the NP surface, either intentionally or incidentally, produces significant changes in reactivity and aggregate characteristics. Additionally, the photocatalytic impact of the ROS generated by a NP depends on the characteristics of potential targets as well as on the characteristics of the NP itself. These are complicating factors, and the myriad potential exposure conditions, endpoints, and environmental systems to be considered for even a single NP highlight the need for functional assays that employ environmentally relevant conditions if risk assessments for engineered NPs are to be made in a timely fashion so as not to be outpaced by, or impede, technological advances.

On the international stability of health care expenditure functions: are government and private functions similar?

PubMed

Clemente, Jesús; Marcuello, Carmen; Montañés, Antonio; Pueyo, Fernando

2004-05-01

This paper studies the stability of health care expenditure functions in a sample of OECD countries. We adopt the cointegration approach and the results show that there is a long-term relationship between total health care expenditure (HCE) and gross domestic product (GDP). However, the existence of cointegration is only shown when we admit the presence of some changes in the elasticities of the model. Our results also provide evidence against the existence of a unique relationship between health and GDP for the sample. Thus, we can conclude that the differences in health systems may cause differences in the aggregate functions. Additionally, we examine aggregate health functions for government (GHCE) and private expenditures (PHCE), again finding evidence of different patterns of behaviour. Finally, we open a discussion on the character of health as a necessary or luxury good. In this context, we find differences between the government and the private function. In order to illustrate these findings, we propose a theoretical model as an example of the influence of political decisions on income elasticity. Copyright 2003 Elsevier B.V.

General pharmacology of loracarbef in animals.

PubMed

Shetler, T; Bendele, A; Buening, M; Clemens, J; Colbert, W; Deldar, A; Helton, D; McGrath, J; Shannon, H; Turk, J

1993-01-01

Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease. The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems. Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response. Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies. Concentrations up to 3 x 10(-3) mol/l were used in vitro. Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation. It had no local anesthetic activity. At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response). In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies. These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses.

The shakeout scenario: Meeting the needs for construction aggregates, asphalt, and concrete

USGS Publications Warehouse

Langer, W.H.

2011-01-01

An Mw 7.8 earthquake as described in the ShakeOut Scenario would cause significantdamage to buildings and infrastructure. Over 6 million tons of newly mined aggregate would be used for emergency repairs and for reconstruction in the five years following the event. This aggregate would be applied mostly in the form of concrete for buildings and bridges, asphalt or concrete for pavement, and unbound gravel for applications such as base course that goes under highway pavement and backfilling for foundations and pipelines. There are over 450 aggregate, concrete, and asphalt plants in the affected area, some of which would be heavily damaged. Meeting the increased demand for construction materials would require readily available permitted reserves, functioning production facilities, a supply of cement and asphalt, a source of water, gas, and electricity, and a trained workforce. Prudent advance preparations would facilitate a timely emergency response and reconstruction following such an earthquake. ?? 2011, Earthquake Engineering Research Institute.

Acute effects of 30 minutes of exposure to a smartphone call on in vitro platelet function

PubMed Central

Lippi, Giuseppe; Danese, Elisa; Brocco, Giorgio; Gelati, Matteo; Salvagno, Gian Luca; Montagnana, Martina

2017-01-01

Background Significant concerns are now regularly raised about the safety of excessive mobile phone use. This study was aimed to assess the acute effects of radiofrequency waves emitted by a commercial smartphone on platelet function. Materials and methods Two sequential citrated blood samples were collected from 16 healthy volunteers recruited from laboratory staff. The first sample was placed in a plastic rack, 1 cm distant from a commercial smartphone receiving a 30-min call and emitting 900 MHz radiofrequency waves. The second sample was placed in another plastic rack, isolated from radiofrequency wave sources, for the same period. The platelet count and the mean platelet volume were then assessed in all blood samples, whereas platelet function was evaluated using the platelet function analyser-100 (PFA-100). Results A 30-min exposure of citrated blood to smartphone radiofrequency waves induced significant prolongation of collagen-epinephrine aggregation (median increase, 10%) and a considerable increase of mean platelet volume (median increase, 5%), whereas collagen-adenosine diphosphate aggregation and platelet count remained unchanged. Discussion This study demonstrates that smartphone radiofrequency waves induce significant perturbation of platelet structure and function, thus providing further support to concerns regarding excessive use of mobile phones. Caution should also be taken with regards to blood products containing platelets, which should be kept far away from mobile phones and smartphones throughout the production pipeline and storage period. PMID:27177410

Acute effects of 30 minutes of exposure to a smartphone call on in vitro platelet function.

PubMed

Lippi, Giuseppe; Danese, Elisa; Brocco, Giorgio; Gelati, Matteo; Salvagno, Gian Luca; Montagnana, Martina

2017-05-01

Significant concerns are now regularly raised about the safety of excessive mobile phone use. This study was aimed to assess the acute effects of radiofrequency waves emitted by a commercial smartphone on platelet function. Two sequential citrated blood samples were collected from 16 healthy volunteers recruited from laboratory staff. The first sample was placed in a plastic rack, 1 cm distant from a commercial smartphone receiving a 30-min call and emitting 900 MHz radiofrequency waves. The second sample was placed in another plastic rack, isolated from radiofrequency wave sources, for the same period. The platelet count and the mean platelet volume were then assessed in all blood samples, whereas platelet function was evaluated using the platelet function analyser-100 (PFA-100). A 30-min exposure of citrated blood to smartphone radiofrequency waves induced significant prolongation of collagen-epinephrine aggregation (median increase, 10%) and a considerable increase of mean platelet volume (median increase, 5%), whereas collagen-adenosine diphosphate aggregation and platelet count remained unchanged. This study demonstrates that smartphone radiofrequency waves induce significant perturbation of platelet structure and function, thus providing further support to concerns regarding excessive use of mobile phones. Caution should also be taken with regards to blood products containing platelets, which should be kept far away from mobile phones and smartphones throughout the production pipeline and storage period.

Protein Aggregation and Its Impact on Product Quality

PubMed Central

Roberts, Christopher J.

2014-01-01

Protein pharmaceutical products are typically active as folded monomers that are composed of one or more protein chains, such as the heavy and light chains in monoclonal antibodies that are a mainstay of current drug pipelines. There are numerous possible aggregated states for a given protein, some of which are potentially useful, while most of which are considered deleterious from the perspective of pharmaceutical product quality and performance. This review provides an overview of how and why different aggregated states of proteins occur, how this potentially impacts product quality and performance, fundamental approaches to control aggregate formation, and the practical approaches that are currently used in the pharmaceutical industry. PMID:25173826

The nation’s top 25 construction aggregates producers

USGS Publications Warehouse

Willett, Jason C.

2014-01-01

U.S. production of construction aggregates in 2012 was 2.18 billion short tons valued at $17.6 billion, free on board (f.o.b.) at plant. In 2012, construction aggregates production remained virtually unchanged from the levels of the last two years because of a very slight increase compared with that of 2011 in the production of both construction sand and gravel and crushed stone. The average unit value, which is the f.o.b. at the plant price of a metric ton of material, increased slightly. Construction aggregates production was 36 percent less than and the associated value was 23 percent less than the record highs reported in 2006.

Use of wastes derived from earthquakes for the production of concrete masonry partition wall blocks.

PubMed

Xiao, Zhao; Ling, Tung-Chai; Kou, Shi-Cong; Wang, Qingyuan; Poon, Chi-Sun

2011-08-01

Utilization of construction and demolition (C&D) wastes as recycled aggregates in the production of concrete and concrete products have attracted much attention in recent years. However, the presence of large quantities of crushed clay brick in some the C&D waste streams (e.g. waste derived collapsed masonry buildings after an earthquake) renders the recycled aggregates unsuitable for high grade use. One possibility is to make use of the low grade recycled aggregates for concrete block production. In this paper, we report the results of a comprehensive study to assess the feasibility of using crushed clay brick as coarse and fine aggregates in concrete masonry block production. The effects of the content of crushed coarse and fine clay brick aggregates (CBA) on the mechanical properties of non-structural concrete block were quantified. From the experimental test results, it was observed that incorporating the crushed clay brick aggregates had a significant influence on the properties of blocks. The hardened density and drying shrinkage of the block specimens decreased with an increase in CBA content. The use of CBA increased the water absorption of block specimens. The results suggested that the amount of crushed clay brick to be used in concrete masonry blocks should be controlled at less than 25% (coarse aggregate) and within 50-75% for fine aggregates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Carbon availability structures microbial community composition and function in soil aggregate fractions

NASA Astrophysics Data System (ADS)

Hofmockel, K. S.; Bach, E.; Williams, R.; Howe, A.

2014-12-01

Identifying the microbial metabolic pathways that most strongly influence ecosystem carbon (C) cycling requires a deeper understanding of the availability and accessibility of microbial substrates. A first step towards this goal is characterizing the relationships between microbial community function and soil C chemistry in a field context. For this perspective, soil aggregate fractions can be used as model systems that scale between microbe-substrate interactions and ecosystem C cycling and storage. The present study addresses how physicochemical variation among soil aggregate fractions influences the composition and functional potential of C cycling microbial communities. We report variation across soil aggregates using plot scale biological replicates from biofuel agroecosystems (fertilized, reconstructed, tallgrass prairie). Our results suggest that C and nitrogen (N) chemistry significantly differ among aggregate fractions. This leads to variation in microbial community composition, which was better characterized among aggregates than by using the whole soil. In fact by considering soil aggregation, we were able to characterize almost 2000 more taxa than whole soil alone, resulting in 65% greater community richness. Availability of C and N strongly influenced the composition of microbial communities among soil aggregate fractions. The normalized abundance of microbial functional guilds among aggregate fractions correlated with C and N chemistry, as did functional potential, measured by extracellular enzyme activity. Metagenomic results suggest that soil aggregate fractions select for functionally distinct microbial communities, which may significantly influence decomposition and soil C storage. Our study provides support for the premise that integration of soil aggregate chemistry, especially microaggregates that have greater microbial richness and occur at spatial scales relevant to microbial community functioning, may be necessary to understand the role of microbial communities on terrestrial C and N cycling.

Persistence of forage fish ‘hot spots’ and its association with foraging Steller sea lions (Eumetopias jubatus) in southeast Alaska

NASA Astrophysics Data System (ADS)

Gende, Scott M.; Sigler, Michael F.

2006-02-01

Whereas primary and secondary productivity at oceanic 'hotspots' may be a function of upwelling and temperature fronts, the aggregation of higher-order vertebrates is a function of their ability to search for and locate these areas. Thus, understanding how predators aggregate at these productive foraging areas is germane to the study of oceanic hot spots. We examined the spatial distribution of forage fish in southeast Alaska for three years to better understand Steller sea lion ( Eumetopias jubatus) aggregations and foraging behavior. Energy densities (millions KJ/km 2) of forage fish were orders of magnitude greater during the winter months (November-February), due to the presence of schools of overwintering Pacific herring ( Clupea pallasi). Within the winter months, herring consistently aggregated at a few areas, and these areas persisted throughout the season and among years. Thus, our study area was characterized by seasonally variable, highly abundant but highly patchily distributed forage fish hot spots. More importantly, the persistence of these forage fish hot spots was an important characteristic in determining whether foraging sea lions utilized them. Over 40% of the variation in the distribution of sea lions on our surveys was explained by the persistence of forage fish hot spots. Using a simple spatial model, we demonstrate that when the density of these hot spots is low, effort necessary to locate these spots is minimized when those spots persist through time. In contrast, under similar prey densities but lower persistence, effort increases dramatically. Thus an important characteristic of pelagic hot spots is their persistence, allowing predators to predict their locations and concentrate search efforts accordingly.

Valorization of lignite combustion residues and ferroalumina in the production of aggregates.

PubMed

Anagnostopoulos, I M; Stivanakis, V E; Angelopoulos, G N; Papamantellos, D C

2010-02-15

The present research study investigates the synergy of industrial solid by-products from lignite combustion (fly ash and bottom ash) and aluminum production (ferroalumina) in the production of lightweight aggregates (LWA). The process consists of two stages, pelletization and sintering. Bottom ash (BA) is used as the principal raw material in mixtures while ferroalumina (FAL) is added in lower percentages (5-30 wt%). BA carbon content is used as the fuel of sintering process in high temperatures, around 1250 degrees C, and gas generation is responsible for porous structure formation. Physical properties such as porosity, water absorption and bulk density, of sintering products are measured. Increase of FAL percentage in sintering mixtures results in decrease of porosity from 61% to 35% and of water absorption from 61% to 21% and in increase of bulk density from 1.02 g/cm(3) to 1.80 g/cm(3) of the produced aggregates. Aggregates produced by FAL addition up to 20 wt% are characterized as LWA. Aggregates formed are used in the production of concrete specimens. Compressive strength of concrete increases by increasing FAL addition in aggregates from 5 wt% to 15 wt% (highest strength value), while decrease by increasing FAL addition from 20 wt% to 30 wt%. FAL addition in lignite ashes sintering mixtures (up to 15 wt%) is considered as an important parameter for enhancing aggregates strength.

COMMERCIAL DEMONSTRATION OF THE MANUFACTURED AGGREGATE PROCESSING TECHNOLOGY UTILIZING SPRAY DRYER ASH

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

Roy Scandrol

2003-04-01

Universal Aggregates, LLC proposes to design, construct and operate a lightweight aggregate manufacturing plant at the Birchwood Power Facility in King George, Virginia. The installation and start-up expenses for the Birchwood Aggregate Facility are $19.5 million. The DOE share is $7.2 million (37%) and the Universal Aggregates share is $12.3 (63%). The project team consists of CONSOL Energy Inc., P.J. Dick, Inc., SynAggs, LLC, and Universal Aggregates, LLC. The Birchwood Facility will transform 115,000 tons per year of spray dryer by-products that are currently being disposed of in an offsite landfill into 167,000 tons of a useful product, lightweight aggregatesmore » that can be used to manufacture lightweight aggregates that can be used to manufacture lightweight and medium weight masonry blocks. In addition to the environmental benefits, the Birchwood Facility will create eight (8) manufacturing jobs plus additional employment in the local trucking industry to deliver the aggregate to customers or reagents to the facility. A successful demonstration would lead to additional lightweight aggregate manufacturing facilities in the United States. There are currently twenty-one (21) spray dryer facilities operating in the United States that produce an adequate amount of spray dryer by-product to economically justify the installation of a lightweight aggregate manufacturing facility. Industry sources believe that as additional scrubbing is required, dry flue gas desulfurization (FGD) technologies will be the technology of choice. Letters from potential lightweight aggregate customers indicate that there is a market for the product once the commercialization barriers are eliminated by this demonstration project.« less

COMMERCIAL DEMONSTRATION OF THE MANUFACTURED AGGREGATE PROCESSING TECHNOLOGY UTILIZING SPRAY DRYER ASH

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

Roy Scandrol

2003-10-01

Universal Aggregates, LLC proposes to design, construct and operate a lightweight aggregate manufacturing plant at the Birchwood Power Facility in King George, Virginia. The installation and start-up expenses for the Birchwood Aggregate Facility are $19.5 million. The DOE share is $7.2 million (37%) and the Universal Aggregates share is $12.3 (63%). The project team consists of CONSOL Energy Inc., P.J. Dick, Inc., SynAggs, LLC, and Universal Aggregates, LLC. The Birchwood Facility will transform 115,000 tons per year of spray dryer by-products that are currently being disposed of in an offsite landfill into 167,000 tons of a useful product, lightweight aggregatesmore » that can be used to manufacture lightweight aggregates that can be used to manufacture lightweight and medium weight masonry blocks. In addition to the environmental benefits, the Birchwood Facility will create nine (9) manufacturing jobs plus additional employment in the local trucking industry to deliver the aggregate to customers or reagents to the facility. A successful demonstration would lead to additional lightweight aggregate manufacturing facilities in the United States. There are currently twenty-one (21) spray dryer facilities operating in the United States that produce an adequate amount of spray dryer by-product to economically justify the installation of a lightweight aggregate manufacturing facility. Industry sources believe that as additional scrubbing is required, dry FGD technologies will be the technology of choice. Letters from potential lightweight aggregate customers indicate that there is a market for the product once the commercialization barriers are eliminated by this demonstration project.« less

A Re-Examination of the Education Production Function Using Individual Participant Data

ERIC Educational Resources Information Center

Pigott, Therese D.; Williams, Ryan T.; Polanin, Joshua R.

2011-01-01

The focus and purpose of this research is to examine the benefits, limitations, and implications of Individual Participant Data (IPD) meta-analysis in education. Comprehensive research reviews in education have been limited to the use of aggregated data (AD) meta- analysis, techniques based on quantitatively combining information from studies on…

Impact of product-related factors on immunogenicity of biotherapeutics.

PubMed

Singh, Satish Kumar

2011-02-01

All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. Copyright © 2010 Wiley-Liss, Inc.

Validation of an aggregate exposure model for substances in consumer products: a case study of diethyl phthalate in personal care products

PubMed Central

Delmaar, Christiaan; Bokkers, Bas; ter Burg, Wouter; Schuur, Gerlienke

2015-01-01

As personal care products (PCPs) are used in close contact with a person, they are a major source of consumer exposure to chemical substances contained in these products. The estimation of realistic consumer exposure to substances in PCPs is currently hampered by the lack of appropriate data and methods. To estimate aggregate exposure of consumers to substances contained in PCPs, a person-oriented consumer exposure model has been developed (the Probabilistic Aggregate Consumer Exposure Model, PACEM). The model simulates daily exposure in a population based on product use data collected from a survey among the Dutch population. The model is validated by comparing diethyl phthalate (DEP) dose estimates to dose estimates based on biomonitoring data. It was found that the model's estimates compared well with the estimates based on biomonitoring data. This suggests that the person-oriented PACEM model is a practical tool for assessing realistic aggregate exposures to substances in PCPs. In the future, PACEM will be extended with use pattern data on other product groups. This will allow for assessing aggregate exposure to substances in consumer products across different product groups. PMID:25352161

Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–)-epigallocatechin-3-gallate

PubMed Central

He, Yan; Cui, Jiankun; Lee, James C-M; Ding, Shinghua; Chalimoniuk, Malgorzata; Simonyi, Agnes; Sun, Albert Y; Gu, Zezong; Weisman∥, Gary A; Gibson Wood, W; Sun, Grace Y

2011-01-01

Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD. PMID:21434871

Separating full-length protein from aggregating proteolytic products using filter flow-through purification.

PubMed

Churion, Kelly A; Rogers, Robert E; Bayless, Kayla J; Bondos, Sarah E

2016-12-01

Separation of full-length protein from proteolytic products is challenging, since the properties used to isolate the protein can also be present in proteolytic products. Many separation techniques risk non-specific protein adhesion and/or require a lot of time, enabling continued proteolysis and aggregation after lysis. We demonstrate that proteolytic products aggregate for two different proteins. As a result, full-length protein can be rapidly separated from these fragments by filter flow-through purification, resulting in a substantial protein purity enhancement. This rapid approach is likely to be useful for intrinsically disordered proteins, whose repetitive sequence composition and flexible nature can facilitate aggregation. Copyright © 2016 Elsevier Inc. All rights reserved.

The Nation's top 25 construction aggregates producers

USGS Publications Warehouse

Willett, Jason Christopher

2013-01-01

U.S. production of construction aggregates in 2011 was 2.17 billion short tons, valued at $17.2 billion, free on board (f.o.b.) at plant. Construction aggregates production decreased by 37 percent, and the associated value decreased by 25 percent, compared with the record highs reported in 2006. In 2011, construction aggregates production increased for the first time since 2006, owing to a very slight increase in the production of both construction sand and gravel and crushed stone. The average unit value, which is the f.o.b. at plant price of a ton of material, increased slightly, but is still less than the average unit value of two years prior.

A microfabricated platform to form three-dimensional toroidal multicellular aggregate.

PubMed

Masuda, Taisuke; Takei, Natsuki; Nakano, Takuma; Anada, Takahisa; Suzuki, Osamu; Arai, Fumihito

2012-12-01

Techniques that allow cells to self-assemble into three-dimensional (3D) spheroid microtissues provide powerful in vitro models that are becoming increasingly popular in fields such as stem cell research, tissue engineering, and cancer biology. Appropriate simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. We have developed a unique multicellular aggregate formation platform that utilizes a maskless gray-scale photolithography. The cellular aggregate formed using this platform has a toroidal-like geometry and includes a micro lumen that facilitates the supply of oxygen and growth factors and the expulsion of waste products. As a result, this platform was capable of rapidly producing hundreds of multicellular aggregates at a time, and of regulating the diameter of aggregates with complex design. These toroidal multicellular aggregates can grow as long-term culture. In addition, the micro lumen can be used as a continuous channel and for the insertion of a vascular system or a nerve system into the assembled tissue. These platform characteristics highlight its potential to be used in a wide variety of applications, e.g. as a bioactuator, as a micro-machine component or in drug screening and tissue engineering.

Skin sensitisation quantitative risk assessment (QRA) based on aggregate dermal exposure to methylisothiazolinone in personal care and household cleaning products.

PubMed

Ezendam, J; Bokkers, B G H; Bil, W; Delmaar, J E

2018-02-01

Contact allergy to preservatives is an important public health problem. Ideally, new substances should be evaluated for the risk on skin sensitisation before market entry, for example by using a quantitative risk assessment (QRA) as developed for fragrances. As a proof-of-concept, this QRA was applied to the preservative methylisothiazolinone (MI), a common cause of contact allergy. MI is used in different consumer products, including personal care products (PCPs) and household cleaning products (HCPs). Aggregate exposure to MI in PCPs and HCPs was therefore assessed with the Probabilistic Aggregated Consumer Exposure Model (PACEM). Two exposure scenarios were evaluated: scenario 1 calculated aggregate exposure on actual MI product concentrations before the restricted use in PCPs and scenario 2 calculated aggregate exposure using the restrictions for MI in PCPs. The QRA for MI showed that in scenarios 1 and 2, the proportion of the population at risk for skin sensitisation is 0.7% and 0.5%, respectively. The restricted use of MI in PCPs does not seem very effective in lowering the risk on skin sensitization. To conclude, it is important to consider aggregate exposure from the most important consumer products into consideration in the risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Generation of urban road dust from anti-skid and asphalt concrete aggregates.

PubMed

Tervahattu, Heikki; Kupiainen, Kaarle J; Räisänen, Mika; Mäkelä, Timo; Hillamo, Risto

2006-04-30

Road dust forms an important component of airborne particulate matter in urban areas. In many winter cities the use of anti-skid aggregates and studded tires enhance the generation of mineral particles. The abrasion particles dominate the PM10 during springtime when the material deposited in snow is resuspended. This paper summarizes the results from three test series performed in a test facility to assess the factors that affect the generation of abrasion components of road dust. Concentrations, mass size distribution and composition of the particles were studied. Over 90% of the particles were aluminosilicates from either anti-skid or asphalt concrete aggregates. Mineral particles were observed mainly in the PM10 fraction, the fine fraction being 12% and submicron size being 6% of PM10 mass. The PM10 concentrations increased as a function of the amount of anti-skid aggregate dispersed. The use of anti-skid aggregate increased substantially the amount of PM10 originated from the asphalt concrete. It was concluded that anti-skid aggregate grains contribute to pavement wear. The particle size distribution of the anti-skid aggregates had great impact on PM10 emissions which were additionally enhanced by studded tires, modal composition, and texture of anti-skid aggregates. The results emphasize the interaction of tires, anti-skid aggregate, and asphalt concrete pavement in the production of dust emissions. They all must be taken into account when measures to reduce road dust are considered. The winter maintenance and springtime cleaning must be performed properly with methods which are efficient in reducing PM10 dust.

A hyper-thermostable α-amylase from Pyrococcus furiosus accumulates in Nicotiana tabacum as functional aggregates.

PubMed

Zhu, Hong; Reynolds, L Bruce; Menassa, Rima

2017-06-19

Alpha amylase hydrolyzes α-bonds of polysaccharides such as starch and produces malto-oligosaccharides. Its starch saccharification applications make it an essential enzyme in the textile, food and brewing industries. Commercially available α-amylase is mostly produced from Bacillus or Aspergillus. A hyper-thermostable and Ca 2++ independent α-amylase from Pyrococcus furiosus (PFA) expressed in E.coli forms insoluble inclusion bodies and thus is not feasible for industrial applications. We expressed PFA in Nicotiana tabacum and found that plant-produced PFA forms functional aggregates with an accumulation level up to 3.4 g/kg FW (fresh weight) in field conditions. The aggregates are functional without requiring refolding and therefore have potential to be applied as homogenized plant tissue without extraction or purification. PFA can also be extracted from plant tissue upon dissolution in a mild reducing buffer containing SDS. Like the enzyme produced in P. furiosus and in E. coli, plant produced PFA preserves hyper-thermophilicity and hyper-thermostability and has a long shelf life when stored in lyophilized leaf tissue. With tobacco's large biomass and high yield, hyper-thermostable α-amylase was produced at a scale of 42 kg per hectare. Tobacco may be a suitable bioreactor for industrial production of active hyperthermostable alpha amylase.

The formulation and immunogenicity of therapeutic proteins: Product quality as a key factor.

PubMed

Richard, Joel; Prang, Nadia

2010-08-01

The formation of anti-drug antibodies represents a risk that should be assessed carefully during biopharmaceutical drug product (DP) development, as such antibodies compromise safety and efficacy and may alter the pharmacokinetic properties of a compound. This feature review discusses immunogenicity issues in biopharmaceutical DP development, with a focus on product quality. Excipient-induced and aggregate-induced immunogenicity are reviewed based on the concepts of 'aggregation-competent' species and 'provocative' aggregates. In addition, the influence of formulation parameters, such as particulates and contaminants appearing in the DP during processing and storage, on aggregate-induced immunogenicity are presented, including the role of fill-and-finish equipments and the effect of interactions with container materials. Furthermore, methods to detect and quantify aggregation and precursor conformational changes in a protein formulation are reviewed, and immunological mechanisms that may lead to aggregate-induced immunogenicity are proposed and discussed.

Study of the Technical Feasibility of Increasing the Amount of Recycled Concrete Waste Used in Ready-Mix Concrete Production.

PubMed

Fraile-Garcia, Esteban; Ferreiro-Cabello, Javier; López-Ochoa, Luis M; López-González, Luis M

2017-07-18

The construction industry generates a considerable amount of waste. Faced with this undesirable situation, the ready-mix concrete sector, in particular, has invested energy and resources into reusing its own waste in its production process as it works towards the goal of more sustainable construction. This study examines the feasibility of incorporating two types of concrete waste, which currently end up in landfill, into the production process of ready-mix concrete: the waste generated during the initial production stage (ready-mix concrete waste), and waste created when demolition waste is treated to obtain artificial aggregate. The first phase of the study's methodology corroborates the suitability of the recycled aggregate through characterization tests. After this phase, the impact of incorporating different percentages of recycled coarse aggregate is evaluated by examining the performance of the produced concrete. The replacement rate varied between 15% and 50%. The results indicate that recycled aggregates are, indeed, suitable to be incorporated into ready-mix concrete production. The impact on the final product's performance is different for the two cases examined herein. Incorporating aggregates from generic concrete blocks led to a 20% decrease in the produced concrete's strength performance. On the other hand, using recycled aggregates made from the demolition waste led to a smaller decrease in the concrete's performance: about 8%. The results indicate that with adequate management and prior treatment, the waste from these plants can be re-incorporated into their production processes. If concrete waste is re-used, concrete production, in general, becomes more sustainable for two reasons: less waste ends up as landfill and the consumption of natural aggregates is also reduced.

Antioxidative and antiplatelet effects of aqueous inflorescence Piper betle extract.

PubMed

Lei, Daniel; Chan, Chiu-Po; Wang, Ying-Jan; Wang, Tong-Mei; Lin, Bor-Ru; Huang, Chun-Hsun; Lee, Jang-Jaer; Chen, Hsin-Ming; Jeng, Jiiang-Huei; Chang, Mei-Chi

2003-03-26

Piper betle, belonging to the Piperaceae family, is a tropical plant, and its leaf and inflorescence are popularly consumed by betel quid (BQ) chewers in Taiwan and many other South and Southeast Asian countries. However, little is known about the biochemical properties of inflorescence Piper betle (IPB) toward reactive oxygen species (ROS) and platelet functions. In the present work, aqueous IPB extract was shown to be a scavenger of H(2)O(2), superoxide radical, and hydroxyl radical with a 50% inhibitory concentration (IC(50)) of about 80, 28, and 73 microg/mL, respectively. IPB extract also prevented the hydroxyl radical induced PUC18 plasmid DNA breaks at concentrations higher than 40 microg/mL. Since ROS are crucial for platelet aggregation, we further found that IPB extract also inhibited the arachidonic acid (AA) induced and collagen-induced platelet aggregation, with an IC(50) of 207 and 335 microg/mL, respectively. IPB extract also inhibited the AA-, collagen- (>100 microg/mL of IPB), and thrombin (>250 microg/mL of IPB)-induced thromboxane B(2) (TXB(2)) production by more than 90%. However, IPB extract showed little effect on thrombin-induced aggregation. These results indicated that aqueous components of IPB are potential ROS scavengers and may prevent the platelet aggregation possibly via scavenging ROS or inhibition of TXB(2) production.

Oxidation of an Exposed Methionine Instigates the Aggregation of Glyceraldehyde-3-phosphate Dehydrogenase*

PubMed Central

Samson, Andre L.; Knaupp, Anja S.; Kass, Itamar; Kleifeld, Oded; Marijanovic, Emilia M.; Hughes, Victoria A.; Lupton, Chris J.; Buckle, Ashley M.; Bottomley, Stephen P.; Medcalf, Robert L.

2014-01-01

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous and abundant protein that participates in cellular energy production. GAPDH normally exists in a soluble form; however, following necrosis, GAPDH and numerous other intracellular proteins convert into an insoluble disulfide-cross-linked state via the process of “nucleocytoplasmic coagulation.” Here, free radical-induced aggregation of GAPDH was studied as an in vitro model of nucleocytoplasmic coagulation. Despite the fact that disulfide cross-linking is a prominent feature of GAPDH aggregation, our data show that it is not a primary rate-determining step. To identify the true instigating event of GAPDH misfolding, we mapped the post-translational modifications that arise during its aggregation. Solvent accessibility and energy calculations of the mapped modifications within the context of the high resolution native GAPDH structure suggested that oxidation of methionine 46 may instigate aggregation. We confirmed this by mutating methionine 46 to leucine, which rendered GAPDH highly resistant to free radical-induced aggregation. Molecular dynamics simulations suggest that oxidation of methionine 46 triggers a local increase in the conformational plasticity of GAPDH that likely promotes further oxidation and eventual aggregation. Hence, methionine 46 represents a “linchpin” whereby its oxidation is a primary event permissive for the subsequent misfolding, aggregation, and disulfide cross-linking of GAPDH. A critical role for linchpin residues in nucleocytoplasmic coagulation and other forms of free radical-induced protein misfolding should now be investigated. Furthermore, because disulfide-cross-linked aggregates of GAPDH arise in many disorders and because methionine 46 is irrelevant to native GAPDH function, mutation of methionine 46 in models of disease should allow the unequivocal assessment of whether GAPDH aggregation influences disease progression. PMID:25086035

Plasmonic properties and enhanced fluorescence of gold and dye-doped silica nanoparticle aggregates

NASA Astrophysics Data System (ADS)

Green, Nathaniel Scott

The development of metal-enhanced fluorescence has prompted a great interest in augmenting the photophysical properties of fluorescent molecules with noble metal nanostructures. Our research efforts, outlined in this dissertation, focus on augmenting properties of fluorophores by conjugation with gold nanostructures. The project goals are split into two separate efforts; the enhancement in brightness of fluorophores and long distance non-radiative energy transfer between fluorophores. We believe that interacting dye-doped silica nanoparticles with gold nanoparticles can facilitate both of these phenomena. Our primary research interest is focused on optimizing brightness, as this goal should open a path to studying the second goal of non-radiative energy transfer. The two major challenges to this are constructing suitable nanomaterials and functionalizing them to promote plasmonically active complexes. The synthesis of dye-doped layered silica nanoparticles allows for control over the discrete location of the dye and a substrate that can be surface functionalized. Controlling the exact location of the dye is important to create a silica spacer, which promotes productive interactions with metal nanostructures. Furthermore, the synthesis of silica nanoparticles allows for various fluorophores to be studied in similar environments (removing solvent and other chemo-sensitive issues). Functionalizing the surface of silica nanoparticles allows control over the degree of silica and gold nanoparticle aggregation in solution. Heteroaggregation in solution is useful for producing well-aggregated clusters of many gold around a single silica nanoparticle. The dye-doped surface functionalized silica nanoparticles can than be mixed efficiently with gold nanomaterials. Aggregating multiple gold nanospheres around a single dye-doped silica nanoparticle can dramatically increase the fluorescent brightness of the sample via metal-enhanced fluorescence due to increase plasmonic scattering. Our aim is to promote heteroaggregation with functionalized silica nanoparticles while minimizing homoaggregation of silica-silica or gold-gold species. Reproducible production of multiple gold nanospheres about a dye-doped silica nanoparticle should lead to dramatic fluorescence brightness enhancements in solution. Gold nanorods can potentially be used to establish radiationless energy transfer between hetero dye-doped silica nanoparticles via gold nanorod plasmon mediated FRET by aggregating two different dye-doped silica nanoparticles preferentially at opposite ends of the nanorod. End-cap binding is accomplished by tuning the strength of gold binding ligands that functionalize the surface of the silica nanoparticles. The gold nanorod can then theoretically serve as a waveguide by employing the longitudinal plasmon as a non-radiative energy transfer agent between the two different fluorophores, giving rise to a new ultrafast signaling paradigm. Heteroaggregation of dye-doped silica nanoparticles and gold nanorods can be potentially employed to as nano waveguides. Construction and aggregation of functionalized silica and gold nano-materials provides an opportunity to advance the field of fluorescence. The synthesis of gold nano-particles allows control over their size and shape, which give rise to useful optical and electronic properties. Silica nanoparticles provide a framework allowing control over a requisite distance for increasing beneficial and deceasing non-radiative dye-metal interactions as well fluorophore protection. Our aim is to take advantage of fine-tuned synthetic control of functionalized nanomaterials to realize the great potential of solution based metal-enhanced fluorescence for future applications.

Sustainable management and supply of natural and recycled aggregates in a medium-size integrated plant.

PubMed

Faleschini, Flora; Zanini, Mariano Angelo; Pellegrino, Carlo; Pasinato, Stefano

2016-03-01

The consumption of natural aggregates in civil engineering applications can cause severe environmental impacts on a regional scale, depleting the stock of bulk resources within a territory. Several methods can improve the environmental sustainability of the whole aggregates' supply process, including natural and recycled aggregates' productive chains, for instance promoting the use of recycled aggregates (RA). However, when quarrying and recycling activities are considered as stand-alone processes, also the RA supply chain may not be as sustainable as expected, due to the high environmental loads associated to transportation, if high distances from the production to the use sites are involved. This work gives some insights on the environmental impact assessment of the aggregates' industry in the Italian context, through a comparative assessment of the environmental loads of natural and recycled aggregates' productive chains. An integrated plant for the extraction of virgin aggregates and recycling of construction and demolition waste (C&DW) was analyzed as significant case study, with the aim to identify the influence of sustainable solutions on the overall emissions of the facility. A Life Cycle Assessment (LCA) approach was used, using site-specific data and paying particular attention on transportation-related impacts, land use, avoided landfill and non-renewable resources preservation. From this work it was possible to evaluate the influence of transportation and PV energy use on the overall environmental emissions of natural and recycled aggregates' productive chains. Copyright © 2016 Elsevier Ltd. All rights reserved.

TOPICAL REVIEW: Smart aggregates: multi-functional sensors for concrete structures—a tutorial and a review

NASA Astrophysics Data System (ADS)

Song, Gangbing; Gu, Haichang; Mo, Yi-Lung

2008-06-01

This paper summarizes the authors' recent pioneering research work in piezoceramic-based smart aggregates and their innovative applications in concrete civil structures. The basic operating principle of smart aggregates is first introduced. The proposed smart aggregate is formed by embedding a waterproof piezoelectric patch with lead wires into a small concrete block. The proposed smart aggregates are multi-functional and can perform three major tasks: early-age concrete strength monitoring, impact detection and structural health monitoring. The proposed smart aggregates are embedded into the desired location before the casting of the concrete structure. The concrete strength development is monitored by observing the high frequency harmonic wave response of the smart aggregate. Impact on the concrete structure is detected by observing the open-circuit voltage of the piezoceramic patch in the smart aggregate. For structural health monitoring purposes, a smart aggregate-based active sensing system is designed for the concrete structure. Wavelet packet analysis is used as a signal-processing tool to analyze the sensor signal. A damage index based on the wavelet packet analysis is used to determine the structural health status. To better describe the time-history and location information of damage, two types of damage index matrices are proposed: a sensor-history damage index matrix and an actuator-sensor damage index matrix. To demonstrate the multi-functionality of the proposed smart aggregates, different types of concrete structures have been used as test objects, including concrete bridge bent-caps, concrete cylinders and a concrete frame. Experimental results have verified the effectiveness and the multi-functionality of the proposed smart aggregates. The multi-functional smart aggregates have the potential to be applied to the comprehensive monitoring of concrete structures from their earliest stages and throughout their lifetime.

The Myxococcus xanthus Spore Cuticula Protein C Is a Fragment of FibA, an Extracellular Metalloprotease Produced Exclusively in Aggregated Cells

PubMed Central

Lee, Bongsoo; Mann, Petra; Grover, Vidhi; Treuner-Lange, Anke; Kahnt, Jörg; Higgs, Penelope I.

2011-01-01

Myxococcus xanthus is a soil bacterium with a complex life cycle involving distinct cell fates, including production of environmentally resistant spores to withstand periods of nutrient limitation. Spores are surrounded by an apparently self-assembling cuticula containing at least Proteins S and C; the gene encoding Protein C is unknown. During analyses of cell heterogeneity in M. xanthus, we observed that Protein C accumulated exclusively in cells found in aggregates. Using mass spectrometry analysis of Protein C either isolated from spore cuticula or immunoprecipitated from aggregated cells, we demonstrate that Protein C is actually a proteolytic fragment of the previously identified but functionally elusive zinc metalloprotease, FibA. Subpopulation specific FibA accumulation is not due to transcriptional regulation suggesting post-transcriptional regulation mechanisms mediate its heterogeneous accumulation patterns. PMID:22174937

Growth of aragonite calcium carbonate nanorods in the biomimetic anodic aluminum oxide template

NASA Astrophysics Data System (ADS)

Lee, Inho; Han, Haksoo; Lee, Sang-Yup

2010-04-01

In this study, a biomimetic template was prepared and applied for growing calcium carbonate (CaCO 3) nanorods whose shape and polymorphism were controlled. A biomimetic template was prepared by adsorbing catalytic dipeptides into the pores of an anodic aluminum oxide (AAO) membrane. Using this peptide-adsorbed template, mineralization and aggregation of CaCO 3 was carried out to form large nanorods in the pores. The nanorods were aragonite and had a structure similar to nanoneedle assembly. This aragonite nanorod formation was driven by both the AAO template and catalytic function of dipeptides. The AAO membrane pores promoted generation of aragonite polymorph and guided nanorod formation by guiding the nanorod growth. The catalytic dipeptides promoted the aggregation and further dehydration of calcium species to form large nanorods. Functions of the AAO template and catalytic dipeptides were verified through several control experiments. This biomimetic approach makes possible the production of functional inorganic materials with controlled shapes and crystalline structures.

Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths.

PubMed Central

Snyder, S W; Ladror, U S; Wade, W S; Wang, G T; Barrett, L W; Matayoshi, E D; Huffaker, H J; Krafft, G A; Holzman, T F

1994-01-01

One of the clinical manifestations of Alzheimer's disease is the deposition of the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile plaques. Characterization of the aggregation behavior of A beta is one of the critical issues in understanding the role of A beta in the disease process. Using solution hydrodynamics, A beta was observed to form three types of species in phosphate-buffered saline: insoluble aggregates with sedimentation coefficients of approximately 50,000 S and molecular masses of approximately 10(9) Da, "soluble aggregates" with sedimentation coefficients of approximately 30 S and masses of approximately 10(6) Da, and monomer. When starting from monomer, the aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42), alone and in combination, reveal large differences in the tendency of these peptides to aggregate as a function of pH and other solution conditions. At pH 4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under all conditions, aggregation of the longer A beta 42 was more rapid than A beta 40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation rate over that of the nonoxidized peptide. Aggregation was found to be dependent upon temperature and to be strongly dependent on peptide concentration and ionic strength, indicating that aggregation is driven by a hydrophobic effect. When A beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing ability to interfere with A beta 42 aggregation. Conversely, the rate of aggregation of A beta 40 can be significantly enhanced by seeding slow aggregating solutions with preformed aggregates of A beta 42. Taken together, the inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40 aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40 suggest that the relative abundance and rates of production of different-length A beta and its exposure to radical damage may be factors in the accumulation of A beta in plaques in vivo. Images FIGURE 6 PMID:7811936

Utilizing dynamic light scattering as a process analytical technology for protein folding and aggregation monitoring in vaccine manufacturing.

PubMed

Yu, Zhou; Reid, Jennifer C; Yang, Yan-Ping

2013-12-01

Protein aggregation is a common challenge in the manufacturing of biological products. It is possible to minimize the extent of aggregation through timely measurement and in-depth characterization of aggregation. In this study, we demonstrated the use of dynamic light scattering (DLS) to monitor inclusion body (IB) solubilization, protein refolding, and aggregation near the production line of a recombinant protein-based vaccine candidate. Our results were in good agreement with those measured by size-exclusion chromatography. DLS was also used to characterize the mechanism of aggregation. As DLS is a quick, nonperturbing technology, it can potentially be used as an at-line process analytical technology to ensure complete IB solubilization and aggregate-free refolding. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

COIN Project: Towards a zero-waste technology for concrete aggregate production in Norway

NASA Astrophysics Data System (ADS)

Cepuritis, Rolands; Willy Danielsen, Svein

2014-05-01

COIN Project: Towards a zero-waste technology for concrete aggregate production in Norway Rolands Cepuritis, Norcem/NTNU and Svein Willy Danielsen, SINTEF Aggregate production is a mining operation where no purification of the "ore" is necessary. Still it is extremely rare that an aggregate production plant is operating on the basis of zero-waste concept. This is since historically the fine crushed aggregate (particles with a size of less than 2, 4 or sometimes 8 mm) has been regarded as a by-product or waste of the more valuable coarse aggregate production. The reason is that the crushed coarse aggregates can easily replace coarse rounded natural stones in almost any concrete composition; while, the situation with the sand is different. The production of coarse aggregate normally yields fine fractions with rough surface texture, flaky or elongated particles an inadequate gradation. When such a material replaces smooth and rounded natural sand grains in a concrete mix, the result is usually poor and much more water and cement has to be used to achieve adequate concrete flow. The consequences are huge stockpiles of the crushed fine fractions that can't be sold (mass balance problems) for the aggregate producers, sustainability problems for the whole industry and environmental issues for society due to dumping and storing of the fine co-generated material. There have been attempts of utilising the material in concrete before; however, they have mostly ended up in failure. There have been attempts to adjust the crushed sand to the properties of the natural sand, which would still give a lot of waste, especially if the grading would have to be adjusted and the high amounts of fines abundantly present in the crushed sand would have to be removed. Another fundamental reason for failure has been that historically such attempts have mainly ended up in a research carried out by people (both industrial and academic) with aggregate background (= parties willing to find market for their crusher fines) providing only conclusions already well known by the engineers involved in concrete production. Due to the pressing situation with the left resources of the natural sand and gravel in Scandinavia, a new and different development approach has been recently attempted with the Concrete Innovation Center (COIN) in Norway. The centre is a research based innovation project that has brought together and served as a source of funding to facilitate the crucial interaction between the professionals from the different involved industries (quarrying machinery supplier, aggregate producers, concrete producers and concrete contractors) and the academic people from universities and research institutions, in order come up with a better crushed sand solution for the future. The concept under development has been a zero-waste technology for aggregate production, where instead of reducing the amount of the crushed fines their properties are rather engineered to crucially increase the overall performance of the sand in concrete. The project also involves collaboration with a state-of-the-art aggregate production plant where the new technology has already been implemented. The production process there is based on the new engineered sand concepts successfully supplying 100% all of the produced fractions to concrete and asphalt producers.

Non-Arrhenius protein aggregation.

PubMed

Wang, Wei; Roberts, Christopher J

2013-07-01

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

Study of the Technical Feasibility of Increasing the Amount of Recycled Concrete Waste Used in Ready-Mix Concrete Production

PubMed Central

Ferreiro-Cabello, Javier; López-González, Luis M.

2017-01-01

The construction industry generates a considerable amount of waste. Faced with this undesirable situation, the ready-mix concrete sector, in particular, has invested energy and resources into reusing its own waste in its production process as it works towards the goal of more sustainable construction. This study examines the feasibility of incorporating two types of concrete waste, which currently end up in landfill, into the production process of ready-mix concrete: the waste generated during the initial production stage (ready-mix concrete waste), and waste created when demolition waste is treated to obtain artificial aggregate. The first phase of the study’s methodology corroborates the suitability of the recycled aggregate through characterization tests. After this phase, the impact of incorporating different percentages of recycled coarse aggregate is evaluated by examining the performance of the produced concrete. The replacement rate varied between 15% and 50%. The results indicate that recycled aggregates are, indeed, suitable to be incorporated into ready-mix concrete production. The impact on the final product’s performance is different for the two cases examined herein. Incorporating aggregates from generic concrete blocks led to a 20% decrease in the produced concrete’s strength performance. On the other hand, using recycled aggregates made from the demolition waste led to a smaller decrease in the concrete’s performance: about 8%. The results indicate that with adequate management and prior treatment, the waste from these plants can be re-incorporated into their production processes. If concrete waste is re-used, concrete production, in general, becomes more sustainable for two reasons: less waste ends up as landfill and the consumption of natural aggregates is also reduced. PMID:28773183

Fluorescence dye-based detection of mAb aggregates in CHO culture supernatants.

PubMed

Paul, Albert Jesuran; Schwab, Karen; Prokoph, Nina; Haas, Elena; Handrick, René; Hesse, Friedemann

2015-06-01

Product yields, efficacy, and safety of monoclonal antibodies (mAbs) are reduced by the formation of higher molecular weight aggregates during upstream processing. In-process characterization of mAb aggregate formation is a challenge since there is a lack of a fast detection method to identify mAb aggregates in cell culture. In this work, we present a rapid method to characterize mAb aggregate-containing Chinese hamster ovary (CHO) cell culture supernatants. The fluorescence dyes thioflavin T (ThT) and 4-4-bis-1-phenylamino-8-naphthalene sulfonate (Bis-ANS) enabled the detection of soluble as well as large mAb aggregates. Partial least square (PLS) regression models were used to evaluate the linearity of the dye-based mAb aggregate detection in buffer down to a mAb aggregate concentration of 2.4 μg mL(-1). Furthermore, mAb aggregates were detected in bioprocess medium using Bis-ANS and ThT. Dye binding to aggregates was stable for 60 min, making the method robust and reliable. Finally, the developed method using 10 μmol L(-1) Bis-ANS enabled discrimination between CHO cell culture supernatants containing different levels of mAb aggregates. The method can be adapted for high-throughput screening, e.g., to screen for cell culture conditions influencing mAb product quality, and hence can contribute to the improvement of production processes of biopharmaceuticals in mammalian cell culture.

The thermal aggregation of ovalbumin as large particles decreases its allergenicity for egg allergic patients and in a murine model.

PubMed

Claude, M; Lupi, R; Bouchaud, G; Bodinier, M; Brossard, C; Denery-Papini, S

2016-07-15

Most egg-allergic children can tolerate extensively cooked eggs. Ovalbumin, a major allergen in egg whites, is prone to aggregate upon heating. This study compares ovalbumin's allergenicity when it is aggregated as large particles to ovalbumin in its native form. Immunoglobulins (Ig)-binding and the degranulation capacities of native and aggregated ovalbumin were measured with sera from egg-allergic children and from mice sensitized to native or aggregated ovalbumin. The influence of ovalbumin structure on Ig production upon sensitization and elicitation potency by challenge was also studied. We showed that heat aggregation of ovalbumin as large particles enhances IgG production and promotes IgG2a production (a shift toward the T helper 1 profile). Aggregated ovalbumin displayed lower Ig-binding and basophil-activation capacities for sera from both allergic patients and mice. This work illustrates the links between ovalbumin structure after heating and allergenicity potential using parameters from both the sensitization and elicitation phases of the allergic reaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Baskin, W. E.; Perez, J.

2013-12-01

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

Changes in particle morphology during illitization: An experimental study

USGS Publications Warehouse

Whitney, Gene; Velde, Bruce

1993-01-01

Smectite was reacted at several temperatures between 200°C and 500°C to produce interstratified illite/smectite (I/S) with different proportions of expandable layers. Dispersed and sedimented products were examined using a transmission electron microscope. Particle size and aspect ratio showed no systematic change as a function of reaction extent during R0 illitization. However, particles exhibited rounded edges during the early stages of the reaction, suggesting some dissolution of primary smectite. Additionally, increasing particle contrast in the electron beam suggests thickening of particles with increasing reaction extent. The thickening of particles is thought to be produced by the nucleation and precipitation of secondary illite layers on primary smectite layers. In the most extensively reacted I/S, particles have become aggregated into clumps or quasicrystals by lateral growth of illite layers. Internal uniformity of crystallographic alignment of individual growing crystals within each aggregate was reflected in the increasing frequency of 60° and 120° interfacial angles within each aggregate. In highly illitic I/S, these aggregates took on an overall euhedral form and became crystallographically contiguous, producing single crystal electron diffraction patterns.

Properties of lightweight cement-based composites containing waste polypropylene

NASA Astrophysics Data System (ADS)

Záleská, Martina; Pavlíková, Milena; Pavlík, Zbyšek

2016-07-01

Improvement of buildings thermal stability represents an increasingly important trend of the construction industry. This work aims to study the possible use of two types of waste polypropylene (PP) for the development of lightweight cement-based composites with enhanced thermal insulation function. Crushed PP waste originating from the PP tubes production is used for the partial replacement of silica sand by 10, 20, 30, 40 and 50 mass%, whereas a reference mixture without plastic waste is studied as well. First, basic physical and thermal properties of granular PP random copolymer (PPR) and glass fiber reinforced PP (PPGF) aggregate are studied. For the developed composite mixtures, basic physical, mechanical, heat transport and storage properties are accessed. The obtained results show that the composites with incorporated PP aggregate exhibit an improved thermal insulation properties and acceptable mechanical resistivity. This new composite materials with enhanced thermal insulation function are found to be promising materials for buildings subsoil or floor structures.

Structural-functional integrated concrete with macro-encapsulated inorganic PCM

NASA Astrophysics Data System (ADS)

Mohseni, Ehsan; Tang, Waiching; Wang, Zhiyu

2017-09-01

Over the last few years the application of thermal energy storage system incorporating phase change materials (PCMs) to foster productivity and efficiency of buildings energy has grown rapidly. In this study, a structural-functional integrated concrete was developed using macro-encapsulated PCM-lightweight aggregate (LWA) as partial replacement (25 and 50% by volume) of coarse aggregate in control concrete. The PCM-LWA was prepared by incorporation of an inorganic PCM into porous LWAs through vacuum impregnation. The mechanical and thermal performance of PCM-LWA concrete were studied. The test results revealed that though the compressive strength of concrete with PCM-LWA was lower than the control concrete, but ranged from 22.02 MPa to 42.88 MPa which above the minimum strength requirement for structural application. The thermal performance test indicated that macro-encapsulated PCM-LWA has underwent the phase change transition reducing the indoor temperature.

ActA Promotes Listeria monocytogenes Aggregation, Intestinal Colonization and Carriage

PubMed Central

Travier, Laetitia; Guadagnini, Stéphanie; Gouin, Edith; Dufour, Alexandre; Chenal-Francisque, Viviane; Cossart, Pascale; Olivo-Marin, Jean-Christophe; Ghigo, Jean-Marc; Disson, Olivier; Lecuit, Marc

2013-01-01

Listeria monocytogenes (Lm) is a ubiquitous bacterium able to survive and thrive within the environment and readily colonizes a wide range of substrates, often as a biofilm. It is also a facultative intracellular pathogen, which actively invades diverse hosts and induces listeriosis. So far, these two complementary facets of Lm biology have been studied independently. Here we demonstrate that the major Lm virulence determinant ActA, a PrfA-regulated gene product enabling actin polymerization and thereby promoting its intracellular motility and cell-to-cell spread, is critical for bacterial aggregation and biofilm formation. We show that ActA mediates Lm aggregation via direct ActA-ActA interactions and that the ActA C-terminal region, which is not involved in actin polymerization, is essential for aggregation in vitro. In mice permissive to orally-acquired listeriosis, ActA-mediated Lm aggregation is not observed in infected tissues but occurs in the gut lumen. Strikingly, ActA-dependent aggregating bacteria exhibit an increased ability to persist within the cecum and colon lumen of mice, and are shed in the feces three order of magnitude more efficiently and for twice as long than bacteria unable to aggregate. In conclusion, this study identifies a novel function for ActA and illustrates that in addition to contributing to its dissemination within the host, ActA plays a key role in Lm persistence within the host and in transmission from the host back to the environment. PMID:23382675

Entrapment of Aβ1-40 peptide in unstructured aggregates

NASA Astrophysics Data System (ADS)

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

2012-06-01

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

Four strategies for the age of smart services.

PubMed

Allmendinger, Glen; Lombreglia, Ralph

2005-10-01

Most industrial manufacturers realize that the real money isn't in products but in services. Companies such as General Electric and IBM have famously made the transition: A large proportion of their revenues and margins come from providing value-added services to customers. But other companies attempting to do the same might miss the boat. It is not enough, the authors say, just to provide services. Businesses must now provide "smart services"--building intelligence (awareness and connectivity) into the products themselves. Citing examples such as Heidelberger Druckmaschinen's Internet-connected printing presses and Eaton Electrical's home-monitoring service, the authors demonstrate how a product that can report its status back to its maker represents an opportunity for the manufacturer to cultivate richer, longer-term relationships with customers. Four business models will emerge in this new, networked world. If you go it alone, it may be as an embedded innovator- that is, your networked product sends back information that can help you optimize service delivery, eliminate waste and inefficiency, and raise service margins. Or, you may pursue a more aggressive solutionist business model- that is, you position your networked product as a "complete solution provider," able to deliver a broader scope of high-value services than those provided by the embedded innovator's product. In the case of a system that aggregates and processes data from multiple products in a building or home, you may be either an aggregator or a synergist, partnering with others to pursue a smart-services opportunity. An aggregator's product is the hub, collecting and processing usage information- and creating a high-value body of data. A synergist's product is the spoke, contributing valuable data or functionality. Woe to the company that takes none of these paths; it'll soon find its former customers locked in--and happily--to other smart service providers.

76 FR 78044 - Controlled Substances: Established Aggregate Production Quotas for 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... that the 2012 aggregate production quotas for the following controlled substances, expressed in grams... Methamphetamine 3,130,000 g [750,000 grams of levo-desoxyephedrine for use in a non-controlled, non- prescription product; 2,331,000 grams for methamphetamine mostly for conversion to a Schedule III product; and 49,000...

77 FR 39737 - Controlled Substances: Proposed Adjustment to the Aggregate Production Quotas for 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... aggregate production quotas for some schedule I and II controlled substances, expressed in grams of.... [750,000 grams of levo-desoxyephedrine for use in a non-controlled, non-prescription product; 2,331,000 grams for methamphetamine mostly for conversion to a schedule III product; and 49,000 grams for...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2013 CFR

2013-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2011 CFR

2011-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

15 CFR 712.5 - Annual declaration requirements for facilities engaged in the production of Schedule 1 chemicals...

Code of Federal Regulations, 2014 CFR

2014-01-01

...)(2) of this section if you produced at your facility in excess of 100 grams aggregate of Schedule 1... you will produce at your facility more than 100 grams aggregate of Schedule 1 chemicals in the next... result in production of more than 100 grams aggregate of Schedule 1 chemicals. (b) Declaration forms to...

Aggregation Pattern Transitions by Slightly Varying the Attractive/Repulsive Function

PubMed Central

Cheng, Zhao; Zhang, Hai-Tao; Chen, Michael Z. Q.; Zhou, Tao; Valeyev, Najl V.

2011-01-01

Among collective behaviors of biological swarms and flocks, the attractive/repulsive (A/R) functional links between particles play an important role. By slightly changing the cutoff distance of the A/R function, a drastic transition between two distinct aggregation patterns is observed. More precisely, a large cutoff distance yields a liquid-like aggregation pattern where the particle density decreases monotonously from the inside to the outwards within each aggregated cluster. Conversely, a small cutoff distance produces a crystal-like aggregation pattern where the distance between each pair of neighboring particles remains constant. Significantly, there is an obvious spinodal in the variance curve of the inter-particle distances along the increasing cutoff distances, implying a legible transition pattern between the liquid-like and crystal-like aggregations. This work bridges the aggregation phenomena of physical particles and swarming of organisms in nature upon revealing some common mechanism behind them by slightly varying their inter-individual attractive/repulsive functions, and may find its potential engineering applications, for example, in the formation design of multi-robot systems and unmanned aerial vehicles (UAVs). PMID:21799776

A test of the cross-scale resilience model: Functional richness in Mediterranean-climate ecosystems

USGS Publications Warehouse

Wardwell, D.A.; Allen, Craig R.; Peterson, G.D.; Tyre, A.J.

2008-01-01

Ecological resilience has been proposed to be generated, in part, in the discontinuous structure of complex systems. Environmental discontinuities are reflected in discontinuous, aggregated animal body mass distributions. Diversity of functional groups within body mass aggregations (scales) and redundancy of functional groups across body mass aggregations (scales) has been proposed to increase resilience. We evaluate that proposition by analyzing mammalian and avian communities of Mediterranean-climate ecosystems. We first determined that body mass distributions for each animal community were discontinuous. We then calculated the variance in richness of function across aggregations in each community, and compared observed values with distributions created by 1000 simulations using a null of random distribution of function, with the same n, number of discontinuities and number of functional groups as the observed data. Variance in the richness of functional groups across scales was significantly lower in real communities than in simulations in eight of nine sites. The distribution of function across body mass aggregations in the animal communities we analyzed was non-random, and supports the contentions of the cross-scale resilience model. ?? 2007 Elsevier B.V. All rights reserved.

Effects of Agaricus lilaceps fairy rings on soil aggregation and microbial community structure in relation to growth stimulation of western wheatgrass (Pascopyrum smithii) in Eastern Montana rangeland.

