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Sample records for intracellular diffusion restrictions

  1. Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout

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    Birkedal Rikke

    2009-12-01

    Full Text Available Abstract Background Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss, which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20°C in the absence and presence of creatine. Results Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria. Conclusions The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that

  2. Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging

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    Tamarand Lee Darling

    2017-09-01

    Full Text Available Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV and Ebolavirus (EBOV. Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking. Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking

  3. Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica.

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    Rakebrandt, Nikolas; Lentes, Sabine; Neumann, Heinz; James, Leo C; Neumann-Staubitz, Petra

    2014-11-01

    TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously expressed cytosolic Fc receptor, which has a potent role in protective immunity against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of antibody-coated viruses, a process called ADIN (antibody-dependent intracellular neutralisation). Our results reveal a similar mechanism to fight bacterial infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica in epithelial cells early in infection. TRIM21 does not bind directly to S. enterica, but to antibodies opsonising it. Most importantly, bacterial restriction is dependent on TRIM21 as well as on the opsonisation state of the bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal marker LC3, and intracellular defence is enhanced in starved cells suggesting an involvement of the autophagocytic pathway. Our data extend the protective role of TRIM21 from viruses to bacteria and thereby strengthening the general role of ADIN in cellular immunity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  4. Demonstration of non-Gaussian restricted diffusion in tumor cells using diffusion-time dependent diffusion weighted MR contrast

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    Tuva Roaldsdatter Hope

    2016-08-01

    Full Text Available The diffusion weighted imaging (DWI technique enables quantification of water mobility for probing microstructural properties of biological tissue, and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated a bi-exponential signal attenuation, ascribed to fast (high ADC and slow (low ADC diffusion components. In this empirical study, we investigate the properties of the diffusion time (∆ - dependent components of the diffusion-weighted (DW signal in a constant b-value experiment. A Xenograft GBM mouse was imaged using ∆ = 11 ms, 20 ms, 40 ms, 60 ms and b=500-4000 s/mm2 in intervals of 500s/mm2. Data was corrected for EPI distortions and the ∆-dependence on the DW signal was measured within three regions of interest (intermediate- and high-density tumor regions and normal appearing brain tissue regions (NAB. In this empirical study we verify the assumption that the slow decaying component of the DW-signal is non-Gaussian and dependent on ∆, consistent with restricted diffusion of the intracellular space. As the DW-signal as a function of ∆ is specific to restricted diffusion, manipulating ∆ at constant b-value (cb provides a complementary and direct approach for separating the restricted from the hindered diffusion component. Our results show that only tumor tissue signal of our data demonstrate ∆-dependence, based on a bi-exponential model with a restricted diffusion component, we successfully estimated the restricted ADC, signal volume fraction and cell size within each tumor ROI.

  5. Variety in intracellular diffusion during the cell cycle

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    Selhuber-Unkel, C.; Yde, P.; Berg-Sørensen, Kirstine

    2009-01-01

    During the cell cycle, the organization of the cytoskeletal network undergoes dramatic changes. In order to reveal possible changes of the viscoelastic properties in the intracellular space during the cell cycle we investigated the diffusion of endogenous lipid granules within the fission yeast...... Schizosaccharomyces Pombe using optical tweezers. The cell cycle was divided into interphase and mitotic cell division, and the mitotic cell division was further subdivided in its stages. During all stages of the cell cycle, the granules predominantly underwent subdiffusive motion, characterized by an exponent...... a that is also linked to the viscoelastic moduli of the cytoplasm. The exponent a was significantly smaller during interphase than during any stage of the mitotic cell division, signifying that the cytoplasm was more elastic during interphase than during division. We found no significant differences...

  6. Loperamide Restricts Intracellular Growth of Mycobacterium tuberculosis in Lung Macrophages.

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    Juárez, Esmeralda; Carranza, Claudia; Sánchez, Guadalupe; González, Mitzi; Chávez, Jaime; Sarabia, Carmen; Torres, Martha; Sada, Eduardo

    2016-12-01

    New approaches for improving tuberculosis (TB) control using adjunct host-directed cellular and repurposed drug therapies are needed. Autophagy plays a crucial role in the response to TB, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary TB. Here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to Mycobacterium tuberculosis (Mtb). Human monocyte-derived macrophages (MDMs) and murine alveolar cells (MACs) were infected with Mtb and treated with loperamide, carbamazepine, valproic acid, verapamil, and rapamycin in vitro. Balb/c mice were intraperitoneally administered loperamide, valproic acid, and verapamil, and MACs were infected in vitro with Mtb. The induction of autophagy, the containment of Mtb within autophagosomes and the intracellular Mtb burden were determined. Autophagy was induced by all of the drugs in human and mouse macrophages, and loperamide significantly increased the colocalization of microtubule-associated protein 1 light chain 3 with Mtb in MDMs. Carbamazepine, loperamide, and valproic acid induced microtubule-associated protein 1 light chain 3 and autophagy related 16- like protein 1 gene expression in MDMs and in MACs. Loperamide also induced a reduction in TNF-α production. Loperamide and verapamil induced autophagy, which was associated with a significant reduction in the intracellular growth of Mtb in MACs and alveolar macrophages. The intraperitoneal administration of loperamide and valproic acid induced autophagy in freshly isolated MACs. The antimycobacterial activity in MACs was higher after loperamide treatment and was associated with the degradation of p62. In conclusion, loperamide shows potential as an adjunctive therapy for the treatment of TB.

  7. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

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    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  8. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    DEFF Research Database (Denmark)

    Vestergaard, Christian L.; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    of the physical and biochemical conditions in plant cells. As model system, we use a H(2)O(2) signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits......Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...

  9. Reaction-diffusion systems in intracellular molecular transport and control.

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    Soh, Siowling; Byrska, Marta; Kandere-Grzybowska, Kristiana; Grzybowski, Bartosz A

    2010-06-07

    Chemical reactions make cells work only if the participating chemicals are delivered to desired locations in a timely and precise fashion. Most research to date has focused on active-transport mechanisms, although passive diffusion is often equally rapid and energetically less costly. Capitalizing on these advantages, cells have developed sophisticated reaction-diffusion (RD) systems that control a wide range of cellular functions-from chemotaxis and cell division, through signaling cascades and oscillations, to cell motility. These apparently diverse systems share many common features and are "wired" according to "generic" motifs such as nonlinear kinetics, autocatalysis, and feedback loops. Understanding the operation of these complex (bio)chemical systems requires the analysis of pertinent transport-kinetic equations or, at least on a qualitative level, of the characteristic times of the constituent subprocesses. Therefore, in reviewing the manifestations of cellular RD, we also describe basic theory of reaction-diffusion phenomena.

  10. Measuring Restriction Sizes Using Diffusion Weighted Magnetic Resonance Imaging: A Review

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    Melanie Martin

    2013-01-01

    Full Text Available This article reviews a new concept in magnetic resonance as applied to cellular and biological systems. Diffusion weighted magnetic resonance imaging can be used to infer information about restriction sizes of samples being measured. The measurements rely on the apparent diffusion coefficient changing with diffusion times as measurements move from restricted to free diffusion regimes. Pulsed gradient spin echo (PGSE measurements are limited in the ability to shorten diffusion times and thus are limited in restriction sizes which can be probed. Oscillating gradient spin echo (OGSE measurements could provide shorter diffusion times so smaller restriction sizes could be probed.

  11. Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

    KAUST Repository

    Flegg, Mark B.

    2013-01-01

    The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, "The two-regime method for optimizing stochastic reaction-diffusion simulations," J. R. Soc., Interface 9, 859-868 (2012)] in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration

  12. A systematic determination of diffusion coefficients of trace elements in open and restricted diffusive layers used by the diffusive gradients in a thin film technique

    DEFF Research Database (Denmark)

    Shiva, Amir Houshang; Teasdale, Peter R.; Bennett, William W.

    2015-01-01

    A systematic comparison of the diffusion coefficients of cations (Al, Cd, Co, Cu, Mn, Ni, Pb, Zn) and oxyanions (Al, As, Mo, Sb, V, W) in open (ODL) and restricted (RDL) diffusive layers used by the DGT technique was undertaken. Diffusion coefficients were measured using both the diffusion cell...... concentrations required with the Dcell measurements. This is the first time that D values have been reported for several oxyanions using RDL. Except for Al at pH 8.30 with ODL, all DDGT measurements were retarded relative to diffusion coefficients in water (DW) for both diffusive hydrogels. Diffusion in RDL...

  13. Intracellular Transport of Cargo in a Sub-diffusive Environment over an Explicit Cytoskeletal Network

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    Maelfeyt, Bryan; Gopinathan, Ajay

    Intracellular transport occurs in nearly all eukaryotic cells, where materials such as proteins, lipids, carbohydrates, and nucleic acids travel to target locations through phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton.We develop a computational model of the process with explicit cytoskeletal filament networks. In the active transport phase, cargo moves in straight lines along these filaments that are spread throughout the cell. To model the passive transport phase of cargo in the cytoplasm, where anomalous sub-diffusion is thought to take place, we implement a continuous-time random walk. We use this approach to provide a stepping stone to a predictive model where we can determine transport properties over a cytoskeletal network provided by experimental images of real filaments. We illustrate our approach by modeling the transport of insulin out of the cell and determining the impact of network geometry, anomalous sub-diffusion and motor number on the first-passage time distributions for insulin granules reaching their target destinations on the membrane.

  14. Restrictive liquid-phase diffusion and reaction in bidispersed catalysts

    International Nuclear Information System (INIS)

    Lee, S.Y.; Seader, J.D.; Tsai, C.H.; Massoth, F.E.

    1991-01-01

    In this paper, the effect of bidispersed pore-size distribution on liquid-phase diffusion and reaction in NiMo/Al 2 O 3 catalysts is investigated by applying two bidispersed-pore-structure models, the random-pore model and a globular-structure model, to extensive experimental data, which were obtained from sorptive diffusion measurements at ambient conditions and catalytic reaction rate measurements on nitrogen-containing compounds. Transport of the molecules in the catalysts was found to be controlled by micropore diffusion, in accordance with the random-pore model, rather than macropore diffusion as predicted by the globular-structure model. A qualitative criterion for micropore-diffusion control is proposed: relatively small macroporosity and high catalyst pellet density. Since most hydrotreating catalysts have high density, diffusion in these types of catalysts may be controlled by micropore diffusion. Accordingly, it is believed in this case that increasing the size of micropores may be more effective to reduce intraparticle diffusion resistance than incorporating macropores alone

  15. A magnetic gradient induced force in NMR restricted diffusion experiments

    International Nuclear Information System (INIS)

    Ghadirian, Bahman; Stait-Gardner, Tim; Castillo, Reynaldo; Price, William S.

    2014-01-01

    We predict that the phase cancellation of a precessing magnetisation field carried by a diffusing species in a bounded geometry under certain nuclear magnetic resonance pulsed magnetic field gradient sequences results in a small force over typically micrometre length scales. Our calculations reveal that the total magnetisation energy in a pore under the influence of a pulsed gradient will be distance-dependent thus resulting in a force acting on the boundary. It is shown that this effect of the magnetisation of diffusing particles will appear as either an attractive or repulsive force depending on the geometry of the pore and magnetic properties of the material. A detailed analysis is performed for the case of a pulsed gradient spin-echo experiment on parallel planes. It is shown that the force decays exponentially in terms of the spin-spin relaxation. The proof is based on classical electrodynamics. An application of this effect to soft matter is suggested

  16. Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen.

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    Pär Larsson

    2009-06-01

    Full Text Available Francisella tularensis is a potent mammalian pathogen well adapted to intracellular habitats, whereas F. novicida and F. philomiragia are less virulent in mammals and appear to have less specialized lifecycles. We explored adaptations within the genus that may be linked to increased host association, as follows. First, we determined the genome sequence of F. tularensis subsp. mediasiatica, the only subspecies that had not been previously sequenced. This genome, and those of 12 other F. tularensis isolates, were then compared to the genomes of F. novicida (three isolates and F. philomiragia (one isolate. Signs of homologous recombination were found in approximately 19.2% of F. novicida and F. philomiragia genes, but none among F. tularensis genomes. In addition, random insertions of insertion sequence elements appear to have provided raw materials for secondary adaptive mutations in F. tularensis, e.g. for duplication of the Francisella Pathogenicity Island and multiplication of a putative glycosyl transferase gene. Further, the five major genetic branches of F. tularensis seem to have converged along independent routes towards a common gene set via independent losses of gene functions. Our observations suggest that despite an average nucleotide identity of >97%, F. tularensis and F. novicida have evolved as two distinct population lineages, the former characterized by clonal structure with weak purifying selection, the latter by more frequent recombination and strong purifying selection. F. tularensis and F. novicida could be considered the same bacterial species, given their high similarity, but based on the evolutionary analyses described in this work we propose retaining separate species names.

  17. Posterior Reversible Encephalopathy Syndrome (PRES): Restricted Diffusion does not Necessarily Mean Irreversibility.

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    Wagih, Alaa; Mohsen, Laila; Rayan, Moustafa M; Hasan, Mo'men M; Al-Sherif, Ashraf H

    2015-01-01

    Restricted diffusion is the second most common atypical presentation of PRES. This has a very important implication, as lesions with cytotoxic edema may progress to infarction. Several studies suggested the role of DWI in the prediction of development of infarctions in these cases. Other studies, however, suggested that PRES is reversible even with cytotoxic patterns. Our aim was to evaluate whether every restricted diffusion in PRES is reversible and what factors affect this reversibility. Thirty-six patients with acute neurological symptoms suggestive of PRES were included in our study. Inclusion criteria comprised imaging features of atypical PRES where DWI images and ADC maps show restricted diffusion. Patients were imaged with 0.2-T and 1.5-T machines. FLAIR images were evaluated for the severity of the disease and a FLAIR/DWI score was used. ADC values were selectively recorded from the areas of diffusion restriction. A follow-up MRI study was carried out in all patients after 2 weeks. Patients were classified according to reversibility into: Group 1 (reversible PRES; 32 patients) and Group 2 (irreversible changes; 4 patients). The study was approved by the University's research ethics committee, which conforms to the declaration of Helsinki. The age and blood pressure did not vary significantly between both groups. The total number of regions involved and the FLAIR/DWI score did not vary significantly between both groups. Individual regions did not reveal any tendency for the development of irreversible lesions. Similarly, ADC values did not reveal any significant difference between both groups. PRES is completely reversible in the majority of patients, even with restricted diffusion. None of the variables under study could predict the reversibility of PRES lesions. It seems that this process is individual-dependent.

  18. Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

    KAUST Repository

    Flegg, Mark B.; Rüdiger, Sten; Erban, Radek

    2013-01-01

    The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While

  19. Reversible Restricted Diffusion in the Corpus Callosum in Various Pediatric Diseases

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    Kim, Won Kyung; Hong, Hyun Sook; Lee, A Leum; Cha, Jang Gyu; Lee, Hae Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Bae, Won Kyung [Dept. of Radiology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of)

    2012-04-15

    To evaluate the reversible restricted diffusion in the corpus callosum in pediatric patients with clinical findings, and to discuss the possible pathogenesis of these lesions. Between 2007 and 2011, seven children with reversible signal abnormalities in the corpus callosum were identified and retrospectively reviewed. Diseases and conditions associated with lesions included: trauma (n = 3), neonatal seizure (n = 1), clinically suspected mild encephalopathy (n = 1), multiple sclerosis (n = 1), and seizure with subdural hygroma (n = 1). The callosal lesions were located in the splenium and the genu (n = 2), the splenium and the body (n = 1), and the splenium only (n 4). The shape of the lesions was round-to-ovoid (n = 4) or linear (n = 3). Follow-up MRI scans showed completely resolved (n = 6) or persistent (n = 1) signal abnormalities on diffusion-weighted imaging as well as apparent diffusion coefficient mapping. Clinical outcomes were good in six of the patents but poor in the seventh. Reversible restricted diffusion in the corpus callosum can develop in various diseases. Knowledge of the MRI findings and associated diseases might be helpful in predicting patients' conditions and clinical outcomes.

  20. Restricted diffusion of CrEDTA and cyanocobalamine across the exchange vessels in rat hindquarters.

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    Haraldsson, B; Rippe, B

    1986-07-01

    The degree of diffusional restriction of skeletal muscle capillary walls to small solutes was estimated from the permeability surface area products (PS) of CrEDTA (MW = 341) and cyanocobalamine (MW = 1355), using computerized 'on-line' recordings of venous single injection indicator dilution curves. Experiments were performed on isolated perfused maximally vasodilated rat hindquarters during largely isogravimetric conditions and the arrangements allowed for measurements of capillary filtration coefficients (CFC). Extraction of tracer varied markedly as a function of transit time and, furthermore, PS increased with increasing flows, both these phenomena indicating tissue and flow heterogeneity. At maximal flows the disturbing influence of heterogeneity will be minimal and hence the diffusion capacities obtained by extrapolating PS area to infinite flows, so called PS tot values, were considered to give the best estimation of the 'true' capillary diffusion capacities. The value of PS tot was 12.9 +/- 0.5 for CrEDTA and 5.1 +/- 0.3 ml min-1 per 100 g for vitamin B12. The calculated PS tot ratio of 2.59 +/- 0.11 indicates restricted diffusion through equivalent pores of radius 53 A, whereas the ratio of the free diffusion coefficients for these solutes is 1.79. Using PS peak for the calculations (totally neglecting heterogeneity) the pore radius was, however, markedly overestimated. Thus, for a PS-ratio of 1.89 +/- 0.04 for CrEDTA vs. B12 an equivalent pore radius of 300 A was calculated. Also, using PS area (only partly correcting for heterogeneity) overestimated the pore radius (70 A) from a mean PS-ratio of 2.33 +/- 0.05. It was concluded that the equivalent pore radius in rat hindquarter microvascular walls is 53 A or even smaller in essential agreement with data from osmotic transient experiments in the same preparation (r approximately 40 A).

  1. Propagator formalism and computer simulation of restricted diffusion behaviors of inter-molecular multiple-quantum coherences

    International Nuclear Information System (INIS)

    Cai Congbo; Chen Zhong; Cai Shuhui; Zhong Jianhui

    2005-01-01

    In this paper, behaviors of single-quantum coherences and inter-molecular multiple-quantum coherences under restricted diffusion in nuclear magnetic resonance experiments were investigated. The propagator formalism based on the loss of spin phase memory during random motion was applied to describe the diffusion-induced signal attenuation. The exact expression of the signal attenuation under the short gradient pulse approximation for restricted diffusion between two parallel plates was obtained using this propagator method. For long gradient pulses, a modified formalism was proposed. The simulated signal attenuation under the effects of gradient pulses of different width based on the Monte Carlo method agrees with the theoretical predictions. The propagator formalism and computer simulation can provide convenient, intuitive and precise methods for the study of the diffusion behaviors

  2. Band shape of IR-absorption of complex molecules and restricted rotational diffusion

    International Nuclear Information System (INIS)

    Ivanov, E.N.; Umidulaev, Sh.U.

    1989-01-01

    The development of the theory of band shape (and Breadth) IR-absorption of complex molecules (regarding the molecules inside motions) is considered. It is supposed that a molecule fragment being responsible for IR-absorption takes part in the restricted rotational diffusion (RRD) with respect to the frame, and the molecule itself in general makes rotational motion (RM). Both kinds of motions are discussed in accordance with the theory of group motions representations. On the basis of correlative functions calculations of dipole moment a simple expression for the IR-absorption band shape have been obtained, which in itself uses to be the super position of two Lorencians with the semibreadths 2D 1 and 2D 1 +ν 2 0 (ν 2 0 +1D R accordingly (here D 1 is the coefficient of RM, D 2 is the coefficient of RRD, ν 2 0 is the well known function of RRD-cone divergence angle) in case of symmetric rotary abrasive disc. Analysis of experimental band shape of IR-absorption on the basis of the expression obtained allows to get information of MR-molecule parameters in general and RRD. It is really possible to determine the RRD-cone divergency angle from experimental weights of Lorencians. In accordance with experimental semibreadths the coefficient of RM D 1 and the coefficient of RRD D 2 are obtained. In conclusion it is noted that D 1 →0 (in the expression for the band shape of IR-absorption obtained), one of the Lorencians turns to the δ-function and finally there is an expression which describes IR-absorption band shape of molecules in polymer-mats. (author)

  3. Dynamic Behaviors of Solvent Molecules Restricted in Poly (Acryl Amide Gels Analyzed by Dielectric and Diffusion NMR Spectroscopy

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    Hironobu Saito

    2018-06-01

    Full Text Available Dynamics of solvent molecules restricted in poly (acryl amide gels immersed in solvent mixtures of acetone–, 1,4-dioxane–, and dimethyl sulfoxide–water were analyzed by the time domain reflectometry method of dielectric spectroscopy and the pulse field gradient method of nuclear magnetic resonance. Restrictions of dynamic behaviors of solvent molecules were evaluated from relaxation parameters such as the relaxation time, its distribution parameter, and the relaxation strength obtained by dielectric measurements, and similar behaviors with polymer concentration dependences for the solutions were obtained except for the high polymer concentration in collapsed gels. Scaling analyses for the relaxation time and diffusion coefficient respectively normalized by those for bulk solvent suggested that the scaling exponent determined from the scaling variable defined as a ratio of the size of solvent molecule to mesh size of polymer networks were three and unity, respectively, except for collapsed gels. The difference in these components reflects characteristic molecular interactions in the rotational and translational diffusions, and offered a physical picture of the restriction of solvent dynamics. A universal treatment of slow dynamics due to the restriction from polymer chains suggests a new methodology of characterization of water structures.

  4. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.; Newby, Jay M.

    2013-01-01

    mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually

  5. Cerebral NMR spectroscopy to study intracellular space in vivo: methodological development for diffusion weighted spectroscopy at short time scale and for pH measurement using 31P detection

    International Nuclear Information System (INIS)

    Marchadour, Charlotte

    2013-01-01

    NMR spectroscopy is a unique modality to evaluate intracellular environment in vivo. Indeed observed molecules are specifically intracellular and generally have a biochemistry role and a specific cellular compartmentation. That could be a useful tool to understand cell functioning in their environment. My thesis work consisted in development of new sequence in both diffusion and phosphorus NMR spectroscopy.My first study was to develop a diffusion-weighted spectroscopy at ultra-short diffusion time to look at the anomalous diffusion in the rat brain. ADC evolution as a function of time shows that brain metabolites motion is mainly due to random diffusion and that active transport (if exist) are negligible. Data modeling evidences that diffusion at short diffusion time is sensitive to cytoplasm viscosity and short scale crowding. In collaboration with the pharmaceutical company, this technique was chosen to follow up transgenic mice (rTg4510), model of tau pathology. Preliminary results show significant differences of ADC at an early stage of neuro-degenerescence (3 and 6 months).Phosphorus spectroscopy allows observation of metabolites directly implicated in energetic processes. During this thesis, localization sequences were developed to measure intracellular pH in the primate striatum. These sequences are supposed to be used to evaluate the potential of pH as a bio-marker of neuro-degenerescence in a phenotypic model of the Huntington disease in the non-human primate. (author) [fr

  6. Diffusion

    International Nuclear Information System (INIS)

    Kubaschewski, O.

    1983-01-01

    The diffusion rate values of titanium, its compounds and alloys are summarized and tabulated. The individual chemical diffusion coefficients and self-diffusion coefficients of certain isotopes are given. Experimental methods are listed which were used for the determination of diffusion coefficients. Some values have been taken over from other studies. Also given are graphs showing the temperature dependences of diffusion and changes in the diffusion coefficient with concentration changes

  7. Spin echoes of nuclear magnetization diffusing in a constant magnetic field gradient and in a restricted geometry

    International Nuclear Information System (INIS)

    Sen, P.N.; Andre, A.; Axelrod, S.

    1999-01-01

    We study the influence of restriction on Carr - Purcell - Meiboom - Gill spin echoes response of magnetization of spins diffusing in a bounded region in the presence of a constant magnetic field gradient. Depending on three main length scales: L S pore size, L G dephasing length and L D diffusion length during half-echo time, three main regimes of decay have been identified: free, localization and motionally averaging regime. In localization regime, the decay exponent depends on a fractional power (2/3) of the gradient, denoting a strong breakdown of the second cumulant or the Gaussian phase approximation (GPA). In the other two regimes, the exponent depends on the gradient squared, and the GPA holds. We find that the transition from the localization to the motionally averaging regime happens when the magnetic field gradients approach special values, corresponding to branch points of the eigenvalues. Transition from one regime to another as a function of echo number for a certain range of parameters is discussed. In this transition region, the signal shows large oscillations with echo number. For large n, asymptotic behavior sets in as a function of n for the decay exponent per echo. This is true for all values of the parameters L S , L G , and L D . copyright 1999 American Institute of Physics

  8. Restricted Diffusion of Pus in the Subarachnoid Space: MRSA Meningo-Vasculitis and Progressive Brainstem Ischemic Strokes – A Case Report

    Directory of Open Access Journals (Sweden)

    David Z. Rose

    2010-08-01

    Full Text Available Extra-axial restriction on diffusion weighted imaging (DWI is an unusual finding on brain magnetic resonance imaging (MRI. Intra-axial restriction on DWI, however, is common, and can represent brain parenchymal infarction, tumor, abscess, or toxic-metabolic process. The infrequency of extra-axial DWI restriction and the paucity of clinico-pathological correlation in the literature limit its differential diagnosis. Scant case reports suggest that extra-axial DWI restriction could be a lymphoma, neurenteric cyst, or, in one patient, subdural empyema [1–3]. We postulate that pus formation must be excluded first, because it can provoke an aggressive meningo-vasculitis with rapidly fatal, intra-axial infarctions. Our patient was a 45-year-old man, presenting to our hospital with left facial droop and right (contralateral arm and leg weakness. Initial MRI revealed DWI restriction in the left lateral pons, consistent with a classic Millard-Gubler stroke. Also noted was a subtle, extra-axial area of curvilinear diffusion restriction in the left cerebellar-pontine angle’s subarachnoid space. Days later, the patient had a headache, and repeat MRI revealed extension of the two DWI lesions – both the intra-axial pontine infarction and the extra-axial area of restricted diffusion in the subarachnoid space. The patient became comatose, a third MRI revealed more extensive DWI restrictions, and he expired despite aggressive care. Autopsy revealed massive brainstem infarcts, a thick lymphoplasmacytic infiltrate, copious Gram-Positive cocci (likely MRSA and arteries partially occluded with fibrointimal proliferation. This emphasizes the concept that extra-axial DWI restriction can represent pus development in the subarachnoid space – a radiographic marker to identify a patient at risk for demise due to septic, meningo-vasculitic infarctions.

  9. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4 + T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  10. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.

    2013-01-09

    The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of adenosine triphosphate hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review a wide range of analytical methods and models of intracellular transport is presented. In the case of diffusive transport, narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion are considered. In the case of active transport, Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasi-steady-state reduction methods, and mean-field approximations are considered. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures. © 2013 American Physical Society.

  11. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Miriam Illa

    Full Text Available BACKGROUND: Intrauterine growth restriction (IUGR affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI parameters and connectivity. METHODOLOGY: At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. PRINCIPAL FINDINGS: The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. CONCLUSIONS: The rabbit model used reproduced long-term functional impairments and their

  12. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

    2013-01-01

    Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR

  13. Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

    Science.gov (United States)

    Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

    2013-01-01

    Background Intrauterine growth restriction (IUGR) affects 5–10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. Methodology At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. Principal Findings The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. Conclusions The rabbit model used reproduced long-term functional impairments and their neurostructural

  14. A model for cell wall dissolution in mating yeast cells: polarized secretion and restricted diffusion of cell wall remodeling enzymes induces local dissolution.

    Science.gov (United States)

    Huberman, Lori B; Murray, Andrew W

    2014-01-01

    Mating of the budding yeast, Saccharomyces cerevisiae, occurs when two haploid cells of opposite mating types signal using reciprocal pheromones and receptors, grow towards each other, and fuse to form a single diploid cell. To fuse, both cells dissolve their cell walls at the point of contact. This event must be carefully controlled because the osmotic pressure differential between the cytoplasm and extracellular environment causes cells with unprotected plasma membranes to lyse. If the cell wall-degrading enzymes diffuse through the cell wall, their concentration would rise when two cells touched each other, such as when two pheromone-stimulated cells adhere to each other via mating agglutinins. At the surfaces that touch, the enzymes must diffuse laterally through the wall before they can escape into the medium, increasing the time the enzymes spend in the cell wall, and thus raising their concentration at the point of attachment and restricting cell wall dissolution to points where cells touch each other. We tested this hypothesis by studying pheromone treated cells confined between two solid, impermeable surfaces. This confinement increases the frequency of pheromone-induced cell death, and this effect is diminished by reducing the osmotic pressure difference across the cell wall or by deleting putative cell wall glucanases and other genes necessary for efficient cell wall fusion. Our results support the model that pheromone-induced cell death is the result of a contact-driven increase in the local concentration of cell wall remodeling enzymes and suggest that this process plays an important role in regulating cell wall dissolution and fusion in mating cells.

  15. A Model for Cell Wall Dissolution in Mating Yeast Cells: Polarized Secretion and Restricted Diffusion of Cell Wall Remodeling Enzymes Induces Local Dissolution

    Science.gov (United States)

    Huberman, Lori B.; Murray, Andrew W.

    2014-01-01

    Mating of the budding yeast, Saccharomyces cerevisiae, occurs when two haploid cells of opposite mating types signal using reciprocal pheromones and receptors, grow towards each other, and fuse to form a single diploid cell. To fuse, both cells dissolve their cell walls at the point of contact. This event must be carefully controlled because the osmotic pressure differential between the cytoplasm and extracellular environment causes cells with unprotected plasma membranes to lyse. If the cell wall-degrading enzymes diffuse through the cell wall, their concentration would rise when two cells touched each other, such as when two pheromone-stimulated cells adhere to each other via mating agglutinins. At the surfaces that touch, the enzymes must diffuse laterally through the wall before they can escape into the medium, increasing the time the enzymes spend in the cell wall, and thus raising their concentration at the point of attachment and restricting cell wall dissolution to points where cells touch each other. We tested this hypothesis by studying pheromone treated cells confined between two solid, impermeable surfaces. This confinement increases the frequency of pheromone-induced cell death, and this effect is diminished by reducing the osmotic pressure difference across the cell wall or by deleting putative cell wall glucanases and other genes necessary for efficient cell wall fusion. Our results support the model that pheromone-induced cell death is the result of a contact-driven increase in the local concentration of cell wall remodeling enzymes and suggest that this process plays an important role in regulating cell wall dissolution and fusion in mating cells. PMID:25329559

  16. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    Science.gov (United States)

    Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

    2015-06-21

    High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

  17. Na/K pump inactivation, subsarcolemmal Na measurements, and cytoplasmic ion turnover kinetics contradict restricted Na spaces in murine cardiac myocytes

    OpenAIRE

    Lu, Fang-Min; Hilgemann, Donald W.

    2017-01-01

    The Na/K pump exports cytoplasmic Na ions while importing K ions, and its activity is thought to be affected by restricted intracellular Na diffusion in cardiac myocytes. Lu and Hilgemann find instead that the pump can enter an inactivated state and that inactivation can be relieved by cytoplasmic Na.

  18. Microstructural changes in ischemic cortical gray matter predicted by a model of diffusion-weighted MRI

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Hansen, Brian; Østergaard, Leif

    2007-01-01

    compartment. A global optimum was found from a wide range of parameter permutations using cluster computing. We also present simulations of cell swelling and changes of exchange rate and intracellular diffusion as possible cellular mechanisms in ischemia. RESULTS: Our model estimates an extracellular volume...... compartments and slow water exchange. Our model reproduces the signal changes observed in ischemia via physiologically credible mechanisms. CONCLUSION: Our modeling suggests that transverse relaxation has a profound influence on the diffusion attenuated MR signal. Our simulations indicate cell swelling...... model to the diffusion-weighted MR signal obtained from cortical gray matter in healthy subjects. Our model includes variable volume fractions, intracellular restriction effects, and exchange between compartments in addition to individual diffusion coefficients and transverse relaxation rates for each...

  19. Microstructural changes in ischemic cortical gray matter predicted by a model of diffusion-weighted MRI.

    Science.gov (United States)

    Vestergaard-Poulsen, Peter; Hansen, Brian; Ostergaard, Leif; Jakobsen, Rikke

    2007-09-01

    To understand the diffusion attenuated MR signal from normal and ischemic brain tissue in order to extract structural and physiological information using mathematical modeling, taking into account the transverse relaxation rates in gray matter. We fit our diffusion model to the diffusion-weighted MR signal obtained from cortical gray matter in healthy subjects. Our model includes variable volume fractions, intracellular restriction effects, and exchange between compartments in addition to individual diffusion coefficients and transverse relaxation rates for each compartment. A global optimum was found from a wide range of parameter permutations using cluster computing. We also present simulations of cell swelling and changes of exchange rate and intracellular diffusion as possible cellular mechanisms in ischemia. Our model estimates an extracellular volume fraction of 0.19 in accordance with the accepted value from histology. The absolute apparent diffusion coefficient obtained from the model was similar to that of experiments. The model and the experimental results indicate significant differences in diffusion and transverse relaxation between the tissue compartments and slow water exchange. Our model reproduces the signal changes observed in ischemia via physiologically credible mechanisms. Our modeling suggests that transverse relaxation has a profound influence on the diffusion attenuated MR signal. Our simulations indicate cell swelling as the primary cause of the diffusion changes seen in the acute phase of brain ischemia. (c) 2007 Wiley-Liss, Inc.

  20. A general framework to quantify the effect of restricted diffusion on the NMR signal with applications to double pulsed field gradient NMR experiments.

    Science.gov (United States)

    Ozarslan, Evren; Shemesh, Noam; Basser, Peter J

    2009-03-14

    Based on a description introduced by Robertson, Grebenkov recently introduced a powerful formalism to represent the diffusion-attenuated NMR signal for simple pore geometries such as slabs, cylinders, and spheres analytically. In this work, we extend this multiple correlation function formalism by allowing for possible variations in the direction of the magnetic field gradient waveform. This extension is necessary, for example, to incorporate the effects of imaging gradients in diffusion-weighted NMR imaging scans and in characterizing anisotropy at different length scales via double pulsed field gradient (PFG) experiments. In cylindrical and spherical pores, respectively, two- and three-dimensional vector operators are employed whose form is deduced from Grebenkov's results via elementary operator algebra for the case of cylinders and the Wigner-Eckart theorem for the case of spheres. The theory was validated by comparison with known findings and with experimental double-PFG data obtained from water-filled microcapillaries.

  1. A general framework to quantify the effect of restricted diffusion on the NMR signal with applications to double pulsed field gradient NMR experiments

    Science.gov (United States)

    Özarslan, Evren; Shemesh, Noam; Basser, Peter J.

    2009-03-01

    Based on a description introduced by Robertson, Grebenkov recently introduced a powerful formalism to represent the diffusion-attenuated NMR signal for simple pore geometries such as slabs, cylinders, and spheres analytically. In this work, we extend this multiple correlation function formalism by allowing for possible variations in the direction of the magnetic field gradient waveform. This extension is necessary, for example, to incorporate the effects of imaging gradients in diffusion-weighted NMR imaging scans and in characterizing anisotropy at different length scales via double pulsed field gradient (PFG) experiments. In cylindrical and spherical pores, respectively, two- and three-dimensional vector operators are employed whose form is deduced from Grebenkov's results via elementary operator algebra for the case of cylinders and the Wigner-Eckart theorem for the case of spheres. The theory was validated by comparison with known findings and with experimental double-PFG data obtained from water-filled microcapillaries.

  2. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time ...

  3. Dynamics of gradient formation by intracellular shuttling

    Energy Technology Data Exchange (ETDEWEB)

    Berezhkovskii, Alexander M. [Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892 (United States); Shvartsman, Stanislav Y. [Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544 (United States)

    2015-08-21

    A number of important cellular functions rely on the formation of intracellular protein concentration gradients. Experimental studies discovered a number of mechanisms for the formation of such gradients. One of the mechanisms relies on the intracellular shuttling of a protein that interconverts between the two states with different diffusivities, under the action of two enzymes, one of which is localized to the plasma membrane, whereas the second is uniformly distributed in the cytoplasm. Recent work reported an analytical solution for the steady state gradient in this mechanism, obtained in the framework of a one-dimensional reaction-diffusion model. Here, we study the dynamics in this model and derive analytical expressions for the Laplace transforms of the time-dependent concentration profiles in terms of elementary transcendental functions. Inverting these transforms numerically, one can obtain time-dependent concentration profiles of the two forms of the protein.

  4. Imaging and controlling intracellular reactions: Lysosome transport as a function of diameter and the intracellular synthesis of conducting polymers

    Science.gov (United States)

    Payne, Christine

    2014-03-01

    Eukaryotic cells are the ultimate complex environment with intracellular chemical reactions regulated by the local cellular environment. For example, reactants are sequestered into specific organelles to control local concentration and pH, motor proteins transport reactants within the cell, and intracellular vesicles undergo fusion to bring reactants together. Current research in the Payne Lab in the School of Chemistry and Biochemistry at Georgia Tech is aimed at understanding and utilizing this complex environment to control intracellular chemical reactions. This will be illustrated using two examples, intracellular transport as a function of organelle diameter and the intracellular synthesis of conducting polymers. Using single particle tracking fluorescence microscopy, we measured the intracellular transport of lysosomes, membrane-bound organelles, as a function of diameter as they underwent transport in living cells. Both ATP-dependent active transport and diffusion were examined. As expected, diffusion scales with the diameter of the lysosome. However, active transport is unaffected suggesting that motor proteins are insensitive to cytosolic drag. In a second example, we utilize intracellular complexity, specifically the distinct micro-environments of different organelles, to carry out chemical reactions. We show that catalase, found in the peroxisomes of cells, can be used to catalyze the polymerization of the conducting polymer PEDOT:PSS. More importantly, we have found that a range of iron-containing biomolecules are suitable catalysts with different iron-containing biomolecules leading to different polymer properties. These experiments illustrate the advantage of intracellular complexity for the synthesis of novel materials.

  5. Restrictive cardiomyopathy

    Science.gov (United States)

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  6. Leishmania hijacking of the macrophage intracellular compartments.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Loiseau, Philippe M

    2016-02-01

    Leishmania spp., transmitted to humans by the bite of the sandfly vector, are responsible for the three major forms of leishmaniasis, cutaneous, diffuse mucocutaneous and visceral. Leishmania spp. interact with membrane receptors of neutrophils and macrophages. In macrophages, the parasite is internalized within a parasitophorous vacuole and engages in a particular intracellular lifestyle in which the flagellated, motile Leishmania promastigote metacyclic form differentiates into non-motile, metacyclic amastigote form. This phenomenon is induced by Leishmania-triggered events leading to the fusion of the parasitophorous vacuole with vesicular members of the host cell endocytic pathway including recycling endosomes, late endosomes and the endoplasmic reticulum. Maturation of the parasitophorous vacuole leads to the intracellular proliferation of the Leishmania amastigote forms by acquisition of host cell nutrients while escaping host defense responses. © 2015 FEBS.

  7. Restrictive Cardiomyopathy

    Science.gov (United States)

    ... up in the circulatory system. In time, the heart fails. What causes it? Restrictive cardiomyopathy is often caused by diseases in other parts of the body. One known cause is cardiac ... build up in the heart tissue, making the tissue stiff and thickened. Cardiac ...

  8. Intracellular calcium homeostasis and signaling.

    Science.gov (United States)

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  9. Data of NODDI diffusion metrics in the brain and computer simulation of hybrid diffusion imaging (HYDI acquisition scheme

    Directory of Open Access Journals (Sweden)

    Chandana Kodiweera

    2016-06-01

    Full Text Available This article provides NODDI diffusion metrics in the brains of 52 healthy participants and computer simulation data to support compatibility of hybrid diffusion imaging (HYDI, “Hybrid diffusion imaging” [1] acquisition scheme in fitting neurite orientation dispersion and density imaging (NODDI model, “NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain” [2]. HYDI is an extremely versatile diffusion magnetic resonance imaging (dMRI technique that enables various analyzes methods using a single diffusion dataset. One of the diffusion data analysis methods is the NODDI computation, which models the brain tissue with three compartments: fast isotropic diffusion (e.g., cerebrospinal fluid, anisotropic hindered diffusion (e.g., extracellular space, and anisotropic restricted diffusion (e.g., intracellular space. The NODDI model produces microstructural metrics in the developing brain, aging brain or human brain with neurologic disorders. The first dataset provided here are the means and standard deviations of NODDI metrics in 48 white matter region-of-interest (ROI averaging across 52 healthy participants. The second dataset provided here is the computer simulation with initial conditions guided by the first dataset as inputs and gold standard for model fitting. The computer simulation data provide a direct comparison of NODDI indices computed from the HYDI acquisition [1] to the NODDI indices computed from the originally proposed acquisition [2]. These data are related to the accompanying research article “Age Effects and Sex Differences in Human Brain White Matter of Young to Middle-Aged Adults: A DTI, NODDI, and q-Space Study” [3].

  10. Glutathionylation-Dependence of Na+-K+-Pump Currents Can Mimic Reduced Subsarcolemmal Na+ Diffusion

    Science.gov (United States)

    Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald J.; Rasmussen, Helge H.

    2016-01-01

    The existence of a subsarcolemmal space with restricted diffusion for Na+ in cardiac myocytes has been inferred from a transient peak electrogenic Na+-K+ pump current beyond steady state on reexposure of myocytes to K+ after a period of exposure to K+-free extracellular solution. The transient peak current is attributed to enhanced electrogenic pumping of Na+ that accumulated in the diffusion-restricted space during pump inhibition in K+-free extracellular solution. However, there are no known physical barriers that account for such restricted Na+ diffusion, and we examined if changes of activity of the Na+-K+ pump itself cause the transient peak current. Reexposure to K+ reproduced a transient current beyond steady state in voltage-clamped ventricular myocytes as reported by others. Persistence of it when the Na+ concentration in patch pipette solutions perfusing the intracellular compartment was high and elimination of it with K+-free pipette solution could not be reconciled with restricted subsarcolemmal Na+ diffusion. The pattern of the transient current early after pump activation was dependent on transmembrane Na+- and K+ concentration gradients suggesting the currents were related to the conformational poise imposed on the pump. We examined if the currents might be accounted for by changes in glutathionylation of the β1 Na+-K+ pump subunit, a reversible oxidative modification that inhibits the pump. Susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na+-K+ pump, and glutathionylation with the pump stabilized in conformations equivalent to those expected to be imposed on voltage-clamped myocytes supported this hypothesis. So did elimination of the transient K+-induced peak Na+-K+ pump current when we included glutaredoxin 1 in patch pipette solutions to reverse glutathionylation. We conclude that transient K+-induced peak Na+-K+ pump current reflects the effect of conformation-dependent β1 pump subunit

  11. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    communities and shopping centres through mobility lenses. The article shows how different mobility systems enable and restrict the public access to private-public spaces, and it points out that proprietary communities create an unequal potential for human movement and access in the city. The main argument......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...... and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private/public spaces...

