Drug-drug interaction between methotrexate and levetiracetam resulting in delayed methotrexate elimination.

PubMed

Bain, Emily; Birhiray, Ruemu E; Reeves, David J

2014-02-01

To report a case of delayed methotrexate (MTX) elimination while receiving concomitant levetiracetam. A 46-year-old man with relapsed osteosarcoma of the base of the skull receiving high-dose MTX tolerated his first cycle of MTX with elimination to nontoxic MTX levels (≤0.1 µmol/L) within 90 hours. After hospital discharge, the patient experienced seizures secondary to brain metastasis and started on levetiracetam, which was continued as maintenance therapy. The patient experienced delayed MTX elimination during cycles 2, 3, and 4 while receiving levetiracetam. On average, elimination to nontoxic MTX levels took 130 hours (106-144 hours). Before the fifth cycle of MTX, lorazepam was substituted for the levetiracetam. MTX was eliminated to nontoxic levels within 95 hours. During all cycles, the patient received standard supportive care and serum creatinine remained stable. No other drugs known to interact with MTX were administered. This possible drug interaction has only been reported once in the pediatric population. With a score of 6 on the Drug Interaction Probability Scale for evaluating causation of drug interactions, it is probable that the delayed MTX elimination was caused by an interaction with levetiracetam. Coadministration of levetiracetam and MTX may result in delayed elimination of MTX, increasing the likelihood of toxicity. Consideration should be given to temporarily switching from levetiracetam to another antiepileptic (ie, lorazepam) to prevent this interaction. This is particularly important in those experiencing delayed elimination with prior cycles of concomitant MTX and levetiracetam or those at greater risk for MTX toxicity.

The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009-2014.

PubMed

Bolotin, Shelly; Lim, Gillian; Dang, Vica; Crowcroft, Natasha; Gubbay, Jonathan; Mazzulli, Tony; Schabas, Richard

2017-01-01

In Canada, measles was eliminated in 1998 and rubella in 2000. Effective measles and rubella surveillance is vital in elimination settings, hinging on reliable laboratory methods. However, low-prevalence settings affect the predictive value of laboratory tests. We conducted an analysis to determine the performance of measles and rubella IgM testing in a jurisdiction where both infections are eliminated. 21,299 test results were extracted from the Public Health Ontario Laboratories database and 1,239 reports were extracted from the Ontario Integrated Public Health Information System (iPHIS) from 2008 and 2010 for measles and rubella, respectively, to 2014. Deterministic linkage resulted in 658 linked measles records (2009-2014) and 189 linked rubella records (2010-2014). Sixty-six iPHIS measles entries were classified as confirmed cases, of which 53 linked to laboratory data. Five iPHIS rubella entries were classified as confirmed, all linked to IgM results. The positive predictive value was 17.4% for measles and 3.6% for rubella. Sensitivity was 79.2% for measles and 100.0% for rubella. Specificity was 65.7% for measles and 25.8% for rubella. Our study confirms that a positive IgM alone does not confirm a measles case in elimination settings. This has important implications for countries that are working towards measles and rubella elimination.

Generating Nice Linear Systems for Matrix Gaussian Elimination

ERIC Educational Resources Information Center

Homewood, L. James

2004-01-01

In this article an augmented matrix that represents a system of linear equations is called nice if a sequence of elementary row operations that reduces the matrix to row-echelon form, through matrix Gaussian elimination, does so by restricting all entries to integers in every step. Many instructors wish to use the example of matrix Gaussian…

Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth

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

Tane, Shoji; Okayama, Hitomi; Ikenishi, Aiko

Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21{sup Cip1} and p27{sup Kip1}, regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21{sup Cip1}more » and p27{sup Kip1} also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21{sup Cip1} knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21{sup Cip1} knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21{sup Cip1} and p27{sup Kip1}) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21{sup Cip1} inhibit M-phase entry of cardiomyocytes which have entered the additional cell cycle. - Highlights: • Many postnatal cardiomyocytes entered an additional cell cycle by cyclin D1 induction. • The majority of cardiomyocytes could not enter M-phase after cyclin D1 induction. • Cell cycle progressed markedly in p21{sup Cip1} knockout mice after postnatal day 14. • Tri- and tetranucleated cardiomyocytes increased in p21{sup Cip1} knockout mice.« less

Multibody Parachute Flight Simulations for Planetary Entry Trajectories Using "Equilibrium Points"

NASA Technical Reports Server (NTRS)

Raiszadeh, Ben

2003-01-01

A method has been developed to reduce numerical stiffness and computer CPU requirements of high fidelity multibody flight simulations involving parachutes for planetary entry trajectories. Typical parachute entry configurations consist of entry bodies suspended from a parachute, connected by flexible lines. To accurately calculate line forces and moments, the simulations need to keep track of the point where the flexible lines meet (confluence point). In previous multibody parachute flight simulations, the confluence point has been modeled as a point mass. Using a point mass for the confluence point tends to make the simulation numerically stiff, because its mass is typically much less that than the main rigid body masses. One solution for stiff differential equations is to use a very small integration time step. However, this results in large computer CPU requirements. In the method described in the paper, the need for using a mass as the confluence point has been eliminated. Instead, the confluence point is modeled using an "equilibrium point". This point is calculated at every integration step as the point at which sum of all line forces is zero (static equilibrium). The use of this "equilibrium point" has the advantage of both reducing the numerical stiffness of the simulations, and eliminating the dynamical equations associated with vibration of a lumped mass on a high-tension string.

Investigating Relationships between and within Entry Pathways on a Sport Related Programme and the Degree Outcome Obtained

ERIC Educational Resources Information Center

Huntley, Tabo; Whitehead, Amy; Cullinane, Danny; Nixon, Sarah; Huntley, Emma

2017-01-01

Research within Higher Education in the United Kingdom has reported conflicting findings when investigating the relationship between undergraduate entry routes and gender, with successful performances across the degree cycle. This paper adds to this body of knowledge and examines the relationship between entry routes and gender on student outcomes…

Aerocapture Inflatable Decelerator for Planetary Entry

NASA Technical Reports Server (NTRS)

Reza, Sajjad; Hund, Richard; Kustas, Frank; Willcockson, William; Songer, Jarvis; Brown, Glen

2007-01-01

Forward Attached Inflatable Decelerators, more commonly known as inflatable aeroshells, provide an effective, cost efficient means of decelerating spacecrafts by using atmospheric drag for aerocapture or planetary entry instead of conventional liquid propulsion deceleration systems. Entry into planetary atmospheres results in significant heating and aerodynamic pressures which stress aeroshell systems to their useful limits. Incorporation of lightweight inflatable decelerator surfaces with increased surface-area footprints provides the opportunity to reduce heat flux and induced temperatures, while increasing the payload mass fraction. Furthermore, inflatable aeroshell decelerators provide the needed deceleration at considerably higher altitudes and Mach numbers when compared with conventional rigid aeroshell entry systems. Inflatable aeroshells also provide for stowage in a compact space, with subsequent deployment of a large-area, lightweight heatshield to survive entry heating. Use of a deployable heatshield decelerator enables an increase in the spacecraft payload mass fraction and may eliminate the need for a spacecraft backshell.

An Analysis of U.S. Army Health Hazard Assessments During the Acquisition of Military Materiel

DTIC Science & Technology

2010-06-03

protective equipment (PPE) (Milz, Conrad, & Soule , 2003). Engineering controls can eliminate hazards through system design, substitution of hazardous...Milz, Conrad, & Soule , 2003). Engineering control measures can serve to 7 minimize hazards where they cannot be eliminated, with preference for...during the materiel acquisitions process, and (c) will evaluate a sample of the database for accuracy by comparing the data entries to original reports

The Hog Cycle of Law Professors: An Econometric Time Series Analysis of the Entry-Level Job Market in Legal Academia.

PubMed

Engel, Christoph; Hamann, Hanjo

2016-01-01

The (German) market for law professors fulfils the conditions for a hog cycle: In the short run, supply cannot be extended or limited; future law professors must be hired soon after they first present themselves, or leave the market; demand is inelastic. Using a comprehensive German dataset, we show that the number of market entries today is negatively correlated with the number of market entries eight years ago. This suggests short-sighted behavior of young scholars at the time when they decide to prepare for the market. Using our statistical model, we make out-of-sample predictions for the German academic market in law until 2020.

Scalloped and Yorkie are required for cell cycle re-entry of quiescent cells after tissue damage.

PubMed

Meserve, Joy H; Duronio, Robert J

2015-08-15

Regeneration of damaged tissues typically requires a population of active stem cells. How damaged tissue is regenerated in quiescent tissues lacking a stem cell population is less well understood. We used a genetic screen in the developing Drosophila melanogaster eye to investigate the mechanisms that trigger quiescent cells to re-enter the cell cycle and proliferate in response to tissue damage. We discovered that Hippo signaling regulates compensatory proliferation after extensive cell death in the developing eye. Scalloped and Yorkie, transcriptional effectors of the Hippo pathway, drive Cyclin E expression to induce cell cycle re-entry in cells that normally remain quiescent in the absence of damage. Ajuba, an upstream regulator of Hippo signaling that functions as a sensor of epithelial integrity, is also required for cell cycle re-entry. Thus, in addition to its well-established role in modulating proliferation during periods of tissue growth, Hippo signaling maintains homeostasis by regulating quiescent cell populations affected by tissue damage. © 2015. Published by The Company of Biologists Ltd.

DCAF1 controls T-cell function via p53-dependent and -independent mechanisms.

PubMed

Guo, Zengli; Kong, Qing; Liu, Cui; Zhang, Song; Zou, Liyun; Yan, Feng; Whitmire, Jason K; Xiong, Yue; Chen, Xian; Wan, Yisong Y

2016-01-05

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1-cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms.

DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

PubMed Central

Guo, Zengli; Kong, Qing; Liu, Cui; Zhang, Song; Zou, Liyun; Yan, Feng; Whitmire, Jason K.; Xiong, Yue; Chen, Xian; Wan, Yisong Y.

2016-01-01

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1–cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms. PMID:26728942

78 FR 51255 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... Rule Change To Eliminate Rule Related to CYCLE Routing August 14, 2013. Pursuant to Section 19(b)(1) of... the CYCLE Routing option, effective as of September 3, 2013. The text of the proposed rule change is... proposing to eliminate Rule 11.13(a)(3)(A), which is the provision that authorizes the CYCLE Routing option...

Robust mitotic entry is ensured by a latching switch.

PubMed

Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novák, Béla

2013-01-01

Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust.

The Hog Cycle of Law Professors: An Econometric Time Series Analysis of the Entry-Level Job Market in Legal Academia

PubMed Central

Hamann, Hanjo

2016-01-01

The (German) market for law professors fulfils the conditions for a hog cycle: In the short run, supply cannot be extended or limited; future law professors must be hired soon after they first present themselves, or leave the market; demand is inelastic. Using a comprehensive German dataset, we show that the number of market entries today is negatively correlated with the number of market entries eight years ago. This suggests short-sighted behavior of young scholars at the time when they decide to prepare for the market. Using our statistical model, we make out-of-sample predictions for the German academic market in law until 2020. PMID:27467518

Construction records study : final report.

DOT National Transportation Integrated Search

1975-09-01

The purpose of this study was to determine the extent of change and revision necessary for efficient record keeping and to revise the record keeping process in the field, eliminating irrelevant entries. This study attempted to standardize field recor...

Double-Entry Bookkeeping.

ERIC Educational Resources Information Center

Snyder, Herbert

1999-01-01

Explains the principles and mechanics of double-entry bookkeeping as a part of the accounting cycle to produce a functioning set of accounting records. Suggests that libraries need to have accurate and timely information about their spending to gain financial control and protect against fraud and abuse. (LRW)

Exploring different photodynamic therapy parameters to optimize elimination of Enterococcus faecalis in planktonic form.

PubMed

Soares, Janir Alves; Soares, Suelleng Maria Cunha Santos; de Jesus Tavarez, Rudys Rodolfo; de Castro Rizzi, Claudia; Vaz Rodrigues, Silvana Cristina Gama; Maia Filho, Etevaldo Matos; Brito-Júnior, Manoel; Pereira, Rodrigo Dantas; Magalhães, Paula Prazeres; de Macêdo Farias, Luiz

2018-06-01

The failure of endodontic treatment is linked to the presence of Enterococcus faecalis in the root canals. The scope of this study was to evaluate the influence of the energy dose and frequency of photodynamic therapy (PDT cycles), as well as the volume of bacterial suspensions (BS) in the elimination of Enterococcus faecalis in planktonic form. In four successive assays BS of Enterococcus faecalis ATCC 19433 were irradiated with a diode laser (40 mW) using the photosensitizer (PS) methylene blue (MB) (0.005 μg/mL). Group 1 - Effect of energy dose: 100 μ L of BS and 100 μ L of PS were irradiated by 1, 2.5, 5, 7.5 and 10 minute s. Group 2 - Effect of PDT cycles: The BS received 1, 2, 3 or 4 PDT cycles (in each cycle 100 m L of PS was added and irradiated by 2.5 minutes). Group 3 - Effect of energy dose and bacterial suspension volume: 10 μ L of BS and 10 μ L of PS were irradiated similar to group 1. Group 4 - Effect of energy dose, bacterial suspension volume and PDT cycles: 10 μ L of BS and 10 μL of PS were irradiated according to group 2. The laser source and MB isolated represented the controls. The mean log reduction after separate applying laser light and MB were 0.01 and 0.07, respectively. It was found that wells with 100 μ L of BS irradiated with 2.4 to 24 J of energy did not cause significant bacterial elimination (p > 0.05), on the other hand PDT cycles above 12 J increased significantly bacterial elimination (p < 0.05). In 10 μ L wells irradiation from 12 J of energy provided higher bacterial elimination (p < 0.05) which combined with PDT cycle resulted in the logarithmic elimination of E. faecalis (p < 0.05). The energy dose, the volume of the bacterial suspension and, especially, the PDT cycles optimized the bacterial elimination of Enterococcus faecalis in planktonic form. Copyright © 2018 Elsevier B.V. All rights reserved.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

PubMed Central

Carén, Helena; Stricker, Stefan H.; Bulstrode, Harry; Gagrica, Sladjana; Johnstone, Ewan; Bartlett, Thomas E.; Feber, Andrew; Wilson, Gareth; Teschendorff, Andrew E.; Bertone, Paul; Beck, Stephan; Pollard, Steven M.

2015-01-01

Summary Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM. PMID:26607953

Amygdala activity associated with social choice in mice.

PubMed

Mihara, Takuma; Mensah-Brown, Kobina; Sobota, Rosanna; Lin, Robert; Featherstone, Robert; Siegel, Steven J

2017-08-14

Studies suggest that the amygdala is a key region for regulation of anxiety, fear and social function. Therefore, dysfunction of the amygdala has been proposed as a potential mechanism for negative symptoms in schizophrenia. This may be due to NMDA receptor-mediated hypofunction, which is thought to be related to the pathogenesis of schizophrenia. In this study, electroencephalographic amygdala activity was assessed in mice during the three-chamber social test. This activity was also evaluated following exposure to the NMDA receptor antagonist ketamine. Vehicle-treated mice spent significantly more time in the social than the non-social chamber. This social preference was eliminated by ketamine. However, ketamine-treated mice spent significantly less time in the social chamber and significantly more time in the nonsocial chamber than vehicle-treated mice. There were no significant differences in induced powers between social and non-social chamber entries in vehicle-treated mice, except for theta frequencies, which featured greater induced theta power during non-social chamber entry. Ketamine eliminated differences in induced theta power between social and non-social chamber entries. Moreover, ketamine increased the induced gamma power during social chamber entry compared to that of vehicle-treated mice. All other frequency ranges were not significantly influenced by zone or drug condition. All significant findings were upon entry to chambers not during interaction. Results suggest that impaired function of NMDA receptor-mediated glutamate transmission can induce social impairments and amygdala dysfunction, similar to the pattern in schizophrenia. Future studies will utilize this method to evaluate mechanisms of social dysfunction and development of treatments of social impairments in schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Stress Testing of the Philips 60W Replacement Lamp L Prize Entry

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

Poplawski, Michael E.; Ledbetter, Marc R.; Smith, Mark

2012-04-24

The Pacific Northwest National Laboratory, operated by Battelle for the U.S. Department of Energy, worked with Intertek to develop a procedure for stress testing medium screw-base light sources. This procedure, composed of alternating stress cycles and performance evaluation, was used to qualitatively compare and contrast the durability and reliability of the Philips 60W replacement lamp L Prize entry with market-proven compact fluorescent lamps (CFLs) with comparable light output and functionality. The stress cycles applied simultaneous combinations of electrical, thermal, vibration, and humidity stresses of increasing magnitude. Performance evaluations measured relative illuminance, x chromaticity and y chromaticity shifts after each stressmore » cycle. The Philips L Prize entry lamps appear to be appreciably more durable than the incumbent energy-efficient technology, as represented by the evaluated CFLs, and with respect to the applied stresses. Through the course of testing, all 15 CFL samples permanently ceased to function as a result of the applied stresses, while only 1 Philips L Prize entry lamp exhibited a failure, the nature of which was minor, non-destructive, and a consequence of a known (and resolved) subcontractor issue. Given that current CFL technology appears to be moderately mature and no Philips L Prize entry failures could be produced within the stress envelope causing 100 percent failure of the benchmark CFLs, it seems that, in this particular implementation, light-emitting diode (LED) technology would be much more durable in the field than current CFL technology. However, the Philips L Prize entry lamps used for testing were carefully designed and built for the competition, while the benchmark CFLs were mass produced for retail sale—a distinction that should be taken into consideration. Further reliability testing on final production samples would be necessary to judge the extent to which the results of this analysis apply to production versions of the Philips L Prize entry.« less

Thermal math model analysis of FRSI test article subjected to cold soak and entry environments. [Flexible Reuseable Surface Insulation in Space Shuttle Orbiter

NASA Technical Reports Server (NTRS)

Gallegos, J. J.

1978-01-01

A multi-objective test program was conducted at the NASA/JSC Radiant Heat Test Facility in which an aluminum skin/stringer test panel insulated with FRSI (Flexible Reusable Surface Insulation) was subjected to 24 simulated Space Shuttle Orbiter ascent/entry heating cycles with a cold soak in between in the 10th and 20th cycles. A two-dimensional thermal math model was developed and utilized to predict the thermal performance of the FRSI. Results are presented which indicate that the modeling techniques and property values have been proven adequate in predicting peak structure temperatures and entry thermal responses from both an ambient and cold soak condition of an FRSI covered aluminum structure.

Chemical and toxicological evaluation of transformation products during advanced oxidation processes.

PubMed

vom Eyser, C; Börgers, A; Richard, J; Dopp, E; Janzen, N; Bester, K; Tuerk, J

2013-01-01

The entry of pharmaceuticals into the water cycle from sewage treatment plants is of growing concern because environmental effects are evident at trace levels. Ozonation, UV- and UV/H(2)O(2)-treatment were tested as an additional step in waste water treatment because they have been proven to be effective in eliminating aqueous organic contaminants. The pharmaceuticals carbamazepine, ciprofloxacin, diclofenac, metoprolol and sulfamethoxazole as well as the personal care products galaxolide and tonalide were investigated in terms of degradation efficiency and by-product formation in consideration of toxic effects. The substances were largely removed from treatment plant effluent by ozonation, UV- and UV/H(2)O(2)-treatment. Transformation products were detected in all tested treatment processes. Accompanying analysis showed no genotoxic, cytotoxic or estrogenic potential for the investigated compounds after oxidative treatment of real waste waters. The results indicate that by-product formation from ozonation and advanced oxidation processes does not have any negative environmental impact.

Field of first magnetic flux entry and pinning strength of superconductors for rf application measured with muon spin rotation

DOE PAGES

Junginger, Tobias; Abidi, S. H.; Maffett, R. D.; ...

2018-03-16

Here, the performance of superconducting radiofrequency (SRF) cavities used for particle accelerators depends on two characteristic material parameters: field of first flux entry H entry and pinning strength. The former sets the limit for the maximum achievable accelerating gradient, while the latter determines how efficiently flux can be expelled related to the maximum achievable quality factor. In this paper, a method based on muon spin rotation (μSR) is developed to probe these parameters on samples. It combines measurements from two different spectrometers, one being specifically built for these studies and samples of different geometries. It is found that annealing atmore » 1400°C virtually eliminates all pinning. Such an annealed substrate is ideally suited to measure H entry of layered superconductors, which might enable accelerating gradients beyond bulk niobium technology.« less

STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

PubMed

Legrand, Julien M D; Roy, Edwige; Ellis, Jonathan J; Francois, Mathias; Brooks, Andrew J; Khosrotehrani, Kiarash

2016-09-01

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Program for creating an operating system generation cross reference index (SGINDEX)

NASA Technical Reports Server (NTRS)

Barth, C. W.

1972-01-01

Computer program to collect key data from Stage Two input of OS/360 system and to prepare formatted listing of index entries collected is discussed. Program eliminates manual paging through system output by providing comprehensive cross reference.

Two essays on electricity markets: Entry into hydroelectric generation industry and the political cycle of regulated prices

NASA Astrophysics Data System (ADS)

Moita, Rodrigo Menon Simoes

This dissertation is about the electricity industry and the problems that arise with the liberalization and de-regulation of the industry. Characteristics intrinsic to the electricity market create problems that can compromise an efficient functioning of this market. Each of the two chapters of this dissertation focus on a specific aspect of this industry. The first chapter analyzes entry in the hydroelectric generation industry. The operation of a generator upstream regularizes the river flow for generators located downstream on the same river, increasing the production capacity of the latter. This positive externality increases the attractiveness of the locations downstream whenever a generator decides to enter upstream. Therefore, the entry decision of a generator in a given location may affect all entry decisions in potential locations for plants located downstream. I first model the problem of generators located in cascade on the same river and show the positive effect of the externality. Second, I use a panel of data on investment decisions of hydro-generation firms to estimate an entry model that takes into account the effect of the externality generated by entry upriver. The results show a positive incentive to locate downstream from existing plants and from locations where entry is likely to occur. Location characteristics also play an important role on the entrants' decisions. The model provides estimates of the average expected market price across the different years covered by the sample and shows that it rose one year before the energy crisis of 2001, evidencing that the market anticipated the crisis. This result has important implications on the evaluation of the Brazilian market design. It shows that entry responded to a rise in expectations about excess demand in the future, contradicting the argument that the crisis was a consequence of mis-designed market institutions. The second chapter deals with the problem of the political cycle in regulated industries. It follows Paiva (1995) in combining elements of both the political cycle approach of Rogoff and Sibert and the political theory of regulation of Peltzman: the idea that policy decisions may change with the proximity of elections is borrowed from the political business cycle theory and added to enhance the traditional, static models of political regulation. More specifically, I combine the main ideas of Peltzman (1976) and Rogoff and Sibert (1988) to model the regulator's problem as a signaling game where politicians set the regulated price trying to maximize electoral support by signaling to voters a pro-consumer behavior. Political incentives and welfare constraints interact in the model yielding an equilibrium in which the real price in a regulated industry falls in periods immediately preceding an election. Besides presenting a new model of political price cycles in regulated industries, this paper empirically test this theory. Using quarterly data from 35 industrial and developing countries over the period 1978-2004, I find a negative but not statistically significant relationship between elections and electricity prices.

Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

PubMed Central

Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

2013-01-01

Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. PMID:23211596

Cell cycle arrest by prostaglandin A1 at the G1/S phase interface with up-regulation of oncogenes in S-49 cyc- cells

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.

1994-01-01

Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the -49 lymphoma variant (cyc-) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc- cells. DNA synthesis is inhibited 42% by dmPGA1 (50 microM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the alpha, beta unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc- cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30-50 microns) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc- cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block.(ABSTRACT TRUNCATED AT 250 WORDS).

Of Butterflies and Beetles: First Graders' Ways of Seeing and Talking about Insect Life Cycles.

ERIC Educational Resources Information Center

Shepardson, Daniel P.

1997-01-01

Explores children's understandings of insect life cycles through pre- and postinstructional interviews, analysis of children's journal entries, and talk that occurred throughout the instructional unit. Contains 38 references. (DDR)

Efficient computer algebra algorithms for polynomial matrices in control design

NASA Technical Reports Server (NTRS)

Baras, J. S.; Macenany, D. C.; Munach, R.

1989-01-01

The theory of polynomial matrices plays a key role in the design and analysis of multi-input multi-output control and communications systems using frequency domain methods. Examples include coprime factorizations of transfer functions, cannonical realizations from matrix fraction descriptions, and the transfer function design of feedback compensators. Typically, such problems abstract in a natural way to the need to solve systems of Diophantine equations or systems of linear equations over polynomials. These and other problems involving polynomial matrices can in turn be reduced to polynomial matrix triangularization procedures, a result which is not surprising given the importance of matrix triangularization techniques in numerical linear algebra. Matrices with entries from a field and Gaussian elimination play a fundamental role in understanding the triangularization process. In the case of polynomial matrices, matrices with entries from a ring for which Gaussian elimination is not defined and triangularization is accomplished by what is quite properly called Euclidean elimination. Unfortunately, the numerical stability and sensitivity issues which accompany floating point approaches to Euclidean elimination are not very well understood. New algorithms are presented which circumvent entirely such numerical issues through the use of exact, symbolic methods in computer algebra. The use of such error-free algorithms guarantees that the results are accurate to within the precision of the model data--the best that can be hoped for. Care must be taken in the design of such algorithms due to the phenomenon of intermediate expressions swell.

HPV-16 virions can remain infectious for 2 weeks on senescent cells but require cell cycle re-activation to allow virus entry.

PubMed

Broniarczyk, Justyna; Ring, Nadja; Massimi, Paola; Giacca, Mauro; Banks, Lawrence

2018-01-16

Successful infection with Human Papillomaviruses requires mitosis, when incoming viral genomes gain access to nuclear components. However, very little is known about how long HPV particles can remain infectious in non-dividing cells or in which cellular compartments these viruses may reside. To investigate these questions we have used BJ cells as a reversible model of senescence and show that HPV-16 can only infect early-passage proliferating cells. Late-passage senescent cells are resistant to HPV infection, but this can be reversed by inducing cell cycle re-entry with a p53 siRNA. In senescent cells we find that efficient virus entry can be attained upon cell cycle re-entry 16 days after infection, demonstrating that HPV can persist for 2 weeks prior to induction of mitosis. However, exposing cells to anti-HPV-16 L1 neutralising antibody blocks infection at these late time points, suggesting that the virions reside near the cell surface. Indeed, immunofluorescence analysis shows that virions accumulate on the cell surface of senescent cells and only enter endocytic vesicles upon stimulation with p53 siRNA. These results demonstrate that HPV-16 virions can remain viable on a non-dividing cell for extended periods of time, but are nonetheless vulnerable to antibody-induced neutralisation throughout.

Evaluation of manhole inserts as structural barriers to mosquito entry into belowground stormwater systems using a simulated treatment device.

PubMed

Harbison, Justin E; Metzger, Marco E; Allen, Vaikko; Hu, Renjie

2009-09-01

Belowground proprietary stormwater treatment devices can produce mosquitoes, including vectors of West Nile virus. Elimination of vertical entry points such as pick holes in manhole covers may reduce the number of mosquitoes entering and reproducing in these structures. Plastic manhole dish inserts were evaluated as structural barriers against mosquito entry through pick holes in a simulated stormwater treatment device. Inserts were 100% effective at preventing mosquito entry through covers when no other openings existed. In devices configured with an open lateral conveyance pipe, the addition of an insert under the cover reduced mosquito oviposition significantly. Subsequent trials to further elucidate mosquito entry through manhole covers found a significant positive correlation between increasing number of pick holes and mosquito oviposition. Results of the study suggest the potential for manhole dish inserts to decrease the number of mosquitoes entering belowground structures. The different available stormwater treatment systems and site-specific installations may, however, provide a much greater variety of possible alternate entry points for mosquitoes than was addressed in the current study. Further work is needed in field installations to quantify the significance of pick holes to mosquito entry and determine under what conditions, if any, manhole dish inserts would be most effective and appropriate.

Genome-wide screen identifies novel machineries required for both ciliogenesis and cell cycle arrest upon serum starvation

PubMed Central

Kim, Ji Hyun; Ki, Soo Mi; Joung, Je-Gun; Scott, Eric; Heynen-Genel, Susanne; Aza-Blanc, Pedro; Kwon, Chang Hyuk; Kim, Joon; Gleeson, Joseph G.; Lee, Ji Eun

2016-01-01

Biogenesis of the primary cilium, a cellular organelle mediating various signaling pathways, is generally coordinated with cell cycle exit/re-entry. Although the dynamic cell cycle-associated profile of the primary cilium has been largely accepted, the mechanism governing the link between ciliogenesis and cell cycle progression has been poorly understood. Using a human genome-wide RNAi screen, we identify genes encoding subunits of the spliceosome and proteasome as novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing-related hits are essential for RNA expression of molecules acting in cilia disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia assembly, such as IFT88 and CPAP. In particular, we show that these screen hit-associated mechanisms are crucial for both cilia assembly and cell cycle arrest in response to serum withdrawal. Finally, our data suggest that the mRNA processing mechanism may modulate the UPS-dependent decay of cilia assembly regulators to control ciliary resorption-coupled cell cycle re-entry. PMID:27033521

Inducing myoblast re-entry into the cell cycle: a potential mechanism for laser-enhanced skeletal muscle regeneration

NASA Astrophysics Data System (ADS)

Liu, T.; Fang, Y.; Zhang, C. P.; Chen, P.; Wang, C. Z.; Kang, H. X.; Shen, B. J.; Liang, J.; Fu, X. B.

2014-09-01

This study investigated the effect of low-level laser irradiation (LLLI) on the cell cycle and proliferative activity of cultured myoblasts, and sought to elucidate the possible cellular mechanism by which LLLI promotes the regeneration of skeletal muscle in vivo. Primary myoblasts isolated from rat hindlegs were irradiated with helium-neon laser light at different energy densities. Distributions of cell-cycle subpopulations and the expression of cell-cycle regulatory proteins in myoblasts were assessed using flow cytometric analysis and western blot assay. It was found that laser irradiation stimulated cell-cycle entry; induced the expression of cyclin A and cyclin D; and increased cell proliferation index and bromodeoxyuridine incorporation as compared to the unirradiated control cells, indicating LLLI augmented the number of proliferative myoblasts in the S phase and G2/M phase of the cell cycle. These results suggest that LLLI at certain fluxes and wavelengths could activate quiescent myoblasts, leading to cell division and facilitating new myofiber formation. This could contribute to the improvement of skeletal muscle regeneration following trauma and myopathic diseases.

Definition ofthe Design Trajectory and Entry Flight Corridor for the NASA Orion Exploration Mission 1 Entry Trajectory Using an Integrated Approach and Optimization

NASA Technical Reports Server (NTRS)

McNamara, Luke W.; Braun, Robert D.

2014-01-01

One of the key design objectives of NASA's Orion Exploration Mission 1 (EM- 1) is to execute a guided entry trajectory demonstrating GN&C capability. The focus of this paper is defining the flyable entry corridor for EM-1 taking into account multiple subsystem constraints such as complex aerothermal heating constraints, aerothermal heating objectives, landing accuracy constraints, structural load limits, Human-System-Integration-Requirements, Service Module debris disposal limits and other flight test objectives. During the EM-1 Design Analysis Cycle 1 design challenges came up that made defining the flyable entry corridor for the EM-1 mission critical to mission success. This document details the optimization techniques that were explored to use with the 6-DOF ANTARES simulation to assist in defining the design entry interface state and entry corridor with respect to key flight test constraints and objectives.

Circumferential and functional re-entry of in vivo slow-wave activity in the porcine small intestine.

PubMed

Angeli, T R; O'Grady, G; Du, P; Paskaranandavadivel, N; Pullan, A J; Bissett, I P; Cheng, L K

2013-05-01

Slow-waves modulate the pattern of small intestine contractions. However, the large-scale spatial organization of intestinal slow-wave pacesetting remains uncertain because most previous studies have had limited resolution. This study applied high-resolution (HR) mapping to evaluate intestinal pacesetting mechanisms and propagation patterns in vivo. HR serosal mapping was performed in anesthetized pigs using flexible arrays (256 electrodes; 32 × 8; 4 mm spacing), applied along the jejunum. Slow-wave propagation patterns, frequencies, and velocities were calculated. Slow-wave initiation sources were identified and analyzed by animation and isochronal activation mapping. Analysis comprised 32 recordings from nine pigs (mean duration 5.1 ± 3.9 min). Slow-wave propagation was analyzed, and a total of 26 sources of slow-wave initiation were observed and classified as focal pacemakers (31%), sites of functional re-entry (23%) and circumferential re-entry (35%), or indeterminate sources (11%). The mean frequencies of circumferential and functional re-entry were similar (17.0 ± 0.3 vs 17.2 ± 0.4 cycle min(-1) ; P = 0.5), and greater than that of focal pacemakers (12.7 ± 0.8 cycle min(-1) ; P < 0.001). Velocity was anisotropic (12.9 ± 0.7 mm s(-1) circumferential vs 9.0 ± 0.7 mm s(-1) longitudinal; P < 0.05), contributing to the onset and maintenance of re-entry. This study has shown multiple patterns of slow-wave initiation in the jejunum of anesthetized pigs. These results constitute the first description and analysis of circumferential re-entry in the gastrointestinal tract and functional re-entry in the in vivo small intestine. Re-entry can control the direction, pattern, and frequency of slow-wave propagation, and its occurrence and functional significance merit further investigation. © 2013 Blackwell Publishing Ltd.

Accurate predictor-corrector skip entry guidance for low lift-to-drag ratio spacecraft

NASA Astrophysics Data System (ADS)

Enmi, Y.; Qian, W.; He, K.; Di, D.

2018-06-01

This paper develops numerical predictor-corrector skip en try guidance for vehicles with low lift-to-drag L/D ratio during the skip entry phase of a Moon return mission. The guidance method is composed of two parts: trajectory planning before entry and closed-loop gu idance during skip entry. The result of trajectory planning before entry is able to present an initial value for predictor-corrector algorithm in closed-loop guidance for fast convergence. The magnitude of bank angle, which is parameterized as a linear function of the range-to-go, is modulated to satisfy the downrange requirements. The sign of the bank ang le is determined by the bank-reversal logic. The predictor-corrector algorithm repeatedly applied onboard in each guidance cycle to realize closed-loop guidance in the skip entry phase. The effectivity of the proposed guidance is validated by simulations in nominal conditions, including skip entry, loft entry, and direct entry, as well as simulations in dispersion conditions considering the combination disturbance of the entry interface, the aerodynamic coefficients, the air density, and the mass of the vehicle.

Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.

PubMed

Santafe, M M; Garcia, N; Lanuza, M A; Tomàs, M; Besalduch, N; Tomàs, J

2009-04-01

We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.

Oxidative stress triggers cytokinesis failure in hepatocytes upon isolation.

PubMed

Tormos, A M; Taléns-Visconti, R; Bonora-Centelles, A; Pérez, S; Sastre, J

2015-01-01

Primary hepatocytes are highly differentiated cells and proliferatively quiescent. However, the stress produced during liver digestion seems to activate cell cycle entry by proliferative/dedifferentiation programs that still remain unclear. The aim of this work was to assess whether the oxidative stress associated with hepatocyte isolation affects cell cycle and particularly cytokinesis, the final step of mitosis. Hepatocytes were isolated from C57BL/6 mice by collagenase perfusion in the absence and presence of N-acetyl cysteine (NAC). Polyploidy, cell cycle, and reactive oxygen species (ROS) were studied by flow cytometry (DNA, phospho-histone 3, and CellROX(®) Deep Red) and Western blotting (cyclins B1 and D1, and proliferating cell nuclear antigen). mRNA expression of cyclins A1, B1, B2, D1, and F by reverse transcription (RT)-PCR was also assessed. Glutathione levels were measured by mass spectrometry. Here we show that hepatocyte isolation enhanced cell cycle entry, increased hepatocyte binucleation, and caused marked glutathione oxidation. Addition of 5 mM NAC to the hepatocyte isolation media prevented glutathione depletion, partially blocked ROS production and cell cycle entry of hepatocytes, and avoided the blockade of mitosis progression, abrogating defective cytokinesis and diminishing the formation of binucleated hepatocytes during isolation. Therefore, addition of NAC to the isolation media decreased the generation of polyploid hepatocytes confirming that oxidative stress occurs during hepatocyte isolation and it is responsible, at least in part, for cytokinesis failure and hepatocyte binucleation.

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

Junginger, Tobias; Abidi, S. H.; Maffett, R. D.

Here, the performance of superconducting radiofrequency (SRF) cavities used for particle accelerators depends on two characteristic material parameters: field of first flux entry H entry and pinning strength. The former sets the limit for the maximum achievable accelerating gradient, while the latter determines how efficiently flux can be expelled related to the maximum achievable quality factor. In this paper, a method based on muon spin rotation (μSR) is developed to probe these parameters on samples. It combines measurements from two different spectrometers, one being specifically built for these studies and samples of different geometries. It is found that annealing atmore » 1400°C virtually eliminates all pinning. Such an annealed substrate is ideally suited to measure H entry of layered superconductors, which might enable accelerating gradients beyond bulk niobium technology.« less

Functional characterization of P2Y1 versus P2X receptors in RBA-2 astrocytes: elucidate the roles of ATP release and protein kinase C.

PubMed

Weng, Ju-Yun; Hsu, Tsan-Ting; Sun, Synthia H

2008-05-15

A physiological concentration of extracellular ATP stimulated biphasic Ca(2+) signal, and the Ca(2+) transient was decreased and the Ca(2+) sustain was eliminated immediately after removal of ATP and Ca(2+) in RBA-2 astrocytes. Reintroduction of Ca(2+) induced Ca(2+) sustain. Stimulation of P2Y(1) receptors with 2-methylthioadenosine 5'-diphosphate (2MeSADP) also induced a biphasic Ca(2+) signaling and the Ca(2+) sustains were eliminated using Ca(2+)-free buffer. The 2MeSADP-mediated biphasic Ca(2+) signals were inhibited by phospholipase C (PLC) inhibitor U73122, and completely blocked by P2Y(1) selective antagonist MRS2179 and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) whereas enhanced by PKC inhibitors GF109203X and Go6979. Inhibition of capacitative Ca(2+) entry (CCE) decreased the Ca(2+)-induced Ca(2+) entry; nevertheless, ATP further enhanced the Ca(2+)-induced Ca(2+) entry in the intracellular Ca(2+) store-emptied and CCE-inhibited cells indicating that ATP stimulated Ca(2+) entry via CCE and ionotropic P2X receptors. Furthermore, the 2MeSADP-induced Ca(2+) sustain was eliminated by apyrase but potentiated by P2X(4) allosteric effector ivermectin (IVM). The agonist ADPbetaS stimulated a lesser P2Y(1)-mediated Ca(2+) signal and caused a two-fold increase in ATP release but that were not affected by IVM whereas inhibited by PMA, PLC inhibitor ET-18-OCH(3) and phospholipase D (PLD) inhibitor D609, and enhanced by removal of intra- or extracellular Ca(2+). Taken together, the P2Y(1)-mediated Ca(2+) sustain was at least in part via P2X receptors activated by the P2Y(1)-induced ATP release, and PKC played a pivotal role in desensitization of P2Y(1) receptors in RBA-2 astrocytes. Copyright 2007 Wiley-Liss, Inc.

Static mechanical strain induces capillary endothelial cell cycle re-entry and sprouting.

PubMed

Zeiger, A S; Liu, F D; Durham, J T; Jagielska, A; Mahmoodian, R; Van Vliet, K J; Herman, I M

2016-08-16

Vascular endothelial cells are known to respond to a range of biochemical and time-varying mechanical cues that can promote blood vessel sprouting termed angiogenesis. It is less understood how these cells respond to sustained (i.e., static) mechanical cues such as the deformation generated by other contractile vascular cells, cues which can change with age and disease state. Here we demonstrate that static tensile strain of 10%, consistent with that exerted by contractile microvascular pericytes, can directly and rapidly induce cell cycle re-entry in growth-arrested microvascular endothelial cell monolayers. S-phase entry in response to this strain correlates with absence of nuclear p27, a cyclin-dependent kinase inhibitor. Furthermore, this modest strain promotes sprouting of endothelial cells, suggesting a novel mechanical 'angiogenic switch'. These findings suggest that static tensile strain can directly stimulate pathological angiogenesis, implying that pericyte absence or death is not necessarily required of endothelial cell re-activation.

Cognate interactions between helper T cells and B cells. IV. Requirements for the expression of effector phase activity by helper T cells.

PubMed

Bartlett, W C; McCann, J; Shepherd, D M; Roy, M; Noelle, R J

1990-12-15

After activation with anti-CD3, activated Th (THCD3), but not resting Th, fixed with paraformaldehyde induce B cell RNA synthesis when co-cultured with resting B cells. This activity is expressed by Th of both Th1 and Th2 subtypes, as well as a third Th clone that is not classified into either subtype. It is proposed that anti-CD3 activation of Th results in the expression of Th membrane proteins that trigger B cell cycle entry. Kinetic studies reveal that 4 to 8 h of activation with anti-CD3 is sufficient for ThCD3 to express B cell-activating function. However, activation of Th with anti-CD3 for extended periods of time results in reduced Th effector activity. Inhibition of Th RNA synthesis during the anti-CD3 activation period ablates the ability of ThCD3 to induce B cell cycle entry. This indicates that de novo synthesis of proteins is required for ThCD3 to express effector function. The ability of fixed ThCD3 to induce entry of B cell into cycle is not due to an increase in expression of CD3, CD4, LFA-1, ICAM-1, class I MHC or Thy-1. Other forms of Th activation (PMA and A23187, Con A) also induced Th effector function. Furthermore, purified plasma membranes from anti-CD3 activated, but not resting Th, induced resting B cells to enter cycle. The addition of IL-4, but not IL-2, IL-5, or IFN-gamma amplified the DNA synthetic response of B cells stimulated with PM from activated Th. Taken together these data indicate that de novo expression of Th surface proteins on activated Th is required for Th to induce B cell cycle entry into G1 and the addition of IL-4 is required for the heightened progression into S phase.

Gas powered fluid gun with recoil mitigation

DOEpatents

Grubelich, Mark C; Yonas, Gerold

2013-11-12

A gas powered fluid gun for propelling a stream or slug of a fluid at high velocity toward a target. Recoil mitigation is provided that reduces or eliminates the associated recoil forces, with minimal or no backwash. By launching a quantity of water in the opposite direction, net momentum forces are reduced or eliminated. Examples of recoil mitigation devices include a cone for making a conical fluid sheet, a device forming multiple impinging streams of fluid, a cavitating venturi, one or more spinning vanes, or an annular tangential entry/exit.

Gas powered fluid gun with recoil mitigation

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

Grubelich, Mark C.; Yonas, Gerold

A gas powered fluid gun for propelling a stream or slug of a fluid at high velocity toward a target. Recoil mitigation is provided that reduces or eliminates the associated recoil forces, with minimal or no backwash. By launching a quantity of water in the opposite direction, net momentum forces are reduced or eliminated. Examples of recoil mitigation devices include a cone for making a conical fluid sheet, a device forming multiple impinging streams of fluid, a cavitating venturi, one or more spinning vanes, or an annular tangential entry/exit.

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Federal Register 2010, 2011, 2012, 2013, 2014

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Federal Register 2010, 2011, 2012, 2013, 2014

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On the Wigner law in dilute random matrices

NASA Astrophysics Data System (ADS)

Khorunzhy, A.; Rodgers, G. J.

1998-12-01

We consider ensembles of N × N symmetric matrices whose entries are weakly dependent random variables. We show that random dilution can change the limiting eigenvalue distribution of such matrices. We prove that under general and natural conditions the normalised eigenvalue counting function coincides with the semicircle (Wigner) distribution in the limit N → ∞. This can be explained by the observation that dilution (or more generally, random modulation) eliminates the weak dependence (or correlations) between random matrix entries. It also supports our earlier conjecture that the Wigner distribution is stable to random dilution and modulation.

Correlation of patient entry rates and physician documentation errors in dictated and handwritten emergency treatment records.