PubMed

Caesar-Tonthat, The Can; Espeland, Erin; Caesar, Anthony J; Sainju, Upendra M; Lartey, Robert T; Gaskin, John F

2013-07-01

Stimulation of plant productivity caused by Agaricus fairy rings has been reported, but little is known about the effects of these fungi on soil aggregation and the microbial community structure, particularly the communities that can bind soil particles. We studied three concentric zones of Agaricus lilaceps fairy rings in Eastern Montana that stimulate western wheatgrass (Pascopyrum smithii): outside the ring (OUT), inside the ring (IN), and stimulated zone adjacent to the fungal fruiting bodies (SZ) to determine (1) soil aggregate proportion and stability, (2) the microbial community composition and the N-acetyl-β-D-glucosaminidase activity associated with bulk soil at 0-15 cm depth, (3) the predominant culturable bacterial communities that can bind to soil adhering to wheatgrass roots, and (4) the stimulation of wheatgrass production. In bulk soil, macroaggregates (4.75-2.00 and 2.00-0.25 mm) and aggregate stability increased in SZ compared to IN and OUT. The high ratio of fungal to bacteria (fatty acid methyl ester) and N-acetyl-β-D-glucosaminidase activity in SZ compared to IN and OUT suggest high fungal biomass. A soil sedimentation assay performed on the predominant isolates from root-adhering soil indicated more soil-binding bacteria in SZ than IN and OUT; Pseudomonas fluorescens and Stenotrophomonas maltophilia isolates predominated in SZ, whereas Bacillus spp. isolates predominated in IN and OUT. This study suggests that growth stimulation of wheatgrass in A. lilaceps fairy rings may be attributed to the activity of the fungus by enhancing soil aggregation of bulk soil at 0-15 cm depth and influencing the amount and functionality of specific predominant microbial communities in the wheatgrass root-adhering soil.

Composition, buoyancy regulation and fate of ice algal aggregates in the Central Arctic Ocean.

PubMed

Fernández-Méndez, Mar; Wenzhöfer, Frank; Peeken, Ilka; Sørensen, Heidi L; Glud, Ronnie N; Boetius, Antje

2014-01-01

Sea-ice diatoms are known to accumulate in large aggregates in and under sea ice and in melt ponds. There is recent evidence from the Arctic that such aggregates can contribute substantially to particle export when sinking from the ice. The role and regulation of microbial aggregation in the highly seasonal, nutrient- and light-limited Arctic sea-ice ecosystem is not well understood. To elucidate the mechanisms controlling the formation and export of algal aggregates from sea ice, we investigated samples taken in late summer 2011 and 2012, during two cruises to the Eurasian Basin of the Central Arctic Ocean. Spherical aggregates densely packed with pennate diatoms, as well as filamentous aggregates formed by Melosira arctica showed sign of different stages of degradation and physiological stoichiometries, with carbon to chlorophyll a ratios ranging from 110 to 66700, and carbon to nitrogen molar ratios of 8-35 and 9-40, respectively. Sub-ice algal aggregate densities ranged between 1 and 17 aggregates m(-2), maintaining an estimated net primary production of 0.4-40 mg C m(-2) d(-1), and accounted for 3-80% of total phototrophic biomass and up to 94% of local net primary production. A potential factor controlling the buoyancy of the aggregates was light intensity, regulating photosynthetic oxygen production and the amount of gas bubbles trapped within the mucous matrix, even at low ambient nutrient concentrations. Our data-set was used to evaluate the distribution and importance of Arctic algal aggregates as carbon source for pelagic and benthic communities.

Composition, Buoyancy Regulation and Fate of Ice Algal Aggregates in the Central Arctic Ocean

PubMed Central

Fernández-Méndez, Mar; Wenzhöfer, Frank; Peeken, Ilka; Sørensen, Heidi L.; Glud, Ronnie N.; Boetius, Antje

2014-01-01

Sea-ice diatoms are known to accumulate in large aggregates in and under sea ice and in melt ponds. There is recent evidence from the Arctic that such aggregates can contribute substantially to particle export when sinking from the ice. The role and regulation of microbial aggregation in the highly seasonal, nutrient- and light-limited Arctic sea-ice ecosystem is not well understood. To elucidate the mechanisms controlling the formation and export of algal aggregates from sea ice, we investigated samples taken in late summer 2011 and 2012, during two cruises to the Eurasian Basin of the Central Arctic Ocean. Spherical aggregates densely packed with pennate diatoms, as well as filamentous aggregates formed by Melosira arctica showed sign of different stages of degradation and physiological stoichiometries, with carbon to chlorophyll a ratios ranging from 110 to 66700, and carbon to nitrogen molar ratios of 8–35 and 9–40, respectively. Sub-ice algal aggregate densities ranged between 1 and 17 aggregates m−2, maintaining an estimated net primary production of 0.4–40 mg C m−2 d−1, and accounted for 3–80% of total phototrophic biomass and up to 94% of local net primary production. A potential factor controlling the buoyancy of the aggregates was light intensity, regulating photosynthetic oxygen production and the amount of gas bubbles trapped within the mucous matrix, even at low ambient nutrient concentrations. Our data-set was used to evaluate the distribution and importance of Arctic algal aggregates as carbon source for pelagic and benthic communities. PMID:25208058

Ceramic ware waste as coarse aggregate for structural concrete production.

PubMed

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

2015-01-01

The manufacture of any kind of product inevitably entails the production of waste. The quantity of waste generated by the ceramic industry, a very important sector in Spain, is between 5% and 8% of the final output and it is therefore necessary to find an effective waste recovery method. The aim of the study reported in the present article was to seek a sustainable means of managing waste from the ceramic industry through the incorporation of this type of waste in the total replacement of conventional aggregate (gravel) used in structural concrete. Having verified that the recycled ceramic aggregates met all the technical requirements imposed by current Spanish legislation, established in the Code on Structural Concrete (EHE-08), then it is prepared a control concrete mix and the recycled concrete mix using 100% recycled ceramic aggregate instead of coarse natural aggregate. The concretes obtained were subjected to the appropriate tests in order to conduct a comparison of their mechanical properties. The results show that the concretes made using ceramic sanitary ware aggregate possessed the same mechanical properties as those made with conventional aggregate. It is therefore possible to conclude that the reuse of recycled ceramic aggregate to produce recycled concrete is a feasible alternative for the sustainable management of this waste.

[Based on Curing Age of Calcined Coal Gangue Fine Aggregate Mortar of X-Ray Diffraction and Scanning Electron Microscopy Analysis].

PubMed

Dong, Zuo-chao; Xia, Jun-wu; Duan, Xiao-mu; Cao, Ji-chang

2016-03-01

By using X-ray diffraction (XRD) and environmental scanning electron microscope (SEM) analysis method, we stud- ied the activity of coal gangue fine aggregate under different calcination temperature. In view of the activity of the highest-700 degrees C high temperature calcined coal gangue fine aggregate mortar of hydration products, microstructure and strength were discussed in this paper, and the change laws of mortar strength with curing age (3, 7, 14, 28, 60 and 90 d) growth were analyzed. Test results showed that coal gangue fine aggregate with the increase of calcination temperature, the active gradually increases. When the calcination temperature reaches 700 degrees C, the activity of coal gangue fine aggregate is the highest. When calcining temperature continues to rise, activity falls. After 700 degrees C high temperature calcined coal gangue fine aggregate has obvious ash activity, the active components of SiO2 and Al2 O3 can be with cement hydration products in a certain degree of secondary hydration reaction. Through on the top of the activity of different curing age 700 degrees C high temperature calcined coal gangue fine aggregate mortar, XRD and SEM analysis showed that with the increase of curing age, secondary hydration reaction will be more fully, and the amount of hydration products also gradually increases. Compared with the early ages of the cement mortar, the products are more stable hydration products filling in mortar microscopic pore, which can further improve the microstructure of mortar, strengthen the interface performance of the mortar. The mortar internal structure is more uniform, calcined coal gangue fine aggregate and cement mortar are more of a strong continuous whole, which increase the later strength of hardened cement mortar, 700 degrees C high temperature calcined coal gangue fine aggregate pozzolanic effect is obvious.

A look at construction aggregates production

USGS Publications Warehouse

Willett, Jason Christopher

2009-01-01

Construction aggregates are defined as the combination of crushed stone and construction sand and gravel. Aggregates are one of the most accessible natural resources on Earth and one of the fundamental building blocks of our society. They have been used from the earliest times of our civilization for a variety of applications that have increased in number and complexity with time and technological progress. Despite the relatively low but increasing unit value of its basic products, the construction aggregates industry is a major contributor to and an indicator of the economic well-being of the nation.

Method for the production of cementitious compositions and aggregate derivatives from said compositions

DOEpatents

Minnick, L. John

1981-01-01

Method for the production of cementitious compositions and aggregate derivatives of said compositions, and cementitious compositions and aggregates produced by said method, wherein fluidized bed combustion residue and pozzolanic material, such as pulverized coal combustion system fly ash, are incorporated in a cementitious mix. The mix is cast into desired shape and cured. If desired, the shape may then be crushed so as to result in a fluidized bed combustion residue-fly ash aggregate material or the shape may be used by itself.

Production of functional bacteriorhodopsin by an Escherichia coli cell-free protein synthesis system supplemented with steroid detergent and lipid.

PubMed

Shimono, Kazumi; Goto, Mie; Kikukawa, Takashi; Miyauchi, Seiji; Shirouzu, Mikako; Kamo, Naoki; Yokoyama, Shigeyuki

2009-10-01

Cell-free expression has become a highly promising tool for the efficient production of membrane proteins. In this study, we used a dialysis-based Escherichia coli cell-free system for the production of a membrane protein actively integrated into liposomes. The membrane protein was the light-driven proton pump bacteriorhodopsin, consisting of seven transmembrane alpha-helices. The cell-free expression system in the dialysis mode was supplemented with a combination of a detergent and a natural lipid, phosphatidylcholine from egg yolk, in only the reaction mixture. By examining a variety of detergents, we found that the combination of a steroid detergent (digitonin, cholate, or CHAPS) and egg phosphatidylcholine yielded a large amount (0.3-0.7 mg/mL reaction mixture) of the fully functional bacteriorhodopsin. We also analyzed the process of functional expression in our system. The synthesized polypeptide was well protected from aggregation by the detergent-lipid mixed micelles and/or lipid disks, and was integrated into liposomes upon detergent removal by dialysis. This approach might be useful for the high yield production of functional membrane proteins.

Feeding on dispersed vs. aggregated particles: The effect of zooplankton feeding behavior on vertical flux.

PubMed

Koski, Marja; Boutorh, Julia; de la Rocha, Christina

2017-01-01

Zooplankton feeding activity is hypothesized to attenuate the downward flux of elements in the ocean. We investigated whether the zooplankton community composition could influence the flux attenuation, due to the differences of feeding modes (feeding on dispersed vs. aggregated particles) and of metabolic rates. We fed 5 copepod species-three calanoid, one harpacticoid and one poecilamastoid-microplankton food, in either dispersed or aggregated form and measured rates of respiration, fecal pellet production and egg production. Calanoid copepods were able to feed only on dispersed food; when their food was introduced as aggregates, their pellet production and respiration rates decreased to rates observed for starved individuals. In contrast, harpacticoids and the poecilamastoid copepod Oncaea spp. were able to feed only when the food was in the form of aggregates. The sum of copepod respiration, pellet production and egg production rates was equivalent to a daily minimum carbon demand of ca. 10% body weight-1 for all non-feeding copepods; the carbon demand of calanoids feeding on dispersed food was 2-3 times greater, and the carbon demand of harpacticoids and Oncaea spp. feeding on aggregates was >7 times greater, than the resting rates. The zooplankton species composition combined with the type of available food strongly influences the calculated carbon demand of a copepod community, and thus also the attenuation of vertical carbon flux.

Feeding on dispersed vs. aggregated particles: The effect of zooplankton feeding behavior on vertical flux

PubMed Central

Boutorh, Julia; de la Rocha, Christina

2017-01-01

Zooplankton feeding activity is hypothesized to attenuate the downward flux of elements in the ocean. We investigated whether the zooplankton community composition could influence the flux attenuation, due to the differences of feeding modes (feeding on dispersed vs. aggregated particles) and of metabolic rates. We fed 5 copepod species—three calanoid, one harpacticoid and one poecilamastoid–microplankton food, in either dispersed or aggregated form and measured rates of respiration, fecal pellet production and egg production. Calanoid copepods were able to feed only on dispersed food; when their food was introduced as aggregates, their pellet production and respiration rates decreased to rates observed for starved individuals. In contrast, harpacticoids and the poecilamastoid copepod Oncaea spp. were able to feed only when the food was in the form of aggregates. The sum of copepod respiration, pellet production and egg production rates was equivalent to a daily minimum carbon demand of ca. 10% body weight-1 for all non-feeding copepods; the carbon demand of calanoids feeding on dispersed food was 2–3 times greater, and the carbon demand of harpacticoids and Oncaea spp. feeding on aggregates was >7 times greater, than the resting rates. The zooplankton species composition combined with the type of available food strongly influences the calculated carbon demand of a copepod community, and thus also the attenuation of vertical carbon flux. PMID:28545095

Extracellular Polymeric Substance Production and Aggregated Bacteria Colonization Influence the Competition of Microbes in Biofilms.

PubMed

Jayathilake, Pahala G; Jana, Saikat; Rushton, Steve; Swailes, David; Bridgens, Ben; Curtis, Tom; Chen, Jinju

2017-01-01

The production of extracellular polymeric substance (EPS) is important for the survival of biofilms. However, EPS production is costly for bacteria and the bacterial strains that produce EPS (EPS+) grow in the same environment as non-producers (EPS-) leading to competition between these strains for nutrients and space. The outcome of this competition is likely to be dependent on factors such as initial attachment, EPS production rate, ambient nutrient levels and quorum sensing. We use an Individual-based Model (IbM) to study the competition between EPS+ and EPS- strains by varying the nature of initial colonizers which can either be in the form of single cells or multicellular aggregates. The microbes with EPS+ characteristics obtain a competitive advantage if they initially colonize the surface as smaller aggregates and are widely spread-out between the cells of EPS-, when both are deposited on the substratum. Furthermore, the results show that quorum sensing-regulated EPS production may significantly reduce the fitness of EPS producers when they initially deposit as aggregates. The results provide insights into how the distribution of bacterial aggregates during initial colonization could be a deciding factor in the competition among different strains in biofilms.

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

PubMed Central

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

2012-01-01

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

Nematode Damage Functions: The Problems of Experimental and Sampling Error

PubMed Central

Ferris, H.

1984-01-01

The development and use of pest damage functions involves measurement and experimental errors associated with cultural, environmental, and distributional factors. Damage predictions are more valuable if considered with associated probability. Collapsing population densities into a geometric series of population classes allows a pseudo-replication removal of experimental and sampling error in damage function development. Recognition of the nature of sampling error for aggregated populations allows assessment of probability associated with the population estimate. The product of the probabilities incorporated in the damage function and in the population estimate provides a basis for risk analysis of the yield loss prediction and the ensuing management decision. PMID:19295865

Meloxicam, 15 mg/day, spares platelet function in healthy volunteers.

PubMed

de Meijer, A; Vollaard, H; de Metz, M; Verbruggen, B; Thomas, C; Novakova, I

1999-10-01

To study the influence of meloxicam, a cyclooxygenase-2 (COX-2) preferential nonsteroidal anti-inflammatory drug, on serum thromboxane and platelet function in healthy volunteers with use of the maximum recommended daily dosage of 15 mg/day. This study used an open, randomized crossover design. Indomethacin (INN, indometacin) was given as a positive control for nonsteroidal anti-inflammatory drug-induced inhibition of platelet function. The following variables were recorded: thromboxane B2 serum concentrations by radioimmunoassay, platelet aggregation by whole blood aggregometry in response to collagen 1.1 microg/L and to arachidonic acid 0.35 mmol/L, and closure time with use of the PFA-100. Serum thromboxane B2 at baseline was 535+/-233 nmol/L (mean +/- SD) and was reduced for 95% by indomethacin to 26+/-19 nmol/L (P < .001) and for 66% by meloxicam to 183+/-62 nmol/L (P < .001). Maximal platelet aggregation in response to collagen at baseline was 18.7+/-1.6 ohms (ohms). It was reduced by indomethacin to 7.3+/-4.5 ohms (P < .001), but not by meloxicam (19+/-2.5 ohms). Platelet aggregation in response to arachidonic acid at baseline was 12.2+/-2.0 ohms. It was reduced by indomethacin in all subjects to 0 ohms, but not by meloxicam (11+/-2.4 ohms). Closure time at baseline was 128+/-24 seconds and was prolonged by indomethacin to 286+/-38 seconds (P < .001). Meloxicam caused a minor prolongation of the closure time (141+/-32 seconds; P < .05). Meloxicam, 15 mg/day caused a major reduction of maximum thromboxane production but no reduction in collagen- or arachidonic acid-induced platelet aggregation and only minor increase of the closure time.

Microhabitat Effects on N2O Emissions from Floodplain Soils under Controlled Conditions

NASA Astrophysics Data System (ADS)

Ley, Martin; Lehmann, Moritz; Niklaus, Pascal; Frey, Beat; Kuhn, Thomas; Luster, Jörg

2015-04-01

Semi-terrestrial soils such as floodplain soils are considered to be potential hotspots of nitrous oxide (N2O) emissions. The quantitative assessment of N2O release from these hot spots under field conditions, and of the microbial pathways that underlie net N2O production (ammonium oxidation, nitrifier-denitrification, and denitrification) is challenging in the environment because of the high spatial and temporal variability. The production and consumption of N2O appears to be linked to the presence or absence of micro-niches, providing specific conditions that may be favorable to either of the microbial pathways that produce or consume N2O. The availability of oxygen, reactive organic carbon, and dissolved nitrogen substrates likely play key roles with regards to the net production of N2O. Previous field studies demonstrated, for example, that flooding can trigger "hot moments" of enhanced N2O emission through a close coupling of niches with high and low oxygen availabilities. Such microhabitat effects likely depend on soil aggregate formation, plant soil interactions in the rhizosphere and the degradation of organic matter accumulations. In order to assess how these factors can modulate N2O production and consumption under simulated flooding/drying conditions, we have set up a mesocosm experiment with model soils comprising various mixtures of N-rich floodplain soil aggregates (4000 - 250 µm representing large aggregates, or <250 µm representing small aggregates) and inert matrix material (glass beads of 150 - 250 µm size, or quartz sand of 2000 - 3200 µm size, respectively). Soils containing the different aggregate size groups were either planted with willow (Salix viminalis L.), mixed with leaf litter or left untreated. At several time points before, during and after a simulated flood event, we measure the net efflux rate of N2O. In addition, soil water content, redox potential as well as carbon and nitrogen substrate availability are monitored. In order to gain insight into the sources of, and biogeochemical controls on N2O production, we will measure the bulk isotopic signature of the produced N2O as well as its intramolecular 15N site preference. Changes in soil microbial communities, potentially controlling the balance between N2O production and consumption under different microhabitat conditions will be assessed using high-throughput DNA sequencing and q-PCR of key functional genes. Our study helps to increase our limited understanding of how microhabitats affect the occurrence of high N2O emissions from floodplain soils.

Innovative Equipment and Production Method for Mixed Fodder in the Conditions of Agricultural Enterprises

NASA Astrophysics Data System (ADS)

Sabiev, U. K.; Demchuk, E. V.; Myalo, V. V.; Soyunov, A. S.

2017-07-01

It is recommended to feed the cattle and poultry with grain fodder in the form of feed mixture balanced according to the content. Feeding of grain fodder in the form of stock feed is inefficient and economically unreasonable. The article is devoted to actual problem - the preparation of mixed fodder in the conditions of agricultural enterprises. Review and critical analyses of mixed fodder assemblies and aggregates are given. Structural and technical schemes of small-size mixed fodder aggregate with intensified attachments of vibrating and percussive action for preparation of bulk feed mixture in the conditions of agricultural enterprises were developed. The mixed fodder aggregate for its preparation in the places of direct consumption from own grain fodder production and purchased protein and vitamin supplements is also suggested. Mixed fodder aggregate allows to get prepared mixed fodder of high uniformity at low cost of energy and price of production that is becoming profitable for livestock breeding. Model line-up of suggested mixed fodder aggregate with different productivity both for small and big agricultural enterprises is considered.

Lipopolysaccharide treatment reduces rat platelet aggregation independent of intracellular reactive-oxygen species generation.

PubMed

Lopes-Pires, M Elisa; Casarin, André L; Pereira-Cunha, Fernanda G; Lorand-Metze, Irene; Antunes, Edson; Marcondes, Sisi

2012-01-01

High production of reactive-oxygen species (ROS) by blood cells is involved in damage of the vascular endothelium and multiple organ dysfunction in sepsis. However, little is known about the intraplatelet ROS production in sepsis and its consequences on platelet reactivity. In this study, we evaluated whether the treatment of rats with lipopolysaccharide (LPS) affects platelet aggregation through intraplatelet ROS generation. Rats were injected with LPS (1 mg/kg, i.p.), and at 2 to 72 h thereafter, adenosine diphosphate (ADP) (3-10 µM) induced platelet aggregation was evaluated. Production of ROS in platelets was measured by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA). Treatment of rats with LPS time-dependently inhibited ADP-induced platelet aggregation within 72 h. The inhibitory effect of LPS on platelet aggregation was further increased when the platelets were incubated with polyethylene glycol-superoxide dismutase (PEG-SOD; 30 U/mL), polyethylene glycol-catalase (PEG-CAT; 1000 U/mL) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI; 10 µM). The ROS production in non-stimulated platelets did not differ between control and LPS-treated rats. However, in ADP-activated platelets, generation of ROS was increased by 3.0- and 7.0-fold, as evaluated at 8 and 48 h after LPS injection, respectively. This increased ROS production was significantly reduced when platelets were incubated in vitro with DPI, PEG-SOD or PEG-CAT. In contrast, treatment of rats with N-acetylcysteine (150 mg/kg, i.p.) significantly reduced the inhibitory effect of LPS on platelet aggregation, and prevented the increased ROS production by in vivo LPS. Our results indicate that the increased intraplatelet ROS production does not contribute to the inhibitory effect of LPS on platelet aggregation; however, the maintenance of redox balance in LPS-treated rats is fundamental to restore the normal platelet response in these animals.

Aggregating Political Dimensions: Of the Feasibility of Political Indicators

ERIC Educational Resources Information Center

Sanin, Francisco Gutierrez; Buitrago, Diana; Gonzalez, Andrea

2013-01-01

Political indicators are widely used in academic writing and decision making, but remain controversial. This paper discusses the problems related to the aggregation functions they use. Almost always, political indicators are aggregated by weighted averages or summations. The use of such functions is based on untenable assumptions (existence of…

Thermal Aggregation of Calcium-Fortified Skim Milk Enhances Probiotic Protection during Convective Droplet Drying.

PubMed

Wang, Juan; Huang, Song; Fu, Nan; Jeantet, Romain; Chen, Xiao Dong

2016-08-03

Probiotic bacteria have been reported to confer benefits on hosts when delivered in an adequate dose. Spray-drying is expected to produce dried and microencapsulated probiotic products due to its low production cost and high energy efficiency. The bottleneck in probiotic application addresses the thermal and dehydration-related inactivation of bacteria during process. A protective drying matrix was designed by modifying skim milk with the principle of calcium-induced protein thermal aggregation. The well-defined single-droplet drying technique was used to monitor the droplet-particle conversion and the protective effect of this modified Ca-aggregated milk on Lactobacillus rhamnosus GG. The Ca-aggregated milk exhibited a higher drying efficiency and superior protection on L. rhamnosus GG during thermal convective drying. The mechanism was explained by the aggregation in milk, causing the lower binding of water in the serum phase and, conversely, local concentrated milk aggregates involved in bacteria entrapment in the course of drying. This work may open new avenues for the development of probiotic products with high bacterial viability and calcium enrichment.

Correlation of the protein structure and gelling properties in dried egg white products.

PubMed

Handa, A; Hayashi, K; Shidara, H; Kuroda, N

2001-08-01

The relationship between protein structure and aggregation, as well as heat-induced gelling properties, of seven dried egg white (DEW) products was investigated. Strong correlations were found between average molecular weight and hydrophobicity plus surface SH groups of DEW-soluble protein aggregate (SPA). This suggests that hydrophobic interactions and disulfide bond formation between protein molecules were involved in the aggregation. The average molecular weight of DEW products with alkaline pHs was relatively higher than those with neutral pHs and the same degree of protein unfolding, probably because of more disulfide bond formation between protein molecules. In addition, strong correlations were found between hydrophobicity, surface SH groups plus average molecular weight of DEW-SPA, and physical properties of the gels from DEW products. These data indicated that controlling the aggregation of DEW proteins in the dry state is crucial to controlling the gelling properties of DEW.

[Economic determinants of the demand for importation of pharmacochemical and pharmaceutical products].

PubMed

Santos, Anderson Moreira Aristides Dos; Tejada, César Augusto Oviedo; Jacinto, Paulo de Andrade

2017-09-28

: This article analyzes the relationship between the demand for importation of pharmacochemical and pharmaceutical products and economic variables (exchange rate, import prices, and aggregate income) in Brazil, using monthly data from 1997-2014. The main results showed that increases in aggregate income and price reductions in imports have a positive and significant impact (elastic and inelastic, respectively) on imports. Exchange rate was only significant in the more aggregate model. Thus, aggregate income was a robust variable with strong impact on the importation of pharmacochemical and pharmaceutical products. The arguments in the literature that this industry's international trade deficit is related to a deficit in knowledge and technology and the current study's results provide evidence that as economic activity grows, there is a greater demand for this type of product. Additionally, if domestic production is insufficient, there is a need for imports, which can generate pressure on the trade deficit in the industry and contribute to Brazil's dependence on other countries.

How important are dual economy effects for aggregate productivity?

PubMed Central

Vollrath, Dietrich

2013-01-01

This paper brings together development accounting techniques and the dual economy model to address the role that factor markets have in creating variation in aggregate total factor productivity (TFP). Development accounting research has shown that much of the variation in income across countries can be attributed to differences in TFP. The dual economy model suggests that aggregate productivity is depressed by having too many factors allocated to low productivity work in agriculture. Data show large differences in marginal products of similar factors within many developing countries, offering prima facie evidence of this misallocation. Using a simple two-sector decomposition of the economy, this article estimates the role of these misallocations in accounting for the cross-country income distribution. A key contribution is the ability to bring sector-specific data on human and physical capital stocks to the analysis. Variation across countries in the degree of misallocation is shown to account for 30–40% of the variation in income per capita, and up to 80% of the variation in aggregate TFP. PMID:23946553

Locally available aggregate and sediment production

Treesearch

Randy B. Foltz; Mark Truebe

2003-01-01

Selection of suitable locally available materials to build strong and durable roads with aggregate surfaces is desired to minimize road construction and maintenance costs and to minimize the detrimental effects of sedimentation. Eighteen aggregates were selected from local sources in Idaho, Oregon, South Dakota, and Washington State. Aggregate was placed in shallow...

Oil-Price Shocks: Beyond Standard Aggregate Demand/Aggregate Supply Analysis.

ERIC Educational Resources Information Center

Elwood, S. Kirk

2001-01-01

Explores the problems of portraying oil-price shocks using the aggregate demand/aggregate supply model. Presents a simple modification of the model that differentiates between production and absorption of goods, which enables it to better reflect the effects of oil-price shocks on open economies. (RLH)

Gut bacteria mediate aggregation in the German cockroach

PubMed Central

Wada-Katsumata, Ayako; Zurek, Ludek; Nalyanya, Godfrey; Roelofs, Wendell L.; Zhang, Aijun; Schal, Coby

2015-01-01

Aggregation of the German cockroach, Blattella germanica, is regulated by fecal aggregation agents (pheromones), including volatile carboxylic acids (VCAs). We demonstrate that the gut microbial community contributes to production of these semiochemicals. Chemical analysis of the fecal extract of B. germanica revealed 40 VCAs. Feces from axenic cockroaches (no microorganisms in the alimentary tract) lacked 12 major fecal VCAs, and 24 of the remaining compounds were represented at extremely low amounts. Olfactory and aggregation bioassays demonstrated that nymphs strongly preferred the extract of control feces over the fecal extract of axenic cockroaches. Additionally, nymphs preferred a synthetic blend of 6 fecal VCAs over a solvent control or a previously identified VCA blend. To test whether gut bacteria contribute to the production of fecal aggregation agents, fecal aerobic bacteria were cultured, isolated, and identified. Inoculation of axenic cockroaches with individual bacterial taxa significantly rescued the aggregation response to the fecal extract, and inoculation with a mix of six bacterial isolates was more effective than with single isolates. The results indicate that the commensal gut microbiota contributes to production of VCAs that act as fecal aggregation agents and that cockroaches discriminate among the complex odors that emanate from a diverse microbial community. Our results highlight the pivotal role of gut bacteria in mediating insect–insect communication. Moreover, because the gut microbial community reflects the local environment, local plasticity in fecal aggregation pheromones enables colony-specific odors and fidelity to persistent aggregation sites. PMID:26644557

Pumice, pumicite review

USGS Publications Warehouse

Crangle, R.D.

2011-01-01

The article focuses on the industrial mineral pumice. It mentions the estimated production of pumice in the U.S. in 2010, price range, and total U.S. exports and imports. Described as an igneous volcanic rock, pumice has low density which allows it float on water and porous enough to be used as building aggregate. Pumice may also function as an absorbent material, a filter aid, and a polishing agent among others.

Biodiversity increases functional and compositional resistance, but decreases resilience in phytoplankton communities.

PubMed

Baert, Jan M; De Laender, Frederik; Sabbe, Koen; Janssen, Colin R

2016-12-01

There is now ample evidence that biodiversity stabilizes aggregated ecosystem functions, such as primary production, in changing environments. In primary producer systems, this stabilizing effect is found to be driven by higher functional resistance (i.e., reduced changes in functions by environmental changes) rather than through higher functional resilience (i.e., rapid recovery following environmental changes) in more diverse systems. The stability of aggregated ecosystem functions directly depends on changes in species composition and by consequence their functional contributions to ecosystem functions. Still, it remains only theoretically explored how biodiversity can stabilize ecosystem functions by affecting compositional stability. Here, we demonstrate how biodiversity effects on compositional stability drive biodiversity effects on functional stability in diatom communities. In a microcosm experiment, we exposed 39 communities of five different levels of species richness (1, 2, 4, 6, and 8 species) to three concentrations of a chemical stressor (0, 25, and 250 μg/L atrazine) for four weeks, after which all communities were transferred to atrazine-free medium for three more weeks. Biodiversity simultaneously increased, increasing functional and compositional resistance, but decreased functional and compositional resilience. These results confirm the theoretically proposed link between biodiversity effects on functional and compositional stability in primary producer systems, and provide a mechanistic underpinning for observed biodiversity-stability relationships. Finally, we discuss how higher compositional stability can be expected to become increasingly important in stabilizing ecosystem functions under field conditions when multiple environmental stressors fluctuate simultaneously. © 2016 by the Ecological Society of America.

Intracellular response to process optimization and impact on productivity and product aggregates for a high-titer CHO cell process.

PubMed

Handlogten, Michael W; Lee-O'Brien, Allison; Roy, Gargi; Levitskaya, Sophia V; Venkat, Raghavan; Singh, Shailendra; Ahuja, Sanjeev

2018-01-01

A key goal in process development for antibodies is to increase productivity while maintaining or improving product quality. During process development of an antibody, titers were increased from 4 to 10 g/L while simultaneously decreasing aggregates. Process development involved optimization of media and feed formulations, feed strategy, and process parameters including pH and temperature. To better understand how CHO cells respond to process changes, the changes were implemented in a stepwise manner. The first change was an optimization of the feed formulation, the second was an optimization of the medium, and the third was an optimization of process parameters. Multiple process outputs were evaluated including cell growth, osmolality, lactate production, ammonium concentration, antibody production, and aggregate levels. Additionally, detailed assessment of oxygen uptake, nutrient and amino acid consumption, extracellular and intracellular redox environment, oxidative stress, activation of the unfolded protein response (UPR) pathway, protein disulfide isomerase (PDI) expression, and heavy and light chain mRNA expression provided an in-depth understanding of the cellular response to process changes. The results demonstrate that mRNA expression and UPR activation were unaffected by process changes, and that increased PDI expression and optimized nutrient supplementation are required for higher productivity processes. Furthermore, our findings demonstrate the role of extra- and intracellular redox environment on productivity and antibody aggregation. Processes using the optimized medium, with increased concentrations of redox modifying agents, had the highest overall specific productivity, reduced aggregate levels, and helped cells better withstand the high levels of oxidative stress associated with increased productivity. Specific productivities of different processes positively correlated to average intracellular values of total glutathione. Additionally, processes with the optimized media maintained an oxidizing intracellular environment, important for correct disulfide bond pairing, which likely contributed to reduced aggregate formation. These findings shed important understanding into how cells respond to process changes and can be useful to guide future development efforts to enhance productivity and improve product quality. © 2017 Wiley Periodicals, Inc.

Does bathymetry drive coastal whale shark (Rhincodon typus) aggregations?

PubMed Central

Stewart, Bryce D.; McClean, Colin J.; Hancock, James; Rees, Richard

2018-01-01

Background The whale shark (Rhincodon typus) is known to aggregate in a number of coastal locations globally, however what causes these aggregations to form where they do is largely unknown. This study examines whether bathymetry is an important driver of coastal aggregation locations for R. typus through bathymetry’s effect on primary productivity and prey availability. This is a global study taking into account all coastal areas within R. typus’ range. Methods R. typus aggregation locations were identified through an extensive literature review. Global bathymetric data were compared at R. typus aggregation locations and a large random selection of non-aggregation areas. Generalised linear models were used to assess which bathymetric characteristic had the biggest influence on aggregation presence. Results Aggregation sites were significantly shallower than non-aggregation sites and in closer proximity to deep water (the mesopelagic zone) by two orders of magnitude. Slope at aggregation sites was significantly steeper than non-aggregation sites. These three bathymetric variables were shown to have the biggest association with aggregation sites, with up to 88% of deviation explained by the GLMs. Discussion The three key bathymetric characteristics similar at the aggregation sites are known to induce upwelling events, increase primary productivity and consequently attract numerous other filter feeding species. The location of aggregation sites in these key areas can be attributed to this increased prey availability, thought to be the main reason R. typus aggregations occur, extensively outlined in the literature. The proximity of aggregations to shallow areas such as reefs could also be an important factor why whale sharks thermoregulate after deep dives to feed. These findings increase our understanding of whale shark behaviour and may help guide the identification and conservation of further aggregation sites.

77 FR 59980 - Established Aggregate Production Quotas for Schedule I and II Controlled Substances and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... certain established aggregate production quotas will mitigate adverse public effects if an unforeseen... Cocaine 240,000 g Codeine (for conversion) 81,250,000 g Codeine (for sale) 49,506,250 g Dextropropoxyphene...

A novel heuristic for optimization aggregate production problem: Evidence from flat panel display in Malaysia

NASA Astrophysics Data System (ADS)

Al-Kuhali, K.; Hussain M., I.; Zain Z., M.; Mullenix, P.

2015-05-01

Aim: This paper contribute to the flat panel display industry it terms of aggregate production planning. Methodology: For the minimization cost of total production of LCD manufacturing, a linear programming was applied. The decision variables are general production costs, additional cost incurred for overtime production, additional cost incurred for subcontracting, inventory carrying cost, backorder costs and adjustments for changes incurred within labour levels. Model has been developed considering a manufacturer having several product types, which the maximum types are N, along a total time period of T. Results: Industrial case study based on Malaysia is presented to test and to validate the developed linear programming model for aggregate production planning. Conclusion: The model development is fit under stable environment conditions. Overall it can be recommended to adapt the proven linear programming model to production planning of Malaysian flat panel display industry.

Applied Technology on Influence of Humic Substances on Fertilizer, Water-use Efficiency and Soil Health

NASA Astrophysics Data System (ADS)

Seyedbagheri, Mir

2017-04-01

In continuation of over 35 years of on-farm studies on soil organic matter from different humates (functional carbon) and compost, I have documented quantitative improvements in soil health and water-use efficiency. The ability of soil organic matter to bind water has become an important theme for research in past years. Research trials were established to evaluate the efficacy of different commercial functional carbon products derived from Leonardite (highly oxidized lignite) in crop production. In each of these trials, functional carbon (Humic and Fulvic acids) products were used in a randomized complete block design. The use of humic substances creates strong organo-mineral complexes (aggregation), chelation, as well as enhanced buffering capacities. We evaluated data from 3 fields and compared the results. Our observation and field demonstrations indicated there was a marked increase in water retention. Data from humic acid (HA) trials showed that different cropping systems responded differently to different products in relation to yield and quality. The functional carbon products used in the study seemed to enhance fertilizer and water-use efficiency by increasing complexation, chelation and buffering. The consistent use of good quality functional carbons in our replicated plots resulted in a yield increase from 6% to 30% over several decades.

Market penetration of biodiesel and ethanol

NASA Astrophysics Data System (ADS)

Szulczyk, Kenneth Ray

This dissertation examines the influence that economic and technological factors have on the penetration of biodiesel and ethanol into the transportation fuels market. This dissertation focuses on four aspects. The first involves the influence of fossil fuel prices, because biofuels are substitutes and have to compete in price. The second involves biofuel manufacturing technology, principally the feedstock-to-biofuel conversion rates, and the biofuel manufacturing costs. The third involves prices for greenhouse gas offsets. The fourth involves the agricultural commodity markets for feedstocks, and biofuel byproducts. This dissertation uses the Forest and Agricultural Sector Optimization Model-Greenhouse Gas (FASOM-GHG) to quantitatively examine these issues and calculates equilibrium prices and quantities, given market interactions, fossil fuel prices, carbon dioxide equivalent prices, government biofuel subsidies, technological improvement, and crop yield gains. The results indicate that for the ranges studied, gasoline prices have a major impact on aggregate ethanol production but only at low prices. At higher prices, one runs into a capacity constraint that limits expansion on the capacity of ethanol production. Aggregate biodiesel production is highly responsive to gasoline prices and increases over time. (Diesel fuel price is proportional to the gasoline price). Carbon dioxide equivalent prices expand the biodiesel industry, but have no impact on ethanol aggregate production when gasoline prices are high again because of refinery capacity expansion. Improvement of crop yields shows a similar pattern, expanding ethanol production when the gasoline price is low and expanding biodiesel. Technological improvement, where biorefinery production costs decrease over time, had minimal impact on aggregate ethanol and biodiesel production. Finally, U.S. government subsidies have a large expansionary impact on aggregate biodiesel production. Finally, U.S. government subsidies have a large expansionary impact on aggregate biodiesel production, but only expand the ethanol industry at low gasoline prices. All of these factors increase agricultural welfare with most expanding producer surplus and mixed effects on consumers.

Accelerated stability studies for moisture-induced aggregation of tetanus toxoid.

PubMed

Jain, Nishant Kumar; Roy, Ipsita

2011-03-01

The study was carried out to evaluate the effect of exposing solid tetanus toxoid to moisture in two different ways on the structure and function of the toxoid. Tetanus toxoid was exposed to moisture by (i) the addition of an optimized amount of buffer and (ii) incubation under an environment provided by a saturated solution of K(2)CrO(4.) The changes in the conformational, structural and antigenic properties of tetanus toxoid were measured and compared. Results show that even at a similar level of moisture-induced aggregation, the amounts of water absorbed by the two preparations of tetanus toxoid are different. Differences in antigenicity and changes in structure of the toxoid at primary, secondary and tertiary structure levels were seen. Although both conditions are used to mimic accelerated stability conditions in the laboratory, the final products are different in the two cases. Thus, conditions for 'accelerated stability studies' for therapeutic proteins need to be selected with care so that they resemble the fate of the actual product.

High individual variation in pheromone production by tree-killing bark beetles (Coleoptera: Curculionidae: Scolytinae)

NASA Astrophysics Data System (ADS)

Pureswaran, Deepa S.; Sullivan, Brian T.; Ayres, Matthew P.

2008-01-01

Aggregation via pheromone signalling is essential for tree-killing bark beetles to overcome tree defenses and reproduce within hosts. Pheromone production is a trait that is linked to fitness, so high individual variation is paradoxical. One explanation is that the technique of measuring static pheromone pools overestimates true variation among individuals. An alternative hypothesis is that aggregation behaviour dilutes the contribution of individuals to the trait under selection and reduces the efficacy of natural selection on pheromone production by individuals. We compared pheromone measurements from traditional hindgut extractions of female southern pine beetles with those obtained by aerating individuals till they died. Aerations showed greater total pheromone production than hindgut extractions, but coefficients of variation (CV) remained high (60-182%) regardless of collection technique. This leaves the puzzle of high variation unresolved. A novel but simple explanation emerges from considering bark beetle aggregation behaviour. The phenotype visible to natural selection is the collective pheromone plume from hundreds of colonisers. The influence of a single beetle on this plume is enhanced by high variation among individuals but constrained by large group sizes. We estimated the average contribution of an individual to the pheromone plume across a range of aggregation sizes and showed that large aggregation sizes typical in mass attacks limit the potential of natural selection because each individual has so little effect on the overall plume. Genetic variation in pheromone production could accumulate via mutation and recombination, despite strong effects of the pheromone plume on the fitness of individuals within the aggregation. Thus, aggregation behaviour, by limiting the efficacy of natural selection, can allow the persistence of extreme phenotypes in nature.

The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease.

PubMed

Benskey, Matthew J; Perez, Ruth G; Manfredsson, Fredric P

2016-05-01

The aggregation of alpha synuclein (α-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α-syn gene result in familial PD. The high correlation between α-syn burden and PD has led to the hypothesis that α-syn aggregation produces toxicity through a gain-of-function mechanism. However, α-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α-syn results in toxicity because of a toxic loss of necessary α-syn function, following sequestration of functional forms α-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α-syn to PD and the knowledge gained from current α-syn-based animal models of PD. We will then interpret these data from the viewpoint of the α-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of α-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between α-synuclein burden and Parkinson's disease pathology has led to the hypothesis that α-synuclein aggregation produces toxicity through a gain-of-function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α-synuclein results in toxicity because of loss of necessary α-synuclein function at the presynaptic terminal, following sequestration of functional forms of α-synuclein into aggregates. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Familial aggregation analysis of gene expressions

PubMed Central

Rao, Shao-Qi; Xu, Liang-De; Zhang, Guang-Mei; Li, Xia; Li, Lin; Shen, Gong-Qing; Jiang, Yang; Yang, Yue-Ying; Gong, Bin-Sheng; Jiang, Wei; Zhang, Fan; Xiao, Yun; Wang, Qing K

2007-01-01

Traditional studies of familial aggregation are aimed at defining the genetic (and non-genetic) causes of a disease from physiological or clinical traits. However, there has been little attempt to use genome-wide gene expressions, the direct phenotypic measures of genes, as the traits to investigate several extended issues regarding the distributions of familially aggregated genes on chromosomes or in functions. In this study we conducted a genome-wide familial aggregation analysis by using the in vitro cell gene expressions of 3300 human autosome genes (Problem 1 data provided to Genetic Analysis Workshop 15) in order to answer three basic genetics questions. First, we investigated how gene expressions aggregate among different types (degrees) of relative pairs. Second, we conducted a bioinformatics analysis of highly familially aggregated genes to see how they are distributed on chromosomes. Third, we performed a gene ontology enrichment test of familially aggregated genes to find evidence to support their functional consensus. The results indicated that 1) gene expressions did aggregate in families, especially between sibs. Of 3300 human genes analyzed, there were a total of 1105 genes with one or more significant (empirical p < 0.05) familial correlation; 2) there were several genomic hot spots where highly familially aggregated genes (e.g., the chromosome 6 HLA genes cluster) were clustered; 3) as we expected, gene ontology enrichment tests revealed that the 1105 genes were aggregating not only in families but also in functional categories. PMID:18466548

Aggregation of a Monoclonal Antibody Induced by Adsorption to Stainless Steel

PubMed Central

Bee, Jared S.; Davis, Michele; Freund, Erwin; Carpenter, John F.; Randolph, Theodore W.

2014-01-01

Stainless steel is a ubiquitous surface in therapeutic protein production equipment and is also present as the needle in some pre-filled syringe biopharmaceutical products. Stainless steel microparticles can cause of aggregation of a monoclonal antibody (mAb). The initial rate of mAb aggregation was second-order in steel surface area and zero-order in mAb concentration, generally consistent with a bimolecular surface aggregation being the rate-limiting step. Polysorbate 20 (PS20) suppressed the aggregation yet was unable to desorb the firmly bound first layer of protein that adsorbs to the stainless steel surface. Also, there was no exchange of mAb from the first adsorbed layer to the bulk phase, suggesting that the aggregation process actually occurs on subsequent adsorption layers. No oxidized Met residues were detected in the mass spectrum of a digest of a highly aggregated mAb, although there was five-fold increase in carbonyl groups due to protein oxidation. PMID:19725039

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Natural product-based amyloid inhibitors.

PubMed

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R; Xu, Bin

2017-09-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural product-based amyloid inhibitors

PubMed Central

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R.; Xu, Bin

2018-01-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. PMID:28390938

76 FR 77016 - Controlled Substances: Final Adjusted Aggregate Production Quotas for 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... substances previously referenced, expressed in grams of anhydrous acid or base, as follows: Final adjusted...), diphenoxylate, fentanyl, gamma hydroxybutyric acid, hydrocodone, meperidine, methadone, methadone [[Page 77017... 2011 aggregate production quotas for alfentanil, diphenoxylate, gamma hydroxybutyric acid, meperidine...

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

NASA Astrophysics Data System (ADS)

Bilim, Niyazi; Çelik, Arif; Kekeç, Bilgehan

2017-10-01

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

Projections of Demand for Waterborne Transportation, Ohio River Basin, 1980, 1990, 2000, 2020, 2040. Volume 6. Group IV. Aggregates.

DTIC Science & Technology

1980-12-01

moved piece by piece rather than by conveyor belt. B-2. Institutional Factors Production of aggregates is highly centralized and vertically integrated ... Marketing of the product is most often done by the producers. Much production is used by the producers themselves; for example, as input into ready

77 FR 46519 - Proposed Aggregate Production Quotas for Schedule I and II Controlled Substances and Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

... Production Quotas for Schedule I and II Controlled Substances and Proposed Assessment of Annual Needs for the... the Controlled Substances Act (CSA) and assessment of annual needs for the list I chemicals ephedrine... proposed 2013 aggregate production quotas and assessment of annual needs, DEA has taken into account the...

Development of long-term primary cell aggregates from Mediterranean octocorals.

PubMed

Huete-Stauffer, Carla; Valisano, Laura; Gaino, Elda; Vezzulli, Luigi; Cerrano, Carlo

2015-09-01

In lower metazoans, the aggregative properties of dissociated cells leading to in vitro stable multicellular aggregates have furnished a remarkable experimental material to carry out investigations in various research fields. One of the main expectations is to find good models for the study in vitro of the first steps of biomineralization processes. In this study, we examined five common Mediterranean gorgonians (Paramuricea clavata, Corallium rubrum, Eunicella singularis, Eunicella cavolinii, and Eunicella verrucosa) using mechanical cell aggregate production techniques. In particular, we investigated the conditions of aggregate formation, their number and survival in experimental conditions, the DNA synthesizing activity using 5'-bromo-2'-deoxyuridine (BrdU) tests, and the response to calcein addition and observed the secretion of newly formed sclerites. The BrdU tests showed that cell proliferation depends on the size of aggregates and on the presence/absence of symbiotic zooxanthellae. With epifluorescent and confocal imaging from calcein addition assays, we observed the presence of calcium ions within cells, a possible clue for prediction of sclerite formation or calcium deposition. The species-specific efficiency in production of cell aggregates is correlated to the size of polyps, showing that the higher density of polyps and their diameter correspond to higher production of cell aggregates. Regarding the long-term maintenance, we obtained the best results from E. singularis, which formed multicellular aggregates of 0.245 mm ± 0.086 mm in size and maintained symbiotic association with zooxanthellae throughout the experimental run. Formation of sclerites within aggregates opens a wide field of investigation on biomineralization, since de novo sclerites were observed around 30 d after the beginning of the experiment.

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

Binukumar, BK; Gupta, Nidhi; Bal, Amanjit

Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q{sub 10} (CoQ{sub 10}) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, {alpha}-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg bodymore » weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, {alpha}-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q{sub 10} (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q{sub 10} administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, {alpha}-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: > CoQ{sub 10} administration attenuates dichlorvos induced nigrostriatal neurodegenaration. > CoQ{sub 10} pre treatment leads to preservation of TH-IR neurons. > CoQ{sub 10} may decrease oxidative damage and {alpha}-synuclin aggregation. > CoQ{sub 10} treatment enhances motor function and protects rats from catalepsy.« less

Spatial and Temporal Uncertainty of Crop Yield Aggregations

NASA Technical Reports Server (NTRS)

Porwollik, Vera; Mueller, Christoph; Elliott, Joshua; Chryssanthacopoulos, James; Iizumi, Toshichika; Ray, Deepak K.; Ruane, Alex C.; Arneth, Almut; Balkovic, Juraj; Ciais, Philippe;

Dynamics of transparent exopolymer particle (TEP) production and aggregation during viral infection of the coccolithophore, Emiliania huxleyi.

PubMed

Nissimov, Jozef I; Vandzura, Rebecca; Johns, Christopher T; Natale, Frank; Haramaty, Liti; Bidle, Kay D

2018-06-19

Emiliania huxleyi produces calcium carbonate (CaCO 3 ) coccoliths and transparent exopolymer particles (TEP), sticky, acidic carbohydrates that facilitate aggregation. E. huxleyi's extensive oceanic blooms are often terminated by coccolithoviruses (EhVs) with the transport of cellular debris and associated particulate organic carbon (POC) to depth being facilitated by TEP-bound "marine snow" aggregates. The dynamics of TEP production and particle aggregation in response to EhV infection are poorly understood. Using flow cytometry, spectrophotometry, and FlowCam visualization of alcian blue (AB)-stained aggregates, we assessed TEP production and the size spectrum of aggregates for E. huxleyi possessing different degrees of calcification and cellular CaCO 3 :POC mass ratios, when challenged with two EhVs (EhV207 and EhV99B1). FlowCam imaging also qualitatively assessed the relative amount of AB-stainable TEP (i.e. blue:red ratio of each particle). We show significant increases in TEP during early phase EhV207-infection (∼24 hours) of calcifying strains and a shift towards large aggregates following EhV99B1-infection. We also observed the formation of large aggregates with low blue:red ratios, suggesting that other exopolymer substances contribute towards aggregation. Our findings show the potential for virus infection and the associated response of their hosts to impact carbon flux dynamics and provide incentive to explore these dynamics in natural populations. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

78 FR 37237 - Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... reserve in certain established aggregate production quotas will mitigate adverse public effects if an...,000 g 47,186,000 g. Carfentanil 6 g No change. Cocaine 240,000 g No change. Codeine (for conversion...

Effect of carbon sources on the aggregation of photo fermentative bacteria induced by L-cysteine for enhancing hydrogen production.

PubMed

Xie, Guo-Jun; Liu, Bing-Feng; Ding, Jie; Wang, Qilin; Ma, Chao; Zhou, Xu; Ren, Nan-Qi

2016-12-01

Poor flocculation of photo fermentative bacteria resulting in continuous biomass washout from photobioreactor is a critical challenge to achieve rapid and stable hydrogen production. In this work, the aggregation of Rhodopseudomonas faecalis RLD-53 was successfully developed in a photobioreactor and the effects of different carbon sources on hydrogen production and aggregation ability were investigated. Extracellular polymeric substances (EPS) production by R. faecalis RLD-53 cultivated using different carbon sources were stimulated by addition of L-cysteine. The absolute ζ potentials of R. faecalis RLD-53 were considerably decreased with addition of L-cysteine, and aggregation barriers based on DLVO dropped to 15-43 % of that in control groups. Thus, R. faecalis RLD-53 flocculated effectively, and aggregation abilities of strain RLD-53 cultivated with acetate, propionate, lactate and malate reached 29.35, 32.34, 26.07 and 24.86 %, respectively. In the continuous test, hydrogen-producing activity was also promoted and reached 2.45 mol H 2 /mol lactate, 3.87 mol H 2 /mol propionate and 5.10 mol H 2 /mol malate, respectively. Therefore, the aggregation of R. faecalis RLD-53 induced by L-cysteine is independent on the substrate types, which ensures the wide application of this technology to enhance hydrogen recovery from wastewater dominated by different organic substrates.

Aggregation of the rhizospheric bacterium Azospirillum brasilense in response to oxygen

NASA Astrophysics Data System (ADS)

Abdoun, Hamid; McMillan, Mary; Pereg, Lily

2016-04-01

Azospirillum brasilense spp. have ecological, scientific and agricultural importance. As model plant growth promoting rhizobacteria they interact with a large variety of plants, including important food and cash crops. Azospirillum strains are known for their production of plant growth hormones that enhance root systems and for their ability to fix nitrogen. Azospirillum cells transform in response to environmental cues. The production of exopolysaccharides and cell aggregation during cellular transformation are important steps in the attachment of Azospirillum to roots. We investigate signals that induce cellular transformation and aggregation in the Azospirillum and report on the importance of oxygen to the process of aggregation in this rhizospheric bacterium.

Yeasts from autochthonal cheese starters: technological and functional properties.

PubMed

Binetti, A; Carrasco, M; Reinheimer, J; Suárez, V

2013-08-01

The aim of this work was to identify 20 yeasts isolated from autochthonal cheese starters and evaluate their technological and functional properties. The capacities of the yeasts to grow at different temperatures, pH, NaCl and lactic acid concentrations as well as the proteolytic and lipolytic activities were studied. Moreover, survival to simulated gastrointestinal digestion, hydrophobicity, antimicrobial activity against pathogens and auto- and co-aggregation abilities were evaluated. The sequentiation of a fragment from the 26S rDNA gene indicated that Kluyveromyces marxianus was the predominant species, followed by Saccharomyces cerevisiae, Clavispora lusitaniae, Kluyveromyces lactis and Galactomyces geotrichum. RAPD with primer M13 allowed a good differentiation among strains from the same species. All strains normally grew at pH 4.7-5.5 and temperatures between 15 and 35°C. Most of them tolerated 10% NaCl and 3% lactic acid. Some strains showed proteolytic (eight isolates) and/or lipolytic (four isolates) capacities. All strains evidenced high gastrointestinal resistance, moderate hydrophobicity, intermediate auto-aggregation and variable co-aggregation abilities. No strains inhibited the growth of the pathogens assayed. Some strains from dairy sources showed interesting functional and technological properties. This study has been the first contribution to the identification and characterization of yeasts isolated from autochthonal cheese starters in Argentina. Many strains could be proposed as potential candidates to be used as probiotics and/or as co-starters in cheese productions. © 2013 The Society for Applied Microbiology.

Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research.

PubMed

George, Mitchell J; Bynum, James; Nair, Prajeeda; Cap, Andrew P; Wade, Charles E; Cox, Charles S; Gill, Brijesh S

2018-07-01

The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction. Platelet function devices like thromboelastography, thromboelastometry, and aggregometry measure these biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the activity of antiplatelet drugs alters measures of platelet function. However, the specific mechanisms governing these alterations in platelet function and how they relate to platelet bioenergetics are still under investigation.

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

PubMed Central

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

2010-01-01

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

Cold rescue of the thermolabile tailspike intermediate at the junction between productive folding and off-pathway aggregation.

PubMed Central

Betts, S. D.; King, J.

1998-01-01

Off-pathway intermolecular interactions between partially folded polypeptide chains often compete with correct intramolecular interactions, resulting in self-association of folding intermediates into the inclusion body state. Intermediates for both productive folding and off-pathway aggregation of the parallel beta-coil tailspike trimer of phage P22 have been identified in vivo and in vitro using native gel electrophoresis in the cold. Aggregation of folding intermediates was suppressed when refolding was initiated and allowed to proceed for a short period at 0 degrees C prior to warming to 20 degrees C. Yields of refolded tailspike trimers exceeding 80% were obtained using this temperature-shift procedure, first described by Xie and Wetlaufer (1996, Protein Sci 5:517-523). We interpret this as due to stabilization of the thermolabile monomeric intermediate at the junction between productive folding and off-pathway aggregation. Partially folded monomers, a newly identified dimer, and the protrimer folding intermediates were populated in the cold. These species were electrophoretically distinguished from the multimeric intermediates populated on the aggregation pathway. The productive protrimer intermediate is disulfide bonded (Robinson AS, King J, 1997, Nat Struct Biol 4:450-455), while the multimeric aggregation intermediates are not disulfide bonded. The partially folded dimer appears to be a precursor to the disulfide-bonded protrimer. The results support a model in which the junctional partially folded monomeric intermediate acquires resistance to aggregation in the cold by folding further to a conformation that is activated for correct recognition and subunit assembly. PMID:9684883

Example MODIS Global Cloud Optical and Microphysical Properties: Comparisons between Terra and Aqua

NASA Technical Reports Server (NTRS)

Hubanks, P. A.; Platnick, S.; King, M. D.; Ackerman, S. A.; Frey, R. A.

2003-01-01

MODIS observations from the NASA EOS Terra spacecraft (launched in December 1999, 1030 local time equatorial crossing) have provided a unique data set of Earth observations. With the launch of the NASA Aqua spacecraft in May 2002 (1330 local time), two MODIS daytime (sunlit) and nighttime observations are now available in a 24 hour period, allowing for some measure of diurnal variability. We report on an initial analysis of several operational global (Level-3) cloud products from the two platforms. The MODIS atmosphere Level-3 products, which include clear-sky and aerosol products in addition to cloud products, are available as three separate files providing daily, eight-day, and monthly aggregations; each temporal aggregation is spatially aggregated to a 1 degree grid. The files contain approximately 600 statisitical datasets (from simple means and standard deviations to 1 - and 2-dimensional histograms). Operational cloud products include detection (cloud fraction), cloud-top properties, and daytimeonly cloud optical thickness and particle effective radius for both water and ice clouds. We will compare example global Terra and Aqua cloud fraction, optical thickness, and effective radius aggregations.

Use of Air-cooled Blast Furnace Slag as Coarse Aggregate in Concrete Pavements

DOT National Transportation Integrated Search

2012-03-01

This report presents available information regarding the use of air-cooled blast furnace slag (ACBFS) as coarse aggregate in concrete pavements. The report discusses ACBFS aggregate production and properties, and the properties of concrete produced w...