  12. In vivo P-31 MR diffusion spectroscopy

    International Nuclear Information System (INIS)

    Moonen, C.T.W.; Vanzijl, P.C.M.; LeBihan, D.

    1988-01-01

    This paper discusses the Stejskal-Tanner diffusion spin-echo sequence modified for the in vivo diffusion spectroscopy. The apparent diffusion constant D α was measured as a function of the diffusion time. Contrary to the results in phantom samples, a strong dependency of the D α for phosphocreatine (PCr) in the rat muscle tissue on diffusion time was observed, clearly indicating restricted diffusion effects and allowing an approximation of the size of the restricted volume (8-13 μm). This size fits well with the known dimensions of a normal muscle cell

  13. Insecticide resistance and intracellular proteases.

    Science.gov (United States)

    Wilkins, Richard M

    2017-12-01

    Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide-resistant insects have constitutively elevated intracellular protease activity compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods. Upregulation and expression of proteases have been characterised in resistant strains of some insect species, including mosquitoes. This increase in proteolysis results in more degradation products (amino acids) of intracellular proteins. These may be utilised in the resistant strain to better protect the cell from stress. There are changes in insect intracellular proteases shortly after insecticide exposure, suggesting a role in stress response. The use of protease and proteasome inhibitors or peptide mimetics as synergists with improved application techniques and through protease gene knockdown using RNA interference (possibly expressed in crop plants) may be potential pest management strategies, in situations where elevated intracellular proteases are relevant. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Advances in genetic manipulation of obligate intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Paul eBeare

    2011-05-01

    Full Text Available Infections by obligate intracellular bacterial pathogens result in significant morbidity and mortality worldwide. These bacteria include Chlamydia spp., which causes millions of cases of sexually transmitted disease and blinding trachoma annually, and members of the α-proteobacterial genera Anaplasma, Ehrlichia, Orientia and Rickettsia, agents of serious human illnesses including epidemic typhus. Coxiella burnetii, the agent of human Q fever, has also been considered a prototypical obligate intracellular bacterium, but recent host cell-free (axenic growth has rescued it from obligatism. The historic genetic intractability of obligate intracellular bacteria has severely limited molecular dissection of their unique lifestyles and virulence factors involved in pathogenesis. Host cell restricted growth is a significant barrier to genetic transformation that can make simple procedures for free-living bacteria, such as cloning, exceedingly difficult. Low transformation efficiency requiring long term culture in host cells to expand small transformant populations is another obstacle. Despite numerous technical limitations, the last decade has witnessed significant gains in genetic manipulation of obligate intracellular bacteria including allelic exchange. Continued development of genetic tools should soon enable routine mutation and complementation strategies for virulence factor discovery and stimulate renewed interest in these refractory pathogens. In this review, we discuss the technical challenges associated with genetic transformation of obligate intracellular bacteria and highlight advances made with individual genera.

  15. Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Walmor eDe Mello

    2015-01-01

    Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

  16. Self-organization of intracellular gradients during mitosis

    Directory of Open Access Journals (Sweden)

    Fuller Brian G

    2010-01-01

    Full Text Available Abstract Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying the robust gradient of Ran-GTP have received little attention. Gradients of phosphorylation have been observed on Aurora B kinase substrates both before and after anaphase onset. In both instances the phosphorylation gradient appears to result from a soluble gradient of Aurora B kinase activity. Regulatory properties that support gradient formation are highlighted. Intracellular activity gradients that regulate localized mitotic events bare several hallmarks of self-organizing biologic systems that designate spatial information during pattern formation. Intracellular pattern formation represents a new paradigm in mitotic regulation.

  17. Spatial Mapping of Translational Diffusion Coefficients Using Diffusion Tensor Imaging: A Mathematical Description.

    Science.gov (United States)

    Shetty, Anil N; Chiang, Sharon; Maletic-Savatic, Mirjana; Kasprian, Gregor; Vannucci, Marina; Lee, Wesley

    2014-01-01

    In this article, we discuss the theoretical background for diffusion weighted imaging and diffusion tensor imaging. Molecular diffusion is a random process involving thermal Brownian motion. In biological tissues, the underlying microstructures restrict the diffusion of water molecules, making diffusion directionally dependent. Water diffusion in tissue is mathematically characterized by the diffusion tensor, the elements of which contain information about the magnitude and direction of diffusion and is a function of the coordinate system. Thus, it is possible to generate contrast in tissue based primarily on diffusion effects. Expressing diffusion in terms of the measured diffusion coefficient (eigenvalue) in any one direction can lead to errors. Nowhere is this more evident than in white matter, due to the preferential orientation of myelin fibers. The directional dependency is removed by diagonalization of the diffusion tensor, which then yields a set of three eigenvalues and eigenvectors, representing the magnitude and direction of the three orthogonal axes of the diffusion ellipsoid, respectively. For example, the eigenvalue corresponding to the eigenvector along the long axis of the fiber corresponds qualitatively to diffusion with least restriction. Determination of the principal values of the diffusion tensor and various anisotropic indices provides structural information. We review the use of diffusion measurements using the modified Stejskal-Tanner diffusion equation. The anisotropy is analyzed by decomposing the diffusion tensor based on symmetrical properties describing the geometry of diffusion tensor. We further describe diffusion tensor properties in visualizing fiber tract organization of the human brain.

  18. Mycobacterium intracellulare Pleurisy Identified on Liquid Cultures of the Pleural Fluid and Pleural Biopsy

    OpenAIRE

    Lim, Jong Gu; O, Sei Won; Lee, Ki Dong; Suk, Dong Keun; Jung, Tae Young; Shim, Tae Sun; Chon, Gyu Rak

    2013-01-01

    Pleural effusion is a rare complication in non-tuberculous mycobacterial infection. We report a case of Mycobacterium intracellulare pleuritis with idiopathic pulmonary fibrosis in a 69-year-old man presenting with dyspnea. Pleural effusion revealed lymphocyte dominant exudate. M. intracellulare was identified using a polymerase chain reaction-restriction fragment length polymorphism method and liquid cultures of pleural effusion and pleural biopsy. After combination therapy for M. intracellu...

  19. Mycobacterium intracellulare Pleurisy Identified on Liquid Cultures of the Pleural Fluid and Pleural Biopsy.

    Science.gov (United States)

    Lim, Jong Gu; O, Sei Won; Lee, Ki Dong; Suk, Dong Keun; Jung, Tae Young; Shim, Tae Sun; Chon, Gyu Rak

    2013-03-01

    Pleural effusion is a rare complication in non-tuberculous mycobacterial infection. We report a case of Mycobacterium intracellulare pleuritis with idiopathic pulmonary fibrosis in a 69-year-old man presenting with dyspnea. Pleural effusion revealed lymphocyte dominant exudate. M. intracellulare was identified using a polymerase chain reaction-restriction fragment length polymorphism method and liquid cultures of pleural effusion and pleural biopsy. After combination therapy for M. intracellulare pulmonary disease, the patient was clinically well at a 1-month follow-up.

  20. Characterization of Leptin Intracellular Trafficking

    Directory of Open Access Journals (Sweden)

    E Walum

    2009-12-01

    Full Text Available Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBRl with an intracellular domain of 303 amino acids and a shorter form (OBRs with an intracellular domain of 34 amino acids. Since OBRl is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor-mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA-soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3- transferrin containing compartments at 37°C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF and the lysosomal marker protein lamp-1. The transport of leptin was also shown

  1. Electron Microscopy of Intracellular Protozoa

    Science.gov (United States)

    1988-12-20

    Classification) " ELECTRON MICROSCOPY OF INTRACELLULAR PROTOZOA 12. PERSONAL AUTHOR(S) Aikawa, Masamichi 13a. TYPE OF REPORT I13b. TIME COVERED 114...authors suggest that anti-CS protein antibody is important in reducing the prevalence of malaria with increasing age among persons in such areas and... Hygine 33, 220-226. 0Giudice, G.D., Engers, H.D., Tougne, C., Biro, S.S., Weiss, N., Verdini, A.S., Pessi, A., Degremont, A.A., Freyvogel, T.A., Lambert

  2. Pathogenic mechanisms of intracellular bacteria.

    Science.gov (United States)

    Niller, Hans Helmut; Masa, Roland; Venkei, Annamária; Mészáros, Sándor; Minarovits, Janos

    2017-06-01

    We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression. Gene silencing by CpG methylation and histone deacetylation, mediated by cellular enzymes, also occurred in M. tuberculosis-infected macrophages. M. tuberculosis elicited cell type-specific epigenetic changes: it caused increased DNA methylation in macrophages, but induced demethylation, deposition of euchromatic histone marks and activation of immune-related genes in dendritic cells. A secreted transposase of Acinetobacter baumannii silenced a cellular gene, whereas Mycobacterium leprae altered the epigenotype, phenotype, and fate of infected Schwann cells. The 'keystone pathogen' oral bacterium Porphyromonas gingivalis induced local DNA methylation and increased the level of histone acetylation in host cells. These epigenetic changes at the biofilm-gingiva interface may contribute to the development of periodontitis. Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells and play an important role in pathogenesis.

  3. Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography.

    Science.gov (United States)

    Lee, Jonghwan; Radhakrishnan, Harsha; Wu, Weicheng; Daneshmand, Ali; Climov, Mihail; Ayata, Cenk; Boas, David A

    2013-06-01

    This paper describes a novel optical method for label-free quantitative imaging of cerebral blood flow (CBF) and intracellular motility (IM) in the rodent cerebral cortex. This method is based on a technique that integrates dynamic light scattering (DLS) and optical coherence tomography (OCT), named DLS-OCT. The technique measures both the axial and transverse velocities of CBF, whereas conventional Doppler OCT measures only the axial one. In addition, the technique produces a three-dimensional map of the diffusion coefficient quantifying nontranslational motions. In the DLS-OCT diffusion map, we observed high-diffusion spots, whose locations highly correspond to neuronal cell bodies and whose diffusion coefficient agreed with that of the motion of intracellular organelles reported in vitro in the literature. Therefore, the present method has enabled, for the first time to our knowledge, label-free imaging of the diffusion-like motion of intracellular organelles in vivo. As an example application, we used the method to monitor CBF and IM during a brief ischemic stroke, where we observed an induced persistent reduction in IM despite the recovery of CBF after stroke. This result supports that the IM measured in this study represent the cellular energy metabolism-related active motion of intracellular organelles rather than free diffusion of intracellular macromolecules.

  4. Oxygen effect and intracellular oxygen content (adaptation hypothesis)

    Energy Technology Data Exchange (ETDEWEB)

    Yarmonenko, S P; Ehpshtejn, I M [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Tsentr

    1977-01-01

    Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation.

  5. Oxygen effect and intracellular oxygen content (adaptation hypothesis)

    International Nuclear Information System (INIS)

    Yarmonenko, S.P.; Ehpshtejn, I.M.

    1977-01-01

    Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation

  6. Diffusion properties of NAA in human corpus callosum as studied with diffusion tensor spectroscopy.

    Science.gov (United States)

    Upadhyay, Jaymin; Hallock, Kevin; Erb, Kelley; Kim, Dae-Shik; Ronen, Itamar

    2007-11-01

    In diffusion tensor imaging (DTI) the anisotropic movement of water is exploited to characterize microstructure. One confounding issue of DTI is the presence of intra- and extracellular components contributing to the measured diffusivity. This causes an ambiguity in determining the underlying cause of diffusion properties, particularly the fractional anisotropy (FA). In this study an intracellular constituent, N-acetyl aspartate (NAA), was used to probe intracellular diffusion, while water molecules were used to probe the combined intra- and extracellular diffusion. NAA and water diffusion measurements were made in anterior and medial corpus callosum (CC) regions, which are referred to as R1 and R2, respectively. FA(NAA) was found to be greater than FA(Water) in both CC regions, thus indicating a higher degree of anisotropy within the intracellular space in comparison to the combined intra- and extracellular spaces. A decreasing trend in the FA of NAA and water was observed between R1 and R2, while the radial diffusivity (RD) for both molecules increased. The increase in RD(NAA) is particularly significant, thus explaining the more significant decrease in FA(NAA) between the two regions. It is suggested that diffusion tensor spectroscopy of NAA can potentially be used to further characterize microscopic anatomic organization in white matter. Copyright 2007 Wiley-Liss, Inc.

  7. Glutathionylation-Dependence of Na(+)-K(+)-Pump Currents Can Mimic Reduced Subsarcolemmal Na(+) Diffusion.

    Science.gov (United States)

    Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald J; Rasmussen, Helge H

    2016-03-08

    The existence of a subsarcolemmal space with restricted diffusion for Na(+) in cardiac myocytes has been inferred from a transient peak electrogenic Na(+)-K(+) pump current beyond steady state on reexposure of myocytes to K(+) after a period of exposure to K(+)-free extracellular solution. The transient peak current is attributed to enhanced electrogenic pumping of Na(+) that accumulated in the diffusion-restricted space during pump inhibition in K(+)-free extracellular solution. However, there are no known physical barriers that account for such restricted Na(+) diffusion, and we examined if changes of activity of the Na(+)-K(+) pump itself cause the transient peak current. Reexposure to K(+) reproduced a transient current beyond steady state in voltage-clamped ventricular myocytes as reported by others. Persistence of it when the Na(+) concentration in patch pipette solutions perfusing the intracellular compartment was high and elimination of it with K(+)-free pipette solution could not be reconciled with restricted subsarcolemmal Na(+) diffusion. The pattern of the transient current early after pump activation was dependent on transmembrane Na(+)- and K(+) concentration gradients suggesting the currents were related to the conformational poise imposed on the pump. We examined if the currents might be accounted for by changes in glutathionylation of the β1 Na(+)-K(+) pump subunit, a reversible oxidative modification that inhibits the pump. Susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na(+)-K(+) pump, and glutathionylation with the pump stabilized in conformations equivalent to those expected to be imposed on voltage-clamped myocytes supported this hypothesis. So did elimination of the transient K(+)-induced peak Na(+)-K(+) pump current when we included glutaredoxin 1 in patch pipette solutions to reverse glutathionylation. We conclude that transient K(+)-induced peak Na(+)-K(+) pump current reflects the effect

  8. Human cellular restriction factors that target HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2009-09-01

    Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

  9. MR imaging of intracellular and extracellular deoxyhemoglobin

    International Nuclear Information System (INIS)

    Janick, P.A.; Grossman, R.I.; Asakura, T.

    1989-01-01

    MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

  10. Conservative diffusions

    International Nuclear Information System (INIS)

    Carlen, E.A.

    1984-01-01

    In Nelson's stochastic mechanics, quantum phenomena are described in terms of diffusions instead of wave functions. These diffusions are formally given by stochastic differential equations with extremely singular coefficients. Using PDE methods, we prove the existence of solutions. This reult provides a rigorous basis for stochastic mechanics. (orig.)

  11. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article discusses three central aspects of the freedoms under European Community law, namely 1) the prohibition against restrictions as an important extension of the prohibition against discrimination, 2) a prohibition against exit restrictions which is just as important as the prohibition...... against host country restrictions, but which is often not recognised to the same extent by national law, and 3) the importance of also identifying and recognising an exit restriction, so that it is possible to achieve the required test of appropriateness and proportionality in relation to the rule...

  12. Dynamics of intracellular information decoding

    International Nuclear Information System (INIS)

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-01-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity

  13. Dynamics of intracellular information decoding.

    Science.gov (United States)

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-10-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity.

  14. Secretome of obligate intracellular Rickettsia

    Science.gov (United States)

    Gillespie, Joseph J.; Kaur, Simran J.; Rahman, M. Sayeedur; Rennoll-Bankert, Kristen; Sears, Khandra T.; Beier-Sexton, Magda; Azad, Abdu F.

    2014-01-01

    The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g. josamycin, ciprofloxacin, chloramphenicol, and azithromycin) are also effective. Much of the recent research geared toward understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial ‘life on the inside’. PMID:25168200

  15. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  16. Restricting wolves risks escape

    Science.gov (United States)

    Mech, L. David; Ballard, Warren; Bangs, Ed; Ream, Bob

    2010-01-01

    Implementing the proposal set forth by Licht and colleagues (BioScience 60: 147–153) requires restricting wolves to tiny "islands," areas that are magnitudes smaller than the ranges of most wolf populations. Wolves naturally have large ranges; restricting their spatial needs increases the risk of wolves escaping, exacerbating public relations and political and legal problems.

  17. Diffusion MRI findings in phenylketonuria

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N. [Dept. of Radiology, Ege Univ. Hospital, Izmir (Turkey)

    2003-12-01

    Two patients with phenylketonuria were studied who were under dietary control since infancy, and who were mentally normal. Diffusion MRI was obtained using a spin-echo, echo-planar sequence with a gradient strength of 30 mT/m at 1.5 T. A trace sequence (TR=5700 ms, and TE=139 ms) was used, acquired in 22 s. Heavily diffusion-weighted (b=1000 mm{sup 2}/s) images, and the apparent diffusion coefficient (ADC) values from automatically generated ADC maps were studied. There were two different patterns in these two patients, restricted and increased diffusion patterns. Restricted diffusion pattern consisted of high-signal on b=1000 s/mm{sup 2} images with low ADC values ranging from 0.46 to 0.57 x 10{sup -3} mm{sup 2}/s. Increased diffusion pattern consisted of normal b=1000 s/mm{sup 2} images with high ADC values ranging from 1.37 to 1.63 x 10{sup -3} mm{sup 2}/s. It is likely that these values reflected presence of two different histopathological changes in phenylketonuria or reflected different stages of the same disease. (orig.)

  18. Diffusion MRI findings in phenylketonuria

    International Nuclear Information System (INIS)

    Sener, R.N.

    2003-01-01

    Two patients with phenylketonuria were studied who were under dietary control since infancy, and who were mentally normal. Diffusion MRI was obtained using a spin-echo, echo-planar sequence with a gradient strength of 30 mT/m at 1.5 T. A trace sequence (TR=5700 ms, and TE=139 ms) was used, acquired in 22 s. Heavily diffusion-weighted (b=1000 mm 2 /s) images, and the apparent diffusion coefficient (ADC) values from automatically generated ADC maps were studied. There were two different patterns in these two patients, restricted and increased diffusion patterns. Restricted diffusion pattern consisted of high-signal on b=1000 s/mm 2 images with low ADC values ranging from 0.46 to 0.57 x 10 -3 mm 2 /s. Increased diffusion pattern consisted of normal b=1000 s/mm 2 images with high ADC values ranging from 1.37 to 1.63 x 10 -3 mm 2 /s. It is likely that these values reflected presence of two different histopathological changes in phenylketonuria or reflected different stages of the same disease. (orig.)

  19. Intracellular localization of Arabidopsis sulfurtransferases.

    Science.gov (United States)

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D; Papenbrock, Jutta

    2004-06-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism.

  20. Nanoparticles for intracellular-targeted drug delivery

    International Nuclear Information System (INIS)

    Paulo, Cristiana S O; Pires das Neves, Ricardo; Ferreira, Lino S

    2011-01-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  1. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    thods of reduction of metal ions using plants or microorganisms are often ... have several advantages over bacteria, they are often pre- ferred. ... in static condition for a period of 7 days. ... work was focused on the production of intracellular gold.

  2. Fractional Diffusion Equations and Anomalous Diffusion

    Science.gov (United States)

    Evangelista, Luiz Roberto; Kaminski Lenzi, Ervin

    2018-01-01

    Preface; 1. Mathematical preliminaries; 2. A survey of the fractional calculus; 3. From normal to anomalous diffusion; 4. Fractional diffusion equations: elementary applications; 5. Fractional diffusion equations: surface effects; 6. Fractional nonlinear diffusion equation; 7. Anomalous diffusion: anisotropic case; 8. Fractional Schrödinger equations; 9. Anomalous diffusion and impedance spectroscopy; 10. The Poisson–Nernst–Planck anomalous (PNPA) models; References; Index.

  3. Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

    DEFF Research Database (Denmark)

    Krabbe, Simon; Engelhart, Merete; Thybo, Sören

    2017-01-01

    This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal......, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma....

  4. From State Dependent Diffusion to Constant Diffusion in Stochastic Differential Equations by the Lamperti Transform

    DEFF Research Database (Denmark)

    Møller, Jan Kloppenborg; Madsen, Henrik

    the Lamperti transform. This note gives an example driven introduction to the Lamperti transform. The general applicability of the Lamperti transform is limited to univariate diffusion processes, but for a restricted class of multivariate diffusion processes Lamperti type transformations are available...

  5. Single quantum dot tracking reveals the impact of nanoparticle surface on intracellular state.

    Science.gov (United States)

    Zahid, Mohammad U; Ma, Liang; Lim, Sung Jun; Smith, Andrew M

    2018-05-08

    Inefficient delivery of macromolecules and nanoparticles to intracellular targets is a major bottleneck in drug delivery, genetic engineering, and molecular imaging. Here we apply live-cell single-quantum-dot imaging and tracking to analyze and classify nanoparticle states after intracellular delivery. By merging trajectory diffusion parameters with brightness measurements, multidimensional analysis reveals distinct and heterogeneous populations that are indistinguishable using single parameters alone. We derive new quantitative metrics of particle loading, cluster distribution, and vesicular release in single cells, and evaluate intracellular nanoparticles with diverse surfaces following osmotic delivery. Surface properties have a major impact on cell uptake, but little impact on the absolute cytoplasmic numbers. A key outcome is that stable zwitterionic surfaces yield uniform cytosolic behavior, ideal for imaging agents. We anticipate that this combination of quantum dots and single-particle tracking can be widely applied to design and optimize next-generation imaging probes, nanoparticle therapeutics, and biologics.

  6. Protein restriction and cancer.

    Science.gov (United States)

    Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong

    2018-03-26

    Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Diffusion processes in dyed detectors

    International Nuclear Information System (INIS)

    Lferde, M.; Seidel, J.-L.; Monnin, M.

    1982-01-01

    In order to get a better understanding of the dyed and fluorescent track detectors, the diffusion speed of the swelling agent, the sensitization molecules and the dye have been measured under various conditions. It is shown that the sensitization affects the entire detector while dyeing is restricted to the upper and lower layers of the detector. By combining the optimal values of the reactions parameters a higher contrast and sensitivity may be achieved. (author)

  8. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    Science.gov (United States)

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  9. Diffusion bonding

    International Nuclear Information System (INIS)

    Anderson, R.C.

    1976-01-01

    A method is described for joining beryllium to beryllium by diffusion bonding. At least one surface portion of at least two beryllium pieces is coated with nickel. A coated surface portion is positioned in a contiguous relationship with another surface portion and subjected to an environment having an atmosphere at a pressure lower than ambient pressure. A force is applied on the beryllium pieces for causing the contiguous surface portions to abut against each other. The contiguous surface portions are heated to a maximum temperature less than the melting temperature of the beryllium, and the applied force is decreased while increasing the temperature after attaining a temperature substantially above room temperature. A portion of the applied force is maintained at a temperature corresponding to about maximum temperature for a duration sufficient to effect the diffusion bond between the contiguous surface portions

  10. Intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-07-01

    Full Text Available It is estimated that the true prevalence of intrauterine growth restriction is 3-10% of all pregnancies, making this fetal condition one of the most frequent obstetric problems, together with premature labor and premature rupture of membranes. The article stresses the importance of early diagnosis because of the associated risks.

  11. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

    Tygesen, Malin Plumhoff; Nielsen, Mette Olaf; Nørgaard, Peder

    2008-01-01

    We investigated the effect of 50% nutrient restriction during the last 6 weeks of gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, ß-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma...

  12. Restricted Variance Interaction Effects

    DEFF Research Database (Denmark)

    Cortina, Jose M.; Köhler, Tine; Keeler, Kathleen R.

    2018-01-01

    Although interaction hypotheses are increasingly common in our field, many recent articles point out that authors often have difficulty justifying them. The purpose of this article is to describe a particular type of interaction: the restricted variance (RV) interaction. The essence of the RV int...

  13. Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy

    International Nuclear Information System (INIS)

    Coppola, S; Pozzi, D; De Sanctis, S Candeloro; Caracciolo, G; Digman, M A; Gratton, E

    2013-01-01

    Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method for characterizing the mode of motion of nanocarriers and for quantifying their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP–DOPC/DNA (DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DOPC: dioleoylphosphocholine) and DC-Chol–DOPE/DNA (DC-Chol: 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol; DOPE: dioleoylphosphatidylethanolamine) lipoplexes in CHO-K1 (CHO: Chinese hamster ovary) live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient: D ≈ 0.003 μm 2 s −1 ). In the cytosol, the lipoplexes’ motion was characterized by active transport with average velocity v ≈ 0.03 μm 2 s −1 and random motion. The method permitted us to generate an intracellular transport map showing several regions of concerted motion of lipoplexes. (paper)

  14. Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy

    Science.gov (United States)

    Coppola, S.; Pozzi, D.; Candeloro De Sanctis, S.; Digman, M. A.; Gratton, E.; Caracciolo, G.

    2013-03-01

    Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method for characterizing the mode of motion of nanocarriers and for quantifying their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP-DOPC/DNA (DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DOPC: dioleoylphosphocholine) and DC-Chol-DOPE/DNA (DC-Chol: 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol; DOPE: dioleoylphosphatidylethanolamine) lipoplexes in CHO-K1 (CHO: Chinese hamster ovary) live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient: D ≈ 0.003 μm2 s-1). In the cytosol, the lipoplexes’ motion was characterized by active transport with average velocity v ≈ 0.03 μm2 s-1 and random motion. The method permitted us to generate an intracellular transport map showing several regions of concerted motion of lipoplexes.

  15. Multipassage diffuser

    International Nuclear Information System (INIS)

    Lalis, A.; Rouviere, R.; Simon, G.

    1976-01-01

    A multipassage diffuser having 2p passages comprises a leak-tight cylindrical enclosure closed by a top cover and a bottom end-wall, parallel porous tubes which are rigidly assembled in sectors between tube plates and through which the gas mixture flows, the tube sectors being disposed at uniform intervals on the periphery of the enclosure. The top tube plates are rigidly fixed to an annular header having the shape of a half-torus and adapted to communicate with the tubes of the corresponding sector. Each passage is constituted by a plurality of juxtaposed sectors in which the mixture circulates in the same direction, the header being divided into p portions limited by radial partition-walls and each constituting two adjacent passages. The diffuser is provided beneath the bottom end-wall with p-1 leak-tight chambers each adapted to open into two different portions of the header, and with two collector-chambers each fitted with a nozzle for introducing the gas mixture and discharging the fraction of the undiffused mixture. By means of a central orifice formed in the bottom end-wall the enclosure communicates with a shaft for discharging the diffused fraction of the gas mixture

  16. Investigating Internalization and Intracellular Trafficking of GPCRs

    DEFF Research Database (Denmark)

    Foster, Simon R; Bräuner-Osborne, Hans

    2017-01-01

    for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling. However, there is accumulating evidence to suggest that GPCRs can signal...... independently of G proteins, as well as from intracellular compartments including endosomes. It is in this context that receptor internalization and intracellular trafficking have attracted renewed interest within the GPCR field. In this chapter, we will review the current understanding and methodologies...

  17. Basic consideration of diffusion/perfusion imaging

    International Nuclear Information System (INIS)

    Tamagawa, Yoichi; Kimura, Hirohiko; Matsuda, Tsuyoshi; Kawamura, Yasutaka; Nakatsugawa, Shigekazu; Ishii, Yasushi; Sakuma, Hajime; Tsukamoto, Tetsuji.

    1990-01-01

    In magnetic resonance imaging (MRI), microscopic motion of biological system such as molecular diffusion of water and microcirculation of blood in the capillary network (perfusion) has been proposed to cause signal attenuation as an intravoxel incoherent motion (IVIM). Quantitative imaging of the IVIM phenomenon was attempted to generate from a set of spin-echo (SE) sequences with or without sensitization by motion probing gradient (MPG). The IVIM imaging is characterized by a parameter, apparent diffusion coefficient (ADC), which is an integration of both the diffusion and the perfusion factor on voxel-by-voxel basis. Hard ware was adjusted to avoid image artifact mainly produced by eddy current. Feasibility of the method was tested using bottle phantom filled with water at different temperature and acetone, and the calculated ADC values of these media corresponded well with accepted values of diffusion. The method was then applied to biological system to investigate mutual participation of diffusion/perfusion on the ADC value. The result of tumor model born on nude mouse suggested considerable participation of perfusion factor which immediately disappeared after sacrificing the animal. Meanwhile, lower value of sacrificed tissue without microcirculation was suggested to have some restriction of diffusion factor by biological tissue. To substantiate the restriction effect on the diffusion, a series of observation have made on a fiber phantom, stalk of celory with botanical fibers and human brain with nerve fibers, in applying unidirectional MPG along the course of these banch of fiber system. The directional restriction effect of diffusion along the course of fiber (diffusion anisotrophy) was clearly visualized as directional change of ADC value. The present method for tissue characterization by diffusion/perfusion on microscopic level will provide a new insight for evaluation of functional derangement in human brain and other organs. (author)

  18. Cationic polymers for intracellular delivery of proteins

    NARCIS (Netherlands)

    Coué, G.M.J.P.C.; Engbersen, Johannes F.J.; Samal, Sangram; Dubruel, Peter

    2015-01-01

    Many therapeutic proteins exert their pharmaceutical action inside the cytoplasm or onto individual organelles inside the cell. Intracellular protein delivery is considered to be the most direct, fastest and safest approach for curing gene-deficiency diseases, enhancing vaccination and triggering

  19. Molecular detection and characterization of sustainable intracellular ...

    African Journals Online (AJOL)

    3Centre for Biopolymer and Bio-Molecular Research, Athlone College of Technology, Republic of Ireland. ... cells was associated with the elongation of micro-villar extension that ... Keywords: Intracellular contaminants, cell cultures, bacteria culture, pre-clinical studies. ... production work involving culture technology.

  20. Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

    Science.gov (United States)

    Hafner, Anne E.; Rieger, Heiko

    2018-03-01

    The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

  1. Biological synthesis and characterization of intracellular gold ...

    Indian Academy of Sciences (India)

    In the present study, Aspergillus fumigatus was used for the intracellular synthesis of gold nanoparticles. Stable nanoparticles were produced when an aqueous solution of chloroauric acid (HAuCl4) was reduced by A. fumigatus biomass as the reducing agent. Production of nanoparticles was confirmed by the colour ...

  2. Membrane barriers for radon gas flow restrictions

    International Nuclear Information System (INIS)

    Archibald, J.F.

    1984-08-01

    Research was performed to assess the feasibility of barrier membrane substances, for use within mining or associated high risk environments, in restricting the diffusion transport of radon gas quantities. Specific tests were conducted to determine permeability parameters of a variety of membrane materials with reference to radon flow capabilities. Tests were conducted both within laboratory and in-situ emanation environments where concentrations and diffusion flows of radon gas were known to exist. Equilibrium radon gas concentrations were monitored in initially radon-free chambers adjacent to gas sources, but separated by specified membrane substances. Membrane barrier effectiveness was demonstrated to result in reduced emanation concentrations of radon gas within the sampling chamber atmosphere. Minimum gas concentrations were evidenced where the barrier membrane material was shown to exhibit lowest radon permeability characteristics

  3. Quantum diffusion

    International Nuclear Information System (INIS)

    Habib, S.

    1994-01-01

    We consider a simple quantum system subjected to a classical random force. Under certain conditions it is shown that the noise-averaged Wigner function of the system follows an integro-differential stochastic Liouville equation. In the simple case of polynomial noise-couplings this equation reduces to a generalized Fokker-Planck form. With nonlinear noise injection new ''quantum diffusion'' terms rise that have no counterpart in the classical case. Two special examples that are not of a Fokker-Planck form are discussed: the first with a localized noise source and the other with a spatially modulated noise source

  4. Optimizing Nanoelectrode Arrays for Scalable Intracellular Electrophysiology.

    Science.gov (United States)

    Abbott, Jeffrey; Ye, Tianyang; Ham, Donhee; Park, Hongkun

    2018-03-20

    Electrode technology for electrophysiology has a long history of innovation, with some decisive steps including the development of the voltage-clamp measurement technique by Hodgkin and Huxley in the 1940s and the invention of the patch clamp electrode by Neher and Sakmann in the 1970s. The high-precision intracellular recording enabled by the patch clamp electrode has since been a gold standard in studying the fundamental cellular processes underlying the electrical activities of neurons and other excitable cells. One logical next step would then be to parallelize these intracellular electrodes, since simultaneous intracellular recording from a large number of cells will benefit the study of complex neuronal networks and will increase the throughput of electrophysiological screening from basic neurobiology laboratories to the pharmaceutical industry. Patch clamp electrodes, however, are not built for parallelization; as for now, only ∼10 patch measurements in parallel are possible. It has long been envisioned that nanoscale electrodes may help meet this challenge. First, nanoscale electrodes were shown to enable intracellular access. Second, because their size scale is within the normal reach of the standard top-down fabrication, the nanoelectrodes can be scaled into a large array for parallelization. Third, such a nanoelectrode array can be monolithically integrated with complementary metal-oxide semiconductor (CMOS) electronics to facilitate the large array operation and the recording of the signals from a massive number of cells. These are some of the central ideas that have motivated the research activity into nanoelectrode electrophysiology, and these past years have seen fruitful developments. This Account aims to synthesize these findings so as to provide a useful reference. Summing up from the recent studies, we will first elucidate the morphology and associated electrical properties of the interface between a nanoelectrode and a cellular membrane

  5. Hereditary Diffuse Gastric Cancer

    Science.gov (United States)

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

  6. Diffusion-weighted MR imaging findings in carbon monoxide poisoning

    International Nuclear Information System (INIS)

    Teksam, M.; Casey, S.O.; Michel, E.; Liu, H.; Truwit, C.L.

    2002-01-01

    Diffusion-weighted MR imaging (DWI) of two patients with carbon monoxide (CO) poisoning demonstrated white matter and cortical hyperintensities. In one patient, the changes on the FLAIR sequence were more subtle than those on DWI. The DWI abnormality in this patient represented true restriction. In the second patient, repeated exposure to CO caused restricted diffusion. DWI may be helpful for earlier identification of the changes of acute CO poisoning. (orig.)

  7. On uniqueness in diffuse optical tomography

    International Nuclear Information System (INIS)

    Harrach, Bastian

    2009-01-01

    A prominent result of Arridge and Lionheart (1998 Opt. Lett. 23 882–4) demonstrates that it is in general not possible to simultaneously recover both the diffusion (aka scattering) and the absorption coefficient in steady-state (dc) diffusion-based optical tomography. In this work we show that it suffices to restrict ourselves to piecewise constant diffusion and piecewise analytic absorption coefficients to regain uniqueness. Under this condition both parameters can simultaneously be determined from complete measurement data on an arbitrarily small part of the boundary

  8. Vector-free intracellular delivery by reversible permeabilization.

    Directory of Open Access Journals (Sweden)

    Shirley O'Dea

    Full Text Available Despite advances in intracellular delivery technologies, efficient methods are still required that are vector-free, can address a wide range of cargo types and can be applied to cells that are difficult to transfect whilst maintaining cell viability. We have developed a novel vector-free method that uses reversible permeabilization to achieve rapid intracellular delivery of cargos with varying composition, properties and size. A permeabilizing delivery solution was developed that contains a low level of ethanol as the permeabilizing agent. Reversal of cell permeabilization is achieved by temporally and volumetrically controlling the contact of the target cells with this solution. Cells are seeded in conventional multi-well plates. Following removal of the supernatant, the cargo is mixed with the delivery solution and applied directly to the cells using an atomizer. After a short incubation period, permeabilization is halted by incubating the cells in a phosphate buffer saline solution that dilutes the ethanol and is non-toxic to the permeabilized cells. Normal culture medium is then added. The procedure lasts less than 5 min. With this method, proteins, mRNA, plasmid DNA and other molecules have been delivered to a variety of cell types, including primary cells, with low toxicity and cargo functionality has been confirmed in proof-of-principle studies. Co-delivery of different cargo types has also been demonstrated. Importantly, delivery occurs by diffusion directly into the cytoplasm in an endocytic-independent manner. Unlike some other vector-free methods, adherent cells are addressed in situ without the need for detachment from their substratum. The method has also been adapted to address suspension cells. This delivery method is gentle yet highly reproducible, compatible with high throughput and automated cell-based assays and has the potential to enable a broad range of research, drug discovery and clinical applications.

  9. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

    Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

  10. Turbulent diffusion of small particles

    International Nuclear Information System (INIS)

    Margolin, L.G.

    1977-11-01

    The diffusion of small, spherical, rigid particles suspended in an incompressible turbulent fluid, but not interacting with each other, was studied. As a stochastic process, the turbulent fluid velocity field is assumed to be homogeneous, isotropic and stationary. Assuming the Stokes regime, a particle of equation of motion is used which includes only the effects of Stokes drag and a virtual mass force and an exact solution is found for the particle velocity correlation function, for all times and initial conditions, in terms of a fluid velocity correlation function measured along the motion of the particle. This shows that for times larger than a certain time scale, the particle velocity correlation becomes stationary. The effect of small shears in the fluid velocity was considered, under the additional restrictions of a certain high frequency regime for the turbulence. The shears convected past the particle much faster than the growth of the boundary layer. New force terms due to the presence of such shears are calculated and incorporated into the equation of motion. A perturbation solution to this equation is constructed, and the resultant particle velocity correlation function and diffusion coefficient are calculated. To lowest order, the particle diffusivity is found to be unaltered by the presence of small mean flow shears. The last model treated is one in which particles traverse a turbulent fluid with a large mean velocity. Among other restrictions, linearized form drag is assumed. The diffusion coefficient for such particles was calculated, and found to be much smaller than the passive scalar diffusion coefficient. This agrees within 5 percent with the experimental results of Snyder and Lumley

  11. Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

    Science.gov (United States)

    Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

    2017-12-01

    Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

  12. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-05-01

    The intracellular glutathione (GSH) content in HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulfoximine (BSO) or diethyl maleate (DEM). Clonogenicity, single strand DNA breaks (ssb) and double strand DNA breaks (dsb) were used as criteria for radiation induced damage after X- or γ irradiation. In survival experiments DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the OER was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (Auth.)

  13. Reduction of intracellular glutathione content and radiosensitivity

    International Nuclear Information System (INIS)

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-01-01

    The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or γ-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (author)

  14. Intracellular mechanisms of solar water disinfection

    Science.gov (United States)

    Castro-Alférez, María; Polo-López, María Inmaculada; Fernández-Ibáñez, Pilar

    2016-12-01

    Solar water disinfection (SODIS) is a zero-cost intervention measure to disinfect drinking water in areas of poor access to improved water sources, used by more than 6 million people in the world. The bactericidal action of solar radiation in water has been widely proven, nevertheless the causes for this remain still unclear. Scientific literature points out that generation of reactive oxygen species (ROS) inside microorganisms promoted by solar light absorption is the main reason. For the first time, this work reports on the experimental measurement of accumulated intracellular ROS in E. coli during solar irradiation. For this experimental achievement, a modified protocol based on the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA), widely used for oxidative stress in eukaryotic cells, has been tested and validated for E. coli. Our results demonstrate that ROS and their accumulated oxidative damages at intracellular level are key in solar water disinfection.

  15. Flow cytometric analysis of cell-surface and intracellular antigens in leukemia diagnosis.

    Science.gov (United States)

    Knapp, W; Strobl, H; Majdic, O

    1994-12-15

    New technology allows highly sensitive flow cytometric detection and quantitative analysis of intracellular antigens in normal and malignant hemopoietic cells. With this technology, the earliest stages of myeloid and lymphoid differentiation can easily and reliably be identified using antibodies directed against (pro-)myeloperoxidase/MPO, CD22 and CD3 antigens, respectively. Particularly for the analysis of undifferentiated acute myeloblastic leukemia (AML) cells, the immunological demonstration of intracellular MPO or its enzymatically inactive proforms is highly relevant, since other myeloid marker molecules such as CD33, CD13, or CDw65 are either not restricted to the granulomonocytic lineage or appear later in differentiation. By combining MPO staining with staining for lactoferrin (LF), undifferentiated cells can be distinguished from the granulomonocytic maturation compartment in bone marrow, since LF is selectively expressed from the myelocyte stage of differentiation onward. The list of informative intracellular antigens to be used in leukemia cell analysis will certainly expand in the near future. One candidate, intracellular CD68, has already been tested by us, and results are presented. Also dealt within this article are surface marker molecules not (as yet) widely used in leukemia cell analysis but with the potential to provide important additional information. Among them are the surface structures CD15, CD15s, CDw65, CD79a (MB-1), CD79b (B29), CD87 (uPA-R), and CD117 (c-kit).

  16. Intracellular serpins, firewalls and tissue necrosis.

    Science.gov (United States)

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

  17. Fluorescent nanoparticles for intracellular sensing: A review

    International Nuclear Information System (INIS)

    Ruedas-Rama, Maria J.; Walters, Jamie D.; Orte, Angel; Hall, Elizabeth A.H.

    2012-01-01

    Highlights: ► Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. ► Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. ► Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  18. Fluorescent nanoparticles for intracellular sensing: A review

    Energy Technology Data Exchange (ETDEWEB)

    Ruedas-Rama, Maria J., E-mail: mjruedas@ugr.esmailto [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Walters, Jamie D. [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QT (United Kingdom); Orte, Angel [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Hall, Elizabeth A.H., E-mail: lisa.hall@biotech.cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT (United Kingdom)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. Black-Right-Pointing-Pointer Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. Black-Right-Pointing-Pointer Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  19. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  20. A bacteriophage endolysin that eliminates intracellular streptococci

    Science.gov (United States)

    Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

    2016-01-01

    PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB–PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities. DOI: http://dx.doi.org/10.7554/eLife.13152.001 PMID:26978792

  1. Delayed onset Mycobacterium intracellulare keratitis after laser in situ keratomileusis: A case report and literature review.

    Science.gov (United States)

    Ko, JaeSang; Kim, Se Kyung; Yong, Dong Eun; Kim, Tae-Im; Kim, Eung Kweon

    2017-12-01

    Infectious keratitis is a relatively uncommon but potentially sight-threatening complication of laser in situ keratomileusis (LASIK). Mycobacterial keratitis is usually regarded as late onset keratitis among post-LASIK keratitis. There has been no documented case of Mycobacterium intracellulare post-LASIK keratitis of a long-latent period. A 36-year-old man was referred to our out-patient clinic, for persistent corneal epithelial defect with intrastromal infiltration. He had undergone uneventful bilateral LASIK procedure 4 years before. He complained decreased vision, accompanied by ocular pain, photophobia, and redness in his left eye for 7 months. Lamellar keratectomy was taken using femtosecond laser. Bacterial culture with sequenced bacterial 16s ribosomal DNA confirmed the organism to be M intracellulare. After 3 months of administration of topical clarithromycin, amikacin, and moxifloxacin, the corneal epithelial defect was resolved and the infiltration was much improved. However, newly developed diffuse haziness with surrounding granular infiltration in the central cornea was noted. Drug toxicity was suspected and topical moxifloxacin was discontinued, resulting in resolution of the diffuse haze with infiltration. The patient was followed up regularly without medication thereafter and recurrence was not found for 7 years. This case presents the first case of M intracellulare keratitis after LASIK. LASIK surgeons should aware that post-LASIK keratitis can develop long after the operation and careful suspicion of infectious disease with meticulous diagnostic test is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  2. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    relies on sampling based approximations of the log-likelihood gradient. I will present an empirical and theoretical analysis of the bias of these approximations and show that the approximation error can lead to a distortion of the learning process. The bias decreases with increasing mixing rate......Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...... of the applied sampling procedure and I will introduce a transition operator that leads to faster mixing. Finally, a different parametrisation of RBMs will be discussed that leads to better learning results and more robustness against changes in the data representation....