PubMed

Dawdy, M R; Munter, D W; Gilmore, R A

1997-03-01

This study was designed to examine the relationship between patient entry rates (a measure of physician work load) and documentation errors/omissions in both handwritten and dictated emergency treatment records. The study was carried out in two phases. Phase I examined handwritten records and Phase II examined dictated and transcribed records. A total of 838 charts for three common chief complaints (chest pain, abdominal pain, asthma/chronic obstructive pulmonary disease) were retrospectively reviewed and scored for the presence or absence of 11 predetermined criteria. Patient entry rates were determined by reviewing the emergency department patient registration logs. The data were analyzed using simple correlation and linear regression analysis. A positive correlation was found between patient entry rates and documentation errors in handwritten charts. No such correlation was found in the dictated charts. We conclude that work load may negatively affect documentation accuracy when charts are handwritten. However, the use of dictation services may minimize or eliminate this effect.

Aerocapture Inflatable Decelerator (AID)

NASA Technical Reports Server (NTRS)

Reza, Sajjad

2007-01-01

Forward Attached Inflatable Decelerators, more commonly known as inflatable aeroshells, provide an effective, cost efficient means of decelerating spacecrafts by using atmospheric drag for aerocapture or planetary entry instead of conventional liquid propulsion deceleration systems. Entry into planetary atmospheres results in significant heating and aerodynamic pressures which stress aeroshell systems to their useful limits. Incorporation of lightweight inflatable decelerator surfaces with increased surface-area footprints provides the opportunity to reduce heat flux and induced temperatures, while increasing the payload mass fraction. Furthermore, inflatable aeroshell decelerators provide the needed deceleration at considerably higher altitudes and Mach numbers when compared with conventional rigid aeroshell entry systems. Inflatable aeroshells also provide for stowage in a compact space, with subsequent deployment of a large-area, lightweight heatshield to survive entry heating. Use of a deployable heatshield decelerator not only enables an increase in the spacecraft payload mass fraction and but may also eliminate the need for a spacecraft backshell and cruise stage. This document is the viewgraph slides for the paper's presentation.

Effect of air-entry angle on performance of a 2-stroke-cycle compression-ignition engine

NASA Technical Reports Server (NTRS)

Earle, Sherod L; Dutee, Francis J

1937-01-01

An investigation was made to determine the effect of variations in the horizontal and vertical air-entry angles on the performance characteristics of a single-cylinder 2-stroke-cycle compression-ignition test engine. Performance data were obtained over a wide range of engine speed, scavenging pressure, fuel quantity, and injection advance angle with the optimum guide vanes. Friction and blower-power curves are included for calculating the indicated and net performances. The optimum horizontal air-entry angle was found to be 60 degrees from the radial and the optimum vertical angle to be zero, under which conditions a maximum power output of 77 gross brake horsepower for a specific fuel consumption of 0.52 pound per brake horsepower-hour was obtained at 1,800 r.p.m. and 16-1/2 inches of Hg scavenging pressure. The corresponding specific output was 0.65 gross brake horsepower per cubic inch of piston displacement. Tests revealed that the optimum scavenging pressure increased linearly with engine speed. The brake mean effective pressure increased uniformly with air quantity per cycle for any given vane angle and was independent of engine speed and scavenging pressure.

Children's School Readiness: Implications for Eliminating Future Disparities in Health and Education

ERIC Educational Resources Information Center

Pagani, Linda S.; Fitzpatrick, Caroline

2014-01-01

Background: School-entry characteristics predict adult educational attainment, which forecasts dispositions toward disease prevention. Health and education risks can also be transmitted from one generation to the next. As such, school readiness forecasts a set of intertwined biopsychosocial trajectories that can influence the developmental…

An analysis of the adaptability of Loran-C to air navigation

NASA Technical Reports Server (NTRS)

Littlefield, J. A.

1981-01-01

The sources of position errors characteristics of the Loran-C navigation system were identified. Particular emphasis was given to their point on entry as well as their elimination. It is shown that the ratio of realized accuracy to theoretical accuracy of the Loran-C is highly receiver dependent.

Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry

PubMed Central

Fasulo, Barbara; Koyama, Carol; Yu, Kristina R.; Homola, Ellen M.; Hsieh, Tao S.; Campbell, Shelagh D.; Sullivan, William

2012-01-01

Defects in DNA replication and chromosome condensation are common phenotypes in cancer cells. A link between replication and condensation has been established, but little is known about the role of checkpoints in monitoring chromosome condensation. We investigate this function by live analysis, using the rapid division cycles in the early Drosophila embryo. We find that S-phase and topoisomerase inhibitors delay both the initiation and the rate of chromosome condensation. These cell cycle delays are mediated by the cell cycle kinases chk1 and wee1. Inhibitors that cause severe defects in chromosome condensation and congression on the metaphase plate result in delayed anaphase entry. These delays are mediated by wee1 and are not the result of spindle assembly checkpoint activation. In addition, we provide the first detailed live analysis of the direct effect of widely used anticancer agents (aclarubicin, ICRF-193, VM26, doxorubicin, camptothecin, aphidicolin, hydroxyurea, cisplatin, mechlorethamine and x-rays) on key nuclear and cytoplasmic cell cycle events. PMID:22262459

HIV/AIDS testing at ports of entry in China.

PubMed

Lai, Dejian; Hwang, Lu-Yu; Beasley, R Palmer

2011-05-01

In 2007 the Chinese government issued regulations requiring HIV/AIDS testing for Chinese citizens returning at ports of entry if they had resided outside China for 1 year or longer. Three years after publication and partial implementation of the regulations, the Chinese government decided to eliminate compulsory HIV/AIDS testing of returning Chinese. We examine the history of China's HIV/AIDS testing regulations on entry-exit populations, showing how China has gradually altered its policy. As of December 2010, the policy of compulsory HIV/AIDS testing of returning Chinese has been abandoned; however, the regulations still compel HIV/AIDS testing for other groups inside China. Our review sheds new light on the dynamics of regulatory changes in the last 3 years. The Chinese experience that we observed may provide useful insights for policymakers in other parts of the world.

DEVELOPING AN IPAD® APPLICATION FOR DATA COLLECTION IN A RHEUMATOLOGY RESEARCH CLINIC.

PubMed

Kaka, Hussam; Ayearst, Renise; Tran, Maithy; Touma, Zahi; Bagovich, Maria; Vinik, Ophir; Somaily, Mansour; Haddad, Amir; Gladman, Dafna D; Chandran, Vinod

2015-01-01

Clinical research data are often collected on paper and later inputted onto an electronic database. This method is time consuming and potentially introduces errors. Therefore, to make primary data collection more efficient and less error prone we aimed to develop a touch-screen application for data collection in a psoriatic arthritis research clinic and compared it with the pre-existing paper-based system. We developed a Web application using Java and optimized it for the iPad®. It highlights missing fields for physicians in real time, and only permits submission of data collection form after corrections are made. For its evaluation, seven physicians participated, and before each patient visit they were randomly assigned paper or iPad® data entry. Number of errors, length of visit, and time between clinic visit and completion of data entry were measured. A total of 106 patients seen in the clinic who agreed to participate were randomly assigned to be evaluated by clinic physicians using the iPad® (fifty-three patients) or a paper protocol (fifty-three patients). On average, 3.34 omissions were found per paper form, of which 2.24 would have been detected on the iPad®. The iPad® increased the mean patient encounter time from 37.2 minutes to 46.5 minutes, but eliminated delay between a clinic visit and its data entry. Entering data using the iPad® application makes the patient encounter slightly longer, but reduces "missing fields." It also eliminates the delay between clinic visit and data entry thus improving the efficiency of clinical data capture in a research setting.

Enhancing signal detection and completely eliminating scattering using quasi-phase-cycling in 2D IR experiments.

PubMed

Bloem, Robbert; Garrett-Roe, Sean; Strzalka, Halina; Hamm, Peter; Donaldson, Paul

2010-12-20

We demonstrate how quasi-phase-cycling achieved by sub-cycle delay modulation can be used to replace optical chopping in a box-CARS 2D IR experiment in order to enhance the signal size, and, at the same time, completely eliminate any scattering contamination. Two optical devices are described that can be used for this purpose, a wobbling Brewster window and a photoelastic modulator. They are simple to construct, easy to incorporate into any existing 2D IR setup, and have attractive features such as a high optical throughput and a fast modulation frequency needed to phase cycle on a shot-to-shot basis.

Through the Lens of TEK - Building GeoScience Pathways for American Indian/Alaska Native Students

NASA Astrophysics Data System (ADS)

Thomas, W. J.; van Cooten, S.; Wrege, B.; Wildcat, D.

2017-12-01

Native American or American Indian/Alaska Native (AI/AN) students come from diverse communities with indigenous knowledges, perspectives and worldviews. These communities and the students they send into our nation's education systems have cultural connectivity to oral histories, documents, and artwork that details climate cycles and weather events prior to colonization through eras of forced relocation and assimilation. Today, these students are the trailblazers as tribal governments exercise their ownership rights to natural resources and the welfare of their citizens as sovereign nations. In universities, especially tribal colleges, our nation's indigenous students are bridge builders. Through the lens of Traditional Ecological Knowledge (TEK), these students have a unique yet overlooked perspective to merge mainstream research with indigenous knowledge systems to develop practical sustainable solutions for local, regional and international resource management issues. The panel will discuss barriers, such as underdeveloped geophysical science curricula at tribal colleges, that limit the pool of indigenous geoscience graduates and examine possible strategies such as entry point opportunities and partnerships, mentoring, and community relevant research experiences, to eliminate barriers that limit the influx of TEK in resiliency planning.

The Shortage of Skilled and Technical Workers; An Inquiry Into Selected Occupations in Short Supply.

ERIC Educational Resources Information Center

Franke, Walter; Sobel, Irvin

The institutional arrangements through which workers are prepared and employed in selected occupations are examined to determine whether barriers to entry and employment are susceptible to elimination or reduction, and how labor shortages effect employers. It covers six occupations in the St. Louis and Chicago metropolitan areas: licensed…

7 CFR 319.74-2 - Conditions governing the entry of cut flowers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... eliminated. (e) Irradiation. Cut flowers and foliage that are required under this part to be treated or subjected to inspection to control one or more of the plant pests for which irradiation is an approved treatment under part 305 of this chapter may instead be treated with irradiation. Irradiation treatment must...

7 CFR 319.74-2 - Conditions governing the entry of cut flowers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... eliminated. (e) Irradiation. Cut flowers and foliage that are required under this part to be treated or subjected to inspection to control one or more of the plant pests for which irradiation is an approved treatment under part 305 of this chapter may instead be treated with irradiation. Irradiation treatment must...

7 CFR 319.74-2 - Conditions governing the entry of cut flowers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... eliminated. (e) Irradiation. Cut flowers and foliage that are required under this part to be treated or subjected to inspection to control one or more of the plant pests for which irradiation is an approved treatment under part 305 of this chapter may instead be treated with irradiation. Irradiation treatment must...

7 CFR 319.74-2 - Conditions governing the entry of cut flowers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... eliminated. (e) Irradiation. Cut flowers and foliage that are required under this part to be treated or subjected to inspection to control one or more of the plant pests for which irradiation is an approved treatment under part 305 of this chapter may instead be treated with irradiation. Irradiation treatment must...

Apparatus and process to eliminate diffusional limitations in a membrane biological reactor by pressure cycling

DOEpatents

Efthymiou, George S.; Shuler, Michael L.

1989-08-29

An improved multilayer continuous biological membrane reactor and a process to eliminate diffusional limitations in membrane reactors in achieved by causing a convective flux of nutrient to move into and out of an immobilized biocatalyst cell layer. In a pressure cycled mode, by increasing and decreasing the pressure in the respective layers, the differential pressure between the gaseous layer and the nutrient layer is alternately changed from positive to negative. The intermittent change in pressure differential accelerates the transfer of nutrient from the nutrient layers to the biocatalyst cell layer, the transfer of product from the cell layer to the nutrient layer and the transfer of byproduct gas from the cell layer to the gaseous layer. Such intermittent cycling substantially eliminates mass transfer gradients in diffusion inhibited systems and greatly increases product yield and throughput in both inhibited and noninhibited systems.

Behavior of HfB2-SiC Materials in Simulated Re-Entry Environments

NASA Technical Reports Server (NTRS)

Ellerby, Don; Beckman, Sarah; Irby, Edward; Johnson, Sylvia M.; Gunsman, Michael; Gasch, Matthew; Ridge, Jerry; Martinez, Ed; Squire, Tom; Olejniczak, Joe

2003-01-01

The objectives of this research are to: 1) Investigate the oxidation/ablation behavior of HfB2/SiC materials in simulated re-entry environments; 2) Use the arc jet test results to define appropriate use environments for these materials for use in vehicle design. The parameters to be investigated include: surface temperature, stagnation pressure, duration, number of cycles, and thermal stresses.

The R2R3 MYB Transcription Factors FOUR LIPS and MYB88 Regulate Female Reproductive Development

PubMed Central

Lamb, Rebecca S.

2012-01-01

Gamete formation is an important step in the life cycle of sexually reproducing organisms. In flowering plants, haploid spores are formed after the meiotic division of spore mother cells. These spores develop into male and female gametophytes containing gametes after undergoing mitotic divisions. In the female, the megaspore mother cell undergoes meiosis forming four megaspores, of which one is functional and three degenerate. The megaspore then undergoes three mitotic cycles thus generating an embryo sac with eight nuclei. The embryo sac undergoes cellularization to form the mature seven-celled female gametophyte. Entry into and progression through meiosis is essential for megasporogenesis and subsequent megagametogenesis, but control of this process is not well understood. FOUR LIPS (FLP) and its paralogue MYB88, encoding R2R3 MYB transcription factors, have been extensively studied for their role in limiting the terminal division in stomatal development by direct regulation of the expression of cell cycle genes. Here it is demonstrated that FLP and MYB88 also regulate female reproduction. Both FLP and MYB88 are expressed during ovule development and their loss significantly increases the number of ovules produced by the placenta. Despite the presence of excess ovules, single and double mutants exhibit reduced seed set due to reduced female fertility. The sterility results at least in part from defective meiotic entry and progression. Therefore, FLP and MYB88 are important regulators of entry into megasporogenesis, and probably act via the regulation of cell cycle genes. PMID:22915737

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

Parvovirus-Induced Depletion of Cyclin B1 Prevents Mitotic Entry of Infected Cells

PubMed Central

Adeyemi, Richard O.; Pintel, David J.

2014-01-01

Parvoviruses halt cell cycle progression following initiation of their replication during S-phase and continue to replicate their genomes for extended periods of time in arrested cells. The parvovirus minute virus of mice (MVM) induces a DNA damage response that is required for viral replication and induction of the S/G2 cell cycle block. However, p21 and Chk1, major effectors typically associated with S-phase and G2-phase cell cycle arrest in response to diverse DNA damage stimuli, are either down-regulated, or inactivated, respectively, during MVM infection. This suggested that parvoviruses can modulate cell cycle progression by another mechanism. In this work we show that the MVM-induced, p21- and Chk1-independent, cell cycle block proceeds via a two-step process unlike that seen in response to other DNA-damaging agents or virus infections. MVM infection induced Chk2 activation early in infection which led to a transient S-phase block associated with proteasome-mediated CDC25A degradation. This step was necessary for efficient viral replication; however, Chk2 activation and CDC25A loss were not sufficient to keep infected cells in the sustained G2-arrested state which characterizes this infection. Rather, although the phosphorylation of CDK1 that normally inhibits entry into mitosis was lost, the MVM induced DDR resulted first in a targeted mis-localization and then significant depletion of cyclin B1, thus directly inhibiting cyclin B1-CDK1 complex function and preventing mitotic entry. MVM infection thus uses a novel strategy to ensure a pseudo S-phase, pre-mitotic, nuclear environment for sustained viral replication. PMID:24415942

Parvovirus-induced depletion of cyclin B1 prevents mitotic entry of infected cells.

PubMed

Adeyemi, Richard O; Pintel, David J

2014-01-01

Parvoviruses halt cell cycle progression following initiation of their replication during S-phase and continue to replicate their genomes for extended periods of time in arrested cells. The parvovirus minute virus of mice (MVM) induces a DNA damage response that is required for viral replication and induction of the S/G2 cell cycle block. However, p21 and Chk1, major effectors typically associated with S-phase and G2-phase cell cycle arrest in response to diverse DNA damage stimuli, are either down-regulated, or inactivated, respectively, during MVM infection. This suggested that parvoviruses can modulate cell cycle progression by another mechanism. In this work we show that the MVM-induced, p21- and Chk1-independent, cell cycle block proceeds via a two-step process unlike that seen in response to other DNA-damaging agents or virus infections. MVM infection induced Chk2 activation early in infection which led to a transient S-phase block associated with proteasome-mediated CDC25A degradation. This step was necessary for efficient viral replication; however, Chk2 activation and CDC25A loss were not sufficient to keep infected cells in the sustained G2-arrested state which characterizes this infection. Rather, although the phosphorylation of CDK1 that normally inhibits entry into mitosis was lost, the MVM induced DDR resulted first in a targeted mis-localization and then significant depletion of cyclin B1, thus directly inhibiting cyclin B1-CDK1 complex function and preventing mitotic entry. MVM infection thus uses a novel strategy to ensure a pseudo S-phase, pre-mitotic, nuclear environment for sustained viral replication.

Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis

PubMed Central

Andrade, Ana Cláudia dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien

2017-01-01

ABSTRACT Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii, causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a new examination of the replication cycle of mimivirus and provide new evidence concerning some stages of the cycle which were previously unclear, mainly entry, uncoating, and morphogenesis. Furthermore, we demonstrate that atypical virion morphologies can occur even in the absence of virophages. Our results, along with previous data, allow us to present an ultimate model for the mimivirus replication cycle. PMID:28878069

Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis.

PubMed

Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

2017-11-15

Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii , causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a new examination of the replication cycle of mimivirus and provide new evidence concerning some stages of the cycle which were previously unclear, mainly entry, uncoating, and morphogenesis. Furthermore, we demonstrate that atypical virion morphologies can occur even in the absence of virophages. Our results, along with previous data, allow us to present an ultimate model for the mimivirus replication cycle. Copyright © 2017 American Society for Microbiology.

Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs.

PubMed

Risal, Sanjiv; Adhikari, Deepak; Liu, Kui

2016-01-01

Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

Distinct mechanisms act in concert to mediate cell cycle arrest.

PubMed

Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

2009-01-20

In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

Teacher Career Stages: Implications for Staff Development. Fastback 214.

ERIC Educational Resources Information Center

Burke, Peter J.; And Others

Literature on adult life stages and career development is synthesized and placed within the perspective of a career cycle model for teachers as adult learners. The teacher career cycle is viewed as a progression affected by personal and environmental factors. The stages a teacher's career proceeds through (e.g., preservice, entry, growing, stable,…

HIV-1 requires Arf6-mediated membrane dynamics to efficiently enter and infect T lymphocytes

PubMed Central

García-Expósito, Laura; Barroso-González, Jonathan; Puigdomènech, Isabel; Machado, José-David; Blanco, Julià; Valenzuela-Fernández, Agustín

2011-01-01

As the initial barrier to viral entry, the plasma membrane along with the membrane trafficking machinery and cytoskeleton are of fundamental importance in the viral cycle. However, little is known about the contribution of plasma membrane dynamics during early human immunodeficiency virus type 1 (HIV-1) infection. Considering that ADP ribosylation factor 6 (Arf6) regulates cellular invasion via several microorganisms by coordinating membrane trafficking, our aim was to study the function of Arf6-mediated membrane dynamics on HIV-1 entry and infection of T lymphocytes. We observed that an alteration of the Arf6–guanosine 5′-diphosphate/guanosine 5′-triphosphate (GTP/GDP) cycle, by GDP-bound or GTP-bound inactive mutants or by specific Arf6 silencing, inhibited HIV-1 envelope–induced membrane fusion, entry, and infection of T lymphocytes and permissive cells, regardless of viral tropism. Furthermore, cell-to-cell HIV-1 transmission of primary human CD4+ T lymphocytes was inhibited by Arf6 knockdown. Total internal reflection fluorescence microscopy showed that Arf6 mutants provoked the accumulation of phosphatidylinositol-(4,5)-biphosphate–associated structures on the plasma membrane of permissive cells, without affecting CD4-viral attachment but impeding CD4-dependent HIV-1 entry. Arf6 silencing or its mutants did not affect fusion, entry, and infection of vesicular stomatitis virus G–pseudotyped viruses or ligand-induced CXCR4 or CCR5 endocytosis, both clathrin-dependent processes. Therefore we propose that efficient early HIV-1 infection of CD4+ T lymphocytes requires Arf6-coordinated plasma membrane dynamics that promote viral fusion and entry. PMID:21346189

Policy Changes in Brunei Teacher Education: Implications for the Selection of Trainee Teachers

ERIC Educational Resources Information Center

Mundia, Lawrence

2012-01-01

To improve quality, teacher education programs in Brunei were recently eliminated at the undergraduate level and changed to master of teaching degree courses. Prospective teachers are required to obtain content-rich initial degrees prior to applying for teacher training. This study argues that the high entry qualification to teaching may, in…

A Computer Support System for the Entry and Analysis of Questionnaire Data.

ERIC Educational Resources Information Center

Shale, Douglas G.; Milinusic, Tomislav O.

This paper describes a computer support system that eliminated many of the problems associated with the usual methods of transcribing and analyzing questionnaire data. The system was created to support the course evaluation system at Athabasca University, a distance education university in Canada. The courses evaluated were all home study courses,…

Development and Validation of Students' Stress Rating Scale (SSRS)

ERIC Educational Resources Information Center

Balamurugan, M.; Kumaran, D.

2008-01-01

Each and every person is under the grip of stress. Starting from a two-year infant to an adult, stress takes an entry in different forms but it alters the normal functioning of a person. One cannot eliminate stress but can reduce stress in their life. The stressors are normative demands and critical life events. Normative stressors include…

Elimination of Dual Slope from the Coffin Manson Relationship of Low-Cycle Fatigue in the Titanium Alloy Timetal 834, by Cold Rolling

NASA Astrophysics Data System (ADS)

Sai Srinadh, K. V.; Singh, Vakil

2007-08-01

Cold rolling of the titanium alloy Timetal 834 was found to cause marked enhancement in low-cycle fatigue (LCF) life at low strain amplitude and to eliminate bilinear behavior from the Coffin Manson (C-M) relationship. It was due to work hardening of surface grains of soft orientation and consequent increase in resistance of the material against crack initiation. The observed effect was not associated with texture.

Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

PubMed

Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

2015-01-01

Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent endocytosis, likely with the help of a cellular surface protein. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Study on Re-entry Predictions of Uncontrolled Space Objects for Space Situational Awareness

NASA Astrophysics Data System (ADS)

Choi, Eun-Jung; Cho, Sungki; Lee, Deok-Jin; Kim, Siwoo; Jo, Jung Hyun

2017-12-01

The key risk analysis technologies for the re-entry of space objects into Earth’s atmosphere are divided into four categories: cataloguing and databases of the re-entry of space objects, lifetime and re-entry trajectory predictions, break-up models after re-entry and multiple debris distribution predictions, and ground impact probability models. In this study, we focused on re- entry prediction, including orbital lifetime assessments, for space situational awareness systems. Re-entry predictions are very difficult and are affected by various sources of uncertainty. In particular, during uncontrolled re-entry, large spacecraft may break into several pieces of debris, and the surviving fragments can be a significant hazard for persons and properties on the ground. In recent years, specific methods and procedures have been developed to provide clear information for predicting and analyzing the re-entry of space objects and for ground-risk assessments. Representative tools include object reentry survival analysis tool (ORSAT) and debris assessment software (DAS) developed by National Aeronautics and Space Administration (NASA), spacecraft atmospheric re-entry and aerothermal break-up (SCARAB) and debris risk assessment and mitigation analysis (DRAMA) developed by European Space Agency (ESA), and semi-analytic tool for end of life analysis (STELA) developed by Centre National d’Etudes Spatiales (CNES). In this study, various surveys of existing re-entry space objects are reviewed, and an efficient re-entry prediction technique is suggested based on STELA, the life-cycle analysis tool for satellites, and DRAMA, a re-entry analysis tool. To verify the proposed method, the re-entry of the Tiangong-1 Space Lab, which is expected to re-enter Earth’s atmosphere shortly, was simulated. Eventually, these results will provide a basis for space situational awareness risk analyses of the re-entry of space objects.

Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals.

PubMed

Sagari, Akira; Iso, Naoki; Moriuchi, Takefumi; Ogahara, Kakuya; Kitajima, Eiji; Tanaka, Koji; Tabira, Takayuki; Higashi, Toshio

2015-01-01

Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed. We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS) in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touch-screen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touch-screen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman's rank correlations. Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC) showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC) and supplementary motor area (SMA) showed negative correlations. We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress.

Development of a Direct Evaporator for the Organic Rankine Cycle

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

Donna Post Guillen; Helge Klockow; Matthew Lehar

2011-02-01

This paper describes research and development currently underway to place the evaporator of an Organic Rankine Cycle (ORC) system directly in the path of a hot exhaust stream produced by a gas turbine engine. The main goal of this research effort is to improve cycle efficiency and cost by eliminating the usual secondary heat transfer loop. The project’s technical objective is to eliminate the pumps, heat exchangers and all other added cost and complexity of the secondary loop by developing an evaporator that resides in the waste heat stream, yet virtually eliminates the risk of a working fluid leakage intomore » the gaseous exhaust stream. The research team comprised of Idaho National Laboratory and General Electric Company engineers leverages previous research in advanced ORC technology to develop a new direct evaporator design that will reduce the ORC system cost by up to 15%, enabling the rapid adoption of ORCs for waste heat recovery.« less

Mineral cycling in southeastern ecosystems. Proceedings of a symposium held at Augusta, Georgia May 1--3, 1974

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

Howell, F.G.; Gentry, J.B.; Smith, M.H.

1975-01-01

Sixty-six papers were presented on cycling of natural and man-made elements, including terrestrial, freshwater and marine environments, as well as current ideas on modeling. Principles governing elemental flow included radiocesium in natural environments, especially in the southeastern United States. Individual entries were made for 47 items.

Tungsten insulated susceptor cup for high temperature induction furnace eliminates contamination

NASA Technical Reports Server (NTRS)

Geringer, H. J.

1966-01-01

METILUR /Materials Experimental Tungsten Induction Laboratory Unit Replacement/ is an improved, unitized design of a susceptor cup and shielding that uses only one type of construction material /tungsten/ which eliminates contamination. Cycling runs can be accomplished with METILUR.

Characterization of resistance to rhabdovirus and retrovirus infection in a human myeloid cell line.

PubMed

Boso, Guney; Somia, Nikunj V

2015-01-01

Viruses interact with various permissive and restrictive factors in host cells throughout their replication cycle. Cell lines that are non-permissive to viral infection have been particularly useful in discovering host cell proteins involved in viral life cycles. Here we describe the characterization of a human myeloid leukemia cell line, KG-1, that is resistant to infection by retroviruses and a Rhabdovirus. We show that KG-1 cells are resistant to infection by Vesicular Stomatits Virus as well as VSV Glycoprotein (VSVG) pseudotyped retroviruses due to a defect in binding. Moreover our results indicate that entry by xenotropic retroviral envelope glycoprotein RD114 is impaired in KG-1 cells. Finally we characterize a post- entry block in the early phase of the retroviral life cycle in KG-1 cells that renders the cell line refractory to infection. This cell line will have utility in discovering proteins involved in infection by VSV and HIV-1.

Automated Welding System

NASA Technical Reports Server (NTRS)

Bayless, E. O.; Lawless, K. G.; Kurgan, C.; Nunes, A. C.; Graham, B. F.; Hoffman, D.; Jones, C. S.; Shepard, R.

1993-01-01

Fully automated variable-polarity plasma arc VPPA welding system developed at Marshall Space Flight Center. System eliminates defects caused by human error. Integrates many sensors with mathematical model of the weld and computer-controlled welding equipment. Sensors provide real-time information on geometry of weld bead, location of weld joint, and wire-feed entry. Mathematical model relates geometry of weld to critical parameters of welding process.

An update on mechanism of entry of white spot syndrome virus into shrimps.

PubMed

Verma, Arunima Kumar; Gupta, Shipra; Singh, Shivesh Pratap; Nagpure, Naresh Sahebrao

2017-08-01

Host-parasite relationships can be best understood at the level of protein-protein interaction between host and pathogen. Such interactions are instrumental in understanding the important stages of life cycle of pathogen such as adsorption of the pathogen on host surface followed by effective entry of pathogen into the host body, movement of the pathogen across the host cytoplasm to reach the host nucleus and replication of the pathogen within the host. White Spot Disease (WSD) is a havoc for shrimps and till date no effective treatment is available against the disease. Moreover information regarding the mechanism of entry of White Spot Syndrome Virus (WSSV) into shrimps, as well as knowledge about the protein interactions occurring between WSSV and shrimp during viral entry are still at very meagre stage. A cumulative and critically assessed information on various viral-shrimp interactions occurring during viral entry can help to understand the exact pathway of entry of WSSV into the shrimp which in turn can be used to device drugs that can stop the entry of virus into the host. In this context, we highlight various WSSV and shrimp proteins that play role in the entry mechanism along with the description of the interaction between host and pathogen proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bovine parvovirus uses clathrin-mediated endocytosis for cell entry.

PubMed

Dudleenamjil, Enkhmart; Lin, Chin-Yo; Dredge, Devin; Murray, Byron K; Robison, Richard A; Johnson, F Brent

2010-12-01

Entry events of bovine parvovirus (BPV) were studied. Transmission electron micrographs of infected cells showed virus particles in cytoplasmic vesicles. Chemical inhibitors that block certain aspects of the cellular machinery were employed to assess viral dependency upon those cellular processes. Chlorpromazine, ammonium chloride, chloroquine and bafilamicin A1 were used to inhibit acidification of endosomes and clathrin-associated endocytosis. Nystatin was used as an inhibitor of the caveolae pathway. Cytochalasin D and ML-7 were used to inhibit actin and myosin functions, respectively. Nocodazole and colchicine were employed to inhibit microtubule activity. Virus entry was assessed by measuring viral transcription using real-time PCR, synthesis of capsid protein and assembly of infectious progeny virus in the presence of inhibitor blockage. The results indicated that BPV entry into embryonic bovine trachael cells utilizes endocytosis in clathrin-coated vesicles, is dependent upon acidification, and appears to be associated with actin and microtubule dependency. Evidence for viral entry through caveolae was not obtained. These findings provide a fuller understanding of the early cell-entry events of the replication cycle for members of the genus Bocavirus.

Phosphatidylinositol 4-Kinase IIIβ Is Required for Severe Acute Respiratory Syndrome Coronavirus Spike-mediated Cell Entry*

PubMed Central

Yang, Ning; Ma, Ping; Lang, Jianshe; Zhang, Yanli; Deng, Jiejie; Ju, Xiangwu; Zhang, Gongyi; Jiang, Chengyu

2012-01-01

Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection. PMID:22253445

Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection

PubMed Central

Chan, Kamfai; Coen, Mauricio; Hardick, Justin; Gaydos, Charlotte A.; Wong, Kah-Yat; Smith, Clayton; Wilson, Scott A.; Vayugundla, Siva Praneeth; Wong, Season

2016-01-01

Most molecular diagnostic assays require upfront sample preparation steps to isolate the target’s nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer’s heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers. PMID:27362424

Progress toward measles elimination in the People's Republic of China, 2000-2009.

PubMed

Ma, Chao; An, Zhijie; Hao, Lixin; Cairns, K Lisa; Zhang, Yan; Ma, Jing; Cao, Lei; Wen, Ning; Xu, Wenbo; Liang, Xiaofeng; Yang, Weizhong; Luo, Huiming

2011-07-01

In 2006, China set a goal of measles elimination by 2012. To describe progress toward this goal, we reviewed relevant policies and strategies and analyzed national data for 2000-2009. In response to implementation of these strategies, including increased routine measles vaccination coverage and province-specific supplementary immunization activities (SIAs), reported measles incidence decreased to a historically low level of 39.5 cases per million in 2009. A synchronized nationwide SIA was scheduled in 2010 to further decrease susceptibility to measles. However, reaching and maintaining measles elimination will require strong political commitment and efforts for strengthening surveillance, increasing 2-dose vaccine coverage to >95%, stricter enforcement of the requirement to check immunization status at school entry, and careful attention to measles susceptibility in those aged ≥15 years. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells.

PubMed

The, Inge; Ruijtenberg, Suzan; Bouchet, Benjamin P; Cristobal, Alba; Prinsen, Martine B W; van Mourik, Tim; Koreth, John; Xu, Huihong; Heck, Albert J R; Akhmanova, Anna; Cuppen, Edwin; Boxem, Mike; Muñoz, Javier; van den Heuvel, Sander

2015-01-06

Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, starting from an unbiased screen in the nematode Caenorhabditis elegans. We found that simultaneous mutation of lin-35, a retinoblastoma (Rb)-related gene, and fzr-1, an orthologue to the APC/C co-activator Cdh1, completely eliminates the essential requirement of CDK4/6-cyclin D (CDK-4/CYD-1) in C. elegans. CDK-4/CYD-1 phosphorylates specific residues in the LIN-35 Rb spacer domain and FZR-1 amino terminus, resembling inactivating phosphorylations of the human proteins. In human breast cancer cells, simultaneous knockdown of Rb and FZR1 synergistically bypasses cell division arrest induced by the CDK4/6-specific inhibitor PD-0332991. Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and point to an APC/C(FZR1) activity as an important determinant in response to CDK4/6-inhibitors.

Rh(I)–Bisphosphine-Catalyzed Asymmetric, Intermolecular Hydroheteroarylation of α-Substituted Acrylate Derivatives

PubMed Central

2015-01-01

Asymmetric hydroheteroarylation of alkenes represents a convenient entry to elaborated heterocyclic motifs. While chiral acids are known to mediate asymmetric addition of electron-rich heteroarenes to Michael acceptors, very few methods exploit transition metals to catalyze alkylation of heterocycles with olefins via a C–H activation, migratory insertion sequence. Herein, we describe the development of an asymmetric, intermolecular hydroheteroarylation reaction of α-substituted acrylates with benzoxazoles. The reaction provides 2-substitued benzoxazoles in moderate to excellent yields and good to excellent enantioselectivities. Notably, a series of mechanistic studies appears to contradict a pathway involving enantioselective protonation of a Rh(I)–enolate, despite the fact that such a mechanism is invoked almost unanimously in the related addition of aryl boronic acids to methacrylate derivatives. Evidence suggests instead that migratory insertion or beta-hydride elimination is enantiodetermining and that isomerization of a Rh(I)–enolate to a Rh(I)–heterobenzyl species insulates the resultant α-stereocenter from epimerization. A bulky ligand, CTH-(R)-Xylyl-P-Phos, is crucial for reactivity and enantioselectivity, as it likely discourages undesired ligation of benzoxazole substrates or intermediates to on- or off-cycle rhodium complexes and attenuates coordination-promoted product epimerization. PMID:25545834

Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells

PubMed Central

The, Inge; Ruijtenberg, Suzan; Bouchet, Benjamin P.; Cristobal, Alba; Prinsen, Martine B. W.; van Mourik, Tim; Koreth, John; Xu, Huihong; Heck, Albert J. R.; Akhmanova, Anna; Cuppen, Edwin; Boxem, Mike; Muñoz, Javier; van den Heuvel, Sander

2015-01-01

Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, starting from an unbiased screen in the nematode Caenorhabditis elegans. We found that simultaneous mutation of lin-35, a retinoblastoma (Rb)-related gene, and fzr-1, an orthologue to the APC/C co-activator Cdh1, completely eliminates the essential requirement of CDK4/6-cyclin D (CDK-4/CYD-1) in C. elegans. CDK-4/CYD-1 phosphorylates specific residues in the LIN-35 Rb spacer domain and FZR-1 amino terminus, resembling inactivating phosphorylations of the human proteins. In human breast cancer cells, simultaneous knockdown of Rb and FZR1 synergistically bypasses cell division arrest induced by the CDK4/6-specific inhibitor PD-0332991. Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and point to an APC/CFZR1 activity as an important determinant in response to CDK4/6-inhibitors. PMID:25562820

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction.

PubMed

D'Angelo, Barbara; Astarita, Carlo; Boffo, Silvia; Massaro-Giordano, Mina; Antonella Ianuzzi, Carmelina; Caporaso, Antonella; Macaluso, Marcella; Giordano, Antonio

2017-01-01

Cell cycle reactivation in adult neurons is an early hallmark of neurodegeneration. The lipopolysaccharide (LPS) is a well-known pro-inflammatory factor that provokes neuronal cell death via glial cells activation. The retinoblastoma (RB) family includes RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastoma-like 2 (Rb2/p130). Several studies have indicated that RB proteins exhibit tumor suppressor activities, and play a central role in cell cycle regulation. In this study, we assessed LPS-mediated inflammatory effect on cell cycle reactivation and apoptosis of neuronally differentiated cells. Also, we investigated whether the LPS-mediated inflammatory response can influence the function and expression of RB proteins. Our results showed that LPS challenges triggered cell cycle reactivation of differentiated neuronal cells, indicated by an accumulation of cells in S and G2/M phase. Furthermore, we found that LPS treatment also induced apoptotic death of neurons. Interestingly, we observed that LPS-mediated inflammatory effect on cell cycle re-entry and apoptosis was concomitant with the aberrant expression of RBL1/p107 and RB1/p105. To the best of our knowledge, our study is the first to indicate a role of LPS in inducing cell cycle re-entry and/or apoptosis of differentiated neuronal cells, perhaps through mechanisms altering the expression of specific members of RB family proteins. This study provides novel information on the biology of post-mitotic neurons and could help in identifying novel therapeutic targets to prevent de novo cell cycle reactivation and/or apoptosis of neurons undergoing neurodegenerative processes.

Methotrexate Elimination When Coadministered With Levetiracetam.

PubMed

Reeves, David; DiDominick, Sarah; Finn, Suzanne; Kim, Hyeon Jin; Shake, Amanda

2016-12-01

Delayed elimination of methotrexate was previously reported in 2 patients receiving concomitant levetiracetam. To explore the potential interaction between methotrexate and levetiracetam in patients receiving high-dose methotrexate. This retrospective study reviewed the records of 81 adults receiving 280 cycles of methotrexate to determine the effects of levetiracetam on methotrexate elimination. Institutional review board approval was obtained. Levetiracetam was administered in 33 (12%) cycles of methotrexate. Patients receiving levetiracetam had significantly lower 24-hour methotrexate concentrations compared with those not receiving levetiracetam (2.91 vs 7.37 µmol/L, P = 0.005). Despite this difference, concentrations at 48 and 72 hours were similar between groups. Times to nontoxic methotrexate concentration (<0.1 µmol/L) were the same regardless of the presence of levetiracetam. The frequency of delayed elimination at 24, 48, and 72 hours was similar in both groups as was the frequency of delayed elimination at any time point. Cox regression demonstrated that levetiracetam was not a significant predictor of time to nontoxic methotrexate concentration (P = 0.796; HR = 1.058; 95% CI = 0.692-1.617), and logistic regression demonstrated that levetiracetam was not a significant predictor of delayed elimination at any time point. Levetiracetam use was similar between groups when comparing patients experiencing delayed elimination at any time point with those without delayed elimination (13% vs 10%, respectively, P = 0.527). This study does not support the previous reports of a significant interaction between levetiracetam and methotrexate. A clinically significant interaction is unlikely in those without additional risk factors for delayed elimination. © The Author(s) 2016.

Evaluation of heterotrophic plate and chromogenic agar colony counting in water quality laboratories.

PubMed

Hallas, Gary; Monis, Paul

2015-01-01

The enumeration of bacteria using plate-based counts is a core technique used by food and water microbiology testing laboratories. However, manual counting of bacterial colonies is both time and labour intensive, can vary between operators and also requires manual entry of results into laboratory information management systems, which can be a source of data entry error. An alternative is to use automated digital colony counters, but there is a lack of peer-reviewed validation data to allow incorporation into standards. We compared the performance of digital counting technology (ProtoCOL3) against manual counting using criteria defined in internationally recognized standard methods. Digital colony counting provided a robust, standardized system suitable for adoption in a commercial testing environment. The digital technology has several advantages:•Improved measurement of uncertainty by using a standard and consistent counting methodology with less operator error.•Efficiency for labour and time (reduced cost).•Elimination of manual entry of data onto LIMS.•Faster result reporting to customers.

Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens.

PubMed

Uchida, Hiroaki; Hamada, Hirofumi; Nakano, Kenji; Kwon, Heechung; Tahara, Hideaki; Cohen, Justus B; Glorioso, Joseph C

2018-01-01

Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations. Here, we summarize the molecular mechanism of HSV entry and recent advances in the development of fully retargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offer an attractive platform for the creation of a new generation of oncolytic HSV with improved efficacy and specificity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Re-entry and reintegration: returning home after combat.

PubMed

Doyle, Michael E; Peterson, Kris A

2005-01-01

Soldier life exists on a continuum of readiness for deployment. Re-entry and reintegration-the return home and reunion with family and community-key the success of the deployment cycle. In current and projected future operations, the Army and society will both bear the burden of this re-entry and re-integration. Programs and procedures in place work towards improving communication, mitigating distress and resolving crises during reentry and reintegration. Key elements include: inclusion of families and communities early into the planning for reentry and reintegration; normalization (non-medicalization of distress); easy access to behavioral health professionals; and education of families on resources and benefits. Through broad collaboration, maximal benefit to the Soldier, family members and society be realized.

Predictive modeling of altitude decompression sickness in humans

NASA Technical Reports Server (NTRS)

Kenyon, D. J.; Hamilton, R. W., Jr.; Colley, I. A.; Schreiner, H. R.

1972-01-01

The coding of data on 2,565 individual human altitude chamber tests is reported as part of a selection procedure designed to eliminate individuals who are highly susceptible to decompression sickness, individual aircrew members were exposed to the pressure equivalent of 37,000 feet and observed for one hour. Many entries refer to subjects who have been tested two or three times. This data contains a substantial body of statistical information important to the understanding of the mechanisms of altitude decompression sickness and for the computation of improved high altitude operating procedures. Appropriate computer formats and encoding procedures were developed and all 2,565 entries have been converted to these formats and stored on magnetic tape. A gas loading file was produced.

Carbon phenolic heat shields for Jupiter/Saturn/Uranus entry probes

NASA Technical Reports Server (NTRS)

Mezines, S.

1974-01-01

Carbon phenolic heat shield technology is reviewed. Heat shield results from the outer planetary probe mission studies are summarized along with results of plasma jet testing of carbon phenolic conducted in a ten megawatt facility. Missile flight data is applied to planetary entry conditions. A carbon phenolic heat shield material is utilized and tailored to accommodate each of the probe missions. An integral heat shield approach is selected over in order to eliminate a high temperature interface problem and permit direct bonding of the carbon phenolic to the structural honeycomb sandwich. The sandwich is filled with a very fine powder to minimize degradation of its insulation properties by the high conductive hydrogen/helium gases during the long atmospheric descent phase.

A Non-Proliferating Fuel Cycle: No Enrichment, Reprocessing or Accessible Spent Fuel - 12375

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

Parker, Frank L.

2012-07-01

Current fuel cycles offer a number of opportunities for access to plutonium, opportunities to create highly enriched uranium and access highly radioactive wastes to create nuclear weapons and 'dirty' bombs. The non-proliferating fuel cycle however eliminates or reduces such opportunities and access by eliminating the mining, milling and enrichment of uranium. The non-proliferating fuel cycle also reduces the production of plutonium per unit of energy created, eliminates reprocessing and the separation of plutonium from the spent fuel and the creation of a stream of high-level waste. It further simplifies the search for land based deep geologic repositories and interim storagemore » sites for spent fuel in the USA by disposing of the spent fuel in deep sub-seabed sediments after storing the spent fuel at U.S. Navy Nuclear Shipyards that have the space and all of the necessary equipment and security already in place. The non-proliferating fuel cycle also reduces transportation risks by utilizing barges for the collection of spent fuel and transport to the Navy shipyards and specially designed ships to take the spent fuel to designated disposal sites at sea and to dispose of them there in deep sub-seabed sediments. Disposal in the sub-seabed sediments practically eliminates human intrusion. Potential disposal sites include Great Meteor East and Southern Nares Abyssal Plain. Such sites then could easily become international disposal sites since they occur in the open ocean. It also reduces the level of human exposure in case of failure because of the large physical and chemical dilution and the elimination of a major pathway to man-seawater is not potable. Of course, the recovery of uranium from sea water and the disposal of spent fuel in sub-seabed sediments must be proven on an industrial scale. All other technologies are already operating on an industrial scale. If externalities, such as reduced terrorist threats, environmental damage (including embedded emissions), long term care, reduced access to 'dirty' bomb materials, the social and political costs of siting new facilities and the psychological impact of no solution to the nuclear waste problem, were taken into account, the costs would be far lower than those of the present fuel cycle. (authors)« less

Benefits of barrier fuel on fuel cycle economics

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

Crowther, R.L.; Kunz, C.L.