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

PubMed

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

2013-09-01

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

Aggregated Recombinant Human Interferon Beta Induces Antibodies but No Memory in Immune-Tolerant Transgenic Mice

PubMed Central

Sauerborn, Melody; Gilli, Francesca; Brinks, Vera; Schellekens, Huub; Jiskoot, Wim

2010-01-01

ABSTRACT Purpose To study the influence of protein aggregation on the immunogenicity of recombinant human interferon beta (rhIFNβ) in wild-type mice and transgenic, immune-tolerant mice, and to evaluate the induction of immunological memory. Methods RhIFNβ-1b and three rhIFNβ-1a preparations with different aggregate levels were injected intraperitoneally in mice 15× during 3 weeks, and the mice were rechallenged with rhIFNβ-1a. The formation of binding (BABs) and neutralizing antibodies (NABs) was monitored. Results Bulk rhIFNβ-1a contained large, mainly non-covalent aggregates and stressed rhIFNβ-1a mainly covalent, homogeneous (ca. 100 nm) aggregates. Reformulated rhIFNβ-1a was essentially aggregate-free. All products induced BABs and NABs in wild-type mice. Immunogenicity in the transgenic mice was product dependent. RhIFNβ-1b showed the highest and reformulated rhIFNβ-1a the lowest immunogenicity. In contrast with wild-type mice, transgenic mice did not show NABs, nor did they respond to the rechallenge. Conclusions The immunogenicity of the products in transgenic mice, unlike in wild-type mice, varied. In the transgenic mice, neither NABs nor immunological memory developed. The immunogenicity of rhIFNβ in a model reflecting the human immune system depends on the presence and the characteristics of aggregates. PMID:20499141

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-09-10

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

Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice.

PubMed

Li, Zhi-Fang; Wu, Xiaohua; Jiang, Yun; Liu, Jianxiang; Wu, Chun; Inagaki, Masaki; Izawa, Ichiro; Mizisin, Andrew P; Engvall, Eva; Shelton, G Diane

2008-01-15

Protein aggregate formation in muscle is thought to be pathogenic and associated with clinical weakness. Over-expression of either wild type or a mutant form of myeloid leukemia factor 1 (MLF1) in transgenic mouse skeletal muscle and in cultured cells resulted in aggregate formation. Aggregates were detected in MLF1 transgenic mice at 6 weeks of age, and increased in size with age. However, histological examination of skeletal muscles of MLF1 transgenic mice revealed no pathological changes other than the aggregates, and RotaRod testing did not detect functional deficits. MLF1 has recently been identified as a protein that could neutralize the toxicity of intracellular protein aggregates in a Drosophila model of Huntington's disease (HD). We also demonstrate that MLF1 interacts with MRJ, a heat shock protein, which can independently neutralize the toxicity of intracellular protein aggregates in the Drosophila HD model. Our data suggest that over-expression of MLF1 has no significant impact on skeletal muscle function in mice; that progressive formation of protein aggregates in muscle are not necessarily pathogenic; and that MLF1 and MRJ may function together to ameliorate the toxic effects of polyglutamine or mutant proteins in myodegenerative diseases such as inclusion body myositis and oculopharyngeal muscular dystrophy, as well as neurodegenerative disease.

Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy

PubMed Central

Wu, Jichao; Tian, Zhiliang; Sun, Yu; Lu, Cuicui; Liu, Ning; Gao, Zhaopeng; Zhang, Linxue; Dong, Shiyun; Yang, Fan; Zhong, Xin; Xu, Changqing; Lu, Fanghao; Zhang, Weihua

2017-01-01

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H2S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H2S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H2S in the context of T2DCM. PMID:28796243

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

PubMed Central

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

2009-01-01

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

Using new aggregation operators in rule-based intelligent control

NASA Technical Reports Server (NTRS)

Berenji, Hamid R.; Chen, Yung-Yaw; Yager, Ronald R.

1990-01-01

A new aggregation operator is applied in the design of an approximate reasoning-based controller. The ordered weighted averaging (OWA) operator has the property of lying between the And function and the Or function used in previous fuzzy set reasoning systems. It is shown here that, by applying OWA operators, more generalized types of control rules, which may include linguistic quantifiers such as Many and Most, can be developed. The new aggregation operators, as tested in a cart-pole balancing control problem, illustrate improved performance when compared with existing fuzzy control aggregation schemes.

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

PubMed

Ebrahimi, Ali; Or, Dani

2018-01-01

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

A study on the performance of concrete containing recycled aggregates and ceramic as materials replacement

NASA Astrophysics Data System (ADS)

Azmi, N. B.; Khalid, F. S.; Irwan, J. M.; Anting, N.; Mazenan, P. N.

2017-11-01

Natural fine aggregate materials are commonly used in development and commercial construction in Malaysia. In fact, concrete production was increased as linear with the growing Malaysia economy. However, an issue was production of concrete was to locate adequate sources of natural fine aggregates. There lot of studies have been conducted in order to replace the fine aggregate in which natural fine aggregate replace with the waste material in concrete preparation. Therefore, this study aims to utilize the Recycled Concrete Aggregate (RCA) and ceramic waste which has great potential to replace the natural aggregate in concrete mix with different type of method, admixture, and parameters. This research were focused on compressive strength and water absorption test to determine the optimum mix ratio of concrete mix. The concrete aggregate was chosen due to improvement capillary bonding mechanisms and ceramic presented similar strength compared to the conventional concrete using natural aggregate. Percent of replacement have been used in this study was at 25%, 35% and 45% of the RCA and 5%, 10% and 15% for ceramic, respectively. Furthermore, this research was conduct to find the optimum percentage of aggregate replacement, using water-cement ratio of 0.55 with concrete grade 25/30. The best percentage of replacement was the RCA35% C15% with the compressive strength of 34.72 MPa and the water absorption was satisfied.

Sound-Triggered Production of Antiaggregation Pheromone Limits Overcrowding of Dendroctonus valens Attacking Pine Trees.

PubMed

Liu, Zhudong; Xin, Yucui; Xu, Bingbing; Raffa, Kenneth F; Sun, Jianghua

2017-01-01

For insects that aggregate on host plants, both attraction and antiaggregation among conspecifics can be important mechanisms for overcoming host resistance and avoiding overcrowding, respectively. These mechanisms can involve multiple sensory modalities, such as sound and pheromones. We explored how acoustic and chemical signals are integrated by the bark beetle Dendroctonus valens to limit aggregation in China. In its native North American range, this insect conducts nonlethal attacks on weakened trees at very low densities, but in its introduced zone in China, it uses mixtures of host tree compounds and the pheromone component frontalin to mass attack healthy trees. We found that exo-brevicomin was produced by both female and male D. valens, and that this pheromone functioned as an antiaggregating signal. Moreover, beetles feeding in pairs or in masses were more likely than were beetles feeding alone to produce exo-brevicomin, suggesting a potential role of sound by neighboring beetles in stimulating exo-brevicomin production. Sound playback showed that an agreement sound was produced by both sexes when exposed to the aggregation pheromone frontalin and attracts males, and an aggressive sound was produced only by males behaving territorially. These signals triggered the release of exo-brevicomin by both females and males, indicating an interplay of chemical and sonic communication. This study demonstrates that the bark beetle D. valens uses sounds to regulate the production of an antiaggregation pheromone, which may provide new approaches to pest management of this invasive species. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Construction aggregates

USGS Publications Warehouse

Nelson, T.I.; Bolen, W.P.

2007-01-01

Construction aggregates, primarily stone, sand and gravel, are recovered from widespread naturally occurring mineral deposits and processed for use primarily in the construction industry. They are mined, crushed, sorted by size and sold loose or combined with portland cement or asphaltic cement to make concrete products to build roads, houses, buildings, and other structures. Much smaller quantities are used in agriculture, cement manufacture, chemical and metallurgical processes, glass production and many other products.

Microstructure investigation on micropore formation in microporous silica materials prepared via a catalytic sol-gel process by small angle X-ray scattering.

PubMed

Shimizu, Wataru; Hokka, Junsuke; Sato, Takaaki; Usami, Hisanao; Murakami, Yasushi

2011-08-04

The so-called sol-gel technique has been shown to be a template-free, efficient way to create functional porous silica materials having uniform micropores. This appears to be closely linked with a postulation that the formation of weakly branched polymer-like aggregates in a precursor solution is a key to the uniform micropore generation. However, how such a polymer-like structure can precisely be controlled, and further, how the generated low-fractal dimension solution structure is imprinted on the solid silica materials still remain elusive. Here we present fabrication of microporous silica from tetramethyl orthosilicate (TMOS) using a recently developed catalytic sol-gel process based on a nonionic hydroxyacetone (HA) catalyst. Small angle X-ray scattering (SAXS), nitrogen adsorption porosimetry, and transmission electron microscope (TEM) allowed us to observe the whole structural evolution, ranging from polymer-like aggregates in the precursor solution to agglomeration with heat treatment and microporous morphology of silica powders after drying and hydrolysis. Using the HA catalyst with short chain monohydric alcohols (methanol or ethanol) in the precursor solution, polymer-like aggregates having microscopic correlation length (or mesh-size) < 2 nm and low fractal dimensions ∼2, which is identical to that of an ideal coil polymer, can selectively be synthesized, yielding the uniform micropores with diameters <2 nm in the solid materials. In contrast, the absence of HA or substitution of 1-propanol led to considerably different scattering behavior reflecting the particle-like aggregate formation in the precursor solution, which resulted in the formation of mesopores (diameter >2 nm) in the solid product due to apertures between the particle-like aggregates. The data demonstrate that the extremely fine porous silica architecture comes essentially from a gaussian polymer-like nature of the silica aggregates in the precursor having the microscopic mesh-size and their successful imprint on the solid product. The result offers a general but significantly efficient route to creating precisely designed fine porous silica materials under mild condition that serve as low refractive index and efficient thermal insulation materials in their practical applications.

Increased nitric oxide production in platelets from severe chronic renal failure patients.

PubMed

Siqueira, Mariana Alves de Sá; Brunini, Tatiana M C; Pereira, Natália Rodrigues; Martins, Marcela Anjos; Moss, Monique Bandeira; Santos, Sérgio F; Lugon, Jocemir R; Mendes-Ribeiro, Antônio C

2011-02-01

Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of the L-arginine-NO-cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet L-arginine-NO-cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells

PubMed Central

Gonzalez Carter, Daniel A.; Motskin, Michael; Pienaar, Ilse S.; Chen, Shu; Hu, Sheng; Ruenraroengsak, Pakatip; Ryan, Mary P.; Shaffer, Milo S. P.; Dexter, David T.

2016-01-01

Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation may have different bioreactivities and propensities to aggregate in the extracellular environment, and both individualised and aggregated MWNTs may be expected to be found in the brain. Before practical application, it is vital to understand how both aggregates and individual MWNTs will interact with local phagocytic immune cells, the microglia, and ultimately to determine their biopersistence in the brain. The processing of extra- and intracellular MWNTs (both pristine and when acid oxidised) by microglia was characterised across multiple length scales by correlating a range of dynamic, quantitative and multi-scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion beam scanning electron microscopy and transmission electron microscopy. Dynamic, live cell imaging revealed the ability of microglia to break apart and internalise micron-sized extracellular agglomerates of acid oxidised MWNT, but not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound to, microglia was quantified as a function of time. Neither the significant uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected microglial viability, pro-inflammatory cytokine release or nitric oxide production. However, after 24 hrs exposure to pristine MWNTs, a significant increase in the production of reactive oxygen species was observed. Small aggregates and individualised oxidised MWNTs were present in the cytoplasm and vesicles, including within multilaminar bodies, after 72 hours. Some evidence of morphological damage to oxidised MWNT structure was observed including highly disordered graphitic structures, suggesting possible biodegradation. This work demonstrates the utility of dynamic, quantitative and multi-scale techniques in understanding the different cellular processing routes of functionalised nanomaterials. This correlative approach has wide implications for assessing the biopersistence of MWNT aggregates elsewhere in the body, in particular their interaction with macrophages in the lung. PMID:26298523

Decomposition of the fluoroethylene carbonate additive and the glue effect of lithium fluoride products for the solid electrolyte interphase: an ab initio study.

PubMed

Okuno, Yukihiro; Ushirogata, Keisuke; Sodeyama, Keitaro; Tateyama, Yoshitaka

2016-03-28

Additives in the electrolyte solution of lithium-ion batteries (LIBs) have a large impact on the performance of the solid electrolyte interphase (SEI) that forms on the anode and is a key to the stability and durability of LIBs. We theoretically investigated effects of fluoroethylene carbonate (FEC), a representative additive, that has recently attracted considerable attention for the enhancement of cycling stability of silicon electrodes and the improvement of reversibility of sodium-ion batteries. First, we intensively examined the reductive decompositions by ring-opening, hydrogen fluoride (HF) elimination to form a vinylene carbonate (VC) additive and intermolecular chemical reactions of FEC in the ethylene carbonate (EC) electrolyte, by using density functional theory (DFT) based molecular dynamics and the blue-moon ensemble technique for the free energy profile. The results show that the most plausible product of the FEC reductive decomposition is lithium fluoride (LiF), and that the reactivity of FEC to anion radicals is found to be inert compared to the VC additive. We also investigated the effects of the generated LiF on the SEI by using two model systems; (1) LiF molecules distributed in a model aggregate of organic SEI film components (SFCs) and (2) a LiF aggregate interfaced with the SFC aggregate. DFT calculations of the former system show that F atoms form strong bindings with the Li atoms of multiple organic SFC molecules and play as a joint connecting them. In the latter interface system, the LiF aggregate adsorbs the organic SFCs through the F-Li bindings. These results suggest that LiF moieties play the role of glue in the organic SFC within the SEI film. We also examined the interface structure between a LiF aggregate and a lithiated silicon anode, and found that they are strongly bound. This strong binding is likely to be related to the effectiveness of the FEC additive in the electrolyte for the silicon anode.

Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides

NASA Astrophysics Data System (ADS)

Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

2017-01-01

Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.

Nonlinear analysis and dynamic structure in the energy market

NASA Astrophysics Data System (ADS)

Aghababa, Hajar

This research assesses the dynamic structure of the energy sector of the aggregate economy in the context of nonlinear mechanisms. Earlier studies have focused mainly on the price of the energy products when detecting nonlinearities in time series data of the energy market, and there is little mention of the production side of the market. Moreover, there is a lack of exploration about the implication of high dimensionality and time aggregation when analyzing the market's fundamentals. This research will address these gaps by including the quantity side of the market in addition to the price and by systematically incorporating various frequencies for sample sizes in three essays. The goal of this research is to provide an inclusive and exhaustive examination of the dynamics in the energy markets. The first essay begins with the application of statistical techniques, and it incorporates the most well-known univariate tests for nonlinearity with distinct power functions over alternatives and tests different null hypotheses. It utilizes the daily spot price observations on five major products in the energy market. The results suggest that the time series daily spot prices of the energy products are highly nonlinear in their nature. They demonstrate apparent evidence of general nonlinear serial dependence in each individual series, as well as nonlinearity in the first, second, and third moments of the series. The second essay examines the underlying mechanism of crude oil production and identifies the nonlinear structure of the production market by utilizing various monthly time series observations of crude oil production: the U.S. field, Organization of the Petroleum Exporting Countries (OPEC), non-OPEC, and the world production of crude oil. The finding implies that the time series data of the U.S. field, OPEC, and the world production of crude oil exhibit deep nonlinearity in their structure and are generated by nonlinear mechanisms. However, the dynamics of the non-OPEC production time series data does not reveal signs of nonlinearity. The third essay explores nonlinear structure in the case of high dimensionality of the observations, different frequencies of sample sizes, and division of the samples into sub-samples. It systematically examines the robustness of the inference methods at various levels of time aggregation by employing daily spot prices on crude oil for 26 years as well as monthly spot price index on crude oil for 41 years. The daily and monthly samples are divided into sub-samples as well. All the tests detect strong evidence of nonlinear structure in the daily spot price of crude oil; whereas in monthly observations the evidence of nonlinear dependence is less dramatic, indicating that the nonlinear serial dependence will not be as intense when the time aggregation increase in time series observations.

Soft learning vector quantization and clustering algorithms based on ordered weighted aggregation operators.

PubMed

Karayiannis, N B

2000-01-01

This paper presents the development and investigates the properties of ordered weighted learning vector quantization (LVQ) and clustering algorithms. These algorithms are developed by using gradient descent to minimize reformulation functions based on aggregation operators. An axiomatic approach provides conditions for selecting aggregation operators that lead to admissible reformulation functions. Minimization of admissible reformulation functions based on ordered weighted aggregation operators produces a family of soft LVQ and clustering algorithms, which includes fuzzy LVQ and clustering algorithms as special cases. The proposed LVQ and clustering algorithms are used to perform segmentation of magnetic resonance (MR) images of the brain. The diagnostic value of the segmented MR images provides the basis for evaluating a variety of ordered weighted LVQ and clustering algorithms.

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

USGS Publications Warehouse

Wilburn, David R.; Goonan, Thomas G.

1998-01-01

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

Selective serotonin reuptake inhibitors: measurement of effect on platelet function.

PubMed

McCloskey, Donna Jo; Postolache, Teodor T; Vittone, Bernard J; Nghiem, Khanh L; Monsale, Jude L; Wesley, Robert A; Rick, Margaret E

2008-03-01

Selective serotonin reuptake inhibitors (SSRIs) reduce platelet serotonin and are associated with increased gastrointestinal bleeding, an effect that is enhanced when taken with NSAIDs or aspirin. The best method to evaluate hemorrhagic events in patients taking SSRIs has not been determined. Platelet aggregation, which is not widely available, shows SSRI inhibition of platelet function; we tested whether a platelet function analyzer could detect SSRI inhibition of platelet function. Two groups of outpatients with mood disorders were recruited; each patient was taking a stable dose of either an SSRI or bupropion for at least 6 weeks. They were tested using the platelet function analyzer-100 (PFA-100; Dade International Inc, Miami, Fla) concomitantly with platelet aggregation. Fifty-eight patients were analyzed. We detected significant differences between the groups using aggregation methods with arachidonic acid (aggregation, P = 0.00001; release, P = 0.009) and collagen (aggregation, P = 0.016; release, P = 0.006). The PFA-100 did not detect differences between the groups or results outside the reference range. The PFA-100 does not detect the inhibitory effects of SSRIs on platelet function, but it can be used to direct evaluation of bleeding in a patient taking an SSRI. Abnormal PFA-100 results suggest additional evaluation for von Willebrand disease, other platelet inhibitory medications, or underlying intrinsic platelet dysfunction.

Interference between Coulombic and CT-mediated couplings in molecular aggregates: H- to J-aggregate transformation in perylene-based π-stacks

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

Hestand, Nicholas J.; Spano, Frank C.

2015-12-28

The spectroscopic differences between J and H-aggregates are traditionally attributed to the spatial dependence of the Coulombic coupling, as originally proposed by Kasha. However, in tightly packed molecular aggregates wave functions on neighboring molecules overlap, leading to an additional charge transfer (CT) mediated exciton coupling with a vastly different spatial dependence. The latter is governed by the nodal patterns of the molecular LUMOs and HOMOs from which the electron (t{sub e}) and hole (t{sub h}) transfer integrals derive. The sign of the CT-mediated coupling depends on the sign of the product t{sub e}t{sub h} and is therefore highly sensitive tomore » small (sub-Angstrom) transverse displacements or slips. Given that Coulombic and CT-mediated couplings exist simultaneously in tightly packed molecular systems, the interference between the two must be considered when defining J and H-aggregates. Generally, such π-stacked aggregates do not abide by the traditional classification scheme of Kasha: for example, even when the Coulomb coupling is strong the presence of a similarly strong but destructively interfering CT-mediated coupling results in “null-aggregates” which spectroscopically resemble uncoupled molecules. Based on a Frenkel/CT Holstein Hamiltonian that takes into account both sources of electronic coupling as well as intramolecular vibrations, vibronic spectral signatures are developed for integrated Frenkel/CT systems in both the perturbative and resonance regimes. In the perturbative regime, the sign of the lowest exciton band curvature, which rigorously defines J and H-aggregation, is directly tracked by the ratio of the first two vibronic peak intensities. Even in the resonance regime, the vibronic ratio remains a useful tool to evaluate the J or H nature of the system. The theory developed is applied to the reversible H to J-aggregate transformations recently observed in several perylene bisimide systems.« less

Modelling the interaction between flooding events and economic growth

NASA Astrophysics Data System (ADS)

Grames, Johanna; Grass, Dieter; Prskawetz, Alexia; Blöschl, Günther

2015-04-01

Socio-hydrology describes the interaction between the socio-economy, water and population dynamics. Recent models analyze the interplay of community risk-coping culture, flooding damage and economic growth (Di Baldassarre, 2013, Viglione, 2014). These models descriptively explain the feedbacks between socio-economic development and natural disasters like floods. Contrary to these descriptive models, our approach develops an optimization model, where the intertemporal decision of an economic agent interacts with the hydrological system. This is the first economic growth model describing the interaction between the consumption and investment decisions of an economic agent and the occurrence of flooding events: Investments in defense capital can avoid floods even when the water level is high, but on the other hand such investment competes with investment in productive capital and hence may reduce the level of consumption. When floods occur, the flood damage therefore depends on the existing defense capital. The aim is to find an optimal tradeoff between investments in productive versus defense capital such as to optimize the stream of consumption in the long-term. We assume a non-autonomous exogenous periodic rainfall function (Yevjevich et.al. 1990, Zakaria 2001) which implies that the long-term equilibrium will be periodic . With our model we aim to derive mechanisms that allow consumption smoothing in the long term, and at the same time allow for optimal investment in flood defense to maximize economic output. We choose an aggregate welfare function that depends on the consumption level of the society as the objective function. I.e. we assume a social planer with perfect foresight that maximizes the aggregate welfare function. Within our model framework we can also study whether the path and level of defense capital (that protects people from floods) is related to the time preference rate of the social planner. Our model also allows to investigate how the frequency and the intensity of floods influence the investment behavior (i.e. the division between investing in productive versus defense capital).

Computer Modeling of Protocellular Functions: Peptide Insertion in Membranes

NASA Technical Reports Server (NTRS)

Rodriquez-Gomez, D.; Darve, E.; Pohorille, A.

2006-01-01

Lipid vesicles became the precursors to protocells by acquiring the capabilities needed to survive and reproduce. These include transport of ions, nutrients and waste products across cell walls and capture of energy and its conversion into a chemically usable form. In modem organisms these functions are carried out by membrane-bound proteins (about 30% of the genome codes for this kind of proteins). A number of properties of alpha-helical peptides suggest that their associations are excellent candidates for protobiological precursors of proteins. In particular, some simple a-helical peptides can aggregate spontaneously and form functional channels. This process can be described conceptually by a three-step thermodynamic cycle: 1 - folding of helices at the water-membrane interface, 2 - helix insertion into the lipid bilayer and 3 - specific interactions of these helices that result in functional tertiary structures. Although a crucial step, helix insertion has not been adequately studied because of the insolubility and aggregation of hydrophobic peptides. In this work, we use computer simulation methods (Molecular Dynamics) to characterize the energetics of helix insertion and we discuss its importance in an evolutionary context. Specifically, helices could self-assemble only if their interactions were sufficiently strong to compensate the unfavorable Free Energy of insertion of individual helices into membranes, providing a selection mechanism for protobiological evolution.

Subtle Effects of Aliphatic Alcohol Structure on Water Extraction and Solute Aggregation in Biphasic Water/ n -Dodecane

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

Knight, Andrew W.; Qiao, Baofu; Chiarizia, Renato

Organic phase aggregation behavior of 1-octanol and its structural isomer, 2-ethylhexanol, in a biphasic n-dodecane water system is studied with a combination of physical measurement, small-angle X-ray scattering (SAXS), and atomistic molecular dynamic simulations. Physical properties of the organic phases are probed following their mixing and equilibration with immiscible water phases. Studies reveal that the interfacial tension decreases as a function of increasing alcohol concentration over the solubility range of the alcohol with no evidence for a critical aggregate concentration (cac). An uptake of water into the organic phases is quantified, as a function of alcohol content, by Karl Fischermore » titrations. The extraction of water into dodecane was further assessed as a function of alcohol concentration via the slope-analysis method sometimes employed in chemical separations. This provides a qualitative understanding of solute (water/alcohol) aggregation in the organic phase. The physical results are supported by analyses of SAXS data that reveals an emergence of aggregates in n-dodecane at elevated alcohol concentrations. The observed aggregate structure is dependent on the alcohol tail group geometry, consistent with surfactant packing parameter. The formation of these aggregates is discussed at a molecular level, where alcohol-alcohol and alcohol-water H-bonding interactions likely dominate the occurrence and morphology of the aggregates.« less

Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic, personal care and air care products.

PubMed

Safford, B; Api, A M; Barratt, C; Comiskey, D; Ellis, G; McNamara, C; O'Mahony, C; Robison, S; Rose, J; Smith, B; Tozer, S

2017-06-01

As part of a joint project between the Research Institute for Fragrance Materials (RIFM) and Creme Global, a Monte Carlo model (here named the Creme RIFM model) has been developed to estimate consumer exposure to ingredients in personal care products. Details of the model produced in Phase 1 of the project have already been published. Further data on habits and practises have been collected which enable the model to estimate consumer exposure from dermal, oral and inhalation routes for 25 product types. . In addition, more accurate concentration data have been obtained which allow levels of fragrance ingredients in these product types to be modelled. Described is the use of this expanded model to estimate aggregate systemic exposure for eight fragrance ingredients. Results are shown for simulated systemic exposure (expressed as μg/kg bw/day) for each fragrance ingredient in each product type, along with simulated aggregate exposure. Highest fragrance exposure generally occurred from use of body lotions, body sprays and hydroalcoholic products. For the fragrances investigated, aggregate exposure calculated using this model was 11.5-25 fold lower than that calculated using deterministic methodology. The Creme RIFM model offers a very comprehensive and powerful tool for estimating aggregate exposure to fragrance ingredients. Copyright © 2017. Published by Elsevier Inc.

Determination of soluble immunoglobulin G in bovine colostrum products by Protein G affinity chromatography-turbidity correction and method validation.

PubMed

Holland, Patrick T; Cargill, Anne; Selwood, Andrew I; Arnold, Kate; Krammer, Jacqueline L; Pearce, Kevin N

2011-05-25

Immunoglobulin-containing food products and nutraceuticals such as bovine colostrum are of interest to consumers as they may provide health benefits. Commercial scale colostrum products are valued for their immunoglobulin G (IgG) content and therefore require accurate analysis. One of the most commonly used methods for determining total soluble IgG in colostrum products is based on affinity chromatography using a Protein G column and UV detection. This paper documents improvements to the accuracy of the Protein G analysis of IgG in colostrum products, especially those containing aggregated forms of IgG. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis confirmed that aggregated IgG measured by Protein G does not contain significant amounts of casein or other milk proteins. Size exclusion chromatography identified the content of soluble IgG as mainly monomeric IgG and aggregated material MW > 450 kDa with small amounts of dimer and trimer. The turbidity of the eluting IgG, mainly associated with aggregated IgG, had a significant effect on the quantitative results. Practical techniques were developed to correct affinity LC data for turbidity on an accurate, consistent, and efficient basis. The method was validated in two laboratories using a variety of colostrum powders. Precision for IgG was 2-3% (RSD(r)) and 3-12% (RSD(R)). Recovery was 100.2 ± 2.4% (mean ± RSD, n = 10). Greater amounts of aggregated IgG were solubilized by a higher solution:sample ratio and extended times of mixing or sonication, especially for freeze-dried material. It is concluded that the method without acid precipitation and with turbidity correction provides accurate, precise, and robust data for total soluble IgG and is suitable for product specification and quality control of colostrum products.

ACCEPTANCE OF FUNCTIONAL FOOD AMONG CHILEAN CONSUMERS: APPLE LEATHER.

PubMed

van Vliet, Maya; Adasme-Berrios, Cristian; Schnettler, Berta

2015-10-01

the aim of this study is to measure acceptance of a specific functional food: apple (fruit) leather, based on organoleptic characteristics and to identify consumer types and preferences for natural additives which increase the product's functionality and meet current nutritional needs. a sample of 800 consumers provided an evaluation of apple leather in terms of acceptance (liking). A sensorial panel was carried out using a 9-point hedonic scale. Cluster analysis was used to identify different acceptance-based consumer types. In addition, a conjoint analysis was carried out to determine preference for different additives. the cluster analysis resulted in four groups with significant differences in the average likings obtained from the sensory panel. Results indicate that the sweetness of the tested apple leather was evaluated best among all groups and, on average, color was rated as the worst attribute. However, overall likings differ significantly between groups. Results from the conjoint analysis indicate that, in general, consumers prefer natural additives included in the product which enhance functionality. although there is a "global acceptance" of the product, there are significant differences between groups. The results of the conjoint analysis indicate that, in general, consumers prefer the aggregation of natural additives which increase the product's functionality. Apple leather with natural additives, such as anticariogenics and antioxidants, can be considered a functional substitute of unhealthy snacks and/or sweets. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Chen, Zhiming; Feng, Yuncheng

1988-08-01

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

Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase Behavior and Molecular Assembly Landscapes.

PubMed

Wang, Jiang; Gayatri, Mohit A; Ferguson, Andrew L

2017-05-11

Asphaltenes constitute the heaviest fraction of the aromatic group in crude oil. Aggregation and precipitation of asphaltenes during petroleum processing costs the petroleum industry billions of dollars each year due to downtime and production inefficiencies. Asphaltene aggregation proceeds via a hierarchical self-assembly process that is well-described by the Yen-Mullins model. Nevertheless, the microscopic details of the emergent cluster morphologies and their relative stability under different processing conditions remain poorly understood. We perform coarse-grained molecular dynamics simulations of a prototypical asphaltene molecule to establish a phase diagram mapping the self-assembled morphologies as a function of temperature, pressure, and n-heptane:toluene solvent ratio informing how to control asphaltene aggregation by regulating external processing conditions. We then combine our simulations with graph matching and nonlinear manifold learning to determine low-dimensional free energy surfaces governing asphaltene self-assembly. In doing so, we introduce a variant of diffusion maps designed to handle data sets with large local density variations, and report the first application of many-body diffusion maps to molecular self-assembly to recover a pseudo-1D free energy landscape. Increasing pressure only weakly affects the landscape, serving only to destabilize the largest aggregates. Increasing temperature and toluene solvent fraction stabilizes small cluster sizes and loose bonding arrangements. Although the underlying molecular mechanisms differ, the strikingly similar effect of these variables on the free energy landscape suggests that toluene acts upon asphaltene self-assembly as an effective temperature.

Modeling of chemical inhibition from amyloid protein aggregation kinetics.

PubMed

Vázquez, José Antonio

2014-02-27

The process of amyloid proteins aggregation causes several human neuropathologies. In some cases, e.g. fibrillar deposits of insulin, the problems are generated in the processes of production and purification of protein and in the pump devices or injectable preparations for diabetics. Experimental kinetics and adequate modelling of chemical inhibition from amyloid aggregation are of practical importance in order to study the viable processing, formulation and storage as well as to predict and optimize the best conditions to reduce the effect of protein nucleation. In this manuscript, experimental data of insulin, Aβ42 amyloid protein and apomyoglobin fibrillation from recent bibliography were selected to evaluate the capability of a bivariate sigmoid equation to model them. The mathematical functions (logistic combined with Weibull equation) were used in reparameterized form and the effect of inhibitor concentrations on kinetic parameters from logistic equation were perfectly defined and explained. The surfaces of data were accurately described by proposed model and the presented analysis characterized the inhibitory influence on the protein aggregation by several chemicals. Discrimination between true and apparent inhibitors was also confirmed by the bivariate equation. EGCG for insulin (working at pH = 7.4/T = 37°C) and taiwaniaflavone for Aβ42 were the compounds studied that shown the greatest inhibition capacity. An accurate, simple and effective model to investigate the inhibition of chemicals on amyloid protein aggregation has been developed. The equation could be useful for the clear quantification of inhibitor potential of chemicals and rigorous comparison among them.

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

PubMed Central

Specht, Sebastian; Miller, Stephanie B.M.

2011-01-01

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID:22065637

Engineering a fibrocartilage spectrum through modulation of aggregate redifferentiation.

PubMed

Murphy, Meghan K; Masters, Taylor E; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Expanded costochondral cells provide a clinically relevant cell source for engineering both fibrous and hyaline articular cartilage. Expanding chondrocytes in a monolayer results in a shift toward a proliferative, fibroblastic phenotype. Three-dimensional aggregate culture may, however, be used to recover chondrogenic matrix production. This study sought to engineer a spectrum of fibrous to hyaline neocartilage from a single cell source by varying the duration of three-dimensional culture following expansion. In third passage porcine costochondral cells, the effects of aggregate culture duration were assessed after 0, 8, 11, 14, and 21 days of aggregate culture and after 4 subsequent weeks of neocartilage formation. Varying the duration of aggregate redifferentiation generated a spectrum of fibrous to hyaline neocartilage. Within 8 days of aggregation, proliferation ceased, and collagen and glycosaminoglycan production increased, compared with monolayer cells. In self-assembled neocartilage, type II-to-I collagen ratio increased with increasing aggregate duration, yet glycosaminoglycan content varied minimally. Notably, 14 days of aggregate redifferentiation increased collagen content by 25%, tensile modulus by over 110%, and compressive moduli by over 50%, compared with tissue formed in the absence of redifferentiation. A spectrum of fibrous to hyaline cartilage was generated using a single, clinically relevant cell source, improving the translational potential of engineered cartilage.

Engineering a Fibrocartilage Spectrum Through Modulation of Aggregate Redifferentiation

PubMed Central

Murphy, Meghan K.; Masters, Taylor E.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2015-01-01

Expanded costochondral cells provide a clinically relevant cell source for engineering both fibrous and hyaline articular cartilage. Expanding chondrocytes in monolayer results in a shift toward a proliferative, fibroblastic phenotype. Three-dimensional aggregate culture may, however, be used to recover chondrogenic matrix production. This study sought to engineer a spectrum of fibrous to hyaline neocartilage from a single cell source by varying the duration of three-dimensional culture following expansion. In third passage porcine costochondral cells, the effects of aggregate culture duration were assessed after 0, 8, 11, 14, and 21 days of aggregate culture and after 4 subsequent weeks of neocartilage formation. Varying the duration of aggregate redifferentiation generated a spectrum of fibrous to hyaline neocartilage. Within 8 days of aggregation, proliferation ceased, and collagen and glycosaminoglycan production increased, compared with monolayer cells. In self-assembled neocartilage, type II to I collagen ratio increased with increasing aggregate duration, yet glycosaminoglycan content varied minimally. Notably, 14 days of aggregate redifferentiation increased collagen content by 25%, tensile modulus by over 110%, and compressive moduli by over 50%, compared with tissue formed in the absence of redifferentiation. A spectrum of fibrous to hyaline cartilage was generated using a single, clinically relevant cell source, improving the translational potential of engineered cartilage. PMID:24380383

The Optimum Production Method for Quality Improvement of Recycled Aggregates Using Sulfuric Acid and the Abrasion Method.

PubMed

Kim, Haseog; Park, Sangki; Kim, Hayong

2016-07-29

There has been increased deconstruction and demolition of reinforced concrete structures due to the aging of the structures and redevelopment of urban areas resulting in the generation of massive amounts of construction. The production volume of waste concrete is projected to increase rapidly over 100 million tons by 2020. However, due to the high cement paste content, recycled aggregates have low density and high absorption ratio. They are mostly used for land reclamation purposes with low added value instead of multiple approaches. This study was performed to determine an effective method to remove cement paste from recycled aggregates by using the abrasion and substituting the process water with acidic water. The aim of this study is to analyze the quality of the recycled fine aggregates produced by a complex method and investigate the optimum manufacturing conditions for recycled fine aggregates based on the design of experiment. The experimental parameters considered were water ratio, coarse aggregate ratio, and abrasion time and, as a result of the experiment, data concerning the properties of recycled sand were obtained. It was found that high-quality recycled fine aggregates can be obtained with 8.57 min of abrasion-crusher time and a recycled coarse aggregate ratio of over 1.5.

Environmental Stress-mediated EPS Production Shape Microbial Activity on Various Hydrated Rough Surfaces

NASA Astrophysics Data System (ADS)

Wang, G.; Liu, L.; Chen, G.

2016-12-01

The complex environmental physical and chemical processes and interplay with the associating biological responses are keys to understanding the environmental microbiology ensconced in environmental remediation, water quality control, food safety, nutrient cycling, and etc., yet remain poorly understood. Using experimental micromodels, we study how environmental conditions (e.g., hydration fluctuation, nutrient limitation, pH variation, etc.) affect microbial extracellular polymeric substances (EPS) production and their configuration within various hydrated surfaces, and impacts on microbial motility, surface attachment, aggregation, and other bioremediation activities. To elucidate the potential mechanisms underlying the complex bio-physicochemical processes, we developed an individual-based and spatio-temporally resolved modeling platform that explicitly considers microscale aqueous-phase configuration and nutrient transport/diffusion and associated biophysical processes affecting individual microbial cell life history. We quantitatively explore the effects of the above microscale environmental processes on bio-physicochemical interactions affecting microbial growth, motility, surface attachment and aggregation, and shaping population interactions and functions. Simulation scenarios of microbial induced pollutant (e.g., roxarsone) biotransformation on various hydrated rough surfaces will also be present.

Marine Synechococcus Aggregation

NASA Astrophysics Data System (ADS)

Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.

2016-02-01

Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

Effects of Phytoplankton Growth Phase on the Formation and Properties of Marine Snow

NASA Astrophysics Data System (ADS)

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

2016-02-01

Marine snow aggregates often dominate carbon export from the upper mixed layer to the deep ocean. Thus, understanding the formation and the properties of these aggregates is essential to the study of the biological pump. Aggregate formation is determined by both the encounter rate and the stickiness of the particles that they are composed of. Stickiness of phytoplankton has been linked to production of transparent exopolymer particles (TEP), which has been previously shown to vary in concentration throughout different parts of the phytoplankton growth cycle. The objective of this study is to determine the effects of the growth phase of the diatom Thalassiosira weissflogii to both TEP production and the properties of the resulting aggregates produced. Cultures of T. weissflogii were stopped at separate phases of the phytoplankton growth curve and incubated in rotating cylindrical tanks to form aggregates. Aggregate properties such as size, density, and porosity were measured at the end of each period of roller incubation. Preliminary results describe little variation in the size of the aggregates formed from different parts of the growth phase, but show a significant effect of growth phase on aggregate density. Density is an important factor in the settling of marine aggregates. Therefore, variations in aggregate density during different growth phases may have large implications for the efficiency of the biological pump during different stages of a phytoplankton bloom. Further examination will be performed on the potential effects of TEP abundance on the properties of the aggregates formed at separate growth phases and the resulting implications for carbon flux.

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

PubMed

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

2017-02-01

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

The chaperonin CCT promotes the formation of fibrillar aggregates of γ-tubulin.

PubMed

Pouchucq, Luis; Lobos-Ruiz, Pablo; Araya, Gissela; Valpuesta, José María; Monasterio, Octavio

2018-04-01

The type II chaperonin CCT is involved in the prevention of the pathogenesis of numerous human misfolding disorders, as it sequesters misfolded proteins, blocks their aggregation and helps them to achieve their native state. In addition, it has been reported that CCT can prevent the toxicity of non-client amyloidogenic proteins by the induction of non-toxic aggregates, leading to new insight in chaperonin function as an aggregate remodeling factor. Here we add experimental evidence to this alternative mechanism by which CCT actively promotes the formation of conformationally different aggregates of γ-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-γ-tubulin interactions. The in vitro-induced aggregates were in some cases long fiber polymers, which compete with the amorphous aggregates. Direct injection of unfolded purified γ-tubulin into single-cell zebra fish embryos allowed us to relate this in vitro activity with the in vivo formation of intracellular aggregates. Injection of a CCT-binding deficient γ-tubulin mutant dramatically diminished the size of the intracellular aggregates, increasing the toxicity of the misfolded protein. These results point to CCT having a role in the remodeling of aggregates, constituting one of its many functions in cellular proteostasis. Copyright © 2018. Published by Elsevier B.V.

Mineral trioxide aggregate: part 2 - a review of the material aspects.

PubMed

Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

2013-03-01

The purpose of this two-part series is to review the composition, properties, and products of mineral trioxide aggregate (MTA) materials. PubMed and MedLine electronic databases were used to identify scientific papers from January 1991 to May 2010. Based on the selected inclusion criteria, citations were referenced from the scientific peer-reviewed dental literature. Mineral trioxide aggregate is a refined form of the parent compound, Portland cement (PC), and demonstrates a strong biocompatibility due to the high pH level and the material's ability to form hydroxyapatite. Mineral trioxide aggregate materials provide better microleakage protection than traditional endodontic materials as observed in findings from dye-leakage, fluid-filtration, protein-leakage, and bacterial penetration-leakage studies and has been recognized as a bioactive material. Various MTA commercial products are available, including gray mineral trioxide aggregate (GMTA), white mineral trioxide aggregate (WMTA), and mineral trioxide aggregate-Angelus (AMTA). Although these materials are indicated for various dental uses and applications, long-term in-vivo clinical studies are needed. Part 1 of this article highlighted and discussed the composition and characteristics of the material. Part 2 provides an overview of commercially available MTA materials.

Transportation and utilization of aggregates for road construction

NASA Astrophysics Data System (ADS)

Fladvad, Marit; Wigum, Børge Johannes; Aurstad, Joralf

2017-04-01

Road construction relies on non-renewable aggregate resources as the main construction material. Sources for high-quality aggregate resources are scattered, and requirements for aggregate quality can cause long transport distances between quarry and road construction site. In European countries, the average aggregate consumption per capita is 5 tonnes per year (European Aggregates Association, 2016), while the corresponding figure for Norway is 11 tonnes (Neeb, 2015). Half the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction. In Norway, aggregate resources have been considered abundant. However, stricter requirement for aggregate quality, and increased concern for sustainability and environmental issues have spurred focus on reduction of transport lengths through better utilization of local aggregate materials. In this research project, information about pavement design and aggregate quality requirements were gathered from a questionnaire sent to selected experts from the World Road Organization (PIARC), European Committee for Standardization (CEN), and Nordic Road Association (NVF). The gathered data was compared to identify differences and similarities for aggregate use in the participating countries. Further, the data was compared to known data from Norway regarding: - amount of aggregates required for a road structure - aggregate transport lengths and related costs A total of 18 countries participated in the survey, represented by either road authorities, research institutions, or contractors. There are large variations in practice for aggregate use among the represented countries, and the selection of countries is sufficient to illustrate a variety in pavement designs, aggregate sizes, and quality requirements for road construction. There are considerable differences in both pavement thickness and aggregate sizes used in the studied countries. Total thicknesses for pavement structures varies from 220 mm to 2400 mm, and aggregate sizes for unbound materials varies from 19 mm to 600 mm. These results imply great differences in the amount of aggregate transport to road construction sites. Another important factor is the distances between the construction sites and the aggregate sources. For many projects, especially in countries in need of importing aggregates, aggregate transport will have considerable impact on sustainability assessment of the construction projects. If pavement design can be altered with the goal of achieving better utilization of local aggregates through adaption to the quality of local aggregates, aggregate transportation can be reduced. Reduced transport will alter the economical balance of a project, allowing reallocation of costs from transport to e.g. improved aggregate production. The overall result can be more profitable construction projects and a more sustainable development of road structures.

Effect of physicochemical action on the aggregative properties of detonation-synthesized nanodiamonds

NASA Astrophysics Data System (ADS)

Fan, Z. W.; Ilnitska, H.; Lysakovskyi, V.; Ivakhnenko, S.; Kovalenko, T.

2018-01-01

The results of researches of physicochemical action on aggregate properties of nanodiamond are presented. The kinetics of aggregation of nanodiamond powder was studied as a function of time, temperature, and pH of the solution. The effect of the sp2-sp3 hybridization ratio of carbon in nanodiamond powders on their aggregation was studied. It is shown that the presence of non-diamond carbon in detonation synthesis nanodiamond powders leads to the increase of the mean diameters of particles, i.e., their agglomeration. The theoretical justification of the aggregation mechanism is proposed. It is shown that it is possible to control aggregative properties of nanodiamond powders by physicochemical influences, e.g., gas-phase thermal treatment to reduce the size of agglomerates and to create a well-developed reconstructed surface of diamond particles with a low content of functional groups on their surface.

Effect of settled diatom‐aggregates on benthic nitrogen cycling

PubMed Central

Thamdrup, Bo; Stief, Peter; Glud, Ronnie N.

2017-01-01

Abstract The marine sediment hosts a mosaic of microhabitats. Recently it has been demonstrated that the settlement of phycodetrital aggregates can induce local changes in the benthic O2 distribution due to confined enrichment of organic material and alteration of the diffusional transport. Here, we show how this microscale O2 shift substantially affects benthic nitrogen cycling. In sediment incubations, the settlement of diatom‐aggregates markedly enhanced benthic O2 and NO3− consumption and stimulated NO2− and NH4+ production. Oxygen microprofiles revealed the rapid development of anoxic niches within and underneath the aggregates. During 120 h following the settling of the aggregates, denitrification of NO3− from the overlying water increased from 13.5 μmol m−2 h−1 to 24.3 μmol m−2 h−1, as quantified by 15N enrichment experiment. Simultaneously, N2 production from coupled nitrification‐denitrification decreased from 33.4 μmol m−2 h−1 to 25.9 μmol m−2 h−1, probably due to temporary inhibition of the benthic nitrifying community. The two effects were of similar magnitude and left the total N2 production almost unaltered. At the aggregate surface, nitrification was, conversely, very efficient in oxidizing NH4+ liberated by mineralization of the aggregates. The produced NO3− was preferentially released into the overlying water and only a minor fraction contributed to denitrification activity. Overall, our data indicate that the abrupt change in O2 microdistribution caused by aggregates stimulates denitrification of NO3− from the overlying water, and loosens the coupling between benthic nitrification and denitrification both in time and space. The study contributes to expanding the conceptual and quantitative understanding of how nitrogen cycling is regulated in dynamic benthic environments. PMID:29456269

GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over-expressed in Escherichia coli.

PubMed

Goyal, Megha; Chaudhuri, Tapan K

2015-07-01

Folding of aggregation prone recombinant proteins through co-expression of chaperonin GroEL and GroES has been a popular practice in the effort to optimize preparation of functional protein in Escherichia coli. Considering the demand for functional recombinant protein products, it is desirable to apply the chaperone assisted protein folding strategy for enhancing the yield of properly folded protein. Toward the same direction, it is also worth attempting folding of multiple recombinant proteins simultaneously over-expressed in E. coli through the assistance of co-expressed GroEL-ES. The genesis of this thinking was originated from the fact that cellular GroEL and GroES assist in the folding of several endogenous proteins expressed in the bacterial cell. Here we present the experimental findings from our study on co-expressed GroEL-GroES assisted folding of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES assisted folding in E. coli cells during over-expression. It has been reported that the relative yield of properly folded functional forms of MalZ and mAco with the exogenous GroEL-ES assistance were comparable with the results when these proteins were overexpressed alone. This observation is quite promising and highlights the fact that GroEL and GroES can assist in the folding of multiple substrate proteins simultaneously when over-expressed in E. coli. This method might be a potential tool for enhanced production of multiple functional recombinant proteins simultaneously in E. coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Extracellular Serine/Threonine-Rich Protein from Lactobacillus plantarum NCIMB 8826 Is a Novel Aggregation-Promoting Factor with Affinity to Mucin

PubMed Central

Hevia, Arancha; Martínez, Noelia; Ladero, Víctor; Álvarez, Miguel A.; Margolles, Abelardo

2013-01-01

Autoaggregation in lactic acid bacteria is directly related to the production of certain extracellular proteins, notably, aggregation-promoting factors (APFs). Production of aggregation-promoting factors confers beneficial traits to probiotic-producing strains, contributing to their fitness for the intestinal environment. Furthermore, coaggregation with pathogens has been proposed to be a beneficial mechanism in probiotic lactic acid bacteria. This mechanism would limit attachment of the pathogen to the gut mucosa, favoring its removal by the human immune system. In the present paper, we have characterized a novel aggregation-promoting factor in Lactobacillus plantarum. A mutant with a knockout of the D1 gene showed loss of its autoaggregative phenotype and a decreased ability to bind to mucin, indicating an adhesion role of this protein. In addition, heterologous production of the D1 protein or an internal fragment of the protein, characterized by its abundance in serine/threonine, strongly induced autoaggregation in Lactococcus lactis. This result strongly suggested that this internal fragment is responsible for the bioactivity of D1 as an APF. To our knowledge, this is the first report on a gene coding for an aggregation-promoting factor in Lb. plantarum. PMID:23892754

MODELING POROUS DUST GRAINS WITH BALLISTIC AGGREGATES. II. LIGHT SCATTERING PROPERTIES

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

Shen Yue; Draine, B. T.; Johnson, Eric T.

2009-05-10

We study the light scattering properties of random ballistic aggregates constructed in Shen et al. Using the discrete-dipole approximation, we compute the scattering phase function and linear polarization for random aggregates with various sizes and porosities, and with two different compositions: 100% silicate and 50% silicate +50% graphite. We investigate the dependence of light scattering properties on wavelength, cluster size, and porosity using these aggregate models. We find that while the shape of the phase function depends mainly on the size parameter of the aggregates, the linear polarization depends on both the size parameter and the porosity of the aggregates,more » with increasing degree of polarization as the porosity increases. Contrary to previous studies, we argue that the monomer size has negligible effects on the light scattering properties of ballistic aggregates, as long as the constituent monomer is smaller than the incident wavelength up to 2{pi}a {sub 0}/{lambda} {approx} 1.6 where a {sub 0} is the monomer radius. Previous claims for such monomer size effects are in fact the combined effects of size parameter and porosity. Finally, we present aggregate models that can reproduce the phase function and polarization of scattered light from the AU Mic debris disk and from cometary dust, including the negative polarization observed for comets at scattering angles 160 deg. {approx}< {theta} < 180 deg. These aggregates have moderate porosities, P{approx}0.6, and are of sub-{mu}m size for the debris disk case, or {mu}m size for the comet case.« less

Improving the quality of care of patients with rheumatic disease using patient-centric electronic redesign software.

PubMed

Newman, Eric D; Lerch, Virginia; Billet, Jon; Berger, Andrea; Kirchner, H Lester

2015-04-01

Electronic health records (EHRs) are not optimized for chronic disease management. To improve the quality of care for patients with rheumatic disease, we developed electronic data capture, aggregation, display, and documentation software. The software integrated and reassembled information from the patient (via a touchscreen questionnaire), nurse, physician, and EHR into a series of actionable views. Core functions included trends over time, rheumatology-related demographics, and documentation for patient and provider. Quality measures collected included patient-reported outcomes, disease activity, and function. The software was tested and implemented in 3 rheumatology departments, and integrated into routine care delivery. Post-implementation evaluation measured adoption, efficiency, productivity, and patient perception. Over 2 years, 6,725 patients completed 19,786 touchscreen questionnaires. The software was adopted for use by 86% of patients and rheumatologists. Chart review and documentation time trended downward, and productivity increased by 26%. Patient satisfaction, activation, and adherence remained unchanged, although pre-implementation values were high. A strong correlation was seen between use of the software and disease control (weighted Pearson's correlation coefficient 0.5927, P = 0.0095), and a relative increase in patients with low disease activity of 3% per quarter was noted. We describe innovative software that aggregates, stores, and displays information vital to improving the quality of care for patients with chronic rheumatic disease. The software was well-adopted by patients and providers. Post-implementation, significant improvements in quality of care, efficiency of care, and productivity were demonstrated. Copyright © 2015 by the American College of Rheumatology.

Quantitative risk assessment of the aggregate dermal exposure to the sensitizing fragrance geraniol in personal care products and household cleaning agents.

PubMed

Nijkamp, M M; Bokkers, B G H; Bakker, M I; Ezendam, J; Delmaar, J E

2015-10-01

A quantitative risk assessment was performed to establish if consumers are at risk for being dermally sensitized by the fragrance geraniol. Aggregate dermal exposure to geraniol was estimated using the Probabilistic Aggregate Consumer Exposure Model, containing data on the use of personal care products and household cleaning agents. Consumer exposure to geraniol via personal care products appeared to be higher than via household cleaning agents. The hands were the body parts receiving the highest exposure to geraniol. Dermal sensitization studies were assessed to derive the point of departure needed for the estimation of the Acceptable Exposure Level (AEL). Two concentrations were derived, one based on human studies and the other from dose-response analysis of the available murine local lymph node assay data. The aggregate dermal exposure assessment resulted in body part specific median exposures up to 0.041 μg/cm(2) (highest exposure 102 μg/cm(2)) for hands. Comparing the exposure to the lowest AEL (55 μg/cm(2)), shows that a range of 0.02-0.86% of the population may have an aggregated exposure which exceeds the AEL. Furthermore, it is demonstrated that personal care products contribute more to the consumer's geraniol exposure compared to household cleaning agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential effects of grape ( Vitis vinifera ) skin polyphenolics on human platelet aggregation and low-density lipoprotein oxidation.

PubMed

Shanmuganayagam, Dhanansayan; Beahm, Mark R; Kuhns, Melissa A; Krueger, Christian G; Reed, Jess D; Folts, John D

2012-06-13

Antioxidant and antiplatelet properties of grape products are thought to be responsible for observed antiatherosclerotic effects. Diverse classes of phenolics are derived from the seed and skin (GSK) of grapes. The relative contributions of the classes of phenolics to observed properties of grape products are unknown. In this paper, GSK fractions were used to examine effects on platelet aggregation, low-density lipoprotein (LDL) oxidation in vitro, and relative binding of phenolics to LDL. GSK was separated into six fractions (fractions 1-6), and primary phenolics were characterized using high-performance liquid chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fractions 4, 5, and 6, enriched in polygalloyl polyflavan-3-ols (PGPFs) with 3-6, 4-8, and 6-15 degrees of polymerization, respectively, inhibited platelet aggregation. Fractions 1-3, containing various amounts of oligosaccharides, hydroxycinnamic acids, anthocyanins, flavanols, and low molecular weight PGPFs, significantly increased platelet aggregation. Fractions 4-6 were most effective in binding LDL and inhibiting LDL oxidation. Fractions 5 and 6 exhibited the greatest inhibition of platelet aggregation and LDL oxidation, suggesting that polymeric PGPFs are responsible for the beneficial effects of grape products. Conversely, phenolics in fractions 1-3 may reduce the net biological potency of the grape products and have undesirable effects on cardiovascular disease risk factors.

On the Role of Aggregation Prone Regions in Protein Evolution, Stability, and Enzymatic Catalysis: Insights from Diverse Analyses

PubMed Central

Buck, Patrick M.; Kumar, Sandeep; Singh, Satish K.

2013-01-01

The various roles that aggregation prone regions (APRs) are capable of playing in proteins are investigated here via comprehensive analyses of multiple non-redundant datasets containing randomly generated amino acid sequences, monomeric proteins, intrinsically disordered proteins (IDPs) and catalytic residues. Results from this study indicate that the aggregation propensities of monomeric protein sequences have been minimized compared to random sequences with uniform and natural amino acid compositions, as observed by a lower average aggregation propensity and fewer APRs that are shorter in length and more often punctuated by gate-keeper residues. However, evidence for evolutionary selective pressure to disrupt these sequence regions among homologous proteins is inconsistent. APRs are less conserved than average sequence identity among closely related homologues (≥80% sequence identity with a parent) but APRs are more conserved than average sequence identity among homologues that have at least 50% sequence identity with a parent. Structural analyses of APRs indicate that APRs are three times more likely to contain ordered versus disordered residues and that APRs frequently contribute more towards stabilizing proteins than equal length segments from the same protein. Catalytic residues and APRs were also found to be in structural contact significantly more often than expected by random chance. Our findings suggest that proteins have evolved by optimizing their risk of aggregation for cellular environments by both minimizing aggregation prone regions and by conserving those that are important for folding and function. In many cases, these sequence optimizations are insufficient to develop recombinant proteins into commercial products. Rational design strategies aimed at improving protein solubility for biotechnological purposes should carefully evaluate the contributions made by candidate APRs, targeted for disruption, towards protein structure and activity. PMID:24146608

Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides.

PubMed

Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

2017-01-15

Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation. Copyright © 2016 Elsevier B.V. All rights reserved.

Graphene oxide-dependent growth and self-aggregation into a hydrogel complex of exoelectrogenic bacteria

PubMed Central

Yoshida, Naoko; Miyata, Yasushi; Doi, Kasumi; Goto, Yuko; Nagao, Yuji; Tero, Ryugo; Hiraishi, Akira

2016-01-01

Graphene oxide (GO) is reduced by certain exoelectrogenic bacteria, but its effects on bacterial growth and metabolism are a controversial issue. This study aimed to determine whether GO functions as the terminal electron acceptor to allow specific growth of and electricity production by exoelectrogenic bacteria. Cultivation of environmental samples with GO and acetate as the sole substrate could specifically enrich exoelectrogenic bacteria with Geobacter species predominating (51–68% of the total populations). Interestingly, bacteria in these cultures self-aggregated into a conductive hydrogel complex together with biologically reduced GO (rGO). A novel GO-respiring bacterium designated Geobacter sp. strain R4 was isolated from this hydrogel complex. This organism exhibited stable electricity production at >1000 μA/cm3 (at 200 mV vs Ag/AgCl) for more than 60 d via rGO while temporary electricity production using graphite felt. The better electricity production depends upon the characteristics of rGO such as a large surface area for biofilm growth, greater capacitance, and smaller internal resistance. This is the first report to demonstrate GO-dependent growth of exoelectrogenic bacteria while forming a conductive hydrogel complex with rGO. The simple put-and-wait process leading to the formation of hydrogel complexes of rGO and exoelectrogens will enable wider applications of GO to bioelectrochemical systems. PMID:26899353

Caspase-1 Specific Light-Up Probe with Aggregation-Induced Emission Characteristics for Inhibitor Screening of Coumarin-Originated Natural Products.

PubMed

Lin, Hao; Yang, Haitao; Huang, Shuai; Wang, Fujia; Wang, Dong-Mei; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

2018-04-18

Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is found to be beneficial to various diseases. Coumarin-originated natural products have an anti-inflammation function, but their direct inhibition effect to caspase-1 remains unexplored. To evaluate their interactions, the widely used commercial coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from coumarin-originated natural products could interfere with the screening results. Therefore, fluorescent probes using a large Stokes shift could help solve this problem. In this work, we chose the fluorophore of tetraphenylethylene-thiophene (TPETH) with aggregation-induced emission characteristics and a large Stokes shift of about 200 nm to develop a molecular probe. Bioconjugation between TPETH and hydrophilic peptides (DDYVADC) through a thiol-ene reaction generated a light-up probe, C1-P3. The probe has little background signal in aqueous media and exerts a fluorescent turn-on effect in the presence of caspase-1. Moreover, when evaluating the inhibition potency of coumarin-originated natural products, the new probe could generate a true and objective result but not for the commercial probe (Ac-YVAD-AMC), which is evidenced by HPLC analysis. The quick light-up response and accurate screening results make C1-P3 very useful in fundamental study and inhibitior screening toward caspase-1.