  3. Diffusion archeology for diffusion progression history reconstruction.

    Science.gov (United States)

    Sefer, Emre; Kingsford, Carl

    2016-11-01

    Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring - perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data.

  4. The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Charles Godbout

    Full Text Available Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.

  5. Protection of Dentate Hilar Cells from Prolonged Stimulation by Intracellular Calcium Chelation

    Science.gov (United States)

    Scharfman, Helen E.; Schwartzkroin, Philip A.

    1989-10-01

    Prolonged afferent stimulation of the rat dentate gyrus in vivo leads to degeneration only of those cells that lack immunoreactivity for the calcium binding proteins parvalbumin and calbindin. In order to test the hypothesis that calcium binding proteins protect against the effects of prolonged stimulation, intracellular recordings were made in hippocampal slices from cells that lack immunoreactivity for calcium binding proteins. Calcium binding protein--negative cells showed electrophysiological signs of deterioration during prolonged stimulation; cells containing calcium binding protein did not. When neurons without calcium binding proteins were impaled with microelectrodes containing the calcium chelator BAPTA, and BAPTA was allowed to diffuse into the cells, these cells showed no deterioration. These results indicate that, in a complex tissue of the central nervous system, an activity-induced increase in intracellular calcium can trigger processes leading to cell deterioration, and that increasing the calcium binding capacity of a cell decreases its vulnerability to damage.

  6. Diffusion-weighted MR images and pineoblastoma. Diagnosis and follow-up

    International Nuclear Information System (INIS)

    Gasparetto, Emerson L.; Cruz Junior, L. Celso Hygino; Doring, Thomas M.; Domingues, Romeu C.; Araujo, Bertha; Dantas, Mario Alberto; Chimelli, Leila

    2008-01-01

    Pineoblastomas are uncommon pineal tumors, which demonstrate rapid growing and poor prognosis. We report the case of a 43-year-old man with an enhancing pineal region mass, which showed restriction of the diffusion on diffusion-weighted (DW) MR images. The surgical biopsy defined the diagnosis of pineoblastoma and the therapy was initiated with radiation and chemotherapy. Three months later, the follow-up MR imaging showed areas suggestive of necrosis and the DW images demonstrate no significant areas of restricted diffusion. The differential diagnosis of pineal region masses that could show restriction of diffusion is discussed. (author)

  7. Diffusion inside living human cells

    DEFF Research Database (Denmark)

    Leijnse, N.; Jeon, J. -H.; Loft, Steffen

    2012-01-01

    of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell...... cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center...

  8. Modeling Intracellular Oscillations and Polarity Transition in Fission Yeast

    Science.gov (United States)

    Drake, Tyler; Das, Maitreyi; Verde, Fulvia; Vavylonis, Dimitrios

    2011-03-01

    Fission yeast, a pill-shaped model organism, restricts growth to its tips. These cells maintain an asymmetric growth state, growing at only one tip, until they meet length and cell-cycle requirements. With these met, they grow at both. The mechanism of this transition, new-end take-off (NETO), remains unclear. We find that NETO occurs due to long-range competition for fast-diffusing signaling protein Cdc42 between the old and new tips. From experimental results, we suppose that symmetric tips compete for Cdc42, which triggers growth. We describe a symmetric growth model based on competition between tips. This model restricts short cells to monopolar states while allowing longer cells to be bipolar. Autocatalytic Cdc42 recruiting at both cells tips leads to broken symmetry, and the recruiting cuts off as tip Cdc42 levels saturate. Non-linear differential equations describe the model, with stable attractors indicating valid distributions. Linear stability analysis and numerical methods identify stable fixed points over a twofold increase in cell length. The model reproduces qualitative behavior of the organism. We show that observed pole-to-pole Cdc42 oscillations may facilitate the polarity transition and discuss their relationship to the Min system in E. Coli.

  9. Azithromycin effectiveness against intracellular infections of Francisella

    Directory of Open Access Journals (Sweden)

    Mann Barbara J

    2010-04-01

    Full Text Available Abstract Background Macrolide antibiotics are commonly administered for bacterial respiratory illnesses. Azithromycin (Az is especially noted for extremely high intracellular concentrations achieved within macrophages which is far greater than the serum concentration. Clinical strains of Type B Francisella (F. tularensis have been reported to be resistant to Az, however our laboratory Francisella strains were found to be sensitive. We hypothesized that different strains/species of Francisella (including Type A may have different susceptibilities to Az, a widely used and well-tolerated antibiotic. Results In vitro susceptibility testing of Az confirmed that F. tularensis subsp. holarctica Live Vaccine Strain (LVS (Type B was not sensitive while F. philomiragia, F. novicida, and Type A F. tularensis (NIH B38 and Schu S4 strain were susceptible. In J774A.1 mouse macrophage cells infected with F. philomiragia, F. novicida, and F. tularensis LVS, 5 μg/ml Az applied extracellularly eliminated intracellular Francisella infections. A concentration of 25 μg/ml Az was required for Francisella-infected A549 human lung epithelial cells, suggesting that macrophages are more effective at concentrating Az than epithelial cells. Mutants of RND efflux components (tolC and ftlC in F. novicida demonstrated less sensitivity to Az by MIC than the parental strain, but the tolC disc-inhibition assay demonstrated increased sensitivity, indicating a complex role for the outer-membrane transporter. Mutants of acrA and acrB mutants were less sensitive to Az than the parental strain, suggesting that AcrAB is not critical for the efflux of Az in F. novicida. In contrast, F. tularensis Schu S4 mutants ΔacrB and ΔacrA were more sensitive than the parental strain, indicating that the AcrAB may be important for Az efflux in F. tularensis Schu S4. F. novicida LPS O-antigen mutants (wbtN, wbtE, wbtQ and wbtA were found to be less sensitive in vitro to Az compared to the wild

  10. Excess Entropy and Diffusivity

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Excess Entropy and Diffusivity. Excess entropy scaling of diffusivity (Rosenfeld,1977). Analogous relationships also exist for viscosity and thermal conductivity.

  11. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  12. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  13. About 'restriction', 'justified' and 'necessary'

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2016-01-01

    The article is an academic fairy tale about why and how all national corporate tax protection legislation should undergo a 3-part test to ensure its consistency with EU law. Each Member State introduce a compulsory 3-step test for each new (corporate) tax provision. The test is simple: (1) Does...... the tax provision constitute a restriction in the sense of EU law? (2) If the answer is yes: Is the restriction justified? (3) If the answer is yes: Is the restriction necessary?"...

  14. 1H diffusion-weighted, 13C and 17O NMR spectroscopy: methodological developments to study brain structure and function in vivo

    International Nuclear Information System (INIS)

    Najac, Chloe

    2014-01-01

    Magnetic Resonance Spectroscopy is a unique tool that allows acquiring brain biochemical profiles and quantifying many cellular parameters in vivo. During this thesis, three different techniques have been developed: (i) 1 H diffusion-weighted, (ii) carbon-13 ( 13 C) and (iii) oxygen-17 ( 17 O) NMR spectroscopy to study brain structure and function in vivo. Brain metabolites are cell-specific endogenous tracers of the intracellular space whose translational diffusion depends on many cellular properties (e.g.: cytosol viscosity and intracellular restriction). Studying the variation of the diffusion coefficient (ADC) as a function of diffusion time (td) allows untangling and quantifying those parameters. In particular, measuring metabolites ADC at long diffusion times gives information about the metabolites compartmentation in cells. In a first study, we measured neuronal and astrocytic metabolites ADC over a large time window (from 80 ms to 1 s) in a large voxel in the macaque brain. No dependence of all metabolites ADC on td was observed suggesting that metabolites primarily diffuse in neuronal (dendrites and axons) and astrocytic processes and are not confined inside the cell body and organelles (nucleus, mitochondria). The large size of the voxel, due to low detection sensitivity, did not allow us to study metabolites compartmentation in pure white (WM) and grey matters (GM). Therefore, we performed a new study in the human brain. Results showed that in both WM and GM metabolites diffuse in fiber-like cell structure. Finally, using an even larger time window (up to 2 s) in the macaque brain and analytical models mimicking the cell structure, we estimated the length of neuronal (∼110 μm) and astrocytic (∼70 μm) processes. ATP (adenosine triphosphate), the main source of energy in the organism, is produced thanks to glucose oxidation inside the mitochondria. 13 C NMR spectroscopy is a well-known technique to study brain energy metabolism and can be used to

  15. Intracellular bacteria: the origin of dinoflagellate toxicity.

    Science.gov (United States)

    Silva, E S

    1990-01-01

    Dinoflagellate blooms of the same species have been registered either as toxic or nontoxic and, in the latter case, toxicity may be of different types. A hypothesis has been formulated according to which the bacteria having in some way taken part in the toxin formation are either inside the dinoflagellate cell or in the nutritive liquid. The presence of intracellular bacteria in those microorganisms has been studied mainly in material from cultures, a few from the sea, and several strains were isolated from different species. Experiments with crossed inoculations have shown that the bacterial strain from Gonyaulax tamarensis caused the cells of some other species to become toxic. From nontoxic clonal cultures of Prorocentrum balticum, Glenodinium foliaceum, and Gyrodinium instriatum, after inoculation of that bacterial strain, cultures were obtained whose cell extracts showed the same kind of toxicity as G. tamarensis. No toxic action could be found in the extracts of the bacterial cells form the assayed strains. The interference of intracellular bacteria in the metabolism of dinoflagellates must be the main cause of their toxicity.

  16. Fluorescent nanoparticles for intracellular sensing: a review.

    Science.gov (United States)

    Ruedas-Rama, Maria J; Walters, Jamie D; Orte, Angel; Hall, Elizabeth A H

    2012-11-02

    Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Mechanisms of cellular invasion by intracellular parasites.

    Science.gov (United States)

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  18. [Intracellular signaling mechanisms in thyroid cancer].

    Science.gov (United States)

    Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

    2016-01-01

    Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  19. Model analysis of the relationship between intracellular Po2 and energy demand in skeletal muscle

    OpenAIRE

    Spires, Jessica; Gladden, L. Bruce; Grassi, Bruno; Saidel, Gerald M.; Lai, Nicola

    2012-01-01

    On the basis of experimental studies, the intracellular O2 (iPo2)-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo2 reached a plateau at 60% of maximal WR, while another found that iPo2 decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O2 gradient, respectively, as alternative dominant factors for determining O2 diffusion changes during exercise. This relationship is affected by several factors, including...

  20. Monitoring changes in the intracellular calcium concentration and synaptic efficacy in the mollusc Aplysia.

    Science.gov (United States)

    Ludwar, Bjoern Ch; Evans, Colin G; Cropper, Elizabeth C

    2012-07-15

    It has been suggested that changes in intracellular calcium mediate the induction of a number of important forms of synaptic plasticity (e.g., homosynaptic facilitation). These hypotheses can be tested by simultaneously monitoring changes in intracellular calcium and alterations in synaptic efficacy. We demonstrate how this can be accomplished by combining calcium imaging with intracellular recording techniques. Our experiments are conducted in a buccal ganglion of the mollusc Aplysia californica. This preparation has a number of experimentally advantageous features: Ganglia can be easily removed from Aplysia and experiments use adult neurons that make normal synaptic connections and have a normal ion channel distribution. Due to the low metabolic rate of the animal and the relatively low temperatures (14-16 °C) that are natural for Aplysia, preparations are stable for long periods of time. To detect changes in intracellular free calcium we will use the cell impermeant version of Calcium Orange which is easily 'loaded' into a neuron via iontophoresis. When this long wavelength fluorescent dye binds to calcium, fluorescence intensity increases. Calcium Orange has fast kinetic properties and, unlike ratiometric dyes (e.g., Fura 2), requires no filter wheel for imaging. It is fairly photo stable and less phototoxic than other dyes (e.g., fluo-3). Like all non-ratiometric dyes, Calcium Orange indicates relative changes in calcium concentration. But, because it is not possible to account for changes in dye concentration due to loading and diffusion, it can not be calibrated to provide absolute calcium concentrations. An upright, fixed stage, compound microscope was used to image neurons with a CCD camera capable of recording around 30 frames per second. In Aplysia this temporal resolution is more than adequate to detect even a single spike induced alteration in the intracellular calcium concentration. Sharp electrodes are simultaneously used to induce and record

  1. Diffusing diffusivity: Rotational diffusion in two and three dimensions

    Science.gov (United States)

    Jain, Rohit; Sebastian, K. L.

    2017-06-01

    We consider the problem of calculating the probability distribution function (pdf) of angular displacement for rotational diffusion in a crowded, rearranging medium. We use the diffusing diffusivity model and following our previous work on translational diffusion [R. Jain and K. L. Sebastian, J. Phys. Chem. B 120, 3988 (2016)], we show that the problem can be reduced to that of calculating the survival probability of a particle undergoing Brownian motion, in the presence of a sink. We use the approach to calculate the pdf for the rotational motion in two and three dimensions. We also propose new dimensionless, time dependent parameters, αr o t ,2 D and αr o t ,3 D, which can be used to analyze the experimental/simulation data to find the extent of deviation from the normal behavior, i.e., constant diffusivity, and obtain explicit analytical expressions for them, within our model.

  2. Diffusion in solids

    International Nuclear Information System (INIS)

    Tiwari, G.P.; Kale, G.B.; Patil, R.V.

    1999-01-01

    The article presents a brief survey of process of diffusion in solids. It is emphasised that the essence of diffusion is the mass transfer through the atomic jumps. To begin with formal equations for diffusion coefficient are presented. This is followed by discussions on mechanisms of diffusion. Except for solutes which form interstitial solid solution, diffusion in majority of cases is mediated through exchange of sites between an atom and its neighbouring vacancy. Various vacancy parameters such as activation volume, correlation factor, mass effect etc are discussed and their role in establishing the mode of diffusion is delineated. The contribution of dislocations and grain boundaries in diffusion process is brought out. The experimental determination of different types of diffusion coefficients are described. Finally, the pervasive nature of diffusion process in number of commercial processes is outlined to show the importance of diffusion studies in materials science and technology. (author)

  3. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

    Science.gov (United States)

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F. L.; Leonhardt, Heinrich

    2018-01-01

    Abstract Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. PMID:28913971

  4. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    Science.gov (United States)

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  5. Intracellular pH in sperm physiology.

    Science.gov (United States)

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.

    Science.gov (United States)

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F L; Leonhardt, Heinrich; Hackenberger, Christian P R

    2018-02-23

    Nanobodies can be seen as next-generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site-specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  7. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  8. Intracellular sphingosine releases calcium from lysosomes.

    Science.gov (United States)

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  9. Wave failure at strong coupling in intracellular C a2 + signaling system with clustered channels

    Science.gov (United States)

    Li, Xiang; Wu, Yuning; Gao, Xuejuan; Cai, Meichun; Shuai, Jianwei

    2018-01-01

    As an important intracellular signal, C a2 + ions control diverse cellular functions. In this paper, we discuss the C a2 + signaling with a two-dimensional model in which the inositol 1,4,5-trisphosphate (I P3 ) receptor channels are distributed in clusters on the endoplasmic reticulum membrane. The wave failure at large C a2 + diffusion coupling is discussed in detail in the model. We show that with varying model parameters the wave failure is a robust behavior with either deterministic or stochastic channel dynamics. We suggest that the wave failure should be a general behavior in inhomogeneous diffusing systems with clustered excitable regions and may occur in biological C a2 + signaling systems.

  10. Aging, adiposity, and calorie restriction.

    Science.gov (United States)

    Fontana, Luigi; Klein, Samuel

    2007-03-07

    Excessive calorie intake and subsequent obesity increases the risk of developing chronic disease and decreases life expectancy. In rodent models, calorie restriction with adequate nutrient intake decreases the risk of developing chronic disease and extends maximum life span. To evaluate the physiological and clinical implications of calorie restriction with adequate nutrient intake. Search of PubMed (1966-December 2006) using terms encompassing various aspects of calorie restriction, dietary restriction, aging, longevity, life span, adiposity, and obesity; hand search of journals that focus on obesity, geriatrics, or aging; and search of reference lists of pertinent research and review articles and books. Reviewed reports (both basic science and clinical) included epidemiologic studies, case-control studies, and randomized controlled trials, with quality of data assessed by taking into account publication in a peer-reviewed journal, number of animals or individuals studied, objectivity of measurements, and techniques used to minimize bias. It is not known whether calorie restriction extends maximum life span or life expectancy in lean humans. However, calorie restriction in adult men and women causes many of the same metabolic adaptations that occur in calorie-restricted rodents and monkeys, including decreased metabolic, hormonal, and inflammatory risk factors for diabetes, cardiovascular disease, and possibly cancer. Excessive calorie restriction causes malnutrition and has adverse clinical effects. Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known. In addition, it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat.

  11. [Limbic encephalitis with antibodies against intracellular antigens].

    Science.gov (United States)

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

    Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

  12. Diffusion archeology for diffusion progression history reconstruction

    OpenAIRE

    Sefer, Emre; Kingsford, Carl

    2015-01-01

    Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring — perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial d...

  13. Diffusion of oriented particles in porous media

    Energy Technology Data Exchange (ETDEWEB)

    Haber, René [Institut für Physik, Technische Universität Chemnitz, D-09107 Chemnitz (Germany); Centre for Nonlinear Studies, Institute of Cybernetics at Tallinn University of Technology, Akadeemia tee 21, 12618 Tallinn (Estonia); Prehl, Janett [Institut für Physik, Technische Universität Chemnitz, D-09107 Chemnitz (Germany); Herrmann, Heiko [Centre for Nonlinear Studies, Institute of Cybernetics at Tallinn University of Technology, Akadeemia tee 21, 12618 Tallinn (Estonia); Hoffmann, Karl Heinz, E-mail: hoffmann@physik.tu-chemnitz.de [Institut für Physik, Technische Universität Chemnitz, D-09107 Chemnitz (Germany)

    2013-11-29

    Diffusion of particles in porous media often shows subdiffusive behavior. Here, we analyze the dynamics of particles exhibiting an orientation. The features we focus on are geometrical restrictions and the dynamical consequences of the interactions between the local surrounding structure and the particle orientation. This interaction can lead to particles getting temporarily stuck in parts of the structure. Modeling this interaction by a particular random walk dynamics on fractal structures we find that the random walk dimension is not affected while the diffusion constant shows a variety of interesting and surprising features.

  14. Diffusion of oriented particles in porous media

    International Nuclear Information System (INIS)

    Haber, René; Prehl, Janett; Herrmann, Heiko; Hoffmann, Karl Heinz

    2013-01-01

    Diffusion of particles in porous media often shows subdiffusive behavior. Here, we analyze the dynamics of particles exhibiting an orientation. The features we focus on are geometrical restrictions and the dynamical consequences of the interactions between the local surrounding structure and the particle orientation. This interaction can lead to particles getting temporarily stuck in parts of the structure. Modeling this interaction by a particular random walk dynamics on fractal structures we find that the random walk dimension is not affected while the diffusion constant shows a variety of interesting and surprising features.

  15. Single-cell intracellular nano-pH probes†

    OpenAIRE

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular p...

  16. Can we restrict the health care menu?

    Science.gov (United States)

    Klein, R

    1994-02-01

    The case of Britain's National Health Service is used to illuminate the cross-national debate about whether the availability of health care should be restricted and, if so, how this should be done. Traditionally, the NHS relied on implicit rationing by clinicians within budgetary constraints set by government. However, the logic of the 1989 reforms appeared to require explicit decisions about the packages of health care to be provided to local populations. In practice, purchasers have refused to define such packages. Explicit rationing remains very much the exception. Exploring the reasons for this suggests that defining a restricted menu of health care, by adopting a cost-utility approach and excluding specific procedures or forms of treatment on the Oregon model, is only one of many policy options. There is a large repertory of policy tools for balancing demands and resources, ranging from diluting the intensity of treatment to its earlier termination. Given that health care is characterised by uncertainty, lack of information about outcomes and patient heterogeneity, it may therefore be more 'rational' to diffuse decision-making among clinicians and managers than to try to move towards a centrally determined menu of entitlements.

  17. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    KAUST Repository

    Knodel, Markus

    2017-10-02

    Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

  18. Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers

    Directory of Open Access Journals (Sweden)

    Muriaux Delphine

    2007-08-01

    Full Text Available Abstract Background The HIV-1 nucleocapsid protein (NC is formed of two CCHC zinc fingers flanked by highly basic regions. HIV-1 NC plays key roles in virus structure and replication via its nucleic acid binding and chaperoning properties. In fact, NC controls proviral DNA synthesis by reverse transcriptase (RT, gRNA dimerization and packaging, and virion assembly. Results We previously reported a role for the first NC zinc finger in virion structure and replication 1. To investigate the role of both NC zinc fingers in intracellular Gag trafficking, and in virion assembly, we generated series of NC zinc fingers mutations. Results show that all Zinc finger mutations have a negative impact on virion biogenesis and maturation and rendered defective the mutant viruses. The NC zinc finger mutations caused an intracellular accumulation of Gag, which was found either diffuse in the cytoplasm or at the plasma membrane but not associated with endosomal membranes as for wild type Gag. Evidences are also provided showing that the intracellular interactions between NC-mutated Gag and the gRNA were impaired. Conclusion These results show that Gag oligomerization mediated by gRNA-NC interactions is required for correct Gag trafficking, and assembly in HIV-1 producing cells and the release of infectious viruses.

  19. Effect of serum proteins on polystyrene nanoparticle uptake and intracellular trafficking in endothelial cells

    International Nuclear Information System (INIS)

    Guarnieri, Daniela; Guaccio, Angela; Fusco, Sabato; Netti, Paolo A.

    2011-01-01

    The physico-chemical properties of nanoparticles (NPs), such as small dimensions, surface charge and surface functionalization, control their capability to interact with cells and, in particular, with sub-cellular components. This interaction can be also influenced by the adsorption of molecules present in biological fluids, like blood, on NP surface. Here, we analysed the effect of serum proteins on 49 and 100 nm red fluorescent polystyrene NP uptake in porcine aortic endothelial (PAE) cells, as a model for vascular transport. To this aim, NP uptake kinetic, endocytic pathway and intracellular trafficking were studied by monitoring NPs inside cells through confocal microscopy and multiple particle tracking (MPT). We demonstrated that NPs are rapidly internalized by cells in serum-free (SF) medium, according to a saturation kinetic. Conversely, in 10% foetal bovine serum-enriched (SE) medium, NP uptake rate results drastically reduced. Moreover, NP internalization depends on an active endocytic mechanism that does not involve clathrin- and caveolae-mediated vesicular transport, in both SE and SF media. Furthermore, MPT data indicate that NP intracellular trafficking is unaffected by protein presence. Indeed, approximately 50–60% of internalized NPs is characterized by a sub-diffusive behaviour, whereas the remaining fraction shows an active motion. These findings demonstrate that the unspecific protein adsorption on NP surface can affect cellular uptake in terms of internalization kinetics, but it is not effective in controlling active and cellular-mediated uptake mechanisms of NPs and their intracellular routes.

  20. Direct and sustained intracellular delivery of exogenous molecules using acoustic-transfection with high frequency ultrasound

    Science.gov (United States)

    Yoon, Sangpil; Kim, Min Gon; Chiu, Chi Tat; Hwang, Jae Youn; Kim, Hyung Ham; Wang, Yingxiao; Shung, K. Kirk

    2016-02-01

    Controlling cell functions for research and therapeutic purposes may open new strategies for the treatment of many diseases. An efficient and safe introduction of membrane impermeable molecules into target cells will provide versatile means to modulate cell fate. We introduce a new transfection technique that utilizes high frequency ultrasound without any contrast agents such as microbubbles, bringing a single-cell level targeting and size-dependent intracellular delivery of macromolecules. The transfection apparatus consists of an ultrasonic transducer with the center frequency of over 150 MHz and an epi-fluorescence microscope, entitled acoustic-transfection system. Acoustic pulses, emitted from an ultrasonic transducer, perturb the lipid bilayer of the cell membrane of a targeted single-cell to induce intracellular delivery of exogenous molecules. Simultaneous live cell imaging using HeLa cells to investigate the intracellular concentration of Ca2+ and propidium iodide (PI) and the delivery of 3 kDa dextran labeled with Alexa 488 were demonstrated. Cytosolic delivery of 3 kDa dextran induced via acoustic-transfection was manifested by diffused fluorescence throughout whole cells. Short-term (6 hr) cell viability test and long-term (40 hr) cell tracking confirmed that the proposed approach has low cell cytotoxicity.

  1. Restriction spectrum imaging of bevacizumab-related necrosis in a patient with GBM

    Directory of Open Access Journals (Sweden)

    Nikdokht eFarid

    2013-09-01

    Full Text Available Importance:With the increasing use of antiangiogenic agents in the treatment of high grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations:We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI, an advanced diffusion-weighted imaging (DWI technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.Conclusions and Relevance:Our report increases the number of pathologically-proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

  2. Generalized hydrodynamic treatment of the interplay between restricted transport and catalytic reactions in nanoporous materials.

    Science.gov (United States)

    Ackerman, David M; Wang, Jing; Evans, James W

    2012-06-01

    Behavior of catalytic reactions in narrow pores is controlled by a delicate interplay between fluctuations in adsorption-desorption at pore openings, restricted diffusion, and reaction. This behavior is captured by a generalized hydrodynamic formulation of appropriate reaction-diffusion equations (RDE). These RDE incorporate an unconventional description of chemical diffusion in mixed-component quasi-single-file systems based on a refined picture of tracer diffusion for finite-length pores. The RDE elucidate the nonexponential decay of the steady-state reactant concentration into the pore and the non-mean-field scaling of the reactant penetration depth.

  3. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L. [University of Colorado Anschutz School of Medicine, Department of Radiology, Aurora, CO (United States); Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Armstrong-Wells, Jennifer [University of Colorado Anschutz School of Medicine, Department of Pediatrics (Neurology) and OB/GYN, Aurora, CO (United States); University of Colorado Hemophilia and Thrombosis Center, Aurora, CO (United States)

    2016-01-15

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm{sup 3} vs. 36,995 mm{sup 3}; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10{sup -6} mm{sup 2}/s vs. 611 x 10{sup -6} mm{sup 2}/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  4. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    International Nuclear Information System (INIS)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L.; Armstrong-Wells, Jennifer

    2016-01-01

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm 3 vs. 36,995 mm 3 ; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10 -6 mm 2 /s vs. 611 x 10 -6 mm 2 /s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  5. Spin-diffusions and diffusive molecular dynamics

    Science.gov (United States)

    Farmer, Brittan; Luskin, Mitchell; Plecháč, Petr; Simpson, Gideon

    2017-12-01

    Metastable configurations in condensed matter typically fluctuate about local energy minima at the femtosecond time scale before transitioning between local minima after nanoseconds or microseconds. This vast scale separation limits the applicability of classical molecular dynamics (MD) methods and has spurned the development of a host of approximate algorithms. One recently proposed method is diffusive MD which aims at integrating a system of ordinary differential equations describing the likelihood of occupancy by one of two species, in the case of a binary alloy, while quasistatically evolving the locations of the atoms. While diffusive MD has shown itself to be efficient and provide agreement with observations, it is fundamentally a model, with unclear connections to classical MD. In this work, we formulate a spin-diffusion stochastic process and show how it can be connected to diffusive MD. The spin-diffusion model couples a classical overdamped Langevin equation to a kinetic Monte Carlo model for exchange amongst the species of a binary alloy. Under suitable assumptions and approximations, spin-diffusion can be shown to lead to diffusive MD type models. The key assumptions and approximations include a well-defined time scale separation, a choice of spin-exchange rates, a low temperature approximation, and a mean field type approximation. We derive several models from different assumptions and show their relationship to diffusive MD. Differences and similarities amongst the models are explored in a simple test problem.

  6. Spirometry, Static Lung Volumes, and Diffusing Capacity.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; Cain, Hilary C; Casaburi, Richard; Lee, Patty J; Iannone, Lynne; Leo-Summers, Linda S; Van Ness, Peter H

    2017-09-01

    Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394]). Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11

  7. How Harmful are Adaptation Restrictions

    OpenAIRE

    Bruin, de, K.C.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  8. Factors influencing intracellular uptake and radiosensitization by 2-nitroimidazoles in vitro

    International Nuclear Information System (INIS)

    Brown, D.M.; Gonzalez-Mendez, R.; Brown, J.M.

    1983-01-01

    In this study it is shown that the radiosensitization of hypoxic Chinese hamster ovary (HA-1) cells in vitro by misonidazole (MIS) and other 1-substituted 2-nitroimidazoles depends on the rate and extent of intracellular uptake of these radiosensitizers, which in turn is governed by their lipophilicity [expressed as the octanol:water partition coefficient (P)]. As the lipophilicity of the compounds decreased, the rate of drug entry into the cells was slower, and below P values of approximately 0.05, peak intracellular drug concentrations were found to be lower than that of MIS (P=0.43). In addition, the number of hydroxyl groups on the side chain of the nitroimidazole molecule influenced the uptake of drug into the cells. For compounds of similar P, but differing in the number of side-chain hydroxyl groups, the addition of a single hydroxyl group to the molecule decreased the amount of drug entering the cell by a factor of approximately 2. These compounds enter the cell by nonmediated passive diffusion since altering the energy (ATP) capacity of the cell by 2-deoxyglucose did not affect uptake. It is also shown that increases in temperature or decreases in pH can increase the intracellular uptake of MIS. For example, equal intracellular and extracellular concentrations (100% uptake) of MIS were obtained if cells were heated to 44-45 0 C for 15 min compared to 20-40% uptake at 37 0 C. Increases in MIS uptake by factors of 2 to 3 could be demonstrated within 30 min when cells were incubated in Hanks' balanced salt solution at pH between 6.0 and 6.3 without loss of cell viability. In addition, MIS uptake in aerobic cultured cells varied from 15 to 60% depending on the cell line and culure conditions used

  9. Speed Limits for Nonvesicular Intracellular Sterol Transport.

    Science.gov (United States)

    Dittman, Jeremy S; Menon, Anant K

    2017-02-01

    Sterol transport between the endoplasmic reticulum (ER) and plasma membrane (PM) occurs by nonvesicular mechanisms requiring sterol transport proteins (STPs). Here we examine the idea that transport is enhanced at membrane contact sites where the ER is closely apposed to the PM. We conclude that sterol desorption from the membrane, rather than STP-mediated diffusion, is rate limiting in the cellular context, so there is no apparent kinetic benefit to having STP-mediated sterol transfer occur at contact sites. Contact sites may instead compartmentalize lipid synthesis or transport machinery, providing opportunities for regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. LIPID SYNTHESIS, INTRACELLULAR TRANSPORT, AND SECRETION

    Science.gov (United States)

    Stein, Olga; Stein, Yechezkiel

    1967-01-01

    In the mammary glands of lactating albino mice injected intravenously with 9, 10-oleic acid-3H or 9, 10-palmitic acid-3H, it has been shown that the labeled fatty acids are incorporated into mammary gland glycerides. The labeled lipid in the mammary gland 1 min after injection was in esterified form (> 95%), and the radioautographic reaction was seen over the rough endoplasmic reticulum and over lipid droplets, both intracellular and intraluminal. At 10–60 min after injection, the silver grains were concentrated predominantly over lipid droplets. There was no concentration of radioactivity over the granules in the Golgi apparatus, at any time interval studied. These findings were interpreted to indicate that after esterification of the fatty acid into glycerides in the rough endoplasmic reticulum an in situ aggregation of lipid occurs, with acquisition of droplet form. The release of the lipid into the lumen proceeds directly and not through the Golgi apparatus, in contradistinction to the mode of secretion of casein in the mammary gland or of lipoprotein in the liver. The presence of strands of endoplasmic reticulum attached to intraluminal lipid droplets provides a structural counterpart to the milk microsomes described in ruminant milk. PMID:6033535

  11. Endothelial remodelling and intracellular calcium machinery.

    Science.gov (United States)

    Moccia, F; Tanzi, F; Munaron, L

    2014-05-01

    Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

  12. Intracellular events regulating cross-presentation

    Directory of Open Access Journals (Sweden)

    Peter eCresswell

    2012-06-01

    Full Text Available Cross-presentation plays a fundamental role in the induction of CD8-T cell immunity. However, although more than three decades have passed since its discovery, surprisingly little is known about the exact mechanisms involved. Here we give an overview of the components involved at different stages of this process. First, antigens must be internalized into the cross-presenting cell. The involvement of different receptors, method of antigen uptake, and nature of the antigen can influence intracellular trafficking and access to the cross-presentation pathway. Once antigens access the endocytic system, different requirements for endosomal/phagosomal processing arise, such as proteolysis and reduction of disulfide bonds. The majority of cross-presented peptides are generated by proteasomal degradation. Therefore, antigens must cross a membrane barrier in a manner analogous to the fate of misfolded proteins in the endoplasmic reticulum (ER that are retrotranslocated into the cytosol for degradation. Indeed, some components of the ER-associated degradation (ERAD machinery have been implicated in cross-presentation. Further complicating the matter, endosomal and phagosomal compartments have been suggested as alternative sites to the ER for loading of peptides on MHC class I molecules. Finally, the antigen presenting cells involved, particularly dendritic cell subsets and their state of maturation, influence the efficiency of cross-presentation.

  13. Intracellular recording from a spider vibration receptor.

    Science.gov (United States)

    Gingl, Ewald; Burger, Anna-M; Barth, Friedrich G

    2006-05-01

    The present study introduces a new preparation of a spider vibration receptor that allows intracellular recording of responses to natural mechanical or electrical stimulation of the associated mechanoreceptor cells. The spider vibration receptor is a lyriform slit sense organ made up of 21 cuticular slits located on the distal end of the metatarsus of each walking leg. The organ is stimulated when the tarsus receives substrate vibrations, which it transmits to the organ's cuticular structures, reducing the displacement to about one tenth due to geometrical reasons. Current clamp recording was used to record action potentials generated by electrical or mechanical stimuli. Square pulse stimulation identified two groups of sensory cells, the first being single-spike cells which generated only one or two action potentials and the second being multi-spike cells which produced bursts of action potentials. When the more natural mechanical sinusoidal stimulation was applied, differences in adaptation rate between the two cell types remained. In agreement with prior extracellular recordings, both cell types showed a decrease in the threshold tarsus deflection with increasing stimulus frequency. Off-responses to mechanical stimuli have also been seen in the metatarsal organ for the first time.

  14. On the Computing Potential of Intracellular Vesicles.

    Science.gov (United States)

    Mayne, Richard; Adamatzky, Andrew

    2015-01-01

    Collision-based computing (CBC) is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a 'vesicle modification' of the archetypal CBC 'billiard ball model' of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle 'programming' in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing.

  15. Modeling HIV-1 intracellular replication: two simulation approaches

    NARCIS (Netherlands)

    Zarrabi, N.; Mancini, E.; Tay, J.; Shahand, S.; Sloot, P.M.A.

    2010-01-01

    Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular

  16. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    Science.gov (United States)

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  17. Diffusion in reactor materials

    International Nuclear Information System (INIS)

    Fedorov, G.B.; Smirnov, E.A.

    1984-01-01

    The monograph contains a brief description of the principles underlying the theory of diffusion, as well as modern methods of studying diffusion. Data on self-diffusion and diffusion of impurities in a nuclear fuel and fissionable materials (uranium, plutonium, thorium, zirconium, titanium, hafnium, niobium, molybdenum, tungsten, beryllium, etc.) is presented. Anomalous diffusion, diffusion of components, and interdiffusion in binary and ternary alloys were examined. The monograph presents the most recent reference material on diffusion. It is intended for a wide range of researchers working in the field of diffusion in metals and alloys and attempting to discover new materials for application in nuclear engineering. It will also be useful for teachers, research scholars and students of physical metallurgy

  18. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Science.gov (United States)

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  19. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

    Directory of Open Access Journals (Sweden)

    Farhana R. Pinu

    2017-10-01

    Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  20. Diffusion in flowing gas

    International Nuclear Information System (INIS)

    Reus, K.W.

    1979-01-01

    This thesis is concerned with the back-diffusion method of calculating the mutual diffusion coefficient of two gases. The applicability of this method for measuring diffusion coefficients at temperatures up to 1300 K is considered. A further aim of the work was to make a contribution to the description of the interatomic potential energy of noble gases at higher energies as a function of the internuclear distance. This was achieved with the measured diffusion coefficients, especially with those for high temperatures. (Auth.)

  1. Diffusion Under Geometrical Constraint

    OpenAIRE

    Ogawa, Naohisa

    2014-01-01

    Here we discus the diffusion of particles in a curved tube. This kind of transport phenomenon is observed in biological cells and porous media. To solve such a problem, we discuss the three dimensional diffusion equation with a confining wall forming a thinner tube. We find that the curvature appears in a effective diffusion coefficient for such a quasi-one-dimensional system. As an application to higher dimensional case, we discuss the diffusion in a curved surface with ...

  2. Diffuse ceiling ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen

    Diffuse ceiling ventilation is an innovative ventilation concept where the suspended ceiling serves as air diffuser to supply fresh air into the room. Compared with conventional ventilation systems, diffuse ceiling ventilation can significantly reduce or even eliminate draught risk due to the low...

  3. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

    Directory of Open Access Journals (Sweden)

    I-Chueh Huang

    2011-01-01

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  4. Measuring nanoparticle diffusion in an ABELtrap

    Science.gov (United States)

    Dienerowitz, M.; Dienerowitz, F.; Börsch, M.

    2018-03-01

    Monitoring the Brownian motion of individual nanoscopic objects is key to investigate their transport properties and interactions with their close environment. Most techniques rely on transient diffusion through a detection volume or immobilisation, which restrict observation times or motility. We measure the diffusion coefficient and surface charge of individual nanoparticles and DNA molecules in an anti-Brownian electrokinetic trap (ABELtrap). This instrument is an active feedback trap confining the Brownian motion of a nanoparticle to the detection site by applying an electric field based on the particle’s current position. We simulate the Brownian motion of nanospheres in our sample geometry, including wall effects, due to partial confinement in the third dimension. The theoretically predicted values are in excellent agreement with our diffusion measurements in the ABELtrap. We also demonstrate the ABELtrap’s ability to measure varying sizes of DNA origami structures during denaturation.

  5. Intracellular Localization of Arabidopsis Sulfurtransferases1

    Science.gov (United States)

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D.; Papenbrock, Jutta

    2004-01-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism. PMID:15181206

  6. Thermal diffusion (1963); Diffusion thermique (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Lemarechal, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    This report brings together the essential principles of thermal diffusion in the liquid and gaseous phases. The macroscopic and molecular aspects of the thermal diffusion constant are reviewed, as well as the various measurement method; the most important developments however concern the operation of the CLUSIUS and DICKEL thermo-gravitational column and its applications. (author) [French] Ce rapport rassemble les principes essentiels de la diffusion thermique en phase liquide et en phase gazeuse. Les aspects macroscopique et moleculaire de la constante de diffusion thermique sont passes en revue ainsi que ses differentes methodes de mesure; mais les developpements les plus importants concernent le fonctionnement de ls colonne thermogravitationnelle de CLUSIUS et DICKEL et ses applications. (auteur)

  7. Fractional diffusion equations and anomalous diffusion

    CERN Document Server

    Evangelista, Luiz Roberto

    2018-01-01

    Anomalous diffusion has been detected in a wide variety of scenarios, from fractal media, systems with memory, transport processes in porous media, to fluctuations of financial markets, tumour growth, and complex fluids. Providing a contemporary treatment of this process, this book examines the recent literature on anomalous diffusion and covers a rich class of problems in which surface effects are important, offering detailed mathematical tools of usual and fractional calculus for a wide audience of scientists and graduate students in physics, mathematics, chemistry and engineering. Including the basic mathematical tools needed to understand the rules for operating with the fractional derivatives and fractional differential equations, this self-contained text presents the possibility of using fractional diffusion equations with anomalous diffusion phenomena to propose powerful mathematical models for a large variety of fundamental and practical problems in a fast-growing field of research.

  8. Diffusion MR findings in cyclosporin-A induced encephalopathy

    International Nuclear Information System (INIS)

    Aydin, Kubilay; Minareci, Ozenc; Donmez, Fuldem; Tuzun, Umit; Atamer, Tanju

    2004-01-01

    Cyclosporin encephalopathy is a well-known entity, which is clinically characterized by altered mental status, vision problems, focal neurological deficits and seizures. The exact pathophysiology of the cyclosporin encephalopathy has not yet been defined. We report the diffusion-weighted MR imaging and proton MR spectroscopy findings in a case of cyclosporin encephalopathy. The white-matter lesions with reversible restricted diffusion supported the hypothesis of reversible vasospasm induced by the cyclosporin. (orig.)

  9. Splitting Schemes & Segregation In Reaction-(Cross-)Diffusion Systems

    OpenAIRE

    Carrillo, José A.; Fagioli, Simone; Santambrogio, Filippo; Schmidtchen, Markus

    2017-01-01

    One of the most fascinating phenomena observed in reaction-diffusion systems is the emergence of segregated solutions, i.e. population densities with disjoint supports. We analyse such a reaction cross-diffusion system. In order to prove existence of weak solutions for a wide class of initial data without restriction about their supports or their positivity, we propose a variational splitting scheme combining ODEs with methods from optimal transport. In addition, this approach allows us to pr...

  10. Diffusion in molybdenum disilicide

    International Nuclear Information System (INIS)

    Salamon, M.; Mehrer, H.

    2005-01-01

    The diffusion behaviour of the high-temperature material molybdenum disilicide (MoSi 2 ) was completely unknown until recently. In this paper we present studies of Mo self-diffusion and compare our present results with our already published studies of Si and Ge diffusion in MoSi 2 . Self-diffusion of molybdenum in monocrystalline MoSi 2 was studied by the radiotracer technique using the radioisotope 99 Mo. Deposition of the radiotracer and serial sectioning after the diffusion anneals to determine the concentration-depth profiles was performed using a sputtering device. Diffusion of Mo is a very slow process. In the entire temperature region investigated (1437 to 2173 K), the 99 Mo diffusivities in both principal directions of the tetragonal MoSi 2 crystals obey Arrhenius laws, where the diffusion perpendicular to the tetragonal axis is faster by two to three orders of magnitude than parallel to it. The activation enthalpies for diffusion perpendicular and parallel to the tetragonal axis are Q perpendicular to = 468 kJ mol -1 (4.85 eV) and Q parallel = 586 kJ mol -1 (6.07 eV), respectively. Diffusion of Si and its homologous element Ge is fast and is mediated by thermal vacancies of the Si sublattice of MoSi 2 . The diffusion of Mo is by several orders of magnitude slower than the diffusion of Si and Ge. This large difference suggests that Si and Mo diffusion are decoupled and that the diffusion of Mo likely takes place via vacancies on the Mo sublattice. (orig.)