1988-01-01

Barrier fuel rod cladding was developed to eliminate fuel rod failures from pellet/cladding stress/corrosion interaction and to eliminate the associated need to restrict the rate at which fuel rod power can be increased. The performance of barrier cladding has been demonstrated through extensive testing and through production application to many boiling water reactors (BWRs). Power reactor data have shown that barrier fuel rod cladding has a significant beneficial effect on plant capacity factor and plant operating costs and significantly increases fuel reliability. Independent of the fuel reliability benefit, it is less obvious that barrier fuel has a beneficial effect ofmore » fuel cycle costs, since barrier cladding is more costly to fabricate. Evaluations, measurements, and development activities, however, have shown that the fuel cycle cost benefits of barrier fuel are large. This paper is a summary of development activities that have shown that application of barrier fuel significantly reduces BWR fuel cycle costs.« less

Raising the cycling stability of aqueous lithium-ion batteries by eliminating oxygen in the electrolyte.

PubMed

Luo, Jia-Yan; Cui, Wang-Jun; He, Ping; Xia, Yong-Yao

2010-09-01

Aqueous lithium-ion batteries may solve the safety problem associated with lithium-ion batteries that use highly toxic and flammable organic solvents, and the poor cycling life associated with commercialized aqueous rechargeable batteries such as lead-acid and nickel-metal hydride systems. But all reported aqueous lithium-ion battery systems have shown poor stability: the capacity retention is typically less than 50% after 100 cycles. Here, the stability of electrode materials in an aqueous electrolyte was extensively analysed. The negative electrodes of aqueous lithium-ion batteries in a discharged state can react with water and oxygen, resulting in capacity fading upon cycling. By eliminating oxygen, adjusting the pH values of the electrolyte and using carbon-coated electrode materials, LiTi(2)(PO(4))(3)/Li(2)SO(4)/LiFePO(4) aqueous lithium-ion batteries exhibited excellent stability with capacity retention over 90% after 1,000 cycles when being fully charged/discharged in 10 minutes and 85% after 50 cycles even at a very low current rate of 8 hours for a full charge/discharge offering an energy storage system with high safety, low cost, long cycling life and appropriate energy density.

Improved turbine disk design to increase reliability of aircraft jet engines

NASA Technical Reports Server (NTRS)

Alver, A. S.; Wong, J. K.

1975-01-01

An analytical study was conducted on a bore entry cooled turbine disk for the first stage of the JT8D-17 high pressure turbine which had the potential to improve disk life over existing design. The disk analysis included the consideration of transient and steady state temperature, blade loading, creep, low cycle fatigue, fracture mechanics and manufacturing flaws. The improvement in life of the bore entry cooled turbine disk was determined by comparing it with the existing disk made of both conventional and advanced (Astroloy) disk materials. The improvement in crack initiation life of the Astroloy bore entry cooled disk is 87% and 67% over the existing disk made of Waspaloy and Astroloy, respectively. Improvement in crack propagation life is 124% over the Waspaloy and 465% over the Astroloy disks. The available kinetic energies of disk fragments calculated for the three disks indicate a lower fragment energy level for the bore entry cooled turbine disk.

Combined high vacuum/high frequency fatigue tester

NASA Technical Reports Server (NTRS)

Honeycutt, C. R.; Martin, T. F.

1971-01-01

Apparatus permits application of significantly greater number of cycles or equivalent number of cycles in shorter time than conventional fatigue test machines. Environment eliminates problems associated with high temperature oxidation and with sensitivity of refractory alloy behavior to atmospheric contamination.

Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

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

Lu, Na; Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114; Chen, Yan

Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We showmore » that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.« less

The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase.

PubMed

Wicky, Sidonie; Tjandra, Hendri; Schieltz, David; Yates, John; Kellogg, Douglas R

2011-01-01

The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2A(Cdc55)). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2A(Cdc55) and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle-dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis.

Work and Family Patterns of American Women. The Family Life Cycle: 1985; [and] Maternity Leave Arrangements: 1961-85. Current Population Reports.

ERIC Educational Resources Information Center

Current Population Reports, 1990

1990-01-01

The two papers in this report focus on some of the social, demographic, and economic consequences of the increasing entry of women into the workforce. Arthur Norton and Louisa Miller in "The Family Life Cycle: 1985" show trends in the frequency and timing of marriage, divorce, remarriage, and fertility across several generations of…

Propionate supplementation improves nitrogen use by reducing urea flux in sheep.

PubMed

Agarwal, U; Hu, Q; Bequette, B J

2015-10-01

Feeding and postruminal infusion of propionate is known to increase N retention in ruminants. Our aim was to determine the role of rumen propionate on urea N recycling and gluconeogenesis in growing sheep. In Exp. 1, wether sheep ( = 6; 32.5 ± 3.57 kg BW) fitted with a rumen cannula were fed to 1.8 × ME requirement a concentrate-type ration (172 g CP/kg DM and 10.4 MJ ME/kg DM) and continuously infused into the rumen with isoenergetic (10% of dietary ME intake) solutions of either sodium acetate (control) or sodium propionate for 9-d periods in a crossover design. In Exp. 2, a different group of wether sheep ( = 5; 33.6 ± 3.70 kg BW) fitted with a rumen cannula were fed, on an isonitrogenous basis, either a control (151 g CP/kg DM and 8.4 MJ ME/kg DM) or sodium propionate-supplemented (139 g CP/kg DM and 8.9 MJ ME/kg DM) diet at 2-h intervals. [N] urea was continuously infused intravenously for the last 5 d of each period, and total urine was collected by vacuum and feces were collected by a harness bag. Over the last 12 h, [C]glucose was continuously infused intravenously and hourly blood samples were collected during the last 5 h. Propionate treatments increased ( < 0.001) the proportion of rumen propionate in both experiments. In Exp. 1, N retention was not affected by propionate infusion as compared with isoenergetic acetate. There was no effect on urea entry (synthesis) rate (UER) in Exp. 1; however, sodium propionate infusion tended ( < 0.1) to increase urinary urea elimination (UUE). In Exp. 2, feeding propionate increased ( < 0.01) N retention by 0.8 g N/d. In addition, UER was reduced by approximately 2 g urea N/d, leading to a reduction ( < 0.05) in UUE (7.0 vs. 6.2 g urea N/d). Between the 2 experiments, the proportion of UER recycled to the gut was greater with the forage-type diet in Exp. 2 (approximately 60%) compared with the concentrate-type diet in Exp. 1 (approximately 40%), although urea N fluxes across the gut remained unchanged in both experiments. In Exp. 1, glucose entry and gluconeogenesis were greater ( < 0.05) and plasma glucose tended ( < 0.1) to be greater with sodium propionate infusion than with sodium acetate infusion, but there was no difference in Cori cycling. In Exp. 2, glucose entry, gluconeogenesis, Cori cycling, and plasma glucose increased ( < 0.05) with dietary propionate. Our studies indicate that propionate inclusion in feed, but not continuous infusion in to the rumen, improves N utilization in growing sheep. The propionate effect is likely mediated by providing additional precursors for gluconeogenesis.

78 FR 51240 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... Change To Eliminate Rules Related to CYCLE Routing August 14, 2013. Pursuant to Section 19(b)(1) of the... that authorize the CYCLE Routing option, effective as of September 3, 2013. The text of the proposed... authorize the CYCLE Routing option on the Exchange's equities platform (``BATS Equities'') and options...

Inhibitors of SARS-CoV Entry - Identification using an Internally-Controlled Dual Envelope Pseudovirion Assay

PubMed Central

Zhou, Yanchen; Agudelo, Juliet; Lu, Kai; Goetz, David H.; Hansell, Elizabeth; Chen, Yen Ting; Roush, William R.; McKerrow, James; Craik, Charles S.; Amberg, Sean M.; Simmons, Graham

2011-01-01

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, Dual Envelope Pseudovirion (DEP) Assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes. PMID:21820471

Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1

PubMed Central

Pal, Gayatri; Paraz, Maria T.Z.; Kellogg, Douglas R.

2008-01-01

The Cdc25 phosphatase promotes entry into mitosis by removing cyclin-dependent kinase 1 (Cdk1) inhibitory phosphorylation. Previous work suggested that Cdc25 is activated by Cdk1 in a positive feedback loop promoting entry into mitosis; however, it has remained unclear how the feedback loop is initiated. To learn more about the mechanisms that regulate entry into mitosis, we have characterized the function and regulation of Mih1, the budding yeast homologue of Cdc25. We found that Mih1 is hyperphosphorylated early in the cell cycle and is dephosphorylated as cells enter mitosis. Casein kinase 1 is responsible for most of the hyperphosphorylation of Mih1, whereas protein phosphatase 2A associated with Cdc55 dephosphorylates Mih1. Cdk1 appears to directly phosphorylate Mih1 and is required for initiation of Mih1 dephosphorylation as cells enter mitosis. Collectively, these observations suggest that Mih1 regulation is achieved by a balance of opposing kinase and phosphatase activities. Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression. PMID:18316413

Mediator can regulate mitotic entry and direct periodic transcription in fission yeast.

PubMed

Banyai, Gabor; Lopez, Marcela Davila; Szilagyi, Zsolt; Gustafsson, Claes M

2014-11-01

Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner, CycC, does not oscillate. Cdk8 is, however, a component of the multiprotein Mediator complex, a conserved coregulator of eukaryotic transcription that is connected to a number of intracellular signaling pathways. We demonstrate here that other Mediator components regulate the activity of Cdk8 in vivo and thereby direct the timing of mitotic entry. Deletion of Mediator components Med12 and Med13 leads to higher cellular Cdk8 protein levels, premature phosphorylation of the Cdk8 target Fkh2, and earlier entry into mitosis. We also demonstrate that Mediator is recruited to clusters of mitotic genes in a periodic fashion and that the complex is required for the transcription of these genes. We suggest that Mediator functions as a hub for coordinated regulation of mitotic progression and cell cycle-dependent transcription. The many signaling pathways and activator proteins shown to function via Mediator may influence the timing of these cell cycle events. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Propellant Reuse/Recovery Technology

DTIC Science & Technology

1988-08-31

viscosity of the nitrocellulose (NC) determine the solvent/solvent and solvent/propellant ratios required to properly resolvate the propellant. It was also...plasticization. An 11-min drying cycle was required to remove the excess solvent from the over-solvated propellant. To improve plasticization using...solvent, and (4) 15-min mix cycle. To eliminate the drying cycle and determine that a 15-min mix cycle will resolvate the propellart, an additional 1 h

Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

PubMed Central

Witte, Kristen; Strickland, Devin; Glotzer, Michael

2017-01-01

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment. DOI: http://dx.doi.org/10.7554/eLife.26722.001 PMID:28682236

Departure Energies, Trip Times and Entry Speeds for Human Mars Missions

NASA Technical Reports Server (NTRS)

Munk, Michelle M.

1999-01-01

The study examines how the mission design variables departure energy, entry speed, and trip time vary for round-trip conjunction-class Mars missions. These three parameters must be balanced in order to produce a mission that is acceptable in terms of mass, cost, and risk. For the analysis, a simple, massless- planet trajectory program was employed. The premise of this work is that if the trans-Mars and trans-Earth injection stages are designed for the most stringent opportunity in the energy cycle, then there is extra energy capability in the "easier" opportunities which can be used to decrease the planetary entry speed, or shorten the trip time. Both of these effects are desirable for a human exploration program.

Departure Energies, Trip Times and Entry Speeds for Human Mars Missions

NASA Technical Reports Server (NTRS)

Munk, Michelle M.

1999-01-01

The study examines how the mission design variables departure energy, entry speed, and trip time vary for round-trip conjunction-class Mars missions. These three parameters must be balanced in order to produce a mission that is acceptable in terms of mass, cost, and risk. For the analysis, a simple, massless-planet trajectory program was employed. The premise of this work is that if the trans-Mars and trans-Earth injection stages are designed for the most stringent opportunity in the energy cycle, then there is extra energy capability in the "easier" opportunities which can be used to decrease the planetary entry speed, or shorten the trip time. Both of these effects are desirable for a human exploration program.

27 CFR 22.163 - Time for making entries.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Records of Transactions § 22.163..., the daily posting of records may be deferred to conform to the permittee's normal accounting cycle if...

27 CFR 20.266 - Time for making entries in records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF DENATURED ALCOHOL AND RUM Records and... permittee's normal accounting cycle if (a) supporting or supplemental records are prepared at the time of...

PLK1 Activation in Late G2 Sets Up Commitment to Mitosis.

PubMed

Gheghiani, Lilia; Loew, Damarys; Lombard, Bérangère; Mansfeld, Jörg; Gavet, Olivier

2017-06-06

Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry. Plk1-dependent Cdc25C1 phosphosites are sufficient to promote mitotic entry, even when Plk1 activity is inhibited. Furthermore, we find that activation of Plk1 during G2 relies on CyclinA2-Cdk activity levels. Our findings thus elucidate a critical role for Plk1 in CyclinB1-Cdk1 activation and mitotic entry and outline how CyclinA2-Cdk, an S-promoting factor, poises cells for commitment to mitosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ebola virus host cell entry.

PubMed

Sakurai, Yasuteru

2015-01-01

Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

On optimal improvements of classical iterative schemes for Z-matrices

NASA Astrophysics Data System (ADS)

Noutsos, D.; Tzoumas, M.

2006-04-01

Many researchers have considered preconditioners, applied to linear systems, whose matrix coefficient is a Z- or an M-matrix, that make the associated Jacobi and Gauss-Seidel methods converge asymptotically faster than the unpreconditioned ones. Such preconditioners are chosen so that they eliminate the off-diagonal elements of the same column or the elements of the first upper diagonal [Milaszewicz, LAA 93 (1987) 161-170], Gunawardena et al. [LAA 154-156 (1991) 123-143]. In this work we generalize the previous preconditioners to obtain optimal methods. "Good" Jacobi and Gauss-Seidel algorithms are given and preconditioners, that eliminate more than one entry per row, are also proposed and analyzed. Moreover, the behavior of the above preconditioners to the Krylov subspace methods is studied.

Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.

PubMed

Bai, Xiufeng; Lei, Mingxing; Shi, Jiazhong; Yu, Yu; Qiu, Weiming; Lai, Xiangdong; Liu, Yingxin; Yang, Tian; Yang, Li; Widelitz, Randall B; Chuong, Cheng-Ming; Lian, Xiaohua

2015-09-01

Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen), and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves that Gsdma3 directly suppresses Wnt signaling. Our findings suggest that Gsdma3 has an important role in catagen-telogen transition by balancing the Wnt signaling pathway and that morphologically typical telogen is not essential for the initiation of a new hair cycle.

Roles of GasderminA3 in catagen- telogen transition during hair cycling

PubMed Central

Bai, Xiufeng; Lei, Mingxing; Shi, Jiazhong; Yu, Yu; Qiu, Weiming; Lai, Xiangdong; Liu, Yingxin; Yang, Tian; Yang, Li; Widelitz, Randall Bruce; Chuong, Cheng-Ming; Lian, Xiaohua

2015-01-01

Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen) and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves Gsdma3 directly suppresses Wnt signaling. Our findings suggest Gsdma3 plays an important role in catagen-telogen transition by balancing the Wnt signaling pathway, and that morphologically typical telogen is not essential for the initiation of a new hair cycle. PMID:25860385

Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion

PubMed Central

Tong, Xuemei; Coulombe, Pierre A.

2006-01-01

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFα. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFα signaling. The activity of NF-κB, a downstream target of TNFα, is increased in K17-null skin. We also find that TNFα is required for a timely anagen–catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFα as two novel and interdependent regulators of hair cycling. PMID:16702408

Lack of anodic capacitance causes power overshoot in microbial fuel cells.

PubMed

Peng, Xinhong; Yu, Han; Yu, Hongbing; Wang, Xin

2013-06-01

Power overshoot commonly makes the performance evaluation of microbial fuel cells (MFCs) inaccurate. Here, three types of carbon with different capacitance (ultracapacitor activated carbon (UAC), plain activated carbon (PAC) and carbon black (CB)) rolled on stainless steel mesh (SSM) as anodes to investigate the relationship between overshoot and anodic capacitance. It was not observed in all cycles of UAC-MFCs (from Cycle 2 to 4) due to the largest abiotic capacitance (Cm(abiotic)) of 2.1F/cm(2), while this phenomenon was eliminated in PAC-MFCs (Cm(abiotic)=1.6 F/cm(2)) from Cycle 3 and in CB-MFCs (Cm(abiotic)=0.5F/cm(2)) from Cycle 4, indicated that the Cm(abiotic) of the anode stored charges and functioned as electron shuttle to overcome the power overshoot. With bacterial colonization, the transient charge storage in biofilm resulted in a 0.1-0.4F/cm(2) increase in total capacitance for anodes, which was the possible reason for the elimination of power overshoot in PAC/CB-MFCs after multi cycle acclimation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.

PubMed

Santaguida, Stefano; Richardson, Amelia; Iyer, Divya Ramalingam; M'Saad, Ons; Zasadil, Lauren; Knouse, Kristin A; Wong, Yao Liang; Rhind, Nicholas; Desai, Arshad; Amon, Angelika

2017-06-19

Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways that limit the prevalence of such cells exist? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to further genomic instability that ultimately causes cell-cycle arrest. We further show that cells with complex karyotypes exhibit features of senescence and produce pro-inflammatory signals that promote their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that may serve as a means for cancer cell immunosurveillance. Copyright © 2017 Elsevier Inc. All rights reserved.

Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.

PubMed

Steukers, Lennert; Weyers, Steven; Yang, Xiaoyun; Vandekerckhove, Annelies P; Glorieux, Sarah; Cornelissen, Maria; Van den Broeck, Wim; Temmerman, Marleen; Nauwynck, Hans J

2014-07-15

We developed and morphologically characterized a human genital mucosa explant model (endocervix and ectocervix/vagina) to mimic genital herpes infections caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis of HSV entry receptor expression throughout the menstrual cycle in genital tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was assessed. Nectin-1 and -2 were expressed in all tissues during the entire menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal spread across the basement membrane and induced prominent epithelial syncytia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.

PubMed

Curreli, Francesca; Belov, Dmitry S; Kwon, Young Do; Ramesh, Ranjith; Furimsky, Anna M; O'Loughlin, Kathleen; Byrge, Patricia C; Iyer, Lalitha V; Mirsalis, Jon C; Kurkin, Alexander V; Altieri, Andrea; Debnath, Asim K

2018-05-12

We are continuing our concerted effort to optimize our first lead entry antagonist, NBD-11021, which targets the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, to improve antiviral potency and ADMET properties. In this report, we present a structure-based approach that helped us to generate working hypotheses to modify further a recently reported advanced lead entry antagonist, NBD-14107, which showed significant improvement in antiviral potency when tested in a single-cycle assay against a large panel of Env-pseudotyped viruses. We report here the synthesis of twenty-nine new compounds and evaluation of their antiviral activity in a single-cycle and multi-cycle assay to derive a comprehensive structure-activity relationship (SAR). We have selected three inhibitors with the high selectivity index for testing against a large panel of 55 Env-pseudotyped viruses representing a diverse set of clinical isolates of different subtypes. The antiviral activity of one of these potent inhibitors, 55 (NBD-14189), against some clinical isolates was as low as 63 nM. We determined the sensitivity of CD4-binding site mutated-pseudoviruses to these inhibitors to confirm that they target HIV-1 gp120. Furthermore, we assessed their ADMET properties and compared them to the clinical candidate attachment inhibitor, BMS-626529. The ADMET data indicate that some of these new inhibitors have comparable ADMET properties to BMS-626529 and can be optimized further to potential clinical candidates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Biological Role of Nestin(+)-Cells in Physiological and Pathological Cardiovascular Remodeling

PubMed Central

Calderone, Angelino

2018-01-01

The intermediate filament protein nestin was identified in diverse populations of cells implicated in cardiovascular remodeling. Cardiac resident neural progenitor/stem cells constitutively express nestin and following an ischemic insult migrate to the infarct region and participate in angiogenesis and neurogenesis. A modest number of normal adult ventricular fibroblasts express nestin and the intermediate filament protein is upregulated during the progression of reparative and reactive fibrosis. Nestin depletion attenuates cell cycle re-entry suggesting that increased expression of the intermediate filament protein in ventricular fibroblasts may represent an activated phenotype accelerating the biological impact during fibrosis. Nestin immunoreactivity is absent in normal adult rodent ventricular cardiomyocytes. Following ischemic damage, the intermediate filament protein is induced in a modest population of pre-existing adult ventricular cardiomyocytes bordering the peri-infarct/infarct region and nestin(+)-ventricular cardiomyocytes were identified in the infarcted human heart. The appearance of nestin(+)-ventricular cardiomyocytes post-myocardial infarction (MI) recapitulates an embryonic phenotype and depletion of the intermediate filament protein inhibits cell cycle re-entry. Recruitment of the serine/threonine kinase p38 MAPK secondary to an overt inflammatory response after an ischemic insult may represent a seminal event limiting the appearance of nestin(+)-ventricular cardiomyocytes and concomitantly suppressing cell cycle re-entry. Endothelial and vascular smooth muscle cells (VSMCs) express nestin and upregulation of the intermediate filament protein may directly contribute to vascular remodeling. This review will highlight the biological role of nestin(+)-cells during physiological and pathological remodeling of the heart and vasculature and discuss the phenotypic advantage attributed to the intermediate filament protein. PMID:29492403

Mobile application for field data collection and query: Example from wildlife research (Invited)

NASA Astrophysics Data System (ADS)

Bateman, H.; Lindquist, T.; Whitehouse, R.

2013-12-01

Field data collection is often used in many scientific disciplines and effective approaches rely on accurate data collection and recording. We designed a smartphone and tablet application (app) for field-collected data and tested it during a study on wildlife. The objective of our study was to determine the effectiveness of mobile applications in wildlife field research. Student software developers designed applications for mobile devices on the iOS and Android operating systems. Both platforms had similar user interactions via data entry on a touch screen using pre-programmed fields, checkboxes, drop-down menus, and keypad entry. The mobile application included features to insure collection of all measurements in the field through pop-up messages and could proof entries for valid formats. We used undergraduate student subjects to compare the duration of data recording and data entry, and the frequency of errors between the mobile application and traditional (paper) techniques. We field-tested the mobile application using an existing study on wildlife. From the field, technicians could query a database stored on a mobile device to view histories of previously captured animals. Overall, we found that because the mobile application allowed us to enter data in a digital format in the field we could eliminate timely steps to process handwritten data sheets and double-checking data entries. We estimated that, for a 2-month project, using the mobile application instead of traditional data entry and proofing reduced our total project time by 10%. To our knowledge, this is the first application developed for mobile devices for wildlife users interesting in viewing animal capture histories from the field and could be developed for use in other areas of field research.