Polyglutamine aggregation in Huntington and related diseases.

PubMed

Polling, Saskia; Hill, Andrew F; Hatters, Danny M

2012-01-01

Polyglutamine (polyQ)-expansions in different proteins cause nine neurodegenerative diseases. While polyQ aggregation is a key pathological hallmark of these diseases, how aggregation relates to pathogenesis remains contentious. In this chapter, we review what is known about the aggregation process and how cells respond and interact with the polyQ-expanded proteins. We cover detailed biophysical and structural studies to uncover the intrinsic features of polyQ aggregates and concomitant effects in the cellular environment. We also examine the functional consequences ofpolyQ aggregation and how cells may attempt to intervene and guide the aggregation process.

Song recorded near a super-group of humpback whales on a mid-latitude feeding ground off South Africa.

PubMed

Gridley, T; Silva, M F P; Wilkinson, C; Seakamela, S M; Elwen, S H

2018-04-01

Humpback whales (Megaptera novaeangliae) are well known for their complex song which is culturally transmitted and produced by males. However, the function of singing behavior remains poorly understood. Song was observed from 57 min of acoustic recording in the presence of feeding humpback whales aggregated in the near-shore waters on the west coast of South Africa. The structural organization of the song components, lack of overlap between song units, and consistency in relative received level suggest the song was produced by one "singer." The unusual timing and location of song production adds further evidence of plasticity in song production.

In vitro functional properties of crude extracts and isolated compounds from banana pseudostem and rhizome.

PubMed

Kandasamy, Saravanan; Ramu, Sasikala; Aradhya, Somaradhya Mallikarjuna

2016-03-15

Pseudostem and rhizome are the significant bio-waste generated (43.48%) from the banana plant post fruit harvest, which are usually left in the plantation or incinerated and wasted. Amounts used in production for consumption are negligible. However, the material has an important part to play in indigenous systems of medicine. Based on the huge volume of bio-waste generated and its traditional medicinal use, it is worth exploiting it as a source of natural bioactive compounds. In the current study, sequential extracts from banana pseudostem (BPS) and rhizome (BR), and isolated compounds including chlorogenic acid, 4-epicyclomusalenone and cycloeucalenol acetate, were tested for their antimicrobial activity, antiplatelet aggregation and cytotoxicity. Isolated compounds and crude extracts exhibited strong antimicrobial activity against a wide range of bacterial and fungal strains, platelet aggregation induced by collagen and cytotoxicity towards human liver cancer (HepG2) cells. Banana plant bio-waste, pseudostem and rhizome may serve as a potential source of multifunctional bioactive compounds and functional ingredient in food and other allied industries. © 2015 Society of Chemical Industry.

Mechanical and Physical Properties of Hydrophobized Lightweight Aggregate Concrete with Sewage Sludge.

PubMed

Suchorab, Zbigniew; Barnat-Hunek, Danuta; Franus, Małgorzata; Łagód, Grzegorz

2016-04-27

This article is focused on lightweight aggregate-concrete modified by municipal sewage sludge and lightweight aggregate-concrete obtained from light aggregates. The article presents laboratory examinations of material physical parameters. Water absorptivity of the examined material was decreased by the admixture of water emulsion of reactive polysiloxanes. Water transport properties were determined using Time Domain Reflectometry, an indirect technique for moisture detection in porous media. Together with basic physical parameters, the heat conductivity coefficient λ was determined for both types of lightweight aggregate-concrete. Analysis of moisture and heat properties of the examined materials confirmed the usefulness of light aggregates supplemented with sewage sludge for prospective production.

Linking Microbial Community Structure to β-Glucosidic Function in Soil Aggregates

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

Bailey, Vanessa L.; Fansler, Sarah J.; Stegen, James C.

2013-10-01

To link microbial community 16S structure to a measured function in a natural soil we have scaled both DNA and β-glucosidase assays down to a volume of soil that may approach a unique microbial community. β-glucosidase activity was assayed in 450 individual aggregates which were then sorted into classes of high or low activities, from which groups of 10 or 11 aggregates were identified and grouped for DNA extraction and pyrosequencing. Tandem assays of ATP were conducted for each aggregate in order to normalize these small groups of aggregates for biomass size. In spite of there being no significant differencesmore » in the richness or diversity of the microbial communities associated with high β-glucosidase activities compared with the communities associated with low β-glucosidase communities, several analyses of variance clearly show that the communities of these two groups differ. The separation of these groups is partially driven by the differential abundances of members of the Chitinophagaceae family. It may be that observed functional differences in otherwise similar soil aggregates can be largely attributed to differences in resource availability, rather than to presence or absence of particular taxonomic groups.« less

Monitoring of conditions inside gas aggregation cluster source during production of Ti/TiOx nanoparticles

NASA Astrophysics Data System (ADS)

Kousal, J.; Kolpaková, A.; Shelemin, A.; Kudrna, P.; Tichý, M.; Kylián, O.; Hanuš, J.; Choukourov, A.; Biederman, H.

2017-10-01

Gas aggregation sources are nowadays rather widely used in the research community for producing nanoparticles. However, the direct diagnostics of conditions inside the source are relatively scarce. In this work, we focused on monitoring the plasma parameters and the composition of the gas during the production of the TiOx nanoparticles. We studied the role of oxygen in the aggregation process and the influence of the presence of the particles on the plasma. The construction of the source allowed us to make a 2D map of the plasma parameters inside the source.

Analytical characterization of ch14.18

PubMed Central

Kallarakal, Abraham T; Michiel, Dennis; Yang, Xiaoyi; Saptharishi, Nirmala; Jiang, Hengguang; Giardina, Steve; Gilly, John; Mitra, George

2012-01-01

Ch14.18 is a mouse-human chimeric monoclonal antibody to the disialoganglioside (GD2) glycolipid. In the clinic, this antibody has been shown to be effective in the treatment of children with high-risk neuroblastoma, either alone or in combination therapy. Extensive product characterization is a prerequisite to addressing the potential issues of product variability associated with process changes and manufacturing scale-up. Charge heterogeneity, glycosylation profile, molecular state and aggregation, interaction (affinity) with Fcγ receptors and functional or biological activities are a few of the critical characterization assays for assessing product comparability for this antibody. In this article, we describe the in-house development and qualification of imaged capillary isoelectric focusing to assess charge heterogeneity, analytical size exclusion chromatography with online static and dynamic light scattering (DLS), batch mode DLS for aggregate detection, biosensor (surface plasmon resonance)-based Fcγ receptor antibody interaction kinetics, N-glycoprofiling with PNGase F digestion, 2-aminobenzoic acid labeling and high performance liquid chromatography and N-glycan analysis using capillary electrophoresis. In addition, we studied selected biological activity assays, such as complement-dependent cytotoxicity. The consistency and reproducibility of the assays are established by comparing the intra-day and inter-day assay results. Applications of the methodologies to address stability or changes in product characteristics are also reported. The study results reveal that the ch14.18 clinical product formulated in phosphate-buffered saline at a concentration of 5 mg/ml and stored at 2–8°C is stable for more than five years. PMID:22327432

Development of a multi-criteria evaluation system to assess growing pig welfare.

PubMed

Martín, P; Traulsen, I; Buxadé, C; Krieter, J

2017-03-01

The aim of this paper was to present an alternative multi-criteria evaluation model to assess animal welfare on farms based on the Welfare Quality® (WQ) project, using an example of welfare assessment of growing pigs. The WQ assessment protocol follows a three-step aggregation process. Measures are aggregated into criteria, criteria into principles and principles into an overall assessment. This study focussed on the first step of the aggregation. Multi-attribute utility theory (MAUT) was used to produce a value of welfare for each criterion. The utility functions and the aggregation function were constructed in two separated steps. The Measuring Attractiveness by a Categorical Based Evaluation Technique (MACBETH) method was used for utility function determination and the Choquet Integral (CI) was used as an aggregation operator. The WQ decision-makers' preferences were fitted in order to construct the utility functions and to determine the CI parameters. The methods were tested with generated data sets for farms of growing pigs. Using the MAUT, similar results were obtained to the ones obtained applying the WQ protocol aggregation methods. It can be concluded that due to the use of an interactive approach such as MACBETH, this alternative methodology is more transparent and more flexible than the methodology proposed by WQ, which allows the possibility to modify the model according, for instance, to new scientific knowledge.

Production of membrane proteins without cells or detergents.

PubMed

Rajesh, Sundaresan; Knowles, Timothy; Overduin, Michael

2011-04-30

The production of membrane proteins in cellular systems is besieged by several problems due to their hydrophobic nature which often causes misfolding, protein aggregation and cytotoxicity, resulting in poor yields of stable proteins. Cell-free expression has emerged as one of the most versatile alternatives for circumventing these obstacles by producing membrane proteins directly into designed hydrophobic environments. Efficient optimisation of expression and solubilisation conditions using a variety of detergents, membrane mimetics and lipids has yielded structurally and functionally intact membrane proteins, with yields several fold above the levels possible from cell-based systems. Here we review recently developed techniques available to produce functional membrane proteins, and discuss amphipols, nanodisc and styrene maleic acid lipid particle (SMALP) technologies that can be exploited alongside cell-free expression of membrane proteins. Copyright © 2010 Elsevier B.V. All rights reserved.

Game-Theoretic strategies for systems of components using product-form utilities

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

Rao, Nageswara S; Ma, Cheng-Yu; Hausken, K.

Many critical infrastructures are composed of multiple systems of components which are correlated so that disruptions to one may propagate to others. We consider such infrastructures with correlations characterized in two ways: (i) an aggregate failure correlation function specifies the conditional failure probability of the infrastructure given the failure of an individual system, and (ii) a pairwise correlation function between two systems specifies the failure probability of one system given the failure of the other. We formulate a game for ensuring the resilience of the infrastructure, wherein the utility functions of the provider and attacker are products of an infrastructuremore » survival probability term and a cost term, both expressed in terms of the numbers of system components attacked and reinforced. The survival probabilities of individual systems satisfy first-order differential conditions that lead to simple Nash Equilibrium conditions. We then derive sensitivity functions that highlight the dependence of infrastructure resilience on the cost terms, correlation functions, and individual system survival probabilities. We apply these results to simplified models of distributed cloud computing and energy grid infrastructures.« less

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A{sub 2} production

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

Chang, Mei-Chi; Chang, Hsiao-Hua; Chan, Chiu-Po

2012-09-15

Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5–25 μM) suppressed AA-induced platelet aggregation and thromboxane B{sub 2} (TXB{sub 2}) production, but not U46619-induced platelet aggregation. Phloroglucinol (100–250 μM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45–74% and 49–72% respectively at concentrations of 10–50 μM. At concentrations of 1 and 5 μM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC{sub 50} ofmore » 13.8 μM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10–25 μM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 μmol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57–71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1β-induced PGE{sub 2} production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use. -- Highlights: ► Phloroglucinol suppressed AA-induced platelet aggregation and thromboxane production. ► Phloroglucinol inhibited COX activity and IL-1b-induced PGE2 production in fibroblast. ► Phloroglucinol declined platelet and PMN ROS production and ERK/p38 phosphorylation. ► Phloroglucinol suppressed ex vivo AA-induced platelet aggregation. ► Phloroglucinol may prevent and for treatment of atherosclerosis/ vascular diseases.« less

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

PubMed Central

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

2015-01-01

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

A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis.

PubMed

Carterson, A J; Höner zu Bentrup, K; Ott, C M; Clarke, M S; Pierson, D L; Vanderburg, C R; Buchanan, K L; Nickerson, C A; Schurr, M J

2005-02-01

A three-dimensional (3-D) lung aggregate model was developed from A549 human lung epithelial cells by using a rotating-wall vessel bioreactor to study the interactions between Pseudomonas aeruginosa and lung epithelial cells. The suitability of the 3-D aggregates as an infection model was examined by immunohistochemistry, adherence and invasion assays, scanning electron microscopy, and cytokine and mucoglycoprotein production. Immunohistochemical characterization of the 3-D A549 aggregates showed increased expression of epithelial cell-specific markers and decreased expression of cancer-specific markers compared to their monolayer counterparts. Immunohistochemistry of junctional markers on A549 3-D cells revealed that these cells formed tight junctions and polarity, in contrast to the cells grown as monolayers. Additionally, the 3-D aggregates stained positively for the production of mucoglycoprotein while the monolayers showed no indication of staining. Moreover, mucin-specific antibodies to MUC1 and MUC5A bound with greater affinity to 3-D aggregates than to the monolayers. P. aeruginosa attached to and penetrated A549 monolayers significantly more than the same cells grown as 3-D aggregates. Scanning electron microscopy of A549 cells grown as monolayers and 3-D aggregates infected with P. aeruginosa showed that monolayers detached from the surface of the culture plate postinfection, in contrast to the 3-D aggregates, which remained attached to the microcarrier beads. In response to infection, proinflammatory cytokine levels were elevated for the 3-D A549 aggregates compared to monolayer controls. These findings suggest that A549 lung cells grown as 3-D aggregates may represent a more physiologically relevant model to examine the interactions between P. aeruginosa and the lung epithelium during infection.

Eco-friendly porous concrete using bottom ash aggregate for marine ranch application.

PubMed

Lee, Byung Jae; Prabhu, G Ganesh; Lee, Bong Chun; Kim, Yun Yong

2016-03-01

This article presents the test results of an investigation carried out on the reuse of coal bottom ash aggregate as a substitute material for coarse aggregate in porous concrete production for marine ranch applications. The experimental parameters were the rate of bottom ash aggregate substitution (30%, 50% and 100%) and the target void ratio (15%, 20% and 25%). The cement-coated granular fertiliser was substituted into a bottom ash aggregate concrete mixture to improve marine ranch applications. The results of leaching tests revealed that the bottom ash aggregate has only a negligible amount of the ten deleterious substances specified in the Ministry of Environment - Enforcement Regulation of the Waste Management Act of Republic Korea. The large amount of bubbles/air gaps in the bottom ash aggregate increased the voids of the concrete mixtures in all target void ratios, and decreased the compressive strength of the porous concrete mixture; however, the mixture substituted with 30% and 10% of bottom ash aggregate and granular fertiliser, respectively, showed an equal strength to the control mixture. The sea water resistibility of the bottom ash aggregate substituted mixture was relatively equal to that of the control mixture, and also showed a great deal of improvement in the degree of marine organism adhesion compared with the control mixture. No fatality of fish was observed in the fish toxicity test, which suggested that bottom ash aggregate was a harmless material and that the combination of bottom ash aggregate and granular fertiliser with substitution rates of 30% and 10%, respectively, can be effectively used in porous concrete production for marine ranch application. © The Author(s) 2015.

A nanoscale bio-inspired light-harvesting system developed from self-assembled alkyl-functionalized metallochlorin nano-aggregates

NASA Astrophysics Data System (ADS)

Ocakoglu, Kasim; Joya, Khurram S.; Harputlu, Ersan; Tarnowska, Anna; Gryko, Daniel T.

2014-07-01

Self-assembled supramolecular organization of nano-structured biomimetic light-harvesting modules inside solid-state nano-templates can be exploited to develop excellent light-harvesting materials for artificial photosynthetic devices. We present here a hybrid light-harvesting system mimicking the chlorosomal structures of the natural photosynthetic system using synthetic zinc chlorin units (ZnChl-C6, ZnChl-C12 and ZnChl-C18) that are self-aggregated inside the anodic aluminum oxide (AAO) nano-channel membranes. AAO nano-templates were modified with a TiO2 matrix and functionalized with long hydrophobic chains to facilitate the formation of supramolecular Zn-chlorin aggregates. The transparent Zn-chlorin nano-aggregates inside the alkyl-TiO2 modified AAO nano-channels have a diameter of ~120 nm in a 60 μm length channel. UV-Vis studies and fluorescence emission spectra further confirm the formation of the supramolecular ZnChl aggregates from monomer molecules inside the alkyl-functionalized nano-channels. Our results prove that the novel and unique method can be used to produce efficient and stable light-harvesting assemblies for effective solar energy capture through transparent and stable nano-channel ceramic materials modified with bio-mimetic molecular self-assembled nano-aggregates.Self-assembled supramolecular organization of nano-structured biomimetic light-harvesting modules inside solid-state nano-templates can be exploited to develop excellent light-harvesting materials for artificial photosynthetic devices. We present here a hybrid light-harvesting system mimicking the chlorosomal structures of the natural photosynthetic system using synthetic zinc chlorin units (ZnChl-C6, ZnChl-C12 and ZnChl-C18) that are self-aggregated inside the anodic aluminum oxide (AAO) nano-channel membranes. AAO nano-templates were modified with a TiO2 matrix and functionalized with long hydrophobic chains to facilitate the formation of supramolecular Zn-chlorin aggregates. The transparent Zn-chlorin nano-aggregates inside the alkyl-TiO2 modified AAO nano-channels have a diameter of ~120 nm in a 60 μm length channel. UV-Vis studies and fluorescence emission spectra further confirm the formation of the supramolecular ZnChl aggregates from monomer molecules inside the alkyl-functionalized nano-channels. Our results prove that the novel and unique method can be used to produce efficient and stable light-harvesting assemblies for effective solar energy capture through transparent and stable nano-channel ceramic materials modified with bio-mimetic molecular self-assembled nano-aggregates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01661k

Building aggregate timber supply models from individual harvest choice

Treesearch

Maksym Polyakov; David N. Wear; Robert Huggett

2009-01-01

Timber supply has traditionally been modelled using aggregate data. In this paper, we build aggregate supply models for four roundwood products for the US state of North Carolina from a stand-level harvest choice model applied to detailed forest inventory. The simulated elasticities of pulpwood supply are much lower than reported by previous studies. Cross price...

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

ERIC Educational Resources Information Center

Kyer, Ben L.; Maggs, Gary E.

1995-01-01

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

Characterization of the aggregation responses of camel platelets.

PubMed

Al Ghumlas, Abeer K; Gader, Abdel Galil M Abdel

2013-09-01

Despite evidence of active hemostasis, camel platelets barely respond to common aggregating agents at standard doses used for human platelet aggregation. The purpose of the study was to find out whether camel platelets can be activated by high doses or combinations of aggregation agonists, and to characterize the receptor that mediates the aggregation response to adenosine diphosphate (ADP), the most potent agonist for camel platelets known so far. Aggregation studies were performed with platelet-rich plasma (PRP) in response to multiple doses or combinations of ADP, epinephrine (EPN), collagen, and arachidonic acid (AA). Aggregation responses to ADP were performed before and after the addition of the ADP receptor (P2Y12) antagonist Clopidogrel. Camel platelets responded to ADP at doses higher than the standard dose for human platelets, and to combinations of EPN and other agonists, while no aggregation was elicited with EPN or AA alone. Clopidogrel blocked the ADP-induced aggregation responses in a dose-dependent fashion in vitro. Camel platelet aggregation can be activated by increasing the dose of some agonists such as ADP, but not AA or EPN. Irreversible aggregation of camel platelets could also be triggered by a combination of EPN and ADP, and collagen and AA. Inhibition with clopidogrel suggests that camel platelets express the ADP receptor, P2Y12. Understanding platelet function in camels will add to the understanding of platelet function in health and disease. © 2013 American Society for Veterinary Clinical Pathology.

Minimizing mixing intensity to improve the performance of rice straw anaerobic digestion via enhanced development of microbe-substrate aggregates.

PubMed

Kim, Moonkyung; Kim, Byung-Chul; Choi, Yongju; Nam, Kyoungphile

2017-12-01

The aim of this work was to study the effect of the differential development of microbe-substrate aggregates at different mixing intensities on the performance of anaerobic digestion of rice straw. Batch and semi-continuous reactors were operated for up to 50 and 300days, respectively, under different mixing intensities. In both batch and semi-continuous reactors, minimal mixing conditions exhibited maximum methane production and lignocellulose biodegradability, which both had strong correlations with the development of microbe-substrate aggregates. The results implied that the aggregated microorganisms on the particulate substrate played a key role in rice straw hydrolysis, determining the performance of anaerobic digestion. Increasing the mixing speed from 50 to 150rpm significantly reduced the methane production rate by disintegrating the microbe-substrate aggregates in the semi-continuous reactor. A temporary stress of high-speed mixing fundamentally affected the microbial communities, increasing the possibility of chronic reactor failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-01-01

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

Use of Cement Kiln Dust, Blast Furnace Slag and Marble Sludge in the Manufacture of Sustainable Artificial Aggregates by Means of Cold Bonding Pelletization.

PubMed

Colangelo, Francesco; Cioffi, Raffaele

2013-07-25

In this work, three different samples of solid industrial wastes cement kiln dust (CKD), granulated blast furnace slag and marble sludge were employed in a cold bonding pelletization process for the sustainable production of artificial aggregates. The activating action of CKD components on the hydraulic behavior of the slag was explored by evaluating the neo-formed phases present in several hydrated pastes. Particularly, the influence of free CaO and sulfates amount in the two CKD samples on slag reactivity was evaluated. Cold bonded artificial aggregates were characterized by determining physical and mechanical properties of two selected size fractions of the granules for each studied mixture. Eighteen types of granules were employed in C28/35 concrete manufacture where coarser natural aggregate were substituted with the artificial ones. Finally, lightweight concretes were obtained, proving the suitability of the cold bonding pelletization process in artificial aggregate sustainable production.

Use of Cement Kiln Dust, Blast Furnace Slag and Marble Sludge in the Manufacture of Sustainable Artificial Aggregates by Means of Cold Bonding Pelletization

PubMed Central

Colangelo, Francesco; Cioffi, Raffaele

2013-01-01

In this work, three different samples of solid industrial wastes cement kiln dust (CKD), granulated blast furnace slag and marble sludge were employed in a cold bonding pelletization process for the sustainable production of artificial aggregates. The activating action of CKD components on the hydraulic behavior of the slag was explored by evaluating the neo-formed phases present in several hydrated pastes. Particularly, the influence of free CaO and sulfates amount in the two CKD samples on slag reactivity was evaluated. Cold bonded artificial aggregates were characterized by determining physical and mechanical properties of two selected size fractions of the granules for each studied mixture. Eighteen types of granules were employed in C28/35 concrete manufacture where coarser natural aggregate were substituted with the artificial ones. Finally, lightweight concretes were obtained, proving the suitability of the cold bonding pelletization process in artificial aggregate sustainable production. PMID:28811427

Self-Healing Capacity of Asphalt Mixtures Including By-Products Both as Aggregates and Heating Inductors.

PubMed

Vila-Cortavitarte, Marta; Jato-Espino, Daniel; Castro-Fresno, Daniel; Calzada-Pérez, Miguel Á

2018-05-15

Major advances have been achieved in the field of self-healing by magnetic induction in which the addition of metallic particles into asphalt mixtures enables repairing their own cracks. This technology has already been proven to increase the life expectancy of roads. Nevertheless, its higher costs in comparison with conventional maintenance caused by the price of virgin metallic particles still makes it unattractive for investment. This research aimed at making this process economically accessible as well as environmentally efficient. To this end, an intense search for suitable industrial by-products to substitute both the virgin metal particles and the natural aggregates forming asphalt mixtures was conducted. The set of by-products used included sand blasting wastes, stainless shot wastes, and polished wastes as metallic particles and other inert by-products as aggregates. The results demonstrated that the by-products were adequately heated, which leads to satisfactory healing ratios in comparison with the reference mixture.

Self-Healing Capacity of Asphalt Mixtures Including By-Products Both as Aggregates and Heating Inductors

PubMed Central

Castro-Fresno, Daniel; Calzada-Pérez, Miguel Á.

2018-01-01

Major advances have been achieved in the field of self-healing by magnetic induction in which the addition of metallic particles into asphalt mixtures enables repairing their own cracks. This technology has already been proven to increase the life expectancy of roads. Nevertheless, its higher costs in comparison with conventional maintenance caused by the price of virgin metallic particles still makes it unattractive for investment. This research aimed at making this process economically accessible as well as environmentally efficient. To this end, an intense search for suitable industrial by-products to substitute both the virgin metal particles and the natural aggregates forming asphalt mixtures was conducted. The set of by-products used included sand blasting wastes, stainless shot wastes, and polished wastes as metallic particles and other inert by-products as aggregates. The results demonstrated that the by-products were adequately heated, which leads to satisfactory healing ratios in comparison with the reference mixture. PMID:29762533

New Insights from Sum Frequency Generation Vibrational Spectroscopy into the Interactions of Islet Amyloid Polypeptides with Lipid Membranes

PubMed Central

Wang, Zhuguang; Batista, Victor S.; Yan, Elsa C. Y.

2016-01-01

Studies of amyloid polypeptides on membrane surfaces have gained increasing attention in recent years. Several studies have revealed that membranes can catalyze protein aggregation and that the early products of amyloid aggregation can disrupt membrane integrity, increasing water permeability and inducing ion cytotoxicity. Nonetheless, probing aggregation of amyloid proteins on membrane surfaces is challenging. Surface-specific methods are required to discriminate contributions of aggregates at the membrane interface from those in the bulk phase and to characterize protein secondary structures in situ and in real time without the use of perturbing spectroscopic labels. Here, we review the most recent applications of sum frequency generation (SFG) vibrational spectroscopy applied in conjunction with computational modeling techniques, a joint experimental and computational methodology that has provided valuable insights into the aggregation of islet amyloid polypeptide (IAPP) on membrane surfaces. These applications show that SFG can provide detailed information about structures, kinetics, and orientation of IAPP during interfacial aggregation, relevant to the molecular mechanisms of type II diabetes. These recent advances demonstrate the promise of SFG as a new approach for studying amyloid diseases at the molecular level and for the rational drug design targeting early aggregation products on membrane surfaces. PMID:26697504

Geologic and societal factors affecting the international oceanic transport of aggregate

USGS Publications Warehouse

Langer, W.H.

1995-01-01

Crushed stone and sand and gravel are the two main sources of natural aggregate, and together comprise approximately half the volume and tonnage of mined material in the United States. Natural aggregate is a bulky, heavy material without special or unique properties, and it is commonly used near its source of production to minimize haulage cost. However, remoteness is no longer an absolute disqualifier for the production of aggregate. Today interstate aggregate routinely is shipped hundreds of kilometers by rail and barge. In addition, during 1992, the United States imported 1,317,000 metric tons of aggregate from Canada and 1,531,000 metric tons from Mexico. A number of ports on the Atlantic Coast and Gulf Coast of the United States receive imports of crushed stone from foreign sources for transport to various parts of the eastern United States. These areas either lack adequate supplies of aggregate or are augmenting their supplies because they have difficulties meeting current demand. These difficulties may include poor stone quality, environmental permitting problems, or transportation. Certain societal and geologic conditions of New York City and Philadelphia along the Atlantic Coast, and Tampa and New Orleans along the Gulf Coast, are discussed to demonstrate the different combinations of issues that contribute to the economic viability of importing crushed stone. ?? 1995 Oxford University Press.

Tyrosine- and tryptophan-coated gold nanoparticles inhibit amyloid aggregation of insulin.

PubMed

Dubey, Kriti; Anand, Bibin G; Badhwar, Rahul; Bagler, Ganesh; Navya, P N; Daima, Hemant Kumar; Kar, Karunakar

2015-12-01

Here, we have strategically synthesized stable gold (AuNPs(Tyr), AuNPs(Trp)) and silver (AgNPs(Tyr)) nanoparticles which are surface functionalized with either tyrosine or tryptophan residues and have examined their potential to inhibit amyloid aggregation of insulin. Inhibition of both spontaneous and seed-induced aggregation of insulin was observed in the presence of AuNPs(Tyr), AgNPs(Tyr), and AuNPs(Trp) nanoparticles. These nanoparticles also triggered the disassembly of insulin amyloid fibrils. Surface functionalization of amino acids appears to be important for the inhibition effect since isolated tryptophan and tyrosine molecules did not prevent insulin aggregation. Bioinformatics analysis predicts involvement of tyrosine in H-bonding interactions mediated by its C=O, -NH2, and aromatic moiety. These results offer significant opportunities for developing nanoparticle-based therapeutics against diseases related to protein aggregation.

Development of the method of aggregation to determine the current storage area using computer vision and radiofrequency identification

NASA Astrophysics Data System (ADS)

Astafiev, A.; Orlov, A.; Privezencev, D.

2018-01-01

The article is devoted to the development of technology and software for the construction of positioning and control systems in industrial plants based on aggregation to determine the current storage area using computer vision and radiofrequency identification. It describes the developed of the project of hardware for industrial products positioning system in the territory of a plant on the basis of radio-frequency grid. It describes the development of the project of hardware for industrial products positioning system in the plant on the basis of computer vision methods. It describes the development of the method of aggregation to determine the current storage area using computer vision and radiofrequency identification. Experimental studies in laboratory and production conditions have been conducted and described in the article.

FUS/TLS acts as an aggregation-dependent modifier of polyglutamine disease model mice.

PubMed

Kino, Yoshihiro; Washizu, Chika; Kurosawa, Masaru; Yamada, Mizuki; Doi, Hiroshi; Takumi, Toru; Adachi, Hiroaki; Katsuno, Masahisa; Sobue, Gen; Hicks, Geoffrey G; Hattori, Nobutaka; Shimogori, Tomomi; Nukina, Nobuyuki

2016-10-14

FUS/TLS is an RNA/DNA-binding protein associated with neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Previously, we found that a prion-like domain in the N-terminus of FUS/TLS mediates co-aggregation between FUS/TLS and mutant huntingtin, the gene product of Huntington's disease (HD). Here, we show that heterozygous knockout of FUS/TLS worsened the phenotypes of model mice of (HD, but not spinal and bulbar muscular atrophy (SBMA). This difference was correlated with the degree of pathological association between disease proteins and FUS/TLS. Co-aggregation between FUS/TLS and mutant huntingtin resulted in the depletion of free FUS/TLS protein in HD mice that was detected as a monomer in SDS-PAGE analysis. Recently, we found that FUS/TLS paralogs, TAF15 and EWS, were up-regulated in homozygous FUS/TLS knockout mice. These two proteins were up-regulated in both HD and FUS/TLS heterozygote mice, and were further elevated in HD-TLS +/- double mutant mice, consistent with the functional impairment of FUS/TLS. These results suggest that FUS/TLS sequestration by co-aggregation is a rate-limiting factor of disease phenotypes of HD and that inclusions may have an adverse aspect, rather than being simply benign or protective. In addition, our results highlight inclusions as repositories of potential modifiers of neurodegeneration.

Lactobacillus rhamnosus GG (ATCC 53103) and platelet aggregation in vitro.

PubMed

Korpela, R; Moilanen, E; Saxelin, M; Vapaatalo, H

1997-06-17

Lactobacillus rhamnosus GG is an experimentally and clinically well documented probiotic used in different dairy products. The present study aimed to investigate the safety aspects of Lactobacillus rhamnosus GG, particularly with respect to platelet aggregation, the initiating event in thrombosis. Platelet rich plasma was separated from the blood of healthy volunteers, and the effects of Lactobacillus rhamnosus GG (ATCC 53103), Lactobacillus rhamnosus (ATCC 7469) and Enterococcus faecium T2L6 in different dilutions on spontaneous, ADP- and adrenaline-induced aggregation were tested. The bacteria did not influence spontaneous aggregation. Only Enterococcus faecium T2L6 enhanced the adrenaline-induced aggregation, with a less clear effect on ADP-induced aggregation.

Mechanical and Physical Properties of Hydrophobized Lightweight Aggregate Concrete with Sewage Sludge

PubMed Central

Suchorab, Zbigniew; Barnat-Hunek, Danuta; Franus, Małgorzata; Łagód, Grzegorz

2016-01-01

This article is focused on lightweight aggregate-concrete modified by municipal sewage sludge and lightweight aggregate-concrete obtained from light aggregates. The article presents laboratory examinations of material physical parameters. Water absorptivity of the examined material was decreased by the admixture of water emulsion of reactive polysiloxanes. Water transport properties were determined using Time Domain Reflectometry, an indirect technique for moisture detection in porous media. Together with basic physical parameters, the heat conductivity coefficient λ was determined for both types of lightweight aggregate-concrete. Analysis of moisture and heat properties of the examined materials confirmed the usefulness of light aggregates supplemented with sewage sludge for prospective production. PMID:28773442

Performance and durability of concrete made with demolition waste and artificial fly ash-clay aggregates

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

Zakaria, M.; Cabrera, J.G.

1996-12-31

Demolition aggregates and artificial aggregates made with waste materials are two alternatives being studied for replacement of natural aggregates in the production of concrete. Natural aggregate sources in Europe are increasingly scarce and subject to restrictions based on environmental regulations. In many areas of the developing world sources of good quality aggregates are very limited or practically not available and therefore it has become necessary to study alternative materials. This paper presents a laboratory study on the use of demolition bricks and artificial aggregates made from fly ash-clay as coarse aggregates to make concrete. The concretes made either with demolitionmore » bricks or artificial aggregates are compared with a control mix made with natural gravel aggregates. The strength and durability characteristics of these concretes are evaluated using as a criteria compressive strength and transport properties, such as gas and water permeability. The results show clearly that concretes of good performance and durability can be produced using aggregates from demolition rubble or using artificial aggregates made with wastes such as fly ash.« less

Automation of aggregate characterization using laser profiling and digital image analysis

NASA Astrophysics Data System (ADS)

Kim, Hyoungkwan

2002-08-01

Particle morphological properties such as size, shape, angularity, and texture are key properties that are frequently used to characterize aggregates. The characteristics of aggregates are crucial to the strength, durability, and serviceability of the structure in which they are used. Thus, it is important to select aggregates that have proper characteristics for each specific application. Use of improper aggregate can cause rapid deterioration or even failure of the structure. The current standard aggregate test methods are generally labor-intensive, time-consuming, and subject to human errors. Moreover, important properties of aggregates may not be captured by the standard methods due to a lack of an objective way of quantifying critical aggregate properties. Increased quality expectations of products along with recent technological advances in information technology are motivating new developments to provide fast and accurate aggregate characterization. The resulting information can enable a real time quality control of aggregate production as well as lead to better design and construction methods of portland cement concrete and hot mix asphalt. This dissertation presents a system to measure various morphological characteristics of construction aggregates effectively. Automatic measurement of various particle properties is of great interest because it has the potential to solve such problems in manual measurements as subjectivity, labor intensity, and slow speed. The main efforts of this research are placed on three-dimensional (3D) laser profiling, particle segmentation algorithms, particle measurement algorithms, and generalized particle descriptors. First, true 3D data of aggregate particles obtained by laser profiling are transformed into digital images. Second, a segmentation algorithm and a particle measurement algorithm are developed to separate particles and process each particle data individually with the aid of various kinds of digital image technologies. Finally, in order to provide a generalized, quantitative, and representative way to characterize aggregate particles, 3D particle descriptors are developed using the multi-resolution analysis feature of wavelet transforms. Verification tests show that this approach could characterize various aggregate properties in a fast, accurate, and reliable way. When implemented, this ability to automatically analyze multiple characteristics of an aggregate sample is expected to provide not only economic but also intangible strategic gains.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1999-10-12

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1996-01-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, C.R.; Niemeyer, C.M.; Smith, C.L.; Sano, Takeshi; Hnatowich, D.J.; Rusckowski, M.

1996-10-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products. 5 figs.

Bacterial Inclusion Bodies: Discovering Their Better Half.

PubMed

Rinas, Ursula; Garcia-Fruitós, Elena; Corchero, José Luis; Vázquez, Esther; Seras-Franzoso, Joaquin; Villaverde, Antonio

2017-09-01

Bacterial inclusion bodies (IBs) are functional, non-toxic amyloids occurring in recombinant bacteria showing analogies with secretory granules of the mammalian endocrine system. The scientific interest in these mesoscale protein aggregates has been historically masked by their status as a hurdle in recombinant protein production. However, progressive understanding of how the cell handles the quality of recombinant polypeptides and the main features of their intriguing molecular organization has stimulated the interest in inclusion bodies and spurred their use in diverse technological fields. The engineering and tailoring of IBs as functional protein particles for materials science and biomedicine is a good example of how formerly undesired bacterial byproducts can be rediscovered as promising functional materials for a broad spectrum of applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal function.

PubMed

Kim, Dong-Kyu; Lim, Hee-Sun; Kawasaki, Ichiro; Shim, Yhong-Hee; Vaikath, Nishant N; El-Agnaf, Omar M A; Lee, He-Jin; Lee, Seung-Jae

2016-10-02

Aging is the major risk factor for neurodegenerative diseases that are also associated with impaired proteostasis, resulting in abnormal accumulation of protein aggregates. However, the role of aging in development and progression of disease remains elusive. Here, we used Caenorhabditis elegans models to show that aging-promoting genetic variations accelerated the rate of cell-to-cell transmission of SNCA/α-synuclein aggregates, hallmarks of Parkinson disease, and the progression of disease phenotypes, such as nerve degeneration, behavioral deficits, and reduced life span. Genetic and pharmacological anti-aging manipulations slowed the spread of aggregates and the associated phenotypes. Lysosomal degradation was significantly impaired in aging models, while anti-aging treatments reduced the impairment. Transgenic expression of hlh-30p::hlh-30, the master controller of lysosomal biogenesis, alleviated intercellular transmission of aggregates in the aging model. Our results demonstrate that the rate of aging closely correlates with the rate of aggregate propagation and that general anti-aging treatments can slow aggregate propagation and associated disease progression by restoring lysosomal function.

A novel approach to a fine particle coating using porous spherical silica as core particles.

PubMed

Ishida, Makoto; Uchiyama, Jumpei; Isaji, Keiko; Suzuki, Yuta; Ikematsu, Yasuyuki; Aoki, Shigeru

2014-08-01

Abstract The applicability of porous spherical silica (PSS) was evaluated as core particles for pharmaceutical products by comparing it with commercial core particles such as mannitol (NP-108), sucrose and microcrystalline cellulose spheres. We investigated the physical properties of core particles, such as particle size distribution, flow properties, crushing strength, plastic limit, drying rate, hygroscopic property and aggregation degree. It was found that PSS was a core particle of small particle size, low friability, high water adsorption capacity, rapid drying rate and lower occurrence of particle aggregation, although wettability is a factor to be carefully considered. The aggregation and taste-masking ability using PSS and NP-108 as core particles were evaluated at a fluidized-bed coating process. The functional coating under the excess spray rate shows different aggregation trends and dissolution profiles between PSS and NP-108; thereby, exhibiting the formation of uniform coating under the excess spray rate in the case of PSS. This expands the range of the acceptable spray feed rates to coat fine particles, and indicates the possibility of decreasing the coating time. The results obtained in this study suggested that the core particle, which has a property like that of PSS, was useful in overcoming such disadvantages as large particle size, which feels gritty in oral cavity; particle aggregation; and the long coating time of the particle coating process. These results will enable the practical fine particle coating method by increasing the range of optimum coating conditions and decreasing the coating time in fluidized bed technology.

Reduction in soil aggregate size distribution due to wind erosion

NASA Astrophysics Data System (ADS)

Swet, Nitzan; Katra, Itzhak

2017-04-01

Soil erosion process by wind causes emission of fine soil particles, and thus alters the topsoil's properties, fertility, and erodibility. Topsoil resistance to erosion depends on its physicochemical properties, especially on the soil aggregation. Although the key role of aggregates in soil erodibility, quantitative information on the relations between soil aggregate size distribution (ASD) and erosion is still lucking. This study focuses on ASD analyses before and after soil erosion by wind. Wind tunnel experiments and soil analyses were conducted on semiarid loess topsoils with different initial conditions of aggregation. The results show that in all initial soil conditions saltation of sand particles caused the breakdown of macro-aggregates > 500 µm, resulting in increase of micro-aggregates (63-250 µm). The micro-aggregate production increases with the wind shear velocity (up to 0.61 m s-1) for soils with available macro-aggregates. The findings highlight dynamics in soil aggregation in response to erosion process, and therefore the significance of ASD in quantifying soil degradation and soil loss potential.

The roles of prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation in man and the rat.

PubMed Central

Emms, H.; Lewis, G. P.

1986-01-01

The effects of aspirin, carboxyheptylimidazole (CHI) and creatine phosphate/creatine phosphokinase (CP/CPK) on platelet aggregation and thromboxane B2 (TxB2) formation induced by collagen have been examined in vitro. Platelets from two species, man and the rat, have been used. In man, aspirin and CHI abolished TxB2 production but only partially inhibited aggregation. CP/CPK partially inhibited aggregation and TxB2 formation. In the rat, aspirin and CHI abolished TxB2 formation but had no effect on aggregation. CP/CPK completely inhibited aggregation and partially inhibited TxB2 generation. In man, collagen-induced aggregation is largely dependent on ADP and to a lesser extent on arachidonate metabolites whereas, in the rat, ADP alone mediates aggregation induced by this agonist. The results with CP/CPK suggest that TxB2 formation is dependent either on the prior release of platelet ADP or on aggregation itself rather than being responsible for the aggregation response. PMID:3082399

Synthesis of Efficient Structures for Concurrent Computation.

DTIC Science & Technology

1983-10-01

formal presentation of these techniques, called virtualisation and aggregation, can be found n [King-83$. 113.2 Census Functions Trees perform broadcast... Functions .. .. .. .. ... .... ... ... .... ... ... ....... 6 4 User-Assisted Aggregation .. .. .. .. ... ... ... .... ... .. .......... 6 5 Parallel...6. Simple Parallel Structure for Broadcasting .. .. .. .. .. . ... .. . .. . .... 4 Figure 7. Internal Structure of a Prefix Computation Network

Aggregation Pheromone System: A Real-parameter Optimization Algorithm using Aggregation Pheromones as the Base Metaphor

NASA Astrophysics Data System (ADS)

Tsutsui, Shigeyosi

This paper proposes an aggregation pheromone system (APS) for solving real-parameter optimization problems using the collective behavior of individuals which communicate using aggregation pheromones. APS was tested on several test functions used in evolutionary computation. The results showed APS could solve real-parameter optimization problems fairly well. The sensitivity analysis of control parameters of APS is also studied.

Influence of gold nanoparticles on platelets functional activity in vitro

NASA Astrophysics Data System (ADS)

Akchurin, Garif G.; Akchurin, George G.; Ivanov, Alexey N.; Kirichuk, Vyacheslav F.; Terentyuk, George S.; Khlebtsov, Boris N.; Khlebtsov, Nikolay G.

2008-02-01

Now in the leading biomedical centers of the world approved new technology of laser photothermal destruction of cancer cells using plasmon gold nanoparticles. Investigations of influence of gold nanoparticles on white rat platelets aggregative activity in vitro have been made. Platelet aggregation was investigated in platelet rich plasma (PRP) with help of laser analyzer 230 LA <>, Russia). Aggregation inductor was ADP solution in terminal concentration 2.5 micromole (<>, Russia). Gold nanoshells soluted in salt solution were used for experiments. Samples of PRP were incubated with 50 or 100 μl gold nanoshells solution in 5 minute, after that we made definition ADP induced platelet aggregation. We found out increase platelet function activity after incubation with nanoparticles solution which shown in maximum ADP-induced aggregation degree increase. Increase platelet function activity during intravenous nanoshells injection can be cause of thrombosis on patients. That's why before clinical application of cancer cell destruction based on laser photothermal used with plasmon gold nanoparticles careful investigations of thrombosis process and detail analyze of physiological blood parameters are very necessary.

Genipin-crosslinked microcarriers mediating hepatocellular aggregates formation and functionalities.

PubMed

Lau, Ting Ting; Wang, Chunming; Png, Sze Wei; Su, Kai; Wang, Dong-An

2011-01-01

In engineered regenerative medicine, various types of scaffolds have been customized to pursue the optimal environment for different types of therapeutic cells. In liver therapeutic research, hepatocytes require attachment to solid anchors for survival and proliferation before they could grow into cellular aggregates with enhanced functionalities. Among the various biomaterials scaffolds and vehicles, microspherical cell carriers are suited to these requirements. Individual spheres may provide two-dimensional (2D) cell-affinitive surfaces for cell adhesion and spreading; whereas multiple microcarriers may form three-dimensional (3D) matrices with inter-spherical space for cell expansion and multicellular aggregation. In this study, we culture human liver carcinoma cell line (HepG2) cells on genipin-crosslinked gelatin microspheres of two different sizes. Results suggest that both microcarriers support cell adhesion, proliferation, and spontaneous formation of hepatocellular aggregates, among which the spheres with bigger size (200-300 μm) seem more favorable than the smaller ones in terms of aggregate formation and liver specific functionalities. These findings suggest that the genipin-crosslinked microcarrier is a competent vehicle for liver cell delivery. Copyright © 2010 Wiley Periodicals, Inc.

Physio-chemical reactions in recycle aggregate concrete.

PubMed

Tam, Vivian W Y; Gao, X F; Tam, C M; Ng, K M

2009-04-30

Concrete waste constitutes the major proportion of construction waste at about 50% of the total waste generated. An effective way to reduce concrete waste is to reuse it as recycled aggregate (RA) for the production of recycled aggregate concrete (RAC). This paper studies the physio-chemical reactions of cement paste around aggregate for normal aggregate concrete (NAC) and RAC mixed with normal mixing approach (NMA) and two-stage mixing approach (TSMA) by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Four kinds of physio-chemical reactions have been recorded from the concrete samples, including the dehydration of C(3)S(2)H(3), iron-substituted ettringite, dehydroxylation of CH and development of C(6)S(3)H at about 90 degrees C, 135 degrees C, 441 degrees C and 570 degrees C, respectively. From the DSC results, it is confirmed that the concrete samples with RA substitution have generated less amount of strength enhancement chemical products when compared to those without RA substitution. However, the results from the TSMA are found improving the RAC quality. The pre-mix procedure of the TSMA can effectively develop some strength enhancing chemical products including, C(3)S(2)H(3), ettringite, CH and C(6)S(3)H, which shows that RAC made from the TSMA can improve the hydration processes.

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

PubMed

Landgraf-Leurs, M M; Ladik, T; Smolka, B; Bock, T; Schramm, W; Spannagl, M; Landgraf, R

1987-07-01

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Mechanisms linking brain insulin resistance to Alzheimer's disease

PubMed Central

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

Decomposition-aggregation stability analysis. [for large scale dynamic systems with application to spinning Skylab control system

NASA Technical Reports Server (NTRS)

Siljak, D. D.; Weissenberger, S.; Cuk, S. M.

1973-01-01

This report presents the development and description of the decomposition aggregation approach to stability investigations of high dimension mathematical models of dynamic systems. The high dimension vector differential equation describing a large dynamic system is decomposed into a number of lower dimension vector differential equations which represent interconnected subsystems. Then a method is described by which the stability properties of each subsystem are aggregated into a single vector Liapunov function, representing the aggregate system model, consisting of subsystem Liapunov functions as components. A linear vector differential inequality is then formed in terms of the vector Liapunov function. The matrix of the model, which reflects the stability properties of the subsystems and the nature of their interconnections, is analyzed to conclude over-all system stability characteristics. The technique is applied in detail to investigate the stability characteristics of a dynamic model of a hypothetical spinning Skylab.

Data on optimum recycle aggregate content in production of new structural concrete.

PubMed

Paul, Suvash Chandra

2017-12-01

This data presented herein are the research summary of "mechanical behavior and durability performance of concrete containing recycled concrete aggregate" (Paul, 2011) [1]. The results reported in this article relate to an important parameter of optimum content of recycle concrete aggregate (RCA) in production of new concrete for both structural and non-structural applications. For the purpose of the research various types of physical, mechanical and durability tests are performed for concrete made with different percentages of RCA. Therefore, this data set can be a great help of the readers to understand the mechanism of RCA in relates to the concrete properties.

Sugeno Fuzzy Integral as a Basis for the Interpretation of Flexible Queries Involving Monotonic Aggregates.

ERIC Educational Resources Information Center

Bosc, P.; Lietard, L.; Pivert, O.

2003-01-01

Considers flexible querying of relational databases. Highlights include SQL languages and basic aggregate operators; Sugeno's fuzzy integral; evaluation examples; and how and under what conditions other aggregate functions could be applied to fuzzy sets in a flexible query. (Author/LRW)

Traffic-induced changes and processes in forest road aggregate particle-size distributions

Treesearch

Hakjun Rhee; James Fridley; Deborah Page-Dumroese

2018-01-01

Traffic can alter forest road aggregate material in various ways, such as by crushing, mixing it with subgrade material, and sweeping large-size, loose particles (gravel) toward the outside of the road. Understanding the changes and physical processes of the aggregate is essential to mitigate sediment production from forest roads and reduce road maintenance efforts. We...

Zebrafish models of BAG3 myofibrillar myopathy suggest a toxic gain of function leading to BAG3 insufficiency.

PubMed

Ruparelia, Avnika A; Oorschot, Viola; Vaz, Raquel; Ramm, Georg; Bryson-Richardson, Robert J

2014-12-01

Mutations in the co-chaperone Bcl2-associated athanogene 3 (BAG3) can cause myofibrillar myopathy (MFM), a childhood-onset progressive muscle disease, characterized by the formation of protein aggregates and myofibrillar disintegration. In contrast to other MFM-causing proteins, BAG3 has no direct structural role, but regulates autophagy and the degradation of misfolded proteins. To investigate the mechanism of disease in BAG3-related MFM, we expressed wild-type BAG3 or the dominant MFM-causing BAG3 (BAG3(P209L)) in zebrafish. Expression of the mutant protein results in the formation of aggregates that contain wild-type BAG3. Through the stimulation and inhibition of autophagy, we tested the prevailing hypothesis that impaired autophagic function is responsible for the formation of protein aggregates. Contrary to the existing theory, our studies reveal that inhibition of autophagy is not sufficient to induce protein aggregation. Expression of the mutant protein, however, did not induce myofibrillar disintegration and we therefore examined the effect of knocking down Bag3 function. Loss of Bag3 resulted in myofibrillar disintegration, but not in the formation of protein aggregates. Remarkably, BAG3(P209L) is able to rescue the myofibrillar disintegration phenotype, further demonstrating that its function is not impaired. Together, our knockdown and overexpression experiments identify a mechanism whereby BAG3(P209L) aggregates form, gradually reducing the pool of available BAG3, which eventually results in BAG3 insufficiency and myofibrillar disintegration. This mechanism is consistent with the childhood onset and progressive nature of MFM and suggests that reducing aggregation through enhanced degradation or inhibition of nucleation would be an effective therapy for this disease.

A nanoscale bio-inspired light-harvesting system developed from self-assembled alkyl-functionalized metallochlorin nano-aggregates.

PubMed

Ocakoglu, Kasim; Joya, Khurram S; Harputlu, Ersan; Tarnowska, Anna; Gryko, Daniel T

2014-08-21

Self-assembled supramolecular organization of nano-structured biomimetic light-harvesting modules inside solid-state nano-templates can be exploited to develop excellent light-harvesting materials for artificial photosynthetic devices. We present here a hybrid light-harvesting system mimicking the chlorosomal structures of the natural photosynthetic system using synthetic zinc chlorin units (ZnChl-C6, ZnChl-C12 and ZnChl-C18) that are self-aggregated inside the anodic aluminum oxide (AAO) nano-channel membranes. AAO nano-templates were modified with a TiO2 matrix and functionalized with long hydrophobic chains to facilitate the formation of supramolecular Zn-chlorin aggregates. The transparent Zn-chlorin nano-aggregates inside the alkyl-TiO2 modified AAO nano-channels have a diameter of ∼120 nm in a 60 μm length channel. UV-Vis studies and fluorescence emission spectra further confirm the formation of the supramolecular ZnChl aggregates from monomer molecules inside the alkyl-functionalized nano-channels. Our results prove that the novel and unique method can be used to produce efficient and stable light-harvesting assemblies for effective solar energy capture through transparent and stable nano-channel ceramic materials modified with bio-mimetic molecular self-assembled nano-aggregates.

The durability of concrete containing recycled tyres as a partial replacement of fine aggregate

NASA Astrophysics Data System (ADS)

Syamir Senin, Mohamad; Shahidan, Shahiron; Syazani Leman, Alif; Othman, Nurulain; Shamsuddin, Shamrul-mar; Ibrahim, M. H. W.; Zuki, S. S. Mohd

2017-11-01

Nowadays, uncontrolled disposal of waste materials such as tyres can affect the environment. Therefore, careful management of waste disposal must be done in order to conserve the environment. Waste tyres can be use as a replacement for both fine aggregate and coarse aggregate in the production of concrete. This research was conducted to assess the durability of concrete containing recycled tyres which have been crushed into fine fragments to replace fine aggregate in the concrete mix. This study presents an overview of the use of waste rubber as a partial replacement of natural fine aggregate in a concrete mix. 36 concrete cubes measuring 100mm × 100mm × 100mm and 12 concrete cubes measuring 150mm × 150mm × 150mm were prepared and added with different percentages of rubber from recycled tyres (0%, 3%, 5% and 7%) as fine aggregate replacement. The results obtained show that the replacement of fine aggregate with 7% of rubber recorded a compressive strength of 43.7MPa while the addition of 3% of rubber in the concrete sample recorded a high compressive strength of 50.8MPa. This shows that there is a decrease in the strength and workability of concrete as the amount of rubber used a replacement for fine aggregate in concrete increases. On the other hand, the water absorption test indicated that concrete which contains rubber has better water absorption ability. In this study, 3% of rubber was found to be the optimal percentage as a partial replacement for fine aggregate in the production of concrete.

Feasibility Study on Manufacturing Lightweight Aggregates from Water Purification Sludge

NASA Astrophysics Data System (ADS)

Peng, Ching-Fang; Chen, How-Ji

2018-02-01

This study mainly discussed the feasibility of manufacturing lightweight aggregates from water purification sludge in Taiwan. They were analysed for the physical and chemical composition before the sintering test for lightweight aggregates in a laboratory. Then the physical and mechanical properties of the synthesized aggregates were assessed. The result showed that the chemical composition of sludge in the water purification plants was within the appropriate range for manufacturing lightweight aggregate as proposed in the literature. The sintering test demonstrated that the particle density of aggregates from the ten types of water purification sludge were mostly less than 1.8 g/cm3. In addition, the dry unit weight, the organic impurity, the ignition loss, and other characteristics of synthesized aggregates met the requirement of CNS standards, while its water absorption and crushing strength also fulfilled the general commercial specifications. Therefore, reclamation of water purification sludge for production of lightweight aggregate is indeed feasible.

Strength of masonry blocks made with recycled concrete aggregates

NASA Astrophysics Data System (ADS)

Matar, Pierre; Dalati, Rouba El

The idea of recycling concrete of demolished buildings aims at preserving the environment. Indeed, the reuse of concrete as aggregate in new concrete mixes helped to reduce the expenses related to construction and demolition (C&D) waste management and, especially, to protect the environment by reducing the development rate of new quarries. This paper presents the results of an experimental study conducted on masonry blocks containing aggregates resulting from concrete recycling. The purpose of this study is to investigate the effect of recycled aggregates on compressive strength of concrete blocks. Tests were performed on series of concrete blocks: five series each made of different proportions of recycled aggregates, and one series of reference blocks exclusively composed of natural aggregates. Tests showed that using recycled aggregates with addition of cement allows the production of concrete blocks with compressive strengths comparable to those obtained on concrete blocks made exclusively of natural aggregates.

Passive RFID Rotation Dimension Reduction via Aggregation

NASA Astrophysics Data System (ADS)

Matthews, Eric

Radio Frequency IDentification (RFID) has applications in object identification, position, and orientation tracking. RFID technology can be applied in hospitals for patient and equipment tracking, stores and warehouses for product tracking, robots for self-localisation, tracking hazardous materials, or locating any other desired object. Efficient and accurate algorithms that perform localisation are required to extract meaningful data beyond simple identification. A Received Signal Strength Indicator (RSSI) is the strength of a received radio frequency signal used to localise passive and active RFID tags. Many factors affect RSSI such as reflections, tag rotation in 3D space, and obstacles blocking line-of-sight. LANDMARC is a statistical method for estimating tag location based on a target tag's similarity to surrounding reference tags. LANDMARC does not take into account the rotation of the target tag. By either aggregating multiple reference tag positions at various rotations, or by determining a rotation value for a newly read tag, we can perform an expected value calculation based on a comparison to the k-most similar training samples via an algorithm called K-Nearest Neighbours (KNN) more accurately. By choosing the average as the aggregation function, we improve the relative accuracy of single-rotation LANDMARC localisation by 10%, and any-rotation localisation by 20%.

Surface properties of heat-induced soluble soy protein aggregates of different molecular masses.