  11. Telomere Restriction Fragment (TRF) Analysis.

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  12. Study on diffusion anisotropy of cerebral ischemia using diffusion weighted echo-planar MRI

    International Nuclear Information System (INIS)

    Kajima, Toshio

    1997-01-01

    Focal cerebral ischemia was produced by occlusion of the intracranial main cerebral artery with a silicone cylinder in Wistar rats. Diffusion-weighted echo-planar images (DW-EPls) using the motion-probing gradient (MPG) method were acquired at 1-3 hours and 24-48 hours after occlusion. Apparent diffusion coefficients (ADCs) were calculated from these images in ischemic lesions and in normal unoccluded regions. Results were as follows. Ischemic lesions could be detected on the DW-EPIs at 1 hour after occlusion. The ADC of water in the brain tissue was smaller than that of free water as a result of restricted diffusion. Anisotropic diffusion that probably can be attributed to the myelin sheath was observed in the normal white matter. In the ischemic lesions, the ADC decreased rapidly within 1-3 hours after occlusion and then decreased gradually after 24-48 hours. In the ischemic white matter, diffusion anisotropy disappeared at 24-48 hours after occlusion. Diffusion-weighted imaging may have applications in the examination of pathophysiological mechanisms in cerebral ischemia by means of evaluation of ADC and diffusion anisotropy. (author)

  13. New perspective in the assessment of total intracellular magnesium

    Directory of Open Access Journals (Sweden)

    Azzurra Sargenti

    2014-01-01

    Full Text Available Magnesium (Mg is essential for biological processes, but its cellular homeostasis has not been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular Mg distribution. Recently, particular interest has been raised by a new family of fluorescent probes, diaza-18-crown-hydroxyquinoline (DCHQ, that shows remarkably high affinity and specificity for Mg, thus permitting the detection of the total intracellular Mg. The data obtained by fluori- metric and cytofluorimetric assays performed with DCHQ5 are in good agreement with atomic absorption spectroscopy, confirming that DCHQ5 probe allows both qualitative and quantitative determination of total intracellular Mg.

  14. [Triexponential diffusion analysis in invasive ductal carcinoma and fibroadenoma].

    Science.gov (United States)

    Nakagawa, Masayuki; Miyati, Tosiaki; Hayashi, Tatsuya; Kanao, Syotaro; Taniguchi, Masahiro; Higashimura, Kyoji; Toi, Masakazu; Togashi, Kaori

    2014-03-01

    To simultaneously obtain information on diffusion and perfusion in breast lesions by diffusion-weighted magnetic resonance imaging (DWI), we analyzed three diffusion components using a triexponential function. Eighteen subjects [10 with invasive ductal carcinoma (IDC), 8 with fibroadenoma] were evaluated using DWI with multiple b-values. We derived perfusion-related diffusion, fast free diffusion, and slow restricted diffusion coefficients (Dp, Df, Ds) calculated from the triexponential function using the DWI data. Moreover, the triexponential analysis was compared with biexponential and monoexponential analyses. Each diffusion coefficient with a triexponential function was correlated to a relative enhancement ratio (RER) using dynamic contrast-enhanced MRI. In triexponential analysis, Dp and Ds in IDC were significantly higher than those for fibroadenoma. There was no correlation between each diffusion coefficient from the triexponential analysis in any of the groups (Dp, Df, and Ds), but biexponential analysis revealed a positive correlation between each diffusion coefficient in breast lesions. Strong correlations were found between Dp and RERs. Triexponential analysis thus makes it possible to obtain, in noninvasive fashion, more detailed diffusion and perfusion information in breast lesions.

  15. Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle.

    Science.gov (United States)

    Kinsey, Stephen T; Locke, Bruce R; Dillaman, Richard M

    2011-01-15

    Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients. It is therefore not surprising that skeletal muscle fibers have long been the focus of reaction-diffusion analyses because they have high and variable rates of ATP turnover, long diffusion distances, and hindered metabolite diffusion due to an abundance of intracellular barriers. Examination of the diversity of skeletal muscle fiber designs found in animals provides insights into the role that diffusion plays in governing both rates of metabolic fluxes and cellular organization. Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction-diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function. Foremost among these is that metabolic processes in muscles do, in fact, appear to be largely reaction controlled and are not greatly limited by diffusion. However, the influence of diffusion is apparent in patterns of fiber growth and metabolic organization that appear to result from selective pressure to maintain reaction control of metabolism in muscle.

  16. Understanding the effects of diffusion and relaxation in magnetic resonance imaging using computational modeling

    Science.gov (United States)

    Russell, Greg

    The work described in this dissertation was motivated by a desire to better understand the cellular pathology of ischemic stroke. Two of the three bodies of research presented herein address and issue directly related to the investigation of ischemic stroke through the use of diffusion weighted magnetic resonance imaging (DWMRI) methods. The first topic concerns the development of a computationally efficient finite difference method, designed to evaluate the impact of microscopic tissue properties on the formation of DWMRI signal. For the second body of work, the effect of changing the intrinsic diffusion coefficient of a restricted sample on clinical DWMRI experiments is explored. The final body of work, while motivated by the desire to understand stroke, addresses the issue of acquiring large amounts of MRI data well suited for quantitative analysis in reduced scan time. In theory, the method could be used to generate quantitative parametric maps, including those depicting information gleaned through the use of DWMRI methods. Chapter 1 provides an introduction to several topics. A description of the use of DWMRI methods in the study of ischemic stroke is covered. An introduction to the fundamental physical principles at work in MRI is also provided. In this section the means by which magnetization is created in MRI experiments, how MRI signal is induced, as well as the influence of spin-spin and spin-lattice relaxation are discussed. Attention is also given to describing how MRI measurements can be sensitized to diffusion through the use of qualitative and quantitative descriptions of the process. Finally, the reader is given a brief introduction to the use of numerical methods for solving partial differential equations. In Chapters 2, 3 and 4, three related bodies of research are presented in terms of research papers. In Chapter 2, a novel computational method is described. The method reduces the computation resources required to simulate DWMRI experiments. In

  17. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured ...

  18. Intracellular chemical gradients: morphing principle in bacteria

    Directory of Open Access Journals (Sweden)

    Endres Robert G

    2012-09-01

    Full Text Available Abstract Advances in computational biology allow systematic investigations to ascertain whether internal chemical gradients can be maintained in bacteria – an open question at the resolution limit of fluorescence microscopy. While it was previously believed that the small bacterial cell size and fast diffusion in the cytoplasm effectively remove any such gradient, a new computational study published in BMC Biophysics supports the emerging view that gradients can exist. The study arose from the recent observation that phosphorylated CtrA forms a gradient prior to cell division in Caulobacter crescentus, a bacterium known for its complicated cell cycle. Tropini et al. (2012 postulate that such gradients can provide an internal chemical compass, directing protein localization, cell division and cell development. More specifically, they describe biochemical and physical constraints on the formation of such gradients and explore a number of existing bacterial cell morphologies. These chemical gradients may limit in vitro analyses, and may ensure timing control and robustness to fluctuations during critical stages in cell development.

  19. Glutathionylation-Dependence of Na+-K+-Pump Currents Can Mimic Reduced Subsarcolemmal Na+ Diffusion

    OpenAIRE

    Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald?J.; Rasmussen, Helge?H.

    2016-01-01

    The existence of a subsarcolemmal space with restricted diffusion for Na+ in cardiac myocytes has been inferred from a transient peak electrogenic Na+-K+ pump current beyond steady state on reexposure of myocytes to K+ after a period of exposure to K+-free extracellular solution. The transient peak current is attributed to enhanced electrogenic pumping of Na+ that accumulated in the diffusion-restricted space during pump inhibition in K+-free extracellular solution. However, there are no know...

  20. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

  1. Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

  2. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Science.gov (United States)

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  3. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection

    DEFF Research Database (Denmark)

    Ernstsen, Christina Lundgaard; Login, Frédéric H.; Jensen, Helene Halkjær

    2017-01-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacteria...

  4. Metric diffusion along foliations

    CERN Document Server

    Walczak, Szymon M

    2017-01-01

    Up-to-date research in metric diffusion along compact foliations is presented in this book. Beginning with fundamentals from the optimal transportation theory and the theory of foliations; this book moves on to cover Wasserstein distance, Kantorovich Duality Theorem, and the metrization of the weak topology by the Wasserstein distance. Metric diffusion is defined, the topology of the metric space is studied and the limits of diffused metrics along compact foliations are discussed. Essentials on foliations, holonomy, heat diffusion, and compact foliations are detailed and vital technical lemmas are proved to aide understanding. Graduate students and researchers in geometry, topology and dynamics of foliations and laminations will find this supplement useful as it presents facts about the metric diffusion along non-compact foliation and provides a full description of the limit for metrics diffused along foliation with at least one compact leaf on the two dimensions.

  5. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    International Nuclear Information System (INIS)

    Park, Ju Young; Lee, In Ho; Song, Chang June; Hwang, Hee Youn

    2012-01-01

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  6. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Young; Lee, In Ho; Song, Chang June [Chungnam National University Hospital, Daejeon (Korea, Republic of); Hwang, Hee Youn [Eulji University Hospital, Daejeon(Korea, Republic of)

    2012-03-15

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  7. Ions cross-B collisional diffusion and electromagnetic wave scattering

    International Nuclear Information System (INIS)

    Tomchuk, B.P.; Gresillon, D.

    2000-01-01

    The calculation is presented of the averaged quadratic displacement of a collisional charged particle in a magnetic field. This calculation is used to obtain the statistical presentation of the electromagnetic field scattered by these particles. These results extend the previous calculations that were restricted to non-magnetized particles (Ornstein equation, Einstein diffusion, etc.). In addition this calculation foresees effects that are absent of the Ornstein equation: a modulation of the averaged quadratic displacement function at the cyclotron frequency and a maximum of the Cross-B diffusion coefficient when the cyclotron frequency is equal to the collision frequency (Bohm diffusion)

  8. Temperature jump boundary conditions in radiation diffusion

    International Nuclear Information System (INIS)

    Alonso, C.T.

    1976-12-01

    The radiation diffusion approximation greatly simplifies radiation transport problems. Yet the application of this method has often been unnecessarily restricted to optically thick regions, or has been extended through the use of such ad hoc devices as flux limiters. The purpose of this paper is to review and draw attention to the use of the more physically appropriate temperature jump boundary conditions for extending the range of validity of the diffusion approximation. Pioneering work has shown that temperature jump boundary conditions remove the singularity in flux that occurs in ordinary diffusion at small optical thicknesses. In this review paper Deissler's equations for frequency-dependent jump boundary conditions are presented and specific geometric examples are calculated analytically for steady state radiation transfer. When jump boundary conditions are applied to radiation diffusion, they yield exact solutions which are naturally flux- limited and geometry-corrected. We believe that the presence of temperature jumps on source boundaries is probably responsible in some cases for the past need for imposing ad hoc flux-limiting constraints on pure diffusion solutions. The solution for transfer between plane slabs, which is exact to all orders of optical thickness, also provides a useful tool for studying the accuracy of computer codes

  9. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

  10. Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection.

    Science.gov (United States)

    Mentzer, Robert M; Lasley, Robert D; Jessel, Andreas; Karmazyn, Morris

    2003-02-01

    Although the mechanisms underlying ischemia/reperfusion injury remain elusive, evidence supports the etiologic role of intracellular calcium overload and oxidative stress induced by reactive oxygen species. Activation of the sodium hydrogen exchanger (NHE) is associated with intracellular calcium accumulation. Inhibition of the NHE-1 isoform may attenuate the consequences of this injury. Although there is strong preclinical and early clinical evidence that NHE inhibitors may be cardioprotective, definitive proof of this concept in humans awaits the results of ongoing clinical trials.

  11. Correlated diffusion imaging

    International Nuclear Information System (INIS)

    Wong, Alexander; Glaister, Jeffrey; Cameron, Andrew; Haider, Masoom

    2013-01-01

    Prostate cancer is one of the leading causes of cancer death in the male population. Fortunately, the prognosis is excellent if detected at an early stage. Hence, the detection and localization of prostate cancer is crucial for diagnosis, as well as treatment via targeted focal therapy. New imaging techniques can potentially be invaluable tools for improving prostate cancer detection and localization. In this study, we introduce a new form of diffusion magnetic resonance imaging called correlated diffusion imaging, where the tissue being imaged is characterized by the joint correlation of diffusion signal attenuation across multiple gradient pulse strengths and timings. By taking into account signal attenuation at different water diffusion motion sensitivities, correlated diffusion imaging can provide improved delineation between cancerous tissue and healthy tissue when compared to existing diffusion imaging modalities. Quantitative evaluation using receiver operating characteristic (ROC) curve analysis, tissue class separability analysis, and visual assessment by an expert radiologist were performed to study correlated diffusion imaging for the task of prostate cancer diagnosis. These results are compared with that obtained using T2-weighted imaging and standard diffusion imaging (via the apparent diffusion coefficient (ADC)). Experimental results suggest that correlated diffusion imaging provide improved delineation between healthy and cancerous tissue and may have potential as a diagnostic tool for cancer detection and localization in the prostate gland. A new form of diffusion magnetic resonance imaging called correlated diffusion imaging (CDI) was developed for the purpose of aiding radiologists in cancer detection and localization in the prostate gland. Preliminary results show CDI shows considerable promise as a diagnostic aid for radiologists in the detection and localization of prostate cancer

  12. Gaseous diffusion system

    International Nuclear Information System (INIS)

    Garrett, G.A.; Shacter, J.

    1978-01-01

    A gaseous diffusion system is described comprising a plurality of diffusers connected in cascade to form a series of stages, each of the diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof

  13. Inpainting using airy diffusion

    Science.gov (United States)

    Lorduy Hernandez, Sara

    2015-09-01

    One inpainting procedure based on Airy diffusion is proposed, implemented via Maple and applied to some digital images. Airy diffusion is a partial differential equation with spatial derivatives of third order in contrast with the usual diffusion with spatial derivatives of second order. Airy diffusion generates the Airy semigroup in terms of the Airy functions which can be rewritten in terms of Bessel functions. The Airy diffusion can be used to smooth an image with the corresponding noise elimination via convolution. Also the Airy diffusion can be used to erase objects from an image. We build an algorithm using the Maple package ImageTools and such algorithm is tested using some images. Our results using Airy diffusion are compared with the similar results using standard diffusion. We observe that Airy diffusion generates powerful filters for image processing which could be incorporated in the usual packages for image processing such as ImageJ and Photoshop. Also is interesting to consider the possibility to incorporate the Airy filters as applications for smartphones and smart-glasses.

  14. Diffusion in compacted betonite

    International Nuclear Information System (INIS)

    Muurinen, A.; Rantanen, J.

    1985-01-01

    The objective of this report is to collect the literature bearing on the diffusion in compacted betonite, which has been suggested as possible buffer material for the disposal of spent fuel. Diffusion in a porous, water-saturated material is usually described as diffusion in the pore-water where sorption on the solid matter can delay the migration in the instationary state. There are also models which take into consideration that the sorbed molecules can also move while being sorbed. Diffusion experiments in compacted bentonite have been reported by many authors. Gases, anions, cations and actinides have been used as diffusing molecules. The report collects the results and the information on the measurement methods. On the basis of the results can be concluded that different particles possibly follow different diffusion mechanisms. The parameters which affect the diffusion seem to be for example the size, the electric charge and the sorption properties of the diffusing molecule. The report also suggest the parameters to be used in the diffusion calculation of the safety analyses of spent fuel disposal. (author)

  15. Uptake and intracellular activity of AM-1155 in phagocytic cells.

    Science.gov (United States)

    Yamamoto, T; Kusajima, H; Hosaka, M; Fukuda, H; Oomori, Y; Shinoda, H

    1996-01-01

    The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity. PMID:9124835

  16. Epithelial Cell Gene Expression Induced by Intracellular Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Xianglu Li

    2009-01-01

    Full Text Available HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several cholesterol biosynthesis genes. These results suggest that epithelial cells respond to intracellular S. aureus by inducing genes affecting immunity and in repairing damage caused by the organism, and are consistent with the possibility that the organism exploits an intracellular environment to subvert host immunity and promote colonization.

  17. Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice.

    Science.gov (United States)

    Varghese, C D; Nair, S C; Panikkar, B; Panikkar, K R

    1993-04-15

    The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect.

  18. Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of Intracellular Proteases for Targeted Cytotoxicity.

    Science.gov (United States)

    Ho, Patrick; Ede, Christopher; Chen, Yvonne Y

    2017-08-18

    Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. We demonstrate that fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We further demonstrate the rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the COVERT platform's modularity and adaptability to diverse protease targets. As an initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we verified that primary human T cells can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. Our findings set the foundation for future intracellular-antigen-responsive therapeutics that can complement surface-targeted therapies.

  19. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.

    Science.gov (United States)

    Wu, Yu; Pons, Valérie; Goudet, Amélie; Panigai, Laetitia; Fischer, Annette; Herweg, Jo-Ana; Kali, Sabrina; Davey, Robert A; Laporte, Jérôme; Bouclier, Céline; Yousfi, Rahima; Aubenque, Céline; Merer, Goulven; Gobbo, Emilie; Lopez, Roman; Gillet, Cynthia; Cojean, Sandrine; Popoff, Michel R; Clayette, Pascal; Le Grand, Roger; Boulogne, Claire; Tordo, Noël; Lemichez, Emmanuel; Loiseau, Philippe M; Rudel, Thomas; Sauvaire, Didier; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien

    2017-11-14

    Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

  20. New diffusion imaging method with a single acquisition sequence

    International Nuclear Information System (INIS)

    Melki, Ph.S.; Bittoun, J.; Lefevre, J.E.

    1987-01-01

    The apparent diffusion coefficient (ADC) is related to the molecular diffusion coefficient and to physiologic information: microcirculation in the capillary network, incoherent slow flow, and restricted diffusion. The authors present a new MR imaging sequence that yields computed ADC images in only one acquisition of 9-minutes with a 1.5-T imager (GE Signa). Compared to the previous method, this sequence is at least two times faster and thus can be used as a routine examination to supplement T1-, T2-, and density-weighted images. The method was assessed by measurement of the molecular diffusion in liquids, and the first clinical images obtained in neurologic diseases demonstrate its efficiency for clinical investigation. The possibility of separately imaging diffusion and perfusion is supported by an algorithm

  1. Assessment of patency capsule retention using MR diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Klang, Eyal; Rozendorn, Noa; Amitai, Michal Marianne [Sheba Medical Center, Department of Diagnostic Imaging, Ramat Gan (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Kopylov, Uri; Ben-Horin, Shomron; Lahat, Adi; Yablecovitch, Doron; Eliakim, Rami [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Sheba Medical Center, Department of Gastroenterology, Ramat Gan (Israel)

    2017-12-15

    Evaluate the ability of MR diffusion-weighted imaging (DWI) to predict patency capsule retention in Crohn's disease (CD). Clinical and imaging data were prospectively reviewed for 80 CD patients following patency capsule administration and MR-DWI under institutional review board (IRB) approval with informed consent. Two radiologists separately assessed the presence/absence of restricted diffusion in the distal ileum. Apparent diffusion coefficients (ADC) from three regions of interest on the ileal wall were averaged. The association between restricted diffusion and retention, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Ability of ADC to predict retention was assessed with receiver operating characteristic (ROC) curve analysis. Restricted diffusion in the distal ileum was associated with capsule retention (p = 0.001, p < 0.0001). Sensitivity, specificity, PPV and NPV of restricted diffusion for capsule retention were 100.0%, 46.2%, 30.0%, 100% and 100.0%, 56.9%, 34.9%, 100%, respectively, for two radiologists. Accuracy of ADC to predict retention was high (area under the curve = 0.851, p < 0.0001). An ADC of 1.47 mm{sup 2}/s showed 90.0% sensitivity and 50.0% specificity for retention. Sensitivity and NPV of restricted diffusion for patency capsule retention were 100%, suggesting that DWI may predict gastrointestinal tract capability to pass video camera endoscopy. (orig.)

  2. Assessment of patency capsule retention using MR diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Klang, Eyal; Rozendorn, Noa; Amitai, Michal Marianne; Kopylov, Uri; Ben-Horin, Shomron; Lahat, Adi; Yablecovitch, Doron; Eliakim, Rami

    2017-01-01

    Evaluate the ability of MR diffusion-weighted imaging (DWI) to predict patency capsule retention in Crohn's disease (CD). Clinical and imaging data were prospectively reviewed for 80 CD patients following patency capsule administration and MR-DWI under institutional review board (IRB) approval with informed consent. Two radiologists separately assessed the presence/absence of restricted diffusion in the distal ileum. Apparent diffusion coefficients (ADC) from three regions of interest on the ileal wall were averaged. The association between restricted diffusion and retention, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Ability of ADC to predict retention was assessed with receiver operating characteristic (ROC) curve analysis. Restricted diffusion in the distal ileum was associated with capsule retention (p = 0.001, p < 0.0001). Sensitivity, specificity, PPV and NPV of restricted diffusion for capsule retention were 100.0%, 46.2%, 30.0%, 100% and 100.0%, 56.9%, 34.9%, 100%, respectively, for two radiologists. Accuracy of ADC to predict retention was high (area under the curve = 0.851, p < 0.0001). An ADC of 1.47 mm 2 /s showed 90.0% sensitivity and 50.0% specificity for retention. Sensitivity and NPV of restricted diffusion for patency capsule retention were 100%, suggesting that DWI may predict gastrointestinal tract capability to pass video camera endoscopy. (orig.)

  3. Measuring Advection and Diffusion of Colloids in Shear Flow

    NARCIS (Netherlands)

    Duits, Michael H.G.; Ghosh, Somnath; Mugele, Friedrich Gunther

    2015-01-01

    An analysis of the dynamics of colloids in shear flow can be challenging because of the superposition of diffusion and advection. We present a method that separates the two motions, starting from the time-dependent particle coordinates. The restriction of the tracking to flow lanes and the

  4. Diffusion and conversion impedance in solid oxide fuel cells

    DEFF Research Database (Denmark)

    Jacobsen, Torben; Hendriksen, Peter Vang; Koch, Søren

    2008-01-01

    to consumption of reactants and accumulation of products. For simplicity this model is restricted to cases dominated by mass transfer and conversion of the gas supply. Qualitatively the predictions by both models are alike. At high frequencies a Warburg diffusion impedance is seen. Depending on the dimensions...

  5. Involvement of intracellular free Ca2+ in enhanced release of herpes simplex virus by hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Ogawa Yuzo

    2006-08-01

    Full Text Available Abstract Background It was reported that elevation of the intracellular concentration of free Ca2+ ([Ca2+]i by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1. Freely diffusible hydrogen peroxide (H2O2 is implied to alter Ca2+ homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H2O2 could affect [Ca2+]i in HSV-1-infected cells had not been investigated. Results H2O2 treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca2+]i was observed and the increase in [Ca2+]i was suppressed when intracellular and cytosolic Ca2+ were buffered by Ca2+ chelators. In the presence of Ca2+ chelators, H2O2-mediated increases of cell-free virus and cell death were also diminished. Electron microscopic analysis revealed enlarged cell junctions and a focal disintegration of the plasma membrane in H2O2-treated cells. Conclusion These results indicate that H2O2 can elevate [Ca2+]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.

  6. Dual-modality single particle orientation and rotational tracking of intracellular transport of nanocargos.

    Science.gov (United States)

    Sun, Wei; Gu, Yan; Wang, Gufeng; Fang, Ning

    2012-01-17

    The single particle orientation and rotational tracking (SPORT) technique was introduced recently to follow the rotational motion of plasmonic gold nanorod under a differential interference contrast (DIC) microscope. In biological studies, however, cellular activities usually involve a multiplicity of molecules; thus, tracking the motion of a single molecule/object is insufficient. Fluorescence-based techniques have long been used to follow the spatial and temporal distributions of biomolecules of interest thanks to the availability of multiplexing fluorescent probes. To know the type and number of molecules and the timing of their involvement in a biological process under investigation by SPORT, we constructed a dual-modality DIC/fluorescence microscope to simultaneously image fluorescently tagged biomolecules and plasmonic nanoprobes in living cells. With the dual-modality SPORT technique, the microtubule-based intracellular transport can be unambiguously identified while the dynamic orientation of nanometer-sized cargos can be monitored at video rate. Furthermore, the active transport on the microtubule can be easily separated from the diffusion before the nanocargo docks on the microtubule or after it undocks from the microtubule. The potential of dual-modality SPORT is demonstrated for shedding new light on unresolved questions in intracellular transport.

  7. Discrimination of thermal diffusivity

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2009-01-01

    Materials such as wood or metal which are at equal temperatures are perceived to be of different ‘coldness’ due to differences in thermal properties, such as the thermal diffusivity. The thermal diffusivity of a material is a parameter that controls the rate with which heat is extracted from the

  8. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Fogh Olsen, Ole; Sporring, Jon

    2007-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......, while eliminating noise. We call our method diffusion based photon mapping....

  9. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Olsen, Ole Fogh; Sporring, Jon

    2006-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......, while eliminating noise. We call our method diffusion based photon mapping....

  10. Adaptation and Cultural Diffusion.

    Science.gov (United States)

    Ormrod, Richard K.

    1992-01-01

    Explores the role of adaptation in cultural diffusion. Explains that adaptation theory recognizes the lack of independence between innovations and their environmental settings. Discusses testing and selection, modification, motivation, and cognition. Suggests that adaptation effects are pervasive in cultural diffusion but require a broader, more…

  11. Modelling of Innovation Diffusion

    Directory of Open Access Journals (Sweden)

    Arkadiusz Kijek

    2010-01-01

    Full Text Available Since the publication of the Bass model in 1969, research on the modelling of the diffusion of innovation resulted in a vast body of scientific literature consisting of articles, books, and studies of real-world applications of this model. The main objective of the diffusion model is to describe a pattern of spread of innovation among potential adopters in terms of a mathematical function of time. This paper assesses the state-of-the-art in mathematical models of innovation diffusion and procedures for estimating their parameters. Moreover, theoretical issues related to the models presented are supplemented with empirical research. The purpose of the research is to explore the extent to which the diffusion of broadband Internet users in 29 OECD countries can be adequately described by three diffusion models, i.e. the Bass model, logistic model and dynamic model. The results of this research are ambiguous and do not indicate which model best describes the diffusion pattern of broadband Internet users but in terms of the results presented, in most cases the dynamic model is inappropriate for describing the diffusion pattern. Issues related to the further development of innovation diffusion models are discussed and some recommendations are given. (original abstract

  12. Thermal diffusion (1963)

    International Nuclear Information System (INIS)

    Lemarechal, A.

    1963-01-01

    This report brings together the essential principles of thermal diffusion in the liquid and gaseous phases. The macroscopic and molecular aspects of the thermal diffusion constant are reviewed, as well as the various measurement method; the most important developments however concern the operation of the CLUSIUS and DICKEL thermo-gravitational column and its applications. (author) [fr

  13. Diffusion of Botulinum Toxins

    Directory of Open Access Journals (Sweden)

    Matthew A. Brodsky

    2012-08-01

    Full Text Available Background: It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion.Methods: This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method. It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB.Results: Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others.Discussion: Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected.

  14. Cytoplasmic electric fields and electroosmosis: possible solution for the paradoxes of the intracellular transport of biomolecules.

    Science.gov (United States)

    Andreev, Victor P

    2013-01-01

    The objective of the paper is to show that electroosmotic flow might play an important role in the intracellular transport of biomolecules. The paper presents two mathematical models describing the role of electroosmosis in the transport of the negatively charged messenger proteins to the negatively charged nucleus and in the recovery of the fluorescence after photobleaching. The parameters of the models were derived from the extensive review of the literature data. Computer simulations were performed within the COMSOL 4.2a software environment. The first model demonstrated that the presence of electroosmosis might intensify the flux of messenger proteins to the nucleus and allow the efficient transport of the negatively charged phosphorylated messenger proteins against the electrostatic repulsion of the negatively charged nucleus. The second model revealed that the presence of the electroosmotic flow made the time of fluorescence recovery dependent on the position of the bleaching spot relative to cellular membrane. The magnitude of the electroosmotic flow effect was shown to be quite substantial, i.e. increasing the flux of the messengers onto the nucleus up to 4-fold relative to pure diffusion and resulting in the up to 3-fold change in the values of fluorescence recovery time, and therefore the apparent diffusion coefficient determined from the fluorescence recovery after photobleaching experiments. Based on the results of the modeling and on the universal nature of the electroosmotic flow, the potential wider implications of electroosmotic flow in the intracellular and extracellular biological processes are discussed. Both models are available for download at ModelDB.

  15. Diffusion in Coulomb crystals.

    Science.gov (United States)

    Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K

    2011-07-01

    Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

  16. Atomic diffusion in stars

    CERN Document Server

    Michaud, Georges; Richer, Jacques

    2015-01-01

    This book gives an overview of atomic diffusion, a fundamental physical process, as applied to all types of stars, from the main sequence to neutron stars. The superficial abundances of stars as well as their evolution can be significantly affected. The authors show where atomic diffusion plays an essential role and how it can be implemented in modelling.  In Part I, the authors describe the tools that are required to include atomic diffusion in models of stellar interiors and atmospheres. An important role is played by the gradient of partial radiative pressure, or radiative acceleration, which is usually neglected in stellar evolution. In Part II, the authors systematically review the contribution of atomic diffusion to each evolutionary step. The dominant effects of atomic diffusion are accompanied by more subtle effects on a large number of structural properties throughout evolution. One of the goals of this book is to provide the means for the astrophysicist or graduate student to evaluate the importanc...

  17. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  18. Oxygen diffusion in monazite

    Science.gov (United States)

    Cherniak, D. J.; Zhang, X. Y.; Nakamura, M.; Watson, E. B.

    2004-09-01

    We report measurements of oxygen diffusion in natural monazites under both dry, 1-atm conditions and hydrothermal conditions. For dry experiments, 18O-enriched CePO4 powder and monazite crystals were sealed in Ag-Pd capsules with a solid buffer (to buffer at NNO) and annealed in 1-atm furnaces. Hydrothermal runs were conducted in cold-seal pressure vessels, where monazite grains were encapsulated with 18O-enriched water. Following the diffusion anneals, oxygen concentration profiles were measured with Nuclear Reaction Analysis (NRA) using the reaction 18O(p,α)15N. Over the temperature range 850-1100 °C, the Arrhenius relation determined for dry diffusion experiments on monazite is given by: Under wet conditions at 100 MPa water pressure, over the temperature range 700-880 °C, oxygen diffusion can be described by the Arrhenius relationship: Oxygen diffusion under hydrothermal conditions has a significantly lower activation energy for diffusion than under dry conditions, as has been found the case for many other minerals, both silicate and nonsilicate. Given these differences in activation energies, the differences between dry and wet diffusion rates increase with lower temperatures; for example, at 600 °C, dry diffusion will be more than 4 orders of magnitude slower than diffusion under hydrothermal conditions. These disparate diffusivities will result in pronounced differences in the degree of retentivity of oxygen isotope signatures. For instance, under dry conditions (presumably rare in the crust) and high lower-crustal temperatures (∼800 °C), monazite cores of 70-μm radii will preserve O isotope ratios for about 500,000 years; by comparison, they would be retained at this temperature under wet conditions for about 15,000 years.

  19. Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

    Directory of Open Access Journals (Sweden)

    Lapin Alexei

    2011-05-01

    Full Text Available Abstract Background In this paper we apply a novel agent-based simulation method in order to model intracellular reactions in detail. The simulations are performed within a virtual cytoskeleton enriched with further crowding elements, which allows the analysis of molecular crowding effects on intracellular diffusion and reaction rates. The cytoskeleton network leads to a reduction in the mobility of molecules. Molecules can also unspecifically bind to membranes or the cytoskeleton affecting (i the fraction of unbound molecules in the cytosol and (ii furthermore reducing the mobility. Binding of molecules to intracellular structures or scaffolds can in turn lead to a microcompartmentalization of the cell. Especially the formation of enzyme complexes promoting metabolic channeling, e.g. in glycolysis, depends on the co-localization of the proteins. Results While the co-localization of enzymes leads to faster reaction rates, the reduced mobility decreases the collision rate of reactants, hence reducing the reaction rate, as expected. This effect is most prominent in diffusion limited reactions. Furthermore, anomalous diffusion can occur due to molecular crowding in the cell. In the context of diffusion controlled reactions, anomalous diffusion leads to fractal reaction kinetics. The simulation framework is used to quantify and separate the effects originating from molecular crowding or the reduced mobility of the reactants. We were able to define three factors which describe the effective reaction rate, namely f diff for the diffusion effect, f volume for the crowding, and f access for the reduced accessibility of the molecules. Conclusions Molecule distributions, reaction rate constants and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of a realistic cell environment. As such, the present simulation can help to bridge the gap between in vivo and in vitro

  20. Restriction coefficients of low molecular weight solutes and macromolecules during peritoneal dialysis

    NARCIS (Netherlands)

    Ho-Dac-Pannekeet, M. M.; Koopmans, J. G.; Struijk, D. G.; Krediet, R. T.

    1997-01-01

    The intrinsic permeability of the peritoneal membrane can be functionally represented by the restriction coefficient (RC). The RC can be calculated as the exponent of the power relation between the mass transfer area coefficients (MTACs) of various solutes and their free diffusion coefficients in

  1. Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

    Directory of Open Access Journals (Sweden)

    Jiang LQ

    2017-08-01

    Full Text Available Li Qun Jiang,1 Ting Yu Wang,1 Thomas J Webster,2 Hua-Jian Duan,1 Jing Ying Qiu,1 Zi Ming Zhao,1 Xiao Xing Yin,1,* Chun Li Zheng3,* 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs in macrophages, a primary cell of the mononuclear phagocyte system (MPS. Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm were prepared, and a murine macrophage cell line (RAW 264.7 was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition

  2. Relevance of intracellular polarity to accuracy of eukaryotic chemotaxis

    International Nuclear Information System (INIS)

    Hiraiwa, Tetsuya; Nishikawa, Masatoshi; Shibata, Tatsuo; Nagamatsu, Akihiro; Akuzawa, Naohiro

    2014-01-01

    Eukaryotic chemotaxis is usually mediated by intracellular signals that tend to localize at the front or back of the cell. Such intracellular polarities frequently require no extracellular guidance cues, indicating that spontaneous polarization occurs in the signal network. Spontaneous polarization activity is considered relevant to the persistent motions in random cell migrations and chemotaxis. In this study, we propose a theoretical model that connects spontaneous intracellular polarity and motile ability in a chemoattractant solution. We demonstrate that the intracellular polarity can enhance the accuracy of chemotaxis. Chemotactic accuracy should also depend on chemoattractant concentration through the concentration-dependent correlation time in the polarity direction. Both the polarity correlation time and the chemotactic accuracy depend on the degree of responsiveness to the chemical gradient. We show that optimally accurate chemotaxis occurs at an intermediate responsiveness of intracellular polarity. Experimentally, we find that the persistence time of randomly migrating Dictyostelium cells depends on the chemoattractant concentration, as predicted by our theory. At the optimum responsiveness, this ameboid cell can enhance its chemotactic accuracy tenfold. (paper)

  3. Intracellular calcium levels can regulate Importin-dependent nuclear import

    International Nuclear Information System (INIS)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A.

    2014-01-01

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca 2+ on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery

  4. Intracellular transport of fat-soluble vitamins A and E.

    Science.gov (United States)

    Kono, Nozomu; Arai, Hiroyuki

    2015-01-01

    Vitamins are compounds that are essential for the normal growth, reproduction and functioning of the human body. Of the 13 known vitamins, vitamins A, D, E and K are lipophilic compounds and are therefore called fat-soluble vitamins. Because of their lipophilicity, fat-soluble vitamins are solubilized and transported by intracellular carrier proteins to exert their actions and to be metabolized properly. Vitamin A and its derivatives, collectively called retinoids, are solubilized by intracellular retinoid-binding proteins such as cellular retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP) and cellular retinal-binding protein (CRALBP). These proteins act as chaperones that regulate the metabolism, signaling and transport of retinoids. CRALBP-mediated intracellular retinoid transport is essential for vision in human. α-Tocopherol, the main form of vitamin E found in the body, is transported by α-tocopherol transfer protein (α-TTP) in hepatic cells. Defects of α-TTP cause vitamin E deficiency and neurological disorders in humans. Recently, it has been shown that the interaction of α-TTP with phosphoinositides plays a critical role in the intracellular transport of α-tocopherol and is associated with familial vitamin E deficiency. In this review, we summarize the mechanisms and biological significance of the intracellular transport of vitamins A and E. © 2014 The Authors. Traffic published by John Wiley & Sons Ltd.

  5. Exploring anti-bacterial compounds against intracellular Legionella.

    Directory of Open Access Journals (Sweden)

    Christopher F Harrison

    Full Text Available Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

  6. Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21

    Directory of Open Access Journals (Sweden)

    William A. McEwan

    2016-11-01

    Full Text Available TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY domain. Following binding of intracellular antibody, TRIM21 acts as both antiviral effector and sensor for innate immune signalling. These activities serve to reduce viral replication by orders of magnitude in vitro and contribute to host survival during in vivo infection. Neutralization occurs rapidly after detection and requires the activity of the ubiquitin-proteasome system. The microbial targets of this arm of intracellular immunity are still being identified: TRIM21 activity has been reported following infection by several non-enveloped viruses and intracellular bacteria. These findings extend the sphere of influence of antibodies to the intracellular domain and have broad implications for immunity. TRIM21 has been implicated in the chronic auto-immune condition systemic lupus erythematosus and is itself an auto-antigen in Sjögren’s syndrome. This review summarises our current understanding of TRIM21’s role as a cytosolic Fc receptor and briefly discusses pathological circumstances where intracellular antibodies have been described, or are hypothesized to occur, and may benefit from further investigations of the role of TRIM21.

  7. Exploring Anti-Bacterial Compounds against Intracellular Legionella

    Science.gov (United States)

    Harrison, Christopher F.; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

    2013-01-01

    Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoeba castellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

  8. Intracellular calcium levels can regulate Importin-dependent nuclear import

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

    2014-07-18

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.

  9. Hemorrhagic brain metastases with high signal intensity on diffusion-weighted MR images. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mori, H.; Abe, O.; Aoki, S.; Masumoto, T.; Yoshikawa, T.; Kunimatsu, A; Hayashi, N.; Ohtomo, K. [Graduate School of Medicine, Univ. of Tokyo (Japan). Dept. of Radiology

    2002-11-01

    Diffusion-weighted MR imaging has been applicable to the differential diagnosis of abscesses and necrotic or cystic brain tumors. However, restricted water diffusion is not necessarily specific for brain abscess. We describe ring-enhancing metastases of lung carcinoma characterized by high signal intensity on diffusion-weighted MR images. The signal pattern probably reflected intralesional hemorrhage. The present report adds to the growing literature regarding the differential diagnosis of ring-enhancing brain lesions.

  10. Diffusion phenomenon for linear dissipative wave equations

    KAUST Repository

    Said-Houari, Belkacem

    2012-01-01

    In this paper we prove the diffusion phenomenon for the linear wave equation. To derive the diffusion phenomenon, a new method is used. In fact, for initial data in some weighted spaces, we prove that for {equation presented} decays with the rate {equation presented} [0,1] faster than that of either u or v, where u is the solution of the linear wave equation with initial data {equation presented} [0,1], and v is the solution of the related heat equation with initial data v 0 = u 0 + u 1. This result improves the result in H. Yang and A. Milani [Bull. Sci. Math. 124 (2000), 415-433] in the sense that, under the above restriction on the initial data, the decay rate given in that paper can be improved by t -γ/2. © European Mathematical Society.

  11. Diffuse interstellar clouds

    International Nuclear Information System (INIS)

    Black, J.H.

    1987-01-01

    The author defines and discusses the nature of diffuse interstellar clouds. He discusses how they contribute to the general extinction of starlight. The atomic and molecular species that have been identified in the ultraviolet, visible, and near infrared regions of the spectrum of a diffuse cloud are presented. The author illustrates some of the practical considerations that affect absorption line observations of interstellar atoms and molecules. Various aspects of the theoretical description of diffuse clouds required for a full interpretation of the observations are discussed

  12. Infrared diffuse interstellar bands

    Science.gov (United States)

    Galazutdinov, G. A.; Lee, Jae-Joon; Han, Inwoo; Lee, Byeong-Cheol; Valyavin, G.; Krełowski, J.

    2017-05-01

    We present high-resolution (R ˜ 45 000) profiles of 14 diffuse interstellar bands in the ˜1.45 to ˜2.45 μm range based on spectra obtained with the Immersion Grating INfrared Spectrograph at the McDonald Observatory. The revised list of diffuse bands with accurately estimated rest wavelengths includes six new features. The diffuse band at 15 268.2 Å demonstrates a very symmetric profile shape and thus can serve as a reference for finding the 'interstellar correction' to the rest wavelength frame in the H range, which suffers from a lack of known atomic/molecular lines.

  13. Self diffusion in tungsten

    International Nuclear Information System (INIS)

    Mundy, J.N.; Rothman, S.J.; Lam, N.Q.; Nowicki, L.J.; Hoff, H.A.

    1978-01-01

    The lack of understanding of self-diffusion in Group VI metals together with the wide scatter in the measured values of tungsten self-diffusion has prompted the present measurements to be made over a wide temperature range (1/2Tsub(m) to Tsub(m)). The diffusion coefficients have been measured in the temperature range 1430-2630 0 C. The present measurements show non-linear Arrhenius behavior but a reliable two-exponential fit of the data should await further measurements. (Auth.)

  14. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli

    2011-02-01

    Full Text Available Two main perspectives of investigation emerge from the study of a territory’s rurality: a geographical approach and a sociological approach. The research examines the sub-regional study case of ‘Nuovo circondario imolese’. The analysis shows that the combination of traditional institutional criteria with detailed informations about the territory, generates more accurate results which determine a better comprehension of the characteristics of restricted areas’ rurality. Over the period 1991-2001, the study highlights an increase in rural areas. This result could be interpreted as an effect of urban sprawl’s intensification, that increases the competition between non-farm residences and agricultural activities.

  15. Quantifying intracellular hydrogen peroxide perturbations in terms of concentration

    Directory of Open Access Journals (Sweden)

    Beijing K. Huang

    2014-01-01

    Full Text Available Molecular level, mechanistic understanding of the roles of reactive oxygen species (ROS in a variety of pathological conditions is hindered by the difficulties associated with determining the concentration of various ROS species. Here, we present an approach that converts fold-change in the signal from an intracellular sensor of hydrogen peroxide into changes in absolute concentration. The method uses extracellular additions of peroxide and an improved biochemical measurement of the gradient between extracellular and intracellular peroxide concentrations to calibrate the intracellular sensor. By measuring peroxiredoxin activity, we found that this gradient is 650-fold rather than the 7–10-fold that is widely cited. The resulting calibration is important for understanding the mass-action kinetics of complex networks of redox reactions, and it enables meaningful characterization and comparison of outputs from endogenous peroxide generating tools and therapeutics across studies.