Sunlight-induced Transformations of Graphene-based Nanomaterials in Aquatic Environments

EPA Science Inventory

Graphene-based nanomaterials and other related carbon nanomaterials (CNMs) can be released from products during their life cycles. Upon entry into aquatic environments, they are potentially transformed by photochemical reactions, oxidation reactions and biological processes, all ...

[Challenge and opportunity of entry to WTO brings to scientific and technological periodical].

PubMed

Tian, Yun-Mei

2004-11-01

After our country enters WTO, confronted with the direct influence in big international market opening, editorial department will face fierce competition. Selecting the superior and eliminate the inferior will test every publishing house and every magazine directly. In order to improve the competition level, author has analyzed the current situation of China's periodical development, and then explored the scientific and technological periodical opportunity and challenge faced under the new situation.

Shop Math for the Metal Trades. Combination Welder Apprentice, Machinist Helper, Precision Metal Finisher, Sheet Metal Worker Apprentice. A Report on Metal Trades Industry Certified, Single-Concept, Mathematical Learning Projects to Eliminate Student Math Fears.

ERIC Educational Resources Information Center

Newton, Lawrence R.

This project (1) identifies basic and functional mathematics skills (shop mathematics skills), (2) provides pretests on these functional mathematics skills, and (3) provides student learning projects (project sheets) that prepare metal trades students to read, understand, and apply mathematics and measuring skills that meet entry-level job…

Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.

PubMed

Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

2015-09-08

B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process.

Wang OIS glossary package for reformatting documents telecommunicated to the OIS system

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

Markow, S.R.

1983-12-09

Documents that are composed on a computer and then transmitted by telecommunications into a Wang Office Information System (OIS) word processing system need to be reformatted and cleaned up before they can be used properly as word processing documents suitable for further revisions or additions. This report describes a group of glossary entries created for the Wang OIS which simplifies the job of cleaning up telecommunicated documents. This glossary is a semi-automated process designed to eliminate most of the tedious work needed to be performed in removing extra spaces and returns, adjusting formats, moving material, repagination, using tabs or indents,more » and similar problems. The report briefly discusses the problems, describes the glossary approach to solving them, and gives instructions for actually using the glossary entries.« less

Field of first magnetic flux entry and pinning strength of superconductors for rf application measured with muon spin rotation

NASA Astrophysics Data System (ADS)

Junginger, T.; Abidi, S. H.; Maffett, R. D.; Buck, T.; Dehn, M. H.; Gheidi, S.; Kiefl, R.; Kolb, P.; Storey, D.; Thoeng, E.; Wasserman, W.; Laxdal, R. E.

2018-03-01

The performance of superconducting radiofrequency (SRF) cavities used for particle accelerators depends on two characteristic material parameters: field of first flux entry Hentry and pinning strength. The former sets the limit for the maximum achievable accelerating gradient, while the latter determines how efficiently flux can be expelled related to the maximum achievable quality factor. In this paper, a method based on muon spin rotation (μ SR ) is developed to probe these parameters on samples. It combines measurements from two different spectrometers, one being specifically built for these studies and samples of different geometries. It is found that annealing at 1400 °C virtually eliminates all pinning. Such an annealed substrate is ideally suited to measure Hentry of layered superconductors, which might enable accelerating gradients beyond bulk niobium technology.

ISG15 Functions as an Interferon-Mediated Antiviral Effector Early in the Murine Norovirus Life Cycle

PubMed Central

Rodriguez, Marisela R.; Monte, Kristen; Thackray, Larissa B.

2014-01-01

ABSTRACT Human noroviruses (HuNoV) are the leading cause of nonbacterial gastroenteritis worldwide. Similar to HuNoV, murine noroviruses (MNV) are enteric pathogens spread via the fecal-oral route and have been isolated from numerous mouse facilities worldwide. Type I and type II interferons (IFN) restrict MNV-1 replication; however, the antiviral effectors impacting MNV-1 downstream of IFN signaling are largely unknown. Studies using dendritic cells, macrophages, and mice deficient in free and conjugated forms of interferon-stimulated gene 15 (ISG15) revealed that ISG15 conjugation contributes to protection against MNV-1 both in vitro and in vivo. ISG15 inhibited a step early in the viral life cycle upstream of viral genome transcription. Directly transfecting MNV-1 RNA into IFN-stimulated mouse embryonic fibroblasts (MEFs) and bone marrow-derived dendritic cells (BMDC) lacking ISG15 conjugates bypassed the antiviral activity of ISG15, further suggesting that ISG15 conjugates restrict the MNV-1 life cycle at the viral entry/uncoating step. These results identify ISG15 as the first type I IFN effector regulating MNV-1 infection both in vitro and in vivo and for the first time implicate the ISG15 pathway in the regulation of early stages of MNV-1 replication. IMPORTANCE Type I IFNs are important in controlling murine norovirus 1 (MNV-1) infections; however, the proteins induced by IFNs that restrict viral growth are largely unknown. This report reveals that interferon-stimulated gene 15 (ISG15) mitigates MNV-1 replication both in vitro and in vivo. In addition, it shows that ISG15 inhibits MNV-1 replication by targeting an early step in the viral life cycle, MNV-1 entry and/or uncoating. These results identify ISG15 as the first type I IFN effector regulating MNV-1 infection both in vitro and in vivo and for the first time implicate the ISG15 pathway in the regulation of viral entry/uncoating. PMID:24899198

Engine Cycle Analysis for a Particle Bed Reactor Nuclear Rocket

DTIC Science & Technology

1991-03-01

0 DTIC USERS UNCLASSIFIED 22a. NAME OF RESPONSIBLE INDIVIDUAL ZZb. TELEPHONE (Include Area Code) 22c. OFFICE SYMBOL Lt Timothy J . Lawrence 805-275...Cycle with 2000 MW PBR and Uncooled Nozzle J : Output for Bleed Cycle with 2000 MW PBR and Cooled Nozzle K: Output for Expander Cycle with 2000 MW PBR L...Mars with carbon dioxide, the primary component of the Martian atmosphere. Carbon dioxide would delivera smaller ! j , but its use would eliminate the

Product differentiation during continuous-flow thermal gradient PCR.

PubMed

Crews, Niel; Wittwer, Carl; Palais, Robert; Gale, Bruce

2008-06-01

A continuous-flow PCR microfluidic device was developed in which the target DNA product can be detected and identified during its amplification. This in situ characterization potentially eliminates the requirement for further post-PCR analysis. Multiple small targets have been amplified from human genomic DNA, having sizes of 108, 122, and 134 bp. With a DNA dye in the PCR mixture, the amplification and unique melting behavior of each sample is observed from a single fluorescent image. The melting behavior of the amplifying DNA, which depends on its molecular composition, occurs spatially in the thermal gradient PCR device, and can be observed with an optical resolution of 0.1 degrees C pixel(-1). Since many PCR cycles are within the field of view of the CCD camera, melting analysis can be performed at any cycle that contains a significant quantity of amplicon, thereby eliminating the cycle-selection challenges typically associated with continuous-flow PCR microfluidics.

PP2ARts1 is a master regulator of pathways that control cell size

PubMed Central

Zapata, Jessica; Dephoure, Noah; MacDonough, Tracy; Yu, Yaxin; Parnell, Emily J.; Mooring, Meghan; Gygi, Steven P.; Stillman, David J.

2014-01-01

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth. PMID:24493588

Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition.

PubMed

Li, Qisheng; Sodroski, Catherine; Lowey, Brianna; Schweitzer, Cameron J; Cha, Helen; Zhang, Fang; Liang, T Jake

2016-07-05

Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.

Reliability-based trajectory optimization using nonintrusive polynomial chaos for Mars entry mission

NASA Astrophysics Data System (ADS)

Huang, Yuechen; Li, Haiyang

2018-06-01

This paper presents the reliability-based sequential optimization (RBSO) method to settle the trajectory optimization problem with parametric uncertainties in entry dynamics for Mars entry mission. First, the deterministic entry trajectory optimization model is reviewed, and then the reliability-based optimization model is formulated. In addition, the modified sequential optimization method, in which the nonintrusive polynomial chaos expansion (PCE) method and the most probable point (MPP) searching method are employed, is proposed to solve the reliability-based optimization problem efficiently. The nonintrusive PCE method contributes to the transformation between the stochastic optimization (SO) and the deterministic optimization (DO) and to the approximation of trajectory solution efficiently. The MPP method, which is used for assessing the reliability of constraints satisfaction only up to the necessary level, is employed to further improve the computational efficiency. The cycle including SO, reliability assessment and constraints update is repeated in the RBSO until the reliability requirements of constraints satisfaction are satisfied. Finally, the RBSO is compared with the traditional DO and the traditional sequential optimization based on Monte Carlo (MC) simulation in a specific Mars entry mission to demonstrate the effectiveness and the efficiency of the proposed method.

Quantitative membrane proteomics reveals a role for tetraspanin enriched microdomains during entry of human cytomegalovirus

PubMed Central

John, Nessy; Malouli, Daniel

2017-01-01

Human cytomegalovirus (HCMV) depends on and modulates multiple host cell membrane proteins during each stage of the viral life cycle. To gain a global view of the impact of HCMV-infection on membrane proteins, we analyzed HCMV-induced changes in the abundance of membrane proteins in fibroblasts using stable isotope labeling with amino acids (SILAC), membrane fractionation and protein identification by two-dimensional liquid chromatography and tandem mass spectrometry. This systematic approach revealed that CD81, CD44, CD98, caveolin-1 and catenin delta-1 were down-regulated during infection whereas GRP-78 was up-regulated. Since CD81 downregulation was also observed during infection with UV-inactivated virus we hypothesized that this tetraspanin is part of the viral entry process. Interestingly, additional members of the tetraspanin family, CD9 and CD151, were also downregulated during HCMV-entry. Since tetraspanin-enriched microdomains (TEM) cluster host cell membrane proteins including known CMV receptors such as integrins, we studied whether TEMs are required for viral entry. When TEMs were disrupted with the cholesterol chelator methyl-β-cylcodextrin, viral entry was inhibited and this inhibition correlated with reduced surface levels of CD81, CD9 and CD151, whereas integrin levels remained unchanged. Furthermore, simultaneous siRNA-mediated knockdown of multiple tetraspanins inhibited viral entry whereas individual knockdown had little effect suggesting essential, but redundant roles for individual tetraspanins during entry. Taken together, our data suggest that TEM act as platforms for receptors utilized by HCMV for entry into cells. PMID:29121670

The new extended-cycle levonorgestrel-ethinyl estradiol oral contraceptives.

PubMed

Bonnema, Rachel A; Spencer, Abby L

2011-09-19

Effective contraceptive counseling requires an understanding of a woman's preferences and medical history as well as the risks, benefits, side effects, and contraindications of each contraceptive method. Hormonal contraceptives using a variety of delivery methods are highly effective and this review highlights the new extended-cycle levonorgestrel-ethinyl estradiol contraceptives. Extended-cycle OCPs are unique in offering fewer or no withdrawal bleeds over the course of one year but providers need to carefully counsel women regarding the initial increased breakthrough bleeding. Extended-cycle OCPs may be of particular benefit in women with medical comorbidities who would benefit from less withdrawal bleeds, those desiring to avoid monthly menses due to increased hormonal withdrawal symptoms, or simply women who don't desire a monthly period. The risks associated with all extended-cycle OCPs have been found to be similar to those of traditional OCPs therefore counseling on the risks and side effects is comparable to that of any combined hormonal contraceptives. Newer extended-cycle regimens shorten or eliminate the hormone-free interval, decrease frequency of menses to four times per year or eliminate menses altogether. This can reduce the risk of common menstrual symptoms, endometriosis, or severe dysmenorrhea by offering potentially greater ovarian suppression and preventing endogenous estradiol production while still providing highly effective, rapidly reversible, and safe contraception.

In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

USGS Publications Warehouse

Wargo, Andrew R.; Kurath, Gael

2011-01-01

The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells

PubMed Central

Laos, Maarja; Anttonen, Tommi; Kirjavainen, Anna; Hällström, Taija af; Laiho, Marikki; Pirvola, Ulla

2014-01-01

Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs hold promise as a platform for therapeutic regeneration of the sensory hair cells. Prior data have shown proliferative restrictions of adult SCs forced to re-enter the cell cycle. By comparing juvenile and adult SCs in explant cultures, we have here studied how proliferative restrictions are linked with DNA damage signaling. Cyclin D1 overexpression, used to stimulate cell cycle re-entry, triggered higher proliferative activity of juvenile SCs. Phosphorylated form of histone H2AX (γH2AX) and p53 binding protein 1 (53BP1) were induced in a foci-like pattern in SCs of both ages as an indication of DNA double-strand break formation and activated DNA damage response. Compared to juvenile SCs, γH2AX and the repair protein Rad51 were resolved with slower kinetics in adult SCs, accompanied by increased apoptosis. Consistent with the in vitro data, in a Rb mutant mouse model in vivo, cell cycle re-entry of SCs was associated with γH2AX foci induction. In contrast to cell cycle reactivation, pharmacological stimulation of SC-to-hair-cell transdifferentiation in vitro did not trigger γH2AX. Thus, DNA damage and its prolonged resolution are critical barriers in the efforts to stimulate proliferation of the adult inner ear SCs. PMID:25063730

iMAST FY2002 Annual Report

DTIC Science & Technology

2002-01-01

of large precision drive train components such as transmission housings. The approach being pursued, under this program structure, is to eliminate the...an optimum coating and/or coating process will be developed and implemented, and will eliminate /minimize fretting and low-cycle fatigue and the blade...maintaining adequate pollution control efficiency. Benefits: ★ Utilizes MCLB infrastructure ★ Avoids costs associated with existing APCS ★ Biofiltration

The Use of Nitrone Cycloadditions in the Synthesis of Beta-Amino Aldehydes and Unsaturated Amines.

DTIC Science & Technology

1986-01-01

with alkenes (dipolarophiles) to produce isoxazolidines (2) in a fashion similar to the (4+2] Diels - Alder reaction.’ The cycloaddition results in...structures to study enzyme inhibition, and they serve as useful intermediates in the synthesis of $-lactams. 3 3 Table IV summarizes attempts to oxidize p...84% yield (Table V, entry 3). Due to the mechanistic imperative, acid catalyzed elimination always yielded the allylic amine in which the alkene

Hazardous-Materials Robot

NASA Technical Reports Server (NTRS)

Stone, Henry W.; Edmonds, Gary O.

1995-01-01

Remotely controlled mobile robot used to locate, characterize, identify, and eventually mitigate incidents involving hazardous-materials spills/releases. Possesses number of innovative features, allowing it to perform mission-critical functions such as opening and unlocking doors and sensing for hazardous materials. Provides safe means for locating and identifying spills and eliminates risks of injury associated with use of manned entry teams. Current version of vehicle, called HAZBOT III, also features unique mechanical and electrical design enabling vehicle to operate safely within combustible atmosphere.

Supersonic Aerodynamic Characteristics of Blunt Body Trim Tab Configurations

NASA Technical Reports Server (NTRS)

Korzun, Ashley M.; Murphy, Kelly J.; Edquist, Karl T.

2013-01-01

Trim tabs are aerodynamic control surfaces that can allow an entry vehicle to meet aerodynamic performance requirements while reducing or eliminating the use of ballast mass and providing a capability to modulate the lift-to-drag ratio during entry. Force and moment data were obtained on 38 unique, blunt body trim tab configurations in the NASA Langley Research Center Unitary Plan Wind Tunnel. The data were used to parametrically assess the supersonic aerodynamic performance of trim tabs and to understand the influence of tab area, cant angle, and aspect ratio. Across the range of conditions tested (Mach numbers of 2.5, 3.5, and 4.5; angles of attack from -4deg to +20deg; angles of sideslip from 0deg to +8deg), the effects of varying tab area and tab cant angle were found to be much more significant than effects from varying tab aspect ratio. Aerodynamic characteristics exhibited variation with Mach number and forebody geometry over the range of conditions tested. Overall, the results demonstrate that trim tabs are a viable approach to satisfy aerodynamic performance requirements of blunt body entry vehicles with minimal ballast mass. For a 70deg sphere-cone, a tab with 3% area of the forebody and canted approximately 35deg with no ballast mass was found to give the same trim aerodynamics as a baseline model with ballast mass that was 5% of the total entry mass.

Conversion of cardiac performance data in analog form for digital computer entry

NASA Technical Reports Server (NTRS)

Miller, R. L.

1972-01-01

A system is presented which will reduce analog cardiac performance data and convert the results to digital form for direct entry into a commercial time-shared computer. Circuits are discussed which perform the measurement and digital conversion of instantaneous systolic and diastolic parameters from the analog blood pressure waveform. Digital averaging over a selected number of heart cycles is performed on these measurements, as well as those of flow and heart rate. The determination of average cardiac output and peripheral resistance, including trends, is the end result after processing by digital computer.

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.

PubMed

Atwood, Craig S; Bowen, Richard L

2015-11-01

This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-β precursor protein processing towards the production of mitogenic Aβ; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease. Published by Elsevier Inc.

40 CFR 92.504 - Right of entry and access.

Code of Federal Regulations, 2010 CFR

2010-07-01

... manufacturer's or remanufacturer's production line testing or auditing program or any procedure or activity... service accumulation, emission test cycles, and maintenance and verification of test equipment calibration... not limited to, clerical, copying, interpretation and translation services; the making available on an...

Two LXXLL motifs in the N terminus of Mps1 are required for Mps1 nuclear import during G(2)/M transition and sustained spindle checkpoint responses.

PubMed

Zhang, Xiaojuan; Yin, Qingqing; Ling, Youguo; Zhang, Yanhong; Ma, Runlin; Ma, Qingjun; Cao, Cheng; Zhong, Hui; Liu, Xuedong; Xu, Quanbin

2011-08-15

Spindle assembly checkpoint kinase Mps1 is spatially and temporally regulated during cell cycle progression. Mps1 is predominately localized to the cytosol in interphase cells, whereas it is concentrated on kinetochores in prophase and prometaphase cells. The timing and mechanism of Mps1 redistribution during cell cycle transition is currently poorly understood. Here, we show that Mps1 relocates from the cytosol to the nucleus at the G 2/M boundary prior to nuclear envelope breakdown (NEB). This timely translocation depends on two tandem LXXLL motifs in the N terminus of Mps1, and mutations in either motif abolish Mps1 nuclear accumulation. Furthermore, we found that phosphorylation of Mps1 Ser80 (which is located between the two LXXLL motifs) also plays a role in regulating timely nuclear entry of Mps1. Mps1 that is defective in LXXLL motifs has near wild-type kinase activity. Moreover, the kinase activity of Mps1 appears to be dispensable for nuclear translocation, as inhibition of Mps1 by a highly specific small-molecule inhibitor did not perturb its nuclear entry. Remarkably, translocation-deficient Mps1 can mediate activation of spindle assembly checkpoint response; however, it fails to support a sustained mitotic arrest upon prolonged treatment with nocodazole. The mitotic slippage can be attributed to precocious degradation of Mps1 in the arrested cells. Our studies reveal a novel cell cycle-dependent nuclear translocation signal in the N terminus of Mps1 and suggest that timely nuclear entry could be important for sustaining spindle assembly checkpoint responses.

Two LXXLL motifs in the N terminus of Mps1 are required for Mps1 nuclear import during G2/M transition and sustained spindle checkpoint responses

PubMed Central

Zhang, Xiaojuan; Yin, Qingqing; Ling, Youguo; Zhang, Yanhong; Ma, Runlin; Ma, Qingjun; Cao, Cheng; Zhong, Hui

2011-01-01

Spindle assembly checkpoint kinase Mps1 is spatially and temporally regulated during cell cycle progression. Mps1 is predominately localized to the cytosol in interphase cells, whereas it is concentrated on kinetochores in prophase and prometaphase cells. The timing and mechanism of Mps1 redistribution during cell cycle transition is currently poorly understood. Here, we show that Mps1 relocates from the cytosol to the nucleus at the G2/M boundary prior to nuclear envelope breakdown (NEB). This timely translocation depends on two tandem LXXLL motifs in the N terminus of Mps1, and mutations in either motif abolish Mps1 nuclear accumulation. Furthermore, we found that phosphorylation of Mps1 Ser80 (which is located between the two LXXLL motifs) also plays a role in regulating timely nuclear entry of Mps1. Mps1 that is defective in LXXLL motifs has near wild-type kinase activity. Moreover, the kinase activity of Mps1 appears to be dispensable for nuclear translocation, as inhibition of Mps1 by a highly specific small-molecule inhibitor did not perturb its nuclear entry. Remarkably, translocation-deficient Mps1 can mediate activation of spindle assembly checkpoint response; however, it fails to support a sustained mitotic arrest upon prolonged treatment with nocodazole. The mitotic slippage can be attributed to precocious degradation of Mps1 in the arrested cells. Our studies reveal a novel cell cycle-dependent nuclear translocation signal in the N terminus of Mps1 and suggest that timely nuclear entry could be important for sustaining spindle assembly checkpoint responses. PMID:21778823

Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.

PubMed Central

Cuadras, M A; Arias, C F; López, S

1997-01-01

In this work, we found that rotavirus infection induces an early membrane permeabilization of MA104 cells and promotes the coentry of toxins, such as alpha-sarcin, into the cell. This cell permeability was shown to depend on infectious virus and was also shown to be virus dose dependent, with 10 infectious particles per cell being sufficient to achieve maximum permeability; transient, lasting no more than 15 min after virus entry and probably occurring concomitantly with virus penetration; and specific, since cells that are poorly permissive for rotavirus were not permeabilized. The rotavirus-mediated coentry of toxins was not blocked by the endocytosis inhibitors dansylcadaverine and cytochalasin D or by the vacuolar proton-ATPase inhibitor bafilomycin A1, suggesting that neither endocytocis nor an intraendosomal acidic pH or a proton gradient is required for permeabilization of the cells. Compounds that raise the intracellular concentration of calcium ([Ca2+]i) by different mechanisms, such as the calcium ionophores A23187 and ionomycin and the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin, did not block the coentry of alpha-sarcin or affect the onset of viral protein synthesis, suggesting that a low [Ca2+]i is not essential for the initial steps of the virus life cycle. Since the entry of alpha-sarcin correlates with virus penetration in all parameters tested, the assay for permeabilization to toxins might be a useful tool for studying and characterizing the route of entry and the mechanism used by rotaviruses to traverse the cell membrane and initiate a productive replication cycle. PMID:9371563

Data Flow Infrastructure Initiative (DFII): Coupling Inventory Practices and Data collection Technology to Enhance Research Productivity and Information Access

NASA Astrophysics Data System (ADS)

Meyer, K.; Malin, R.; Rich, R. L.; Pierce, S. A.