PubMed

Guo, Fengxian; Xiong, Youling L; Qin, Fang; Jian, Huajun; Huang, Xiaolin; Chen, Jie

2015-02-01

Suspensions (2% and 5%, w/v) of soy protein isolate (SPI) were heated at 80, 90, or 100 °C for different time periods to produce soluble aggregates of different molecular sizes to investigate the relationship between particle size and surface properties (emulsions and foams). Soluble aggregates generated in these model systems were characterized by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heat treatment increased surface hydrophobicity, induced SPI aggregation via hydrophobic interaction and disulfide bonds, and formed soluble aggregates of different sizes. Heating of 5% SPI always promoted large-size aggregate (LA; >1000 kDa) formation irrespective of temperature, whereas the aggregate size distribution in 2% SPI was temperature dependent: the LA fraction progressively rose with temperature (80→90→100 °C), corresponding to the attenuation of medium-size aggregates (MA; 670 to 1000 kDa) initially abundant at 80 °C. Heated SPI with abundant LA (>50%) promoted foam stability. LA also exhibited excellent emulsifying activity and stabilized emulsions by promoting the formation of small oil droplets covered with a thick interfacial protein layer. However, despite a similar influence on emulsion stability, MA enhanced foaming capacity but were less capable of stabilizing emulsions than LA. The functionality variation between heated SPI samples is clearly related to the distribution of aggregates that differ in molecular size and surface activity. The findings may encourage further research to develop functional SPI aggregates for various commercial applications. © 2015 Institute of Food Technologists®

Amyloid Formation by Human Carboxypeptidase D Transthyretin-like Domain under Physiological Conditions*

PubMed Central

Garcia-Pardo, Javier; Graña-Montes, Ricardo; Fernandez-Mendez, Marc; Ruyra, Angels; Roher, Nerea; Aviles, Francesc X.; Lorenzo, Julia; Ventura, Salvador

2014-01-01

Protein aggregation is linked to a growing list of diseases, but it is also an intrinsic property of polypeptides, because the formation of functional globular proteins comes at the expense of an inherent aggregation propensity. Certain proteins can access aggregation-prone states from native-like conformations without the need to cross the energy barrier for unfolding. This is the case of transthyretin (TTR), a homotetrameric protein whose dissociation into its monomers initiates the aggregation cascade. Domains with structural homology to TTR exist in a number of proteins, including the M14B subfamily carboxypeptidases. We show here that the monomeric transthyretin-like domain of human carboxypeptidase D aggregates under close to physiological conditions into amyloid structures, with the population of folded but aggregation-prone states being controlled by the conformational stability of the domain. We thus confirm that the TTR fold keeps a generic residual aggregation propensity upon folding, resulting from the presence of preformed amyloidogenic β-strands in the native state. These structural elements should serve for functional/structural purposes, because they have not been purged out by evolution, but at the same time they put proteins like carboxypeptidase D at risk of aggregation in biological environments and thus can potentially lead to deposition diseases. PMID:25294878

The infrared spectral transmittance of Aspergillus niger spore aggregated particle swarm

NASA Astrophysics Data System (ADS)

Zhao, Xinying; Hu, Yihua; Gu, Youlin; Li, Le

2015-10-01

Microorganism aggregated particle swarm, which is quite an important composition of complex media environment, can be developed as a new kind of infrared functional materials. Current researches mainly focus on the optical properties of single microorganism particle. As for the swarm, especially the microorganism aggregated particle swarm, a more accurate simulation model should be proposed to calculate its extinction effect. At the same time, certain parameters deserve to be discussed, which helps to better develop the microorganism aggregated particle swarm as a new kind of infrared functional materials. In this paper, take Aspergillus Niger spore as an example. On the one hand, a new calculation model is established. Firstly, the cluster-cluster aggregation (CCA) model is used to simulate the structure of Aspergillus Niger spore aggregated particle. Secondly, the single scattering extinction parameters for Aspergillus Niger spore aggregated particle are calculated by using the discrete dipole approximation (DDA) method. Thirdly, the transmittance of Aspergillus Niger spore aggregated particle swarm is simulated by using Monte Carlo method. On the other hand, based on the model proposed above, what influences can wavelength causes has been studied, including the spectral distribution of scattering intensity of Aspergillus Niger spore aggregated particle and the infrared spectral transmittance of the aggregated particle swarm within the range of 8-14μm incident infrared wavelengths. Numerical results indicate that the scattering intensity of Aspergillus Niger spore aggregated particle reduces with the increase of incident wavelengths at each scattering angle. Scattering energy mainly concentrates on the scattering angle between 0-40°, forward scattering has an obvious effect. In addition, the infrared transmittance of Aspergillus Niger spore aggregated particle swarm goes up with the increase of incident wavelengths. However, some turning points of the trend are associated with the absorption capacity of the swarm. When parameters of the swarm are set as follows: each Aspergillus Niger spore aggregated particle contains 40 original particles, the radius of original particle is 1.5μm, the density of aggregated particles is around 200/cm3, the measurement area is 4 meters thick, under conditions mentioned above, the infrared transmittance can be less than 10% between the incident wavelengths of 9.5-13μm. In the end, all the results provide the basis for better developing the microorganism aggregated particle swarm as a new kind of infrared functional materials and precisely choosing the effective defiladed infrared band.

Modeling cereal starch hydrolysis during simultaneous saccharification and lactic acid fermentation; case of a sorghum-based fermented beverage, gowé.

PubMed

Mestres, Christian; Bettencourt, Munanga de J C; Loiseau, Gérard; Matignon, Brigitte; Grabulos, Joël; Achir, Nawel

2017-10-01

Gowé is an acidic beverage obtained after simultaneous saccharification and fermentation (SSF) of sorghum. A previous paper focused on modeling the growth of lactic acid bacteria during gowé processing. This paper focuses on modeling starch amylolysis to build an aggregated SSF model. The activity of α-amylase was modeled as a function of temperature and pH, and the hydrolysis rates of both native and soluble starch were modeled via a Michaelis-Menten equation taking into account the maltose and glucose inhibition constants. The robustness of the parameter estimators was ensured by step by step identification in sets of experiments conducted with different proportions of native and gelatinized starch by modifying the pre-cooking temperature. The aggregated model was validated on experimental data and showed that both the pre-cooking and fermentation parameters, particularly temperature, are significant levers for controlling not only acid and sugar contents but also the expected viscosity of the final product. This generic approach could be used as a tool to optimize the sanitary and sensory quality of fermentation of other starchy products. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level

PubMed Central

Khan, Mohd Adnan; Arif, Zarina; Khan, Mohd Asad; Moinuddin

2018-01-01

Hyperglycaemia triggers increased production of methylglyoxal which can cause gross modification in proteins’ structure vis-a-vis function though advanced glycation end products (AGEs). The AGEs may initiate vascular and nonvascular pathologies. In this study, we have examined the biochemical and biophysical changes in human IgG under normal and high glucose after introducing methylglyoxal into the assay mixture. This non-enzymatic reaction mainly engaged lysine residues as indicated by TNBS results. The UV results showed hyperchromicity in modified-IgG samples while fluorescence data supported AGEs formation during the course of reaction. Shift in amide I and amide II band position indicated perturbations in secondary structure. Increase carbonyl content and decrease in sulfhydryl suggests that the modification is accompanied by oxidative stress. All modified-IgG samples showed more thermostability than native IgG; the highest Tm was shown by IgG-high glucose-MGO variant. Results of ANS, Congo red and Thioflavin T dyes clearly suggest increase in hydrophobic patches and aggregation, respectively. SEM and TEM images support aggregates generation in modified-IgG samples. PMID:29351321

Prediction and Reduction of the Aggregation of Monoclonal Antibodies.

PubMed

van der Kant, Rob; Karow-Zwick, Anne R; Van Durme, Joost; Blech, Michaela; Gallardo, Rodrigo; Seeliger, Daniel; Aßfalg, Kerstin; Baatsen, Pieter; Compernolle, Griet; Gils, Ann; Studts, Joey M; Schulz, Patrick; Garidel, Patrick; Schymkowitz, Joost; Rousseau, Frederic

2017-04-21

Protein aggregation remains a major area of focus in the production of monoclonal antibodies. Improving the intrinsic properties of antibodies can improve manufacturability, attrition rates, safety, formulation, titers, immunogenicity, and solubility. Here, we explore the potential of predicting and reducing the aggregation propensity of monoclonal antibodies, based on the identification of aggregation-prone regions and their contribution to the thermodynamic stability of the protein. Although aggregation-prone regions are thought to occur in the antigen binding region to drive hydrophobic binding with antigen, we were able to rationally design variants that display a marked decrease in aggregation propensity while retaining antigen binding through the introduction of artificial aggregation gatekeeper residues. The reduction in aggregation propensity was accompanied by an increase in expression titer, showing that reducing protein aggregation is beneficial throughout the development process. The data presented show that this approach can significantly reduce liabilities in novel therapeutic antibodies and proteins, leading to a more efficient path to clinical studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Coal Combustion Wastes Reuse in Low Energy Artificial Aggregates Manufacturing.

PubMed

Ferone, Claudio; Colangelo, Francesco; Messina, Francesco; Iucolano, Fabio; Liguori, Barbara; Cioffi, Raffaele

2013-10-31

Sustainable building material design relies mostly on energy saving processes, decrease of raw materials consumption, and increase of waste and by-products recycling. Natural and lightweight artificial aggregates production implies relevant environmental impact. This paper addresses both the issues of residues recycling and energy optimization. Particularly, three coal combustion wastes (Weathered Fly Ash, WFA; Wastewater Treatment Sludge, WTS; Desulfurization Device Sludge, DDS) supplied by the Italian electric utility company (ENEL) have been employed in the manufacture of cold bonded artificial aggregates. Previously, the residues have been characterized in terms of chemical and mineralogical compositions, water content, particle size distribution, and heavy metal release behavior. These wastes have been used in the mix design of binding systems with the only addition of lime. Finally, the artificial aggregates have been submitted to physical, mechanical, and leaching testing, revealing that they are potentially suitable for many civil engineering applications.

Rational Design of Biobetters with Enhanced Stability.

PubMed

Courtois, Fabienne; Schneider, Curtiss P; Agrawal, Neeraj J; Trout, Bernhardt L

2015-08-01

Biotherapeutics are the fastest growing class of pharmaceutical with a rapidly evolving market facing the rise of biosimilar and biobetter products. In contrast to a biosimilar, which is derived from the same gene sequence as the innovator product, a biobetter has enhanced properties, such as enhanced efficacy or reduced immunogenicity. Little work has been carried out so far to increase the intrinsic stability of biotherapeutics via sequence changes, even though, aggregation, the primary degradation pathway of proteins, leads to issues ranging from manufacturing failure to immunological response and to loss of therapeutic activity. Using our spatial aggregation propensity tool as a first step to a rational design approach to identify aggregation-prone regions, biobetters of rituximab have been produced with enhanced stability by introducing site-specific mutations. Significant stabilization against aggregation was achieved for rituximab with no decrease in its binding affinity to the antigen. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effects of oxidative modification on thermal aggregation and gel properties of soy protein by malondialdehyde.

PubMed

Wu, Wei; Hua, Yufei; Lin, Qinlu

2014-03-01

Malondialdehyde (MDA) was selected as a representative of lipid peroxidation products to investigate the effects of oxidative modification on thermal aggregation and gel properties of soy protein by lipid peroxidation products. Incubation of soy protein with increasing concentration of MDA resulted in gradual decrease of particle size and content of thermal aggregates during heat denaturation. Oxidative modification by MDA resulted in a decrease in water holding capacity, gel hardness, and gel strength of soy protein gel. An increase in coarseness and interstice of MDA modified protein gel network was accompanied by uneven distribution of interstice as MDA concentration increased. The results showed that degree of thermal aggregation of MDA-modified soy protein gradually decreased as MDA concentration increased, which contributed to a decrease in water holding capacity, gel hardness, and gel strength of MDA-modified soy protein gel.

Coal Combustion Wastes Reuse in Low Energy Artificial Aggregates Manufacturing

PubMed Central

Ferone, Claudio; Colangelo, Francesco; Messina, Francesco; Iucolano, Fabio; Liguori, Barbara; Cioffi, Raffaele

2013-01-01

Sustainable building material design relies mostly on energy saving processes, decrease of raw materials consumption, and increase of waste and by-products recycling. Natural and lightweight artificial aggregates production implies relevant environmental impact. This paper addresses both the issues of residues recycling and energy optimization. Particularly, three coal combustion wastes (Weathered Fly Ash, WFA; Wastewater Treatment Sludge, WTS; Desulfurization Device Sludge, DDS) supplied by the Italian electric utility company (ENEL) have been employed in the manufacture of cold bonded artificial aggregates. Previously, the residues have been characterized in terms of chemical and mineralogical compositions, water content, particle size distribution, and heavy metal release behavior. These wastes have been used in the mix design of binding systems with the only addition of lime. Finally, the artificial aggregates have been submitted to physical, mechanical, and leaching testing, revealing that they are potentially suitable for many civil engineering applications. PMID:28788372

Photo-fermentative bacteria aggregation triggered by L-cysteine during hydrogen production

PubMed Central

2013-01-01

Background Hydrogen recovered from organic wastes and solar energy by photo-fermentative bacteria (PFB) has been suggested as a promising bioenergy strategy. However, the use of PFB for hydrogen production generally suffers from a serious biomass washout from photobioreactor, due to poor flocculation of PFB. In the continuous operation, PFB cells cannot be efficiently separated from supernatant and rush out with effluent from reactor continuously, which increased the effluent turbidity, meanwhile led to increases in pollutants. Moreover, to replenish the biomass washout, substrate was continuously utilized for cell growth rather than hydrogen production. Consequently, the poor flocculability not only deteriorated the effluent quality, but also decreased the potential yield of hydrogen from substrate. Therefore, enhancing the flocculability of PFB is urgent necessary to further develop photo-fermentative process. Results Here, we demonstrated that L-cysteine could improve hydrogen production of Rhodopseudomonas faecalis RLD-53, and more importantly, simultaneously trigger remarkable aggregation of PFB. Experiments showed that L-cysteine greatly promoted the production of extracellular polymeric substances, especially secretion of protein containing more disulfide bonds, and help for enhancement stability of floc of PFB. Through formation of disulfide bonds, L-cysteine not only promoted production of EPS, in particular the secretion of protein, but also stabilized the final confirmation of protein in EPS. In addition, the cell surface elements and functional groups, especially surface charged groups, have also been changed by L-cysteine. Consequently, absolute zeta potential reached a minimum value at 1.0 g/l of L-cysteine, which obviously decreased electrostatic repulsion interaction energy based on DLVO theory. Total interaction energy barrier decreased from 389.77 KT at 0.0 g/l of L-cysteine to 127.21 kT at 1.0 g/l. Conclusions Thus, the strain RLD-53 overcame the total energy barrier and flocculated effectively. After a short settlement, the biomass rush out will be significantly reduced and the effluent quality will be greatly improved in the continuous operation. Furthermore, aggregation of PFB could enable high biomass hold-up of photobioreactor, which allows the photobioreactor to operate at low hydraulic retention time and high organic loading rate. Therefore, the described flocculation behaviour during photo-hydrogen production is potentially suitable for practicable application. PMID:23639008

Analytical characterization of ch14.18: a mouse-human chimeric disialoganglioside-specific therapeutic antibody.

PubMed

Soman, Gopalan; Kallarakal, Abraham T; Michiel, Dennis; Yang, Xiaoyi; Saptharish, Nirmala; Jiang, Hengguang; Giardina, Steve; Gilly, John; Mitra, George

2012-01-01

Ch14.18 is a mouse-human chimeric monoclonal antibody to the disialoganglioside (GD2) glycolipid. In the clinic, this antibody has been shown to be effective in the treatment of children with high-risk neuroblastoma, either alone or in combination therapy. Extensive product characterization is a prerequisite to addressing the potential issues of product variability associated with process changes and manufacturing scale-up. Charge heterogeneity, glycosylation profile, molecular state and aggregation, interaction (affinity) with Fcγ receptors and functional or biological activities are a few of the critical characterization assays for assessing product comparability for this antibody. In this article, we describe the in-house development and qualification of imaged capillary isoelectric focusing to assess charge heterogeneity, analytical size exclusion chromatography with online static and dynamic light scattering (DLS), batch mode DLS for aggregate detection, biosensor (surface plasmon resonance)-based Fcγ receptor antibody interaction kinetics, N-glycoprofiling with PNGase F digestion, 2-aminobenzoic acid labeling and high performance liquid chromatography and N-glycan analysis using capillary electrophoresis. In addition, we studied selected biological activity assays, such as complement-dependent cytotoxicity. The consistency and reproducibility of the assays are established by comparing the intra-day and inter-day assay results. Applications of the methodologies to address stability or changes in product characteristics are also reported. The study results reveal that the ch14.18 clinical product formulated in phosphate-buffered saline at a concentration of 5 mg/ml and stored at 2-8°C is stable for more than five years.

Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

PubMed

Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

2014-12-01

The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean chromatophores share various features with those of vertebrate pigment cells. Copyright © 2014 Elsevier Inc. All rights reserved.

NoGOA: predicting noisy GO annotations using evidences and sparse representation.

PubMed

Yu, Guoxian; Lu, Chang; Wang, Jun

2017-07-21

Gene Ontology (GO) is a community effort to represent functional features of gene products. GO annotations (GOA) provide functional associations between GO terms and gene products. Due to resources limitation, only a small portion of annotations are manually checked by curators, and the others are electronically inferred. Although quality control techniques have been applied to ensure the quality of annotations, the community consistently report that there are still considerable noisy (or incorrect) annotations. Given the wide application of annotations, however, how to identify noisy annotations is an important but yet seldom studied open problem. We introduce a novel approach called NoGOA to predict noisy annotations. NoGOA applies sparse representation on the gene-term association matrix to reduce the impact of noisy annotations, and takes advantage of sparse representation coefficients to measure the semantic similarity between genes. Secondly, it preliminarily predicts noisy annotations of a gene based on aggregated votes from semantic neighborhood genes of that gene. Next, NoGOA estimates the ratio of noisy annotations for each evidence code based on direct annotations in GOA files archived on different periods, and then weights entries of the association matrix via estimated ratios and propagates weights to ancestors of direct annotations using GO hierarchy. Finally, it integrates evidence-weighted association matrix and aggregated votes to predict noisy annotations. Experiments on archived GOA files of six model species (H. sapiens, A. thaliana, S. cerevisiae, G. gallus, B. Taurus and M. musculus) demonstrate that NoGOA achieves significantly better results than other related methods and removing noisy annotations improves the performance of gene function prediction. The comparative study justifies the effectiveness of integrating evidence codes with sparse representation for predicting noisy GO annotations. Codes and datasets are available at http://mlda.swu.edu.cn/codes.php?name=NoGOA .

Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective.

PubMed

Türkay, Metin; Saraçoğlu, Öztürk; Arslan, Mehmet Can

2016-01-01

Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers.

Quantification of alginate by aggregation induced by calcium ions and fluorescent polycations.

PubMed

Zheng, Hewen; Korendovych, Ivan V; Luk, Yan-Yeung

2016-01-01

For quantification of polysaccharides, including heparins and alginates, the commonly used carbazole assay involves hydrolysis of the polysaccharide to form a mixture of UV-active dye conjugate products. Here, we describe two efficient detection and quantification methods that make use of the negative charges of the alginate polymer and do not involve degradation of the targeted polysaccharide. The first method utilizes calcium ions to induce formation of hydrogel-like aggregates with alginate polymer; the aggregates can be quantified readily by staining with a crystal violet dye. This method does not require purification of alginate from the culture medium and can measure the large amount of alginate that is produced by a mucoid Pseudomonas aeruginosa culture. The second method employs polycations tethering a fluorescent dye to form suspension aggregates with the alginate polyanion. Encasing the fluorescent dye in the aggregates provides an increased scattering intensity with a sensitivity comparable to that of the conventional carbazole assay. Both approaches provide efficient methods for monitoring alginate production by mucoid P. aeruginosa. Copyright © 2015 Elsevier Inc. All rights reserved.

Activated stress response pathways within multicellular aggregates utilize an autocrine component.

PubMed

Jack, Graham D; Cabrera, M Carla; Manning, Michael L; Slaughter, Stephen M; Potts, Malcolm; Helm, Richard F

2007-04-01

Multicellular aggregates (spheroids) of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) entered and exited from long term (2 weeks) metabolic arrest utilizing an autocrine response. Cytokine production (specifically IFN-gamma) activated a Gadd45alpha/p38 pathway that led to increased AP-1 (c-jun and ATF3) transcription factor levels, augmenting cytokine production in an autocrine fashion. Whereas HFF-2 aggregates were capable of surviving long term arrest and recovery during NF-kappaB inhibition independent of JNK activation, T98G aggregates were not. Such endogenous processes are not easily observed with adherent monolayer cell culturing systems, strongly suggesting that more emphasis needs to be placed on determining the operational signal transduction cascades within multicellular aggregates. Extracellular inputs such as spheroid formation, arrest, and regrowth as monolayers invoke intracellular signaling responses converging at the AP-1 transcription factor level. Variations in responses are both cell type and transformation state dependent and require an autocrine cytokine component. The data are discussed in relation to the wounding response and avascular tumor growth mechanisms.

Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective

PubMed Central

Türkay, Metin; Saraçoğlu, Öztürk; Arslan, Mehmet Can

2016-01-01

Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers. PMID:26807848

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells.

PubMed

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S; Harvey, Richard P; Aghdami, Nasser; Baharvand, Hossein

2015-12-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. ©AlphaMed Press.

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells

PubMed Central

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M.; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S.; Harvey, Richard P.; Aghdami, Nasser

2015-01-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Significance Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. PMID:26511653

Properties of cold-bonded lightweight artificial aggregate containing bottom ash with different curing regime

NASA Astrophysics Data System (ADS)

Mohamad Ibrahim, Norlia; Nizar Ismail, Khairul; Che Amat, Roshazita; Mohamad Ghazali, Mohamad Iqbal

2018-03-01

Cold-bonded pelletizing technique is frequently used in aggregate manufacturing process as it can minimise the energy consumption. It has contributed to both economical and environmental advantages because it helps to reduce the gas emissions problems. Bottom ash collected from municipal solid waste incineration (MSWI) plant was selected as raw material in this study and was utilised as a partial replacement for cement for artificial aggregate production. Several percentage of ash replacement was selected ranged from 10 to 50%. Aggregate pellets were subjected to different types of curing condition which is room-water (RW), room-room (RR), oven-room (OR) and oven-water (OW) condition. Properties of aggregate pellets were examined to obtain its density, water absorption, aggregate impact value (AIV) and specific gravity (SG). The results indicated that the most efficient curing regime is by exposing the aggregate in RW condition. The optimum aggregate was selected at 20% where it has satisfied the required density of 739.5kg/m3, and classified as strong aggregate with AIV 14. However, the water absorption of aggregate increased proportionately with the increment of ash content.

Crushed cement concrete substitution for construction aggregates; a materials flow analysis

USGS Publications Warehouse

Kelly, Thomas

1998-01-01

An analysis of the substitution of crushed cement concrete for natural construction aggregates is performed by using a materials flow diagram that tracks all material flows into and out of the cement concrete portion of the products made with cement concrete: highways, roads, and buildings. Crushed cement concrete is only one of the materials flowing into these products, and the amount of crushed cement concrete substituted influences the amount of other materials in the flow. Factors such as availability and transportation costs, as well as physical properties, that can affect stability and finishability, influence whether crushed cement concrete or construction aggregates should be used or predominate for a particular end use.

Aggregation of the Inflammatory S100A8 Precedes Aβ Plaque Formation in Transgenic APP Mice: Positive Feedback for S100A8 and Aβ Productions.

PubMed

Lodeiro, Maria; Puerta, Elena; Ismail, Muhammad-Al-Mustafa; Rodriguez-Rodriguez, Patricia; Rönnbäck, Annica; Codita, Alina; Parrado-Fernandez, Cristina; Maioli, Silvia; Gil-Bea, Francisco; Merino-Serrais, Paula; Cedazo-Minguez, Angel

2017-03-01

Inflammation plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Although chronic inflammation in later stages of AD is well described, little is known about the inflammatory processes in preclinical or early stages of the disease prior to plaque deposition. In this study, we report that the inflammatory mediator S100A8 is increased with aging in the mouse brain. It is observed as extracellular aggregates, which do not correspond to corpora amylacea. S100A8 aggregation is enhanced in the hippocampi of two different mouse models for amyloid-β (Aβ) overproduction (Tg2576 and TgAPParctic mice). S100A8 aggregates are seen prior the formation of Aβ plaques and do not colocalize. In vitro treatment of glial cells from primary cultures with Aβ42 resulted in an increased production of S100A8. In parallel, treatment of a neuronal cell line with recombinant S100A8 protein resulted in enhanced Aβ42 and decreased Aβ40 production. Our results suggest that important inflammatory processes are occurring prior to Aβ deposition and the existence of a positive feedback between S100A8 and Aβ productions. The possible relevance of aging- or AD-dependent formation of S100A8 aggregates in the hippocampus thus affecting learning and memory processes is discussed. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Roles of biology, chemistry, and physics in soil macroaggregate formation and stabilization

USDA-ARS?s Scientific Manuscript database

Soil functions or ecosystem services depend on the distribution of macro- (= 0.25 mm) and micro- (< 0.25 mm) aggregates and open space between aggregates. It is the arrangement of the aggregates and pore space which allows air and water movement in and out of soil; reduces compaction; and stimulates...

Species, functional groups, and thresholds in ecological resilience

USGS Publications Warehouse

Sundstrom, Shana M.; Allen, Craig R.; Barichievy, Chris

2012-01-01

The cross-scale resilience model states that ecological resilience is generated in part from the distribution of functions within and across scales in a system. Resilience is a measure of a system's ability to remain organized around a particular set of mutually reinforcing processes and structures, known as a regime. We define scale as the geographic extent over which a process operates and the frequency with which a process occurs. Species can be categorized into functional groups that are a link between ecosystem processes and structures and ecological resilience. We applied the cross-scale resilience model to avian species in a grassland ecosystem. A species’ morphology is shaped in part by its interaction with ecological structure and pattern, so animal body mass reflects the spatial and temporal distribution of resources. We used the log-transformed rank-ordered body masses of breeding birds associated with grasslands to identify aggregations and discontinuities in the distribution of those body masses. We assessed cross-scale resilience on the basis of 3 metrics: overall number of functional groups, number of functional groups within an aggregation, and the redundancy of functional groups across aggregations. We assessed how the loss of threatened species would affect cross-scale resilience by removing threatened species from the data set and recalculating values of the 3 metrics. We also determined whether more function was retained than expected after the loss of threatened species by comparing observed loss with simulated random loss in a Monte Carlo process. The observed distribution of function compared with the random simulated loss of function indicated that more functionality in the observed data set was retained than expected. On the basis of our results, we believe an ecosystem with a full complement of species can sustain considerable species losses without affecting the distribution of functions within and across aggregations, although ecological resilience is reduced. We propose that the mechanisms responsible for shaping discontinuous distributions of body mass and the nonrandom distribution of functions may also shape species losses such that local extinctions will be nonrandom with respect to the retention and distribution of functions and that the distribution of function within and across aggregations will be conserved despite extinctions.

Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology

PubMed Central

Yang, Hui; Li, Jing-Jing; Liu, Shuai; Zhao, Jian; Jiang, Ya-Jun; Song, Ai-Xin; Hu, Hong-Yu

2014-01-01

Expansion of polyglutamine (polyQ) tract may cause protein misfolding and aggregation that lead to cytotoxicity and neurodegeneration, but the underlying mechanism remains to be elucidated. We applied ataxin-3 (Atx3), a polyQ tract-containing protein, as a model to study sequestration of normal cellular proteins. We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells. Moreover, this specific sequestration impairs the normal cellular function of P97 in down-regulating neddylation. However, expansion of polyQ tract in Atx3 does not alter the conformation of its surrounding regions and the interaction affinities with the interacting partners, although it indeed facilitates misfolding and aggregation of the Atx3 protein. Thus, we propose a loss-of-function pathology for polyQ diseases that sequestration of the cellular essential proteins via specific interactions into inclusions by the polyQ aggregates causes dysfunction of the corresponding proteins, and consequently leads to neurodegeneration. PMID:25231079

Application of adjusted data in calculating fission-product decay energies and spectra

NASA Astrophysics Data System (ADS)

George, D. C.; Labauve, R. J.; England, T. R.

1982-06-01

The code ADENA, which approximately calculates fussion-product beta and gamma decay energies and spectra in 19 or fewer energy groups from a mixture of U235 and Pu239 fuels, is described. The calculation uses aggregate, adjusted data derived from a combination of several experiments and summation results based on the ENDF/B-V fission product file. The method used to obtain these adjusted data and the method used by ADENA to calculate fission-product decay energy with an absorption correction are described, and an estimate of the uncertainty of the ADENA results is given. Comparisons of this approximate method are made to experimental measurements, to the ANSI/ANS 5.1-1979 standard, and to other calculational methods. A listing of the complete computer code (ADENA) is contained in an appendix. Included in the listing are data statements containing the adjusted data in the form of parameters to be used in simple analytic functions.

Mechanistic modeling of microbial interactions at pore to profile scale resolve methane emission dynamics from permafrost soil

NASA Astrophysics Data System (ADS)

Ebrahimi, Ali; Or, Dani

2017-05-01

The sensitivity of polar regions to raising global temperatures is reflected in rapidly changing hydrological processes associated with pronounced seasonal thawing of permafrost soil and increased biological activity. Of particular concern is the potential release of large amounts of soil carbon and stimulation of other soil-borne greenhouse gas emissions such as methane. Soil methanotrophic and methanogenic microbial communities rapidly adjust their activity and spatial organization in response to permafrost thawing and other environmental factors. Soil structural elements such as aggregates and layering affect oxygen and nutrient diffusion processes thereby contributing to methanogenic activity within temporal anoxic niches (hot spots). We developed a mechanistic individual-based model to quantify microbial activity dynamics in soil pore networks considering transport processes and enzymatic activity associated with methane production in soil. The model was upscaled from single aggregates to the soil profile where freezing/thawing provides macroscopic boundary conditions for microbial activity at different soil depths. The model distinguishes microbial activity in aerate bulk soil from aggregates (or submerged profile) for resolving methane production and oxidation rates. Methane transport pathways by diffusion and ebullition of bubbles vary with hydration dynamics. The model links seasonal thermal and hydrologic dynamics with evolution of microbial community composition and function affecting net methane emissions in good agreement with experimental data. The mechanistic model enables systematic evaluation of key controlling factors in thawing permafrost and microbial response (e.g., nutrient availability and enzyme activity) on long-term methane emissions and carbon decomposition rates in the rapidly changing polar regions.

Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation

PubMed Central

Hoppe, Cindy C; Nguyen, Lida T; Kirsch, Lee E; Wiencek, John M

2008-01-01

Background Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation. Results High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled. Conclusion The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations. PMID:18613970

On the climate policy implications of substitutability and flexibility in the economy: An in-depth integrated assessment model diagnostic

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

Craxton, Melanie; Merrick, James; Makridis, Christos

This paper conducts an in-depth model diagnostic exercise for two parameters, 1) the elasticity of substitution between the capital/labour aggregate and the energy aggregate in the Integrated Assessment Model (IAM) MERGE's production function and 2) the rate at which new technologies can be deployed within the energy system. We show that in a more complementary world the model's ability to adjust the carbon intensity of its energy sector is more important whereas in a more substitutable world the ability to expand carbon free technologies is of lesser relative importance. The uncertainty in the literature surrounding the elasticity of substitution parameter,more » its interaction with the mechanisms of technical change, and the associated danger of grounding forward-looking analyses in historically based parameters lend support to the importance of such a diagnostic exercise. Building on work from model intercomparison studies, we investigate whether a given model's choice of strategy is primarily a function of the choice of its parameter values or its structure. As a result, a deeper understanding of what drives model behaviour is beneficial to both modellers and the policymakers who utilise their insights and output.« less

On the climate policy implications of substitutability and flexibility in the economy: An in-depth integrated assessment model diagnostic

DOE PAGES

Craxton, Melanie; Merrick, James; Makridis, Christos; ...

2017-07-12

This paper conducts an in-depth model diagnostic exercise for two parameters, 1) the elasticity of substitution between the capital/labour aggregate and the energy aggregate in the Integrated Assessment Model (IAM) MERGE's production function and 2) the rate at which new technologies can be deployed within the energy system. We show that in a more complementary world the model's ability to adjust the carbon intensity of its energy sector is more important whereas in a more substitutable world the ability to expand carbon free technologies is of lesser relative importance. The uncertainty in the literature surrounding the elasticity of substitution parameter,more » its interaction with the mechanisms of technical change, and the associated danger of grounding forward-looking analyses in historically based parameters lend support to the importance of such a diagnostic exercise. Building on work from model intercomparison studies, we investigate whether a given model's choice of strategy is primarily a function of the choice of its parameter values or its structure. As a result, a deeper understanding of what drives model behaviour is beneficial to both modellers and the policymakers who utilise their insights and output.« less

A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng.

PubMed

Fung, Foon Yin; Wong, Wan Hui; Ang, Seng Kok; Koh, Hwee Ling; Kun, Mei Ching; Lee, Lai Heng; Li, Xiaomei; Ng, Heng Joo; Tan, Chuen Wen; Zhao, Yan; Linn, Yeh Ching

2017-08-15

Herbs with "blood-activating" properties by traditional medicine theory often raise concerns for their possible anti-platelet or anticoagulation effects based on reports from in vitro studies. Such herbs have been implicated for bleeding manifestations based on only anecdotal reports. In particular, the combination of such herbs with anti-platelet agents is often empirically advised against despite lack of good clinical evidence. Here we studied 3 commonly used herbal preparations Curcuma longa, Angelica sinensis and Panax ginseng on their respective anti-platelet and anticoagulation effect, alone and in combination with aspirin. This is a randomized, double-blind, placebo-controlled trial involving 25 healthy volunteers for each herbal preparation. Each subject underwent 3 phases comprising of herbal product alone, aspirin alone and aspirin with herbal product, where each phase lasted for 3 weeks with 2 weeks of washout between phases. PT/APTT, platelet function by light transmission aggregometry and thrombin generation assay by calibrated automated thrombogram were measured at baseline and after each phase. Information on adverse reaction including bleeding manifestations was collected after each phase. On the whole there was no clinically relevant impact on platelet and coagulation function. With the exception of 5 of 24 subjects in the Curcuma longa group, 2 of 24 subjects in the Angelica sinensis group and 1 of 23 subjects in the Panax ginseng group who had an inhibition in arachidonic-acid induced platelet aggregation, there was no effect of these 3 herbals products on platelet aggregation by other agonists. Combination of these herbal products with aspirin respectively did not further aggravate platelet inhibition caused by aspirin. None of the herbs impaired PT/APTT or thrombin generation. There was no significant bleeding manifestation. This study on healthy volunteers provides good evidence on the lack of bleeding risks of Curcuma longa, Angelica sinensis and Panax ginseng either used alone or in combination with aspirin. Copyright © 2017 Elsevier GmbH. All rights reserved.

Method and apparatus for forming ceramic oxide superconductors with ordered structure

DOEpatents

Nellis, W.J.; Maple, M.B.

1987-12-23

Disclosed are products and processes for making improved magnetic and superconducting articles from anisotropic starting materials by initially reducing the starting materials into a powdered form composed of particles of uniform directional crystal structures, forming a directionally uniform aggregate of particles by exposing the aggregate to a magnetic field of desired magnitude and direction, and then compacting the aggregate into an integral solid body. 2 Figs.

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

PubMed

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

2014-04-21

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

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

PubMed

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

2014-09-12

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

Investigation of Physico-Chemical Properties of Sand-Lime Products Modified of Diabase Aggregate and Chalcedonite Meal

NASA Astrophysics Data System (ADS)

Dachowski, Ryszard; Komisarczyk, Katarzyna

2017-10-01

In the era of rapid development in the construction industry, particular attention is focused on harmless and natural materials. Some of the best materials for building masonry walls are sand-lime products. Silicates are obtained from a mixture of quartz, sand and a small amount of water. They emerge as a result of the hydrothermal treatment conducted under high pressure and at a temperature of app. 203 °C. Silicates were modified of different kinds of aggregates, glass or plastics, and the content of dry ingredients was changed because of this fact. The paper describes the studies where the combination of diabase aggregate and chalcedonite meal was used. Microstructure of the products was analyzed with the use of mercury intrusion porosimetry, SEM and XRD methods. Variable content of chalcedonite meal changes the internal structure and the physico-chemical properties.

Process for producing an aggregate suitable for inclusion into a radiation shielding product

DOEpatents

Lessing, Paul A.; Kong, Peter C.

2000-01-01

The present invention is directed to methods for converting depleted uranium hexafluoride to a stable depleted uranium silicide in a one-step reaction. Uranium silicide provides a stable aggregate material that can be added to concrete to increase the density of the concrete and, consequently, shield gamma radiation. As used herein, the term "uranium silicide" is defined as a compound generically having the formula U.sub.x Si.sub.y, wherein the x represents the molecules of uranium and the y represent the molecules of silicon. In accordance with the present invention, uranium hexafluoride is converted to a uranium silicide by contacting the uranium hexafluoride with a silicon-containing material at a temperature in a range between about 1450.degree. C. and about 1750.degree. C. The stable depleted uranium silicide is included as an aggregate in a radiation shielding product, such as a concrete product.

Functionalized Carbon Nanotubes in Modified Plant Oil Composites.

NASA Astrophysics Data System (ADS)

McAninch, Ian M.; Wool, Richard P.

2007-03-01

Carbon nanotubes (CNTs) with their impressive mechanical properties are ideal reinforcement material. Acrylated epoxidized soy oil (AESO) has been previously shown to have favorable interactions with carbon nanotubes; however a mixture of aggregates and dispersed tubes were found even at low CNT concentrations. In order to prevent re-aggregation, the CNTs were functionalized with a 10 carbon long aliphatic chain. These aliphatic chains are similar to the fatty acids that make up soy oil. Functionalization was verified using XPS and IR spectroscopy. These functionalized CNTs were dispersed by mechanical shear mixing into AESO both with and without styrene as a comonomer. No large aggregates were observed in the liquid, uncured, samples or in the final cured composites. Dispersion in the solid composites was verified using optical and electron microscopy. Better dispersion also resulted in improved mechanical properties.

A GIS analysis of suitability for construction aggregate recycling sites using regional transportation network and population density features

USGS Publications Warehouse

Robinson, G.R.; Kapo, K.E.

2004-01-01

Aggregate is used in road and building construction to provide bulk, strength, support, and wear resistance. Reclaimed asphalt pavement (RAP) and reclaimed Portland cement concrete (RPCC) are abundant and available sources of recycled aggregate. In this paper, current aggregate production operations in Virginia, Maryland, and the District of Columbia are used to develop spatial association models for the recycled aggregate industry with regional transportation network and population density features. The cost of construction aggregate to the end user is strongly influenced by the cost of transporting processed aggregate from the production site to the construction site. More than 60% of operations recycling aggregate in the mid-Atlantic study area are located within 4.8 km (3 miles) of an interstate highway. Transportation corridors provide both sites of likely road construction where aggregate is used and an efficient means to move both materials and on-site processing equipment back and forth from various work sites to the recycling operations. Urban and developing areas provide a high market demand for aggregate and a ready source of construction debris that may be processed into recycled aggregate. Most aggregate recycling operators in the study area are sited in counties with population densities exceeding 77 people/km2 (200 people/mile 2). No aggregate recycling operations are sited in counties with less than 19 people/km2 (50 people/mile2), reflecting the lack of sufficient long-term sources of construction debris to be used as an aggregate source, as well as the lack of a sufficient market demand for aggregate in most rural areas to locate a recycling operation there or justify the required investment in the equipment to process and produce recycled aggregate. Weights of evidence analyses (WofE), measuring correlation on an area-normalized basis, and weighted logistic regression (WLR), are used to model the distribution of RAP and RPCC operations relative to transportation network and population distribution data. The models can be used on a regional scale to quickly map the relative site suitability for a RAP or RPCC aggregate recycling operation in a particular area based on transportation network and population parameters. The results can be used to identify general areas to be further evaluated on a site-specific basis using more detailed marketplace information. As transportation or population features change due to planning or actual development, the models can be easily revised to reflect these changes. ?? 2004 Elsevier B.V. All rights reserved.

Auto-aggregation properties of a novel aerobic denitrifier Enterobacter sp. strain FL.

PubMed

Wang, Xia; An, Qiang; Zhao, Bin; Guo, Jin Song; Huang, Yuan Sheng; Tian, Meng

2018-02-01

Enterobacter sp. strain FL was newly isolated from activated sludge and exhibited significant capability of auto-aggregation as well as aerobic denitrification. The removal efficiencies of NO 3 - -N, total nitrogen (TN), and TOC by strain FL in batch culture reached 94.6, 63.9, and 72.5% in 24 h, respectively. The production of N 2 O and N 2 in the presence of oxygen demonstrated the occurrence of aerobic denitrification. The auto-aggregation index of strain FL reached 54.3%, suggesting a high tendency that the cells would agglomerate into aggregates. The production of extracellular polymeric substances (EPSs), which were mainly composed of proteins followed by polysaccharides, was considered to be related to the cell aggregation according to Fourier transform infrared (FT-IR) and confocal laser scanning microscopy (CLSM). The proteins in EPS were evenly and tightly combined to cells and altered the protein secondary structures of cell surface from random coils to β-sheets and three-turn helices. The alteration of protein secondary structures of cell surface caused by the proteins in EPS might play a dominant role in the auto-aggregation of strain FL. To further assess the feasibility of strain FL for synthetic wastewater treatment, a sequencing batch reactor (SBR), solely inoculated with strain FL, was conducted. During the 16 running cycles, the removal efficiency of NO 3 - -N was 90.2-99.7% and the auto-aggregation index was stabilized at 35.0-41.5%. The EPS promoted the biomass of strain FL to aggregate in the SBR.

Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

PubMed

Raguideau, Sébastien; Plancade, Sandra; Pons, Nicolas; Leclerc, Marion; Laroche, Béatrice

2016-12-01

Whole Genome Shotgun (WGS) metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs) accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF) problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other metabolic processes in the gut or in other ecosystems.

Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy

PubMed Central

Gianni, Davide; Li, Airong; Tesco, Giuseppina; McKay, Kenneth M.; Moore, John; Raygor, Kunal; Rota, Marcello; Gwathmey, Judith K; Dec, G William; Aretz, Thomas; Leri, Annarosa; Semigran, Marc J; Anversa, Piero; Macgillivray, Thomas E; Tanzi, Rudolph E.; Monte, Federica del

2010-01-01

Background Heart failure (HF) is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as Idiopathic Dilated Cardiomyopathy (iDCM), the origin of HF is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of β-amyloid impair cell function and lead to cell death. Methods and Results We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca2+ homeostasis. Additionally, we have identified two new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 co-immunoprecipitates with SERCA2a. Conclusions Based on these findings we propose that two mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca2+ handling and a direct effect of PSEN1 sequence variants on EC-coupling protein function. PMID:20194882

Utilization of lignite power generation residues for the production of lightweight aggregates.

PubMed

Anagnostopoulos, Iason M; Stivanakis, Victor E

2009-04-15

A novel process is proposed for the utilization of lignite combustion solid residues in the production of inflammable lightweight aggregates (LWA). The process consists of two stages, pelletization and sintering, and carbon contained in BA was used as the process fuel. The main residues bottom ash (BA) and fly ash (FA) from Megalopolis power plant were characterized, mixed in different proportions and treated through pelletization and sintering process. Sintering benefits from combustion of BA carbon content and the product is a hardened porous cake. The energy required for achievement of high temperatures, in the range of 1250 degrees C, was offered by carbon combustion and CO(2) evolution is responsible for porous structure formation. Selected physical properties of sintered material relevant to use as lightweight aggregates were determined, including bulk density, porosity and water absorption. Bulk density varies from 0.83 to 0.91 g/cm(3), porosity varies from 60% to 64% and water absorption varies from 66% to 80%. LWA formed is used for the production of lightweight aggregate concrete (LWAC). Thermal conductivity coefficient varies from 0.25 to 0.37 W/mK (lower than maximum limit 0.43 W/mK) and compressive strength varies from 19 to 23 MPa (higher than minimum limit 17 MPa). The results indicate that sintering of lignite combustion residues is an efficient method of utilization of carbon containing BA and production of LWA for structural and insulating purposes. Carbon content of BA is a key factor in LWA production. Finally, this research work comprises the first proposed application for utilization of BA in Greece.

The association of peroxisomes with the developing cell plate in dividing onion root cells depends on actin microfilaments and myosin.

PubMed

Collings, David A; Harper, John D I; Vaughn, Kevin C

2003-12-01

We have investigated changes in the distribution of peroxisomes through the cell cycle in onion ( Allium cepa L.) root meristem cells with immunofluorescence and electron microscopy, and in leek ( Allium porrum L.) epidermal cells with immunofluorescence and peroxisomal-targeted green fluorescent protein. During interphase and mitosis, peroxisomes distribute randomly throughout the cytoplasm, but beginning late in anaphase, they accumulate at the division plane. Initially, peroxisomes occur within the microtubule phragmoplast in two zones on either side of the developing cell plate. However, as the phragmoplast expands outwards to form an annulus, peroxisomes redistribute into a ring immediately inside the location of the microtubules. Peroxisome aggregation depends on actin microfilaments and myosin. Peroxisomes first accumulate in the division plane prior to the formation of the microtubule phragmoplast, and throughout cytokinesis, always co-localise with microfilaments. Microfilament-disrupting drugs (cytochalasin and latrunculin), and a putative inhibitor of myosin (2,3-butanedione monoxime), inhibit aggregation. We propose that aggregated peroxisomes function in the formation of the cell plate, either by regulating hydrogen peroxide production within the developing cell plate, or by their involvement in recycling of excess membranes from secretory vesicles via the beta-oxidation pathway. Differences in aggregation, a phenomenon which occurs in onion, some other monocots and to a lesser extent in tobacco BY-2 suspension cells, but which is not obvious in the roots of Arabidopsis thaliana (L.) Heynh., may reflect differences within the primary cell walls of these plants.

In situ formation of pyridyl-functionalized poly(3-hexylthiophene)s via quenching of the Grignard metathesis polymerization: Toward ligands for semiconductor quantum dots

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

Kochemba, William Michael; Pickel, Deanna L.; Sumpter, Bobby G.

The synthesis of well-defined, end-functional poly(3-hexylthiophene)s (P3HTs) by in situ quenching of the Grignard metathesis (GRIM) polymerization is complicated by the extreme tendency to favor difunctional products in all but a few cases. A facile one-pot method for preparing 2-pyridyl and 3-pyridyl P3HTs with high abundance of monofunctional products is established via an examination of the kinetics of the end-functionalization quenching reaction with lithium chloride complexes of 2- and 3-pyridyl Grignard reagents. Density functional theory calculations guide the selection of pyridine as the end group, which provides the capacity to ligate cadmium selenide (CdSe) nanocrystals and arrests aggregation upon thermalmore » annealing when dispersed in a P3HT matrix. The relative abundances of various end-functional products, as ascertained by high-resolution matrix assisted laser desorption ionization time-of-flight mass spectrometry, can be altered through the use of 1-pentene as an additive: GRIM polymerizations quenched with 3-pyridyl and 2-pyridyl Grignard reagents show 5% and 18% abundances of difunctional, pyridyl-capped P3HTs, respectively, when 1-pentene is present at 1000:1 relative to the nickel catalyst. This represents a significant improvement compared to quenching with aryl Grignard reagents, where difunctional products predominate. Furthermore, the ability to manipulate end group compositions coupled with the propensity of pyridyl-functionalized P3HTs to ligate semiconductor quantum dots (SQDs) opens new possibilities for tuning the morphology of conjugated polymer/SQD blends.« less

Critical radius in the organisation of synuclein-alpha interacting protein in living cells

NASA Astrophysics Data System (ADS)

Narayanan, Arjun; Meriin, Anatoli; Sherman, Michael; Cisse, Ibrahim

We report a super-resolution imaging study of protein aggregation in the living cell. Focusing on the aggregation of the Parkinsons's disease linked Synuclein-alpha interacting protein, we found and characterized sub-diffraction aggregates in healthy cells and studied the progression of these aggregates in stressed cells. Our results allowed us to establish the aggregation process as amenable to a simple physical description - the well-established thermodynamics of condensation phenomena. This description turned out to be both robust and useful. Not only did the distribution of aggregate sizes fit exceedingly well to the thermodynamic predictions in all tested conditions, but its evolving shape under pharmacological and genetic perturbations correlated intuitively with predictions from cell biology. The picture emerging from measurements in different genetic and pharmacological states is a view of protein aggregate size distribution as resulting from a non-equilibrium steady state maintained - even in healthy cells - with continuous and concurrent aggregate production and clearance.

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

PubMed

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

2018-03-26

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

Role of asymmetric cell division in lifespan control in Saccharomyces cerevisiae

PubMed Central

Higuchi-Sanabria, Ryo; Pernice, Wolfgang M A; Vevea, Jason D; Alessi Wolken, Dana M; Boldogh, Istvan R; Pon, Liza A

2014-01-01

Aging determinants are asymmetrically distributed during cell division in S. cerevisiae, which leads to production of an immaculate, age-free daughter cell. During this process, damaged components are sequestered and retained in the mother cell, and higher functioning organelles and rejuvenating factors are transported to and/or enriched in the bud. Here, we will describe the key quality control mechanisms in budding yeast that contribute to asymmetric cell division of aging determinants including mitochondria, endoplasmic reticulum (ER), vacuoles, extrachromosomal rDNA circles (ERCs), and protein aggregates. PMID:25263578

Characterization of subvisible particle formation during the filling pump operation of a monoclonal antibody solution.

PubMed

Nayak, Arpan; Colandene, James; Bradford, Victor; Perkins, Melissa

2011-10-01

Characterization and control of aggregate and subvisible particle formation during fill-finish process steps are important for biopharmaceutical products. The filling step is of key importance as there is no further filtration of the drug product beyond sterile filtration. Filling processes can impact product quality by introducing physical stresses such as shear, friction, and cavitation. Other detrimental factors include temperature generated in the process of filling, foaming, and contact with filling system materials, including processing aids such as silicone oil. Certain pumps may shed extrinsic particles that may lead to heterogeneous nucleation-induced aggregation. In this work, microflow imaging, size-exclusion chromatography (SEC), and turbidimetry were utilized to quantify subvisible particles, aggregation, and opalescence, respectively. The filling process was performed using several commonly used filling systems, including rotary piston pump, rolling diaphragm pump, peristaltic pump, and time-pressure filler. The rolling diaphragm pump, peristaltic pump, and time-pressure filler generated notably less protein subvisible particles than the rotary piston pump, although no change in aggregate content by SEC was observed by any pump. An extreme increase in subvisible particles was also reflected in an increase in turbidity. Copyright © 2011 Wiley-Liss, Inc.

Effect of long-term combined application of organic and inorganic fertilizers on soil nematode communities within aggregates

PubMed Central

Zhang, Zhiyong; Zhang, Xiaoke; Mahamood, Md.; Zhang, Shuiqing; Huang, Shaomin; Liang, Wenju

2016-01-01

A long-term fertilization experiment was conducted to examine the effects of different fertilization practices on nematode community composition within aggregates in a wheat-maize rotation system. The study was a randomized complete block design with three replicates. The experiment involved the following four treatments: no fertilizer, inorganic N, P and K fertilizer (NPK), NPK plus manure (NPKM) and NPK plus maize straw (NPKS). Soil samples were taken at 0–20 cm depth during the wheat harvest stage. Based on our results, NPKS contributed to soil aggregation and moisture retention, with a positive effect on soil total nitrogen accumulation, particularly within small macroaggregates (0.25–1 mm) and microaggregates (<0.25 mm). The C/N ratio was correlated to the distribution of the soil nematode community. Both manure application and straw incorporation increased the nematode functional metabolic footprints within all aggregates. Additionally, the functional metabolic footprints decreased with a decline in aggregate size. The accumulation of total nitrogen within <1 mm aggregates under NPKS might play a key role in maintaining the survival of soil nematodes. In our study, both crop straw incorporation and inorganic fertilizer application effectively improved soil physicochemical properties and were also beneficial for nematode survival within small aggregate size fractions. PMID:27502433

Effect of long-term combined application of organic and inorganic fertilizers on soil nematode communities within aggregates.

PubMed

Zhang, Zhiyong; Zhang, Xiaoke; Mahamood, Md; Zhang, Shuiqing; Huang, Shaomin; Liang, Wenju

2016-08-09

A long-term fertilization experiment was conducted to examine the effects of different fertilization practices on nematode community composition within aggregates in a wheat-maize rotation system. The study was a randomized complete block design with three replicates. The experiment involved the following four treatments: no fertilizer, inorganic N, P and K fertilizer (NPK), NPK plus manure (NPKM) and NPK plus maize straw (NPKS). Soil samples were taken at 0-20 cm depth during the wheat harvest stage. Based on our results, NPKS contributed to soil aggregation and moisture retention, with a positive effect on soil total nitrogen accumulation, particularly within small macroaggregates (0.25-1 mm) and microaggregates (<0.25 mm). The C/N ratio was correlated to the distribution of the soil nematode community. Both manure application and straw incorporation increased the nematode functional metabolic footprints within all aggregates. Additionally, the functional metabolic footprints decreased with a decline in aggregate size. The accumulation of total nitrogen within <1 mm aggregates under NPKS might play a key role in maintaining the survival of soil nematodes. In our study, both crop straw incorporation and inorganic fertilizer application effectively improved soil physicochemical properties and were also beneficial for nematode survival within small aggregate size fractions.

Lactobacillus kefiri shows inter-strain variations in the amino acid sequence of the S-layer proteins.

PubMed

Malamud, Mariano; Carasi, Paula; Bronsoms, Sílvia; Trejo, Sebastián A; Serradell, María de Los Angeles

2017-04-01

The S-layer is a proteinaceous envelope constituted by subunits that self-assemble to form a two-dimensional lattice that covers the surface of different species of Bacteria and Archaea, and it could be involved in cell recognition of microbes among other several distinct functions. In this work, both proteomic and genomic approaches were used to gain knowledge about the sequences of the S-layer protein (SLPs) encoding genes expressed by six aggregative and sixteen non-aggregative strains of potentially probiotic Lactobacillus kefiri. Peptide mass fingerprint (PMF) analysis confirmed the identity of SLPs extracted from L. kefiri, and based on the homology with phylogenetically related species, primers located outside and inside the SLP-genes were employed to amplify genomic DNA. The O-glycosylation site SASSAS was found in all L. kefiri SLPs. Ten strains were selected for sequencing of the complete genes. The total length of the mature proteins varies from 492 to 576 amino acids, and all SLPs have a calculated pI between 9.37 and 9.60. The N-terminal region is relatively conserved and shows a high percentage of positively charged amino acids. Major differences among strains are found in the C-terminal region. Different groups could be distinguished regarding the mature SLPs and the similarities observed in the PMF spectra. Interestingly, SLPs of the aggregative strains are 100% homologous, although these strains were isolated from different kefir grains. This knowledge provides relevant data for better understanding of the mechanisms involved in SLPs functionality and could contribute to the development of products of biotechnological interest from potentially probiotic bacteria.

Sternal gland structures in males of bean flower thrips, Megalurothrips sjostedti, and Poinsettia thrips, Echinothrips americanus, in comparison with those of western flower thrips, Frankliniella occidentalis (Thysanoptera: Thripidae).

PubMed

Krueger, Stephanie; Subramanian, Sevgan; Niassy, Saliou; Moritz, Gerald B

2015-09-01

Sternal pores are important features for identification of male thrips, especially within the subfamily Thripinae. They vary in shape, size and distribution even between species of one genus. Their functional role is speculated to be that of sex- and/or aggregation pheromone production. Yet, sexual aggregations are not reported in Echinothrips americanus, known to have sternal pores, while we observed aggregations in Megalurothrips sjostedti, previously reported to lack them. We examined the sternal glands and pores of the thripine species E. americanus and M. sjostedti males, in comparison with those of Frankliniella occidentalis using light microscopy, as well as scanning and transmission electron microscopy. Pore plates of F. occidentalis were ellipsoid and medial on sternites III-VII, while in E. americanus they were distributed as multiple micro pore plates on sternites III-VIII. In M. sjostedti they appeared as an extremely small pore in front of the posterior margin of each of sternites IV-VII. Pore plate and pore plate area were distributed similarly on sternites III-VII in F. occidentalis. However, in E. americanus the total pore plate area increased significantly from sternites III to VIII. Ultrastructure of cells associated with sternal glands showed typical characteristics of gland cells that differ in size, shape and number. The function of sternal glands is further discussed on the basis of morphological comparisons with other thrips species. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Aggregation, adsorption, and surface properties of multiply end-functionalized polystyrenes.

PubMed

Ansari, Imtiyaz A; Clarke, Nigel; Hutchings, Lian R; Pillay-Narrainen, Amilcar; Terry, Ann E; Thompson, Richard L; Webster, John R P

2007-04-10

The properties of polystyrene blends containing deuteriopolystyrene, multiply end-functionalized with C8F17 fluorocarbon groups, are strikingly analogous to those of surfactants in solution. These materials, denoted FxdPSy, where x is the number of fluorocarbon groups and y is the molecular weight of the dPS chain in kg/mol, were blended with unfunctionalized polystyrene, hPS. Nuclear reaction analysis experiments show that FxdPSy polymers adsorb spontaneously to solution and blend surfaces, resulting in a reduction in surface energy inferred from contact angle analysis. Aggregation of functionalized polymers in the bulk was found to be sensitive to FxdPSy structure and closely related to surface properties. At low concentrations, the functionalized polymers are freely dispersed in the hPS matrix, and in this range, the surface excess concentration grows sharply with increasing bulk concentration. At higher concentrations, surface excess concentrations and contact angles reach a plateau, small-angle neutron scattering data indicate small micellar aggregates of six to seven F2dPS10 polymer chains and much larger aggregates of F4dPS10. Whereas F2dPS10 aggregates are miscible with the hPS matrix, F4dPS10 forms a separate phase of multilamellar vesicles. Using neutron reflectometry (NR), we found that the extent of the adsorbed layer was approximately half the lamellar spacing of the multilamellar vesicles. NR data were fitted using an error function profile to describe the concentration profile of the adsorbed layer, and reasonable agreement was found with concentration profiles predicted by the SCFT model. The thermodynamic sticking energy of the fluorocarbon-functionalized polymer chains to the blend surface increases from 5.3kBT for x = 2 to 6.6kBT for x = 4 but appears to be somewhat dependent upon the blend concentration.

Development of ODOT guidelines for the use of geogrids in aggregate bases.

DOT National Transportation Integrated Search

2012-11-01

A primary objective of the current study was to help ODOT expand its selection of approved : geogrid products for base reinforcement applications by producing measured data on selected : geogrids and a dense-graded base aggregate commonly used in ODO...

Matrix-assisted laser-induced gas-phase aggregation of C 60 oxides

NASA Astrophysics Data System (ADS)

Barrow, Mark P.; Tower, Nicole J.; Taylor ^*, , Roger; Drewello, Thomas

1998-08-01

Matrix-assisted laser desorption/ionisation of C 60 oxides, in conjunction with reflectron time-of-flight mass spectrometry, leads to an unprecedented gas-phase aggregation resulting in the formation of C 120O n- ·. products. The analysis of the product distribution obtained for oxides of varying oxygen content strongly suggests that the structures of these species are closely related to oxo-bridged isolated fullerene cages rather than to species featuring a fused giant fullerene core.

Potential source for crushed granite aggregate in Heard County, Georgia

USGS Publications Warehouse

Atkins, R.L.; Higgins, Michael W.; Dickerson, Robert P.

1981-01-01

The production of crushed stone suitable for highway and general construction is a major industry in Georgia. The state ranks eighth in the nation in overall crushed stone production, and first in crushed granite production. Crushed stone production in Georgia in 1979 was 40,902,000 short tons worth $154,021,000 (D.H. White, Jr., US Bureau of Mines, personal commun., Aug. 1980). More than 3,000 people were employed by the crushed stone industry in Georgia during that year.Presently, the only active quarry in Heard County is located in an amphibolite. Amphibolite is not a conventional aggregate. It has a high specific gravity, a tendency to make elongate fragments, and varies considerably in abrasion tests.Because the nearest approved aggregate quarry is more than 25 miles from Franklin, the county seat, the purpose of this brief report is to describe a body of granite gneiss that may provide suitable aggregate for the crushed stone industry, potential quarry operators and various agencies in Heard County. This report is part of a project to study the geology and mineral resources of the Piedmont south of the Brevard Zone, and is not intended to supplant detailed site investigations by industry or consultants. The report is a joint effort between the Georgia Geologic Survey and the Office of Materials and Research of the Georgia Department of Transportation.

To what extent clay mineralogy affect soil aggregation? Insights from fractionation analyses conducted on soils under different land-uses.

NASA Astrophysics Data System (ADS)

Fernandez-Ugalde, O.; Barré, P.; Hubert, F.; Virto, I.; Girardin, C.; Ferrage, E.; Caner, L.; Chenu, C.