  16. Simple Recovery of Intracellular Gold Nanoparticles from Peanut Seedling Roots.

    Science.gov (United States)

    Raju, D; Mehta, Urmil J; Ahmad, Absar

    2015-02-01

    Fabrication of inorganic nanomaterials via a biological route witnesses the formation either extracellularly, intracellulary or both. Whereas extracellular formation of these nanomaterials is cherished owing to their easy and economical extraction and purification processes; the intracellular formation of nanomaterials, due to the lack of a proper recovery protocol has always been dreaded, as the extraction processes used so far were tedious, costly, time consuming and often resulting in very low recovery. The aim of the present study was to overcome the problems related with the extraction and recovery of intracellularly synthesized inorganic nanoparticles, and to devise a method to increasing the output, the shape, size, composition and dispersal of nanoparticles is not altered. Water proved to be much better system as it provided well dispersed, stable gold nanoparticles and higher recovery. This is the first report, where intracellular nanoparticles have been recovered using a very cost-effective and eco-friendly approach.

  17. Diffusion-weighted imaging in acute demyelinating myelopathy

    International Nuclear Information System (INIS)

    Zecca, Chiara; Cereda, Carlo; Tschuor, Silvia; Staedler, Claudio; Nadarajah, Navarajah; Bassetti, Claudio L.; Gobbi, Claudio; Wetzel, Stephan; Santini, Francesco

    2012-01-01

    Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions. Six consecutive patients (two males, four females; aged 28-64 years) with acute spinal cord demyelinating lesions were studied in a prospective case series design from June 2009 to October 2010. We performed magnetic resonance imaging studies from 2 to 14 days from symptom onset on the patients with relapsing remitting multiple sclerosis (n = 3) or clinically isolated syndrome (n = 3). Main outcome measures were diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of acute spinal cord demyelinating lesions. All spinal lesions showed a restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A good correlation between clinical presentation and lesion site was observed. Acute demyelinating spinal cord lesions show a uniform restricted diffusion pattern. Clinicians and neuro-radiologists should be aware that this pattern is not necessarily confirmatory for an ischaemic aetiology. (orig.)

  18. Diffusion-weighted imaging in acute demyelinating myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zecca, Chiara; Cereda, Carlo; Tschuor, Silvia; Staedler, Claudio; Nadarajah, Navarajah; Bassetti, Claudio L.; Gobbi, Claudio [Ospedale Regionale di Lugano, Servizio di Neurologia e Neuroradiologia, Neurocenter of Southern Switzerland, Lugano (Switzerland); Wetzel, Stephan [Swiss Neuro Institute (SNI), Abteilung fuer Neuroradiologie, Hirslanden Klinik Zuerich, Zuerich (Switzerland); Santini, Francesco [University of Basel Hospital, Division of Radiological Physics, Basel (Switzerland)

    2012-06-15

    Diffusion-weighted imaging (DWI) has become a reference MRI technique for the evaluation of neurological disorders. Few publications have investigated the application of DWI for inflammatory demyelinating lesions. The purpose of the study was to describe diffusion-weighted imaging characteristics of acute, spinal demyelinating lesions. Six consecutive patients (two males, four females; aged 28-64 years) with acute spinal cord demyelinating lesions were studied in a prospective case series design from June 2009 to October 2010. We performed magnetic resonance imaging studies from 2 to 14 days from symptom onset on the patients with relapsing remitting multiple sclerosis (n = 3) or clinically isolated syndrome (n = 3). Main outcome measures were diffusion-weighted imaging and apparent diffusion coefficient pattern (ADC) of acute spinal cord demyelinating lesions. All spinal lesions showed a restricted diffusion pattern (DWI+/ADC-) with a 24% median ADC signal decrease. A good correlation between clinical presentation and lesion site was observed. Acute demyelinating spinal cord lesions show a uniform restricted diffusion pattern. Clinicians and neuro-radiologists should be aware that this pattern is not necessarily confirmatory for an ischaemic aetiology. (orig.)

  19. Ultrasonic Examination of Jet Pump Diffuser Assemblies

    International Nuclear Information System (INIS)

    Hacker, M.; Levesque, M.; Whitman, G.

    1998-01-01

    In October 1997 the Boiling Water REactor Vessel and Internals Project (BWRVIP) issued the BWR Jet Pump Assembly Inspection and Flaw Evaluation Guidelines (BWRVIP-41). This document identified several welds on the jet pump diffuser assembly that are susceptible to Intergranular Stress Corrosion Cracking (IGSCC) or fatigue, and whose failure could result in jet pump disassembly. Based on the potential for failures, the document recommends inspection of 50% of the high priority welds at the next refueling outage for each BWR, with 100% expansion if flaws are identified. Because each diffuser assembly contains as many as six high priority welds, and access to these welds from the annulus is very restricted, implementing these recommendations can have a significant impact on outage critical path. In an effort to minimize the impact of implementing these recommendations, Framatome Technologies, Inc (FTI) developed a method to perform ultrasonic examinations of the jet pump diffuser assembly welds utilizing remotely operated equipment from the inner diameter (ID) of the diffuser assembly. This paper will discuss the tooling, ultrasonic methods, and delivery techniques used to perform the examinations, as well as the results obtained from a spring 1998 deployment of the system at a U.S. Nuclear Generating Plant. (Author)

  20. Parenting and restrictions in childhood epilepsy

    NARCIS (Netherlands)

    Rodenburg, R.; Meijer, A.M.; Scherphof, C.; Carpay, J.A.; Augustijn, P.; Aldenkamp, A.P.; Deković, M.

    2013-01-01

    Purpose: From the overprotection literature, the predictive and interactional (moderation) effects of controlling and indulgent parenting on restrictions in children with epilepsy were examined. Methods: Parents of 73 children with epilepsy completed questionnaires on parenting, restrictions, and

  1. Clinical application of diffusion-weighted magnetic resonance imaging to intracranial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yanaka, Kiyoyuki; Shirai, Shizuo; Kimura, Hiroshi [Soujinkai Hospital, Ibaraki (Japan); Kamezaki, Takao; Matsumura, Akira; Nose, Tadao

    1995-09-01

    Diffusion-weighted magnetic resonance imaging was performed to determine the changes in water diffusion and to investigate the detectability of diffusion anisotropy in patients with intracranial disorders. Diffusion maps of the apparent diffusion coefficient (ADC) were created of 19 patients with cerebral infarction, five with intracerebral hematoma, four with glioma, four with meningioma, four with hydrocephalus, and five with subdural hematoma. ADC was increased in chronic cerebral infarction and glioma, and decreased in acute cerebral infarction, meningioma, and the marginal area of glioma compared with the ADC of the normal gray matter. There was a significant difference in ADC between the marginal and internal areas of glioma. Increased ADC may be due to increased vasogenic edema in infarction and a lack of significant restriction of diffusion within glioma. Decreased ADC can be attributed to restricted diffusion caused by cytotoxic edema in infarction and the underlying histological pattern of densely packed tumor cells in glioma. Diffusion anisotropy of the internal capsule was less detectable in pathological than normal hemispheres. Diffusion anisotropy was less detectable in patients with hydrocephalus and subdural hematoma. Intracranial lesions were thought to have influenced the compression of the brain structures and cells, resulting in decreased diffusion. The measurement of ADC by diffusion-weighted magnetic resonance imaging has the potential for greater understanding of the biophysical changes in various intracranial disorders, including correct diagnosis of cerebral infarction, and histological diagnosis of brain tumor. (author).

  2. Tethering factors as organizers of intracellular vesicular traffic.

    Science.gov (United States)

    Yu, I-Mei; Hughson, Frederick M

    2010-01-01

    Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

  3. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    Science.gov (United States)

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  4. Diffusion of Wilson loops

    International Nuclear Information System (INIS)

    Brzoska, A.M.; Lenz, F.; Thies, M.; Negele, J.W.

    2005-01-01

    A phenomenological analysis of the distribution of Wilson loops in SU(2) Yang-Mills theory is presented in which Wilson loop distributions are described as the result of a diffusion process on the group manifold. It is shown that, in the absence of forces, diffusion implies Casimir scaling and, conversely, exact Casimir scaling implies free diffusion. Screening processes occur if diffusion takes place in a potential. The crucial distinction between screening of fundamental and adjoint loops is formulated as a symmetry property related to the center symmetry of the underlying gauge theory. The results are expressed in terms of an effective Wilson loop action and compared with various limits of SU(2) Yang-Mills theory

  5. Diffusion between evolving interfaces

    International Nuclear Information System (INIS)

    Juntunen, Janne; Merikoski, Juha

    2010-01-01

    Diffusion in an evolving environment is studied by continuous-time Monte Carlo simulations. Diffusion is modeled by continuous-time random walkers on a lattice, in a dynamic environment provided by bubbles between two one-dimensional interfaces driven symmetrically towards each other. For one-dimensional random walkers constrained by the interfaces, the bubble size distribution dominates diffusion. For two-dimensional random walkers, it is also controlled by the topography and dynamics of the interfaces. The results of the one-dimensional case are recovered in the limit where the interfaces are strongly driven. Even with simple hard-core repulsion between the interfaces and the particles, diffusion is found to depend strongly on the details of the dynamical rules of particles close to the interfaces.

  6. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements

  7. Diffusing Best Practices

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    2014-01-01

    approach. The study context is a design case in which an organization desires to diffuse its best practices across different groups. The design goal is embodied in organizational mechanisms to achieve this diffusion. The study used Theory of Planned Behavior (TPB) as a kernel theory. The artifacts...... resulting from the design were two-day training workshops conceptually anchored to TBP. The design theory was evaluated through execution of eight diffusion workshops involving three different groups in the same company. The findings indicate that the match between the practice and the context materialized...... that the behavior will be effective). These two factors were especially critical if the source context of the best practice is qualitatively different from the target context into which the organization is seeking to diffuse the best practice....

  8. Detection of diffusible substances

    Energy Technology Data Exchange (ETDEWEB)

    Warembourg, M [Lille-1 Univ., 59 - Villeneuve-d' Ascq (France)

    1976-12-01

    The different steps of a radioautographic technique for the detection of diffusible substances are described. Using this radioautographic method, the topographic distribution of estradiol-concentrating neurons was studied in the nervous system and pituitary of the ovariectomized mouse and guinea-pig. A relatively good morphological preservation of structures can be ascertained on sections from unfixed, unembedded tissues prepared at low temperatures and kept-under relatively low humidity. The translocation or extraction of diffusible substances is avoided by directly mounting of frozen sections on dried photographic emulsion. Since no solvent is used, this technique excludes the major sources of diffusion artifacts and permits to be in favourable conditions for the localization of diffusible substances.

  9. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    Diffusion and permeation are discussed within the context of irreversible thermodynamics. A new expression for the generalized Stokes-Einstein equation is obtained which links the permeability to the diffusivity of a two-component solution and contains the poroelastic Biot-Willis coefficient. The theory is illustrated by predicting the concentration and pressure profiles during the filtration of a protein solution. At low concentrations the proteins diffuse independently while at higher concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements. © 2009 Walter de Gruyter, Berlin, New York.

  10. 49 CFR 383.95 - Restrictions.

    Science.gov (United States)

    2010-10-01

    ... the skills test and the restriction, air brakes shall include any braking system operating fully or...; REQUIREMENTS AND PENALTIES Vehicle Groups and Endorsements § 383.95 Restrictions. (a) Air brake restrictions... skills test in a vehicle not equipped with air brakes, the State must indicate on the CDL, if issued...

  11. 9 CFR 92.3 - Movement restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Movement restrictions. 92.3 Section 92... ANIMAL PRODUCTS: PROCEDURES FOR REQUESTING RECOGNITION OF REGIONS § 92.3 Movement restrictions. Whenever... exist and the EC imposes prohibitions or other restrictions on the movement of animals or animal...

  12. 21 CFR 203.20 - Sales restrictions.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sales restrictions. 203.20 Section 203.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Sales Restrictions § 203.20 Sales restrictions. Except as provided in § 203.22 or...

  13. Intracellular localization of Treponema denticola chymotrypsin-like proteinase in chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Emilia Marttila

    2014-07-01

    Full Text Available Treponema denticola is an important periodontal pathogen capable of tissue invasion. Its chymotrypsin-like proteinase (CTLP can degrade a number of basement membrane components in vitro, thus suggesting a contribution to tissue invasion by the spirochete. The aim of this study was to analyze the localization of CTLP in chronic periodontitis tissues ex vivo. A polyclonal antibody specific to T. denticola cell-bound CTLP was used to detect the spirochetes in the gingival tissues of patients with moderate to severe chronic periodontitis (n=25 by immunohistochemistry and periodic acid-Schiff staining (PAS. The presence of T. denticola in the periodontal tissue samples was analyzed by PCR. Periodontal tissue samples of 12 of the 25 patients were found to be positive for T. denticola by PCR. Moreover, CTLP could be detected in the periodontal tissues of all these patients by immunohistochemistry. In the epithelium, the CTLP was mostly intracellular. Typically, the positive staining could be seen throughout the whole depth of the epithelium. When detected extracellularly, CTLP was localized mainly as granular deposits. The connective tissue stained diffusely positive in four cases. The positive staining co-localized with the PAS stain in nine cases. T. denticola and its CTLP could be detected in diseased human periodontium both intra- and extracellularly. The granular staining pattern was suggestive of the presence of T. denticola bacteria, whereas the more diffused staining pattern was indicative of the recent presence of the bacterium and shedding of the cell-bound proteinase.

  14. Drift-Diffusion Equation

    Directory of Open Access Journals (Sweden)

    K. Banoo

    1998-01-01

    equation in the discrete momentum space. This is shown to be similar to the conventional drift-diffusion equation except that it is a more rigorous solution to the Boltzmann equation because the current and carrier densities are resolved into M×1 vectors, where M is the number of modes in the discrete momentum space. The mobility and diffusion coefficient become M×M matrices which connect the M momentum space modes. This approach is demonstrated by simulating electron transport in bulk silicon.

  15. Intracellular crowding effects on the self-association of the bacterial cell division protein FtsZ.

    Science.gov (United States)

    Naddaf, Lamis; Sayyed-Ahmad, Abdallah

    2014-12-15

    The dimerization rate of the bacterial cell division protein FtsZ is strongly affected by the intracellular crowding. Yet the complexity of the intracellular environment makes it difficult to investigate via all-atom molecular dynamics or other detailed theoretical methods. We study the crowding effect on FtsZ dimerization which is the first step of an oligomerization process that results in more elaborate supramolecular structures. In particular, we consider the effect of intracellular crowding on the reaction rates, and their dependence on the different concentrations of crowding agents. We achieved this goal by using Brownian dynamics (BD) simulation techniques and a modified post-processing approach in which we decompose the rate constant in crowded media as a product of the rate constant in the dilute solution times a factor that incorporates the crowding effect. The latter factor accounts for the diffusion reduction and crowder induced energy. In addition we include the crowding effects on water viscosity in the BD simulations of crowded media. We finally show that biomolecular crowding has a considerable effect on the FtsZ dimerization by increasing the dimerization rate constant from 2.6×10(7)M(-1)s(-1) in the absence of crowders to 1.0×10(8)M(-1)s(-1) at crowding level of 0.30. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Advanced manufacturing: Technology diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Tesar, A.

    1995-12-01

    In this paper we examine how manufacturing technology diffuses rom the developers of technology across national borders to those who do not have the capability or resources to develop advanced technology on their own. None of the wide variety of technology diffusion mechanisms discussed in this paper are new, yet the opportunities to apply these mechanisms are growing. A dramatic increase in technology diffusion occurred over the last decade. The two major trends which probably drive this increase are a worldwide inclination towards ``freer`` markets and diminishing isolation. Technology is most rapidly diffusing from the US In fact, the US is supplying technology for the rest of the world. The value of the technology supplied by the US more than doubled from 1985 to 1992 (see the Introduction for details). History shows us that technology diffusion is inevitable. It is the rates at which technologies diffuse to other countries which can vary considerably. Manufacturers in these countries are increasingly able to absorb technology. Their manufacturing efficiency is expected to progress as technology becomes increasingly available and utilized.

  17. Now consider diffusion

    International Nuclear Information System (INIS)

    Dungey, J.W.

    1984-01-01

    The authors want to talk about future work, but first he will reply to Stan Cowley's comment on his naivety in believing in the whole story to 99% confidence in '65, when he knew about Fairfield's results. Does it matter whether you make the right judgment about theories? Yes, it does, particularly for experimentalists perhaps, but also for theorists. The work you do later depends on the judgment you've made on previous work. People have wasted a lot of time developing on insecure or even wrong foundations. Now for future work. One mild surprise the authors have had is that they haven't heard more about diffusion, in two contexts. Gordon Rostoker is yet to come and he may talk about particles getting into the magnetosphere by diffusion. Lots of noise is observed and so diffusion must happen. If time had not been short, the authors were planning to discuss in a handwaving way what sort of diffusion mechanisms one might consider. The other aspect of diffusion he was going to talk about is at the other end of things and is velocity diffusion, which is involved in anomalous resistivity

  18. Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

    Science.gov (United States)

    Caro-Domínguez, Pablo; Gupta, Abha A; Chavhan, Govind B

    2018-01-01

    There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions. To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions. We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis. We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test Pbenign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10 -3  mm 2 /s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions. Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the

  19. The epithelial cell cytoskeleton and intracellular trafficking. I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more.

    Science.gov (United States)

    Johannes, Ludger

    2002-07-01

    Many intracellular transport routes are still little explored. This is particularly true for retrograde transport between the plasma membrane and the endoplasmic reticulum. Shiga toxin B subunit has become a powerful tool to study this pathway, and recent advances on the molecular mechanisms of transport in the retrograde route and on its physiological function(s) are summarized. Furthermore, it is discussed how the study of retrograde transport of Shiga toxin B subunit allows one to design new methods for the intracellular delivery of therapeutic compounds.

  20. Fractional diffusion models of transport in magnetically confined plasmas

    International Nuclear Information System (INIS)

    Castillo-Negrete, D. del; Carreras, B. A.; Lynch, V. E.

    2005-01-01

    Experimental and theoretical evidence suggests that transport in magnetically confined fusion plasmas deviates from the standard diffusion paradigm. Some examples include the confinement time scaling in L-mode plasmas, rapid pulse propagation phenomena, and inward transport in off-axis fueling experiments. The limitations of the diffusion paradigm can be traced back to the restrictive assumptions in which it is based. In particular, Fick's law, one of the cornerstones of diffusive transport, assumes that the fluxes only depend on local quantities, i. e. the spatial gradient of the field (s). another key issue is the Markovian assumption that neglects memory effects. Also, at a microscopic level, standard diffusion assumes and underlying Gaussian, uncorrelated stochastic process (i. e. a Brownian random walk) with well defined characteristic spatio-temporal scales. Motivated by the need to develop models of non-diffusive transport, we discuss here a class of transport models base on the use of fractional derivative operators. The models incorporates in a unified way non-Fickian transport, non-Markovian processes or memory effects, and non-diffusive scaling. At a microscopic level, the models describe an underlying stochastic process without characteristic spatio-temporal scales that generalizes the Brownian random walk. As a concrete case study to motivate and test the model, we consider transport of tracers in three-dimensional, pressure-gradient-driven turbulence. We show that in this system transport is non-diffusive and cannot be described in the context of the standard diffusion parading. In particular, the probability density function (pdf) of the radial displacements of tracers is strongly non-Gaussian with algebraic decaying tails, and the moments of the tracer displacements exhibit super-diffusive scaling. there is quantitative agreement between the turbulence transport calculations and the proposed fractional diffusion model. In particular, the model

  1. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

    Science.gov (United States)

    There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

  2. FLIPR assays of intracellular calcium in GPCR drug discovery

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Bräuner-Osborne, Hans

    2009-01-01

    Fluorescent dyes sensitive to changes in intracellular calcium have become increasingly popular in G protein-coupled receptor (GPCR) drug discovery for several reasons. First of all, the assays using the dyes are easy to perform and are of low cost compared to other assays. Second, most non...

  3. Intracellular localization of Na + /H + antiporter from Malus zumi ...

    African Journals Online (AJOL)

    In this study, we examined the intracellular localization of the product of Na+/H+ antiporter gene (MzNHX1) cloned from Malus zumi. Analysis using yeast cells expressing a fusion protein of MzNHX1 and green fluorescent protein confirmed the localization of MzNHX1 on the tonoplast.

  4. Intracellular pH gradients in migrating cells

    DEFF Research Database (Denmark)

    Martin, Christine; Pedersen, Stine Helene Falsig; Schwab, Albrecht

    2011-01-01

    might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of p...

  5. Structural rearrangement of the intracellular domains during AMPA receptor activation

    DEFF Research Database (Denmark)

    Zachariassen, Linda Grønborg; Katchan, Ljudmila; Jensen, Anna Guldvang

    2016-01-01

    -clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence...

  6. The interferon response to intracellular DNA: why so many receptors?

    Science.gov (United States)

    Unterholzner, Leonie

    2013-11-01

    The detection of intracellular DNA has emerged to be a key event in the innate immune response to viruses and intracellular bacteria, and during conditions of sterile inflammation and autoimmunity. One of the consequences of the detection of DNA as a 'stranger' and a 'danger' signal is the production of type I interferons and pro-inflammatory cytokines. Much work has been dedicated to the elucidation of the signalling cascades that activate this DNA-induced gene expression programme. However, while many proteins have been proposed to act as sensors for intracellular DNA in recent years, none has been met with universal acceptance, and a theory linking all the recent observations is, as yet, lacking. This review presents the evidence for the various interferon-inducing DNA receptors proposed to date, and examines the hypotheses that might explain why so many different receptors appear to be involved in the innate immune recognition of intracellular DNA. Copyright © 2013 Elsevier GmbH. All rights reserved.

  7. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

    Directory of Open Access Journals (Sweden)

    Dhritiman Samanta

    2017-05-01

    Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

  8. Engineering of obligate intracellular bacteria: progress, challenges and paradigms

    Science.gov (United States)

    Over twenty years have passed since the first report of genetic manipulation of an obligate intracellular bacterium. Through progress interspersed by bouts of stagnation, microbiologists and geneticists have developed approaches to genetically manipulate obligates. A brief overview of the current ge...

  9. Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

    DEFF Research Database (Denmark)

    Carlsson, Carl Michael; Bengtson, Per; Cucak, Helena

    2013-01-01

    these transferrin glycoforms differently after preloading with exogenously added galectin-3. In all, this study provides the first evidence of a functional role for transferrin glycans, in intracellular trafficking after uptake. Moreover, the galectin-3 bound glycoform increased in cancer, suggesting...

  10. Dihydroceramide biology - Structure-specific metabolism and intracellular localization

    NARCIS (Netherlands)

    Kok, JW; NikolovaKarakashian, M; Klappe, K; Alexander, C; Merrill, AH

    1997-01-01

    This study utilized fluorescent analogs to characterize the intracellular transport and metabolism of dihydroceramide (DN-Cer), an intermediate in de novo sphingolipid biosynthesis, When 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoyl-DH-Cer (C-6-NBD-DH-Cer) was incubated with HT29, NRK, BHK,

  11. CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

    Directory of Open Access Journals (Sweden)

    Samuel eGoodchild

    2012-06-01

    Full Text Available Voltage sensing domains of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. However, several other factors not directly linked to the voltage dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

  12. Biomineralization Patterns of Intracellular Carbonatogenesis in Cyanobacteria: Molecular Hypotheses

    Directory of Open Access Journals (Sweden)

    Jinhua Li

    2016-02-01

    Full Text Available The recent discovery of intracellular carbonatogenesis in several cyanobacteria species has challenged the traditional view that this process was extracellular and not controlled. However, a detailed analysis of the size distribution, chemical composition and 3-D-arrangement of carbonates in these cyanobacteria is lacking. Here, we characterized these features in Candidatus Gloeomargarita lithophora C7 and Candidatus Synechococcus calcipolaris G9 by conventional transmission electron microscopy, tomography, ultramicrotomy, and scanning transmission X-ray microscopy (STXM. Both Ca. G. lithophora C7 and Ca. S. calcipolaris G9 formed numerous polyphosphate granules adjacent or engulfing Ca-carbonate inclusions when grown in phosphate-rich solutions. Ca-carbonates were scattered within Ca. G. lithophora C7 cells under these conditions, but sometimes arranged in one or several chains. In contrast, Ca-carbonates formed at cell septa in Ca. S. calcipolaris G9 and were segregated equally between daughter cells after cell division, arranging as distorted disks at cell poles. The size distribution of carbonates evolved from a positively to a negatively skewed distribution as particles grew. Conventional ultramicrotomy did not preserve Ca-carbonates explaining partly why intracellular calcification has been overlooked in the past. All these new observations allow discussing with unprecedented insight some nucleation and growth processes occurring in intracellularly calcifying cyanobacteria with a particular emphasis on the possible involvement of intracellular compartments and cytoskeleton.

  13. Cytoplasmic tail of coronavirus spike protein has intracellular

    Indian Academy of Sciences (India)

    https://www.ias.ac.in/article/fulltext/jbsc/042/02/0231-0244. Keywords. Coronavirus spike protein trafficking; cytoplasmic tail signal; endoplasmic reticulum–Golgi intermediate complex; lysosome. Abstract. Intracellular trafficking and localization studies of spike protein from SARS and OC43 showed that SARS spikeprotein is ...

  14. Facilitating Intracellular Drug Delivery by Ultrasound-Activated Microbubbles

    NARCIS (Netherlands)

    Lammertink, BHA

    2017-01-01

    The goal of this thesis was to investigate the combination of ultrasound and microbubbles (USMB) for intracellular delivery of (model) drugs in vitro. We have focused on clinically approved drugs, i.e. cisplatin, and microbubbles, i.e. SonoVue™, to facilitate clinical translation. In addition, model

  15. NMR diffusion simulation based on conditional random walk.

    Science.gov (United States)

    Gudbjartsson, H; Patz, S

    1995-01-01

    The authors introduce here a new, very fast, simulation method for free diffusion in a linear magnetic field gradient, which is an extension of the conventional Monte Carlo (MC) method or the convolution method described by Wong et al. (in 12th SMRM, New York, 1993, p.10). In earlier NMR-diffusion simulation methods, such as the finite difference method (FD), the Monte Carlo method, and the deterministic convolution method, the outcome of the calculations depends on the simulation time step. In the authors' method, however, the results are independent of the time step, although, in the convolution method the step size has to be adequate for spins to diffuse to adjacent grid points. By always selecting the largest possible time step the computation time can therefore be reduced. Finally the authors point out that in simple geometric configurations their simulation algorithm can be used to reduce computation time in the simulation of restricted diffusion.

  16. Restricted Predicates for Hypothetical Datalog

    Directory of Open Access Journals (Sweden)

    Fernando Sáenz-Pérez

    2015-12-01

    Full Text Available Hypothetical Datalog is based on an intuitionistic semantics rather than on a classical logic semantics, and embedded implications are allowed in rule bodies. While the usual implication (i.e., the neck of a Horn clause stands for inferring facts, an embedded implication plays the role of assuming its premise for deriving its consequence. A former work introduced both a formal framework and a goal-oriented tabled implementation, allowing negation in rule bodies. While in that work positive assumptions for both facts and rules can occur in the premise, negative assumptions are not allowed. In this work, we cover this subject by introducing a new concept: a restricted predicate, which allows negative assumptions by pruning the usual semantics of a predicate. This new setting has been implemented in the deductive system DES.

  17. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Anjali Kumari

    Full Text Available Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl ethylenediamine (TPEN and Zinc Sulfate (ZnSO4. Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death

  18. A Traffic Restriction Scheme for Enhancing Carpooling

    Directory of Open Access Journals (Sweden)

    Dong Ding

    2017-01-01

    Full Text Available For the purpose of alleviating traffic congestion, this paper proposes a scheme to encourage travelers to carpool by traffic restriction. By a variational inequity we describe travelers’ mode (solo driving and carpooling and route choice under user equilibrium principle in the context of fixed demand and detect the performance of a simple network with various restriction links, restriction proportions, and carpooling costs. Then the optimal traffic restriction scheme aiming at minimal total travel cost is designed through a bilevel program and applied to a Sioux Fall network example with genetic algorithm. According to various requirements, optimal restriction regions and proportions for restricted automobiles are captured. From the results it is found that traffic restriction scheme is possible to enhance carpooling and alleviate congestion. However, higher carpooling demand is not always helpful to the whole network. The topology of network, OD demand, and carpooling cost are included in the factors influencing the performance of the traffic system.

  19. Lead diffusion in monazite

    International Nuclear Information System (INIS)

    Gardes, E.

    2006-06-01

    Proper knowledge of the diffusion rates of lead in monazite is necessary to understand the U-Th-Pb age anomalies of this mineral, which is one of the most used in geochronology after zircon. Diffusion experiments were performed in NdPO 4 monocrystals and in Nd 0.66 Ca 0.17 Th 0.17 PO 4 polycrystals from Nd 0.66 Pb 0.17 Th 0.17 PO 4 thin films to investigate Pb 2+ + Th 4+ ↔ 2 Nd 3+ and Pb 2+ ↔ Ca 2+ exchanges. Diffusion annealings were run between 1200 and 1500 Celsius degrees, at room pressure, for durations ranging from one hour to one month. The diffusion profiles were analysed using TEM (transmission electronic microscopy) and RBS (Rutherford backscattering spectroscopy). The diffusivities extracted for Pb 2+ + Th 4+ ↔ 2 Nd 3+ exchange follow an Arrhenius law with parameters E equals 509 ± 24 kJ mol -1 and log(D 0 (m 2 s -1 )) equals -3.41 ± 0.77. Preliminary data for Pb 2+ ↔ Ca 2+ exchange are in agreement with this result. The extrapolation of our data to crustal temperatures yields very slow diffusivities. For instance, the time necessary for a 50 μm grain to lose all of its lead at 800 Celsius degrees is greater than the age of the Earth. From these results and other evidence from the literature, we conclude that most of the perturbations in U-Th-Pb ages of monazite cannot be attributed to lead diffusion, but rather to interactions with fluids. (author)

  20. Single-cell intracellular nano-pH probes†

    Science.gov (United States)

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

  1. Single-cell intracellular nano-pH probes.

    Science.gov (United States)

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

  2. Legionella pneumophila transcriptome during intracellular multiplication in human macrophages

    Directory of Open Access Journals (Sweden)

    Sebastien P Faucher

    2011-04-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires’ disease, an acute pulmonary infection. L. pneumophila is able to infect and multiply in both phagocytic protozoa, such as Acanthamoeba castellanii, and mammalian professional phagocytes. The best-known L. pneumophila virulence determinant is the Icm/Dot Type IVB secretion system (TFBSS, which is used to translocate more than 150 effector proteins to host cells. While the transcriptional response of Legionella to the intracellular environment of A. castellanii has been investigated, much less is known about the Legionella transcriptional response inside human macrophages. In this study, the transcriptome of L. pneumophila was monitored during exponential and post-exponential phase in rich AYE broth as well as during infection of human cultured macrophages. This was accomplished with microarrays and an RNA amplification procedure called SCOTS to detect small amounts of mRNA from low numbers of intracellular bacteria. Among the genes induced intracellularly are those involved in amino acid biosynthetic pathways leading to L-arginine, L-histidine and L-proline as well as many transport systems involved in amino acid and iron uptake. Gene involved in catabolism of glycerol is also induced during intracellular growth and could be used as a carbon source. The genes encoding the Icm/Dot system are not differentially expressed inside cells compared to control bacteria grown in rich broth, but the genes encoding several translocated effectors are strongly induced. Moreover, we used the transcriptome data to predict previously unrecognized Icm/Dot effector genes based on their expression pattern and confirmed translocation for three candidates. This study provides a comprehensive view of how L. pneumophila responds to the human macrophage intracellular environment.

  3. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Troemel, Emily R; Félix, Marie-Anne; Whiteman, Noah K; Barrière, Antoine; Ausubel, Frederick M

    2008-12-09

    For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes.

  4. Restricted Interval Valued Neutrosophic Sets and Restricted Interval Valued Neutrosophic Topological Spaces

    Directory of Open Access Journals (Sweden)

    Anjan Mukherjee

    2016-08-01

    Full Text Available In this paper we introduce the concept of restricted interval valued neutrosophic sets (RIVNS in short. Some basic operations and properties of RIVNS are discussed. The concept of restricted interval valued neutrosophic topology is also introduced together with restricted interval valued neutrosophic finer and restricted interval valued neutrosophic coarser topology. We also define restricted interval valued neutrosophic interior and closer of a restricted interval valued neutrosophic set. Some theorems and examples are cites. Restricted interval valued neutrosophic subspace topology is also studied.

  5. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole 1

    Science.gov (United States)

    Tucker, Joseph E.; Mauzerall, David; Tucker, Edward B.

    1989-01-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water. PMID:16666864

  6. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole.

    Science.gov (United States)

    Tucker, J E; Mauzerall, D; Tucker, E B

    1989-07-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water.

  7. Diffusion-Weighted Magnetic Resonance Imaging of Cerebrospinal Fluid in Patients with and without Communicating Hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Nasel, C.; Gentzsch, S.; Heimberger, K. [Cerebrovascular Imaging Workgroup of the Div. of Neuroradiology, Dept. of Radiology, Medical Univ. Vienna, Vienna (Austria)

    2007-09-15

    Background: Recent concepts about cerebrospinal fluid (CSF) circulation in communicating hydrocephalus (CoHy), which is also termed 'restricted arterial pulsation hydrocephalus,' suggest reduced arterial pulsations of subarachnoid vessels with a smaller amount of CSF shifted in subarachnoid spaces during the early systole. The postulated restriction of subarachnoid arterial pulsations in CoHy should induce a smaller motion artifact and reduced local stream effects in CSF in magnetic resonance (MR) diffusion-weighted imaging (DWI). Purpose: To investigate the maximum diffusivity in CSF in patients with and without CoHy using DWI. Material and Methods: 12 patients without CSF circulation disturbances and six cases with proven CoHy were assessed. Diffusion was measured in six non collinear directions without triggering the arterial pulse wave (scan time 6:45 min, voxel size 2x2x2 mm). Due to expected artifacts, the calculated maximum diffusivity was called apparent diffusivity. Regional high and low apparent diffusivity was assessed in CSF spaces on newly created 3D CSF motion maps. Results: Patients with regular CSF circulation exhibited high apparent diffusivity in CSF in basal subarachnoid spaces, whereas apparent diffusivity was low there in patients with CoHy. Conclusion: DWI opens a feasible approach to study CSF motion in the neurocranium. Restricted arterial pulsations seem to be involved in CoHy.

  8. Diffusion-Weighted Magnetic Resonance Imaging of Cerebrospinal Fluid in Patients with and without Communicating Hydrocephalus

    International Nuclear Information System (INIS)

    Nasel, C.; Gentzsch, S.; Heimberger, K.

    2007-01-01

    Background: Recent concepts about cerebrospinal fluid (CSF) circulation in communicating hydrocephalus (CoHy), which is also termed 'restricted arterial pulsation hydrocephalus,' suggest reduced arterial pulsations of subarachnoid vessels with a smaller amount of CSF shifted in subarachnoid spaces during the early systole. The postulated restriction of subarachnoid arterial pulsations in CoHy should induce a smaller motion artifact and reduced local stream effects in CSF in magnetic resonance (MR) diffusion-weighted imaging (DWI). Purpose: To investigate the maximum diffusivity in CSF in patients with and without CoHy using DWI. Material and Methods: 12 patients without CSF circulation disturbances and six cases with proven CoHy were assessed. Diffusion was measured in six non collinear directions without triggering the arterial pulse wave (scan time 6:45 min, voxel size 2x2x2 mm). Due to expected artifacts, the calculated maximum diffusivity was called apparent diffusivity. Regional high and low apparent diffusivity was assessed in CSF spaces on newly created 3D CSF motion maps. Results: Patients with regular CSF circulation exhibited high apparent diffusivity in CSF in basal subarachnoid spaces, whereas apparent diffusivity was low there in patients with CoHy. Conclusion: DWI opens a feasible approach to study CSF motion in the neurocranium. Restricted arterial pulsations seem to be involved in CoHy

  9. Diffusion Influenced Adsorption Kinetics.

    Science.gov (United States)

    Miura, Toshiaki; Seki, Kazuhiko

    2015-08-27

    When the kinetics of adsorption is influenced by the diffusive flow of solutes, the solute concentration at the surface is influenced by the surface coverage of solutes, which is given by the Langmuir-Hinshelwood adsorption equation. The diffusion equation with the boundary condition given by the Langmuir-Hinshelwood adsorption equation leads to the nonlinear integro-differential equation for the surface coverage. In this paper, we solved the nonlinear integro-differential equation using the Grünwald-Letnikov formula developed to solve fractional kinetics. Guided by the numerical results, analytical expressions for the upper and lower bounds of the exact numerical results were obtained. The upper and lower bounds were close to the exact numerical results in the diffusion- and reaction-controlled limits, respectively. We examined the validity of the two simple analytical expressions obtained in the diffusion-controlled limit. The results were generalized to include the effect of dispersive diffusion. We also investigated the effect of molecular rearrangement of anisotropic molecules on surface coverage.

  10. Bicarbonate diffusion through mucus.

    Science.gov (United States)

    Livingston, E H; Miller, J; Engel, E

    1995-09-01

    The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

  11. Changes in diffusion properties of biological tissues associated with mechanical strain

    International Nuclear Information System (INIS)

    Tanaka, Kenichiro; Imae, T.; Mima, Kazuo; Sekino, Masaki; Ohsaki, Hiroyuki; Ueno, Shogo

    2007-01-01

    Mechanical strain in biological tissues causes a change in the diffusion properties of water molecules. This paper proposes a method of estimating mechanical strain in biological tissues using diffusion magnetic resonance imaging (MRI). Measurements were carried out on uncompressed and compressed chicken skeletal muscles. A theoretical model of the diffusion of water molecules in muscle fibers was derived based on Tanner's equation. Diameter of the muscle fibers was estimated by fitting the model equation to the measured signals. Changes in the mean diffusivity (MD), the fractional anisotropy (FA), and diameter of the muscle fiber did not have any statistical significance. The intracellular diffusion coefficient (D int ) was changed by mechanical strain (p<.05). This method has potential applications in the quantitative evaluation of strain in biological tissues, a though it poses several technical challenges. (author)

  12. Cesium diffusion in graphite

    International Nuclear Information System (INIS)

    Evans, R.B. III; Davis, W. Jr.; Sutton, A.L. Jr.

    1980-05-01

    Experiments on diffusion of 137 Cs in five types of graphite were performed. The document provides a completion of the report that was started and includes a presentation of all of the diffusion data, previously unpublished. Except for data on mass transfer of 137 Cs in the Hawker-Siddeley graphite, analyses of experimental results were initiated but not completed. The mass transfer process of cesium in HS-1-1 graphite at 600 to 1000 0 C in a helium atmosphere is essentially pure diffusion wherein values of (E/epsilon) and ΔE of the equation D/epsilon = (D/epsilon) 0 exp [-ΔE/RT] are about 4 x 10 -2 cm 2 /s and 30 kcal/mole, respectively

  13. Apparatus for diffusion separation

    International Nuclear Information System (INIS)

    Nierenberg, W.A.; Pontius, R.B.

    1976-01-01

    The method of testing the separation efficiency of porous permeable membranes is described which comprises causing a stream of a gaseous mixture to flow into contact with one face of a finely porous permeable membrane under such conditions that a major fraction of the mixture diffuses through the membrane, maintaining a rectangular cross section of the gaseous stream so flowing past said membrane, continuously recirculating the gas that diffuses through said membrane and continuously withdrawing the gas that does not diffuse through said membrane and maintaining the volume of said recirculating gas constant by continuously introducing into said continuously recirculating gas stream a mass of gas equivalent to that which is continuously withdrawn from said gas stream and comparing the concentrations of the light component in the entering gas, the withdrawn gas and the recirculated gas in order to determine the efficiency of said membrane

  14. Diffusion in flexible pipes

    Energy Technology Data Exchange (ETDEWEB)

    Brogaard Kristensen, S.

    2000-06-01

    This report describes the work done on modelling and simulation of the complex diffusion of gas through the wall of a flexible pipe. The diffusion and thus the pressure in annulus depends strongly on the diffusion and solubility parameters of the gas-polymer system and on the degree of blocking of the outer surface of the inner liner due to pressure reinforcements. The report evaluates the basis modelling required to describe the complex geometries and flow patterns. Qualitatively results of temperature and concentration profiles are shown in the report. For the program to serve any modelling purpose in 'real life' the results need to be validated and possibly the model needs corrections. Hopefully, a full-scale test of a flexible pipe will provide the required temperatures and pressures in annulus to validate the models. (EHS)

  15. Distributed Control Diffusion

    DEFF Research Database (Denmark)

    Schultz, Ulrik Pagh

    2007-01-01

    . Programming a modular, self-reconfigurable robot is however a complicated task: the robot is essentially a real-time, distributed embedded system, where control and communication paths often are tightly coupled to the current physical configuration of the robot. To facilitate the task of programming modular....... This approach allows the programmer to dynamically distribute behaviors throughout a robot and moreover provides a partial abstraction over the concrete physical shape of the robot. We have implemented a prototype of a distributed control diffusion system for the ATRON modular, self-reconfigurable robot......, self-reconfigurable robots, we present the concept of distributed control diffusion: distributed queries are used to identify modules that play a specific role in the robot, and behaviors that implement specific control strategies are diffused throughout the robot based on these role assignments...

  16. Diffuse Ceiling Ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen; Yu, Tao; Heiselberg, Per Kvols

    cooling capacity, energy saving, low investment cost and low noise level; while the limitations include condensation risk and the limit on the room geometry. Furthermore, the crucial design parameters are summarized and their effects on the system performance are discussed. In addition to the stand...... is not well structured with this system. These become the motivations in developing the design guide. This design guide aims to establish a systematic understanding of diffuse ceiling ventilation and provide assistance in designing of such a system. The guide is targeted at design engineers, architects...... and manufacturers and the users of diffuse ceiling technology. The design guide introduces the principle and key characteristics of room air distribution with diffuse ceiling ventilation. It provides an overview of potential benefit and limitations of this technology. The benefits include high thermal comfort, high...

  17. Diffusion and mass transfer

    CERN Document Server

    Vrentas, James S

    2013-01-01

    The book first covers the five elements necessary to formulate and solve mass transfer problems, that is, conservation laws and field equations, boundary conditions, constitutive equations, parameters in constitutive equations, and mathematical methods that can be used to solve the partial differential equations commonly encountered in mass transfer problems. Jump balances, Green’s function solution methods, and the free-volume theory for the prediction of self-diffusion coefficients for polymer–solvent systems are among the topics covered. The authors then use those elements to analyze a wide variety of mass transfer problems, including bubble dissolution, polymer sorption and desorption, dispersion, impurity migration in plastic containers, and utilization of polymers in drug delivery. The text offers detailed solutions, along with some theoretical aspects, for numerous processes including viscoelastic diffusion, moving boundary problems, diffusion and reaction, membrane transport, wave behavior, sedime...