2011-12-01

Shortening the cycle from data collection to research publications is a competitive advantage for researchers. Existing technologies for inventory systems such as UPC barcoding systems can be coupled with flexible mobile or handheld devices to advance efficiency, productivity, automation, and integrity in data flows, from data collection to sample processing to database management and analysis, and finally publication. At the University of Texas, the Data Flow Infrastructure Initiative (DFII) has introduced handheld devices with integrated barcode scanners as a mechanism to enhance research productivity and information access. These devices are established technology and provide a flexible but consistent platform for research data collection and data management. They are not in widespread use yet in the research community. Additional application benefits will accrue by using handheld devices to deliver data on demand in teaching applications. Introducing research scientists, graduate students, and the UT community to the merits and flexibility of these data collection technologies will provide avenues for innovation as well as improving efficiency. The objective of this project is to bring the technology and expertise with handheld systems to a diverse set of pilot projects and establish proficiency at The University of Texas at Austin necessary for widespread application. We have implemented a pilot project in three research labs covering the fields of microbial ecology, water resources decision support, and biogeochemistry to introduce these technologies. We used NautizX5 handheld devices that feature: barcode scanning, bluetooth, stylus, and keypad data inputs coupled with Pendragon Forms Software, a program that allows users to create custom data collection forms structured into an SQL or Access platform thus allowing concurrent data management, data collection and analysis in field and lab settings. Results include the elimination of most manual data entry, reducing data entry error, tracking effectiveness at data collection, and increased sampling efficiency and consistency over multi-year experiments.

MODIS polarization performance and anomalous four-cycle polarization phenomenon

NASA Astrophysics Data System (ADS)

Young, James B.; Knight, Ed; Merrow, Cindy

1998-10-01

The Moderate Resolution Imaging Spectroradiometer (MODIS) will be one of the primary instruments observing the earth on the Earth Observing System (EOS) scheduled for launch in 1999. MODIS polarization performance characterization was required for the 0.4 to 0.6 micrometers (VIS), 0.6 micrometers to 1.0 micrometers (NIR), and 1.0 micrometers to 2.3 micrometers (SWIR) regions. A polarized source assembly (PSA) consisting of a collimator with a rotatable Ahrens polarizer was used to illuminate MODIS with a linearly polarized beam. MODIS signal function having two-cycles per 360 degrees prism rotation signal function was expected. However, some spectral bands had a distinct four-cycle anomalous signal. The expected two-cycle function was present in all regions with the four-cycle anomaly being limited to the NIR region. Fourier analysis was very useful tooling determining the cause of the anomaly. A simplified polarization model of the PSA and MODIS was generated using Mueller matrices-Stokes vector formalism. Parametric modeling illustrated that this anomaly could be produced by energy having multiple passes between PSA Ahrens prism and the MODIS focal plane filters. Furthermore, the model gave NIR four-cycle magnitudes that were consistent with observations. The IVS and SWIR optical trans had birefringent elements that served to scramble the multiple pass anomaly. The model validity was demonstrated with an experimental setup that had partial aperture illumination which eliminated the possibility of multiple passes. The four-cycle response was eliminated while producing the same two-cycle polarization response. Data will be shown to illustrate the four-cycle phenomenon.

50 CFR 660.55 - Allocations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... biennial fishing period's open access allocation. (B) [Reserved] (f) Catch accounting. Catch accounting... allocations in a given biennial cycle, catch of those species are counted against the limited entry/open... fisheries—(i) Catch accounting for the trawl allocation. Any groundfish caught by a vessel registered to a...

Small G Rac1 is involved in replication cycle of dengue serotype 2 virus in EAhy926 cells via the regulation of actin cytoskeleton.

PubMed

Zhang, Jing; Wu, Na; Gao, Na; Yan, Wenli; Sheng, Ziyang; Fan, Dongying; An, Jing

2016-05-01

Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the pathogenesis of severe dengue remains unclear. In this study, we showed that the Rac1-microfilament signal pathway was involved in the process of DENV serotype 2 (DENV2) infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Rac1 activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Rac1 promoted DENV2 entry but inhibited viral assembly, maturation and release. Our findings demonstrated that Rac1 plays an important role in the DENV2 life cycle by regulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.

iMAST FY2003 Annual Report

DTIC Science & Technology

2003-01-01

The approach being pursued, under this program structure, is to eliminate the use of physical surfaces on the component as datum. The use of physical...will eliminate /minimize fretting and low-cycle fatigue and the blade-disk interface. This optimum coating and/or coating process will be evaluated both...Utilizes MCLB infrastructure Avoids costs associated with existing APCS Biofiltration produces no secondary emissions Biofiltration is the most

Operating and hydrodynamic characteristics of a reversed flow jet loop bioreactor (RFJLB) with ejector.

PubMed

Wagh, Sameer M; Koranne, Kishore V; Sonolikar, Ram L

2012-04-01

The hydrodynamic characteristics of RFJLB was studied with superficial liquid velocity (Ul), nozzle diameter (Dn) and nozzle height (Hn) in the range of 0.0293-0.094m/s, 17.4-22.0mm and 50-400mm, respectively. For Dn=17.4mm, Hn=50 and 200mm, with ejector mode and regular operating procedure i.e. simultaneous entry of gas with increasing liquid velocity, had limitation of not establishing the circulation loop. To overcome this limitation a modified operating procedure i.e. entry of gas after established liquid circulation loop is proposed. Also the comparison of gas holdups with ejector and injector mode proves the effectiveness of ejector mode and can eliminate the supply of compressed gas. Thus proper choice of Dn, Hn and also the operating procedure becomes necessary. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Radiobiological effects of total mice irradiation with Bragg's peak protons].

PubMed

Ivanov, A A; Molokanov, A G; Ushakov, I B; Bulynina, T M; Vorozhtsova, S V; Abrosimova, A N; Kryuchkova, D M; Gaevsky, V N

2013-01-01

Outbred CD-1 female mice were irradiated in a proton beam (171 MeV, 5 Gy) on the phasotron at the Joint Institute of Nuclear Research (Dubna, Russia). Radiation was delivered in two points of the depth dose distribution: at the beam entry and on Bragg's peak. Technical requirements for studying the effects of Bragg's peak protons on organism of experimental animals were specified. It was recognized that protons with high linear energy transfer (mean LET = 1.6 keV/microm) cause a more severe damaging effect to the hemopoietic system and cytogenetic apparatus in bone marrow cells as compared with entry protons and 60Co gamma-quanta. It was shown that recovery of the main hemopoietic organs and immunity as well as elimination of chromosomal aberrations take more time following irradiation with Bragg's peak protons but not protons with the energy of 171 MeV.

Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

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

Kroken, Abby R.; Karalewitz, Andrew P.-A.; Fu, Zhuji

2012-02-07

Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing amore » ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.« less

Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase▿

PubMed Central

Park, Hyun Jung; Costa, Robert H.; Lau, Lester F.; Tyner, Angela L.; Raychaudhuri, Pradip

2008-01-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G1 phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G1 phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G1 phase and that its proteolysis is important for regulated entry into S phase. PMID:18573889

Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase.

PubMed

Park, Hyun Jung; Costa, Robert H; Lau, Lester F; Tyner, Angela L; Raychaudhuri, Pradip

2008-09-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G(1) phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G(1) phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase.

mei-41 and bub1 block mitosis at two distinct steps in response to incomplete DNA replication in Drosophila embryos.

PubMed

Garner, M; van Kreeveld, S; Su, T T

2001-10-16

Drosophila double park encodes a homolog of Cdt1 that functions in initiation of DNA replication in fission yeast and Xenopus. dup mutants complete the first 15 embryonic cell cycles, presumably via maternal dup products, and show defects in the 16(th) S phase (S16). Cells carrying dup(a1) allele forgo S16 altogether but enter mitosis 16 (M16). We find that the timing of entry into M16 is similar in dup(a1) and heterozygous or wild-type (wt) controls. In contrast, we find that mutant cells carrying another allele, dup(a3), undergo a partial S16 and delay the entry into M16. Thus, initiation of S16 appears necessary for delaying M16. This delay is absent in double mutants of dup(a3) and mei-41 (Drosophila ATR), indicating that a mei-41-dependent checkpoint acts to delay the entry into mitosis in response to incomplete DNA replication. dup(a3) and dup(a1) mutant cells that enter M16 become arrested in M16. We find that mitotic cyclins are stabilized and that a spindle checkpoint protein, Bub1, localizes onto chromosomes during mitotic arrest in dup mutants. These features suggest an arrest prior to metaphase-anaphase transition. dup(a3) bub1 double mutant cells exit M16, indicating that a bub1-mediated checkpoint acts to block mitotic exit in dup mutants. To our knowledge, this is the first report of (1) incomplete DNA replication affecting both the entry into and the exit from mitosis in a single cell cycle via different mechanisms and (2) the role of bub1 in regulating mitotic exit in response to incomplete DNA replication.

Development of a rapid and quantitative method for the analysis of viral entry and release using a NanoLuc luciferase complementation assay.

PubMed

Sasaki, Michihito; Anindita, Paulina D; Phongphaew, Wallaya; Carr, Michael; Kobayashi, Shintaro; Orba, Yasuko; Sawa, Hirofumi

2018-01-02

Subviral particles (SVPs) self-assemble and are released from cells transfected with expression plasmids encoding flavivirus structural proteins. Flavivirus-like particles (VLPs), consisting of flavivirus structural proteins and a subgenomic replicon, can enter cells and cause single-round infections. Neither SVPs or VLPs possess complete viral RNA genomes, therefore are replication-incompetent systems; however, they retain the capacity to fuse and bud from target cells and follow the same maturation process as whole virions. SVPs and VLPs have been previously employed in studies analyzing entry and release steps of viral life cycles. In this study, we have developed quantitative methods for the detection of cellular entry and release of SVPs and VLPs by applying a luciferase complementation assay based on the high affinity interaction between the split NanoLuc luciferase protein, LgBiT and the small peptide, HiBiT. We introduced HiBiT into the structural protein of West Nile virus and generated SVPs and VLPs harboring HiBiT (SVP-HiBiT and VLP-HiBiT, respectively). As SVP-HiBiT emitted strong luminescence upon exposure to LgBiT and its substrate, the nascently budded SVP-HiBiT in the supernatant was readily quantified by luminometry. Similarly, the cellular entry of VLP-HiBiT generated luminescence when VLP-HiBiT was infected into LgBiT-expressing cells. These methods utilizing SVP-HiBiT and VLP-HiBiT will facilitate research into life cycles of flaviviruses, including WNV. Copyright © 2017 Elsevier B.V. All rights reserved.

Web-based data collection: detailed methods of a questionnaire and data gathering tool

PubMed Central

Cooper, Charles J; Cooper, Sharon P; del Junco, Deborah J; Shipp, Eva M; Whitworth, Ryan; Cooper, Sara R

2006-01-01

There have been dramatic advances in the development of web-based data collection instruments. This paper outlines a systematic web-based approach to facilitate this process through locally developed code and to describe the results of using this process after two years of data collection. We provide a detailed example of a web-based method that we developed for a study in Starr County, Texas, assessing high school students' work and health status. This web-based application includes data instrument design, data entry and management, and data tables needed to store the results that attempt to maximize the advantages of this data collection method. The software also efficiently produces a coding manual, web-based statistical summary and crosstab reports, as well as input templates for use by statistical packages. Overall, web-based data entry using a dynamic approach proved to be a very efficient and effective data collection system. This data collection method expedited data processing and analysis and eliminated the need for cumbersome and expensive transfer and tracking of forms, data entry, and verification. The code has been made available for non-profit use only to the public health research community as a free download [1]. PMID:16390556

Ca2+ Entry is Required for Mechanical Stimulation-induced ATP Release from Astrocyte

PubMed Central

Lee, Jaekwang; Chun, Ye-Eun; Han, Kyung-Seok; Lee, Jungmoo; Woo, Dong Ho

2015-01-01

Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca2+ oscillations. ATP is known to be released from astrocytes by Ca2+-dependent manner. However, the precise source of Ca2+, whether it is Ca2+ entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca2+ was released from intracellular stores by activation of Gαq-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca2+ was omitted. Our results suggest that Ca2+ entry, but not release from intracellular Ca2+ store, is critical for MS-induced ATP release from astrocyte. PMID:25792866

The Temporal Regulation of S Phase Proteins During G1

PubMed Central

Grant, Gavin D.; Cook, Jeanette G.

2018-01-01

Successful DNA replication requires intimate coordination with cell cycle progression. Prior to DNA replication initiation in S phase, a series of essential preparatory events in G1 phase ensures timely, complete, and precise genome duplication. Among the essential molecular processes are regulated transcriptional upregulation of genes that encode replication proteins, appropriate post-transcriptional control of replication factor abundance and activity, and the assembly of DNA-loaded protein complexes to license replication origins. In this chapter we describe these critical G1 events necessary for DNA replication and their regulation in the context of both cell cycle entry and cell cycle progression. PMID:29357066

Human exposure to aluminium.

PubMed

Exley, Christopher

2013-10-01

Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus

PubMed Central

Okubo, Yu; Wakata, Aika; Suzuki, Takuma; Shibata, Tomoko; Ikeda, Hitomi; Yamaguchi, Miki; Cohen, Justus B.; Glorioso, Joseph C.; Tagaya, Mitsuo; Hamada, Hirofumi; Tahara, Hideaki

2016-01-01

ABSTRACT Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR). We introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted HSV and found that these mutations, especially when combined, enabled formation of extensive syncytia by human cancer cell lines that express the target receptor; these syncytia were substantially larger than the plaques formed by the parental retargeted HSV strain. We assessed the EGFR dependence of entry and spread separately by using direct entry and infectious center assays, respectively, and we found that the syncytial mutations did not override the receptor specificity of the retargeted viruses at either stage. We discuss the implications of these results for the development of more effective targeted oncolytic HSV vectors. IMPORTANCE Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors. PMID:27707922

System for information discovery

DOEpatents

Pennock, Kelly A [Richland, WA; Miller, Nancy E [Kennewick, WA

2002-11-19

A sequence of word filters are used to eliminate terms in the database which do not discriminate document content, resulting in a filtered word set and a topic word set whose members are highly predictive of content. These two word sets are then formed into a two dimensional matrix with matrix entries calculated as the conditional probability that a document will contain a word in a row given that it contains the word in a column. The matrix representation allows the resultant vectors to be utilized to interpret document contents.

Eliminating Space Debris: Applied Technology and Policy Prescriptions, Fall 2007 - Project 07-02

DTIC Science & Technology

2008-01-01

plan to transfer ownership of the constellation, Iridium satellites were (presume that there was more than one) scheduled to be sent out of orbit to...told the research team that administrators are “not shy” about saying, “We have a problem with your debris plan .” Usually, the licensee will work... planned maneuvers • End-of-life (EOL) support. Includes re-entry support and planned de-orbit operations • Anomaly re configuration • Emergency ser

Technology requirements for a generic aerocapture system. [for atmospheric entry

NASA Technical Reports Server (NTRS)

Cruz, M. I.

1980-01-01

The technology requirements for the design of a generic aerocapture vehicle system are summarized. These spacecraft have the capability of completely eliminating fuel-costly retropropulsion for planetary orbit capture through a single aerodynamically controlled atmospheric braking pass from a hyperbolic trajectory into a near circular orbit. This generic system has application at both the inner and outer planets. Spacecraft design integration, navigation, communications, and aerothermal protection system design problems were assessed in the technology requirements study and are discussed in this paper.

Cholesterol effectively blocks entry of flavivirus.

PubMed

Lee, Chyan-Jang; Lin, Hui-Ru; Liao, Ching-Len; Lin, Yi-Ling

2008-07-01

Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells through receptor-mediated endocytosis and low pH-triggered membrane fusion and then replicate in intracellular membrane structures. Lipid rafts, cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion with methyl-beta-cyclodextrin or cholesterol chelation with filipin III reduces JEV and DEN-2 infection, mainly at the intracellular replication steps and, to a lesser extent, at viral entry. Using a membrane flotation assay, we found that several flaviviral nonstructural proteins are associated with detergent-resistant membrane structures, indicating that the replication complex of JEV and DEN-2 localizes to the membranes that possess the lipid raft property. Interestingly, we also found that addition of cholesterol readily blocks flaviviral infection, a result that contrasts with previous reports of other viruses, such as Sindbis virus, whose infectivity is enhanced by cholesterol. Cholesterol mainly affected the early step of the flavivirus life cycle, because the presence of cholesterol during viral adsorption greatly blocked JEV and DEN-2 infectivity. Flavirial entry, probably at fusion and RNA uncoating steps, was hindered by cholesterol. Our results thus suggest a stringent requirement for membrane components, especially with respect to the amount of cholesterol, in various steps of the flavivirus life cycle.

How to achieve customer service through short-cycle paperwork.

PubMed

Hunter, M

1998-02-01

The ultimate goal of short-cycle paperwork is to satisfy customers by filling their orders as quickly as possible. Tools and techniques that can help achieve this goal include Just-in-Time paperwork elimination, process mapping, paper flow mapping, function/process mapping, work cells, and electronic kanban. Each of these is described briefly in the article.

A system for automatic analysis of blood pressure data for digital computer entry

NASA Technical Reports Server (NTRS)

Miller, R. L.

1972-01-01

Operation of automatic blood pressure data system is described. Analog blood pressure signal is analyzed by three separate circuits, systolic, diastolic, and cycle defect. Digital computer output is displayed on teletype paper tape punch and video screen. Illustration of system is included.

Mechanistic insights into iron catalyzed dehydrogenation of formic acid: β-hydride elimination vs. direct hydride transfer.

PubMed

Yang, Xinzheng

2013-09-07

Density functional theory calculations reveal a complete reaction mechanism with detailed energy profiles and transition state structures for the dehydrogenation of formic acid catalyzed by an iron complex, [P(CH2CH2PPh2)3FeH](+). In the cationic reaction pathway, a β-hydride elimination process is confirmed to be the rate-determining step in this catalytic reaction. A potential reaction pathway starting with a direct hydride transfer from HCOO(-) to Fe is found to be possible, but slightly less favorable than the catalytic cycle with a β-hydride elimination step.

Misfit of Three Different Implant-Abutment Connections Before and After Cyclic Load Application: An In Vitro Study.

PubMed

Gehrke, Sergio Alexandre; Delgado-Ruiz, Rafael Arcesio; Prados Frutos, Juan Carlos; Prados-Privado, María; Dedavid, Berenice Anina; Granero Marín, Jose Manuel; Calvo Guirado, José Luiz

This study aimed to evaluate the misfit of three different implant-abutment connections before and after cycling load. One hundred twenty dental implants and correspondent prefabricated titanium abutments were used. Three different implant-abutment connections were evaluated: Morse taper (MT group), external hexagon (EH group), and internal hexagon (IH group). Forty implants and 40 abutments were used per group. The parameters for the mechanical evaluation were set as: 360,000 cycles, load of 150 N, and frequency of 4 Hz. Samples were sectioned in their longitudinal and transversal axes, and the misfit of the implant-abutment connection was evaluated by scanning electron microscopy analysis. One-way analyses of variance, Tukey post hoc analyses (α = .05), and t test (P < .05) were used to determine differences between groups. At the longitudinal direction, all the groups showed the presence of microgaps before cycling load; after cycling load, microgaps were reduced in all groups (P > .05). Transversally, only the MT group showed full fitting after cycling load compared with the other groups (EH and IH) (P < .0001). The application of cycling load produces an accommodation of the implant-abutment connection in internal, external, and Morse taper connections. In the longitudinal direction, the accommodation decreases and/or eliminates the gap observed initially (before load). In the horizontal direction, Morse cone implant-abutment connections experience a complete accommodation with the elimination of the gap.

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

Elimination of active tad elements during the sexual phase of the Neurospora crassa life cycle.

PubMed

Anderson, C; Tang, Q; Kinsey, J A

2001-06-01

Tad is an active LINE-like retrotransposon isolated from the Adiopodoumé strain of Neurospora crassa. Extensive analysis of other Neurospora strains has revealed no other strain with active Tad, but all strains tested have multiple copies of defective Tad elements. We have examined the ability of Tad to survive during the sexual cycle of Neurospora and find that active Tad is rapidly eliminated. The characteristics of this elimination suggest that the repeat-induced point mutation (RIP) mechanism was responsible. By the use of transformation to switch the mating type of the Adiopodoumé strain we concluded that this strain is not defective in the RIP process. Analysis of defective Tad elements isolated from a variety of strains indicates that the major difference between these elements and active Tad is due to the presence of a large number of G-C to A-T transition mutations. This would be expected if the changes were due primarily to the RIP process. Mapping of a selection of defective Tad elements reveals that they are present on all of the chromosomes; however, many of the elements are not widely shared among strains. This suggests that repeated introduction and elimination of Tad elements has occurred. Mechanisms that might be responsible for this repeated introduction are discussed. Copyright 2001 Academic Press.

Mathematical Model of Naive T Cell Division and Survival IL-7 Thresholds.