2012-04-01

Aggregation is a key process for soil functioning as it influences C storage, vulnerability to erosion and water holding capacity. While the influence of soil C content or tillage on aggregation has been documented, much less is known about the role of soil mineralogy. The aim of this study is to determine quantitatively if different clay minerals of a temperate soil contribute differently to aggregation and if their contribution is modulated by soil management. We compared the aggregate-size distribution of three cropping systems in a silt loam soil in Versailles (France): organic cropping system (ORG, tilled yearly), direct seeding mulch-based cropping system (DMC, tilled every 4 years), both from a long-term trial, and a nearby grassland. Soil samples from 0-5 cm were wet-sieved to 5 mm and air-dried before aggregate-size separation. For each aggregate class, fraction <2 µm was separated and analysed using X-ray diffraction. Organic C content was determined both in aggregates and <2-µm fractions. C content was lower in ORG than in the two other treatments. The proportion of large-macroaggregates (500-5000 µm) was greater in DMC and grassland; while microaggregates (50-250 µm) showed greater proportions in ORG. In the three treatments, microaggregates had the greatest amount of clays, with preferential accumulation of smectitic phases. In grassland, clays from all aggregated fractions showed more smectitic phases than free-clay fraction. The results indicate that smectitic phases contributed particularly to the microaggregates dynamics. Their contribution to aggregation was lower for larger aggregate sizes where the influence of organic matter was preponderant. Moreover, it was observed that cultivation (ORG and DMC treatments) reduced the relative enrichment of smectitic phases in stable aggregates which makes them more vulnerable to slaking erosion and alters their physico-chemical functions.

Piecewise Polynomial Aggregation as Preprocessing for Data Numerical Modeling

NASA Astrophysics Data System (ADS)

Dobronets, B. S.; Popova, O. A.

2018-05-01

Data aggregation issues for numerical modeling are reviewed in the present study. The authors discuss data aggregation procedures as preprocessing for subsequent numerical modeling. To calculate the data aggregation, the authors propose using numerical probabilistic analysis (NPA). An important feature of this study is how the authors represent the aggregated data. The study shows that the offered approach to data aggregation can be interpreted as the frequency distribution of a variable. To study its properties, the density function is used. For this purpose, the authors propose using the piecewise polynomial models. A suitable example of such approach is the spline. The authors show that their approach to data aggregation allows reducing the level of data uncertainty and significantly increasing the efficiency of numerical calculations. To demonstrate the degree of the correspondence of the proposed methods to reality, the authors developed a theoretical framework and considered numerical examples devoted to time series aggregation.

The Green Berry Consortia of the Sippewissett Salt Marsh: Millimeter-Sized Aggregates of Diazotrophic Unicellular Cyanobacteria.

PubMed

Wilbanks, Elizabeth G; Salman-Carvalho, Verena; Jaekel, Ulrike; Humphrey, Parris T; Eisen, Jonathan A; Buckley, Daniel H; Zinder, Stephen H

2017-01-01

Microbial interactions driving key biogeochemical fluxes often occur within multispecies consortia that form spatially heterogeneous microenvironments. Here, we describe the "green berry" consortia of the Sippewissett salt marsh (Falmouth, MA, United States): millimeter-sized aggregates dominated by an uncultured, diazotrophic unicellular cyanobacterium of the order Chroococcales (termed GB-CYN1). We show that GB-CYN1 is closely related to Crocosphaera watsonii (UCYN-B) and " Candidatus Atelocyanobacterium thalassa" (UCYN-A), two groups of unicellular diazotrophic cyanobacteria that play an important role in marine primary production. Other green berry consortium members include pennate diatoms and putative heterotrophic bacteria from the Alphaproteobacteria and Bacteroidetes . Tight coupling was observed between photosynthetic oxygen production and heterotrophic respiration. When illuminated, the green berries became supersaturated with oxygen. From the metagenome, we observed that GB-CYN1 encodes photosystem II genes and thus has the metabolic potential for oxygen production unlike UCYN-A. In darkness, respiratory activity rapidly depleted oxygen creating anoxia within the aggregates. Metagenomic data revealed a suite of nitrogen fixation genes encoded by GB-CYN1, and nitrogenase activity was confirmed at the whole-aggregate level by acetylene reduction assays. Metagenome reads homologous to marker genes for denitrification were observed and suggest that heterotrophic denitrifiers might co-occur in the green berries, although the physiology and activity of facultative anaerobes in these aggregates remains uncharacterized. Nitrogen fixation in the surface ocean was long thought to be driven by filamentous cyanobacterial aggregates, though recent work has demonstrated the importance of unicellular diazotrophic cyanobacteria (UCYN) from the order Chroococcales. The green berries serve as a useful contrast to studies of open ocean UCYN and may provide a tractable model system to investigate microbial dynamics within phytoplankton aggregates, a phenomenon of global importance to the flux of particulate organic carbon and nitrogen in surface waters.

The Green Berry Consortia of the Sippewissett Salt Marsh: Millimeter-Sized Aggregates of Diazotrophic Unicellular Cyanobacteria

PubMed Central

Wilbanks, Elizabeth G.; Salman-Carvalho, Verena; Jaekel, Ulrike; Humphrey, Parris T.; Eisen, Jonathan A.; Buckley, Daniel H.; Zinder, Stephen H.

2017-01-01

Microbial interactions driving key biogeochemical fluxes often occur within multispecies consortia that form spatially heterogeneous microenvironments. Here, we describe the “green berry” consortia of the Sippewissett salt marsh (Falmouth, MA, United States): millimeter-sized aggregates dominated by an uncultured, diazotrophic unicellular cyanobacterium of the order Chroococcales (termed GB-CYN1). We show that GB-CYN1 is closely related to Crocosphaera watsonii (UCYN-B) and “Candidatus Atelocyanobacterium thalassa” (UCYN-A), two groups of unicellular diazotrophic cyanobacteria that play an important role in marine primary production. Other green berry consortium members include pennate diatoms and putative heterotrophic bacteria from the Alphaproteobacteria and Bacteroidetes. Tight coupling was observed between photosynthetic oxygen production and heterotrophic respiration. When illuminated, the green berries became supersaturated with oxygen. From the metagenome, we observed that GB-CYN1 encodes photosystem II genes and thus has the metabolic potential for oxygen production unlike UCYN-A. In darkness, respiratory activity rapidly depleted oxygen creating anoxia within the aggregates. Metagenomic data revealed a suite of nitrogen fixation genes encoded by GB-CYN1, and nitrogenase activity was confirmed at the whole-aggregate level by acetylene reduction assays. Metagenome reads homologous to marker genes for denitrification were observed and suggest that heterotrophic denitrifiers might co-occur in the green berries, although the physiology and activity of facultative anaerobes in these aggregates remains uncharacterized. Nitrogen fixation in the surface ocean was long thought to be driven by filamentous cyanobacterial aggregates, though recent work has demonstrated the importance of unicellular diazotrophic cyanobacteria (UCYN) from the order Chroococcales. The green berries serve as a useful contrast to studies of open ocean UCYN and may provide a tractable model system to investigate microbial dynamics within phytoplankton aggregates, a phenomenon of global importance to the flux of particulate organic carbon and nitrogen in surface waters. PMID:28928719

Interaction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction.

PubMed

Chiang, T M; Beachey, E H; Kang, A H

1975-09-10

The denatured alpha1(I) chain and the cyanogen bromide peptide, alpha1(I)-CB5, of chick skin collagen cause the release of serotonin and leakage of lactic dehydrogenase from human platelets in a manner similar to the release reaction mediated by adenosine diphosphate and native collagen. These peptides also cause a decrease in the level of adenosine 3':5'-monophosphate (cAMP) in platelets. Adenylate cyclase activity of platelets is partially inhibited by these peptides as well as by native collagen, ADP, and epinephrine, but cAMP phosphodiesterase activity is unaltered by these substances. In contrast, the level of platelet guanosine 3':5'-monophosphate (cGMP) is increased by the collagen peptides as well as the other aggregating agents. The increase is associated with increased guanylate cyclase, but normal cGMP phosphodiesterase activities of platelets. Optical rotatory and viscometric measurements of the alpha1 chains and alpha1-CB5 of chick skin in 0.01 M phosphate/0.15 M sodium chloride, pH 7.4, at various temperatures as a function of time indicate that no detectable renaturation occurs at 37 degrees for at least 30 min of observation. Molecular sieve chromatography of alpha1-CB5 in the phosphate buffer at 37 degrees shows that its elution position is identical to that performed under denaturing conditions (at 45 degrees) with no evidence of higher molecular weight aggregates, and the alpha1-CB5 glycopeptide fraction eluting from the column at the position of its monomer retains the platelet aggregating activity. Additionally, electron microscopic examination of the platelet-rich plasma that had been reacted with these peptides fail to show any ordered collagen structures. These data indicate that the denatured alpha1 chain and alpha1-CB5 glycopeptide of chick skin collagen mediate platelet aggregation through the "physiologic" release reaction in a manner similar to that induced by other aggregating agents such as ADP, epinephrine, or native collagen, and support the conclusion that the aggregating activity of the alpha1 chain and alpha1-CB5 is not likely to be due to the formation of polymerized products.

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

NASA Astrophysics Data System (ADS)

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

2011-04-01

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

A comparative study on carbon footprint of rice production between household and aggregated farms from Jiangxi, China.

PubMed

Yan, Ming; Luo, Ting; Bian, Rongjun; Cheng, Kun; Pan, Genxing; Rees, Robert

2015-06-01

Quantifying the carbon footprint (CF) for crop production can help identify key options to mitigate greenhouse gas (GHG) emissions in agriculture. In the present study, both household and aggregated farm scales were surveyed to obtain the data of rice production and farming management practices in a typical rice cultivation area of Northern Jiangxi, China. The CFs of the different rice systems including early rice, late rice, and single rice under household and aggregated farm scale were calculated. In general, early rice had the lower CF in terms of land use and grain production being 4.54 ± 0.44 t CO2-eq./ha and 0.62 ± 0.1 t CO2-eq./t grain than single rice (6.84 ± 0.79 t CO2-eq./ha and 0.80 ± 0.13 t CO2-eq./t grain) and late rice (8.72 ± 0.54 t CO2-eq./ha and 1.1 ± 0.17 t CO2-eq./t grain). The emissions from nitrogen fertilizer use accounted for 33 % of the total CF on average and the direct CH4 emissions for 57 %. The results indicated that the CF of double rice cropping under aggregated farm being 0.86 ± 0.11 t CO2-eq./t grain was lower by 25 % than that being 1.14 ± 0.25 t CO2-eq./t grain under household farm, mainly due to high nitrogen use efficiency and low methane emissions. Therefore, developing the aggregated farm scale with efficient use of agro-chemicals and farming operation for greater profitability could offer a strategy for reducing GHG emissions in China's agriculture.

Natural aggregates of the conterminous United States

USGS Publications Warehouse

Langer, William H.

1988-01-01

Crushed stone and sand and gravel are the two main sources of natural aggregates. These materials are commonly used construction materials and frequently can be interchanged with one another. They are widely used throughout the United States, with every State except two producing crushed stone. Together they amount to about half the mining volume in the United States. Approximately 96 percent of sand and gravel and 77 percent of the crushed stone produced in the United States are used in the construction industry. Natural aggregates are widely distributed throughout the United States in a variety of geologic environments. Sand and gravel deposits commonly are the results of the weathering of bedrock and subsequent transportation and deposition of the material by water or ice (glaciers). As such, they commonly occur as river or stream deposits or in glaciated areas as glaciofluvial and other deposits. Crushed stone aggregates are derived from a wide variety of parent bedrock materials. Limestone and other carbonates account for approximately three quarters of the rocks used for crushed stone, with granite and other igneous rocks making up the bulk of the remainder. Limestone deposits are widespread throughout the Central and Eastern United States and are scattered in the West. Granites are widely distributed in the Eastern and Western United States, with few exposures in the Midwest. Igneous rocks (excluding granites) are largely concentrated in the Western United States and in a few isolated localities in the East. Even though natural aggregates are widely distributed throughout the United States, they are not universally available for consumptive use. Some areas are devoid of sand and gravel, and potential sources of crushed stone may be covered with sufficient unconsolidated material to make surface mining impractical. In some areas many aggregates do not meet the physical property requirements for certain uses, or they may contain mineral constituents that react adversely when used as concrete aggregate. In areas where suitable natural aggregate is not available or accessible, it may become necessary to improve the quality of existing aggregate, to import aggregate from outside the area, or to substitute artificial aggregate for natural aggregate. In most cases, all of these alternatives add substantially to the cost of the final product. Even though an area may be blessed with an abundance of aggregate suitable for the intended purpose, existing land uses, zoning, or regulations may preclude commercial exploitation of the aggregate. This report also discusses the aggregate industry in general terms, including exploration, mining, and processing, as well as aggregate production rates. Proper long-range planning based on an understanding of the aggregate industry can help assure adequate supplies of aggregate.

Standardization of databases for AMDB taxi routing functions

NASA Astrophysics Data System (ADS)

Pschierer, C.; Sindlinger, A.; Schiefele, J.

2010-04-01

Input, management, and display of taxi routes on airport moving map displays (AMM) have been covered in various studies in the past. The demonstrated applications are typically based on Aerodrome Mapping Databases (AMDB). Taxi routing functions require specific enhancements, typically in the form of a graph network with nodes and edges modeling all connectivities within an airport, which are not supported by the current AMDB standards. Therefore, the data schemas and data content have been defined specifically for the purpose and test scenarios of these studies. A standardization of the data format for taxi routing information is a prerequisite for turning taxi routing functions into production. The joint RTCA/EUROCAE special committee SC-217, responsible for updating and enhancing the AMDB standards DO-272 [1] and DO-291 [2], is currently in the process of studying different alternatives and defining reasonable formats. Requirements for taxi routing data are primarily driven by depiction concepts for assigned and cleared taxi routes, but also by database size and the economic feasibility. Studied concepts are similar to the ones described in the GDF (geographic data files) specification [3], which is used in most car navigation systems today. They include - A highly aggregated graph network of complex features - A modestly aggregated graph network of simple features - A non-explicit topology of plain AMDB taxi guidance line elements This paper introduces the different concepts and their advantages and disadvantages.

Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry*.

PubMed

Hanke, A A; Dellweg, C; Kienbaum, P; Weber, C F; Görlinger, K; Rahe-Meyer, N

2010-07-01

Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Wine as a biological fluid: history, production, and role in disease prevention.

PubMed

Soleas, G J; Diamandis, E P; Goldberg, D M

1997-01-01

Wine has been part of human culture for 6,000 years, serving dietary and socio-religious functions. Its production takes place on every continent, and its chemical composition is profoundly influenced by enological techniques, the grape cultivar from which it originates, and climatic factors. In addition to ethanol, which in moderate consumption can reduce mortality from coronary heart disease by increasing high-density lipoprotein cholesterol and inhibiting platelet aggregation, wine (especially red wine) contains a range of polyphenols that have desirable biological properties. These include the phenolic acids (p-coumaric, cinnamic, caffeic, gentisic, ferulic, and vanillic acids), trihydroxy stilbenes (resveratrol and polydatin), and flavonoids (catechin, epicatechin, and quercetin). They are synthesized by a common pathway from phenylalanine involving polyketide condensation reactions. Metabolic regulation is provided by competition between resveratrol synthase and chalcone synthase for a common precursor pool of acyl-CoA derivatives. Polymeric aggregation gives rise, in turn to the viniferins (potent antifungal agents) and procyanidins (strong antioxidants that also inhibit platelet aggregation). The antioxidant effects of red wine and of its major polyphenols have been demonstrated in many experimental systems spanning the range from in vitro studies (human low-density lipoprotein, liposomes, macrophages, cultured cells) to investigations in healthy human subjects. Several of these compounds (notably catechin, quercetin, and resveratrol) promote nitric oxide production by vascular endothelium; inhibit the synthesis of thromboxane in platelets and leukotriene in neutrophils, modulate the synthesis and secretion of lipoproteins in whole animals and human cell lines, and arrest tumour growth as well as inhibit carcinogenesis in different experimental models. Target mechanisms to account for these effects include inhibition of phospholipase A2 and cyclo-oxygenase, inhibition of phosphodiesterase with increase in cyclic nucleotide concentrations, and inhibition of several protein kinases involved in cell signalling. Although their bioavailability remains to be fully established, red wine provides a more favourable milieu than fruits and vegetables, their other dietary source in humans.

Aggregation and metal-complexation behaviour of THPP porphyrin in ethanol/water solutions as function of pH

NASA Astrophysics Data System (ADS)

Zannotti, Marco; Giovannetti, Rita; Minofar, Babak; Řeha, David; Plačková, Lydie; D'Amato, Chiara A.; Rommozzi, Elena; Dudko, Hanna V.; Kari, Nuerguli; Minicucci, Marco

2018-03-01

The effect of pH change on 5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine (THPP) with its aggregation as function of water-ethanol mixture was studied with UV-vis, fluorescence, Raman and computational analysis. In neutral pH, THPP was present as free-base and, increasing the water amount, aggregation occurred with the formation of H- and J-aggregates. The aggregation constant and the concentration of dimers were calculated, other information about the dimer aggregation were evaluated by computational study. In acidic pH, by the insertions of two hydrogens in the porphyrin rings, the porphyrin changed its geometry with a ring deformation confirmed by red-shifted spectrum and quenching in fluorescence; at this low pH, increasing the water amount, the acidic form (THPPH2)2 + resulted more stable due to a polar environment with stronger interaction by hydrogen bonding. In basic pH, reached by NH4OH, THPP porphyrin was able to react with alkali metals in order to form sitting-atop complex (M2THPP) confirmed by the typical absorption spectrum of metallo-porphyrin, Raman spectroscopy and by computational analysis.

Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment.

PubMed

Sabek, Omaima M; Farina, Marco; Fraga, Daniel W; Afshar, Solmaz; Ballerini, Andrea; Filgueira, Carly S; Thekkedath, Usha R; Grattoni, Alessandro; Gaber, A Osama

2016-01-01

Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow-derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates' survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland-islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy.

On/off switching of capillary vessel flow controls mitochondrial and glycolysis pathways for energy production.

PubMed

Abo, Toru; Watanabe, Mayumi; Tomiyama, Chikako; Kanda, Yasuhiro

2014-07-01

Capillary vessel flow in the base of the fingernail can be observed by microscopy. This flow is switched off under some conditions, such as coldness, surprise, and anger and is switched on again under other conditions, such as warming, relaxation, and mild exercise. In other words, capillary vessels perform two functions: switching flow on and off. It is speculated that the switch-off function is necessary to direct energy production to the glycolysis pathway, while the switch-on function is necessary for the mitochondrial pathway. This is because glycolysis takes place under anaerobic conditions, while oxidative phosphorylation in the mitochondria proceeds under aerobic conditions in the body. To switch off circulation, the negative electric charges on the surface of erythrocytes and the capillary wall may be decreased by stimulation of the sympathetic nerves and secretion of steroid hormones. Negative charge usually acts as repulsive force between erythrocytes and between erythrocytes and the capillary wall. By decreasing the negative charge, erythrocytes can aggregate and also adhere to the capillary wall. These behaviors may be related to the capillary flow switch-off function. Here, it is emphasized that the capillary vessels possess not only a switch-on function but also a switch-off function for circulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost-Efficient and Multi-Functional Secure Aggregation in Large Scale Distributed Application

PubMed Central

Zhang, Ping; Li, Wenjun; Sun, Hua

2016-01-01

Secure aggregation is an essential component of modern distributed applications and data mining platforms. Aggregated statistical results are typically adopted in constructing a data cube for data analysis at multiple abstraction levels in data warehouse platforms. Generating different types of statistical results efficiently at the same time (or referred to as enabling multi-functional support) is a fundamental requirement in practice. However, most of the existing schemes support a very limited number of statistics. Securely obtaining typical statistical results simultaneously in the distribution system, without recovering the original data, is still an open problem. In this paper, we present SEDAR, which is a SEcure Data Aggregation scheme under the Range segmentation model. Range segmentation model is proposed to reduce the communication cost by capturing the data characteristics, and different range uses different aggregation strategy. For raw data in the dominant range, SEDAR encodes them into well defined vectors to provide value-preservation and order-preservation, and thus provides the basis for multi-functional aggregation. A homomorphic encryption scheme is used to achieve data privacy. We also present two enhanced versions. The first one is a Random based SEDAR (REDAR), and the second is a Compression based SEDAR (CEDAR). Both of them can significantly reduce communication cost with the trade-off lower security and lower accuracy, respectively. Experimental evaluations, based on six different scenes of real data, show that all of them have an excellent performance on cost and accuracy. PMID:27551747

In vitro effect of sodium nitrite on platelet aggregation in human platelet rich plasma--preliminary report.

PubMed

Kadan, M; Doğanci, S; Yildirim, V; Özgür, G; Erol, G; Karabacak, K; Avcu, F

2015-10-01

The role of nitrates and nitric oxide on platelet functions has obtained an increasing attention with respect to their potential effects on cardiovascular disorders. In this study we aimed to analyze the effect of sodium nitrite on platelet functions in human platelets. This in vitro study was designed to show the effect of sodium nitrite on platelet functions in seven healthy volunteers. Blood samples were centrifuged to prepare platelet rich plasma and platelet poor plasma. Platelet rich plasma was diluted with the platelet poor plasma to have a final count of 300,000 ± 25,000 platelets. Platelet rich plasma was incubated with six different increasing doses (from 10 μM to 5 mM) of sodium nitrite for 1 hour at 37°C. Then stimulating agents including collagen (3 μg ml-1), adenosine diphosphate (10 μM), and epinephrine (10 μM) were added to the cuvette. Changes in light transmission were observed for 10 minutes. In addition spontaneous aggregation were performed in control group with all aggregating agents separately. Effect of sodium nitrite on agonist-induced platelet aggregation depends on the concentration of sodium nitrite. Compared with control group, agonist-induced platelet aggregations were significantly suppressed by sodium nitrite at the concentration of 5, 1.0 and 0.5 mM. Our results suggested that sodium nitrite has inhibitory effects in vitro on platelet aggregation in a dose-dependent manner.

Cost-Efficient and Multi-Functional Secure Aggregation in Large Scale Distributed Application.

PubMed

Zhang, Ping; Li, Wenjun; Sun, Hua

2016-01-01

Secure aggregation is an essential component of modern distributed applications and data mining platforms. Aggregated statistical results are typically adopted in constructing a data cube for data analysis at multiple abstraction levels in data warehouse platforms. Generating different types of statistical results efficiently at the same time (or referred to as enabling multi-functional support) is a fundamental requirement in practice. However, most of the existing schemes support a very limited number of statistics. Securely obtaining typical statistical results simultaneously in the distribution system, without recovering the original data, is still an open problem. In this paper, we present SEDAR, which is a SEcure Data Aggregation scheme under the Range segmentation model. Range segmentation model is proposed to reduce the communication cost by capturing the data characteristics, and different range uses different aggregation strategy. For raw data in the dominant range, SEDAR encodes them into well defined vectors to provide value-preservation and order-preservation, and thus provides the basis for multi-functional aggregation. A homomorphic encryption scheme is used to achieve data privacy. We also present two enhanced versions. The first one is a Random based SEDAR (REDAR), and the second is a Compression based SEDAR (CEDAR). Both of them can significantly reduce communication cost with the trade-off lower security and lower accuracy, respectively. Experimental evaluations, based on six different scenes of real data, show that all of them have an excellent performance on cost and accuracy.

Recovery of MSWI and soil washing residues as concrete aggregates.

PubMed

Sorlini, Sabrina; Abbà, Alessandro; Collivignarelli, Carlo

2011-02-01

The aim of the present work was to study if municipal solid waste incinerator (MSWI) residues and aggregates derived from contaminated soil washing could be used as alternative aggregates for concrete production. Initially, chemical, physical and geometric characteristics (according to UNI EN 12620) of municipal solid waste incineration bottom ashes and some contaminated soils were evaluated; moreover, the pollutants release was evaluated by means of leaching tests. The results showed that the reuse of pre-treated MSWI bottom ash and washed soil is possible, either from technical or environmental point of view, while it is not possible for the raw wastes. Then, the natural aggregate was partially and totally replaced with these recycled aggregates for the production of concrete mixtures that were characterized by conventional mechanical and leaching tests. Good results were obtained using the same dosage of a high resistance cement (42.5R calcareous Portland cement instead of 32.5R); the concrete mixture containing 400 kg/m(3) of washed bottom ash and high resistance cement was classified as structural concrete (C25/30 class). Regarding the pollutants leaching, all concrete mixtures respected the limit values according to the Italian regulation. Copyright © 2010 Elsevier Ltd. All rights reserved.

48 CFR 1408.802 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Printing and Related Supplies 1408.802... the aggregate of multiple pages. Such duplicating units shall require Departmental approval to be... to 2,500 production units in the aggregate of multiple pages. This volume standard is referred to as...

Reuse of municipal solid wastes incineration fly ashes in concrete mixtures.

PubMed

Collivignarelli, Carlo; Sorlini, Sabrina

2002-01-01

This study is aimed at assessing the feasibility of concrete production using stabilized m.s.w. (municipal solid waste) incineration fly ashes in addition to natural aggregates. The tested fly ashes were washed and milled, then stabilized by a cement-lime process and finally were reused as a "recycled aggregate" for cement mixture production, in substitution of a natural aggregate (with dosage of 200-400 kg m(-3)). These mixtures, after curing, were characterized with conventional physical-mechanical tests (compression, traction, flexure, modulus of elasticity, shrinkage). In samples containing 200 kg(waste) m(-3)(concrete), a good compressive strength was achieved after 28 days of curing. Furthermore, concrete leaching behavior was evaluated by means of different leaching tests, both on milled and on monolithic samples. Experimental results showed a remarkable reduction of metal leaching in comparison with raw waste. In some cases, similar behavior was observed in "natural" concrete (produced with natural aggregates) and in "waste containing" concrete.

Microhabitat Effects on N2O Emissions from Floodplain Soils under Controlled Conditions

NASA Astrophysics Data System (ADS)

Ley, Martin; Lehmann, Moritz F.; Niklaus, Pascal A.; Kuhn, Thomas; Luster, Jörg

2016-04-01

Semi-terrestrial soils such as floodplain soils are considered to be potential hotspots of nitrous oxide (N2O) emissions. The quantitative assessment of N2O release from these hotspots under field conditions, and of the microbial pathways that underlie net N2O production (ammonium oxidation, nitrifier-denitrification, and denitrification) is challenging because of their high spatial and temporal variability. The production and consumption of N2O appears to be linked to the presence or absence of micro-niches, providing specific conditions that may be favorable to either of the relevant microbial pathways. Flood events have been shown to trigger moments of enhanced N2O emission through a close coupling of niches with high and low oxygen availabilities. This coupling might be modulated by microhabitat effects related to soil aggregate formation, root soil interactions and the degradation of organic matter accumulations. In order to assess how these factors can modulate N2O production and consumption under simulated flooding/drying conditions, we have set up a mesocosm experiment with N-rich floodplain soils comprising different combinations of soil aggregate size classes and inert matrix material. These model soils were either planted with basket willow (Salix viminalis L.), mixed with leaf litter, or left untreated. Throughout a simulated flood event, we repeatedly measured the net N2O production rate. In addition, soil water content, redox potential, as well as C and N substrate availability were monitored. In order to gain insight into the sources of, and biogeochemical controls on N2O production, we also measured the bulk δ15N signature of the produced N2O, as well as its intramolecular 15N site preference (SP). In this presentation we focus on a period of enhanced N2O emission during the drying phase after 48 hrs of flooding. We will discuss the observed emission patterns in the context of possible treatment effects. Soils with large aggregates showed a tendency to emit more N2O than small-aggregate soils. Salix viminalis strongly suppressed the N2O emissions, fully compensating for any aggregate effects. Litter accumulation on the other hand enhanced N2O emission from well-aggregated soils, but showed only a small effect in combination with small aggregates. In moments of highest emission rates, the measured δ15Nbulk of headspace N2O was considerably lower relative to atmospheric N2O (δ15N between -20 ‰ and -25 ‰) in the amended treatments, suggesting N2O production by denitrification or by nitrifier-denitrification. Untreated mesocosms produced an even lower δ15Nbulk (-40‰). Similarly, aggregate formation/size seemed to affect the N2O δ15Nbulk values, suggesting different net N2O production dynamics under different microhabitat conditions, which will be elucidated further, using 15N site preference SP data. Combining stable isotope techniques with quantitative flux data from a mesoscale laboratory experiment, our data highlight the importance of microhabitat effects in modulating N2O emission from floodplain soils. It also underscores their influence on the N2O production pathways involved in the occurrence of N2O emission hot spots and moments.

Combined research effort on aggregate road materials

NASA Astrophysics Data System (ADS)

Kuznetsova, Elena; Hoff, Inge; Willy Danielsen, Svein; Wigum, Børge Johannes; Fladvad, Marit; Rieksts, Karlis; Loranger, Benoit; Barbieri, Diego

2017-04-01

In European countries, the average aggregate consumption per capita is 5 tons per year (European Aggregates Association 2016), while the corresponding number in Norway is 11 tons (Neeb 2015). Due to the increased demand for sand and gravel for construction purposes, e.g. in road construction, the last decade has seen a significant trend towards the use of crushed rock aggregates. Neeb (2015) reports that half of the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction, and 33 % of the overall sold tonnage of crushed rock is exported. This resource has been more and more preferred over sand and gravel due to the significant technological development of its process and utilization phase. In Norway, the development and implementation of crushed aggregate technology has been the main approach to solve natural resource scarcity (Danielsen and Kuznetsova 2015). In order to reduce aggregates transportation, it is aimed to use local aggregates and aggregates processed from rock excavations, tunneling, road cuts, etc. One issue focused in this research is the influence from blasting and processing on the final quality of the crushed aggregates, specifically relating to the properties for road construction purposes. It is therefor crucial to plan utilization of available materials for use in different road layers following the same production line. New developments and improved availability of mobile crushing and screening equipment could produce more sustainable and profitable sources of good quality aggregate materials from small volume deposits in proximity to construction sites. One of the biggest challenges today to use these materials is that the pavement design manual sets rigid requirements for pavement layers. Four research projects are being conducted in Norway to improve the use of local materials for road construction. Four aspects are to be covered by the research: a) geological characteristics of the materials, their b) mechanical and c) thermal properties, and d) frost action and susceptibility. The main goal of the PhD topic N1 is to achieve better utilization of aggregate resources through adjusting the production process according to local geological conditions and construction needs. The objective of the PhD project N2 is to look at the design stage and find the way to use these aggregates anyway by changing the road's design (e.g. increasing the thickness of asphalt layer). Fine particles content will also be harder to control due to rock type variability from site to site. Thus, PhD project N3 is going to investigate the effect of the increasing of fines and their mineralogy on frost action related problems during freezing and thawing seasons. Finally, PhD project N4 is investigating how the grading and mineralogy of the crushed rock material affects the heat exchange in road's granular layers and consequently, the frost penetration depth. Combining these PhD studies we aim to create a holistic approach for a new understanding within this very complex area.

Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

NASA Astrophysics Data System (ADS)

Singh, Raman Preet; Jain, Sanyog; Ramarao, Poduri

2013-10-01

Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation.

Cluster-cluster aggregation with particle replication and chemotaxy: a simple model for the growth of animal cells in culture

NASA Astrophysics Data System (ADS)

Alves, S. G.; Martins, M. L.

2010-09-01

Aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and in vitro drug testing. In the present paper, a cluster-cluster aggregation model with stochastic particle replication and chemotactically driven motility is investigated as a model for the growth of animal cells in culture. The focus is on the scaling laws governing the aggregation kinetics. Our simulations reveal that in the absence of chemotaxy the mean cluster size and the total number of clusters scale in time as stretched exponentials dependent on the particle replication rate. Also, the dynamical cluster size distribution functions are represented by a scaling relation in which the scaling function involves a stretched exponential of the time. The introduction of chemoattraction among the particles leads to distribution functions decaying as power laws with exponents that decrease in time. The fractal dimensions and size distributions of the simulated clusters are qualitatively discussed in terms of those determined experimentally for several normal and tumoral cell lines growing in culture. It is shown that particle replication and chemotaxy account for the simplest cluster size distributions of cellular aggregates observed in culture.

Red blood cell generation by three-dimensional aggregate cultivation of late erythroblasts.

PubMed

Lee, EunMi; Han, So Yeon; Choi, Hye Sook; Chun, Bokhwan; Hwang, Byunghee; Baek, Eun Jung

2015-02-01

Stem cell-derived erythroid cells hold great potential for the treatment of blood-loss anemia and for erythropoiesis research; however, cultures using conventional flat plates or bioreactors have failed to show promising results. By mimicking the in vivo bone marrow (BM) environment in which most erythroid cells are physically aggregated, we show that a three-dimensional (3D) aggregate culture system facilitates erythroid cell maturation and red blood cell (RBC) production more effectively than two-dimensional high-density cell cultivation. Late erythroblasts (polychromatic or orthochromatic erythroblasts) were differentiated from cord blood CD34(+) cells over 15 days and then allowed to form tight aggregates at a minimum density of 1×10(7) cells/mL for 2-3 days. To scale up the cell culture and to make the media supply efficient throughout the cell aggregates, several macroporous microcarriers and porous scaffolds were applied to the 3D culture system. In comparison to control culture conditions, erythroid cells in 3D aggregates were significantly more differentiated toward RBCs with significantly reduced nuclear dysplasia. When 3D culture was performed inside macroporous microcarriers, the cell culture scale was increased and cells exhibited enhanced differentiation and enucleation. Microcarriers with a pore diameter of approximately 400 μm produced more mature cells than those with a smaller pore diameter. In addition, this aggregate culture method minimized the culture space and media volume required. In conclusion, a 3D aggregate culture system can be used to generate transfusable human erythrocytes at the terminal maturation stage, mimicking the in vivo BM microenvironment. Porous structures can efficiently maximize the culture scale, enabling large-scale production of RBCs. These results enhance our understanding of the importance of physical contact among late erythroblasts for their final maturation into RBCs.

Chemoreception to aggregation pheromones in the common bed bug, Cimex lectularius.

PubMed

Liu, Feng; Xiong, Caixing; Liu, Nannan

2017-03-01

The common bed bug, Cimex lectularius, is an obligate blood-feeding insect that is resurgent worldwide, posing a threat to human beings through its biting nuisance and disease transmission. Bed bug aggregation pheromone is considered a very promising attractant for use in the monitoring and management of bed bugs, but as yet little is known regarding the sensory physiology of bed bugs related to this pheromone. This study examined how the individual components of aggregation pheromone are perceived by the olfactory receptor neurons (ORNs) housed in different types of olfactory sensilla in bed bugs and the molecular basis for the ORNs' responses to the aggregation pheromone. We found that the ORNs in the D olfactory sensilla played a predominant role in detecting all the components of aggregation pheromone except for histamine, which was only recognized by the C sensilla. Bed bugs' E sensilla, which include four functionally distinct groups, showed only a very weak but variant sensitivity (both excitatory and inhibitory) to the components of aggregation pheromone. Functional tests of 15 odorant receptors (ORs) in response to the components of aggregation pheromone revealed that most of these components were encoded by multiple ORs with various tuning properties. This study provides a comprehensive understanding of how bed bug aggregation pheromone is perceived and recognized in the peripheral olfactory system and will contribute useful information to support the development of synthetic attractants for bed bug monitoring and control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-aggregation and coaggregation of the p53 core fragment with its aggregation gatekeeper variant.

PubMed

Lei, Jiangtao; Qi, Ruxi; Wei, Guanghong; Nussinov, Ruth; Ma, Buyong

2016-03-21

Recent studies suggested that p53 aggregation can lead to loss-of-function (LoF), dominant-negative (DN) and gain-of-function (GoF) effects, with adverse cancer consequences. The p53 aggregation-nucleating (251)ILTIITL(257) fragment is a key segment in wild-type p53 aggregation; however, an I254R mutation can prevent it. It was suggested that self-assembly of wild-type p53 and its cross-interaction with mutants differ from the classical amyloid nucleation-growth mechanism. Here, using replica exchange molecular dynamics (REMD) simulations, we studied the cross-interactions of this p53 core fragment and its aggregation rescue I254R mutant. We found that the core fragment displays strong aggregation propensity, whereas the gatekeeper I254R mutant tends to be disordered, consistent with experiments. Our cross-interaction results reveal that the wild-type p53 fragment promotes β-sheet formation of the I254R mutant by shifting the disordered mutant peptides into aggregating states. As a result, the system has similar oligomeric structures, inter-peptide interactions and free energy landscape as the wild type fragment does, revealing a prion-like process. We also found that in the cross-interaction system, the wild-type species has higher tendency to interact with the mutant than with itself. This phenomenon illustrates synergistic effects between the p53 (251)ILTIITL(257) fragment and the mutant resembling prion cross-species propagation, cautioning against exploiting it in drug discovery.

Spatially aggregated multiclass pattern classification in functional MRI using optimally selected functional brain areas.

PubMed

Zheng, Weili; Ackley, Elena S; Martínez-Ramón, Manel; Posse, Stefan

2013-02-01

In previous works, boosting aggregation of classifier outputs from discrete brain areas has been demonstrated to reduce dimensionality and improve the robustness and accuracy of functional magnetic resonance imaging (fMRI) classification. However, dimensionality reduction and classification of mixed activation patterns of multiple classes remain challenging. In the present study, the goals were (a) to reduce dimensionality by combining feature reduction at the voxel level and backward elimination of optimally aggregated classifiers at the region level, (b) to compare region selection for spatially aggregated classification using boosting and partial least squares regression methods and (c) to resolve mixed activation patterns using probabilistic prediction of individual tasks. Brain activation maps from interleaved visual, motor, auditory and cognitive tasks were segmented into 144 functional regions. Feature selection reduced the number of feature voxels by more than 50%, leaving 95 regions. The two aggregation approaches further reduced the number of regions to 30, resulting in more than 75% reduction of classification time and misclassification rates of less than 3%. Boosting and partial least squares (PLS) were compared to select the most discriminative and the most task correlated regions, respectively. Successful task prediction in mixed activation patterns was feasible within the first block of task activation in real-time fMRI experiments. This methodology is suitable for sparsifying activation patterns in real-time fMRI and for neurofeedback from distributed networks of brain activation. Copyright © 2013 Elsevier Inc. All rights reserved.

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

PubMed

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Nontronite Particle Aggregation Induced by Microbial Fe(III) Reduction and Exopolysaccharide Production

DTIC Science & Technology

2007-01-01

polymers to achieve desired properties (such Chenu el al., 1979; Kimn el al., 2005). Among these as aggregation. dispersion ) without any structural...performed with and without Na pyrophosphate as a term ’aggregation’ broadly to include all processes that dispersant (25 mM) with shaking in a water...coagulation, at 25 mM was found to be optimal to disperse individual flocculation, agglutination, etc.). The results of this clay particles without

Comparison Pore Aggregate Levels After Extraction With Solvents Pertamax Plus And Gasoline

NASA Astrophysics Data System (ADS)

Anggraini, Muthia

2017-12-01

Loss of asphalt content extraction results become problems in Field Work For implementing parties. The use of solvents with high octane (pertamax plus) for the extraction, dissolving the asphalt more than gasoline. By comparing the levels of aggregate pores after using solvent extraction pertamax plus compared to gasoline could answer that pertamax plus more solvent dissolves the bitumen compared to gasoline. This study aims to obtain comparative levels of porous aggregate mix AC-WC after using solvent extraction pertamax plus compared to gasoline. This study uses the aggregate that has been extracted from the production of asphalt mixtures, when finisher and after compaction field. The method used is the assay of coarse and fine aggregate pores, extraction of bitumen content to separate the aggregate with bitumen. Results of testing the total absorption after extraction using a solvent preta max plus in the production of asphalt mixtures 0.80%, while gasoline solvent 0.67% deviation occurs 0.13%. In the finisher after the solvent extraction preta max plus 0.77%, while 0.67% gasoline solvent occurs deviation of 0.1%. At the core after extraction and solvent pertamax plus 0.71%, while gasoline solvent 0.60% 0.11% deviation occurs. The total water absorption after extraction using a solvent pertamax plus greater than gasoline. This proves that the solvent dissolves pertamax plus more asphalt than gasoline.

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

PubMed Central

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

2014-01-01

The main strategy to reduce the environmental impact of the concrete industry is to reuse the waste materials. This research has considered the combination of cement replacement by industrial by-products, and natural coarse aggregate substitution by recycled aggregate. The aim is to evaluate the behavior of concretes with a reduced impact on the environment by replacing a 50% of cement by industrial by-products (15% of spent fluid catalytic cracking catalyst and 35% of fly ash) and a 100% of natural coarse aggregate by recycled aggregate. The concretes prepared according to these considerations have been tested in terms of mechanical strengths and the protection offered against steel reinforcement corrosion under carbonation attack and chloride-contaminated environments. The proposed concrete combinations reduced the mechanical performance of concretes in terms of elastic modulus, compressive strength, and flexural strength. In addition, an increase in open porosity due to the presence of recycled aggregate was observed, which is coherent with the changes observed in mechanical tests. Regarding corrosion tests, no significant differences were observed in the case of the resistance of these types of concretes under a natural chloride attack. In the case of carbonation attack, although all concretes did not stand the highly aggressive conditions, those concretes with cement replacement behaved worse than Portland cement concretes. PMID:28788613

Engineering cell aggregates through incorporated polymeric microparticles.

PubMed

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

2017-10-15

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

Brain Aggregates: An Effective In Vitro Cell Culture System Modeling Neurodegenerative Diseases.

PubMed

Ahn, Misol; Kalume, Franck; Pitstick, Rose; Oehler, Abby; Carlson, George; DeArmond, Stephen J

2016-03-01

Drug discovery for neurodegenerative diseases is particularly challenging because of the discrepancies in drug effects between in vitro and in vivo studies. These discrepancies occur in part because current cell culture systems used for drug screening have many limitations. First, few cell culture systems accurately model human aging or neurodegenerative diseases. Second, drug efficacy may differ between dividing and stationary cells, the latter resembling nondividing neurons in the CNS. Brain aggregates (BrnAggs) derived from embryonic day 15 gestation mouse embryos may represent neuropathogenic processes in prion disease and reflect in vivo drug efficacy. Here, we report a new method for the production of BrnAggs suitable for drug screening and suggest that BrnAggs can model additional neurological diseases such as tauopathies. We also report a functional assay with BrnAggs by measuring electrophysiological activities. Our data suggest that BrnAggs could serve as an effective in vitro cell culture system for drug discovery for neurodegenerative diseases. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

0-6656 : ASR testing : a new approach to aggregate classification and mix design verification : [project summary].

DOT National Transportation Integrated Search

2014-08-01

In the past 5.5 years, the Texas Department of Transportation (TxDOT) spent approximately $2 million for recasting precast concrete products that had alkali-silica reaction (ASR). Aggregates belonging to false positive and negative categories based o...

Lymphoid microenvironments and innate lymphoid cells in the gut.

PubMed

Pearson, Claire; Uhlig, Holm H; Powrie, Fiona

2012-06-01

Gut-associated lymphoid tissue (GALT) is a sensor region for luminal content and plays an important role in lymphoid maturation, activation and differentiation. It comprises isolated and aggregated lymphoid follicles, cryptopatches (CPs) and tertiary lymphoid tissue. Innate lymphoid cells (ILCs) play a central role within GALT. Prenatal GALT development is dependent on ILC lymphoid-inducer function. Postnatally, these cells rapidly respond to commensal and pathogenic intestinal bacteria, parasites and food components by polarized cytokine production [such as interleukin (IL)-22, IL-17 or IL-13] and further contribute to GALT formation and function. Here, we discuss how ILCs shape lymphoid intestinal microenvironments and act as amplifier cells for innate and adaptive immune responses. Copyright © 2012. Published by Elsevier Ltd.

Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and β-Lactoglobulin.

PubMed

Chihi, Mohamed-Lazhar; Mession, Jean-luc; Sok, Nicolas; Saurel, Rémi

2016-04-06

The present work investigates the formation of protein aggregates (85 °C, 60 min incubation) upon heat treatment of β-lactoglobulin (βlg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various βlg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured βlg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures.

Flocculation kinetics and aggregate structure of kaolinite mixtures in laminar tube flow.

PubMed

Vaezi G, Farid; Sanders, R Sean; Masliyah, Jacob H

2011-03-01

Flocculation is commonly used in various solid-liquid separation processes in chemical and mineral industries to separate desired products or to treat waste streams. This paper presents an experimental technique to study flocculation processes in laminar tube flow. This approach allows for more realistic estimation of the shear rate to which an aggregate is exposed, as compared to more complicated shear fields (e.g. stirred tanks). A direct sampling method is used to minimize the effect of sampling on the aggregate structure. A combination of aggregate settling velocity and image analysis was used to quantify the structure of the aggregate. Aggregate size, density, and fractal dimension were found to be the most important aggregate structural parameters. The two methods used to determine aggregate fractal dimension were in good agreement. The effects of advective flow through an aggregate's porous structure and transition-regime drag coefficient on the evaluation of aggregate density were considered. The technique was applied to investigate the flocculation kinetics and the evolution of the aggregate structure of kaolin particles with an anionic flocculant under conditions similar to those of oil sands fine tailings. Aggregates were formed using a well controlled two-stage aggregation process. Detailed statistical analysis was performed to investigate the establishment of dynamic equilibrium condition in terms of aggregate size and density evolution. An equilibrium steady state condition was obtained within 90 s of the start of flocculation; after which no further change in aggregate structure was observed. Although longer flocculation times inside the shear field could conceivably cause aggregate structure conformation, statistical analysis indicated that this did not occur for the studied conditions. The results show that the technique and experimental conditions employed here produce aggregates having a well-defined, reproducible structure. Copyright © 2011. Published by Elsevier Inc.

Rapid Aggregation of Biofuel-Producing Algae by the Bacterium Bacillus sp. Strain RP1137

PubMed Central

Powell, Ryan J.

2013-01-01

Algal biofuels represent one of the most promising means of sustainably replacing liquid fuels. However, significant challenges remain before alga-based fuels become competitive with fossil fuels. One of the largest challenges is the ability to harvest the algae in an economical and low-energy manner. In this article, we describe the isolation of a bacterial strain, Bacillus sp. strain RP1137, which can rapidly aggregate several algae that are candidates for biofuel production, including a Nannochloropsis sp. This bacterium aggregates algae in a pH-dependent and reversible manner and retains its aggregation ability after paraformaldehyde fixation, opening the possibility for reuse of the cells. The optimal ratio of bacteria to algae is described, as is the robustness of aggregation at different salinities and temperatures. Aggregation is dependent on the presence of calcium or magnesium ions. The efficiency of aggregation of Nannochloropsis oceanica IMET1 is between 70 and 95% and is comparable to that obtained by other means of harvest; however, the rate of harvest is fast, with aggregates forming in 30 s. PMID:23892750

An overview of aggregate resources in the United States

USGS Publications Warehouse

Langer, William H.; Scott, P.W.; Bristow, C.M.

2002-01-01

In 2000 the USA produced about 2.7 billion tonnes of aggregate worth about $13.7 billion. Both crushed stone and sand and gravel are produced in virtually every State, although limited quantities are available in the Gulf Coastal Plain, the Colorado Plateau , the Wyoming Basin and the Great Plains. Prices vary depending on the product and location. Most aggregates are transported by road, and minor amounts by railroad, barge on navigable inland channels, and through the Great Lake ports. Imports and exports of aggregates are very minor. A major amount f crushed stone aggregates is consumed by concrete aggregate. Recycled aggregates account for about 8% of total demand, although the amount recycled is thought to be increasing. Current issues facing the inductry unclude the differences in quality specifications between States, adjusting to the increasing concern for the impact of aggregate mining on the environmentm, health issues from particulate matter and crystalline silica, and the complexity of obtaining permits for extraction. Redcustion in the number od companies extracting aggregrates is likely to occur through acquisitions.

Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.

PubMed

Fierro, Fernando A; Sierralta, Walter D; Epuñan, Maria J; Minguell, José J

2004-01-01

Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.

Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates.

PubMed

Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B

2015-01-01

Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA.

Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates

PubMed Central

Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B.

2015-01-01

Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA. PMID:26161440

Diatom aggregation and dimethylsulfide production in phytoplankton blooms

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

Crocker, K.M.

1994-01-01

Phytoplankton blooms are crucial links in many of the earth's biogeochemical cycles. Blooms take up atmospheric carbon through photosynthesis, and sequester it on the ocean floor by sinking. Aggregation of single cells into [open quote]marine snow[close quote] particles speeds up the sinking of algal cells. Laboratory studies investigating the process of aggregation show that some species have a higher probability of aggregating than others, and that there exist several mechanisms for causing aggregation. Field studies confirm that some species are more likely to be found in aggregates than in the surrounding seawater. High latitude Premnesiophyte blooms are found to producemore » large amounts of dimethylsulflde (DMS), believed to be an important chemical in global thermoregulation. DMS is found to vary diurnally, possibly due to photooxidation by ultraviolet light. This possibility links the effects of DMS on cloud formation with the effects of increased ultraviolet light penetrating the earths ozone layer.« less

Mechanical properties of concrete containing recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate replacement

NASA Astrophysics Data System (ADS)

Khalid, Faisal Sheikh; Azmi, Nurul Bazilah; Sumandi, Khairul Azwa Syafiq Mohd; Mazenan, Puteri Natasya

2017-10-01

Many construction and development activities today consume large amounts of concrete. The amount of construction waste is also increasing because of the demolition process. Much of this waste can be recycled to produce new products and increase the sustainability of construction projects. As recyclable construction wastes, concrete and ceramic can replace the natural aggregate in concrete because of their hard and strong physical properties. This research used 25%, 35%, and 45% recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate in producing concrete. Several tests, such as concrete cube compression and splitting tensile tests, were also performed to determine and compare the mechanical properties of the recycled concrete with those of the normal concrete that contains 100% natural aggregate. The concrete containing 35% RCA and 35% ceramic waste showed the best properties compared with the normal concrete.

A common antigenic motif recognized by naturally occurring human VH5-51/VL4-1 anti-tau antibodies with distinct functionalities.

PubMed

Apetri, Adrian; Crespo, Rosa; Juraszek, Jarek; Pascual, Gabriel; Janson, Roosmarijn; Zhu, Xueyong; Zhang, Heng; Keogh, Elissa; Holland, Trevin; Wadia, Jay; Verveen, Hanneke; Siregar, Berdien; Mrosek, Michael; Taggenbrock, Renske; Ameijde, Jeroenvan; Inganäs, Hanna; van Winsen, Margot; Koldijk, Martin H; Zuijdgeest, David; Borgers, Marianne; Dockx, Koen; Stoop, Esther J M; Yu, Wenli; Brinkman-van der Linden, Els C; Ummenthum, Kimberley; van Kolen, Kristof; Mercken, Marc; Steinbacher, Stefan; de Marco, Donata; Hoozemans, Jeroen J; Wilson, Ian A; Koudstaal, Wouter; Goudsmit, Jaap

2018-05-31

Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer's Disease (AD). By interrogating IgG + memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated V H 5-51/V L 4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of V H 5-51 and V L 4-1 recognizes a common Pro-X n -Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD.

Aggregation of endosomal-vacuolar compartments in the Aovps24-deleted strain in the filamentous fungus Aspergillus oryzae

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

Tatsumi, Akinori; Shoji, Jun-ya; Kikuma, Takashi

2007-10-19

Previously, we found that deletion of Aovps24, an ortholog of Saccharomyces cerevisiae VPS24, that encodes an ESCRT (endosomal sorting complex required for transport)-III component required for late endosomal function results in fragmented and aggregated vacuoles. Although defective late endosomal function is likely responsible for this phenotype, critical lack of our knowledge on late endosomes in filamentous fungi prevented us from further characterization. In this study, we identified late endosomes of Aspergillus oryzae, by expressing a series of fusion proteins of fluorescent proteins with orthologs of late endosomal proteins. Using these fusion proteins as markers, we observed late endosomes in themore » wild type strain and the Aovps24 disruptant and demonstrated that late endosomes are aberrantly aggregated in the Aovps24 disruptant. Moreover, we revealed that the aggregated late endosomes have features of vacuoles as well. As deletion of another ESCRT-III component-encoding gene, Aovps2, resulted in similar phenotypes to that in the Aovps24 disruptant, phenotypes of the Aovps24 disruptant are probably due to defective late endosomal function.« less

Aggregation-Induced Emission of Multiphenyl-Substituted 1,3-Butadiene Derivatives: Synthesis, Property and Application.

PubMed

Zhang, Yahui; Mao, Huiling; Xu, Weiquan; Shi, Jianbing; Cai, Zhengxu; Tong, Bin; Dong, Yuping

2018-05-29

Organic functional materials, including conjugated molecules and fluorescent dyes, have been rapidly developed in recent years because they can be applied in many fields, such as solar cells, biosensing and bioimaging, and medical adjuvant therapy. Organic functional materials with aggregation-induced emission or aggregation-enhanced emission (AIE/AEE) characteristics have increasingly attracted attention due to their high quantum efficiency in the aggregated or solid state. A large variety of AIE/AEE materials have been designed and applied during the exponential growth of research interest in the abovementioned fields. Multiphenyl-substituted 1,3-butadiene (MPB), as a core structure that includes tetraphenyl-1,3-butadiene, hexaphenyl-1,3-butadiene and their derivatives, show a typical AIE/AEE feature and can be potentially used in all the abovementioned fields. This review summarizes the design principles, the corresponding syntheses, and the structure-property relationships of MPBs, as well as their excellent innovative functionalities and applications. This review will be very useful for scientists conducting chemistry, materials, and biomedical research in AIE/AEE-related fields. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pedogenesis on ice (Invited)

NASA Astrophysics Data System (ADS)

Hodson, A. J.

2010-12-01

It is well known from ice cores that organic and mineral debris accumulates within glacier ice following atmospheric deposition. However, the concentrations of such debris are usually greatest upon the ice surface, especially at the margins of continental glaciers and ice sheets, where it forms mm-scale aggregate particles called “cryoconite”. According to the literature, cryoconite covers about 2 % of the ablation areas of glaciers outside Greenland and Antarctica, equivalent to a mass loading of ca. 25 g/m2. Of the great ice sheets not included in this figure, Greenland is the easiest to estimate, and new observations from the NE and SW sectors indicate mass loadings in the range 17 - 440 g/m2. Studies of cryoconite often report the presence of a significant biomass (usually 10^4 - 10^7 cells/g) that is capable of a wide range of biogeochemical functions. The first part of this presentation will therefore explore the contention that the formation of cryoconite represents the first stages of pedogenesis, resulting in the production of soil-type aggregates that inoculate glacial forefields following glacier retreat. Emphasis will be given to the relevant processes that result in aggregate formation, including rapid cell-mineral attachment within melting snowpacks and the slower, biological processes of cementation within thermodynamically stable habitats such as cryoconite holes. The second part of the presentation will use examples from Svalbard, Greenland and Antarctica to consider the carbon balance of the cryoconite during the longest phase of its life cycle: upon the ice. It will be demonstrated how the efficacy of photosynthesis is strongly influenced by thermodynamic conditions at or near this surface. Data from the Greenland and Antarctic ice sheets will show how thermal equilibration decouples variations in photosynthesis from variations in incident radiation over timescales > 1 d, resulting in an equitable, low-carbon economy for aggregates within deep cryoconite holes. Here rates of primary production can be low (e.g. average 2.2 µg C/g (cryoconite)/d in East Antarctica). However, upon maritime glaciers and perhaps parts of the Greenland Ice Sheet margin, high rates of sensible heat transfer maintain cryoconite aggregates close to or upon the ice surface, rendering a communal existence far less likely. This near-surface habitat enables higher rates of photosynthesis (e.g. average 17 µgC/g/d in Svalbard), but also means the probability of meltwater flushing from the ice surface is greatly increased.

Lightweight aggregate production from claystone and shale in Bangladesh

USGS Publications Warehouse

Parker, Norbert A.; Khan, M.A.

1976-01-01

Muffle furnace tests were made on samples of clay, claystone, and shale collected in the Chittagong and Dacca areas of East Pakistan to determine their amenability to bloating for the commercial production of light-weight aggregate. Several areas, sampled in some detail, were selected for investigation because of their proximity to market, and accessibility to fuel and electricity. Muffle furnace tests show that the clay, claystone, and shale are natural bloaters at temperatures in the 1700? to 2200? F range, and do not require additives. The most desirable deposit, insofar as producing a strong aggregate is concerned, can be determined only by pilot-kiln testing and by crushing-strength tests made on concrete test cylinders. Reserves of suitable raw material are large in both the Chittagong and Dacca areas.

Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

PubMed

Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

2011-10-07

Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes.

Application of an E. coli signal sequence as a versatile inclusion body tag.

PubMed

Jong, Wouter S P; Vikström, David; Houben, Diane; van den Berg van Saparoea, H Bart; de Gier, Jan-Willem; Luirink, Joen

2017-03-21

Heterologous protein production in Escherichia coli often suffers from bottlenecks such as proteolytic degradation, complex purification procedures and toxicity towards the expression host. Production of proteins in an insoluble form in inclusion bodies (IBs) can alleviate these problems. Unfortunately, the propensity of heterologous proteins to form IBs is variable and difficult to predict. Hence, fusing the target protein to an aggregation prone polypeptide or IB-tag is a useful strategy to produce difficult-to-express proteins in an insoluble form. When screening for signal sequences that mediate optimal targeting of heterologous proteins to the periplasmic space of E. coli, we observed that fusion to the 39 amino acid signal sequence of E. coli TorA (ssTorA) did not promote targeting but rather directed high-level expression of the human proteins hEGF, Pla2 and IL-3 in IBs. Further analysis revealed that ssTorA even mediated IB formation of the highly soluble endogenous E. coli proteins TrxA and MBP. The ssTorA also induced aggregation when fused to the C-terminus of target proteins and appeared functional as IB-tag in E. coli K-12 as well as B strains. An additive effect on IB-formation was observed upon fusion of multiple ssTorA sequences in tandem, provoking almost complete aggregation of TrxA and MBP. The ssTorA-moiety was successfully used to produce the intrinsically unstable hEGF and the toxic fusion partner SymE, demonstrating its applicability as an IB-tag for difficult-to-express and toxic proteins. We present proof-of-concept for the use of ssTorA as a small, versatile tag for robust E. coli-based expression of heterologous proteins in IBs.