  18. Diffusion in flexible pipes

    Energy Technology Data Exchange (ETDEWEB)

    Brogaard Kristensen, S

    2000-06-01

    This report describes the work done on modelling and simulation of the complex diffusion of gas through the wall of a flexible pipe. The diffusion and thus the pressure in annulus depends strongly on the diffusion and solubility parameters of the gas-polymer system and on the degree of blocking of the outer surface of the inner liner due to pressure reinforcements. The report evaluates the basis modelling required to describe the complex geometries and flow patterns. Qualitatively results of temperature and concentration profiles are shown in the report. For the program to serve any modelling purpose in 'real life' the results need to be validated and possibly the model needs corrections. Hopefully, a full-scale test of a flexible pipe will provide the required temperatures and pressures in annulus to validate the models. (EHS)

  19. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-23

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

  20. The Trouble with Diffusion

    Directory of Open Access Journals (Sweden)

    R.T. DeHoff

    2002-09-01

    Full Text Available The phenomenological formalism, which yields Fick's Laws for diffusion in single phase multicomponent systems, is widely accepted as the basis for the mathematical description of diffusion. This paper focuses on problems associated with this formalism. This mode of description of the process is cumbersome, defining as it does matrices of interdiffusion coefficients (the central material properties that require a large experimental investment for their evaluation in three component systems, and, indeed cannot be evaluated for systems with more than three components. It is also argued that the physical meaning of the numerical values of these properties with respect to the atom motions in the system remains unknown. The attempt to understand the physical content of the diffusion coefficients in the phenomenological formalism has been the central fundamental problem in the theory of diffusion in crystalline alloys. The observation by Kirkendall that the crystal lattice moves during diffusion led Darken to develop the concept of intrinsic diffusion, i.e., atom motion relative to the crystal lattice. Darken and his successors sought to relate the diffusion coefficients computed for intrinsic fluxes to those obtained from the motion of radioactive tracers in chemically homogeneous samples which directly report the jump frequencies of the atoms as a function of composition and temperature. This theoretical connection between tracer, intrinsic and interdiffusion behavior would provide the basis for understanding the physical content of interdiffusion coefficients. Definitive tests of the resulting theoretical connection have been carried out for a number of binary systems for which all three kinds of observations are available. In a number of systems predictions of intrinsic coefficients from tracer data do not agree with measured values although predictions of interdiffusion coefficients appear to give reasonable agreement. Thus, the complete

  1. Nonlinear diffusion equations

    CERN Document Server

    Wu Zhuo Qun; Li Hui Lai; Zhao Jun Ning

    2001-01-01

    Nonlinear diffusion equations, an important class of parabolic equations, come from a variety of diffusion phenomena which appear widely in nature. They are suggested as mathematical models of physical problems in many fields, such as filtration, phase transition, biochemistry and dynamics of biological groups. In many cases, the equations possess degeneracy or singularity. The appearance of degeneracy or singularity makes the study more involved and challenging. Many new ideas and methods have been developed to overcome the special difficulties caused by the degeneracy and singularity, which

  2. Phase transformation and diffusion

    CERN Document Server

    Kale, G B; Dey, G K

    2008-01-01

    Given that the basic purpose of all research in materials science and technology is to tailor the properties of materials to suit specific applications, phase transformations are the natural key to the fine-tuning of the structural, mechanical and corrosion properties. A basic understanding of the kinetics and mechanisms of phase transformation is therefore of vital importance. Apart from a few cases involving crystallographic martensitic transformations, all phase transformations are mediated by diffusion. Thus, proper control and understanding of the process of diffusion during nucleation, g

  3. Ambipolar diffusion in plasma

    International Nuclear Information System (INIS)

    Silva, T.L. da.

    1987-01-01

    Is this thesis, a numerical method for the solution of the linear diffusion equation for a plasma containing two types of ions, with the possibility of charge exchange, has been developed. It has been shown that the decay time of the electron and ion densities is much smaller than that in a plasma containing only a single type of ion. A non-linear diffusion equation, which includes the effects of an external electric field varying linearly in time, to describe a slightly ionized plasma has also been developed. It has been verified that the decay of the electron density in the presence of such an electric field is very slow. (author)

  4. Bulk diffusion in a kinetically constrained lattice gas

    Science.gov (United States)

    Arita, Chikashi; Krapivsky, P. L.; Mallick, Kirone

    2018-03-01

    In the hydrodynamic regime, the evolution of a stochastic lattice gas with symmetric hopping rules is described by a diffusion equation with density-dependent diffusion coefficient encapsulating all microscopic details of the dynamics. This diffusion coefficient is, in principle, determined by a Green-Kubo formula. In practice, even when the equilibrium properties of a lattice gas are analytically known, the diffusion coefficient cannot be computed except when a lattice gas additionally satisfies the gradient condition. We develop a procedure to systematically obtain analytical approximations for the diffusion coefficient for non-gradient lattice gases with known equilibrium. The method relies on a variational formula found by Varadhan and Spohn which is a version of the Green-Kubo formula particularly suitable for diffusive lattice gases. Restricting the variational formula to finite-dimensional sub-spaces allows one to perform the minimization and gives upper bounds for the diffusion coefficient. We apply this approach to a kinetically constrained non-gradient lattice gas in two dimensions, viz. to the Kob-Andersen model on the square lattice.

  5. Interpretation of diffuse low-energy electron diffraction intensities

    International Nuclear Information System (INIS)

    Saldin, D.K.; Pendry, J.B.; Van Hove, M.A.; Somorjai, G.A.

    1985-01-01

    It is shown that the diffuse low-energy electron diffraction (LEED) that occurs between sharp LEED beams can be used to determine the local bonding configuration near disordered surface atoms. Two approaches to the calculation of diffuse LEED intensities are presented for the case of lattice-gas disorder of an adsorbate on a crystalline substrate. The capabilities of this technique are most similar to those of near-edge extended x-ray absorption fine structure, but avoid the restrictions due to the use of photons

  6. Diffuse cosmic x-rays below 1 keV

    International Nuclear Information System (INIS)

    Kraushaar, W.L.

    1973-01-01

    A description of those features of the low energy diffuse x-ray flux on which there is general observational agreement is given. Most of the discussion is restricted to the energy region below 280 eV, the carbon K edge. Topics include intensity, spatial structure, nature of the local emission, and the extragalactic component. It is concluded that the diffuse soft x-ray measurements cannot, taken alone, be said to provide positive evidence for a hot dense intergalactic medium. (U.S.)

  7. Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Chan, J.H.M.; Tsui, E.Y.K.; Yuen, M.K.; Peh, W.C.G.; Fong, D.; Fok, K.F.; Leung, K.M.; Fung, K.K.L.

    2003-01-01

    Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury. (orig.)

  8. Intrauterine growth restriction - part 2.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2016-12-01

    Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

  9. Placental Adaptations in Growth Restriction

    Science.gov (United States)

    Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

    2015-01-01

    The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

  10. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  11. Assessing restrictiveness of national alcohol marketing policies.

    Science.gov (United States)

    Esser, Marissa B; Jernigan, David H

    2014-01-01

    To develop an approach for monitoring national alcohol marketing policies globally, an area of the World Health Organization's (WHO) Global Alcohol Strategy. Data on restrictiveness of alcohol marketing policies came from the 2002 and 2008 WHO Global Surveys on Alcohol and Health. We included four scales in a sensitivity analysis to determine optimal weights to score countries on their marketing policies and applied the selected scale to assess national marketing policy restrictiveness. Nearly, 36% of countries had no marketing restrictions. The overall restrictiveness levels were not significantly different between 2002 and 2008. The number of countries with strict marketing regulations did not differ across years. This method of monitoring alcohol marketing restrictiveness helps track progress towards implementing WHO'S Global Alcohol Strategy. Findings indicate a consistent lack of restrictive policies over time, making this a priority area for national and global action. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  12. Anisotropy in "isotropic diffusion" measurements due to nongaussian diffusion

    DEFF Research Database (Denmark)

    Jespersen, Sune Nørhøj; Olesen, Jonas Lynge; Ianuş, Andrada

    2017-01-01

    Designing novel diffusion-weighted NMR and MRI pulse sequences aiming to probe tissue microstructure with techniques extending beyond the conventional Stejskal-Tanner family is currently of broad interest. One such technique, multidimensional diffusion MRI, has been recently proposed to afford...... model-free decomposition of diffusion signal kurtosis into terms originating from either ensemble variance of isotropic diffusivity or microscopic diffusion anisotropy. This ability rests on the assumption that diffusion can be described as a sum of multiple Gaussian compartments, but this is often...

  13. Modeling of Reaction Processes Controlled by Diffusion

    International Nuclear Information System (INIS)

    Revelli, Jorge

    2003-01-01

    Stochastic modeling is quite powerful in science and technology.The technics derived from this process have been used with great success in laser theory, biological systems and chemical reactions.Besides, they provide a theoretical framework for the analysis of experimental results on the field of particle's diffusion in ordered and disordered materials.In this work we analyze transport processes in one-dimensional fluctuating media, which are media that change their state in time.This fact induces changes in the movements of the particles giving rise to different phenomena and dynamics that will be described and analyzed in this work.We present some random walk models to describe these fluctuating media.These models include state transitions governed by different dynamical processes.We also analyze the trapping problem in a lattice by means of a simple model which predicts a resonance-like phenomenon.Also we study effective diffusion processes over surfaces due to random walks in the bulk.We consider different boundary conditions and transitions movements.We derive expressions that describe diffusion behaviors constrained to bulk restrictions and the dynamic of the particles.Finally it is important to mention that the theoretical results obtained from the models proposed in this work are compared with Monte Carlo simulations.We find, in general, excellent agreements between the theory and the simulations

  14. Diffusion-Weighted MR Imaging of Unusual White Matter Lesion in a Patient with Menkes Disease

    International Nuclear Information System (INIS)

    Lee, Eun Shin; Ryoo, Jae Wook; Choi, Dae Seob; Cho, Jae Min; Kwon, Soo Hyun; Shin, Hee Suk

    2007-01-01

    We report here on the diffusion-weighted imaging of unusual white matter lesions in a case of Menkes disease. On the initial MR imaging, the white matter lesions were localized in the deep periventricular white matter in the absence of diffuse cortical atrophy. The lesion showed diffuse high signal on the diffusion weighted images and diffuse progression and persistent hyperintensity on the follow up imaging. Our case suggests that the white matter lesion may precede diffuse cortical atrophy in a patient with Menkes disease. Menkes disease is an X-linked disorder that's caused by impaired intracellular transport of copper. We describe here the DWI findings of unusual and progressive white matter lesions in a case of Menkes disease. Menkes disease is an X-linked recessive disorder, and it is due to an inborn error of copper metabolism. The cause of Menkes disease has been isolated to a genetic defect in copper-transporting adenosine triphosphatase, and this results in low levels of intracellular copper. It is characterized clinically by failure to thrive, retarded mental and motor development, clonic seizure and peculiarly coarse, sparse and colorless scalp hair. These clinical findings can be explained by a dysfunction of the copper-dependent enzymes

  15. Curves of restricted type in euclidean spaces

    Directory of Open Access Journals (Sweden)

    Bengü Kılıç Bayram

    2014-01-01

    Full Text Available Submanifolds of restricted type were introduced in [7]. In the present study we consider restricted type of curves in Em. We give some special examples. We also show that spherical curve in S2(r C E3 is of restricted type if and only if either ƒ(s is constant or a linear function of s of the form ƒ(s = ±s + b and every closed W - curve of rank k and of length 2(r in E2k is of restricted type.

  16. Diffusion in building wakes

    International Nuclear Information System (INIS)

    Ramsdell, J.V.

    1988-03-01

    Straight-line Gaussian models adequately describe atmospheric diffusion for many applications. They have been modified for use in estimating diffusion in building wakes by adding terms that include projected building area and by redefining the diffusion coefficients so that the coefficients have minimum values that are related to building dimensions. In a recent study, Ramsdell reviewed the building-wake dispersion models used by the Nuclear Regulatory Commission (NRC) in its control room habitability assessments. The review included comparison of model estimates of centerline concentrations with concentrations observed in experiments at seven nuclear reactors. In general, the models are conservative in that they tend to predict concentrations that are greater than those actually observed. However, the models show little skill in accounting for variations in the observed concentrations. Subsequently, the experimental data and multiples linear regression techniques have been used to develop a new building wake diffusion model. This paper describes the new building wake model and compares it with other models. 8 refs., 2 figs

  17. Osmosis and Diffusion

    Science.gov (United States)

    Sack, Jeff

    2005-01-01

    OsmoBeaker is a CD-ROM designed to enhance the learning of diffusion and osmosis by presenting interactive experimentation to the student. The software provides several computer simulations that take the student through different scenarios with cells, having different concentrations of solutes in them.

  18. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Sporring, Jon; Fogh Olsen, Ole

    2008-01-01

    . To address this problem, we introduce a photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way, we preserve important illumination features, while...

  19. Bronnen van diffuse bodembelasting

    NARCIS (Netherlands)

    Lijzen JPA; Ekelenkamp A; LBG; DGM/BO

    1995-01-01

    The aim of this study was to support the policy on preventive soil protection with information on the diffuse (non-local) emissions to soil and the influence on future soil quality. This study is related to inventories on (potential) sources of local soil pollution (e.g. industrial areas,

  20. Diffusion in glass

    Energy Technology Data Exchange (ETDEWEB)

    Mubarak, A S

    1991-12-31

    Rutherford backscattering spectromertry technique (RBS) was used to characterize and investigate the depth distribution profiles of Ca-impurities of Ca-doped soda-time glass. The purposely added Ca-impurities were introduced inti the glass matrix by a normal ion exchange diffusion process. The measurements and analysis were performed using 2 MeV {sup 2}He{sup +} ions supplied from the University of Jordan Van de Graff acceierator (JOVAG). The normalized concetration versus depth profile distributions for the Ca-imourities were determined, both theoretically and experimentally. The theoretical treatment was carried out by setting up and soiving the diffusion equation under the conditions of the experiment. The resulting profiles are characterized by a compiementary error function. the theoretical treeatment was extended to include the various methods of enhancing the diffusion process, e.g. using an electric field. The diffusion coefficient, assumed constant, of the Ca-impurities exchanged in the soda-lime glass was determined to be 1.23 x 10{sup 13} cm{sup 2}/s. A comparison between theoretically and experimentally determined profiles is made and commented at, where several conclusions are drawn and suggestions for future work are mentioned. (author). 38 refs., 21 figs., 10 Tabs.

  1. Diffusion or bulk flow

    DEFF Research Database (Denmark)

    Schulz, Alexander

    2015-01-01

    is currently matter of discussion, called passive symplasmic loading. Based on the limited material available, this review compares the different loading modes and suggests that diffusion is the driving force in apoplasmic loaders, while bulk flow plays an increasing role in plants having a continuous...

  2. Multienergy anomalous diffuse scattering

    Czech Academy of Sciences Publication Activity Database

    Kopecký, Miloš; Fábry, Jan; Kub, Jiří; Lausi, A.; Busetto, E.

    2008-01-01

    Roč. 100, č. 19 (2008), 195504/1-195504/4 ISSN 0031-9007 R&D Projects: GA AV ČR IAA100100529 Institutional research plan: CEZ:AV0Z10100523 Keywords : diffuse scattering * x-rays * structure determination Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 7.180, year: 2008

  3. Diffuse Ceiling Ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen; Yu, Tao; Heiselberg, Per Kvols

    with conventional ventilation systems (mixing or displacement ventilation), diffuse ceiling ventilation can significantly reduce or even eliminate draught risk in the occupied zone. Moreover, this ventilation system presents a promising opportunity for energy saving, because of the low pressure loss, extended free...

  4. Diffuse Ceiling Ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen; Heiselberg, Per; Nielsen, Peter V.

    2014-01-01

    As a novel air distribution system, diffuse ceiling ventilation combines the suspended acoustic ceiling with ventilation supply. Due to the low-impulse supply from the large ceiling area, the system does not generate draught when supplying cold air. However, heat sources play an important role...

  5. Diffusion in ceramics

    CERN Document Server

    Pelleg, Joshua

    2016-01-01

    This textbook provides an introduction to changes that occur in solids such as ceramics, mainly at high temperatures, which are diffusion controlled, as well as presenting research data. Such changes are related to the kinetics of various reactions such as precipitation, oxidation and phase transformations, but are also related to some mechanical changes, such as creep. The book is composed of two parts, beginning with a look at the basics of diffusion according to Fick's Laws. Solutions of Fick’s second law for constant D, diffusion in grain boundaries and dislocations are presented along with a look at the atomistic approach for the random motion of atoms. In the second part, the author discusses diffusion in several technologically important ceramics. The ceramics selected are monolithic single phase ones, including: A12O3, SiC, MgO, ZrO2 and Si3N4. Of these, three refer to oxide ceramics (alumina, magnesia and zirconia). Carbide based ceramics are represented by the technologically very important Si-ca...

  6. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang

    2006-01-01

    -induced cell surface DAT redistribution may result in long-lasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent...... alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wild-type human DAT (WT-hDAT). However, AMPH did not induce cytosolic...... redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn(2+)) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn(2+) and AMPH consistently reduced WT-hDAT trafficking but stimulated cytosolic redistribution of Y335A...

  7. Pico gauges for minimally invasive intracellular hydrostatic pressure measurements

    DEFF Research Database (Denmark)

    Knoblauch, Jan; Mullendore, Daniel L.; Jensen, Kaare Hartvig

    2014-01-01

    Intracellular pressure has a multitude of functions in cells surrounded by a cell wall or similar matrix in all kingdoms of life. The functions include cell growth, nastic movements, and penetration of tissue by parasites. The precise measurement of intracellular pressure in the majority of cells......, however, remains difficult or impossible due to their small size and/or sensitivity to manipulation. Here, we report on a method that allows precise measurements in basically any cell type over all ranges of pressure. It is based on the compression of nanoliter and picoliter volumes of oil entrapped...... in the tip of microcapillaries, which we call pico gauges. The production of pico gauges can be accomplished with standard laboratory equipment, and measurements are comparably easy to conduct. Example pressure measurements are performed on cells that are difficult or impossible to measure with other methods....

  8. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  9. Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

    Science.gov (United States)

    Ngo, Anh H; Bose, Sohini; Do, Loi H

    2018-03-23

    This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Diffusion Magnetic Resonance Imaging Patterns in Metabolic and Toxic Brain Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N. [Ege Univ. Hospital, Bornova, Izmir (Turkey). Dept. of Radiology

    2004-08-01

    Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 s. b=1000 s/mm{sup 2} images and apparent diffusion coefficient (ADC) maps with ADC values were studied. Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm{sup 2} images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease. Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated

  11. Diffusion Magnetic Resonance Imaging Patterns in Metabolic and Toxic Brain Disorders

    International Nuclear Information System (INIS)

    Sener, R.N.

    2004-01-01

    Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 s. b=1000 s/mm 2 images and apparent diffusion coefficient (ADC) maps with ADC values were studied. Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm 2 images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease. Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated diffusion pattern

  12. Chelation of intracellular calcium blocks insulin action in the adipocyte

    International Nuclear Information System (INIS)

    Pershadsingh, H.A.; Shade, D.L.; Delfert, D.M.; McDonald, J.M.

    1987-01-01

    The hypothesis that intracellular Ca 2+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca 2+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl 2 and the Ca 2+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl 2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 μM quin-2 or quin-2 AM had no effect on intracellular ATP concentration or the specific binding of 125 I=labeled insulin to adipocytes. These findings suggest that intracellular Ca 2+ is an essential component in the coupling of the insulin-activated receptor complex to cellular physiological/metabolic machinery. Furthermore, differing quin-2 AM dose-response profiles suggest the presence of dual Ca 2+ -dependent pathways in the adipocyte. One involves insulin stimulation of glucose transport and oxidation, whereas the other involves the antilipolytic action of insulin

  13. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...only allow entirely new investigations into the replication of these viruses, but also how this method can be applied to any virus with a known...localization, TurboFISH, hemorrhagic fever virus replication 1. Introduction RNA FISH was developed as a method to visualize cellular RNA by binding a

  14. Mycobacterium avium-intracellulare: a rare cause of subacromial bursitis.

    Science.gov (United States)

    Sinha, Raj; Tuckett, John; Hide, Geoff; Dildey, Petra; Karsandas, Alvin

    2015-01-01

    Septic subacromial bursitis is an uncommon disorder with only a few reported cases in the literature. The most common causative organism is Staphylococcus aureus. We report the case of a 61-year-old female with a septic subacromial bursitis where the causative organism was found to be Mycobacterium avium-intracellulare (MAI). The diagnosis was only made following a biopsy, and we use this case to highlight the importance of recognising the need to consider a biopsy and aspiration in atypical situations.

  15. Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes

    DEFF Research Database (Denmark)

    Westgate, G E; Weaver, A C; Couchman, J R

    1985-01-01

    immunofluorescent staining for BPA is linear at the basement membrane zone (BMZ) of skin and many other epithelial tissues. At higher magnification however, we observed a punctate staining pattern for BPA which was regular in appearance and suggested localization of BPA to discrete structures at the BMZ. Subsequent...... intracellularly both in vivo and in vitro. We suggest that BPA is not normally a lamina lucida component, but that it may form part of a linkage between the cytoskeleton and the basement membrane....

  16. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Onkar Sharma

    2016-03-01

    Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

  17. Molecular evolution, intracellular organization, and the quinary structure of proteins.

    OpenAIRE

    McConkey, E H

    1982-01-01

    High-resolution two-dimensional polyacrylamide gel electrophoresis shows that at least half of 370 denatured polypeptides from hamster cells and human cells are indistinguishable in terms of isoelectric points and molecular weights. Molecular evolution may have been more conservative for this set of proteins than sequence studies on soluble proteins have implied. This may be a consequence of complexities of intracellular organization and the numerous macromolecular interactions in which most ...

  18. Control of intracellular heme levels: Heme transporters and heme oxygenases

    OpenAIRE

    Khan, Anwar A.; Quigley, John G.

    2011-01-01

    Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number...

  19. Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors.

    Directory of Open Access Journals (Sweden)

    Hannah Karlsson

    Full Text Available CD19-targeting CAR T cells have shown potency in clinical trials targeting B cell leukemia. Although mainly second generation (2G CARs carrying CD28 or 4-1BB have been investigated in patients, preclinical studies suggest that third generation (3G CARs with both CD28 and 4-1BB have enhanced capacity. However, little is known about the intracellular signaling pathways downstream of CARs. In the present work, we have analyzed the signaling capacity post antigen stimulation in both 2G and 3G CARs. 3G CAR T cells expanded better than 2G CAR T cells upon repeated stimulation with IL-2 and autologous B cells. An antigen-driven accumulation of CAR+ cells was evident post antigen stimulation. The cytotoxicity of both 2G and 3G CAR T cells was maintained by repeated stimulation. The phosphorylation status of intracellular signaling proteins post antigen stimulation showed that 3G CAR T cells had a higher activation status than 2G. Several proteins involved in signaling downstream the TCR were activated, as were proteins involved in the cell cycle, cell adhesion and exocytosis. In conclusion, 3G CAR T cells had a higher degree of intracellular signaling activity than 2G CARs which may explain the increased proliferative capacity seen in 3G CAR T cells. The study also indicates that there may be other signaling pathways to consider when designing or evaluating new generations of CARs.

  20. Fatty Acid Signaling: The New Function of Intracellular Lipases

    Directory of Open Access Journals (Sweden)

    Zuzana Papackova

    2015-02-01

    Full Text Available Until recently, intracellular triacylglycerols (TAG stored in the form of cytoplasmic lipid droplets have been considered to be only passive “energy conserves”. Nevertheless, degradation of TAG gives rise to a pleiotropic spectrum of bioactive intermediates, which may function as potent co-factors of transcription factors or enzymes and contribute to the regulation of numerous cellular processes. From this point of view, the process of lipolysis not only provides energy-rich equivalents but also acquires a new regulatory function. In this review, we will concentrate on the role that fatty acids liberated from intracellular TAG stores play as signaling molecules. The first part provides an overview of the transcription factors, which are regulated by fatty acids derived from intracellular stores. The second part is devoted to the role of fatty acid signaling in different organs/tissues. The specific contribution of free fatty acids released by particular lipases, hormone-sensitive lipase, adipose triacylglycerol lipase and lysosomal lipase will also be discussed.

  1. Estimating the biophysical properties of neurons with intracellular calcium dynamics.

    Science.gov (United States)

    Ye, Jingxin; Rozdeba, Paul J; Morone, Uriel I; Daou, Arij; Abarbanel, Henry D I

    2014-06-01

    We investigate the dynamics of a conductance-based neuron model coupled to a model of intracellular calcium uptake and release by the endoplasmic reticulum. The intracellular calcium dynamics occur on a time scale that is orders of magnitude slower than voltage spiking behavior. Coupling these mechanisms sets the stage for the appearance of chaotic dynamics, which we observe within certain ranges of model parameter values. We then explore the question of whether one can, using observed voltage data alone, estimate the states and parameters of the voltage plus calcium (V+Ca) dynamics model. We find the answer is negative. Indeed, we show that voltage plus another observed quantity must be known to allow the estimation to be accurate. We show that observing both the voltage time course V(t) and the intracellular Ca time course will permit accurate estimation, and from the estimated model state, accurate prediction after observations are completed. This sets the stage for how one will be able to use a more detailed model of V+Ca dynamics in neuron activity in the analysis of experimental data on individual neurons as well as functional networks in which the nodes (neurons) have these biophysical properties.

  2. Extracellular and Intracellular Mechanisms Mediating Metastatic Activity of Exogenous Osteopontin

    Science.gov (United States)

    Mandelin, Jami; Lin, Emme C. K.; Hu, Dana D.; Knowles, Susan K.; Do, Kim-Anh; Wang, Xuemei; Sage, E. Helene; Smith, Jeffrey W.; Arap, Wadih; Pasqualini, Renata

    2009-01-01

    BACKGROUND Osteopontin affects several steps of the metastatic cascade. Despite direct correlation with metastasis in experimental systems and in patient studies, the extracellular and intracellular basis for these observations remains unsolved. We used human melanoma and sarcoma cell lines to evaluate the effects of soluble osteopontin on metastasis. METHODS Exogenous osteopontin or negative controls, including a site-directed mutant osteopontin, were used in functional assays in vitro, ex vivo, and in vivo designed to test extracellular and intracellular mechanisms involved in experimental metastasis. RESULTS In the extracellular environment, we confirm that soluble osteopontin is required for its pro-metastatic effects; this phenomenon is specific, RGD-dependent, and evident in experimental models of metastasis. In the intracellular environment, osteopontin initially induces rapid Tyr-418 dephosphorylation of c-Src, with decreases in actin stress fibers and increased binding to the vascular endothelium. This heretofore undescribed Tyr dephosphorylation is followed by a tandem c-Src phosphorylation after tumor cell attachment to the metastatic site. CONCLUSION Our results reveal a complex molecular interaction as well as a dual role for osteopontin in metastasis that is dependent on whether tumor cells are in circulation or attached. Such context-dependent functional insights may contribute to anti-metastasis strategies. PMID:19224553

  3. New intracellular activities of matrix metalloproteinases shine in the moonlight.

    Science.gov (United States)

    Jobin, Parker G; Butler, Georgina S; Overall, Christopher M

    2017-11-01

    Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders. However, growing evidence has convincingly identified select MMPs in intracellular compartments with unexpected physiological and pathological roles. Intracellular MMPs have both proteolytic and non-proteolytic functions, including signal transduction and transcription factor activity thereby challenging their traditional designation as extracellular proteases. This review highlights current knowledge of subcellular location and activity of these "moonlighting" MMPs. Intracellular roles herald a new era of MMP research, rejuvenating interest in targeting these proteases in therapeutic strategies. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Intracellular Hg(0) Oxidation in Desulfovibrio desulfuricans ND132.

    Science.gov (United States)

    Wang, Yuwei; Schaefer, Jeffra K; Mishra, Bhoopesh; Yee, Nathan

    2016-10-03

    The disposal of elemental mercury (Hg(0)) wastes in mining and manufacturing areas has caused serious soil and groundwater contamination issues. Under anoxic conditions, certain anaerobic bacteria can oxidize dissolved elemental mercury and convert the oxidized Hg to neurotoxic methylmercury. In this study, we conducted experiments with the Hg-methylating bacterium Desulfovibrio desulfuricans ND132 to elucidate the role of cellular thiols in anaerobic Hg(0) oxidation. The concentrations of cell-surface and intracellular thiols were measured, and specific fractions of D. desulfuricans ND132 were examined for Hg(0) oxidation activity and analyzed with extended X-ray absorption fine structure (EXAFS) spectroscopy. The experimental data indicate that intracellular thiol concentrations are approximately six times higher than those of the cell wall. Cells reacted with a thiol-blocking reagent were severely impaired in Hg(0) oxidation activity. Spheroplasts lacking cell walls rapidly oxidized Hg(0) to Hg(II), while cell wall fragments exhibited low reactivity toward Hg(0). EXAFS analysis of spheroplast samples revealed that multiple different forms of Hg-thiols are produced by the Hg(0) oxidation reaction and that the local coordination environment of the oxidized Hg changes with reaction time. The results of this study indicate that Hg(0) oxidation in D. desulfuricans ND132 is an intracellular process that occurs by reaction with thiol-containing molecules.

  5. Assessment of GABARAP self-association by its diffusion properties

    International Nuclear Information System (INIS)

    Pacheco, Victor; Ma Peixiang; Thielmann, Yvonne; Hartmann, Rudolf; Weiergraeber, Oliver H.; Mohrlueder, Jeannine; Willbold, Dieter

    2010-01-01

    Gamma-aminobutyric acid type A receptor-associated protein (GABARAP) belongs to a family of small ubiquitin-like adaptor proteins implicated in intracellular vesicle trafficking and autophagy. We have used diffusion-ordered nuclear magnetic resonance spectroscopy to study the temperature and concentration dependence of the diffusion properties of GABARAP. Our data suggest the presence of distinct conformational states and provide support for self-association of GABARAP molecules. Assuming a monomer-dimer equilibrium, a temperature-dependent dissociation constant could be derived. Based on a temperature series of 1 H 15 N heteronuclear single quantum coherence nuclear magnetic resonance spectra, we propose residues potentially involved in GABARAP self-interaction. The possible biological significance of these observations is discussed with respect to alternative scenarios of oligomerization.

  6. The Role of Diffusion-Weighted MRI in Differentiation of Idiopathic Acute Transverse Myelitis and Acute Spinal Cord Infarction

    International Nuclear Information System (INIS)

    Kim, Yeo Goon; Lee, Joon Woo; Kim, Jae Hyoung; Kang, Heung Sik; Park, Kyung Seok

    2011-01-01

    To compare the diffusion characteristics of idiopathic acute transverse myelitis (ATM) and acute spinal cord infarction (SCI). Diffusion-weighted images (DWI) and an apparent diffusion coefficient (ADC) map were prospectively obtained from patients diagnosed with myelopathy between February 2006 and April 2009. Inclusion criteria included 1) the presence of an intramedullary T2-high signal intensity and 2) a final diagnosis of idiopathic ATM or SCI established by one neurologist. In total, 13 patients (M : F = 8 : 5; mean age, 39.5 years; range, 29-50 years) with idiopathic ATM and seven patients (M : F = 2 : 5; mean age, 58 years; range, 48-75 years) with SCI were included in this study. Two radiologists evaluated the DWIs and ADC map in consensus. The extent of the cord signal change was also evaluated on T2-weighted sagittal images. Among the 16 patients with ATM, 14 patients showed iso-signal on an ADC map, but one case showed restricted diffusion and another showed increased diffusion on the ADC map. Among the seven patients with SCI, five patients showed restricted diffusion. Idiopathic ATM usually does not demonstrate restricted diffusion, which can be a clue to differentiate it from SCI. However, idiopathic ATM with larger segment involvement can show focal diffusion restriction.

  7. Oxygen diffusion in zircon

    Science.gov (United States)

    Watson, E. B.; Cherniak, D. J.

    1997-05-01

    Oxygen diffusion in natural, non-metamict zircon was characterized under both dry and water-present conditions at temperatures ranging from 765°C to 1500°C. Dry experiments were performed at atmospheric pressure by encapsulating polished zircon samples with a fine powder of 18O-enriched quartz and annealing the sealed capsules in air. Hydrothermal runs were conducted in cold-seal pressure vessels (7-70 MPa) or a piston cylinder apparatus (400-1000 MPa) on zircon samples encapsulated with both 18O-enriched quartz and 18O water. Diffusive-uptake profiles of 18O were measured in all samples with a particle accelerator, using the 18O(p, α) 15N reaction. For dry experimental conditions at 1100-1500°C, the resulting oxygen diffusivities (24 in all) are well described by: D dry (m 2/s) = 1.33 × 10 -4exp(-53920/T) There is no suggestion of diffusive anisotropy. Under wet conditions at 925°C, oxygen diffusion shows little or no dependence upon P H 2O in the range 7-1000 MPa, and is insensitive to total pressure as well. The results of 27 wet experiments at 767-1160°C and 7-1000 MPa can be described a single Arrhenius relationship: D wet (m 2/s) = 5.5 × 10 -12exp(-25280/T) The insensitivity of oxygen diffusion to P H 2O means that applications to geologic problems can be pursued knowing only whether the system of interest was 'wet' (i.e., P H 2O > 7MPa ) or 'dry'. Under dry conditions (presumably rare in the crust), zircons are extremely retentive of their oxygen isotopic signatures, to the extent that δ 18O would be perturbed at the center of a 200 μm zircon only during an extraordinarily hot and protracted event (e.g., 65 Ma at 900°C). Under wet conditions, δ 18O may or may not be retained in the central regions of individual crystals, cores or overgrowth rims, depending upon the specific thermal history of the system.

  8. The Pearson diffusions: A class of statistically tractable diffusion processes

    DEFF Research Database (Denmark)

    Forman, Julie Lyng; Sørensen, Michael

    The Pearson diffusions is a flexible class of diffusions defined by having linear drift and quadratic squared diffusion coefficient. It is demonstrated that for this class explicit statistical inference is feasible. Explicit optimal martingale estimating func- tions are found, and the corresponding...

  9. Universal Cycles of Restricted Classes of Words

    OpenAIRE

    Leitner, Arielle; Godbole, Anant

    2008-01-01

    It is well known that Universal Cycles of $k$-letter words on an $n$-letter alphabet exist for all $k$ and $n$. In this paper, we prove that Universal Cycles exist for restricted classes of words, including: non-bijections, equitable words (under suitable restrictions), ranked permutations, and "passwords".

  10. Freedom and Restrictions in Language Use.

    Science.gov (United States)

    O'Donnell, Roy C.

    Since freedom of thought and expression is essential in a democracy, censorship of language is rightly regarded as a threat to all other freedoms. Still, it is inevitable that certain restrictions will occasionally be imposed on language in America and in other societies. Restrictions on language date back to the Ten Commandments, which condemned…

  11. Protein restriction in chronic renal failure

    NARCIS (Netherlands)

    ECHTEN, JEKT; NAUTA, J; HOP, WCJ; de Jong, MCJ; REITSMABIERENS, WCC; VANAMSTEL, SLBP; VANACKER, KJ; NOORDZIJ, CM; WOLFF, ED

    The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1

  12. Relationship Between Calorie Restriction, Lipid Peroxidation ...

    African Journals Online (AJOL)

    In the brain of the caloric restricted rats, there was little or no change in the tGSH and GSH, although the GSSG and GSSG/GSH% ratio were increased significantly. These results suggest that aging of rats had been decelerated by caloric restriction due to the decrease in the peroxidative damage in the lungs and brain.

  13. Eclampsia despite strict dietary sodium restriction.

    NARCIS (Netherlands)

    Delemarre, F.M.C.; Steegers, E.A.P.; Berendes, J.N.

    2001-01-01

    The classic indication for prescribing dietary sodium restriction in pregnancy has been the prevention of eclampsia. We describe a case of intrapartum eclampsia in a 24-year-old nulliparous woman. A strongly sodium restricted diet was prescribed because of pre-eclampsia. Compliance to the diet was

  14. 7 CFR 3430.205 - Funding restrictions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Funding restrictions. 3430.205 Section 3430.205... Funding restrictions. (a) Prohibition against construction. Funds made available under this subpart shall not be used for the construction of a new building or facility or the acquisition, expansion...

  15. 28 CFR 804.3 - Restrictions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Restrictions. 804.3 Section 804.3 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR THE DISTRICT OF COLUMBIA ACCEPTANCE OF GIFTS § 804.3 Restrictions. (a) The Agency is not authorized to accept gifts of money, stock...

  16. Steady state solution of the Fokker-Planck equation combined with unidirectional quasilinear diffusion under detailed balance conditions

    International Nuclear Information System (INIS)

    Hizanidis, K.

    1984-04-01

    The relativistic collisional Fokker-Planck equation combined with an externally imposed unidirectional quasilinear (rf) diffusion is solved for arbitrary values of rf diffusion coefficient under conditions of detailed balance of the staionary joint distribution involved. The detailed balance condition imposes a restriction on the functional form of the quasilinear diffusion coefficient which might be associated with the existence of a saturated spectrum of fluctuation in a quasilinearly rf-driven plasma

  17. DMPD: Intracellular DNA sensors in immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18573338 Intracellular DNA sensors in immunity. Takeshita F, Ishii KJ. Curr Opin Im...munol. 2008 Aug;20(4):383-8. Epub 2008 Jun 23. (.png) (.svg) (.html) (.csml) Show Intracellular DNA sensors ...in immunity. PubmedID 18573338 Title Intracellular DNA sensors in immunity. Authors Takeshita F, Ishii KJ. P

  18. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  19. Restricted gravity: Abelian projection of Einstein's theory

    International Nuclear Information System (INIS)

    Cho, Y.M.

    2013-01-01

    Treating Einstein's theory as a gauge theory of Lorentz group, we decompose the gravitational connection Γμ into the restricted connection made of the potential of the maximal Abelian subgroup H of Lorentz group G and the valence connection made of G/H part of the potential which transforms covariantly under Lorentz gauge transformation. With this we show that Einstein's theory can be decomposed into the restricted gravity made of the restricted connection which has the full Lorentz gauge invariance which has the valence connection as gravitational source. The decomposition shows the existence of a restricted theory of gravitation which has the full general invariance but is much simpler than Einstein's theory. Moreover, it tells that the restricted gravity can be written as an Abelian gauge theory,

  20. Regulation of NF-κB oscillation by spatial parameters in true intracellular space (TiCS)

    Science.gov (United States)

    Ohshima, Daisuke; Sagara, Hiroshi; Ichikawa, Kazuhisa

    2013-10-01

    Transcription factor NF-κB is activated by cytokine stimulation, viral infection, or hypoxic environment leading to its translocation to the nucleus. The nuclear NF-κB is exported from the nucleus to the cytoplasm again, and by repetitive import and export, NF-κB shows damped oscillation with the period of 1.5-2.0 h. Oscillation pattern of NF-κB is thought to determine the gene expression profile. We published a report on a computational simulation for the oscillation of nuclear NF-κB in a 3D spherical cell, and showed the importance of spatial parameters such as diffusion coefficient and locus of translation for determining the oscillation pattern. Although the value of diffusion coefficient is inherent to protein species, its effective value can be modified by organelle crowding in intracellular space. Here we tested this possibility by computer simulation. The results indicate that the effective value of diffusion coefficient is significantly changed by the organelle crowding, and this alters the oscillation pattern of nuclear NF-κB.

  1. Urban diffusion problems

    International Nuclear Information System (INIS)

    Hanna, S.R.

    1976-01-01

    It is hoped that urban diffusion models of air pollutants can eventually confidently be used to make major decisions, such as in planning the layout of a new industrial park, determining the effects of a new highway on air quality, or estimating the results of a new automobile emissions exhaust system. The urban diffusion model itself should be able to account for point, line, and area sources, and the local aerodynamic effects of street canyons and building wakes. Removal or transformations due to dry or wet deposition and chemical reactions are often important. It would be best if the model included meteorological parameters such as wind speed and temperature as dependent variables, since these parameters vary significantly when air passes from rural surfaces over urban surfaces

  2. Diffused Religion and Prayer

    Directory of Open Access Journals (Sweden)

    Roberto Cipriani

    2011-06-01

    Full Text Available It is quite likely that the origins of prayer are to be found in ancient mourning and bereavement rites. Primeval ritual prayer was codified and handed down socially to become a deep-rooted feature of people’s cultural behavior, so much so, that it may surface again several years later, in the face of death, danger, need, even in the case of relapse from faith and religious practice. Modes of prayer depend on religious experience, on relations between personal prayer and political action, between prayer and forgiveness, and between prayer and approaches to religions. Various forms of prayer exist, from the covert-hidden to the overt-manifest kind. How can they be investigated? How can one, for instance, explore mental prayer? These issues regard the canon of diffused religion and, therefore, of diffused prayer.

  3. Magnetic diffuse scattering

    International Nuclear Information System (INIS)

    Cable, J.W.

    1987-01-01

    The diffuse scattering of neutrons from magnetic materials provides unique and important information regarding the spatial correlations of the atoms and the spins. Such measurements have been extensively applied to magnetically ordered systems, such as the ferromagnetic binary alloys, for which the observed correlations describe the magnetic moment fluctuations associated with local environment effects. With the advent of polarization analysis, these techniques are increasingly being applied to study disordered paramagnetic systems such as the spin-glasses and the diluted magnetic semiconductors. The spin-pair correlations obtained are essential in understanding the exchange interactions of such systems. In this paper, we describe recent neutron diffuse scattering results on the atom-pair and spin-pair correlations in some of these disordered magnetic systems. 56 refs

  4. Combined radiation-protective and radiation-sensitizing agents. IV. Measurement of intracellular protector concentrations

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Hettiaratchi, P.

    1989-01-01

    Radiosensitization of hypoxic V79 Chinese hamster cells by 0.5 mM misonidazole at approximately 0-4 degrees C is substantially enhanced by pretreating the cells overnight with 0.1 mM buthionine sulfoximine, which lowers the cellular glutathione content to 5% of control values (from 4 mM to approximately 0.2 mM). The enhanced sensitization is reversed by concentrations of exogenous cysteine that are much lower (0.02 mM) than the original glutathione content. Reduced Co-enzyme A affords reversal of the enhancing effect at concentrations of about 1 mM. Sodium ascorbate gives no protection at all even at concentrations of 2 mM. The intracellular concentration of the reducing agents was measured using a spin-through oil technique. There was no diffusion of Co-A (MW greater than 750) or ascorbate (excluded by charge) into the cells. In contrast, cysteine was rapidly concentrated by factors of 4-10, even at the low temperatures used. Extracellular ascorbate's inability to radioprotect argues against electron transfer across the cell membrane as a mechanism for radioprotection. This mechanism could have explained the ability of exogenous thiols to radioprotect in former studies using glutathione, and in the present studies using Co-A. The potential of cysteine to be concentrated by cells poses a problem in the interpretation of exogenous protection by non-diffusing thiols, since trace contamination by cysteine could lead to the actual protection observed. Cysteine could also be formed by exchange reactions of exogenous thiols with the disulfide of cysteine, present in all media formulations

  5. Diffusion in heterogeneous lattices

    Czech Academy of Sciences Publication Activity Database

    Tarasenko, Alexander; Jastrabík, Lubomír

    2010-01-01

    Roč. 256, č. 17 (2010), s. 5137-5144 ISSN 0169-4332 R&D Projects: GA AV ČR KAN301370701; GA MŠk(CZ) 1M06002 Institutional research plan: CEZ:AV0Z10100522 Keywords : lattice- gas systems * diffusion * Monte Carlo simulations Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.795, year: 2010

  6. Diffusion bonding techniques

    International Nuclear Information System (INIS)

    Peters, R.D.