Mechanistic modeling of thermo-hydrological processes and microbial interactions at pore to profile scales resolve methane emission dynamics from permafrost soil

NASA Astrophysics Data System (ADS)

Ebrahimi, Ali; Or, Dani

2017-04-01

The sensitivity of the Earth's polar regions to raising global temperatures is reflected in rapidly changing hydrological processes with pronounced seasonal thawing of permafrost soil and increased biological activity. Of particular concern is the potential release of large amounts of soil carbon and the stimulation of other soil-borne GHG emissions such as methane. Soil methanotrophic and methanogenic microbial communities rapidly adjust their activity and spatial organization in response to permafrost thawing and a host of other environmental factors. Soil structural elements such as aggregates and layering and hydration status affect oxygen and nutrient diffusion processes thereby contributing to methanogenic activity within temporal anoxic niches (hotspots or hot-layers). We developed a mechanistic individual based model to quantify microbial activity dynamics within soil pore networks considering, hydration, temperature, transport processes and enzymatic activity associated with methane production in soil. The model was the upscaled from single aggregates (or hotspots) to quantifying emissions from soil profiles in which freezing/thawing processes provide macroscopic boundary conditions for microbial activity at different soil depths. The model distinguishes microbial activity in aerate bulk soil from aggregates (or submerged parts of the profile) for resolving methane production and oxidation rates. Methane transport pathways through soil by diffusion and ebullition of bubbles vary with hydration dynamics and affect emission patterns. The model links seasonal thermal and hydrologic dynamics with evolution of microbial community composition and function affecting net methane emissions in good agreement with experimental data. The mechanistic model enables systematic evaluation of key controlling factors in thawing permafrost and microbial response (e.g., nutrient availability, enzyme activity, PH) on long term methane emissions and carbon decomposition rates in the rapidly changing polar regions.

Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease

PubMed Central

Bender, Tom; Lewrenz, Ilka; Franken, Sebastian; Baitzel, Catherina; Voos, Wolfgang

2011-01-01

Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the importance of adequate cellular protein quality control measures to counteract aggregate formation. To secure protein homeostasis, mitochondria contain an elaborate protein quality control system, consisting of chaperones and ATP-dependent proteases. To determine the effects of protein aggregation on the functional integrity of mitochondria, we set out to identify aggregation-prone endogenous mitochondrial proteins. We could show that major metabolic pathways in mitochondria were affected by the aggregation of key enzyme components, which were largely inactivated after heat stress. Furthermore, treatment with elevated levels of reactive oxygen species strongly influenced the aggregation behavior, in particular in combination with elevated temperatures. Using specific chaperone mutant strains, we showed a protective effect of the mitochondrial Hsp70 and Hsp60 chaperone systems. Moreover, accumulation of aggregated polypeptides was strongly decreased by the AAA-protease Pim1/LON. We therefore propose that the proteolytic breakdown of aggregation-prone polypeptides represents a major protective strategy to prevent the in vivo formation of aggregates in mitochondria. PMID:21209324

Floating Ice-Algal Aggregates below Melting Arctic Sea Ice

PubMed Central

Assmy, Philipp; Ehn, Jens K.; Fernández-Méndez, Mar; Hop, Haakon; Katlein, Christian; Sundfjord, Arild; Bluhm, Katrin; Daase, Malin; Engel, Anja; Fransson, Agneta; Granskog, Mats A.; Hudson, Stephen R.; Kristiansen, Svein; Nicolaus, Marcel; Peeken, Ilka; Renner, Angelika H. H.; Spreen, Gunnar; Tatarek, Agnieszka; Wiktor, Jozef

2013-01-01

During two consecutive cruises to the Eastern Central Arctic in late summer 2012, we observed floating algal aggregates in the melt-water layer below and between melting ice floes of first-year pack ice. The macroscopic (1-15 cm in diameter) aggregates had a mucous consistency and were dominated by typical ice-associated pennate diatoms embedded within the mucous matrix. Aggregates maintained buoyancy and accumulated just above a strong pycnocline that separated meltwater and seawater layers. We were able, for the first time, to obtain quantitative abundance and biomass estimates of these aggregates. Although their biomass and production on a square metre basis was small compared to ice-algal blooms, the floating ice-algal aggregates supported high levels of biological activity on the scale of the individual aggregate. In addition they constituted a food source for the ice-associated fauna as revealed by pigments indicative of zooplankton grazing, high abundance of naked ciliates, and ice amphipods associated with them. During the Arctic melt season, these floating aggregates likely play an important ecological role in an otherwise impoverished near-surface sea ice environment. Our findings provide important observations and measurements of a unique aggregate-based habitat during the 2012 record sea ice minimum year. PMID:24204642

Floating ice-algal aggregates below melting arctic sea ice.

PubMed

Assmy, Philipp; Ehn, Jens K; Fernández-Méndez, Mar; Hop, Haakon; Katlein, Christian; Sundfjord, Arild; Bluhm, Katrin; Daase, Malin; Engel, Anja; Fransson, Agneta; Granskog, Mats A; Hudson, Stephen R; Kristiansen, Svein; Nicolaus, Marcel; Peeken, Ilka; Renner, Angelika H H; Spreen, Gunnar; Tatarek, Agnieszka; Wiktor, Jozef

2013-01-01

During two consecutive cruises to the Eastern Central Arctic in late summer 2012, we observed floating algal aggregates in the melt-water layer below and between melting ice floes of first-year pack ice. The macroscopic (1-15 cm in diameter) aggregates had a mucous consistency and were dominated by typical ice-associated pennate diatoms embedded within the mucous matrix. Aggregates maintained buoyancy and accumulated just above a strong pycnocline that separated meltwater and seawater layers. We were able, for the first time, to obtain quantitative abundance and biomass estimates of these aggregates. Although their biomass and production on a square metre basis was small compared to ice-algal blooms, the floating ice-algal aggregates supported high levels of biological activity on the scale of the individual aggregate. In addition they constituted a food source for the ice-associated fauna as revealed by pigments indicative of zooplankton grazing, high abundance of naked ciliates, and ice amphipods associated with them. During the Arctic melt season, these floating aggregates likely play an important ecological role in an otherwise impoverished near-surface sea ice environment. Our findings provide important observations and measurements of a unique aggregate-based habitat during the 2012 record sea ice minimum year.

Influence of mechanical cell salvage on red blood cell aggregation, deformability, and 2,3-diphosphoglycerate in patients undergoing cardiac surgery with cardiopulmonary bypass.

PubMed

Gu, Y John; Vermeijden, Wytze J; de Vries, Adrianus J; Hagenaars, J Ans M; Graaff, Reindert; van Oeveren, Willem

2008-11-01

Mechanical cell salvage is increasingly used during cardiac surgery. Although this procedure is considered safe, it is unknown whether it affects the red blood cell (RBC) function, especially the RBC aggregation, deformability, and the contents of 2,3-diphosphoglycerate (2,3-DPG). This study examines the following: (1) whether the cell salvage procedure influences RBC function; and (2) whether retransfusion of the salvaged blood affects RBC function in patients. Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly allocated to a cell saver group (n = 20) or a control group (n = 20). In the cell saver group, the blood aspirated from the wound area and the residual blood from the heart-lung machine were processed with a continuous-flow cell saver before retransfusion. In the control group this blood was retransfused without processing. The RBC aggregation and deformability were measured with a laser-assisted optical rotational cell analyzer and 2,3,-DPG by conventional laboratory test. The cell saver procedure did not influence the RBC aggregation but significantly reduced the RBC deformability (p = 0.007) and the content of RBC 2,3-DPG (p = 0.032). However, in patients receiving the processed blood, their intraoperative and postoperative RBC aggregation, deformability, and 2,3-DPG content did not differ from those of the control patients. Both groups of patients had a postoperative drop of RBC function as a result of hemodilution. The mechanical cell salvage procedure reduces the RBC deformability and the cell 2,3-DPG content. Retransfusion of the processed blood by cell saver does not further compromise the RBC function in patients undergoing cardiac surgery with cardiopulmonary bypass.

Prediction, scenarios and insight: The uses of an end-to-end model

NASA Astrophysics Data System (ADS)

Steele, John H.

2012-09-01

A major function of ecosystem models is to provide extrapolations from observed data in terms of predictions or scenarios or insight. These models can be at various levels of taxonomic resolution such as total community production, abundance of functional groups, or species composition, depending on the data input as drivers. A 40-year dynamic simulation of end-to-end processes in the Georges Bank food web is used to illustrate the input/output relations and the insights gained at the three levels of food web aggregation. The focus is on the intermediate level and the longer term changes in three functional fish guilds - planktivores, benthivores and piscivores - in terms of three ecosystem-based metrics - nutrient input, relative productivity of plankton and benthos, and food intake by juvenile fish. These simulations can describe the long term constraints imposed on guild structure and productivity by energy fluxes over the 40 years but cannot explain concurrent switches in abundance of individual species within guilds. Comparing time series data for individual species with model output provides insights; but including the data in the model would confer only limited extra information. The advantages and limitations of the three levels of resolution of models in relation to ecosystem-based management are: The correlations between primary production and total yield of fish imply a “bottom-up” constraint on end-to-end energy flow through the food web that can provide predictions of such yields. Functionally defined metrics such as nutrient input, relative productivity of plankton and benthos and food intake by juvenile fish, represent bottom-up, mid-level and top-down forcing of the food web. Model scenarios using these metrics can demonstrate constraints on the productivity of these functionally defined guilds within the limits set by (1). Comparisons of guild simulations with time series of fish species provide insight into the switches in species dominance that accompany changes in guild productivity and can illuminate the top-down aspects of regime shifts.

A new efficient method for calculation of Frenkel exciton parameters in molecular aggregates

NASA Astrophysics Data System (ADS)

Plötz, Per-Arno; Niehaus, Thomas; Kühn, Oliver

2014-05-01

The Frenkel exciton Hamiltonian is at the heart of many simulations of excitation energy transfer in molecular aggregates. It separates the aggregate into Coulomb-coupled monomers. Here it is shown that the respective parameters, i.e., monomeric excitation energies and Coulomb couplings between transition densities can be efficiently calculated using time-dependent tight-binding-based density functional theory (TD-DFTB). Specifically, Coulomb couplings are expressed in terms of self-consistently determined Mulliken transition charges. The approach is applied to two dimer systems. First, formaldehyde oxime for which a detailed comparison with standard DFT using the B3LYP and the PBE functionals as well as with SCS-CC2 is provided. Second, the Coulomb coupling is explored in dependence on the intermolecular coordinates for a perylene bisimide dimer. This provides structural evidence for the previously observed biphasic aggregation behavior of this dye.

Ballistic aggregation in systems of inelastic particles: Cluster growth, structure, and aging

NASA Astrophysics Data System (ADS)

Paul, Subhajit; Das, Subir K.

2017-07-01

We study far-from-equilibrium dynamics in models of freely cooling granular gas and ballistically aggregating compact clusters. For both the cases, from event-driven molecular dynamics simulations, we have presented detailed results on structure and dynamics in space dimensions d =1 and 2. Via appropriate analyses it has been confirmed that the ballistic aggregation mechanism applies in d =1 granular gases as well. Aging phenomena for this mechanism, in both the dimensions, have been studied via the two-time density autocorrelation function. This quantity is demonstrated to exhibit scaling property similar to that in the standard phase transition kinetics. The corresponding functional forms have been quantified and the outcomes have been discussed in connection with the structural properties. Our results on aging establish a more complete equivalence between the granular gas and the ballistic aggregation models in d =1 .

Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins.

PubMed

Naranjo, Yandi; Pons, Miquel; Konrat, Robert

2012-01-01

The number of existing protein sequences spans a very small fraction of sequence space. Natural proteins have overcome a strong negative selective pressure to avoid the formation of insoluble aggregates. Stably folded globular proteins and intrinsically disordered proteins (IDPs) use alternative solutions to the aggregation problem. While in globular proteins folding minimizes the access to aggregation prone regions, IDPs on average display large exposed contact areas. Here, we introduce the concept of average meta-structure correlation maps to analyze sequence space. Using this novel conceptual view we show that representative ensembles of folded and ID proteins show distinct characteristics and respond differently to sequence randomization. By studying the way evolutionary constraints act on IDPs to disable a negative function (aggregation) we might gain insight into the mechanisms by which function-enabling information is encoded in IDPs.

Evaporation rate-based selection of supramolecular chirality.

PubMed

Hattori, Shingo; Vandendriessche, Stefaan; Koeckelberghs, Guy; Verbiest, Thierry; Ishii, Kazuyuki

2017-03-09

We demonstrate the evaporation rate-based selection of supramolecular chirality for the first time. P-type aggregates prepared by fast evaporation, and M-type aggregates prepared by slow evaporation are kinetic and thermodynamic products under dynamic reaction conditions, respectively. These findings provide a novel solution reaction chemistry under the dynamic reaction conditions.

Thermodynamics between RAP/RAS and virgin aggregates during asphalt concrete production : a literature review.

DOT National Transportation Integrated Search

2015-09-01

In hot-mix asphalt (HMA) plants, virgin aggregates are heated and dried separately before being mixed with : RAP/RAS and virgin asphalt binder. RAP/RAS materials are not heated or dried directly by a burner to avoid : burning of aged binder coating o...

Weighting and Aggregation in Composite Indicator Construction: A Multiplicative Optimization Approach

ERIC Educational Resources Information Center

Zhou, P.; Ang, B. W.; Zhou, D. Q.

2010-01-01

Composite indicators (CIs) have increasingly been accepted as a useful tool for benchmarking, performance comparisons, policy analysis and public communication in many different fields. Several recent studies show that as a data aggregation technique in CI construction the weighted product (WP) method has some desirable properties. However, a…

High-throughput dietary exposure predictions for chemical migrants from food contact substances for use in chemical prioritization.

PubMed

Biryol, Derya; Nicolas, Chantel I; Wambaugh, John; Phillips, Katherine; Isaacs, Kristin

2017-11-01

Under the ExpoCast program, United States Environmental Protection Agency (EPA) researchers have developed a high-throughput (HT) framework for estimating aggregate exposures to chemicals from multiple pathways to support rapid prioritization of chemicals. Here, we present methods to estimate HT exposures to chemicals migrating into food from food contact substances (FCS). These methods consisted of combining an empirical model of chemical migration with estimates of daily population food intakes derived from food diaries from the National Health and Nutrition Examination Survey (NHANES). A linear regression model for migration at equilibrium was developed by fitting available migration measurements as a function of temperature, food type (i.e., fatty, aqueous, acidic, alcoholic), initial chemical concentration in the FCS (C 0 ) and chemical properties. The most predictive variables in the resulting model were C 0 , molecular weight, log K ow , and food type (R 2 =0.71, p<0.0001). Migration-based concentrations for 1009 chemicals identified via publicly-available data sources as being present in polymer FCSs were predicted for 12 food groups (combinations of 3 storage temperatures and food type). The model was parameterized with screening-level estimates of C 0 based on the functional role of chemicals in FCS. By combining these concentrations with daily intakes for food groups derived from NHANES, population ingestion exposures of chemical in mg/kg-bodyweight/day (mg/kg-BW/day) were estimated. Calibrated aggregate exposures were estimated for 1931 chemicals by fitting HT FCS and consumer product exposures to exposures inferred from NHANES biomonitoring (R 2 =0.61, p<0.001); both FCS and consumer product pathway exposures were significantly predictive of inferred exposures. Including the FCS pathway significantly impacted the ratio of predicted exposures to those estimated to produce steady-state blood concentrations equal to in-vitro bioactive concentrations. While these HT methods have large uncertainties (and thus may not be appropriate for assessments of single chemicals), they can provide critical refinement to aggregate exposure predictions used in risk-based chemical priority-setting. Published by Elsevier Ltd.

Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

PubMed

Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

2014-08-01

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

Synthesis, surface modification and biological imaging of aggregation-induced emission (AIE) dye doped silica nanoparticles

NASA Astrophysics Data System (ADS)

Mao, Liucheng; Liu, Meiying; Xu, Dazhuang; Wan, Qing; Huang, Qiang; Jiang, Ruming; Shi, Yingge; Deng, Fengjie; Zhang, Xiaoyong; Wei, Yen

2017-05-01

Fluorescent silica nanoparticles (FSNPs) have been extensively investigated for various biomedical applications in recently years. However, the aggregation of organic dyes in silica nanoparticles also leads the significant fluorescence quenching owing to the aggregation caused quenching effects of organic dyes. Herein, we developed a rather facile strategy to fabricate FSNPs with desirable fluorescent properties through non-covalent incorporation of fluorophores with aggregation-induced emission (AIE) feature into silica nanoparticles, which were subsequently modified with functional polymers. The resultant FSNPs polymer nanocomposites (named as FSNPs-poly(IA-co-PEGMA)) exhibited uniform spherical morphology, high water dispersiity, and bright red fluorescence. Cytotoxicity results indicate that FSNPs-poly(IA-co-PEGMA) possess excellent biocompatibility. Cell uptake behavior suggests FSNPs-poly(IA-co-PEGMA) are of great potential for biological imaging applications. Taken together, we have reported a facile method for the fabrication of FSNPs through non-covalent encapsulation using an AIE-active dye. These FSNPs can be further functionalized with functional polymers through ring-opening reaction and the resultant FSNPs-poly(IA-co-PEGMA) showed great potential for biological imaging. More importantly, we believe that many other functional components could also be integrated into these FSNPs through the facile ring-opening reaction. Therefore, this method should be a facile and general tool for fabrication of polymer functionalized AIE-active FSNPs.

Proteins containing expanded polyglutamine tracts and neurodegenerative disease

PubMed Central

Adegbuyiro, Adewale; Sedighi, Faezeh; Pilkington, Albert W.; Groover, Sharon; Legleiter, Justin

2017-01-01

Several hereditary neurological and neuromuscular diseases are caused by an abnormal expansion of trinucleotide repeats. To date, there have been ten of these trinucleotide repeat disorders associated with an expansion of the codon CAG encoding glutamine (Q). For these polyglutamine (polyQ) diseases, there is a critical threshold length of the CAG repeat required for disease, and further expansion beyond this threshold is correlated with age of onset and symptom severity. PolyQ expansion in the translated proteins promotes their self-assembly into a variety of oligomeric and fibrillar aggregate species that accumulate into the hallmark proteinaceous inclusion bodies associated with each disease. Here, we review aggregation mechanisms of proteins with expanded polyQ-tracts, structural consequences of expanded polyQ ranging from monomers to fibrillar aggregates, the impact of protein context and post translational modifications on aggregation, and a potential role for lipids membranes in aggregation. As the pathogenic mechanisms that underlie these disorders are often classified as either a gain of toxic function or loss of normal protein function, some toxic mechanisms associated with mutant polyQ tracts will also be discussed. PMID:28170216

[Chapter 7. Big Data or the illusion of a synthesis by aggregation. Epistemological, ethical and political critics].

PubMed

Coutellec, Léo; Weil-Dubuc, Paul-Loup

2017-10-27

In this article, we propose a critical approach to the big data phenomenon by deconstructing the methodological principle that structures its logic : the principle of aggregation. Our hypothesis is upstream of the critics who make the use of big data a new mode of government. Aggregation, as a mode of processing the heterogeneity of data, structures the thinking big data, it is its very logic. Fragmentation in order to better aggregate, to aggregate to better fragment, a dialectic based on a presumption of generalized aggregability and on the claim to make aggregation the preferred route for the production of new syntheses. We proceed in three steps to deconstruct this idea and undo the claim of aggregation to assert itself as a new way to produce knowledge, as a new synthesis of identity and finally as a new model of solidarity. Each time we show that these attempts at aggregation fail to produce their objects : no knowledge, no identity, no solidarity can result from a process of amalgamation. In all three cases, aggregation is always accompanied by a moment of fragmentation whose dissociation, dislocation and separation are different figures. The bet we are making then is to make hesitate what presents itself as a new way of thinking man and the world.

When Brain Beats Behavior: Neuroforecasting Crowdfunding Outcomes

PubMed Central

Yoon, Carolyn

2017-01-01

Although traditional economic and psychological theories imply that individual choice best scales to aggregate choice, primary components of choice reflected in neural activity may support even more generalizable forecasts. Crowdfunding represents a significant and growing platform for funding new and unique projects, causes, and products. To test whether neural activity could forecast market-level crowdfunding outcomes weeks later, 30 human subjects (14 female) decided whether to fund proposed projects described on an Internet crowdfunding website while undergoing scanning with functional magnetic resonance imaging. Although activity in both the nucleus accumbens (NAcc) and medial prefrontal cortex predicted individual choices to fund on a trial-to-trial basis in the neuroimaging sample, only NAcc activity generalized to forecast market funding outcomes weeks later on the Internet. Behavioral measures from the neuroimaging sample, however, did not forecast market funding outcomes. This pattern of associations was replicated in a second study. These findings demonstrate that a subset of the neural predictors of individual choice can generalize to forecast market-level crowdfunding outcomes—even better than choice itself. SIGNIFICANCE STATEMENT Forecasting aggregate behavior with individual neural data has proven elusive; even when successful, neural forecasts have not historically supplanted behavioral forecasts. In the current research, we find that neural responses can forecast market-level choice and outperform behavioral measures in a novel Internet crowdfunding context. Targeted as well as model-free analyses convergently indicated that nucleus accumbens activity can support aggregate forecasts. Beyond providing initial evidence for neuropsychological processes implicated in crowdfunding choices, these findings highlight the ability of neural features to forecast aggregate choice, which could inform applications relevant to business and policy. PMID:28821681

Influence of race and crossbreeding on casein micelles size.

PubMed

Freitas, Denise R; Fonseca, Leorges M; Souza, Fernando N; Ladeira, Cristiane V G; Diniz, Soraia A; Haddad, João Paulo A; Ferreira, Diêgo S; Santoro, Marcelo M; Cerqueira, Mônica M O P

2015-05-01

Casein (CN) micelles are colloidal aggregates of protein dispersed in milk, the importance of which in the dairy industry is related to functionality and yield in dairy products. The objective of this work was to investigate the correlation of milk CN micelles diameter from Holstein and Zebu crossbreds with milk composition (protein, fat, lactose, total and nonfat solids and milk urea nitrogen), somatic cell count (SCC), age, lactation stage and production. Average casein micelles diameters of milk samples obtained from 200 cows were measured using photon correlation spectroscopy and multiple regression analysis was used to find relationship between variables. CN micelle diameter, SCC and nonfat solids were different between animals with different Holstein crossbreed ratios, which suggests influence of genetic factors, mammary gland health and milk composition. Overall, results indicate the potential use of CN micelle diameter as a tool to select animals to produce milk more suitable to cheese production. © 2014 Japanese Society of Animal Science.

Comparison of effect of gamma ray irradiation on wild-type and N-terminal mutants of αA-crystallin.

PubMed

Ramkumar, Srinivasagan; Fujii, Noriko; Fujii, Norihiko; Thankappan, Bency; Sakaue, Hiroaki; Ingu, Kim; Natarajaseenivasan, Kalimuthusamy; Anbarasu, Kumarasamy

2014-01-01

To study the comparative structural and functional changes between wild-type (wt) and N-terminal congenital cataract causing αA-crystallin mutants (R12C, R21L, R49C, and R54C) upon exposure to different dosages of gamma rays. Alpha A crystallin N-terminal mutants were created with the site-directed mutagenesis method. The recombinantly overexpressed and purified wt and mutant proteins were used for further studies. A (60)Co source was used to generate gamma rays to irradiate wild and mutant proteins at dosages of 0.5, 1.0, and 2.0 kGy. The biophysical property of the gamma irradiated (GI) and non-gamma irradiated (NGI) αA-crystallin wt and N-terminal mutants were determined. Oligomeric size was determined by size exclusion high-performance liquid chromatography (HPLC), the secondary structure with circular dichroism (CD) spectrometry, conformation of proteins with surface hydrophobicity, and the functional characterization were determined regarding chaperone activity using the alcohol dehydrogenase (ADH) aggregation assay. αA-crystallin N-terminal mutants formed high molecular weight (HMW) cross-linked products as well as aggregates when exposed to GI compared to the NGI wt counterparts. Furthermore, all mutants exhibited changed β-sheet and random coil structure. The GI mutants demonstrated decreased surface hydrophobicity when compared to αA-crystallin wt at 0, 1.0, and 1.5 kGy; however, at 2.0 kGy a drastic increase in hydrophobicity was observed only in the mutant R54C, not the wt. In contrast, chaperone activity toward ADH was gradually elevated at the minimum level in all GI mutants, and significant elevation was observed in the R12C mutant. Our findings suggest that the N-terminal mutants of αA-crystallin are structurally and functionally more sensitive to GI when compared to their NGI counterparts and wt. Protein oxidation as a result of gamma irradiation drives the protein to cross-link and aggregate culminating in cataract formation.

Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish β-Amyloid or Tau Polymorphic Aggregates

PubMed Central

Klingstedt, Therése; Shirani, Hamid; Mahler, Jasmin; Wegenast-Braun, Bettina M; Nyström, Sofie; Goedert, Michel; Jucker, Mathias; Nilsson, K Peter R

2015-01-01

The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that can be utilized for spectral assignment of different morphotypes of β-amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates. PMID:26013403

An Outline of Data Aggregation Security in Heterogeneous Wireless Sensor Networks.

PubMed

Boubiche, Sabrina; Boubiche, Djallel Eddine; Bilami, Azzedine; Toral-Cruz, Homero

2016-04-12

Data aggregation processes aim to reduce the amount of exchanged data in wireless sensor networks and consequently minimize the packet overhead and optimize energy efficiency. Securing the data aggregation process is a real challenge since the aggregation nodes must access the relayed data to apply the aggregation functions. The data aggregation security problem has been widely addressed in classical homogeneous wireless sensor networks, however, most of the proposed security protocols cannot guarantee a high level of security since the sensor node resources are limited. Heterogeneous wireless sensor networks have recently emerged as a new wireless sensor network category which expands the sensor nodes' resources and capabilities. These new kinds of WSNs have opened new research opportunities where security represents a most attractive area. Indeed, robust and high security level algorithms can be used to secure the data aggregation at the heterogeneous aggregation nodes which is impossible in classical homogeneous WSNs. Contrary to the homogeneous sensor networks, the data aggregation security problem is still not sufficiently covered and the proposed data aggregation security protocols are numberless. To address this recent research area, this paper describes the data aggregation security problem in heterogeneous wireless sensor networks and surveys a few proposed security protocols. A classification and evaluation of the existing protocols is also introduced based on the adopted data aggregation security approach.

Receptor mechanisms in fish chromatophores--VII. Muscarinic cholinoceptors and alpha adrenoceptors, both mediating pigment aggregation, strangely coexist in Corydoras melanophores.

PubMed

Kasukawa, H; Fujii, R

1985-01-01

Both acetylcholine and catecholamines showed melanin-aggregating action within melanophores on an isolated bony plate of the mailed catfish Corydoras paleatus. Chromatic nervous stimulation either by an electrical field or by an elevation of [K+]0 brought about melanosome aggregation. Alpha adrenolytic agents antagonized the melanin-aggregating effects either of catecholamines or of nervous stimuli. Muscarinic cholinolytics interfered with the action of acetylcholine, but did not have any effect on the responses to nervous stimuli. In addition to the alpha adrenoceptors which participate in sympathetic-melanophore transmission, muscarinic cholinoceptors of unknown functional significance, which also mediate melanosome aggregation in the cell, exist in Corydoras melanophores.

Production efficiencies of U.S. electric generation plants: Effects of data aggregation and greenhouse gas and renewable energy policy

NASA Astrophysics Data System (ADS)

Lynes, Melissa Kate

Over the last few decades there has been a shift in electricity production in the U.S. Renewable energy sources are becoming more widely used. In addition, electric generation plants that use coal inputs are more heavily regulated than a couple decades ago. This shift in electricity production was brought on by changes in federal policy -- a desire for electricity produced in the U.S. which led to policies being adopted that encourage the use of renewable energy. The change in production practices due to policies may have led to changes in the productivity of electric generation plants. Multiple studies have examined the most efficient electric generation plants using the data envelopment analysis (DEA) approach. This study builds on past research to answer three questions: 1) Does the level of aggregation of fuel input variables affect the plant efficiency scores and how does the efficiency of renewable energy input compare to nonrenewable energy inputs; 2) Are policies geared toward directly or indirectly reducing greenhouse gas emissions affecting the production efficiencies of greenhouse gas emitting electric generation plants; and 3) Do renewable energy policies and the use of intermittent energy sources (i.e. wind and solar) affect the productivity growth of electric generation plants. All three analysis, presented in three essays, use U.S. plant level data obtained from the Energy Information Administration to answer these questions. The first two essays use DEA to determine the pure technical, overall technical, and scale efficiencies of electric generation plants. The third essay uses DEA within the Malmquist index to assess the change in productivity over time. Results indicate that the level of aggregation does matter particularly for scale efficiency. This implies that valuable information is likely lost when fuel inputs are aggregated together. Policies directly focused on reducing greenhouse gas emissions may improve the production efficiencies of greenhouse gas emitting electric generation plants. However, renewable energy policies do not have an effect on productivity growth. Renewable energy inputs are found to be as efficient if not more efficient than traditional energy sources.

An integrated platform for assessing biologics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Schein, Perry; O'Dell, Dakota; Erickson, David

2016-04-01

Protein therapeutics are a rapidly growing portion of the pharmaceuticals market and have many significant advantages over traditional small molecule drugs. As this market expands, however, critical regulatory and quality control issues remain, most notably the problem of protein aggregation. Individual target proteins often aggregate into larger masses which trigger an immune response in the body, which can reduce the efficacy of the drug for its intended purpose, or cause serious anaphylactic side-effects. Although detecting and minimizing aggregate formation is critical to ensure an effective product, aggregation dynamics are often highly complicated and there is little hope of reliable prediction and prevention from first principles. This problem is compounded for aggregates in the subvisible range of 100 nm to 10 micrometers where traditional techniques for detecting aggregates have significant limitations. Here, we present an integrated optofluidic platform for detecting nanoscale protein aggregates and characterizing interactions between these aggregates and a reference surface. By delivering light to a solution of proteins with an optical waveguide, scattered light from individual protein aggregates can be detected and analyzed to determine the force profile between each particle and the waveguide surface. Unlike existing methods which only determine size or charge, our label-free screening technique can directly measure the surface interaction forces between single aggregates and the glass substrate. This direct measurement capability may allow for better empirical predictions of the stability of protein aggregates during drug manufacturing and storage.

The Functional Quality of Soluble Recombinant Polypeptides Produced in Escherichia coli Is Defined by a Wide Conformational Spectrum▿

PubMed Central

Martínez-Alonso, Mónica; González-Montalbán, Nuria; García-Fruitós, Elena; Villaverde, Antonio

2008-01-01

We have observed that a soluble recombinant green fluorescent protein produced in Escherichia coli occurs in a wide conformational spectrum. This results in differently fluorescent protein fractions in which morphologically diverse soluble aggregates abound. Therefore, the functional quality of soluble versions of aggregation-prone recombinant proteins is defined statistically rather than by the prevalence of a canonical native structure. PMID:18836021

The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver function.

PubMed

Feng, Zhang-Qi; Chu, Xuehui; Huang, Ning-Ping; Wang, Tao; Wang, Yichun; Shi, Xiaolei; Ding, Yitao; Gu, Zhong-Ze

2009-05-01

Liver tissue engineering requires a perfect extracellular matrix (ECM) for primary hepatocytes culture to maintain high level of liver-specific functions and desirable mechanical stability. The aim of this study was to develop a novel natural nanofibrous scaffold with surface-galactose ligands to enhance the bioactivity and mechanical stability of primary hepatocytes in culture. The nanofibrous scaffold was fabricated by electrospinning a natural material, galactosylated chitosan (GC), into nanofibers with an average diameter of approximately 160 nm. The GC nanofibrous scaffolds displayed slow degradation and suitable mechanical properties as an ECM for hepatocytes according to the evaluation of disintegration and Young's modulus testing. The results of morphology characterization, double-staining fluorescence assay and function detection showed that hepatocytes cultured on GC nanofibrous scaffold formed stably immobilized 3D flat aggregates and exhibited superior cell bioactivity with higher levels of liver-specific function maintenance in terms of albumin secretion, urea synthesis and cytochrome P-450 enzyme than 3D spheroid aggregates formed on GC films. These spheroid aggregates could be detached easily during culture period from the flat GC films. We suggest such GC-based nanofibrous scaffolds could be useful for various applications such as bioartificial liver-assist devices and tissue engineering for liver regeneration as primary hepatocytes culture substrates.

Injury Profile SIMulator, a Qualitative Aggregative Modelling Framework to Predict Injury Profile as a Function of Cropping Practices, and Abiotic and Biotic Environment. II. Proof of Concept: Design of IPSIM-Wheat-Eyespot

PubMed Central

Robin, Marie-Hélène; Colbach, Nathalie; Lucas, Philippe; Montfort, Françoise; Cholez, Célia; Debaeke, Philippe; Aubertot, Jean-Noël

2013-01-01

IPSIM (Injury Profile SIMulator) is a generic modelling framework presented in a companion paper. It aims at predicting a crop injury profile as a function of cropping practices and abiotic and biotic environment. IPSIM's modelling approach consists of designing a model with an aggregative hierarchical tree of attributes. In order to provide a proof of concept, a model, named IPSIM-Wheat-Eyespot, has been developed with the software DEXi according to the conceptual framework of IPSIM to represent final incidence of eyespot on wheat. This paper briefly presents the pathosystem, the method used to develop IPSIM-Wheat-Eyespot using IPSIM's modelling framework, simulation examples, an evaluation of the predictive quality of the model with a large dataset (526 observed site-years) and a discussion on the benefits and limitations of the approach. IPSIM-Wheat-Eyespot proved to successfully represent the annual variability of the disease, as well as the effects of cropping practices (Efficiency = 0.51, Root Mean Square Error of Prediction = 24%; bias = 5.0%). IPSIM-Wheat-Eyespot does not aim to precisely predict the incidence of eyespot on wheat. It rather aims to rank cropping systems with regard to the risk of eyespot on wheat in a given production situation through ex ante evaluations. IPSIM-Wheat-Eyespot can also help perform diagnoses of commercial fields. Its structure is simple and permits to combine available knowledge in the scientific literature (data, models) and expertise. IPSIM-Wheat-Eyespot is now available to help design cropping systems with a low risk of eyespot on wheat in a wide range of production situations, and can help perform diagnoses of commercial fields. In addition, it provides a proof of concept with regard to the modelling approach of IPSIM. IPSIM-Wheat-Eyespot will be a sub-model of IPSIM-Wheat, a model that will predict injury profile on wheat as a function of cropping practices and the production situation. PMID:24146783

Injury profile SIMulator, a Qualitative aggregative modelling framework to predict injury profile as a function of cropping practices, and abiotic and biotic environment. II. Proof of concept: design of IPSIM-wheat-eyespot.

PubMed

Robin, Marie-Hélène; Colbach, Nathalie; Lucas, Philippe; Montfort, Françoise; Cholez, Célia; Debaeke, Philippe; Aubertot, Jean-Noël

2013-01-01

IPSIM (Injury Profile SIMulator) is a generic modelling framework presented in a companion paper. It aims at predicting a crop injury profile as a function of cropping practices and abiotic and biotic environment. IPSIM's modelling approach consists of designing a model with an aggregative hierarchical tree of attributes. In order to provide a proof of concept, a model, named IPSIM-Wheat-Eyespot, has been developed with the software DEXi according to the conceptual framework of IPSIM to represent final incidence of eyespot on wheat. This paper briefly presents the pathosystem, the method used to develop IPSIM-Wheat-Eyespot using IPSIM's modelling framework, simulation examples, an evaluation of the predictive quality of the model with a large dataset (526 observed site-years) and a discussion on the benefits and limitations of the approach. IPSIM-Wheat-Eyespot proved to successfully represent the annual variability of the disease, as well as the effects of cropping practices (Efficiency = 0.51, Root Mean Square Error of Prediction = 24%; bias = 5.0%). IPSIM-Wheat-Eyespot does not aim to precisely predict the incidence of eyespot on wheat. It rather aims to rank cropping systems with regard to the risk of eyespot on wheat in a given production situation through ex ante evaluations. IPSIM-Wheat-Eyespot can also help perform diagnoses of commercial fields. Its structure is simple and permits to combine available knowledge in the scientific literature (data, models) and expertise. IPSIM-Wheat-Eyespot is now available to help design cropping systems with a low risk of eyespot on wheat in a wide range of production situations, and can help perform diagnoses of commercial fields. In addition, it provides a proof of concept with regard to the modelling approach of IPSIM. IPSIM-Wheat-Eyespot will be a sub-model of IPSIM-Wheat, a model that will predict injury profile on wheat as a function of cropping practices and the production situation.

Key role of the N-terminus of chicken annexin A5 in vesicle aggregation.

PubMed

Turnay, Javier; Guzmán-Aránguez, Ana; Lecona, Emilio; Barrasa, Juan I; Olmo, Nieves; Lizarbe, Ma Antonia

2009-05-01

Annexins are calcium-dependent phospholipid-binding proteins involved in calcium signaling and intracellular membrane trafficking among other functions. Vesicle aggregation is a crucial event to make possible the membrane remodeling but this process is energetically unfavorable, and phospholipid membranes do not aggregate and fuse spontaneously. This issue can be circumvented by the presence of different agents such as divalent cations and/or proteins, among them some annexins. Although human annexin A5 lacks the ability to aggregate vesicles, here we demonstrate that its highly similar chicken ortholog induces aggregation of vesicles containing acidic phospholipids even at low protein and/or calcium concentration by establishment of protein dimers. Our experiments show that the ability to aggregate vesicles mainly resides in the N-terminus as truncation of the N-terminus of chicken annexin A5 significantly decreases this process and replacement of the N-terminus of human annexin A5 by that of chicken switches on aggregation; in both cases, there are no changes in the overall protein structure and only minor changes in phospholipid binding. Electrostatic repulsions between negatively charged residues in the concave face of the molecule, mainly in the N-terminus, seem to be responsible for the impairment of dimer formation in human annexin A5. Taking into account that chicken annexin A5 presents a high sequence and structural similarity with mammalian annexins absent in birds, as annexins A3 and A4, some of the physiological functions exerted by these proteins may be carried out by chicken annexin A5, even those that could require calcium-dependent membrane aggregation.

Ecosystem services driven by the diversity of soil biota - understanding and management in agriculture - The Biodiversa SoilMan-Project

NASA Astrophysics Data System (ADS)

Potthoff, Martin; Pérès, Guénola; Taylor, Astrid; Schrader, Stefan; Landa, Blanca; Nicolai, Annegret; Sandor, Mignon; Öptik, Maarja; Gema, Guzmán; Bergmann, Holger; Cluzeau, Daniel; Banse, Martin; Bengtsson, Jan; Guernion, Muriel; Zaller, Johann; Roslin, Tomas; Scheu, Stefan; Gómez Calero, José Alfonso

2017-04-01

Soil biota diversity is ensuring primary production in terrestrial ecosystems and agricultural productivity. Water and nutrient cycling, soil formation and aggregation, decomposition and carbon sequestration as well as control of pest organisms are important functions in soil that are driven by biota and biota interactions. In agricultural systems these functions support and regulate ecosystem services directed to agricultural production and agricultural sustainability. A main goal of future cropping systems will be to maintain or raise agricultural productivity while keeping production sustainable in spite of increasing food demands and ongoing soil degradation caused by inappropriate soil management practices. Farm based tools that farmers use to engineer soils for plant production depend as soil management factors on decisions by farmers, which are triggered by regional traditions, knowledge and also by agriculture policies as a governance impact. However, biological impacts on soil fertility and soil health are often neglected or overseen when planning and shaping soil management in annual cropping systems or perennial systems like vineyards. In order to get progress in conservation farming and in agricultural sustainability not only knowledge creation is in need, but also a clash of perspectives has to be overcome within the societies (generals public, farmers associations, NGOs) The talk will present the conception of the recently startet SoilMan-project and summaries selected results from current and recent European research projects.

An improved size exclusion-HPLC method for molecular size distribution analysis of immunoglobulin G using sodium perchlorate in the eluent.

PubMed

Wang, Hsiaoling; Levi, Mark S; Del Grosso, Alfred V; McCormick, William M; Bhattacharyya, Lokesh

2017-05-10

Size exclusion (SE) high performance liquid chromatography (HPLC) is widely used for the molecular size distribution (MSD) analyses of various therapeutic proteins. We report development and validation of a SE-HPLC method for MSD analyses of immunoglobulin G (IgG) in products using a TSKgel SuperSW3000 column and eluting it with 0.4M NaClO 4 , a chaotropic salt, in 40mM phosphate buffer, pH 6.8. The chromatograms show distinct peaks of aggregates, tetramer, and two dimers, as well as the monomer and fragment peaks. In addition, the method offers about half the run time (12min), better peak resolution, improved peak shape and more stable base-line compared to HPLC methods reported in the literature, including that in the European Pharmacopeia (EP). A comparison of MSD analysis results between our method and the EP method shows interactions between the protein and the stationary phase and partial adsorption of aggregates and tetramer on the stationary phase, when the latter method is used. Thus, the EP method shows lower percent of aggregates and tetramer than are actually present in the products. In view of the fact that aggregates have been attributed to playing a critical role in adverse reactions due to IgG products, our observation raises a major concern regarding the actual aggregate content in these products since the EP method is widely used for MSD analyses of IgG products. Our method eliminates (or substantially reduces) the interactions between the proteins and stationary phase as well as the adsorption of proteins onto the column. Our results also show that NaClO 4 in the eluent is more effective in overcoming the protein/column interactions compared to Arg-HCl, another chaotropic salt. NaClO 4 is shown not to affect the molecular size and relative distribution of different molecular forms of IgG. The method validated as per ICH Q2(R1) guideline using IgG products, shows good specificity, accuracy, precision and a linear concentration dependence of peak areas for different molecular forms. In summary, our method gives more reliable results than the SE-HPLC methods for MSD analyses of IgG reported in the literature, including the EP, particularly for aggregates and tetramer. The results are interpreted in terms of ionic (polar) and hydrophobic interactions between the stationary phase and the IgG protein. Published by Elsevier B.V.

Protein aggregation induced during glass bead lysis of yeast

PubMed Central

Papanayotou, Irene; Sun, Beimeng; Roth, Amy F.; Davis, Nicholas G.

2013-01-01

Yeast cell lysates produced by mechanical glass bead disruption are widely used in a variety of applications, including for the analysis of native function, e.g. protein–protein interaction, enzyme assays and membrane fractionations. Below, we report a striking case of protein denaturation and aggregation that is induced by this lysis protocol. Most of this analysis focuses on the type 1 casein kinase Yck2, which normally tethers to the plasma membrane through C-terminal palmitoylation. Surprisingly, when cells are subjected to glass bead disruption, non-palmitoylated, cytosolic forms of the kinase denature and aggregate, while membrane-associated forms, whether attached through their native palmitoyl tethers or through a variety of artificial membrane-tethering sequences, are wholly protected from denaturation and aggregation. A wider look at the yeast proteome finds that, while the majority of proteins resist glass bead-induced aggregation, a significant subset does, in fact, succumb to such denaturation. Thus, yeast researchers should be aware of this potential artifact when embarking on biochemical analyses that employ glass bead lysates to look at native protein function. Finally, we demonstrate an experimental utility for glass bead-induced aggregation, using its fine discrimination of membrane-associated from non-associated Yck2 forms to discern fractional palmitoylation states of Yck2 mutants that are partially defective for palmitoylation. PMID:20641011

Microstructured block copolymer surfaces for control of microbe capture and aggregation

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

Hansen, Ryan R; Shubert, Katherine R; Morrell, Jennifer L.

2014-01-01

The capture and arrangement of surface-associated microbes is influenced by biochemical and physical properties of the substrate. In this report, we develop lectin-functionalized substrates containing patterned, three-dimensional polymeric structures of varied shapes and densities and use these to investigate the effects of topology and spatial confinement on lectin-mediated microbe capture. Films of poly(glycidyl methacrylate)-block-4,4-dimethyl-2-vinylazlactone (PGMA-b-PVDMA) were patterned on silicon surfaces into line or square grid patterns with 5 m wide features and varied edge spacing. The patterned films had three-dimensional geometries with 900 nm film thickness. After surface functionalization with wheat germ agglutinin, the size of Pseudomonas fluorescens aggregates capturedmore » was dependent on the pattern dimensions. Line patterns with edge spacing of 5 m or less led to the capture of individual microbes with minimal formation of aggregates, while grid patterns with the same spacing also captured individual microbes with further reduction in aggregation. Both geometries allowed for increases in aggregate size distribution with increased in edge spacing. These engineered surfaces combine spatial confinement with affinity-based microbe capture based on exopolysaccharide content to control the degree of microbe aggregation, and can also be used as a platform to investigate intercellular interactions and biofilm formation in microbial populations of controlled sizes.« less

The economic impact of NASA R and D spending Appendices

NASA Technical Reports Server (NTRS)

Evans, M. K.

1976-01-01

Seven appendices related to a previous report on the economic impact of NASA R and D spending were presented. They dealt with: (1) theoretical and empirical development of aggregate production functions, (2) the calculation of the time series for the rate of technological progress, (3) the calculation of the industry mix variable, (4) the estimation of distributed lags, (5) the estimation of the equations for gamma, (6) a ten-year forecast of the U.S. economy, (7) simulations of the macroeconomic model for increases in NASA R and D spending of $1.0, $.0.5, and 0.1 billions.

Production of Normal Mammalian Organ Culture Using a Medium Containing Mem-Alpha, Leibovitz L 15, Glucose Galactose Fructose

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor); Prewett, Tacey L. (Inventor)

1999-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under micro- gravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel. The medium used for culturing the cells, especially a mixture of epithelial and mesenchymal cells contains a mixture of Mem-alpha and Leibovits L15 supplemented with glucose, galactose and fructose.

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™.

PubMed

Pisupati, Karthik; Benet, Alexander; Tian, Yuwei; Okbazghi, Solomon; Kang, Jukyung; Ford, Michael; Saveliev, Sergei; Sen, K Ilker; Carlson, Eric; Tolbert, Thomas J; Ruotolo, Brandon T; Schwendeman, Steven P; Schwendeman, Anna

2017-10-01

Remsima™ (infliximab) is the first biosimilar monoclonal antibody (mAb) approved by the European Medical Agency and the US Food and Drug Administration. Remsima™ is highly similar to its reference product, Remicade®, with identical formulation components. The 2 products, however, are not identical; Remsima™ has higher levels of soluble aggregates, C-terminal lysine truncation, and fucosylated glycans. To understand if these attribute differences could be amplified during forced degradation, solutions and lyophilized powders of the 2 products were subjected to stress at elevated temperature (40-60°C) and humidity (dry-97% relative humidity). Stress-induced aggregation and degradation profiles were similar for the 2 products and resulted in loss of infliximab binding to tumor necrosis factor and FcγRIIIa. Appearances of protein aggregates and hydrolysis products were time- and humidity-dependent, with similar degradation rates observed for the reference and biosimilar products. Protein powder incubations at 40°C/97% relative humidity resulted in partial mAb unfolding and increased asparagine deamidation. Minor differences in heat capacity, fluorescence, levels of subvisible particulates, deamidation and protein fragments were observed in the 2 stressed products, but these differences were not statistically significant. The protein solution instability at 60°C, although quite significant, was also similar for both products. Despite the small initial analytical differences, Remicade® and Remsima™ displayed similar degradation mechanisms and kinetics. Thus, our results show that the 2 products are highly similar and infliximab's primary sequence largely defines their protein instabilities compared with the limited influence of small initial purity and glycosylation differences in the 2 products.

Aggregate breakdown of nanoparticulate titania

NASA Astrophysics Data System (ADS)

Venugopal, Navin

Six nanosized titanium dioxide powders synthesized from a sulfate process were investigated. The targeted end-use of this powder was for a de-NOx catalyst honeycomb monolith. Alteration of synthesis parameters had resulted principally in differences in soluble ion level and specific surface area of the powders. The goal of this investigation was to understand the role of synthesis parameters in the aggregation behavior of these powders. Investigation via scanning electron microscopy of the powders revealed three different aggregation iterations at specific length scales. Secondary and higher order aggregate strength was investigated via oscillatory stress rheometry as a means of simulating shear conditions encountered during extrusion. G' and G'' were measured as a function of the applied oscillatory stress. Oscillatory rheometry indicated a strong variation as a function of the sulfate level of the particles in the viscoelastic yield strengths. Powder yield stresses ranged from 3.0 Pa to 24.0 Pa of oscillatory stress. Compaction curves to 750 MPa found strong similarities in extrapolated yield point of stage I and II compaction for each of the powders (at approximately 500 MPa) suggesting that the variation in sulfate was greatest above the primary aggregate level. Scanning electron microscopy of samples at different states of shear in oscillatory rheometry confirmed the variation in the linear elastic region and the viscous flow regime. A technique of this investigation was to approach aggregation via a novel perspective: aggregates are distinguished as being loose open structures that are highly disordered and stochastic in nature. The methodology used was to investigate the shear stresses required to rupture the various aggregation stages encountered and investigate the attempt to realign the now free-flowing constituents comprising the aggregate into a denser configuration. Mercury porosimetry was utilized to measure the pore size of the compact resulting from compaction via dry pressing and tape casting secondary scale aggregates. Mercury porosimetry of tapes cast at 0.85 and 9.09 cm/sec exhibited pore sizes ranging from 200-500 nm suggesting packing of intact micron-sized primary aggregates. Porosimetry further showed that this peak was absent in pressed pellets corroborating arguments of ruptured primary aggregates during compaction to 750 MPa.

Inhibition of neuroinflammation and mitochondrial dysfunctions by carbenoxolone in the rotenone model of Parkinson's disease.

PubMed

Thakur, Poonam; Nehru, Bimla

2015-02-01

α-Synuclein aggregation contributes to the Parkinson's disease (PD) pathology in multiple ways-the two most important being the activation of neuroinflammation and mitochondrial dysfunction. Our recent studies have shown the beneficial effects of a heat shock protein (HSP) inducer, carbenoxolone (Cbx), in reducing the aggregation of α-synuclein in a rotenone-based rat model of PD. The present study was designed to explore its ability to attenuate the α-synuclein-mediated alterations in neuroinflammation and mitochondrial functions. The PD model was generated by the rotenone administration (2 mg/kg b.wt.) to the male SD rats for a period of 5 weeks. Cbx (20 mg/kg b.wt.) co-administration was seen to reduce the activation of astrocytes incited by rotenone. Subsequently, the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β was inhibited. Further, the expression level of various inflammatory mediators such as COX-2, iNOS, and NF-κB was also reduced following Cbx co-treatment. Cbx was also shown to reduce the rotenone-induced decline in activity of mitochondrial complexes-I, -II, and -IV. Protection of mitochondrial functions and reduction in neuroinflammation lead to the lesser production of ROS and subsequently reduced oxidative stress. This was reflected by the increase in both the cytosolic and mitochondrial GSH levels as well as SOD activity during Cbx co-treatment. Thus, Cbx reduces the inflammatory response and improves the mitochondrial dysfunctions by reducing α-synuclein aggregation. In addition, it also reduces the associated oxidative stress. Due to its ability to target the multiple pathways implicated in the PD, Cbx can serve as a highly beneficial prophylactic agent.

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs.

PubMed

Brainard, Benjamin M; Meredith, Craig P; Callan, Mary Beth; Budsberg, Steven C; Shofer, Francis S; Driessen, Bernd; Otto, Cynthia M

2007-03-01

To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. 8 client-owned dogs with clinical signs of osteoarthritis. Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.

Coupling of Peripheral Tolerance to Endogenous Interleukin 10 Promotes Effective Modulation of Myelin-Activated T Cells and Ameliorates Experimental Allergic Encephalomyelitis

PubMed Central

Legge, Kevin L.; Min, Booki; Bell, J. Jeremiah; Caprio, Jacque C.; Li, Lequn; Gregg, Randal K.; Zaghouani, Habib

2000-01-01

Several immune-based approaches are being considered for modulation of inflammatory T cells and amelioration of autoimmune diseases. The most recent strategies include simulation of peripheral self-tolerance by injection of adjuvant free antigen, local delivery of cytokines by genetically altered T cells, and interference with the function of costimulatory molecules. Although promising results have been obtained from these studies that define mechanisms of T cell modulation, efficacy, practicality, and toxicity, concerns remain unsolved, thereby justifying further investigations to define alternatives for effective downregulation of aggressive T cells. In prior studies, we demonstrated that an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP)1 peptide corresponding to amino acid sequence 139–151 of PLP, Ig-PLP1, is presented to T cells ∼100-fold better than free PLP1. Here, we demonstrate that aggregation endows Ig-PLP1 with an additional feature, namely, induction of interleukin (IL)-10 production by macrophages and dendritic cells, both of which are antigen-presenting cells (APCs). These functions synergize in vivo and drive effective modulation of autoimmunity. Indeed, it is shown that animals with ongoing active experimental allergic encephalomyelitis dramatically reduce the severity of their paralysis when treated with adjuvant free aggregated Ig-PLP1. Moreover, IL-10 displays bystander antagonism on unrelated autoreactive T cells, allowing for reversal of disease involving multiple epitopes. Therefore, aggregated Ig-PLP1 likely brings together a peripheral T cell tolerance mechanism emanating from peptide presentation by APCs expressing suboptimal costimulatory molecules and IL-10 bystander suppression to drive a dual-modal T cell modulation system effective for reversal of autoimmunity involving several epitopes and diverse T cell specificities. PMID:10859329

Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation

PubMed Central

Starossom, Sarah C.; Veremeyko, Tatyana; Yung, Amanda W. Y.; Dukhinova, Marina; Au, Cheryl; Lau, Alexander Y.; Weiner, Howard L.; Ponomarev, Eugene D.

2015-01-01

Rationale Platelets are known to participate in vascular pathologies; however, their role in neuroinflammatory diseases such as multiples sclerosis (MS) is unknown. Autoimmune CD4 T cells have been the main focus of studies of MS, although the factors that regulate T cell differentiation towards pathogenic Th1/Th17 phenotypes are not completely understood. Objectives We investigated the role of platelets in the modulation of CD4 T cell functions in MS patients and in mice with experimental autoimmune encephalitis (EAE), an animal model for MS. Methods and Results We found that early in MS and EAE platelets degranulated and produced a number of soluble factors serotonin (5HT), PF4 and PAF, which specifically stimulated differentiation of T cells towards pathogenic Th1, Th17 and IFN-γ/IL-17-producing CD4 T cells. At the later stages of MS and EAE platelets became exhausted in their ability to produce proinflammatory factors and stimulate CD4 T cells, but substantially increased their ability to form aggregates with CD4 T cells. Formation of platelet-CD4 T cell aggregates involved interaction of CD62P on activated platelets with adhesion molecule CD166 on activated CD4 T cells, contributing to downmodulation of CD4 T cell activation, proliferation and production of IFN-γ. Blocking of formation of platelet-CD4 T cell aggregates during progression of EAE substantially enhanced proliferation of CD4 T cell in the CNS and the periphery leading to exacerbation of the disease. Conclusion Our study indicates differential roles for platelets in the regulation of functions of pathogenic CD4 T cells during initiation and progression of CNS autoimmune inflammation. PMID:26294656

Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis.

PubMed

Benitez, Bruno A; Sands, Mark S

2017-07-24

Mutations in the co- chaperone protein, CSPα, cause an autosomal dominant, adult-neuronal ceroid lipofuscinosis (AD-ANCL). The current understanding of CSPα function exclusively at the synapse fails to explain the autophagy-lysosome pathway (ALP) dysfunction in cells from AD-ANCL patients. Here, we demonstrate unexpectedly that primary dermal fibroblasts from pre-symptomatic mutation carriers recapitulate in vitro features found in the brains of AD-ANCL patients including auto-fluorescent storage material (AFSM) accumulation, CSPα aggregates, increased levels of lysosomal proteins and lysosome enzyme activities. AFSM accumulation correlates with CSPα aggregation and both are susceptible to pharmacological modulation of ALP function. In addition, we demonstrate that endogenous CSPα is present in the lysosome-enriched fractions and co-localizes with lysosome markers in soma, neurites and synaptic boutons. Overexpression of CSPα wild-type (WT) decreases lysotracker signal, secreted lysosomal enzymes and SNAP23-mediated lysosome exocytosis. CSPα WT, mutant and aggregated CSPα are degraded mainly by the ALP but this disease-causing mutation exhibits a faster rate of degradation. Co-expression of both WT and mutant CSPα cause a block in the fusion of autophagosomes/lysosomes. Our data suggest that aggregation-dependent perturbation of ALP function is a relevant pathogenic mechanism for AD-ANCL and supports the use of AFSM or CSPα aggregation as biomarkers for drug screening purposes.

[Survival strategy of photosynthetic organisms. 1. Variability of the extent of light-harvesting pigment aggregation as a structural factor optimizing the function of oligomeric photosynthetic antenna. Model calculations].

PubMed

Fetisova, Z G

2004-01-01

In accordance with our concept of rigorous optimization of photosynthetic machinery by a functional criterion, this series of papers continues purposeful search in natural photosynthetic units (PSU) for the basic principles of their organization that we predicted theoretically for optimal model light-harvesting systems. This approach allowed us to determine the basic principles for the organization of a PSU of any fixed size. This series of papers deals with the problem of structural optimization of light-harvesting antenna of variable size controlled in vivo by the light intensity during the growth of organisms, which accentuates the problem of antenna structure optimization because optimization requirements become more stringent as the PSU increases in size. In this work, using mathematical modeling for the functioning of natural PSUs, we have shown that the aggregation of pigments of model light-harvesting antenna, being one of universal optimizing factors, furthermore allows controlling the antenna efficiency if the extent of pigment aggregation is a variable parameter. In this case, the efficiency of antenna increases with the size of the elementary antenna aggregate, thus ensuring the high efficiency of the PSU irrespective of its size; i.e., variation in the extent of pigment aggregation controlled by the size of light-harvesting antenna is biologically expedient.

Physical soil architectural traits are functionally linked to carbon decomposition and bacterial diversity.

PubMed

Rabbi, S M F; Daniel, H; Lockwood, P V; Macdonald, C; Pereg, L; Tighe, M; Wilson, B R; Young, I M

2016-09-12

Aggregates play a key role in protecting soil organic carbon (SOC) from microbial decomposition. The objectives of this study were to investigate the influence of pore geometry on the organic carbon decomposition rate and bacterial diversity in both macro- (250-2000 μm) and micro-aggregates (53-250 μm) using field samples. Four sites of contrasting land use on Alfisols (i.e. native pasture, crop/pasture rotation, woodland) were investigated. 3D Pore geometry of the micro-aggregates and macro-aggregates were examined by X-ray computed tomography (μCT). The occluded particulate organic carbon (oPOC) of aggregates was measured by size and density fractionation methods. Micro-aggregates had 54% less μCT observed porosity but 64% more oPOC compared with macro-aggregates. In addition, the pore connectivity in micro-aggregates was lower than macro-aggregates. Despite both lower μCT observed porosity and pore connectivity in micro-aggregates, the organic carbon decomposition rate constant (Ksoc) was similar in both aggregate size ranges. Structural equation modelling showed a strong positive relationship of the concentration of oPOC with bacterial diversity in aggregates. We use these findings to propose a conceptual model that illustrates the dynamic links between substrate, bacterial diversity, and pore geometry that suggests a structural explanation for differences in bacterial diversity across aggregate sizes.