    1978-01-01

    The applications of diffusion bonding at the General Electric Neutron Devices Department are briefly discussed, with particular emphasis on the gold/gold or gold/indium joints made between metallized alumina ceramic parts in the vacuum switch tube and the crystal resonator programs. Fixtures which use the differential expansion of dissimilar metals are described and compared to one that uses hydraulic pressure to apply the necessary bonding force

  7. Enrichment by diffusion

    International Nuclear Information System (INIS)

    Mezin, M.

    1976-01-01

    The report presents an introduction to general basic principles of the gaseous diffusion process for the separation of uranium isotopes. Dealt with are: a) theoretical background and basic considerations of separation work and production costs, b) construction of a single separation stage and a multistage plant, c) the components of a plant and the optimization factors, d) cost factors. The text is illustrated by instructive diagrammes and flow charts. (RB) [de

  8. A reaction-diffusion model of CO2 influx into an oocyte

    Science.gov (United States)

    Somersalo, Erkki; Occhipinti, Rossana; Boron, Walter F.; Calvetti, Daniela

    2012-01-01

    We have developed and implemented a novel mathematical model for simulating transients in surface pH (pHS) and intracellular pH (pHi) caused by the influx of carbon dioxide (CO2) into a Xenopus oocyte. These transients are important tools for studying gas channels. We assume that the oocyte is a sphere surrounded by a thin layer of unstirred fluid, the extracellular unconvected fluid (EUF), which is in turn surrounded by the well-stirred bulk extracellular fluid (BECF) that represents an infinite reservoir for all solutes. Here, we assume that the oocyte plasma membrane is permeable only to CO2. In both the EUF and intracellular space, solute concentrations can change because of diffusion and reactions. The reactions are the slow equilibration of the CO2 hydration-dehydration reactions and competing equilibria among carbonic acid (H2CO3)/bicarbonate ( HCO3-) and a multitude of non-CO2/HCO3- buffers. Mathematically, the model is described by a coupled system of reaction-diffusion equations that—assuming spherical radial symmetry—we solved using the method of lines with appropriate stiff solvers. In agreement with experimental data (Musa-Aziz et al, PNAS 2009, 106:5406–5411), the model predicts that exposing the cell to extracellular 1.5% CO2/10 mM HCO3- (pH 7.50) causes pHi to fall and pHS to rise rapidly to a peak and then decay. Moreover, the model provides insights into the competition between diffusion and reaction processes when we change the width of the EUF, membrane permeability to CO2, native extra-and intracellular carbonic anhydrase-like activities, the non-CO2/HCO3- (intrinsic) intracellular buffering power, or mobility of intrinsic intracellular buffers. PMID:22728674

  9. Surface diffusion of sorbed radionuclides

    International Nuclear Information System (INIS)

    Berry, J.A.; Bond, K.A.

    1991-01-01

    Surface diffusion has in the past been invoked to explain rates of radionuclide migration which were greater than those predicted. Results were generally open to interpretation but the possible existence of surface diffusion, whereby sorbed radionuclides could potentially migrate at much enhanced rates, necessitated investigation. In this work through-diffusion experiments have shown that although surface diffusion does exist for some nuclides, the magnitude of the phenomenon is not sufficient to affect repository safety assessment modelling. (author)

  10. R Factor-Controlled Restriction and Modification of Deoxyribonucleic Acid: Restriction Mutants

    Science.gov (United States)

    Yoshimori, Robert; Roulland-Dussoix, Daisy; Boyer, Herbert W.

    1972-01-01

    Restriction mutants of two different R factor-controlled host specificities (RI and RII) were isolated. All of the restriction mutants examined had a normal modification phenotype. No complementation was observed between the RI and RII host specificities. It is concluded that for each host specificity no protein subunit is shared by the restriction endonuclease and modification methylase. PMID:4565538

  11. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction

    Science.gov (United States)

    Rauktis, Mary E.; Huefner, Jonathan C.; O'Brien, Kirk; Pecora, Peter J.; Doucette, Ann; Thompson, Ronald W.

    2009-01-01

    The "Restrictiveness of Living Environment Scale" has long been the primary way to conceptualize the "restrictiveness" of a child's living situation. However, changes in systems of care and other factors have created a need to revisit how restrictiveness is conceptualized and measured. A measure was created to assess an environment's level of…

  12. Diffusion in cladding materials

    International Nuclear Information System (INIS)

    Anand, M.S.; Pande, B.M.; Agarwala, R.P.

    1992-01-01

    Aluminium has been used as a cladding material in most research reactors because its low neutron absorption cross section and ease of fabrication. However, it is not suitable for cladding in power reactors and as such zircaloy-2 is normally used as a clad because it can withstand high temperature. It has low neutron absorption cross section, good oxidation, corrosion, creep properties and possesses good mechanical strength. With the passage of time, further development in this branch of science took place and designers started looking for better neutron economy and less hydrogen pickup in PHW reactors. The motion of fission products in the cladding material could pose a problem after long operation. In order to understand their behaviour under reactor environment, it is essential to study first the diffusion under normal conditions. These studies will throw light on the interaction of defects with impurities which would in turn help in understanding the mechanism of diffusion. In this article, it is intended to discuss the diffusion behaviour of impurities in cladding materials.(i.e. aluminium, zircaloy-2, zirconium-niobium alloy etc.). (author). 94 refs., 4 figs., 3 tabs

  13. The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

    Directory of Open Access Journals (Sweden)

    Oliveira S.C.

    1998-01-01

    Full Text Available Cellular immune responses are a critical part of the host's defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene transfer

  14. Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors.

    Science.gov (United States)

    Terenzio, Marco; Golding, Matthew; Russell, Matthew R G; Wicher, Krzysztof B; Rosewell, Ian; Spencer-Dene, Bradley; Ish-Horowicz, David; Schiavo, Giampietro

    2014-07-17

    We have identified a new function for the dynein adaptor Bicaudal D homolog 1 (BICD1) by screening a siRNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor (BDNF)-activated TrkB and p75 neurotrophin receptor (p75(NTR)) by disrupting the endosomal sorting, reducing lysosomal degradation and increasing the co-localisation of these neurotrophin receptors with retromer-associated sorting nexin 1. The resulting re-routing of active receptors increased their recycling to the plasma membrane and altered the repertoire of signalling-competent TrkB isoforms and p75(NTR) available for ligand binding on the neuronal surface. This resulted in attenuated, but more sustained, AKT activation in response to BDNF stimulation. These data, together with our observation that Bicd1 expression is restricted to the developing nervous system when neurotrophin receptor expression peaks, indicate that BICD1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand-activated receptors. © 2014 The Authors.

  15. Formalization of common power and efficiency definitions for energy-converting intracellular biochemical processes

    Energy Technology Data Exchange (ETDEWEB)

    Santillan, M.; Angulo-Brown, F.; Chavoya-Aceves, O. [Instituto Politecnico Nacional, Mexico, D. F. (Mexico)

    2001-04-01

    The definitions of power and efficiency for energy-converting intracellular biochemical processes, introduced by Caplan and Essig are studied. These definitions are recovered in the present work with the formalism of De Groot and Mazure for First-Order Irreversible Thermodynamics, rather than the formalism of Prigogine, as done by Caplan and Essig. The approach here employed permits to keep track of all the assumptions in a more clear manner, and to get rid of a very strong restriction in the approach of Caplan and Essig which assumes that the chemical potentials are homogeneous inside the cell. [Spanish] Se estudian las definiciones de potencia y eficiencia para procesos bioquimicos intracelulares convertidores de energia, introducidas por Caplan y Essig. En el presente trabajo, dichas definiciones se recuperan usando el formalismo de De Groot y Mazur para la termodinamica irreversible de primer orden, en vez del formalismo de Prigogine, empleado por Caplan y Essig. El punto de vista empleado en el presente manuscrito permite seguir las suposiciones hechas de una manera mas clara, ademas de que hace innecesaria una suposicion bastante fuerte usada por Caplan y Essig, la cual da por hecho que los potenciales quimicos son homogeneos en el interior de la celula.

  16. The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Figulla Hans R

    2004-05-01

    Full Text Available Abstract Background Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels. Methods We measured the effects of statins on the intracellular free calcium concentration ([Ca2+]i in human umbilical vein endothelial cells (HUVEC after acute application and 24-h-preincubation of statins. Results Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca2+]i. For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca2+]i in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca2+ release induced by histamine was not affected. Conclusions The increase of resting [Ca2+]i after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo.

  17. Intracellular responsive dual delivery by endosomolytic polyplexes carrying DNA anchored porous silicon nanoparticles.

    Science.gov (United States)

    Shahbazi, Mohammad-Ali; Almeida, Patrick Vingadas; Correia, Alexandra; Herranz-Blanco, Barbara; Shrestha, Neha; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2017-03-10

    Bioresponsive cytosolic nanobased multidelivery has been emerging as an enormously challenging novel concept due to the intrinsic protective barriers of the cells and hardly controllable performances of nanomaterials. Here, we present a new paradigm to advance nano-in-nano integration technology amenable to create multifunctional nanovehicles showing considerable promise to overcome restrictions of intracellular delivery, solve impediments of endosomal localization and aid effectual tracking of nanoparticles. A redox responsive intercalator chemistry comprised of cystine and 9-aminoacridine is designed as a cross-linker to cap carboxylated porous silicon nanoparticles with DNA. These intelligent nanocarriers are then encapsulated within novel one-pot electrostatically complexed nano-networks made of a zwitterionic amino acid (cysteine), an anionic bioadhesive polymer (poly(methyl vinyl ether-alt-maleic acid)) and a cationic endosomolytic polymer (polyethyleneimine). This combined nanocomposite is successfully tested for the co-delivery of hydrophobic (sorafenib) or hydrophilic (calcein) molecules loaded within the porous core, and an imaging agent covalently integrated into the polyplex shell by click chemistry. High loading capacity, low cyto- and hemo-toxicity, glutathione responsive on-command drug release, and superior cytosolic delivery are shown as achievable key features of the proposed formulation. Overall, formulating drug molecules, DNA and imaging agents, without any interference, in a physico-chemically optimized carrier may open a path towards broad applicability of these cost-effective multivalent nanocomposites for treating different diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Research and development of groundwater dating (Part 3). A proposal of determination method for diffusion coefficients of dissolved helium in rock and applicability of estimation of diffusion coefficients using anions

    International Nuclear Information System (INIS)

    Higashihara, Tomohiro; Nakata, Kotaro; Hasegawa, Takuma

    2006-01-01

    Dissolved helium in groundwater is one of the most suitable tracers for the groundwater dating. The diffusion coefficients in aquitard and aquifer were important to estimate an accumulation of the helium in groundwater. However, few papers have been reported about the diffusion of helium in rocks. In this study, effective diffusion coefficients of the helium in sandstones and mudstone were determined using a through-diffusion method. The effective diffusion coefficients of helium were in the range of 1.5 x 10 -10 to 1.1 x 10 -9 m 2 s -1 and larger than those of Br - ions. Geometrical factors for the diffusion of helium were also larger than those for the diffusion of Br - ions. This fact suggests that diffusion path of helium in the rocks is not more restricted than that of Br - ions. The diffusion coefficients of helium were also estimated using the diffusion coefficient of helium in bulk water and formation factors for diffusion of Br - ions. The estimated diffusion coefficients of helium were larger than the effective diffusion coefficients. It is clarified that the effective diffusion coefficients of helium are underestimated by the estimation method using anions. (author)

  19. Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism

    OpenAIRE

    Carper, Ruth A.; Treiber, Jeffrey M.; White, Nathan S.; Kohli, Jiwandeep S.; M?ller, Ralph-Axel

    2017-01-01

    Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted i...

  20. Solute diffusivity in undisturbed soil

    DEFF Research Database (Denmark)

    Lægdsmand, Mette; Møldrup, Per; Schjønning, Per

    2012-01-01

    Solute diffusivity in soil plays a major role in many important processes with relation to plant growth and environmental issues. Soil solute diffusivity is affected by the volumetric water content as well as the morphological characteristics of water-filled pores. The solute diffusivity in intact...

  1. Diffusion of Zonal Variables Using Node-Centered Diffusion Solver

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T B

    2007-08-06

    Tom Kaiser [1] has done some preliminary work to use the node-centered diffusion solver (originally developed by T. Palmer [2]) in Kull for diffusion of zonal variables such as electron temperature. To avoid numerical diffusion, Tom used a scheme developed by Shestakov et al. [3] and found their scheme could, in the vicinity of steep gradients, decouple nearest-neighbor zonal sub-meshes leading to 'alternating-zone' (red-black mode) errors. Tom extended their scheme to couple the sub-meshes with appropriate chosen artificial diffusion and thereby solved the 'alternating-zone' problem. Because the choice of the artificial diffusion coefficient could be very delicate, it is desirable to use a scheme that does not require the artificial diffusion but still able to avoid both numerical diffusion and the 'alternating-zone' problem. In this document we present such a scheme.

  2. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

    Science.gov (United States)

    Mei, Szu-Chieh; Brenner, Charles

    2015-01-01

    In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell. PMID:25633578

  3. Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

    Directory of Open Access Journals (Sweden)

    Szu-Chieh Mei

    2015-01-01

    Full Text Available In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA, are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

  4. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

    Science.gov (United States)

    Viswanathan, Preeti; Sharma, Yogeshwar; Gupta, Priya; Gupta, Sanjeev

    2018-03-05

    Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure. © 2018 John Wiley & Sons Ltd.

  5. Identification of Differentially Abundant Proteins of Edwardsiella ictaluri during Iron Restriction.

    Directory of Open Access Journals (Sweden)

    Pradeep R Dumpala

    Full Text Available Edwardsiella ictaluri is a Gram-negative facultative anaerobe intracellular bacterium that causes enteric septicemia in channel catfish. Iron is an essential inorganic nutrient of bacteria and is crucial for bacterial invasion. Reduced availability of iron by the host may cause significant stress for bacterial pathogens and is considered a signal that leads to significant alteration in virulence gene expression. However, the precise effect of iron-restriction on E. ictaluri protein abundance is unknown. The purpose of this study was to identify differentially abundant proteins of E. ictaluri during in vitro iron-restricted conditions. We applied two-dimensional difference in gel electrophoresis (2D-DIGE for determining differentially abundant proteins and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS for protein identification. Gene ontology and pathway-based functional modeling of differentially abundant proteins was also conducted. A total of 50 unique differentially abundant proteins at a minimum of 2-fold (p ≤ 0.05 difference in abundance due to iron-restriction were detected. The numbers of up- and down-regulated proteins were 37 and 13, respectively. We noted several proteins, including EsrB, LamB, MalM, MalE, FdaA, and TonB-dependent heme/hemoglobin receptor family proteins responded to iron restriction in E. ictaluri.

  6. Distinct cell stress responses induced by ATP restriction in quiescent human fibroblasts

    Directory of Open Access Journals (Sweden)

    Nirupama Yalamanchili

    2016-10-01

    Full Text Available Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly little is known about how quiescent cells respond to energetic and metabolic challenges. To better understand compensatory responses of quiescent cells to metabolic stress, we established, in human primary dermal fibroblasts, an experimental ‘energy restriction’ model. Quiescence was achieved by short-term culture in serum-deprived media and ATP supply restricted using a combination of glucose transport inhibitors and mitochondrial uncouplers. In aggregate, these measures led to markedly reduced intracellular ATP levels while not compromising cell viability over the observation period of 48 h. Analysis of the transcription factor landscape induced by this treatment revealed alterations in several signal transduction nodes beyond the expected biosynthetic adaptations. These included increased abundance of NF-κB regulated transcription factors and altered transcription factor subsets regulated by Akt and p53. The observed changes in gene regulation and corresponding alterations in key signaling nodes are likely to contribute to cell survival at intracellular ATP concentrations substantially below those achieved by growth factor deprivation alone. This experimental model provides a benchmark for the investigation of cell survival pathways and related molecular targets that are associated with restricted energy supply associated with biological aging and metabolic diseases.

  7. Posterior reversible encephalopathy syndrome: a case of unusual diffusion-weighted MR images.

    Science.gov (United States)

    Benziada-Boudour, A; Schmitt, E; Kremer, S; Foscolo, S; Rivière, A-S; Tisserand, M; Boudour, A; Bracard, S

    2009-05-01

    Posterior reversible encephalopathy (PRES) represents an uncommon entity related to multiple pathologies, the most common of which is hypertensive crisis. PRES is classically characterized as symmetrical parieto-occipital edema, but may affect other areas of the brain. Diffusion-weighted magnetic resonance imaging (DWI) is important for differentiating between vasogenic and cytotoxic edema. We present here the case of a 43-year-old woman, known to suffer from arterial hypertension and severe renal failure, who developed PRES with restricted apparent diffusion coefficients (ADC) in various cerebral areas, suggesting irreversible tissue damage. Nevertheless, follow-up cranial MRI revealed complete remission, indicating that restricted diffusion does not always lead to cell death in this pathology. The underlying pathophysiological mechanism is not well understood. Such reversibility of diffusion anomalies has already been reported with transient ischemia, vasospasm after subarachnoid hemorrhage and epilepsy but, to our knowledge, never before in PRES.

  8. The hormesis effect of plasma-elevated intracellular ROS on HaCaT cells

    Science.gov (United States)

    Szili, Endre J.; Harding, Frances J.; Hong, Sung-Ha; Herrmann, Franziska; Voelcker, Nicolas H.; Short, Robert D.

    2015-12-01

    We have examined the link between ionized-gas plasma delivery of reactive oxygen species (ROS) to immortalized keratinocyte (HaCaT) cells and cell fate, defined in terms of cell viability versus death. Phospholipid vesicles were used as cell mimics to measure the possible intracellular ROS concentration, [ROSi], delivered by various plasma treatments. Cells were exposed to a helium cold atmospheric plasma (CAP) jet for different plasma exposure times (5-60 s) and gas flow rates (50-1000 ml min-1). Based upon the [ROSi] data we argue that plasma-generated ROS in the cell culture medium can readily diffuse into real cells. Plasma exposure that equated to an [ROSi] in the range of 3.81  ×  10-10-9.47  ×  10-8 M, measured at 1 h after the plasma exposure, resulted in increased cell viability at 72 h; whereas a higher [ROSi] at 1 h decreased cell viability after 72 h of culture. This may be because of the manner in which the ROS are delivered by the plasma: HaCaT cells better tolerate a low ROS flux over an extended plasma exposure period of 1 min, compared to a high flux delivered in a few seconds, although the final [ROSi] may be the same. Our results suggest that plasma stimulation of HaCaT cells follows the principle of hormesis.

  9. Intracellular water distribution and aging as examined by X-ray microanalysis

    International Nuclear Information System (INIS)

    von Zglinicki, T.

    1988-01-01

    The results reviewed here demonstrate that 1. the distribution of dry mass as observed in frozen-dried cryosections might be used as an unbiased measure of intracellular dry mass resp. water distributions in the tissue in vivo and 2. the well-known loss of water from cells during aging is solely due to a water loss from mitochondria without changes in the water content of all other components of the cell in the case of rat liver and heart muscle. The reason for the water loss might be increased counter ion binding by membrane-bound enzymes due to decreased fluidity of the inner mitochondrial membrane with aging rather than changes of the permeability of the membrane or chemical modifications of mitochondrial proteins or DNA. It is assumed that the observed changes lead to decreased intramitochondrial diffusion of substrates and to conformational changes of enzymes. This would decrease both the velocity and the binding constants of certain energy-supplying reactions and could therefore play an important role in the aging process

  10. Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90

    International Nuclear Information System (INIS)

    Picard, Didier

    2006-01-01

    p23 is a component of the Hsp90 molecular chaperone machine. It binds and stabilizes the ATP-bound dimeric form of Hsp90. Since Hsp90 binds protein substrates in the ATP conformation, p23 has been proposed to stabilize Hsp90-substrate complexes. In addition, p23 can also function as a molecular chaperone by itself and even possesses an unrelated enzymatic activity. Whether it fulfills the latter functions in cells while bound to Hsp90 remains unknown and is difficult to extrapolate from cell-free biochemical experiments. Using the 'fluorescence recovery after photobleaching' (FRAP) technology, I have examined the dynamics of human p23, expressed as a fusion protein with the green fluorescent protein (GFP), in living human HeLa cells. GFP-p23 is distributed throughout the cell, and its mobility is identical in the cytoplasm and in the nucleus. When the Hsp90 interaction is disrupted either with the Hsp90 inhibitor geldanamycin or by introduction of point mutations into p23, the mobility of p23 is greatly accelerated. Under these conditions, its intracellular movement may be diffusion-controlled. In contrast, when wild-type p23 is able to bind Hsp90, a more complex FRAP behavior is observed, suggesting that it is quantitatively bound in Hsp90 complexes undergoing a multitude of other interactions

  11. Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

    International Nuclear Information System (INIS)

    Ying Xiaoying; Du Yongzhong; Hong Linghong; Yuan Hong; Hu Fuqiang

    2011-01-01

    Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and -30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs. - Research highlights: → A simple solvent diffusion method was developed to prepare magnetic lipid nanoparticles. → The doxorubicin-loaded magnetic lipid nanoparticles could be controlled by preparation recipe. → Magnetic lipid nanoparticles had internalization ability into tumor cells.

  12. Development of an image Mean Square Displacement (iMSD)-based method as a novel approach to study the intracellular trafficking of nanoparticles.

    Science.gov (United States)

    Digiacomo, Luca; Digman, Michelle A; Gratton, Enrico; Caracciolo, Giulio

    2016-09-15

    Fluorescence microscopy and spectroscopy techniques are commonly used to investigate complex and interacting biological systems (e.g. proteins and nanoparticles in living cells), since these techniques can explore intracellular dynamics with high time resolution at the nanoscale. Here we extended one of the Image Correlation Spectroscopy (ICS) methods, i.e. the image Mean Square Displacement, in order to study 2-dimensional diffusive and flow motion in confined systems, whose driving speed is uniformly distributed in a variable angular range. Although these conditions are not deeply investigated in the current literature, they can be commonly found in the intracellular trafficking of nanocarriers, which diffuse in the cytoplasm and/or may move along the cytoskeleton in different directions. The proposed approach could reveal the underlying system's symmetry using methods derived from fluorescence correlation concepts and could recover dynamic and geometric features which are commonly done by single particle analyses. Furthermore, it improves the characterization of low-speed flow motions, when compared to SpatioTemporal Image Correlation Spectroscopy (STICS). Although we present a specific example (lipoplexes in living cells), the emphasis is in the discussion of the method, its basic assumptions and its validation on numeric simulations. Recent advances in nanoparticle-based drug and gene delivery systems have pointed out the interactions at cellular and subcellular levels as key-factors for the efficiency of the adopted biomaterials. Such biochemical and biophysical interactions drive and affect the intracellular dynamics, that is commonly characterized by means of fluorescence microscopy and spectroscopy techniques. Here we present a novel Image Correlation Spectroscopy (ICS) method as a promising tool to capture the intracellular behavior of nanoparticles with high resolution and low background's sensitivity. This study overcomes some of the approximations

  13. Urban water restrictions: Attitudes and avoidance

    Science.gov (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin

    2011-12-01

    In most urban cities across Australia, water restrictions remain the dominant policy mechanism to restrict urban water consumption. The extensive adoption of water restrictions as a means to limit demand, over several years, means that Australian urban water prices have consistently not reflected the opportunity cost of water. Given the generally strong political support for water restrictions and the likelihood that they will persist for some time, there is value in understanding households' attitudes in this context. More specifically, identifying the welfare gains associated with avoiding urban water restrictions entirely would be a nontrivial contribution to our knowledge and offer insights into the benefits of alternative policy responses. This paper describes the results from a contingent valuation study that investigates consumers' willingness to pay to avoid urban water restrictions. Importantly, the research also investigates the influence of cognitive and exogenous dimensions on the utility gain associated with avoiding water restrictions. The results provide insights into the impact of the current policy mechanism on economic welfare.

  14. Transient fluctuations of intracellular zinc ions in cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Maret, Wolfgang, E-mail: womaret@utmb.edu [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2009-08-15

    Zinc is essential for cell proliferation, differentiation, and viability. When zinc becomes limited for cultured cells, DNA synthesis ceases and the cell cycle is arrested. The molecular mechanisms of actions of zinc are believed to involve changes in the availability of zinc(II) ions (Zn{sup 2+}). By employing a fluorescent Zn{sup 2+} probe, FluoZin-3 acetoxymethyl ester, intracellular Zn{sup 2+} concentrations were measured in undifferentiated and in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Intracellular Zn{sup 2+} concentrations are pico- to nanomolar in PC12 cells and are higher in the differentiated than in the undifferentiated cells. When following cellular Zn{sup 2+} concentrations for 48 h after the removal of serum, a condition that is known to cause cell cycle arrest, Zn{sup 2+} concentrations decrease after 30 min but, remarkably, increase after 1 h, and then decrease again to about one half of the initial concentration. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, decreases after both serum starvation and zinc chelation. Two peaks of Zn{sup 2+} concentrations occur within one cell cycle: one early in the G1 phase and the other in the late G1/S phase. Thus, fluctuations of intracellular Zn{sup 2+} concentrations and established modulation of phosphorylation signaling, via an inhibition of protein tyrosine phosphatases at commensurately low Zn{sup 2+} concentrations, suggest a role for Zn{sup 2+} in the control of the cell cycle. Interventions targeted at these picomolar Zn{sup 2+} fluctuations may be a way of controlling cell growth in hyperplasia, neoplasia, and diseases associated with aberrant differentiation.

  15. Polymeric gel nanoparticle pH sensors for intracellular measurements

    OpenAIRE

    Almdal, Kristoffer; Andresen, Thomas Lars; Benjaminsen, Rikke Vicki; Christensen, Nynne Meyn; Henriksen, Jonas Rosager; Sun, Honghao

    2011-01-01

    Precise measurements of pH in cells and intracellular compartments are of importance to both the fundamental understanding of metabolism and to the development of drugs that are released from the endosomes-lysome pathway. We have developed polymer gel nanoparticles as carriers of covalently bound fluorophores for ratiometric measurements of pH. One pH insensitive fluorophore serves as a reference while one or more pH sensitive fluorophores serve to give the desired pH dependence of the output...

  16. Dependence of cerebral arterial contractions on intracellularly stored Ca++.

    Science.gov (United States)

    Sasaki, T; Kassell, N F; Zuccarello, M

    1986-01-01

    The purpose of the present study was to evaluate the dependence of the arterial contractions induced by different vasoactive agents upon intracellularly stored calcium in canine versus monkey cerebral arteries. The potency for inducing contractions in Ca++-free media was in the order of 9,11-epithio-11,12-metano-thromboxane A2 (STXA2) greater than prostaglandin F2 alpha (PGF2 alpha) much greater than serotonin greater than K+ in canine basilar arteries, and STXA2 greater than PGF2 alpha much greater than serotonin = K+ in monkey basilar arteries.

  17. Subcellular site and nature of intracellular cadmium in plants

    International Nuclear Information System (INIS)

    Wagner, G.J.

    1979-01-01

    The mechanisms underlying heavy metal accumulation, toxicity, and tolerance in higher plants are poorly understood. Since subcellular processes are undoubtedly involved in all these phenomena, it is of interest to study the extent, subcellular site and nature of intracellularly accumulated cadmium in higher plants. Whole plants supplied 109 CdCl 2 or 112 CdSO 4 accumulated Cd into roots and aerial tissues. Preparation of protoplasts from aerial tissues followed by subcellular fractionation of the protoplasts to obtain intact vacuoles, chloroplasts and cytosol revealed the presence of Cd in the cytosol but not in vacuoles or chloroplasts. No evidence was obtained for the production of volatile Cd complexes in tobacco

  18. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema: Correlation with variation in apparent diffusion coefficient.

    Science.gov (United States)

    Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong

    2012-07-25

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

  19. Subcellular localization of an intracellular serine protease of 68 kDa in Leishmania (Leishmania amazonensis promastigotes

    Directory of Open Access Journals (Sweden)

    José Andrés Morgado-Díaz

    2005-07-01

    Full Text Available Here we report the subcellular localization of an intracellular serine protease of 68 kDa in axenic promastigotes of Leishmania (Leishmania amazonensis, using subcellular fractionation, enzymatic assays, immunoblotting, and immunocytochemistry. All fractions were evaluated by transmission electron microscopy and the serine protease activity was measured during the cell fractionation procedure using a-N-r-tosyl-L-arginine methyl ester (L-TAME as substrate, phenylmethylsulphone fluoride (PMSF and L-1-tosylamino-2-phenylethylchloromethylketone (TPCK as specific inhibitors. The enzymatic activity was detected mainly in a membranous vesicular fraction (6.5-fold enrichment relative to the whole homogenate, but also in a crude plasma membrane fraction (2.0-fold. Analysis by SDS-PAGE gelatin under reducing conditions demonstrated that the major proteolytic activity was found in a 68 kDa protein in all fractions studied. A protein with identical molecular weight was also recognized in immunoblots by a polyclonal antibody against serine protease (anti-SP, with higher immunoreactivity in the vesicular fraction. Electron microscopic immunolocalization using the same polyclonal antibody showed the enzyme present at the cell surface, as well as in cytoplasmic membranous compartments of the parasite. Our findings indicate that the internal location of this serine protease in L. amazonensis is mainly restricted to the membranes of intracellular compartments resembling endocytic/exocytic elements.

  20. Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

    Science.gov (United States)

    Evstratova, Alesya; Tóth, Katalin

    2011-12-01

    The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

  1. Particle diffusion in a spheromak

    International Nuclear Information System (INIS)

    Meyerhofer, D.D.; Levinton, F.M.; Yamada, M.

    1988-01-01

    The local carbon particle diffusion coefficient was measured in the Proto S-1/C spheromak using a test particle injection scheme. When the plasma was not in a force-free Taylor state, and when there were pressure gradients in the plasma, the particle diffusion was five times that predicted by Bohm and was consistent with collisional drift wave diffusion. The diffusion appears to be driven by correlations of the fluctuating electric field and density. During the decay phase of the discharge when the plasma was in the Taylor state, the diffusion coefficient of the carbon was classical. 23 refs., 4 figs

  2. Advanced diffusion processes and phenomena

    CERN Document Server

    Öchsner, Andreas; Belova, Irina

    2014-01-01

    This topical volume on Advanced Diffusion Processes and Phenomena addresses diffusion in a wider sense of not only mass diffusion but also heat diffusion in fluids and solids. Both diffusion phenomena play an important role in the characterization of engineering materials and corresponding structures. Understanding these different transport phenomena at many levels, from atomistic to macro, has therefore long attracted the attention of many researchers in materials science and engineering and related disciplines. The present topical volume captures a representative cross-section of some of the

  3. Measuring methods of matrix diffusion

    International Nuclear Information System (INIS)

    Muurinen, A.; Valkiainen, M.

    1988-03-01

    In Finland the spent nuclear fuel is planned to be disposed of at large depths in crystalline bedrock. The radionuclides which are dissolved in the groundwater may be able to diffuse into the micropores of the porous rock matrix and thus be withdrawn from the flowing water in the fractures. This phenomenon is called matrix diffusion. A review over matrix diffusion is presented in the study. The main interest is directed to the diffusion of non-sorbing species. The review covers diffusion experiments and measurements of porosity, pore size, specific surface area and water permeability

  4. Restricted diffusion of DNA segments within the isolated Escherichia coli nucleoid.

    NARCIS (Netherlands)

    Cunha, S.; Woldringh, C.L.; Odijk, T.

    2005-01-01

    To study the dynamics and organization of the DNA within isolated Escherichia coli nucleoids, we track the movement of a specific DNA region. Labeling of such a region is achieved using the Lac-O/Lac-I system. The Lac repressor-GFP fusion protein binds to the DNA section where tandem repeats of the

  5. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    Energy Technology Data Exchange (ETDEWEB)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O. (Dept. of Radiology, Univ. of Louisville, Louisville (United States)), e-mail: sdtalb02@gwise.louisville.edu; Plato, Brian M (Dept. of Neurology, Univ. of Louisville, Louisville (United States)); Parker, John (Dept. of Pathology and Laboratory Medicine, Univ. of Louisville, Louisville (United States))

    2011-04-15

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  6. Restricted pulmonary diffusion capacity after exercise is not an ARDS-like injury

    DEFF Research Database (Denmark)

    Nielsen, H.B.; Hanel, B.; Loft, Steffen

    1995-01-01

    Farmakologi, frie iltradikaler, oksidativ stress, lungefunktion, fysisk aktivitet, oksidativ DNA skade......Farmakologi, frie iltradikaler, oksidativ stress, lungefunktion, fysisk aktivitet, oksidativ DNA skade...

  7. Cortical restricted diffusion as the predominant MRI finding in sporadic Creutzfeldt-Jakob disease

    International Nuclear Information System (INIS)

    Talbott, Sabrina D.; Sattenberg, Ronald J.; Heidenreich, Jens O.; Plato, Brian M; Parker, John

    2011-01-01

    Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder with MR findings predominantly limited to the grey matter of the cortex and the basal ganglia. Sporadic Creutzfeldt-Jakob disease can produce a spectrum of MR imaging findings of the brain, most notably on DWI and FLAIR sequences. Involvement of the basal ganglia and neocortex is the most common finding, but isolated involvement of the cortex can also be seen. We describe the clinical history and MRI findings of three patients with sporadic Creutzfeldt-Jakob disease confirmed by brain biopsy or autopsy and review the literature of imaging manifestations of this disease

  8. Decoding restricted participation in sequential electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Knaut, Andreas; Paschmann, Martin

    2017-06-15

    Restricted participation in sequential markets may cause high price volatility and welfare losses. In this paper we therefore analyze the drivers of restricted participation in the German intraday auction which is a short-term electricity market with quarter-hourly products. Applying a fundamental electricity market model with 15-minute temporal resolution, we identify the lack of sub-hourly market coupling being the most relevant driver of restricted participation. We derive a proxy for price volatility and find that full market coupling may trigger quarter-hourly price volatility to decrease by a factor close to four.

  9. Investigation of restricted baby Skyrme models

    International Nuclear Information System (INIS)

    Adam, C.; Romanczukiewicz, T.; Wereszczynski, A.; Sanchez-Guillen, J.

    2010-01-01

    A restriction of the baby Skyrme model consisting of the quartic and potential terms only is investigated in detail for a wide range of potentials. Further, its properties are compared with those of the corresponding full baby Skyrme models. We find that topological (charge) as well as geometrical (nucleus/shell shape) features of baby Skyrmions are captured already by the soliton solutions of the restricted model. Further, we find a coincidence between the compact or noncompact nature of solitons in the restricted model, on the one hand, and the existence or nonexistence of multi-Skyrmions in the full baby Skyrme model, on the other hand.

  10. Statistical error in simulations of Poisson processes: Example of diffusion in solids

    Science.gov (United States)

    Nilsson, Johan O.; Leetmaa, Mikael; Vekilova, Olga Yu.; Simak, Sergei I.; Skorodumova, Natalia V.

    2016-08-01

    Simulations of diffusion in solids often produce poor statistics of diffusion events. We present an analytical expression for the statistical error in ion conductivity obtained in such simulations. The error expression is not restricted to any computational method in particular, but valid in the context of simulation of Poisson processes in general. This analytical error expression is verified numerically for the case of Gd-doped ceria by running a large number of kinetic Monte Carlo calculations.

  11. Diffusion-weighted imaging as a problem-solving tool in the evaluation of patients with acute strokelike syndromes.

    Science.gov (United States)

    Schaefer, P W

    2000-10-01

    This article addresses syndromes that clinically and/or radiologically resemble acute stroke. These syndromes generally fall into four categories. (1) Patients with acute neurological deficits with nonischemic lesions and no acute abnormality on diffusion-weighted images. These patients may have peripheral vertigo, migraines, seizures, dementia, functional disorders, amyloid angiopathy, or metabolic disorders. When these patients present, we can confidently predict that they are not undergoing infarction. (2) Patients with ischemic lesions with reversible clinical deficits. Nearly 50% of patients with transient ischemic attacks have lesions with restricted diffusion. Patients with transient global amnesia may have punctate lesions with restricted diffusion in the medial hippocampus, parahippocampal gyms, and corpus callosum. (3) Vasogenic edema syndromes that may mimic acute infarction clinically and on conventional imaging. These include eclampsia/hypertensive encephalopathy, other posterior leukoencephalopathies, human immunodeficiency virus encephalopathy, hyperperfusion syndrome following carotid endarterectomy, venous sinus thrombosis, acute demyelination, and neoplasm. These syndromes demonstrate elevated diffusion rather than the restricted diffusion associated with acute ischemic stroke. (4) Entities in which restricted diffusion may resemble acute infarction. These include pyogenic infections, herpes virus encephalitis, Creutzfeldt-Jakob disease, diffuse axonal injury, tumors with dense cell packing, and rare acute demyelinative lesions.

  12. Use and abuse of diffusion

    International Nuclear Information System (INIS)

    Kwiotek, A.; Grzywna, Z.J.

    2005-01-01

    Diffusion in a bounded region (or diffusive mass transport) can be seen from at least three platforms: - chemistry of he Fick's equation; - chemical engineering. To pose a particular problem we have to provide some additional conditions (initial conditions, boundary conditions and further). As we understood it in all cases diffusion is considered in an open region (in other words in one phase). Chemical engineering however brings an idea of 'diffusion' between phases. We claim that there isn't diffusion between phases. One can only consider mass transport between phases. Mass transport (or transfer in chemical engineering jargon) from one phase to another composes of: diffusion in first phase partition at an interface diffusion in second phase. (author)

  13. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

    OpenAIRE

    Friew, Yeshitila N; Boyko, Vitaly; Hu, Wei-Shau; Pathak, Vinay K

    2009-01-01

    Abstract Background Host restriction factor APOBEC3G (A3G) blocks human immunodeficiency virus type 1 (HIV-1) replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC) to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Ga...

  14. Synchronized Anti-Phase and In-Phase Oscillations of Intracellular Calcium Ions in Two Coupled Hepatocytes System

    International Nuclear Information System (INIS)

    Chuan-Sheng, Shen; Han-Shuang, Chen; Ji-Qian, Zhang

    2008-01-01

    We study the dynamic behaviour of two intracellular calcium oscillators that are coupled through gap junctions both to Ca 2+ and inositol(1,4,5)-trisphosphate (IP 3 ). It is found that synchronized anti-phase and in-phase oscillations of cytoplasmic calcium coexist in parameters space. Especially, synchronized anti-phase oscillations only occur near the onset of a Hopf bifurcation point when the velocity of IP 3 synthesis is increased. In addition, two kinds of coupling effects, i.e., the diffusions of Ca 2+ and IP 3 among cells on synchronous behaviour, are considered. We find that small coupling of Ca 2+ and large coupling of IP 3 facilitate the emergence of synchronized anti-phase oscillations. However, the result is contrary for the synchronized in-phase case. Our findings may provide a qualitative understanding about the mechanism of synchronous behaviour of intercellular calcium signalling

  15. Diffusion in amorphous media

    Science.gov (United States)

    Iotov, Mihail S.

    The goals of this research are twofold: First, to develop methods and tools for studying problems in chemistry, material science and biology, as well as accurate prediction of the properties of structures and materials of importance to those fields. Second, use those tools to apply the methods to practical problems. In terms of methodology development this thesis focuses on two topics: One: Development of a massively parallel computer program to perform electronic, atomic, molecular levels simulations of problems in chemistry, material science and biology. This computer program uses existing and emerging hardware platforms and parallel tools and is based on decades long research in computer modeling and algorithms. We report on that development in Chapter 3. Two: Development of tools for Molecular Dynamics simulation and methods and tools for course-grained meso-scale modeling of transport properties and especially diffusion of gas penetrants in polymers. We have formulated a new method for extracting coarse-grained information from short (0.2-0.5 nanoseconds [ns]) MD simulations and use this in a meso-scale simulation to calculate diffusion constants in polymer matrices. This is a grid-based method, which calculates the average probability of each grid point of being a void and performs constrained and biased Monte Carlo (MC) dynamics to reach much longer time regimes than possible in MD. The MC method mimics the three regimes of mean square deviation (MSD) behavior seen in MD, thus accounting for the proper mobility of the voids and the compressibility of the polymer matrix. Theoretical discussions and justification for the method is presented in chapter 6. Initial results on He diffusion in a low-density polyethylene (PE) matrix are presented in chapter 7. The behavior at different temperatures follows closely the trend observed from calibrating long term MD for this particular system.

  16. Diffusion in silicon isotope heterostructures

    Energy Technology Data Exchange (ETDEWEB)

    Silvestri, Hughes Howland [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    The simultaneous diffusion of Si and the dopants B, P, and As has been studied by the use of a multilayer structure of isotopically enriched Si. This structure, consisting of 5 pairs of 120 nm thick natural Si and 28Si enriched layers, enables the observation of 30Si self-diffusion from the natural layers into the 28Si enriched layers, as well as dopant diffusion from an implanted source in an amorphous Si cap layer, via Secondary Ion Mass Spectrometry (SIMS). The dopant diffusion created regions of the multilayer structure that were extrinsic at the diffusion temperatures. In these regions, the Fermi level shift due to the extrinsic condition altered the concentration and charge state of the native defects involved in the diffusion process, which affected the dopant and self-diffusion. The simultaneously recorded diffusion profiles enabled the modeling of the coupled dopant and self-diffusion. From the modeling of the simultaneous diffusion, the dopant diffusion mechanisms, the native defect charge states, and the self- and dopant diffusion coefficients can be determined. This information is necessary to enhance the physical modeling of dopant diffusion in Si. It is of particular interest to the modeling of future electronic Si devices, where the nanometer-scale features have created the need for precise physical models of atomic diffusion in Si. The modeling of the experimental profiles of simultaneous diffusion of B and Si under p-type extrinsic conditions revealed that both species are mediated by neutral and singly, positively charged Si self-interstitials. The diffusion of As and Si under extrinsic n-type conditions yielded a model consisting of the interstitialcy and vacancy mechanisms of diffusion via singly negatively charged self-interstitials and neutral vacancies. The simultaneous diffusion of P and Si has been modeled on the basis of neutral and singly negatively charged self-interstitials and neutral and singly

  17. Planar Dirac diffusion

    International Nuclear Information System (INIS)

    Leo, Stefano de; Rotelli, Pietro

    2009-01-01

    We present the results of the planar diffusion of a Dirac particle by step and barrier potentials, when the incoming wave impinges at an arbitrary angle with the potential. Except for right-angle incidence this process is characterized by the appearance of spin flip terms. For the step potential, spin flip occurs for both transmitted and reflected waves. However, we find no spin flip in the transmitted barrier result. This is surprising because the barrier result may be derived directly from a two-step calculation. We demonstrate that the spin flip cancellation indeed occurs for each ''particle'' (wave packet) contribution. (orig.)

  18. Radon diffusion chamber

    International Nuclear Information System (INIS)

    Pretzsch, G.; Boerner, E.; Lehmann, R.; Sarenio, O.

    1986-01-01

    The invention relates to the detection of radioactive gases emitting alpha particles like radon, thoron and their alpha-decaying daughters by means of a diffusion chamber with a passive detector, preferably with a solid state track detector. In the chamber above and towards the detector there is a single metallized electret with negative polarity. The distance between electret and detector corresponds to the range of the alpha particles of radon daughters in air at the most. The electret collects the positively charged daughters and functions as surface source. The electret increases the sensitivity by the factor 4

  19. Diffuse esophageal spasm

    International Nuclear Information System (INIS)

    Ott, D.J.; Chen, Y.M.; Hewson, E.G.; Richter, J.E.; Wu, W.C.; Gelfand, D.W.; Castell, D.O.

    1988-01-01

    Radiologic and manometric findings were correlated in 17 patients with diffuse esophageal spasm (DES). All patients initially had chest pain and/or dysphagia and had a manometric diagnosis of DES. Mean percentage of normal peristalsis manometrically was 46% (range, 20%-80%). Based on radiologic examination, an esophageal motor disorder consistent with DES was diagnosed in 12 of 17 patients, and there was one misinterpretation of achalasia. Radiologic detection was not related significantly to the percentage of peristalsis seen on manometric examination. Mean esophageal wall thickness as measured radiographically in patients with DES was 2.6 mm, compared with 2.5 mm in 17 individuals with normal results of manometry

  20. Elemental diffusion in stars

    International Nuclear Information System (INIS)

    Michaud, Georges; Montmerle, Thierry

    1977-01-01

    This paper is dealing with the origin of the elements in the universe. The scheme of nucleosynthesis is kept to explain the stellar generation of helium, carbon, etc... from the initial hydrogen; but a nonlinear theory is then elaborated to account for the anomalous abundances which were observed. The chemical elements would diffuse throughout the outer layers of a star under the action of the opposite forces of gravitation and radiation. This theory, with completing the nucleosynthesis, would contribute to give a consistent scheme of the elemental origin and abundances [fr

  1. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

    International Nuclear Information System (INIS)

    Sanson, Benoît; Wang, Tao; Sun, Jing; Wang, Liqun; Kaczocha, Martin; Ojima, Iwao; Deutsch, Dale; Li, Huilin

    2014-01-01

    FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels

  2. Imaging the intracellular degradation of biodegradable polymer nanoparticles

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Barthel

    2014-10-01

    Full Text Available In recent years, the development of smart drug delivery systems based on biodegradable polymeric nanoparticles has become of great interest. Drug-loaded nanoparticles can be introduced into the cell interior via endocytotic processes followed by the slow release of the drug due to degradation of the nanoparticle. In this work, poly(L-lactic acid (PLLA was chosen as the biodegradable polymer. Although common degradation of PLLA has been studied in various biological environments, intracellular degradation processes have been examined only to a very limited extent. PLLA nanoparticles with an average diameter of approximately 120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal stem cells (MSCs. The release of the magnetite particles from the surface of the PLLA nanoparticles during the intracellular residence was monitored by transmission electron microscopy (TEM over a period of 14 days. It was demonstrated by the release of the magnetite nanocrystals from the PLLA surface that the PLLA nanoparticles do in fact undergo degradation within the cell. Furthermore, even after 14 days of residence, the PLLA nanoparticles were found in the MSCs. Additionally, the ultrastructural TEM examinations yield insight into the long term intercellular fate of these nanoparticles. From the statistical analysis of ultrastructural details (e.g., number of detached magnetite crystals, and the number of nanoparticles in one endosome, we demonstrate the importance of TEM studies for such applications in addition to fluorescence studies (flow cytometry and confocal laser scanning microscopy.

  3. Fluorescent nanosensors for intracellular measurements: synthesis, characterisation, calibration and measurement

    Directory of Open Access Journals (Sweden)

    Arpan Shailesh Desai

    2014-01-01

    Full Text Available Measurement of intracellular acidification is important for understanding fundamental biological pathways as well as developing effective therapeutic strategies. Fluorescent pH nanosensors are an enabling technology for real-time monitoring of intracellular acidification. The physicochemical characteristics of nanosensors can be engineered to target specific cellular compartments and respond to external stimuli. Therefore nanosensors represent a versatile approach for probing biological pathways inside cells. The fundamental components of nanosensors comprise a pH-sensitive fluorophore (signal transducer and a pH-insensitive reference fluorophore (internal standard immobilised in an inert non-toxic matrix. The inert matrix prevents interference of cellular components with the sensing elements as well as minimizing potentially harmful effects of some fluorophores on cell function. Fluorescent nanosensors are synthesised using standard laboratory equipment and are detectable by non-invasive widely accessibly imaging techniques. The outcomes of studies employing this technology are dependent on reliable methodology for performing measurements. In particular special consideration must be given to conditions for sensor calibration, uptake conditions and parameters for image analysis. We describe procedures for: 1 synthesis and characterisation of polyacrylamide and silica based nanosensors 2 nanosensor calibration and 3 performing measurements using fluorescence microscopy.

  4. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Energy Technology Data Exchange (ETDEWEB)

    Dobay, M. P. D., E-mail: maria.pamela.david@physik.uni-muenchen.de; Alberola, A. Piera; Mendoza, E. R.; Raedler, J. O., E-mail: joachim.raedler@physik.uni-muenchen.de [Ludwig-Maximilians University, Faculty of Physics, Center for NanoScience (Germany)

    2012-03-15

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  5. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    International Nuclear Information System (INIS)

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-01-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  6. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Science.gov (United States)

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-03-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  7. Molecular characterization of a novel intracellular ADP-ribosyl cyclase.

    Directory of Open Access Journals (Sweden)

    Dev Churamani

    2007-08-01

    Full Text Available ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates.Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1 is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained.Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized.

  8. Light irradiation helps magnetotactic bacteria eliminate intracellular reactive oxygen species.

    Science.gov (United States)

    Li, Kefeng; Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Lulu; Song, Tao

    2017-09-01

    Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Cell fate reprogramming by control of intracellular network dynamics

    Science.gov (United States)

    Zanudo, Jorge G. T.; Albert, Reka

    Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

  10. Transient light-induced intracellular oxidation revealed by redox biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Kolossov, Vladimir L., E-mail: viadimer@illinois.edu [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Beaudoin, Jessica N. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Hanafin, William P. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); DiLiberto, Stephen J. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Kenis, Paul J.A. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801 (United States); Rex Gaskins, H. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana, IL 61801 (United States); Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Urbana, IL 61801 (United States)

    2013-10-04

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

  11. Detection of ubiquitinated huntingtin species in intracellular aggregates

    Directory of Open Access Journals (Sweden)

    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  12. Downregulation of transferrin receptor surface expression by intracellular antibody

    International Nuclear Information System (INIS)

    Peng Jilin; Wu Sha; Zhao Xiaoping; Wang Min; Li Wenhan; Shen Xin; Liu Jing; Lei Ping; Zhu Huifen; Shen Guanxin

    2007-01-01

    To deplete cellular iron uptake, and consequently inhibit the proliferation of tumor cells, we attempt to block surface expression of transferrin receptor (TfR) by intracellular antibody technology. We constructed two expression plasmids (scFv-HAK and scFv-HA) coding for intracellular single-chain antibody against TfR with or without endoplasmic reticulum (ER) retention signal, respectively. Then they were transfected tumor cells MCF-7 by liposome. Applying RT-PCR, Western blotting, immunofluorescence microscopy and immunoelectron microscope experiments, we insure that scFv-HAK intrabody was successfully expressed and retained in ER contrasted to the secreted expression of scFv-HA. Flow cytometric analysis confirmed that the TfR surface expression was markedly decreased approximately 83.4 ± 2.5% in scFv-HAK transfected cells, while there was not significantly decrease in scFv-HA transfected cells. Further cell growth and apoptosis characteristics were evaluated by cell cycle analysis, nuclei staining and MTT assay. Results indicated that expression of scFv-HAK can dramatically induce cell cycle G1 phase arrest and apoptosis of tumor cells, and consequently significantly suppress proliferation of tumor cells compared with other control groups. For First time this study demonstrates the potential usage of anti-TfR scFv-intrabody as a growth inhibitor of TfR overexpressing tumors

  13. Cyanobacteria perceive nitrogen status by sensing intracellular 2-oxoglutarate levels.

    Science.gov (United States)

    Muro-Pastor, M I; Reyes, J C; Florencio, F J

    2001-10-12

    The regulatory circuits that control nitrogen metabolism are relatively well known in several bacterial model groups. However, much less is understood about how the nitrogen status of the cell is perceived in vivo. In cyanobacteria, the transcription factor NtcA is required for regulation (activation or repression) of an extensive number of genes involved in nitrogen metabolism. In contrast, how NtcA activity is regulated is largely unknown. Assimilation of ammonium by most microorganisms occurs through the sequential action of two enzymes: glutamine synthetase (GS) and glutamate synthase. Interestingly, regulation of the expression of NtcA-dependent genes in the cyanobacterium Synechocystis sp. PCC 6803 is altered in mutants with modified levels of GS activity. Two types of mutants were analyzed: glnA null mutants that lack GS type I and gif mutants unable to inactivate GS in the presence of ammonium. Changes in the intracellular pools of 19 different amino acids and the keto acid 2-oxoglutarate were recorded in wild-type and mutant strains under different nitrogen conditions. Our data strongly indicate that the nitrogen status in cyanobacteria is perceived as changes in the intracellular 2-oxoglutarate pool.

  14. Optochemokine Tandem for Light-Control of Intracellular Ca2.

    Directory of Open Access Journals (Sweden)

    Katrin Feldbauer

    Full Text Available An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C, CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas. As shown by patch-clamp measurements and confocal laser scanning microscopy, heterologously expressed tCXCR4/CatCh was internalized via the endocytic SDF1/CXCR4 signaling pathway. The kinetics of internalization could be followed electrophysiologically via the amplitude of the CatCh signal. The light-induced release of Ca2+ by tandem endosomes into the cytosol via CatCh was visualized using the Ca2+-sensitive dyes rhod2 and rhod2-AM showing an increase of intracellular Ca2+ in response to light.

  15. Horizontal Transmission of Intracellular Insect Symbionts via Plants

    Directory of Open Access Journals (Sweden)

    Ewa Chrostek

    2017-11-01

    Full Text Available Experimental evidence is accumulating that endosymbionts of phytophagous insects may transmit horizontally via plants. Intracellular symbionts known for manipulating insect reproduction and altering fitness (Rickettsia, Cardinium, Wolbachia, and bacterial parasite of the leafhopper Euscelidius variegatus have been found to travel from infected insects into plants. Other insects, either of the same or different species can acquire the symbiont from the plant through feeding, and in some cases transfer it to their progeny. These reports prompt many questions regarding how intracellular insect symbionts are delivered to plants and how they affect them. Are symbionts passively transported along the insect-plant-insect path, or do they actively participate in the process? How widespread are these interactions? How does symbiont presence influence the plant? And what conditions are required for the new infection to establish in an insect? From an ecological, evolutionary, and applied perspective, this mode of horizontal transmission could have profound implications if occurring frequently enough or if new stable symbiont infections are established. Transmission of symbionts through plants likely represents an underappreciated means of infection, both in terms of symbiont epidemiology and the movement of symbionts to new host species.

  16. Transient light-induced intracellular oxidation revealed by redox biosensor

    International Nuclear Information System (INIS)

    Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

    2013-01-01

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition

  17. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter

    Energy Technology Data Exchange (ETDEWEB)

    Sanson, Benoît; Wang, Tao [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Sun, Jing; Wang, Liqun; Kaczocha, Martin [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Ojima, Iwao [Stony Brook University, Stony Brook, NY 1794-3400 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Deutsch, Dale, E-mail: dale.deutsch@stonybrook.edu [Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States); Li, Huilin, E-mail: dale.deutsch@stonybrook.edu [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Stony Brook University, Stony Brook, NY 11794-5213 (United States); Stony Brook University, Stony Brook, NY 11794-3400 (United States)

    2014-02-01

    FABP5 was recently found to intracellularly transport endocannabinoid signaling lipids. The structures of FABP5 complexed with two endocannabinoids and an inhibitor were solved. Human FABP5 was found to dimerize via a domain-swapping mechanism. This work will help in the development of inhibitors to raise endocannabinoid levels. In addition to binding intracellular fatty acids, fatty-acid-binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2-AG and the inhibitor BMS-309403 were determined. These ligands are shown to interact primarily with the substrate-binding pocket via hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small-molecule inhibitors to raise endocannabinoid levels.

  18. CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Keli Cristina Simões da SILVEIRA

    2015-03-01

    Full Text Available Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

  19. distribution, abundance and properties of restriction enzymes

    African Journals Online (AJOL)

    DNA of granule-bound starch synthase (GBSS) I and II with a view to ... properties for manipulation of the genes for production of modified starch. .... procurement, storage and handling of the ..... been made on restriction enzymes of potato,.

  20. Health Benefits of Fasting and Caloric Restriction.

    Science.gov (United States)

    Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

    2017-10-23

    Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

  1. Compensatory mechanisms activated with intermittent energy restriction

    DEFF Research Database (Denmark)

    Coutinho, Sílvia Ribeiro; Halset, Eline Holli; Gåsbakk, Sigrid

    2018-01-01

    Background & aims: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy...... restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. Methods: 35 adults (age......: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting...

  2. Restricted Coherent Risk Measures and Actuarial Solvency

    Directory of Open Access Journals (Sweden)

    Christos E. Kountzakis

    2012-01-01

    Full Text Available We prove a general dual representation form for restricted coherent risk measures, and we apply it to a minimization problem of the required solvency capital for an insurance company.

  3. Evolutionary genomics and HIV restriction factors.

    Science.gov (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

    2015-03-01

    To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

  4. Avoidant/Restrictive Food Intake Disorder

    Science.gov (United States)

    ... Eating Disorder Bulimia Nervosa Pica Rumination Disorder Avoidant/restrictive food intake disorder is characterized by eating very little food and/or avoiding eating certain foods. People with this disorder eat ...

  5. The welfare effects of mobility restrictions

    Czech Academy of Sciences Publication Activity Database

    Jeong, Byeongju

    2003-01-01

    Roč. 6, č. 3 (2003), s. 685-696 ISSN 1094-2025 Institutional research plan: CEZ:AV0Z7085904 Keywords : mobility restriction * partnership * search Subject RIV: AH - Economics Impact factor: 0.600, year: 2003

  6. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Sqd to produce spatially-restricted Egfr activation...

  7. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Squid to produce spatially-restricted EGFR activation...

  8. A topological insight into restricted Boltzmann machines

    NARCIS (Netherlands)

    Mocanu, D.C.; Mocanu, E.; Nguyen, H.P.; Gibescu, M.; Liotta, A.

    Restricted Boltzmann Machines (RBMs) and models derived from them have been successfully used as basic building blocks in deep artificial neural networks for automatic features extraction, unsupervised weights initialization, but also as density estimators. Thus, their generative and discriminative

  9. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  10. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  11. Public Investment, Revenue Shocks, and Borrowing Restrictions

    OpenAIRE

    Büttner, Thiess; Wildasin, David E.

    2010-01-01

    This paper lays out a theory of taxation and public investment in an intertemporal setting under conditions of revenue shocks. Without borrowing restrictions, the optimal policy is characterized by smooth time paths of taxes and public investment. While the introduction of formal borrowing restrictions leads to some precautionary savings, it gives rise to fluctuations in public investment in response to adverse but also favorable revenue shocks. This theoretical result is tested empirically u...

  12. Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

    Science.gov (United States)

    Simões, Rui V; Muñoz-Moreno, Emma; Cruz-Lemini, Mónica; Eixarch, Elisenda; Bargalló, Núria; Sanz-Cortés, Magdalena; Gratacós, Eduard

    2017-01-01

    Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. A total of 26 prematurely born intrauterine growth restriction infants (birthweight intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset. Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which

  13. Diffusion in Solids Fundamentals, Methods, Materials, Diffusion-Controlled Processes

    CERN Document Server

    Mehrer, Helmut

    2007-01-01

    Diffusion is a vital topic in solid-state physics and chemistry, physical metallurgy and materials science. Diffusion processes are ubiquitous in solids at elevated temperatures. A thorough understanding of diffusion in materials is crucial for materials development and engineering. This book first gives an account of the central aspects of diffusion in solids, for which the necessary background is a course in solid state physics. It then provides easy access to important information about diffuson in metals, alloys, semiconductors, ion-conducting materials, glasses and nanomaterials. Several diffusion-controlled phenomena, including ionic conduction, grain-boundary and dislocation pipe diffusion, are considered as well. Graduate students in solid-state physics, physical metallurgy, materials science, physical and inorganic chemistry or geophysics will benefit from this book as will physicists, chemists, metallurgists, materials engineers in academic and industrial research laboratories.

  14. Apparatus for diffusion separation

    International Nuclear Information System (INIS)

    Nierenberg, W.A.

    1976-01-01

    A diffuser separator apparatus is described which comprises a plurality of flow channels in a single stage. Each of said channels has an inlet port and an outlet port and a constant cross sectional area between said ports. At least a portion of the defining surface of each of said channels is a diffusion separation membrane, and each of said channels is a different cross sectional area. Means are provided for connecting said channels in series so that each successive channel of said series has a smaller cross sectional area than the previous channel of said series. Also provided are a source of gaseous mixture, individual means for flowing said gaseous mixture to the inlet port of each of said channels, gas receiving and analyzing means, individual means for flowing gas passing from each of said outlet ports and means for flowing gas passing through said membranes to said receiving and analyzing means, and individual means for connecting the outlet port of each channel with the inlet port of the channel having the next smaller cross sectional area

  15. The diffusion of microfinance.

    Science.gov (United States)

    Banerjee, Abhijit; Chandrasekhar, Arun G; Duflo, Esther; Jackson, Matthew O

    2013-07-26

    To study the impact of the choice of injection points in the diffusion of a new product in a society, we developed a model of word-of-mouth diffusion and then applied it to data on social networks and participation in a newly available microfinance loan program in 43 Indian villages. Our model allows us to distinguish information passing among neighbors from direct influence of neighbors' participation decisions, as well as information passing by participants versus nonparticipants. The model estimates suggest that participants are seven times as likely to pass information compared to informed nonparticipants, but information passed by nonparticipants still accounts for roughly one-third of eventual participation. An informed household is not more likely to participate if its informed friends participate. We then propose two new measures of how effective a given household would be as an injection point. We show that the centrality of the injection points according to these measures constitutes a strong and significant predictor of eventual village-level participation.

  16. Diffuse infiltrative lung disease

    International Nuclear Information System (INIS)

    Niden, A.H.; Mishkin, F.S.

    1984-01-01

    The authors discuss their approach to the diagnosis and management of patients with DILD. Gallium scans play a central role in this process. Not only do they help them decide whom to biopsy, but also where to biopsy. The scans can be used for the early detection of disease in a high-risk population, for following the progression and regression of disease, for the regulation of medication, and for the evaluation of therapy. Bronchoalveolar lung lavage appears to be equally sensitive. However, patients are less willing to undergo repeated fiberoptic bronchoscopies than lung scans. Both tests may prove useful, one complementing the other. Gallium imaging has also been utilized by the authors in select patients with questionable diffuse lung infiltrates roentgenographically or with a normal chest roentgenogram, chronic respiratory symptoms, and abnormal pulmonary function studies. An abnormal gallium lung scan in these clinical situations helps them select which patients have a diffuse active pulmonary process meriting transbronchial biopsies. This has proven to be of particular value in the management of older patients

  17. Brain Metabolite Diffusion from Ultra-Short to Ultra-Long Time Scales: What Do We Learn, Where Should We Go?

    Directory of Open Access Journals (Sweden)

    Julien Valette

    2018-01-01

    Full Text Available In vivo diffusion-weighted MR spectroscopy (DW-MRS allows measuring diffusion properties of brain metabolites. Unlike water, most metabolites are confined within cells. Hence, their diffusion is expected to purely reflect intracellular properties, opening unique possibilities to use metabolites as specific probes to explore cellular organization and structure. However, interpretation and modeling of DW-MRS, and more generally of intracellular diffusion, remains difficult. In this perspective paper, we will focus on the study of the time-dependency of brain metabolite apparent diffusion coefficient (ADC. We will see how measuring ADC over several orders of magnitude of diffusion times, from less than 1 ms to more than 1 s, allows clarifying our understanding of brain metabolite diffusion, by firmly establishing that metabolites are neither massively transported by active mechanisms nor massively confined in subcellular compartments or cell bodies. Metabolites appear to be instead diffusing in long fibers typical of neurons and glial cells such as astrocytes. Furthermore, we will evoke modeling of ADC time-dependency to evaluate the effect of, and possibly quantify, some structural parameters at various spatial scales, departing from a simple model of hollow cylinders and introducing additional complexity, either short-ranged (such as dendritic spines or long-ranged (such as cellular fibers ramification. Finally, we will discuss the experimental feasibility and expected benefits of extending the range of diffusion times toward even shorter and longer values.

  18. Intracellular Trafficking Modulation by Ginsenoside Rg3 Inhibits Brucella abortus Uptake and Intracellular Survival within RAW 264.7 Cells.

    Science.gov (United States)

    Huy, Tran Xuan Ngoc; Reyes, Alisha Wehdnesday Bernardo; Hop, Huynh Tan; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Rhee, Man Hee; Chang, Hong Hee; Kim, Suk

    2017-03-28

    Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus -infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus -containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

  19. The Role of Membrane Curvature in Nanoscale Topography-Induced Intracellular Signaling.

    Science.gov (United States)

    Lou, Hsin-Ya; Zhao, Wenting; Zeng, Yongpeng; Cui, Bianxiao

    2018-05-15

    Over the past decade, there has been growing interest in developing biosensors and devices with nanoscale and vertical topography. Vertical nanostructures induce spontaneous cell engulfment, which enhances the cell-probe coupling efficiency and the sensitivity of biosensors. Although local membranes in contact with the nanostructures are found to be fully fluidic for lipid and membrane protein diffusions, cells appear to actively sense and respond to the surface topography presented by vertical nanostructures. For future development of biodevices, it is important to understand how cells interact with these nanostructures and how their presence modulates cellular function and activities. How cells recognize nanoscale surface topography has been an area of active research for two decades before the recent biosensor works. Extensive studies show that surface topographies in the range of tens to hundreds of nanometers can significantly affect cell functions, behaviors, and ultimately the cell fate. For example, titanium implants having rough surfaces are better for osteoblast attachment and host-implant integration than those with smooth surfaces. At the cellular level, nanoscale surface topography has been shown by a large number of studies to modulate cell attachment, activity, and differentiation. However, a mechanistic understanding of how cells interact and respond to nanoscale topographic features is still lacking. In this Account, we focus on some recent studies that support a new mechanism that local membrane curvature induced by nanoscale topography directly acts as a biochemical signal to induce intracellular signaling, which we refer to as the curvature hypothesis. The curvature hypothesis proposes that some intracellular proteins can recognize membrane curvatures of a certain range at the cell-to-material interface. These proteins then recruit and activate downstream components to modulate cell signaling and behavior. We discuss current technologies

  20. Dietary restriction with and without caloric restriction for healthy aging [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Changhan Lee

    2016-01-01

    Full Text Available Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.

  1. Mechanism of H. pylori intracellular entry: an in vitro study

    Directory of Open Access Journals (Sweden)

    Hui eLiu

    2012-03-01

    Full Text Available The majority of H. pylori reside on gastric epithelial cell surfaces and in the overlying mucus, but a small fraction of H. pylori enter host epithelial and immune cells. To explore the role of the nudA invasin in host cell entry, a ΔnudA deletion derivative of strain J99 was constructed and transformants were verified by PCR and by fluorescence in situ hybridization. AGS cells were inoculated with either wild type (WT strain J99 or its ΔnudA mutant to determine the fraction of bacteria that were bound to the cells and inside these cells using the gentamicin protection assay. We observed no significant difference between either the density of H. pylori bound to AGS cell membranes or the density of intracellular H. pylori. To further explore this finding, separate chambers of each culture were fixed in glutaraldehyde for transmission electron microscopy (TEM and immunogold TEM. This addition to the classical gentamicin assay demonstrated that there were significantly more intracellular, and fewer membrane-bound, H. pylori in WT-infected AGS cells than in ΔnudA allele infected cells. Thus, the sum of intracellular and membrane-bound H. pylori was similar in the two groups. Since no other similar TEM study has been performed, it is at present unknown whether our observations can be reproduced by others Taken together however, our observations suggest that the classical gentamicin protection assay is not sufficiently sensitive to analyze H. pylori cell entry and that the addition of TEM to the test demonstrate that nudA plays a role in H. pylori entry into AGS cells in vitro. In addition, deletion of the invasin gene appears to limit H. pylori to the AGS cell surface, where it may be partly protected against gentamicin. In contrast, this specific environment may render H. pylori more vulnerable to host defense and therapeutic intervention, and less prone to trigger normal immune, carcinogenic, and other developmental response pathways.

  2. LDL Receptors as Gateways for Intracellular Porphyrin Uptake

    International Nuclear Information System (INIS)

    Novick, S.; Laster, B.; Quastel, M.

    2004-01-01

    Boronated compounds are currently being studied for possible use in Boron Neutron Capture Therapy (BNCT). We found that one of these agents, BOPP (tetrakis-carborane-carboxylate, esters of 2,4-bis (a,b- dihydroxyethyl) deuteroporphyrin IX), could also be labeled with indium (In-BOPP) and, therefore, could also be used potentially to transport high Z atoms into tumor cell DNA for AET (Auger Electron Therapy). In order to assess the uptake of these agents into cells, the role of the LDL receptor in the intracellular accumulation of BOPP and In-BOPP was investigated. Pre-incubation of V-79 Chinese hamster cells in medium containing delipidized fetal bovine serum (FBS) markedly increased the subsequent uptake of intracellular boron transported by both BOPP and In-BOPP when compared with cells that had been pre-incubated with medium containing 10% normal FBS (lipidized). The increased uptake was characterized by elevated levels of receptor, and greater affinity was shown for both BOPP and In-BOPP, although less marked with the latter. Positive cooperativity was demonstrated by sigmoid saturation curves, Scatchard analysis and Hill plots. Increasing the amount of LDL in the incubation medium had a relatively small effect on the total accumulation of either indium or boron atoms inside the cell. Furthermore, chemical acetylation of LDL did not decrease the intracellular uptake of either boron or indium transported by BOPP or In-BOPP. It is thus concluded that BOPP and In-BOPP preferentially enter the cells directly by way of the LDL receptor and that only a small fraction of these molecules are transported into the cells indirectly using serum LDLs as their carriers. These data suggest a novel way of bringing greater amounts of boron and indium (and perhaps other agents) into tissues. Porphyrins can be used to transport different agents into tumor cells because they are tumor affinic molecules. Tumors express a higher number of LDL receptors than do most normal tissues

  3. Fluorescence Correlation Spectroscopy to find the critical balance between extracellular association and intracellular dissociation of mRNA-complexes.

    Science.gov (United States)

    Zhang, Heyang; De Smedt, Stefaan C; Remaut, Katrien

    2018-05-10

    Fluorescence Correlation Spectroscopy (FCS) is a promising tool to study interactions on a single molecule level. The diffusion of fluorescent molecules in and out of the excitation volume of a confocal microscope leads to the fluorescence fluctuations that give information on the average number of fluorescent molecules present in the excitation volume and their diffusion coefficients. In this context, we complexed mRNA into lipoplexes and polyplexes and explored the association/dissociation degree of complexes by using gel electrophoresis and FCS. FCS enabled us to measure the association and dissociation degree of mRNA-based complexes both in buffer and protein-rich biological fluids such as human serum and ascitic fluid, which is a clear advantage over gel electrophoresis that was only applicable in protein-free buffer solutions. Furthermore, following the complex stability in buffer and biological fluids by FCS assisted to understand how complex characteristics, such as charge ratio and strength of mRNA binding, correlated to the transfection efficiency. We found that linear polyethyleneimine prevented efficient translation of mRNA, most likely due to a too strong mRNA binding, whereas the lipid based carrier Lipofectamine ® messengerMAX did succeed in efficient release and subsequent translation of mRNA in the cytoplasm of the cells. Overall, FCS is a reliable tool for the in depth characterization of mRNA complexes and can help us to find the critical balance keeping mRNA bound in complexes in the extracellular environment and efficient intracellular mRNA release leading to protein production. The delivery of messenger RNA (mRNA) to cells is promising to treat a variety of diseases. Therefore, the mRNA is typically packed in small lipid particles or polymer particles that help the mRNA to reach the cytoplasm of the cells. These particles should bind and carry the mRNA in the extracellular environment (e.g. blood, peritoneal fluid, ...), but should release

  4. Self-diffusion coefficients of the metastable Lennard-Jones vapor

    International Nuclear Information System (INIS)

    Nie Chu; Zhou Youhua; Marlow, W H; Hassan, Y A

    2008-01-01

    Self-diffusion coefficients of a metastable Lennard-Jones vapor were obtained using the memory function formalism and the frequency moments of the velocity autocorrelation function at reduced temperatures from 0.75 to 1.0. The radial density distribution functions used to evaluate the second, fourth and sixth frequency moments of the velocity autocorrelation function were obtained from the restricted canonical ensemble Monte Carlo simulation (Corti and Debenedetti 1994 Chem. Eng. Sci. 49 2717). The self-diffusion coefficients at reduced temperature 0.75 do not vary monotonically as the density increases, and for the other three temperatures the self-diffusion coefficients vary normally

  5. Self-diffusion coefficients of the metastable Lennard-Jones vapor

    Energy Technology Data Exchange (ETDEWEB)

    Nie Chu; Zhou Youhua [School of Physics and Information Engineering, Jianghan University, Wuhan 430056 (China); Marlow, W H; Hassan, Y A [Department of Nuclear Engineering, Texas A and M University, College Station, TX 77843 (United States)], E-mail: yhzhou@jhun.edu.cn

    2008-10-15

    Self-diffusion coefficients of a metastable Lennard-Jones vapor were obtained using the memory function formalism and the frequency moments of the velocity autocorrelation function at reduced temperatures from 0.75 to 1.0. The radial density distribution functions used to evaluate the second, fourth and sixth frequency moments of the velocity autocorrelation function were obtained from the restricted canonical ensemble Monte Carlo simulation (Corti and Debenedetti 1994 Chem. Eng. Sci. 49 2717). The self-diffusion coefficients at reduced temperature 0.75 do not vary monotonically as the density increases, and for the other three temperatures the self-diffusion coefficients vary normally.

  6. Generalized random walk algorithm for the numerical modeling of complex diffusion processes

    CERN Document Server

    Vamos, C; Vereecken, H

    2003-01-01

    A generalized form of the random walk algorithm to simulate diffusion processes is introduced. Unlike the usual approach, at a given time all the particles from a grid node are simultaneously scattered using the Bernoulli repartition. This procedure saves memory and computing time and no restrictions are imposed for the maximum number of particles to be used in simulations. We prove that for simple diffusion the method generalizes the finite difference scheme and gives the same precision for large enough number of particles. As an example, simulations of diffusion in random velocity field are performed and the main features of the stochastic mathematical model are numerically tested.

  7. Generalized random walk algorithm for the numerical modeling of complex diffusion processes

    International Nuclear Information System (INIS)

    Vamos, Calin; Suciu, Nicolae; Vereecken, Harry

    2003-01-01

    A generalized form of the random walk algorithm to simulate diffusion processes is introduced. Unlike the usual approach, at a given time all the particles from a grid node are simultaneously scattered using the Bernoulli repartition. This procedure saves memory and computing time and no restrictions are imposed for the maximum number of particles to be used in simulations. We prove that for simple diffusion the method generalizes the finite difference scheme and gives the same precision for large enough number of particles. As an example, simulations of diffusion in random velocity field are performed and the main features of the stochastic mathematical model are numerically tested

  8. Confinement and diffusion in tokamaks

    International Nuclear Information System (INIS)

    McWilliams, R.

    1988-01-01

    The effect of electric field fluctuations on confinement and diffusion in tokamak is discussed. Based on the experimentally determined cross-field turbolent diffusion coefficient, D∼3.7*cT e /eB(δn i /n i ) rms which is also derived by a simple theory, the cross-field diffusion time, tp=a 2 /D, is calculated and compared to experimental results from 51 tokamak for standard Ohmic operation

  9. Diffuse scattering of neutrons

    International Nuclear Information System (INIS)

    Novion, C.H. de.

    1981-02-01

    The use of neutron scattering to study atomic disorder in metals and alloys is described. The diffuse elastic scattering of neutrons by a perfect crystal lattice leads to a diffraction spectrum with only Bragg spreads. the existence of disorder in the crystal results in intensity and position modifications to these spreads, and above all, to the appearance of a low intensity scatter between Bragg peaks. The elastic scattering of neutrons is treated in this text, i.e. by measuring the number of scattered neutrons having the same energy as the incident neutrons. Such measurements yield information on the static disorder in the crystal and time average fluctuations in composition and atomic displacements [fr

  10. Diffuse lung disease: Pneumoconioses

    International Nuclear Information System (INIS)

    McLoud, T.C.

    1987-01-01

    This paper begins with a discussion of the 1980 International Labour Organization classification of the pneumoconioses. Emphasis is on the common pneumoconioses, that is, silicosis, coalworker's pneumoconiosis, and asbestos-related pleural and parenchymal disease. Examples of the five radiographic forms of silicosis-simple and complicated silicosis, Caplan syndrome, silicotuberculosis, and acute silicosis- are presented, and the differential diagnoses are discussed. Discussion of asbestos-related disease included pleural manifestations such as plaques, diffuse pleural thickening, and asbestos pleural effusion as well as asbestosis and malignancies associated with asbestos exposure, such as bronchogenic carcinoma and malignant mesothelioma. Although the standard radiographic findings are stressed, the use of CT in the diagnosis of pneumoconiosis and the staging of dust-related malignancies is also discussed

  11. On Diffusive Climatological Models.

    Science.gov (United States)

    Griffel, D. H.; Drazin, P. G.

    1981-11-01

    A simple, zonally and annually averaged, energy-balance climatological model with diffusive heat transport and nonlinear albedo feedback is solved numerically. Some parameters of the model are varied, one by one, to find the resultant effects on the steady solution representing the climate. In particular, the outward radiation flux, the insulation distribution and the albedo parameterization are varied. We have found an accurate yet simple analytic expression for the mean annual insolation as a function of latitude and the obliquity of the Earth's rotation axis; this has enabled us to consider the effects of the oscillation of the obliquity. We have used a continuous albedo function which fits the observed values; it considerably reduces the sensitivity of the model. Climatic cycles, calculated by solving the time-dependent equation when parameters change slowly and periodically, are compared qualitatively with paleoclimatic records.

  12. Diffuse parenchymal lung disease

    Directory of Open Access Journals (Sweden)

    Sara Tomassetti

    2017-04-01

    Full Text Available Between September 2015 and August 2016 there were >1500 publications in the field of diffuse parenchymal lung diseases (DPLDs. For the Clinical Year in Review session at the European Respiratory Society Congress that was held in London, UK, in September 2016, we selected only five articles. This selection, made from the enormous number of published papers, does not include all the relevant studies that will significantly impact our knowledge in the field of DPLDs in the near future. This review article provides our personal view on the following topics: early diagnosis of idiopathic pulmonary fibrosis, current knowledge on the multidisciplinary team diagnosis of DPLDs and the diagnostic role of transbronchial cryobiopsy in this diagnostic setting, insights on the new entity of interstitial pneumonia with autoimmune features, and new therapeutic approaches for scleroderma-related interstitial lung disease.

  13. Convergence of Nelson diffusions

    International Nuclear Information System (INIS)

    Dell'Antonio, G.; Posilicano, A.

    1991-01-01

    Let ψ t , ψ t n , n≥1, be solutions of Schroedinger equations with potentials form-bounded by -1/2 Δ and initial data in H 1 (R d ). Let P, P n , n≥1, be the probability measures on the path space Ω=C(R + , R d ) given by the corresponding Nelson diffusions. We show that if {ψ t n } n≥1 converges to ψ t in H 2 (R d ), uniformly in t over compact intervals, then {P n } n≥1 converges to P in total variation. Moreover, if the potentials are in the Kato class K d , we show that the above result follows from H 1 -convergence of initial data, and K d -convergence of potentials. (orig.)

  14. Hereditary diffuse gastric cancer

    DEFF Research Database (Denmark)

    van der Post, Rachel S; Vogelaar, Ingrid P; Carneiro, Fátima

    2015-01-01

    Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects......, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3...... the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic...

  15. The diffuse interstellar medium

    Science.gov (United States)

    Cox, Donald P.

    1990-01-01

    The last 20 years of the efforts to understand the diffuse ISM are reviewed, with recent changes of fundamental aspects being highlighted. Attention is given to the interstellar pressure and its components, the weight of the ISM, the midplane pressure contributions, and pressure contributions at 1 kpc. What velocity dispersions, cosmic ray pressure, and magnetic field pressure that can be expected for a gas in a high magnetic field environment is addressed. The intercloud medium is described, with reference to the work of Cox and Slavin (1989). Various caveats are discussed and a number of areas for future investigation are identified. Steps that could be taken toward a successful phase segregation model are discussed.

  16. Nonlocal diffusion and applications

    CERN Document Server

    Bucur, Claudia

    2016-01-01

    Working in the fractional Laplace framework, this book provides models and theorems related to nonlocal diffusion phenomena. In addition to a simple probabilistic interpretation, some applications to water waves, crystal dislocations, nonlocal phase transitions, nonlocal minimal surfaces and Schrödinger equations are given. Furthermore, an example of an s-harmonic function, its harmonic extension and some insight into a fractional version of a classical conjecture due to De Giorgi are presented. Although the aim is primarily to gather some introductory material concerning applications of the fractional Laplacian, some of the proofs and results are new. The work is entirely self-contained, and readers who wish to pursue related subjects of interest are invited to consult the rich bibliography for guidance.

  17. Measurement of the apparent diffusion coefficient in paediatric mitochondrial encephalopathy cases and a comparison of parenchymal changes associated with the disease using follow-up diffusion coefficient measurements

    Energy Technology Data Exchange (ETDEWEB)

    Uysal, Fatma, E-mail: afatmauysal@gmail.com [Dokuz Eylül University, Department of Pediatric Radiology, Izmir (Turkey); Çakmakçı, Handan, E-mail: handan.cakmakci@deu.edu.tr [Dokuz Eylül University, Department of Pediatric Radiology, Izmir (Turkey); Yiş, Uluç, E-mail: ulucyis@deu.edu.tr [Dokuz Eylül University, Department of Pediatric Neurology, Izmir (Turkey); Ellidokuz, Hülya, E-mail: hulyaellidokuz@deu.edu.tr [Dokuz Eylül University, Department of Medical Statistics, Izmir (Turkey); Hız, Ayşe Semra, E-mail: aysesemrahiz@deu.edu.tr [Dokuz Eylül University, Department of Pediatric Neurology, Izmir (Turkey)

    2014-01-15

    Objectives: To reveal the contribution of MRI and diffusion-weighted imaging (DWI) to the diagnosis of mitochondrial encephalopathy (ME) and to evaluate the parenchymal changes associated with this disease in the involved parenchymal areas using the apparent diffusion coefficient (ADC) parameter. Methods: Ten patients who had undergone MRI and DWI analysis with a pre-diagnosis of neurometabolic disease, and who were subsequently diagnosed with ME in laboratory and/or genetic studies, were included in our study. ADC values were compared with a control group composed of 20 patients of similar age with normal brains. Evaluations involved measurements made in 20 different areas determined on the ADC map. The dominance or contribution of ADC coefficient measurements to the conventional sequences was compared with the controls. Results: In the first examination, an increase in both diffusion and ADC values was detected in six cases and diffusion restriction and a decrease in ADC values in three patients. While an increase in both diffusion and ADC values was demonstrated in four cases, there was diffusion restriction and a decrease in ADC values in three cases in the control examinations. Conclusions: DWI provides information that complements conventional MRI sequences in the diagnosis of ME.

  18. MHD diffuser model test program

    Energy Technology Data Exchange (ETDEWEB)

    Idzorek, J J

    1976-07-01

    Experimental results of the aerodynamic performance of seven candidate diffusers are presented to assist in determining their suitability for joining an MHD channel to a steam generator at minimum spacing. The three dimensional diffusers varied in area ratio from 2 to 3.8 and wall half angle from 2 to 5 degrees. The program consisted of five phases: (1) tailoring a diffuser inlet nozzle to a 15 percent blockage; (2) comparison of isolated diffusers at enthalpy ratios 0.5 to 1.0 with respect to separation characteristics and pressure recovery coefficients; (3) recording the optimum diffuser exit flow distribution; (4) recording the internal flow distribution within the steam generator when attached to the diffuser; and (5) observing isolated diffuser exhaust dynamic characteristics. The 2 and 2-1/3 degree half angle rectangular diffusers showed recovery coefficients equal to 0.48 with no evidence of flow separation or instability. Diffusion at angles greater than these produced flow instabilities and with angles greater than 3 degrees random flow separation and reattachment.

  19. MHD diffuser model test program

    International Nuclear Information System (INIS)

    Idzorek, J.J.

    1976-07-01

    Experimental results of the aerodynamic performance of seven candidate diffusers are presented to assist in determining their suitability for joining an MHD channel to a steam generator at minimum spacing. The three dimensional diffusers varied in area ratio from 2 to 3.8 and wall half angle from 2 to 5 degrees. The program consisted of five phases: (1) tailoring a diffuser inlet nozzle to a 15 percent blockage; (2) comparison of isolated diffusers at enthalpy ratios 0.5 to 1.0 with respect to separation characteristics and pressure recovery coefficients; (3) recording the optimum diffuser exit flow distribution; (4) recording the internal flow distribution within the steam generator when attached to the diffuser; and (5) observing isolated diffuser exhaust dynamic characteristics. The 2 and 2-1/3 degree half angle rectangular diffusers showed recovery coefficients equal to 0.48 with no evidence of flow separation or instability. Diffusion at angles greater than these produced flow instabilities and with angles greater than 3 degrees random flow separation and reattachment

  20. Diffusion rates for elevated releases

    International Nuclear Information System (INIS)

    Ramsdell, J.V.

    1983-11-01

    A search of the literature related to diffusion from elevated sources has determined that an adequate data base exists for use in developing parameterizations for estimating diffusion rates for material released from free standing stacks at nuclear power plants. A review of published data analyses indicates that a new parameterization of horizontal diffusion rates specifically for elevated releases is not likely to significantly change the magnitudes of horizontal diffusion coefficients on the average. However, the uncertainties associated with horizontal diffusion coefficient estimates under any given set of atmospheric conditions could be reduced by a new parameterization. Similarly, a new parameterization of vertical diffusion rates would be unlikely to significantly alter the magnitudes of diffusion coefficients for unstable atmospheric conditons. However, for neutral and stable atmospheric conditions, a new parameterization of vertical diffusion rates might increase vertical diffusion coefficients significantly. The increase would move ground-level time-integrated concentration maxima closer to the plant and would increase the maxima. 55 references, 2 figures, 4 tables