Physical soil architectural traits are functionally linked to carbon decomposition and bacterial diversity

PubMed Central

Rabbi, S. M. F.; Daniel, H.; Lockwood, P. V.; Macdonald, C.; Pereg, L.; Tighe, M.; Wilson, B. R.; Young, I. M.

2016-01-01

Aggregates play a key role in protecting soil organic carbon (SOC) from microbial decomposition. The objectives of this study were to investigate the influence of pore geometry on the organic carbon decomposition rate and bacterial diversity in both macro- (250–2000 μm) and micro-aggregates (53–250 μm) using field samples. Four sites of contrasting land use on Alfisols (i.e. native pasture, crop/pasture rotation, woodland) were investigated. 3D Pore geometry of the micro-aggregates and macro-aggregates were examined by X-ray computed tomography (μCT). The occluded particulate organic carbon (oPOC) of aggregates was measured by size and density fractionation methods. Micro-aggregates had 54% less μCT observed porosity but 64% more oPOC compared with macro-aggregates. In addition, the pore connectivity in micro-aggregates was lower than macro-aggregates. Despite both lower μCT observed porosity and pore connectivity in micro-aggregates, the organic carbon decomposition rate constant (Ksoc) was similar in both aggregate size ranges. Structural equation modelling showed a strong positive relationship of the concentration of oPOC with bacterial diversity in aggregates. We use these findings to propose a conceptual model that illustrates the dynamic links between substrate, bacterial diversity, and pore geometry that suggests a structural explanation for differences in bacterial diversity across aggregate sizes. PMID:27615807

Designing cross-linked xylanase aggregates for bioconversion of agroindustrial waste biomass towards potential production of nutraceuticals.

PubMed

Hero, J S; Romero, C M; Pisa, J H; Perotti, N I; Olivaro, C; Martinez, M A

2018-05-01

Immobilized biocatalysts design has the potential to efficiently produce valuable bioproducts from lignocellulosic biomass. Among them, the carrier-free immobilization through the cross-linked enzyme aggregates technology is a simple and low-cost alternative. A two steps statistical approach was utilized to evaluate the synthesis of a cross-linked enzyme aggregate from a xylanolytic preparation, which was produced by Cohnella sp. AR92 grown in a peptone-based culture medium. The resulting immobilized biocatalyst, Xyl-CLEA, was significate more stable (25 to 45%) towards temperatures up to 50°C with respect to the free enzyme, and retained over 50% of its initial activity after 5 consecutive cycles of reuse. By means of infrared spectroscopy and electron microscopy, the Xyl-CLEA showed architectural features described as signature of type I and type II of protein aggregates. These, were the result of the simultaneous aggregation of a multiplicity of proteins from the crude enzymatic extract. The enzymatic activity was assessed using alkali pretreated sugar cane bagasse as substrate. Whereas the free enzymatic preparation released xylose as the main product, the immobilized xylanase produced xylooligosaccharides, thus showing that the immobilization procedure modified the potential application of the extracellular xylanase from Conhella sp. AR92. Copyright © 2018 Elsevier B.V. All rights reserved.

Construction of the Free Energy Landscape of Peptide Aggregation from Molecular Dynamics Simulations.

PubMed

Riccardi, Laura; Nguyen, Phuong H; Stock, Gerhard

2012-04-10

To describe the structure and dynamics of oligomers during peptide aggregation, a method is proposed that considers both the intramolecular and intermolecular structures of the multimolecule system and correctly accounts for its degeneracy. The approach is based on the "by-parts" strategy, which partitions a complex molecular system into parts, determines the metastable conformational states of each part, and describes the overall conformational state of the system in terms of a product basis of the states of the parts. Starting from a molecular dynamics simulation of n molecules, the method consists of three steps: (i) characterization of the intramolecular structure, that is, of the conformational states of a single molecule in the presence of the other molecules (e.g., β-strand or random coil); (ii) characterization of the intermolecular structure through the identification of all occurring aggregate states of the peptides (dimers, trimers, etc.); and (iii) construction of the overall conformational states of the system in terms of a product basis of the n "single-molecule" states and the aggregate states. Considering the Alzheimer β-amyloid peptide fragment Aβ16-22 as a first application, about 700 overall conformational states of the trimer (Aβ16-22)3 were constructed from all-atom molecular dynamics simulation in explicit water. Based on these states, a transition network reflecting the free energy landscape of the aggregation process can be constructed that facilitates the identification of the aggregation pathways.

ASR prevention — Effect of aluminum and lithium ions on the reaction products

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

Leemann, Andreas, E-mail: andreas.leemann@empa.ch; Bernard, Laetitia; Alahrache, Salaheddine

2015-10-15

In spite of the recent progress in the understanding of the mechanisms enabling aluminum-containing SCM like metakaolin and added LiNO{sub 3} to limit the extent of ASR in mortar and concrete, some gaps still remain. They concern mainly the effect of aluminum-containing SCM on the formed ASR products and the influence of aggregate characteristics on the effectiveness of LiNO{sub 3}. In this study, a model system, concrete and mortar were investigated by pore solution analysis, TGA, XRD, NMR, SEM combined with EDX and ToF-SIMS to address these questions. The amount of aluminum present in the pore solution of concrete andmore » mortar is only able to slow down SiO{sub 2} dissolution but not to alter morphology, structure and composition of the reaction products. LiNO{sub 3} can suppress ASR by forming dense products protecting reactive minerals from further reaction. But its effectiveness is decreasing with increasing specific surface area of the reactive minerals in aggregates. - Highlights: • Aluminum of SCM slows down SiO{sub 2} dissolution. • Aluminum of SCM does not alter morphology and structure of ASR product. • ASR suppressing effect of LiNO{sub 3} depends on specific surface area of the aggregates.« less

Handling of quarry waste from schist production at Oppdal, Norway

NASA Astrophysics Data System (ADS)

Willy Danielsen, Svein; Alnæs, Lisbeth; Azrague, Kamal; Suleng, Jon

2017-04-01

Handling of quarry waste from schist production at Oppdal, Norway Svein Willy Danielsen1), Lisbeth Alnæs2), Kamal Azrague2), Jon Suleng3) 1) Geomaterials Consultant, Trondheim Norway, 2) SINTEF, Trondheim, Norway, 3) AF Gruppen AS, Oppdal, Norway A significant amount of aggregate research in Norway has been focused on the recovery and use of surplus sizes from hard rock aggregate quarries. The use of sand sized quarry waste (QW) from crushing/processing has been motivated by the rapid depletion of traditional sand/gravel resources, increasing land-use conflicts, and the need to minimise QW deposits which for some quarries are becoming a critical factor for economy as well as for environmental reasons. With an annual aggregate production of 77 million tons, out of which approximately 83 % comes from hard rock, the annual volume of size < 4 mm will be of the order of 19 million tons. Converting this into construction aggregates is a major challenge in order to obtain satisfactory mass balance. This challenge is even bigger for quarries producing decorative stones. E.g. the quarrying and production of schist products for building purpose normally utilises as little as 10-15 % of the excavated rock. Oppdal in central Norway is a main supplier of schist products for flooring, roofing and decorative purpose. The high percentage of QW is due to strict requirements to the finished products, both regarding processing and the character of the parent rock. The need to deposit large amounts of QW is a serious setback for the quarry economy. Within a limited time horizon the volumes of QW can threaten the further exploitation by merely choking the quarry. On the opposite side - any process that can convert the QW into sellable products will give a tremendous added value for the producer. Besides, the area in question is about to drain out its available aggregate resources, having to rely on long-transported sand and gravel. This has consequences not only for the economy, but also for the environment since heavy lorry transport will not be sustainable. An on-going project is now looking into converting the QW into quality aggregate both for road construction and concrete. Novel crusher technology and processing strategy is being applied and adapted, and the finished products will be tested in laboratories to establish the relevant application parameters and obtainable quality. By producing coarse aggregates for primarily road purpose, it is estimated that the QW can be reduced from todaýs approx. 90 % to approx. 40 %. The potential by also installing the latest inventions of crusher technology designed for making manufactured sand, is to further reduce QW down to < 10 %. Making all these materials sellable in the market, the economic - and also environmental - potential will be considerable. Understanding the geological conditions and petrographic properties of the rock is vital. This is a quartz-feldspar rich metamorphic rock - a meta-arkose - containing rhythmically distributed planar lamina (less than 2 mm thick) or scattered occurrence of mica, separated by layers composed predominately of quartz and feldspar. The rock can be split along the lamina to slabs varying from 0.5 cm to more than 10 cm in thickness, and the microstructure can be characterized as being granoblastic to gneissic. . This makes it possible by well designed crushing process and careful selection of the in-going rock particles, to obtain well shaped aggregates up to at least 20 mm. The on-going project will also study the total cost situation depending on the QW utilisation, discuss the environmental and sustainability issues with a societal perspective, and also consider the market opportunities.

LACIE performance predictor final operational capability program description, volume 3

NASA Technical Reports Server (NTRS)

1976-01-01

The requirements and processing logic for the LACIE Error Model program (LEM) are described. This program is an integral part of the Large Area Crop Inventory Experiment (LACIE) system. LEM is that portion of the LPP (LACIE Performance Predictor) which simulates the sample segment classification, strata yield estimation, and production aggregation. LEM controls repetitive Monte Carlo trials based on input error distributions to obtain statistical estimates of the wheat area, yield, and production at different levels of aggregation. LEM interfaces with the rest of the LPP through a set of data files.

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

ERIC Educational Resources Information Center

Kidd, Michael P.; Shannon, Michael

1996-01-01

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

Aggregate Timber Supply: From the Forest to the Market

Treesearch

David N. Wear; Subhrendu K. Pattanayak

2003-01-01

Timber supply modeling is a means of formalizing the production behavior of heterogeneous landowners managing a wide variety of forest types and vintages within a region. The critical challenge of timber supply modeling is constructing theoretically valid and empirically practical aggregate descriptions of harvest behavior. Understanding timber supply is essential for...

75 FR 41449 - Procurement List Additions and Deletion

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... the requirement of the U.S. Army, as aggregated by the Department of the Army Research, Development..., Philadelphia, PA Coverage: C-List for 100% of the requirement of the Department of Defense, as aggregated by... Acquisition Service, GSA/FSS OFC SUP CTR--Paper Products, New York, NY Coverage: A-List for the Total...

The Use of Multiple Regression Models to Determine if Conjoint Analysis Should Be Conducted on Aggregate Data.

ERIC Educational Resources Information Center

Fraas, John W.; Newman, Isadore

1996-01-01

In a conjoint-analysis consumer-preference study, researchers must determine whether the product factor estimates, which measure consumer preferences, should be calculated and interpreted for each respondent or collectively. Multiple regression models can determine whether to aggregate data by examining factor-respondent interaction effects. This…

Recycling of quarry waste as part of sustainable aggregate production: Norwegian and Italian point of view

NASA Astrophysics Data System (ADS)

Antonella Dino, Giovanna; Willy Danielsen, Svein; Chiappino, Claudia; Primavori, Piero; Engelsen, Christian John

2016-04-01

Resource preservation is one of the main challenges in Europe, together with waste management and recycling; recently several researchers are interested in the recovering of critical raw materials and secondary raw materials from landfill. Aggregate supply, even if it is not "critical" sensus stricto (s.s.), is one of the European priorities (low value but high volume needs). On the other side, the management of quarry waste , mainly from dimension stones, but also as fines from aggregate crushing, is still a matter of concern. Such materials are managed in different ways both locally and nationwide, and often they are landfilled, because of an unclear legislation and a general lack of data. Most of time the local authorities adopt the maximum precaution principle or the enterprises find it little profitable to recover them, so that the sustainable recycling of such material is not valued. Several studies have shown, depending on the material specific characteristics, the viability of recycling quarry waste into new raw materials used in glass and ceramic industries, precast concrete production, infrastructures etc. (Loudes et al. 2012, Dino&Marian 2015, Bozzola et al 2012, Dino et al. 2012, etc.). Thus, aggregate production may be one of the profitable ways to use quarry waste and is falling under the priority of EU (aggregate supply). Positive economic and environmental effects are likely to be achieved by systematic recycling of quarry waste planned by industries (industrial planning) and public authorities (national and local planning of aggregate exploitation). Today, the recycling level varies to a great extent and systematic recovery is not common among European Countries. In Italy and Norway no significant incentives on recycling or systematic approaches for local aggregate exploitation exist. The environmental consequences can be overexploitation of the natural resources, land take for the landfills, environmental contamination and landscape alteration by the quarry waste heaps. The environmentally sustainable management of quarry waste, which aims to recover and recycle both clean and contaminated materials, would therefore help to reduce the pressure on natural resources, reduce the land take and the environmental contamination. The present paper shows the main challenges connected to quarry waste management, focusing on several possibilities for quarry waste recovering, in order to produce recycled aggregates.

Biphasic cultivation strategy to avoid Epo-Fc aggregation and optimize protein expression.

PubMed

Kaisermayer, Christian; Reinhart, David; Gili, Andreas; Chang, Martina; Aberg, Per-Mikael; Castan, Andreas; Kunert, Renate

2016-06-10

In biphasic cultivations, the culture conditions are initially kept at an optimum for rapid cell growth and biomass accumulation. In the second phase, the culture is shifted to conditions ensuring maximum specific protein production and the protein quality required. The influence of specific culture parameters is cell line dependent and their impact on product quality needs to be investigated. In this study, a biphasic cultivation strategy for a Chinese hamster ovary (CHO) cell line expressing an erythropoietin fusion protein (Epo-Fc) was developed. Cultures were run in batch mode and after an initial growth phase, cultivation temperature and pH were shifted. Applying a DoE (Design of Experiments) approach, a fractional factorial design was used to systematically evaluate the influence of cultivation temperature and pH as well as their synergistic effect on cell growth as well as on recombinant protein production and aggregation. All three responses were influenced by the cultivation temperature. Additionally, an interaction between pH and temperature was found to be related to protein aggregation. Compared with the initial standard conditions of 37°C and pH 7.05, a parameter shift to low temperature and acidic pH resulted in a decrease in the aggregate fraction from 75% to less than 1%. Furthermore, the synergistic effect of temperature and pH substantially lowered the cell-specific rates of glucose and glutamine consumption as well as lactate and ammonium production. The optimized culture conditions also led to an increase of the cell-specific rates of recombinant Epo-Fc production, thus resulting in a more economic bioprocess. Copyright © 2016. Published by Elsevier B.V.

Efficient solubilization of inclusion bodies.

PubMed

Freydell, Esteban J; Ottens, Marcel; Eppink, Michel; van Dedem, Gijs; van der Wielen, Luuk

2007-06-01

The overexpression of recombinant proteins in Escherichia coli leads in most cases to their accumulation in the form of insoluble aggregates referred to as inclusion bodies (IBs). To obtain an active product, the IBs must be solubilized and thereafter the soluble monomeric protein needs to be refolded. In this work we studied the solubilization behavior of a model-protein expressed as IBs at high protein concentrations, using a statistically designed experiment to determine which of the process parameters, or their interaction, have the greatest impact on the amount of soluble protein and the fraction of soluble monomer. The experimental methodology employed pointed out an optimum balance between maximum protein solubility and minimum fraction of soluble aggregates. The optimized conditions solubilized the IBs without the formation of insoluble aggregates; moreover, the fraction of soluble monomer was approximately 75% while the fraction of soluble aggregates was approximately 5%. Overall this approach guarantees a better use of the solubilization reagents, which brings an economical and technical benefit, at both large and lab scale and may be broadly applicable for the production of recombinant proteins.

Optimization the composition of sand-lime products modified of diabase aggregate

NASA Astrophysics Data System (ADS)

Komisarczyk, K.; Stępień, A.

2017-10-01

The problem of optimizing the composition of building materials is currently of great importance due to the increasing competitiveness and technological development in the construction industry. This phenomenon also applies to catalog sand-lime. The respective arrangement of individual components or their equivalents, and linking them with the main parameters of the composition of the mixture, i.e. The lime/sand/water should lead to the intended purpose. The introduction of sand-lime diabase aggregate is concluded with a positive effect of final products. The paper presents the results of optimization with the addition of diabase aggregate. The constant value was the amount of water, variable - the mass of the dry ingredients. The program of experimental studies was taken for 6 series of silicates made in industrial conditions. Final samples were tested for mechanical and physico-chemical expanding the analysis of the mercury intrusion porosimetry, SEM and XRD. The results show that, depending on the aggregate’s contribution, exhibit differences. The sample in an amount of 10% diabase aggregate the compressive strength was higher than in the case of reference sample, while modified samples absorbed less water.

Formation of manganese nanoclusters in a sputtering/aggregation source and the roles of individual operating parameters

NASA Astrophysics Data System (ADS)

Khojasteh, Malak; Kresin, Vitaly V.

2016-12-01

We describe the production of size selected manganese nanoclusters using a dc magnetron sputtering/aggregation source. Since nanoparticle production is sensitive to a range of overlapping operating parameters (in particular, the sputtering discharge power, the inert gas flow rates, and the aggregation length) we focus on a detailed map of the influence of each parameter on the average nanocluster size. In this way it is possible to identify the main contribution of each parameter to the physical processes taking place within the source. The discharge power and argon flow supply the atomic vapor, and argon also plays the crucial role in the formation of condensation nuclei via three-body collisions. However, neither the argon flow nor the discharge power have a strong effect on the average nanocluster size in the exiting beam. Here the defining role is played by the source residence time, which is governed by the helium supply and the aggregation path length. The size of mass selected nanoclusters was verified by atomic force microscopy of deposited particles.

Influence of source parameters on the growth of metal nanoparticles by sputter-gas-aggregation

NASA Astrophysics Data System (ADS)

Khojasteh, Malak; Kresin, Vitaly V.

2017-11-01

We describe the production of size-selected manganese nanoclusters using a magnetron sputtering/aggregation source. Since nanoparticle production is sensitive to a range of overlapping operating parameters (in particular, the sputtering discharge power, the inert gas flow rates, and the aggregation length), we focus on a detailed map of the influence of each parameter on the average nanocluster size. In this way, it is possible to identify the main contribution of each parameter to the physical processes taking place within the source. The discharge power and argon flow supply the metal vapor, and argon also plays a crucial role in the formation of condensation nuclei via three-body collisions. However, the argon flow and the discharge power have a relatively weak effect on the average nanocluster size in the exiting beam. Here the defining role is played by the source residence time, governed by the helium supply (which raises the pressure and density of the gas column inside the source, resulting in more efficient transport of nanoparticles to the exit) and by the aggregation path length.

Investigating the feasibility of scale up and automation of human induced pluripotent stem cells cultured in aggregates in feeder free conditions☆

PubMed Central

Soares, Filipa A.C.; Chandra, Amit; Thomas, Robert J.; Pedersen, Roger A.; Vallier, Ludovic; Williams, David J.

2014-01-01

The transfer of a laboratory process into a manufacturing facility is one of the most critical steps required for the large scale production of cell-based therapy products. This study describes the first published protocol for scalable automated expansion of human induced pluripotent stem cell lines growing in aggregates in feeder-free and chemically defined medium. Cells were successfully transferred between different sites representative of research and manufacturing settings; and passaged manually and using the CompacT SelecT automation platform. Modified protocols were developed for the automated system and the management of cells aggregates (clumps) was identified as the critical step. Cellular morphology, pluripotency gene expression and differentiation into the three germ layers have been used compare the outcomes of manual and automated processes. PMID:24440272

Autologous Platelet-Rich Plasma Preparations

PubMed Central

Schippinger, Gert; Prüller, Florian; Divjak, Manuela; Mahla, Elisabeth; Fankhauser, Florian; Rackemann, Steve; Raggam, Reinhard Bernd

2015-01-01

Background Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration. Hypothesis The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury. Study Design Controlled laboratory study. Methods PRP was collected from patients receiving NSAIDs after elective orthopaedic surgery, and platelet function was evaluated using light transmission aggregometry (LTA). Results were compared with those obtained from healthy volunteers without a history of NSAID intake during the previous 2 weeks. Two different systems for blood collection and PRP production (Arthrex ACP double-syringe system and standard 4.5-mL sodium citrate blood collection tubes) were used and compared regarding the quality of PRP that was produced. Results For both groups, the baseline platelet counts of whole blood and the platelet counts of PRP formulations were found to be in the normal range. Both collection systems for PRP produced comparable results without significant differences between the groups. Platelet function testing with LTA revealed significantly impaired platelet aggregation in both PRP preparations, obtained from patients taking NSAIDs, irrespective of the type of NSAID (P < .001). All subjects from the control group showed normal platelet aggregation patterns when tested with LTA. Conclusion Autologous PRP produced from subjects after NSAID medication shows significantly impaired platelet function and may result in lower quality regarding the content of bioactive compounds. Clinical Relevance If required, the administration of NSAIDs should be performed after blood collection for preparation of autologous PRP; otherwise, the therapeutic effect may be limited. PMID:26665098

Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces.

PubMed Central

Sluzky, V; Tamada, J A; Klibanov, A M; Langer, R

1991-01-01

The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration. Images PMID:1946348

Aggregate consumer exposure to UV filter ethylhexyl methoxycinnamate via personal care products.

PubMed

Manová, Eva; von Goetz, Natalie; Hungerbuehler, Konrad

2015-01-01

Ultraviolet (UV) filters are substances designed to protect our skin from UV-induced damage and can be found in many categories of personal care products (PCPs). The potential endocrine-disrupting effects attributed to UV filter ethylhexyl methoxycinnamate (EHMC) are being debated. We evaluated the aggregate exposure of the Swiss-German population (N=1196; ages ≤1-97years) to EHMC via the use of PCPs; thus we provide the first comprehensive information about the current EHMC exposure sources and aggregate exposure levels. In our probabilistic modeling method performed at an individual level, PCP use data obtained by a postal questionnaire were linked to concentration data on EHMC gained from chemical analyses of PCPs used by the questionnaire respondents. The modeled median and 99.9th percentile of the internal aggregate exposure for the general population were 0.012 and 0.873mgday(-1)kg(-1) and 0.008 and 0.122mgday(-1)kg(-1) for the summer/autumn and winter/spring period, respectively. The major contributors to internal aggregate exposure were sunscreen products in summer/autumn (females: 64%; males: 85%; children aged ≤12years 93%). In winter/spring, lip care dominated for females (30%) and sunscreen for males (38%) and children aged ≤12years (50%). Overall, the internal aggregate exposure estimates for the studied population are shown to be below the Derived No Effect Level (DNEL) for EHMC i.e., the level of exposure above which humans should not be exposed; however, when an intense short-term exposure via sunscreen is accounted for during a sunbathing day, at the high-end percentiles (99.9th) the predicted aggregate exposure exceeds the DNEL for thyroid-disrupting effects such as for children aged ≤4years, who might be particularly susceptible to endocrine disrupting events. It is nevertheless critical to acknowledge that quantitative data on transdermal penetration of EHMC from PCPs are currently insufficient. Since long-term effects of endocrine disruptors are not known, future studies are warranted to provide accurate quantitative data on transdermal penetration of EHMC and to determine its metabolic fate in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Structure of Intrinsically Disordered Peptides Implicated in Amyloid Diseases: Insights from Fully Atomistic Simulations

NASA Astrophysics Data System (ADS)

Wu, Chun; Shea, Joan-Emma

Protein aggregation involves the self-assembly of proteins into large β-sheet-rich complexes. This process can be the result of aberrant protein folding and lead to "amyloidosis," a condition characterized by deposits of protein aggregates known as amyloids on various organs of the body [1]. Amyloid-related diseases include, among others, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and type II diabetes [2, 3, 4]. In other instances, however, protein aggregation is not a pathological process, but rather a functional one, with aggregates serving as structural scaffolds in a number of organisms [5].

Particle Aggregation During Fe(III) Bioreduction in Nontronite

NASA Astrophysics Data System (ADS)

Jaisi, D. P.; Dong, H.; Hi, Z.; Kim, J.

2005-12-01

This study was performed to evaluate the rate and mechanism of particle aggregation during bacterial Fe (III) reduction in different size fractions of nontronite and to investigate the role of different factors contributing to particle aggregation. To achieve this goal, microbial Fe(III) reduction experiments were performed with lactate as an electron donor, Fe(III) in nontronite as an electron acceptor, and AQDS as an electron shuttle in bicarbonate buffer using Shewanella putrefaceins CN32. These experiments were performed with and without Na- pyrophosphate as a dispersant in four size fractions of nontronite (0.12-0.22, 0.41-0.69, 0.73-0.96 and 1.42-1.8 mm). The rate of nontronite aggregation during the Fe(III) bioreduction was measured by analyzing particle size distribution using photon correlation spectroscopy (PCS) and SEM images analysis. Similarly, the changes in particle morphology during particle aggregation were determined by analyses of SEM images. Changes in particle surface charge were measured with electrophoretic mobility analyzer. The protein and carbohydrate fraction of EPS produced by cells during Fe(III) bioreduction was measured using Bradford and phenol-sulfuric acid extraction method, respectively. In the presence of the dispersant, the extent of Fe(III) bioreduction was 11.5-12.2% within the first 56 hours of the experiment. There was no measurable particle aggregation in control experiments. The PCS measurements showed that the increase in the effective diameter (95% percentile) was by a factor of 3.1 and 1.9 for particle size of 0.12-0.22 mm and 1.42-1.80 mm, respectively. The SEM image analyses also gave the similar magnitude of increase in particle size. In the absence of the dispersant, the extent of Fe(III) bioreduction was 13.4-14.5% in 56 hours of the experiment. The rate of aggregation was higher than that in the presence of the dispersant. The increase in the effective diameter (95% percentile) was by a factor of 13.6 and 4.1 for the particles size of 0.12-0.22 and 1.42-1.8 mm, respectively. The particle aggregation was limited in control experiment to the factor of 2.8 and 2.1 for these two size fractions, respectively. The measured electrophoretic mobility decreased with increase in the extent of bioreduction and aggregation, but the rate of decrease was greatest in the finest size fraction. The EPS measurements showed the increase in the carbohydrate and protein fractions as a result of bioreduction. Separate experiments were performed to understand the relative contribution of Fe(III) reduction and EPS production in controlling nontronite particle aggregation The rate of particle aggregation was measured for nontronite that was chemically pre-reduced by dithionite to various extents, both with and without addition of dextran, a neutral and pure EPS. The aggregation rate was greater in the nontronite that were pre-reduced to a higher extent than those with a lower extent of reduction. The relative contribution to particle aggregation due to Fe(III) reduction and polysaccharide bridging was about 4:1. However, in the real system where bacterial cells are involved, and amount of EPS production and extent of Fe(III) bioreduction increase with time, the relative contribution may be different than in this simple system. In summary, we conclude that both Fe(III) reduction and microbial production of EPS contribute to the observed nontronite particle aggregation with Fe(III) reduction playing more dominant role.

Self-assembly and omniphobic property of fluorinated unit end-functionalized poly(methyl methacrylate)

NASA Astrophysics Data System (ADS)

Junyan, Liang; Pingdi, Xu; Jingxian, Bao; Ling, He; Nan, Zhu

2018-03-01

The self-assembly behavior of fluorinated unit end-functionalized poly(methyl methacrylate) (PDFHM-ef-PMMA) in solution and its influence on the surface microstructure, elemental composition and omniphobic property of cast film was investigated in this work. Specifically, three mixed solutions of tetrahydrofuran (THF)/methanol (MeOH), THF/H2O and THF/H2O/MeOH in various compositions were employed separately as the selective solvents. In THF/MeOH solution, the aggregate morphologies of PDFHM-ef-PMMA changed gradually from core-shell spheres to worm, and then to elliptical vesicles as MeOH content increased. In THF/H2O solution, spherical and bowl-shaped aggregates with significantly larger sizes than those in THF/MeOH solution were favored despite lower H2O content. The further addition of MeOH to THF/H2O mixture could reduce the size of aggregate but hardly change original aggregate morphology. During the film formation process, those self-assembled aggregates in THF/MeOH solution fused with one another to form a smooth surface. When such surface was fully covered by fluorinated segments, the outstanding hexadecane and water slide-off properties and ink-resistant property required for antifouling application were demonstrated. Instead, the aggregates formed in THF/H2O/MeOH mixture were subjected to secondary aggregation of PDFHM-ef-PMMA chains during solvent evaporation, leading to the formation of a particulate film with poor adhesion towards glass plate and hexadecane-repellent property.

21 CFR 1303.11 - Aggregate production quotas.

Code of Federal Regulations, 2010 CFR

2010-04-01

... are manufactured from it, the economic and physical availability of raw materials for use in manufacturing and for inventory purposes, yield and stability problems, potential disruptions to production...

Gain-of-function profilin 1 mutations linked to familial amyotrophic lateral sclerosis cause seed-dependent intracellular TDP-43 aggregation.

PubMed

Tanaka, Yoshinori; Nonaka, Takashi; Suzuki, Genjiro; Kametani, Fuyuki; Hasegawa, Masato

2016-04-01

Profilin 1 (PFN1) is an actin monomer-binding protein essential for regulating cytoskeletal dynamics in all cell types. Recently, mutations in the PFN1 gene have been identified as a cause of familial amyotrophic lateral sclerosis (ALS). The co-aggregation of PFN1 bearing mutations that cause ALS with TDP-43 (a key molecule in both sporadic and some familial forms of ALS), together with the classical TDP-43 pathology detected in post-mortem tissues of patients with autosomal dominant PFN1 mutation, imply that gain-of-toxic-function of PFN1 mutants is associated with the onset of ALS. However, it remains unknown how PFN1 mutants cause ALS. We found mutant PFN1 that causes ALS formed cytoplasmic aggregates positive for ubiquitin and p62, and these aggregates sequestered endogenous TDP-43. In cells harboring PFN1 aggregates, formation of aggresome-like structures was inhibited in the presence of proteasome inhibitor, and conversion of LC3-I to LC3-II was suppressed in the presence of lysosome inhibitor. Further, insoluble TDP-43 was increased in both cases. Co-expression of ALS-linked mutant PFN1 and TDP-43 increased insoluble and phosphorylated TDP-43 levels. The C-terminal region of TDP-43, essential for aggregation of TDP-43, was also indispensable for the interaction with PFN1. Interestingly, insoluble fractions prepared from cells expressing ALS-linked mutant PFN1 functioned as a seed to induce accumulation and phosphorylation of TDP-43, indicating that TDP-43 accumulated in the presence of the PFN1 mutants is converted to prion-like species. These findings provide new insight into the mechanisms of neurodegeneration in ALS, suggesting that gain-of-toxic-function PFN1 gene mutation leads to conformational change of TDP-43. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of Inherent Particles and Mechanism of Thermal Stress Induced Particle Formation in HSV-2 Viral Vaccine Candidate.

PubMed

Li, Lillian; Kirkitadze, Marina; Bhandal, Kamaljit; Roque, Cristopher; Yang, Eric; Carpick, Bruce; Rahman, Nausheen

2017-11-10

Vaccine formulations may contain visible and/or subvisible particles, which can vary in both size and morphology. Extrinsic particles, which are particles not part of the product such as foreign contaminants, are generally considered undesirable and should be eliminated or controlled in injectable products. However, biological products, in particular vaccines, may also contain particles that are inherent to the product. Here we focus on the characterization of visible and subvisible particles in a live, replication-deficient viral vaccine candidate against HSV genital herpes in an early developmental stage. HSV-2 viral vaccine was characterized using a panel of analytical methods, including Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, liquid chromatography-mass spectrometry (LC-MS), light microscopy, transmission electron microscopy (TEM), micro-flow imaging (MFI), dynamic light scattering (DLS), right angle light scattering (RALS), and intrinsic fluorescence. Particles in HSV-2 vaccine typically ranged from hundreds of nanometers to hundreds of micrometers in size and were determined to be inherent to the product. The infectious titer did not correlate with any trend in subvisible particle concentration and size distribution as shown by DLS, MFI, and TEM under stressed conditions. This suggested that particle changes in the submicron range were related to HSV-2 virion structure and had direct impact on biological activity. It was also observed that subvisible and visible particles could induce aggregation in the viral product. The temperature induced aggregation was observed by RALS, intrinsic fluorescence, and DLS. The increase of subvisible particle size with temperature could be fitted to a two-step thermokinetic model. Visible and subvisible particles were found to be inherent to the HSV-2 viral vaccine product. The mechanism of protein aggregation was discussed and a two-step thermokinetic aggregation profile was proposed. The approaches reported in this study may be applied to a variety of vaccines and other biological products, as a way to assess the consistency of the manufacturing process and identify key product quality attributes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of conceptual models of natural organic matter (humus) from a consideration of the chemical and biochemical processes of humification

USGS Publications Warehouse

Wershaw, Robert L.

2004-01-01

Natural organic matter (NOM) has been studied for more than 200 years because of its importance in enhancing soil fertility, soil structure, and water-holding capacity and as a carbon sink in the global carbon cycle. Two different types of models have been proposed for NOM: (1) the humic polymer models and (2) the molecular aggregate models. In the humic polymer models, NOM molecules are depicted as large (humic) polymers that have unique chemical structures that are different from those of the precursor plant degradation products. In the molecular aggregate models, NOM is depicted as being composed of molecular aggregates (supramolecular aggregates) of plant degradation products held together by non-covalent bonds. The preponderance of evidence favors the supramolecular aggregate models. These models were developed by studying the properties of NOM extracted from soils and natural waters, and as such, they provide only a very generalized picture of the structure of NOM aggregates in soils and natural waters prior to extraction. A compartmental model, in which the structure of the NOM in each of the compartments is treated separately, should provide a more accurate representation of NOM in soil and sediment systems. The proposed NOM compartments are: (1) partially degraded plant tissue, (2) biomass from microorganisms, (3) organic coatings on mineral grains, (4) pyrolytic carbon, (5) organic precipitates, and (6) dissolved organic matter (DOM) in interstitial water. Within each of these compartments there are NOM supramolecular aggregates that will be dissolved by the solvent systems that are used by researchers for extraction of NOM from soils and sediments. In natural water systems DOM may be considered as existing in two subcompartments: (1) truly dissolved DOM and (2) colloidal DOM.

Lightweight alumina refractory aggregate. Final report

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

Swansiger, T.G.; Pearson, A.

1996-07-16

Objective was to develop a lightweight, high alumina refractory aggregate for use in various high performance insulating (low thermal conductivity) refractory applications (e.g., in the aluminium, glass, cement, and iron and steel industries). A new aggregate process was developed through bench and pilot-scale experiments involving extrusion of a blend of calcined and activated alumina powders and organic extrusion aids and binders. The aggregate, with a bulk density approaching 2.5 g/cc, exhibited reduced thermal conductivity and adequate fired strength compared to dense tabular aggregate. Refractory manufacturers were moderately enthusiastic over the results. Alcoa prepared an economic analysis for producing lightweight aggregate,more » based on a retrofit of this process into existing Alcoa production facilities. However, a new, competing lightweight aggregate material was developed by another company; this material (Plasmal{trademark})had a significantly more favorable cost base than the Alcoa/DOE material, due to cheap raw materials and fewer processing steps. In late 1995, Alcoa became a distributor of Plasmal. Alcoa estimated that {ge}75% of the market originally envisioned for the Alcoa/DOE aggregate would be taken by Plasmal. Hence, it was decided to terminate the contract without the full- scale demonstration.« less

Suspension properties of whole blood and its components under glucose influence studied in patients with acute coronary syndrome

NASA Astrophysics Data System (ADS)

Malinova, Lidia I.; Simonenko, Georgy V.; Denisova, Tatyana P.; Dovgalevsky, Pavel Y.; Tuchin, Valery V.

2004-05-01

The protocol of our study includes men with acute myocardial infarction, stable angina pectoris of II and III functional classes and unstable angina pectoris. Patients with arterial hypertension, disorders in carbohydrate metabolism were excluded from the study. Blood samples taken under standardized conditions, were stabilized with citrate sodium 3,8% (1:9). Erythrocytes and platelets aggregation activity under glucose influence (in vitro) was studied by means of computer aided microphotometer -- a visual analyzer. Erythrocyte and platelets were united in special subsystem of whole blood. Temporal and functional characteristics of their aggregation were analyzed by creation of phase patterns fragments. The received data testify to interrelation of erythrocytes and platelets processes of aggregation under conditions of increasing of glucose concentration of the incubatory environment, which temporal and functional characteristics may be used for diagnostics and the prognosis of destabilization coronary blood flow at an acute coronary syndrome.

Colorimetric As (V) detection based on S-layer functionalized gold nanoparticles.

PubMed

Lakatos, Mathias; Matys, Sabine; Raff, Johannes; Pompe, Wolfgang

2015-11-01

Herein, we present simple and rapid colorimetric and UV/VIS spectroscopic methods for detecting anionic arsenic (V) complexes in aqueous media. The methods exploit the aggregation of S-layer-functionalized spherical gold nanoparticles of sizes between 20 and 50 nm in the presence of arsenic species. The gold nanoparticles were functionalized with oligomers of the S-layer protein of Lysinibacillus sphaericus JG-A12. The aggregation of the nanoparticles results in a color change from burgundy-red for widely dispersed nanoparticles to blue for aggregated nanoparticles. A detailed signal analysis was achieved by measuring the shift of the particle plasmon resonance signal with UV/VIS spectroscopy. To further improve signal sensitivity, the influence of larger nanoparticles was tested. In the case of 50 nm gold nanoparticles, a concentration of the anionic arsenic (V) complex lower than 24 ppb was detectable. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduction in soil aggregation in response to dust emission processes

NASA Astrophysics Data System (ADS)

Swet, Nitzan; Katra, Itzhak

2016-09-01

Dust emission by aeolian (wind) soil erosion depends on the topsoil properties of the source area, especially on the nature of the aggregates where most dust particles are held. Although the key role of soil aggregates in dust emission, the response of soil aggregation to aeolian processes and its implications for dust emission remain unknown. This study focuses on aggregate size distribution (ASD) analyses before and after in-situ aeolian experiments in semiarid loess soils that are associated with dust emission. Wind tunnel simulations show that particulate matter (PM) emission and saltation rates depend on the initial ASD and shear velocity. Under all initial ASD conditions, the content of saltator-sized aggregates (63-250 μm) increased by 10-34% due to erosion of macro-aggregates (> 500 μm), resulting in a higher size ratio (SR) between the saltators and macro-aggregates following the aeolian erosion. The results revealed that the saltator production increases significantly for soils that are subjected to short-term (anthropogenic) disturbance of the topsoil. The findings highlight a decrease in soil aggregation for all initial ASD's in response to aeolian erosion, and consequently its influence on the dust emission potential. Changes in ASD should be considered as a key parameter in dust emission models of complex surfaces.

New methods allowing the detection of protein aggregates

PubMed Central

Demeule, Barthélemy; Palais, Caroline; Machaidze, Gia; Gurny, Robert

2009-01-01

Aggregation compromises the safety and efficacy of therapeutic proteins. According to the manufacturer, the therapeutic immunoglobulin trastuzumab (Herceptin®) should be diluted in 0.9% sodium chloride before administration. Dilution in 5% dextrose solutions is prohibited. The reason for the interdiction is not mentioned in the Food and Drug Administration (FDA) documentation, but the European Medicines Agency (EMEA) Summary of Product Characteristics states that dilution of trastuzumab in dextrose solutions results in protein aggregation. In this paper, asymmetrical flow field-flow fractionation (FFF), fluorescence spectroscopy, fluorescence microscopy and transmission electron microscopy (TEM) have been used to characterize trastuzumab samples diluted in 0.9% sodium chloride, a stable infusion solution, as well as in 5% dextrose (a solution prone to aggregation). When trastuzumab samples were injected in the FFF channel using a standard separation method, no difference could be seen between trastuzumab diluted in sodium chloride and trastuzumab diluted in dextrose. However, during FFF measurements made with appropriate protocols, aggregates were detected in 5% dextrose. The parameters enabling the detection of reversible trastuzumab aggregates are described. Aggregates could also be documented by fluorescence microscopy and TEM. Fluorescence spectroscopy data were indicative of conformational changes consistent with increased aggregation and adsorption to surfaces. The analytical methods presented in this study were able to detect and characterize trastuzumab aggregates. PMID:20061815

Effects of the size and content of protein aggregates on the rheological and structural properties of soy protein isolate emulsion gels induced by CaSO4.

PubMed

Wang, Xufeng; He, Zhiyong; Zeng, Maomao; Qin, Fang; Adhikari, Benu; Chen, Jie

2017-04-15

The effects of the size and content of soy protein isolate (SPI) aggregates on the rheological and textural properties of CaSO 4 -induced SPI emulsion gels were investigated. Considerable differences in the rheological, water-holding, and micro-structural properties were observed. The gels with larger and/or more SPI aggregates showed substantial increase in the elastic modulus and had lower gelation temperatures. Creep data suggested that the size of the SPI aggregates contributed more to the elastic modulus, whereas the increase of aggregate content enhanced the elastic modulus and viscous component of the gels. The water-holding capacity was markedly enhanced (p<0.05) with the increase in both the size and content of SPI aggregates. Confocal laser scanning microscopy and scanning electron microscopy showed that larger and/or more SPI aggregates resulted in more homogeneous networks with smaller oil droplets. These insights provide important information for the product development in relation to soy protein-stabilized emulsions and emulsion gels. Copyright © 2016. Published by Elsevier Ltd.

Computational study of aggregation mechanism in human lysozyme[D67H

PubMed Central

Patel, Dharmeshkumar

2017-01-01

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

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies.

PubMed

Danesh, B J; Saniabadi, A R; Russell, R I; Lowe, G D

1987-12-01

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation.

PubMed

Bou Khzam, Lara; Bouchereau, Olivier; Boulahya, Rahma; Hachem, Ahmed; Zaid, Younes; Abou-Saleh, Haissam; Merhi, Yahye

2015-11-09

Endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs). We aimed at characterizing these two EPC subtypes and at identifying their role in platelet aggregation. EOCs and ECFCs were generated from human peripheral blood mononuclear cells (PBMCs) seeded in conditioned media on fibronectin and collagen, respectively. The morphological, phenotypical and functional characteristics of EOCs and ECFCs were assessed by optical and confocal laser scanning microscopes, cell surface markers expression, and Matrigel tube formation. The impact of EOCs and ECFCs on platelet aggregation was monitored in collagen-induced optical aggregometry and compared with PBMCs and human umbilical vein endothelial cells (HUVECs). The levels of the anti-platelet agents' nitric oxide (NO) and prostacyclin (PGI2) released from cultured cells as well as the expression of their respective producing enzymes NO synthases (NOS) and cyclooxygenases (COX) were also assessed. We showed that EOCs display a monocytic-like phenotype whereas ECFCs have an endothelial-like phenotype. We demonstrated that both EOCs and ECFCs and their supernatants inhibited platelet aggregation; however ECFCs were more efficient than EOCs. This could be related to the release of significantly higher amounts of NO and PGI2 from ECFCs, in comparison to EOCs. Indeed, ECFCs, like HUVECs, constitutively express the endothelial (eNOS)-and inducible (iNOS)-NOS isoforms, and COX-1 and weakly express COX-2, whereas EOCs do not constitutively express these NO and PGI2 producing enzymes. The different morphological, phenotypic and more importantly the release of the anti-aggregating agents PGI2 and NO in each EPC subtype are implicated in their respective roles in platelet function and thus, may be linked to the increased efficiency of ECFCs in inhibiting platelet aggregation as compared to EOCs.

Wind induces variations in spider web geometry and sticky spiral droplet volume.

PubMed

Wu, Chao-Chia; Blamires, Sean J; Wu, Chung-Lin; Tso, I-Min

2013-09-01

Trap building by animals is rare because it comes at a substantial cost. Using materials with properties that vary across environments maintains trap functionality. The sticky spiral silks of spider orb webs are used to catch flying prey. Web geometry, accompanied by compensatory changes in silk properties, may change across environments to sustain web functionality. We exposed the spider Cyclosa mulmeinensis to wind to test whether wind-induced changes in web geometry are accompanied by changes in aggregate silk droplet morphology, axial thread width or spiral stickiness. We compared: (i) web catching area, (ii) length of total silks, (iii) mesh height, (iv) number of radii, (v) aggregate droplet morphology and (vi) spiral thread stickiness, between webs made by spiders exposed to wind and those made by spiders not exposed to wind. We interpreted co-variation in droplet morphology or spiral stickiness with web capture area, mesh height or spiral length as the silk properties functionally compensating for changes in web geometry to reduce wind drag. Wind-exposed C. mulmeinensis built webs with smaller capture areas, shorter capture spiral lengths and more widely spaced capture spirals, resulting in the expenditure of less silk. Individuals that were exposed to wind also deposited larger droplets of sticky silk but the stickiness of the spiral threads remained unchanged. The larger droplets may be a product of a greater investment in water, or low molecular weight compounds facilitating atmospheric water uptake. Either way, droplet dehydration in wind is likely to be minimized.

The Impact of Aerosols on Cloud and Precipitation Processes: Cloud-Resolving Model Simulations

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Li, X.; Khain, A.; Simpson, S.

2005-01-01

Cloud microphysics are inevitable affected by the smoke particle (CCN, cloud condensation nuclei) size distributions below the clouds, Therefore, size distributions parameterized as spectral bin microphysics are needed to explicitly study the effect of atmospheric aerosol concentration on cloud development, rainfall production, and rainfall rates for convective clouds. Recently, a detailed spectral-bin microphysical scheme was implemented into the the Goddard Cumulus Ensemble (GCE) model. The formulation for the explicit spectral-bim microphysical processes is based on solving stochastic kinetic equations for the size distribution functions of water droplets (i.e., cloud droplets and raindrops), and several types of ice particles [i.e., pristine ice crystals (columnar and plate-like), snow (dendrites and aggregates), graupel and frozen drops/hail]. Each type is described by a special size distribution function containing many categories (i.e., 33 bins). Atmospheric aerosols are also described using number density size-distribution functions.

1D Self-Assembly and Ice Recrystallization Inhibition Activity of Antifreeze Glycopeptide-Functionalized Perylene Bisimides.

PubMed

Adam, Madeleine K; Jarrett-Wilkins, Charles; Beards, Michael; Staykov, Emiliyan; MacFarlane, Liam R; Bell, Toby D M; Matthews, Jacqueline M; Manners, Ian; Faul, Charl F J; Moens, Pierre D J; Ben, Robert N; Wilkinson, Brendan L

2018-06-04

Antifreeze glycoproteins (AFGPs) are polymeric natural products that have drawn considerable interest in diverse research fields owing to their potent ice recrystallization inhibition (IRI) activity. Self-assembled materials have emerged as a promising class of biomimetic ice growth inhibitor, yet the development of AFGP-based supramolecular materials that emulate the aggregative behavior of AFGPs have not yet been reported. This work reports the first example of the 1D self-assembly and IRI activity of AFGP-functionalized perylene bisimides (AFGP-PBIs). Glycopeptide-functionalized PBIs underwent 1D self-assembly in water and showed modest IRI activity, which could be tuned through substitution of the PBI core. This work presents essential proof-of-principle for the development of novel IRIs as potential supramolecular cryoprotectants and glycoprotein mimics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Outline of Data Aggregation Security in Heterogeneous Wireless Sensor Networks

PubMed Central

Boubiche, Sabrina; Boubiche, Djallel Eddine; Bilami, Azzedine; Toral-Cruz, Homero

2016-01-01

Data aggregation processes aim to reduce the amount of exchanged data in wireless sensor networks and consequently minimize the packet overhead and optimize energy efficiency. Securing the data aggregation process is a real challenge since the aggregation nodes must access the relayed data to apply the aggregation functions. The data aggregation security problem has been widely addressed in classical homogeneous wireless sensor networks, however, most of the proposed security protocols cannot guarantee a high level of security since the sensor node resources are limited. Heterogeneous wireless sensor networks have recently emerged as a new wireless sensor network category which expands the sensor nodes’ resources and capabilities. These new kinds of WSNs have opened new research opportunities where security represents a most attractive area. Indeed, robust and high security level algorithms can be used to secure the data aggregation at the heterogeneous aggregation nodes which is impossible in classical homogeneous WSNs. Contrary to the homogeneous sensor networks, the data aggregation security problem is still not sufficiently covered and the proposed data aggregation security protocols are numberless. To address this recent research area, this paper describes the data aggregation security problem in heterogeneous wireless sensor networks and surveys a few proposed security protocols. A classification and evaluation of the existing protocols is also introduced based on the adopted data aggregation security approach. PMID:27077866

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

PubMed Central

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

2014-01-01

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

Synthesis of coupled resonator optical waveguides by cavity aggregation.

PubMed

Muñoz, Pascual; Doménech, José David; Capmany, José

2010-01-18

In this paper, the layer aggregation method is applied to coupled resonator optical waveguides. Starting from the frequency transfer function, the method yields the coupling constants between the resonators. The convergence of the algorithm developed is examined and the related parameters discussed.

21 CFR 864.7040 - Adenosine triphosphate release assay.

Code of Federal Regulations, 2014 CFR

2014-04-01

... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet function...

21 CFR 864.7040 - Adenosine triphosphate release assay.

Code of Federal Regulations, 2011 CFR

2011-04-01

... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet function...

21 CFR 864.7040 - Adenosine triphosphate release assay.

Code of Federal Regulations, 2013 CFR

2013-04-01

... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet function...

21 CFR 864.7040 - Adenosine triphosphate release assay.

Code of Federal Regulations, 2010 CFR

2010-04-01

... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet function...

21 CFR 864.7040 - Adenosine triphosphate release assay.

Code of Federal Regulations, 2012 CFR

2012-04-01

... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet function...

A Novel Method to Quantify Soil Aggregate Stability by Measuring Aggregate Bond Energies

NASA Astrophysics Data System (ADS)

Efrat, Rachel; Rawlins, Barry G.; Quinton, John N.; Watts, Chris W.; Whitmore, Andy P.

2016-04-01

Soil aggregate stability is a key indicator of soil quality because it controls physical, biological and chemical functions important in cultivated soils. Micro-aggregates are responsible for the long term sequestration of carbon in soil, therefore determine soils role in the carbon cycle. It is thus vital that techniques to measure aggregate stability are accurate, consistent and reliable, in order to appropriately manage and monitor soil quality, and to develop our understanding and estimates of soil as a carbon store to appropriately incorporate in carbon cycle models. Practices used to assess the stability of aggregates vary in sample preparation, operational technique and unit of results. They use proxies and lack quantification. Conflicting results are therefore drawn between projects that do not provide methodological or resultant comparability. Typical modern stability tests suspend aggregates in water and monitor fragmentation upon exposure to an un-quantified amount of ultrasonic energy, utilising a laser granulometer to measure the change in mean weight diameter. In this project a novel approach has been developed based on that of Zhu et al., (2009), to accurately quantify the stability of aggregates by specifically measuring their bond energies. The bond energies are measured operating a combination of calorimetry and a high powered ultrasonic probe, with computable output function. Temperature change during sonication is monitored by an array of probes which enables calculation of the energy spent heating the system (Ph). Our novel technique suspends aggregates in heavy liquid lithium heteropolytungstate, as opposed to water, to avoid exposing aggregates to an immeasurable disruptive energy source, due to cavitation, collisions and clay swelling. Mean weight diameter is measured by a laser granulometer to monitor aggregate breakdown after successive periods of calculated ultrasonic energy input (Pi), until complete dispersion is achieved and bond energy (Pb; input energy used in aggregate breakdown) can be calculated by the following equation: ΣPi - Ph = Pb The novel technique was tested by comparing the bond energies measured from a series of soil aggregates sampled from different land management histories, to the samples corresponding stability measurement obtained from standard modern stability tests. The effectiveness of the heavy liquid as a suspension (as opposed to water) was evaluated by comparing the bond energies of samples measured in both suspensions. Our results determine i) how disruptive water is in aggregate stability tests, ii) how accurate and representative standard aggregate stability tests are, and iii) how bond strength varies depending on land use. Keywords: Aggregate; Bond; Fragmentation; Soil; Sonication; Stability References: Zhu, Z. L., Minasny, B. & Field D. J. 2009. Measurement of aggregate bond energy using ultrasonic dispersion. European Journal of Soil Science, 60, 695-705

Rhamnolipid biosurfactant and soy protein act as effective stabilizers in the aggregation and transport of palladium-doped zerovalent iron nanoparticles in saturated porous media.

PubMed

Basnet, Mohan; Ghoshal, Subhasis; Tufenkji, Nathalie

2013-01-01

Palladium-doped nanosized zerovalent iron (Pd-NZVI) particles can contribute to the transformation of chlorinated solvents and various other contaminants into innocuous products. To make Pd-NZVI an effective in situ subsurface remediation agent, these particles need to migrate through a targeted contaminated area. However, previous studies have reported very limited mobility of these particles in the groundwater environment and attributed it to rapid aggregation and subsequent pore plugging. In this study, we systematically investigated the influence of selected natural and nontoxic organic macromolecules (carboxymethyl cellulose, rhamnolipid biosurfactants, and soy protein) on the aggregation and transport behavior of bare and coated Pd-NZVI. Aggregation behavior was investigated using dynamic light scattering by monitoring the evolution of hydrodynamic diameter as a function of time, whereas transport behavior was investigated by conducting water-saturated sand-packed column experiments. While bare Pd-NZVI is prone to rapid aggregation, we observed good colloidal stability and concurrent enhanced transport of Pd-NZVI coated with carboxymethyl cellulose, rhamnolipid biosurfactants, and soy protein. Each surface modifier performed well at lower ionic strength (IS) (10 mM NaHCO3), and one of the rhamnolipid surface modifiers (JBR215) significantly enhanced transport of 150 mg/L Pd-NZVI at concentrations as low as 10 mg/L total organic carbon. However, an increase in the solution IS induced significant Pd-NZVI aggregation with a simultaneous decrease in the transport potential in accordance with the DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory of colloidal stability. Nonetheless, at the highest IS (300 mM NaHCO3) investigated, the mobility of rhamnolipid-coated Pd-NZVI is significantly higher than that of Pd-NZVI coated with the other surface modifiers, suggesting that biosurfactants may be the most suitable surface modifiers in field application. Overall, this study emphasizes how stabilization of Pd-NZVI with natural macromolecules such as rhamnolipids can improve the transport potential of these reactive nanoparticles in subsurface remediation applications at concentrations significantly lower than those of other commonly used polymers.

In-silico analysis on biofabricating vascular networks using kinetic Monte Carlo simulations.

PubMed

Sun, Yi; Yang, Xiaofeng; Wang, Qi

2014-03-01

We present a computational modeling approach to study the fusion of multicellular aggregate systems in a novel scaffold-less biofabrication process, known as 'bioprinting'. In this novel technology, live multicellular aggregates are used as fundamental building blocks to make tissues or organs (collectively known as the bio-constructs,) via the layer-by-layer deposition technique or other methods; the printed bio-constructs embedded in maturogens, consisting of nutrient-rich bio-compatible hydrogels, are then placed in bioreactors to undergo the cellular aggregate fusion process to form the desired functional bio-structures. Our approach reported here is an agent-based modeling method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a lattice. In this method, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material's points on a three-dimensional (3D) lattice, where the cell-cell and cell-medium interactions are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, where the effect of cell differentiation, proliferation and death are tactically neglected, the interaction energy is primarily dictated by the interfacial energy between cell and cell as well as between cell and medium particles on the lattice, respectively, based on the differential adhesion hypothesis. By using the transition state theory to track the time evolution of the multicellular system while minimizing the interfacial energy, KMC is shown to be an efficient time-dependent simulation tool to study the evolution of the multicellular aggregate system. In this study, numerical experiments are presented to simulate fusion and cell sorting during the biofabrication process of vascular networks, in which the bio-constructs are fabricated via engineering designs. The results predict the feasibility of fabricating the vascular structures via the bioprinting technology and demonstrate the morphological development process during cellular aggregate fusion in various engineering designed structures. The study also reveals that cell sorting will perhaps not significantly impact the final fabricated products, should the maturation process be well-controlled in bioprinting.

The Feasibility of Palm Kernel Shell as a Replacement for Coarse Aggregate in Lightweight Concrete

NASA Astrophysics Data System (ADS)

Itam, Zarina; Beddu, Salmia; Liyana Mohd Kamal, Nur; Ashraful Alam, Md; Issa Ayash, Usama

2016-03-01

Implementing sustainable materials into the construction industry is fast becoming a trend nowadays. Palm Kernel Shell is a by-product of Malaysia’s palm oil industry, generating waste as much as 4 million tons per annum. As a means of producing a sustainable, environmental-friendly, and affordable alternative in the lightweight concrete industry, the exploration of the potential of Palm Kernel Shell to be used as an aggregate replacement was conducted which may give a positive impact to the Malaysian construction industry as well as worldwide concrete usage. This research investigates the feasibility of PKS as an aggregate replacement in lightweight concrete in terms of compressive strength, slump test, water absorption, and density. Results indicate that by using PKS for aggregate replacement, it increases the water absorption but decreases the concrete workability and strength. Results however, fall into the range acceptable for lightweight aggregates, hence it can be concluded that there is potential to use PKS as aggregate replacement for lightweight concrete.

Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

PubMed

Xu, You-hai; Xu, Kui; Sun, Ying; Liou, Benjamin; Quinn, Brian; Li, Rong-hua; Xue, Ling; Zhang, Wujuan; Setchell, Kenneth D R; Witte, David; Grabowski, Gregory A

2014-08-01

Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Oil-derived marine aggregates - hot spots of polysaccharide degradation by specialized bacterial communities

NASA Astrophysics Data System (ADS)

Arnosti, Carol; Ziervogel, Kai; Yang, Tingting; Teske, Andreas

2016-07-01

Aggregates generated in the laboratory from incubations of seawater and surface-water oil collected in the initial phase of the Deepwater Horizon oil spill resemble the oil-aggregates observed in situ. Here, we investigated the enzyme activities and microbial community composition of laboratory generated oil-aggregates, focusing on the abilities of these communities to degrade polysaccharides, which are major components of marine organic matter and are abundant constituents of exopolymeric substances (EPS) generated by oil-associated bacteria in response to the presence of oil. The patterns of polysaccharide-hydrolyzing enzyme activities in oil aggregates were very different from those in the water surrounding the aggregates after formation, and in the surface water that did not contain the oil. Specific oil aggregate-associated hydrolysis rates were also considerably higher than in the water surrounding the aggregates. The differences in initial hydrolysis profiles, and in evolution of these profiles with time, points to specialized metabolic abilities among the oil-aggregate communities compared to oil-water and ambient water communities. The composition of the oil-aggregate community indicates a multifunctional microbial assemblage containing primary oil-degrading and exopolysaccharide-producing members of the Gammaproteobacteria, and diverse members of the Alphaproteobacteria, Bacteroidetes and Planktomycetales that most likely participate in the breakdown of oil-derived bacterial biopolymers. Formation and aging of oil-aggregates encourages the growth and transformation of microbial communities that are specialized in degradation of petroleum, as well as their secondary degradation products.