PubMed

Reynolds, Joseph; Coles, Mark; Lythe, Grant; Molina-París, Carmen

2013-01-01

We develop a mathematical model of the peripheral naive T cell population to study the change in human naive T cell numbers from birth to adulthood, incorporating thymic output and the availability of interleukin-7 (IL-7). The model is formulated as three ordinary differential equations: two describe T cell numbers, in a resting state and progressing through the cell cycle. The third is introduced to describe changes in IL-7 availability. Thymic output is a decreasing function of time, representative of the thymic atrophy observed in aging humans. Each T cell is assumed to possess two interleukin-7 receptor (IL-7R) signaling thresholds: a survival threshold and a second, higher, proliferation threshold. If the IL-7R signaling strength is below its survival threshold, a cell may undergo apoptosis. When the signaling strength is above the survival threshold, but below the proliferation threshold, the cell survives but does not divide. Signaling strength above the proliferation threshold enables entry into cell cycle. Assuming that individual cell thresholds are log-normally distributed, we derive population-average rates for apoptosis and entry into cell cycle. We have analyzed the adiabatic change in homeostasis as thymic output decreases. With a parameter set representative of a healthy individual, the model predicts a unique equilibrium number of T cells. In a parameter range representative of persistent viral or bacterial infection, where naive T cell cycle progression is impaired, a decrease in thymic output may result in the collapse of the naive T cell repertoire.

Amiodarone affects Ebola virus binding and entry into target cells.

PubMed

Salata, Cristiano; Munegato, Denis; Martelli, Francesco; Parolin, Cristina; Calistri, Arianna; Baritussio, Aldo; Palù, Giorgio

2018-03-02

Ebola Virus Disease is one of the most lethal transmissible infections characterized by a high fatality rate. Several research studies have aimed to identify effective antiviral agents. Amiodarone, a drug used for the treatment of arrhythmias, has been shown to inhibit filovirus infection in vitro by acting at the early step of the viral replication cycle. Here we demonstrate that amiodarone reduces virus binding to target cells and slows down the progression of the viral particles along the endocytic pathway. Overall our data support the notion that amiodarone interferes with Ebola virus infection by affecting cellular pathways/targets involved in the viral entry process.

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed

Nain, Minu; Mukherjee, Sriparna; Karmakar, Sonali Porey; Paton, Adrienne W; Paton, James C; Abdin, M Z; Basu, Anirban; Kalia, Manjula; Vrati, Sudhanshu

2017-03-15

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target. IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric population with a high mortality rate. This study is focused on identification of crucial host factors that could be targeted to cripple virus infection and ultimately lead to development of effective antivirals. We have identified a cellular protein, GRP78, that plays a dual role in virus entry and virus replication, two crucial steps of the virus life cycle, and thus is a novel host factor that could be a potential therapeutic target. Copyright © 2017 American Society for Microbiology.

Measles Virus Enters Breast and Colon Cancer Cell Lines through a PVRL4-Mediated Macropinocytosis Pathway

PubMed Central

Delpeut, Sebastien; Sisson, Gary; Black, Karen M.

2017-01-01

ABSTRACT Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease but has emerged as a promising oncolytic platform. Previous studies of MeV entry focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express the MeV receptors SLAM (signaling lymphocyte-activating molecule) and PVRL4 (poliovirus receptor-like 4) (nectin-4). Recombinant MeVs expressing either firefly luciferase or green fluorescent protein together with a variety of inhibitors were used. The results showed that MeV uptake was dynamin independent in the Vero.hPVRL4, Vero.hSLAM, and PVRL4-positive MCF7 breast cancer cell lines. However, MeV infection was blocked by 5-(N-ethyl-N-propyl)amiloride (EIPA), the hallmark inhibitor of macropinocytosis, as well as inhibitors of actin polymerization. By using phalloidin staining, MeV entry was shown to induce actin rearrangements and the formation of membrane ruffles accompanied by transient elevated fluid uptake. Small interfering RNA (siRNA) knockdown of p21-activated kinase 1 (PAK1) demonstrated that MeV enters both Vero.hPVRL4 and Vero.hSLAM cells in a PAK1-independent manner using a macropinocytosis-like pathway. In contrast, MeV entry into MCF7 human breast cancer cells relied upon Rac1 and its effector PAK1 through a PVRL4-mediated macropinocytosis pathway. MeV entry into DLD-1 colon and HTB-20 breast cancer cells also appeared to use the same pathway. Overall, these findings provide new insight into the life cycle of MeV, which could lead to therapies that block virus entry or methods that improve the uptake of MeV by cancer cells during oncolytic therapy. IMPORTANCE In the past decades, measles virus (MeV) has emerged as a promising oncolytic platform. Previous studies concerning MeV entry focused mainly on the identification of putative receptors for MeV. Nectin-4 (PVRL4) was recently identified as the epithelial cell receptor for MeV. However, the specific endocytic and trafficking pathways utilized during MeV infections are poorly documented. In this study, we demonstrated that MeV enters host cells via a dynamin-independent and actin-dependent endocytic pathway. Moreover, we show that MeV gains entry into MCF7, DLD-1, and HTB-20 cancer cells through a PVRL4-mediated macropinocytosis pathway and identified the typical cellular GTPase and kinase involved. Our findings provide new insight into the life cycle of MeV, which may lead to the development of therapies that block the entry of the virus into the host cell or alternatively promote the uptake of oncolytic MeV into cancer cells. PMID:28250131

Hood entry coefficients of compound exhaust hoods.

PubMed

Figueroa, Crescente E

2011-12-01

A traditional method for assessing the flow rate in ventilation systems is based on multiple readings of velocity or velocity pressure (VP) (usually 10 or 20 points) taken in ductwork sections located away from fittings (> seven × diameters of straight duct). This study seeks to eliminate the need for a multiple-point evaluation and replace it with a simplified method that requires only a single measurement of hood static pressure (SP(h)) taken at a more accessible location (< three × diameters of straight duct from the hood entry). The SP(h) method is widely used for the assessment of flow rate in simple hoods. However, industrial applications quite often use compound hoods that are regularly of the slot/plenum type. For these hoods, a "compound coefficient of entry" has not been published, which makes the use of the hood static pressure method unfeasible. This study proposes a model for the computation of a "compound coefficient of entry" and validates the use of this model to assess flow rate in two systems of well-defined geometry (multi-slotted/plenum and single-slotted/tapered or "fish-tail" types). When using a conservative value of the slot loss factor (1.78), the proposed model yielded an estimate of the volumetric flow rate within 10% of that provided by a more comprehensive method of assessment. The simplicity of the hood static pressure method makes it very desirable, even in the upper range of experimental error found in this study.

Lifting Entry & Atmospheric Flight (LEAF) System Concept Applications at Solar System Bodies With an Atmosphere

NASA Astrophysics Data System (ADS)

Lee, Greg; Polidan, Ronald; Ross, Floyd; Sokol, Daniel; Warwick, Steve

2015-11-01

Northrop Grumman and L’Garde have continued the development of a hypersonic entry, semi-buoyant, maneuverable platform capable of performing long-duration (months to a year) in situ and remote measurements at any solar system body that possesses an atmosphere.The Lifting Entry & Atmospheric Flight (LEAF) family of vehicles achieves this capability by using a semi-buoyant, ultra-low ballistic coefficient vehicle whose lifting entry allows it to enter the atmosphere without an aeroshell. The mass savings realized by eliminating the heavy aeroshell allows significantly more payload to be accommodated by the platform for additional science collection and return.In this presentation, we discuss the application of the LEAF system at various solar system bodies: Venus, Titan, Mars, and Earth. We present the key differences in platform design as well as operational differences required by the various target environments. The Venus implementation includes propulsive capability to reach higher altitudes during the day and achieves full buoyancy in the mid-cloud layer of Venus’ atmosphere at night.Titan also offers an attractive operating environment, allowing LEAF designs that can target low or medium altitude operations, also with propulsive capabilities to roam within each altitude regime. The Mars version is a glider that descends gradually, allowing targeted delivery of payloads to the surface or high resolution surface imaging. Finally, an Earth version could remain in orbit in a stowed state until activated, allowing rapid response type deployments to any region of the globe.

Linear model analysis of the influencing factors of boar longevity in Southern China.

PubMed

Wang, Chao; Li, Jia-Lian; Wei, Hong-Kui; Zhou, Yuan-Fei; Jiang, Si-Wen; Peng, Jian

2017-04-15

This study aimed to investigate the factors influencing the boar herd life month (BHLM) in Southern China. A total of 1630 records of culling boars from nine artificial insemination centers were collected from January 2013 to May 2016. A logistic regression model and two linear models were used to analyze the effects of breed, housing type, age at herd entry, and seed stock herd on boar removal reason and BHLM, respectively. Boar breed and the age at herd entry had significant effects on the removal reasons (P < 0.001). Results of the two linear models (with or without removal reason including) showed boars raised individually in stalls exhibited shorter BHLM than those raised in pens (P < 0.001). Boars aged 5 and 6 months at herd entry (44.6%) showed shorter BHLM than those aged 8 and 9 months at herd entry (P < 0.05). Approximately 95% boars were culled for different reasons other than old age, and the BHLM of these boars was at least 12.3 months longer than that of boars culled for other reasons (P < 0.001). In conclusion, abnormal elimination in boars is serious and it had a negative effect on boar BHLM. Boar removal reason and BHLM can be affected by breed, housing type, and seed stock herd. Importantly, 8 months is suggested as the most suitable age for boar introduction. Copyright © 2017. Published by Elsevier Inc.

Facilitating treatment entry among out-of-treatment injection drug users.

PubMed Central

Booth, R E; Kwiatkowski, C; Iguchi, M Y; Pinto, F; John, D

1998-01-01

OBJECTIVE: High risk injection practices are common among injecting drug users (IDUs), even following intervention efforts. Moreover, relapse to risk behaviors has been reported among those who initiate risk reduction. Substance abuse treatment offers the potential to reduce or eliminate injecting risk behaviors through drug cessation. We report on the effectiveness of two intervention strategies in facilitating treatment entry among out-of-treatment IDUs: motivational interviewing (MI), and intervention developed to help individuals resolve their ambivalence about behavior change, and free treatment for 90 days. These conditions were compared with an intervention focusing on a hierarchy of safer injecting practice, referred to here as risk reduction (RR), and no free treatment. METHODS: Nearly 200 out-of-treatment IDUs were randomly assigned to one of four experimental conditions: MI/free treatment, MI/no free treatment, RR/free treatment, and RR/no free treatment. Regardless of assignment, we assisted anyone desiring treatment by calling to schedule the appointment, providing transportation, and waiving the intake fee. RESULTS: Overall, 42% of study participants entered treatment. No significant differences were found between MI and RR; however, 52% of those assigned free treatment entered compare with 32% for those who had to pay. Other predictors of treatment entry included prior treatment experiences, perceived chance of contracting acquired immunodeficiency syndrome (AIDS) greater than 50%, "determination" stage of change, greater frequency of heroin injecting, and fewer drug-using friends. CONCLUSIONS: These findings support the importance of removing barriers to treatment entry. PMID:9722817

Inhibition of Dengue Virus Entry into Target Cells Using Synthetic Antiviral Peptides

PubMed Central

Alhoot, Mohammed Abdelfatah; Rathinam, Alwin Kumar; Wang, Seok Mui; Manikam, Rishya; Sekaran, Shamala Devi

2013-01-01

Despite the importance of DENV as a human pathogen, there is no specific treatment or protective vaccine. Successful entry into the host cells is necessary for establishing the infection. Recently, the virus entry step has become an attractive therapeutic strategy because it represents a barrier to suppress the onset of the infection. Four putative antiviral peptides were designed to target domain III of DENV-2 E protein using BioMoDroid algorithm. Two peptides showed significant inhibition of DENV when simultaneously incubated as shown by plaque formation assay, RT-qPCR, and Western blot analysis. Both DET4 and DET2 showed significant inhibition of virus entry (84.6% and 40.6% respectively) using micromolar concentrations. Furthermore, the TEM images showed that the inhibitory peptides caused structural abnormalities and alteration of the arrangement of the viral E protein, which interferes with virus binding and entry. Inhibition of DENV entry during the initial stages of infection can potentially reduce the viremia in infected humans resulting in prevention of the progression of dengue fever to the severe life-threatening infection, reduce the infected vector numbers, and thus break the transmission cycle. Moreover these peptides though designed against the conserved region in DENV-2 would have the potential to be active against all the serotypes of dengue and might be considered as Hits to begin designing and developing of more potent analogous peptides that could constitute as promising therapeutic agents for attenuating dengue infection. PMID:23630436

Acute amiodarone promotes drift and early termination of spiral wave re-entry.

PubMed

Nakagawa, Harumichi; Honjo, Haruo; Ishiguro, Yuko S; Yamazaki, Masatoshi; Okuno, Yusuke; Harada, Masahide; Takanari, Hiroki; Sakuma, Ichiro; Kamiya, Kaichiro; Kodama, Itsuo

2010-07-01

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 microM) caused prolongation of action potential duration (APD) by 5.6%-9.1%, whereas lidocaine (15 microM) caused APD shortening by 5.0%-6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.

Multi-modal assessment of on-road demand of voice and manual phone calling and voice navigation entry across two embedded vehicle systems.

PubMed

Mehler, Bruce; Kidd, David; Reimer, Bryan; Reagan, Ian; Dobres, Jonathan; McCartt, Anne

2016-03-01

One purpose of integrating voice interfaces into embedded vehicle systems is to reduce drivers' visual and manual distractions with 'infotainment' technologies. However, there is scant research on actual benefits in production vehicles or how different interface designs affect attentional demands. Driving performance, visual engagement, and indices of workload (heart rate, skin conductance, subjective ratings) were assessed in 80 drivers randomly assigned to drive a 2013 Chevrolet Equinox or Volvo XC60. The Chevrolet MyLink system allowed completing tasks with one voice command, while the Volvo Sensus required multiple commands to navigate the menu structure. When calling a phone contact, both voice systems reduced visual demand relative to the visual-manual interfaces, with reductions for drivers in the Equinox being greater. The Equinox 'one-shot' voice command showed advantages during contact calling but had significantly higher error rates than Sensus during destination address entry. For both secondary tasks, neither voice interface entirely eliminated visual demand. Practitioner Summary: The findings reinforce the observation that most, if not all, automotive auditory-vocal interfaces are multi-modal interfaces in which the full range of potential demands (auditory, vocal, visual, manipulative, cognitive, tactile, etc.) need to be considered in developing optimal implementations and evaluating drivers' interaction with the systems. Social Media: In-vehicle voice-interfaces can reduce visual demand but do not eliminate it and all types of demand need to be taken into account in a comprehensive evaluation.

Descriptive analysis and spatial epidemiology of porcine reproductive and respiratory syndrome (PRRS) for swine sites participating in area regional control and elimination programs from 3 regions of Ontario

PubMed Central

Arruda, Andreia G.; Poljak, Zvonimir; Friendship, Robert; Carpenter, Jane; Hand, Karen

2015-01-01

The objectives of this study were to describe demographics, basic biosecurity practices, ownership structure, and prevalence of porcine reproductive and respiratory syndrome (PRRS) in swine sites located in 3 regions in Ontario, and investigate the presence of spatial clustering and clusters of PRRS positive sites in the 3 regions. A total of 370 swine sites were enrolled in Area Regional Control and Elimination projects in Niagara, Watford, and Perth from 2010 to 2013. Demographics, biosecurity, and site ownership data were collected using a standardized questionnaire and site locations were obtained from an industry organization. Status was assigned on the basis of available diagnostic tests and/or assessment by site veterinarians. Spatial dependence was investigated using the D-function, the spatial scan statistic test and the spatial relative risk method. Results showed that the use of strict all-in all-out (AIAO) pig flow and shower before entry are uncommon biosecurity practices in swine sites, but a larger proportion of sites reported having a Danish entry. The prevalence of PRRS in the 3 regions ranged from 17% to 48% and localized high and low risk clusters were detected. Sites enrolled in the PRRS control projects were characterized by membership in multiple and overlapping ownership structures and networks, which complicates the way the results of monitoring and disease management measures are communicated to the target population. PMID:26424906

Multi-modal assessment of on-road demand of voice and manual phone calling and voice navigation entry across two embedded vehicle systems

PubMed Central

Mehler, Bruce; Kidd, David; Reimer, Bryan; Reagan, Ian; Dobres, Jonathan; McCartt, Anne

2016-01-01

Abstract One purpose of integrating voice interfaces into embedded vehicle systems is to reduce drivers’ visual and manual distractions with ‘infotainment’ technologies. However, there is scant research on actual benefits in production vehicles or how different interface designs affect attentional demands. Driving performance, visual engagement, and indices of workload (heart rate, skin conductance, subjective ratings) were assessed in 80 drivers randomly assigned to drive a 2013 Chevrolet Equinox or Volvo XC60. The Chevrolet MyLink system allowed completing tasks with one voice command, while the Volvo Sensus required multiple commands to navigate the menu structure. When calling a phone contact, both voice systems reduced visual demand relative to the visual–manual interfaces, with reductions for drivers in the Equinox being greater. The Equinox ‘one-shot’ voice command showed advantages during contact calling but had significantly higher error rates than Sensus during destination address entry. For both secondary tasks, neither voice interface entirely eliminated visual demand. Practitioner Summary: The findings reinforce the observation that most, if not all, automotive auditory–vocal interfaces are multi-modal interfaces in which the full range of potential demands (auditory, vocal, visual, manipulative, cognitive, tactile, etc.) need to be considered in developing optimal implementations and evaluating drivers’ interaction with the systems. Social Media: In-vehicle voice-interfaces can reduce visual demand but do not eliminate it and all types of demand need to be taken into account in a comprehensive evaluation. PMID:26269281

Overview of entry risk predictions

NASA Astrophysics Data System (ADS)

Mrozinski, R.; Mendeck, G.; Cutri-Kohart, R.

Risk to people on the ground from uncontrolled entries of spacecraft is a primary concern when analyzing end-of-life disposal options for satellites. Countries must balance this risk with the need to mitigate an exponentially growing space debris population. Currently the United States does this via guidelines that call for a satellite to be disposed of in a controlled manner if an uncontrolled entry would be too risky to people on the ground. This risk is measured by a quantity called "casualty expectation", or E , where casualty expectation is defined as the expectedc number of people suffering death or injury due to a spacecraft entry event. If Ec exceeds 1 in 10,000, U. S. guidelines state that the entry should be controlled rather than uncontrolled. Since this guideline can have serious impacts on the cost, lifetime, and even the mission and functionality of a satellite, it is critical that this quantity be estimated well, and decision makers understand all assumptions and limitations inherent in the resulting value. This paper discusses several issues regarding estimates of casualty expectation, beginning with an overview of relevant United States policies and guidelines. The equation the space industry typically uses to estimate casualty expectation is presented, along with a look at the sensitivity of the results to the typical assumptions, models, and initial condition uncertainties. Differences in these modeling issues with respect to launch failure Ec estimates are included in the discussion. An alternate quantity to assess risks due to spacecraft entries is introduced. "Probability of casualty", or Pc , is defined as the probability of one or more instances of people suffering death or injury due to a spacecraft entry event. The equation to estimate Pc is derived, where the same assumptions, modeling, and initial condition issues for Ec apply. Several examples are then given of both Ec and Pc estimate calculations. Due to the difficult issues in estimating both Ec and Pc, it is argued that "true" absolute quantities can never be computed. However, E and Pc are ideal for relativec analyses against a standard tool that eliminates these issues. Such a tool is recommended for assessing compliance with requirements of regulating institutions.

Current State of Military Hybrid Vehicle Development

DTIC Science & Technology

2011-08-31

Integrated starter generator for engine shut down, regenerative braking and avoidance of inefficient engine operation [28]. FMTV VI Composite 6-9% Fuel...and eliminating the inefficiencies associated with idling, vehicle braking and low engine speed part load efficiency, many improvements could be...different drive cycles were being used to evaluate vehicle performance. These cycles can be divided into the following two categories : (1) Time

Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

DTIC Science & Technology

2016-05-27

the start-stop-start-stop cycle over a stretched period of time and that’s a big cost impact . But the challenge is by the same token, the build cycle...well as trying to balance the impacts on geographic locations. Q: What will happen to the aircraft from the eliminated squadrons? A: Where applicable

Navy Ford (CVN 78) Class Aircraft Carrier Program: Background and Issues for Congress

DTIC Science & Technology

2016-05-27

the start-stop-start-stop cycle over a stretched period of time and that’s a big cost impact . But the challenge is by the same token, the build cycle...well as trying to balance the impacts on geographic locations. Q: What will happen to the aircraft from the eliminated squadrons? A: Where applicable

Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes.

PubMed

Yang, Bing-Bing; Savin, Michael A; Green, Michael

2012-01-01

Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim. Copyright © 2012 S. Karger AG, Basel.

Bonding core mating surfaces improves transformer

NASA Technical Reports Server (NTRS)

Mclyman, W. T.

1978-01-01

Modifications to assembly procedures for C-core transformers virtually eliminates changes in core end gaps due to temperature cycling during impregnation and potting stages, thus stabilizing magnetization properties of core.

Apparatus and Method for Elimination of Polarization-Induced Fading in Fiber-optic Sensor System

NASA Technical Reports Server (NTRS)

Chan, Hon Man (Inventor); Parker, Jr., Allen R. (Inventor)

2015-01-01

The invention is an apparatus and method of eliminating polarization-induced fading in interferometric fiber-optic sensor system having a wavelength-swept laser optical signal. The interferometric return signal from the sensor arms are combined and provided to a multi-optical path detector assembly and ultimately to a data acquisition and processing unit by way of a switch that is time synchronized with the laser scan sweep cycle.

E-wave generated intraventricular diastolic vortex to L-wave relation: model-based prediction with in vivo validation.

PubMed

Ghosh, Erina; Caruthers, Shelton D; Kovács, Sándor J

2014-08-01

The Doppler echocardiographic E-wave is generated when the left ventricle's suction pump attribute initiates transmitral flow. In some subjects E-waves are accompanied by L-waves, the occurrence of which has been correlated with diastolic dysfunction. The mechanisms for L-wave generation have not been fully elucidated. We propose that the recirculating diastolic intraventricular vortex ring generates L-waves and based on this mechanism, we predict the presence of L-waves in the right ventricle (RV). We imaged intraventricular flow using Doppler echocardiography and phase-contrast magnetic resonance imaging (PC-MRI) in 10 healthy volunteers. L-waves were recorded in all subjects, with highest velocities measured typically 2 cm below the annulus. Fifty-five percent of cardiac cycles (189 of 345) had L-waves. Color M-mode images eliminated mid-diastolic transmitral flow as the cause of the observed L-waves. Three-dimensional intraventricular flow patterns were imaged via PC-MRI and independently validated our hypothesis. Additionally as predicted, L-waves were observed in the RV, by both echocardiography and PC-MRI. The re-entry of the E-wave-generated vortex ring flow through a suitably located echo sample volume can be imaged as the L-wave. These waves are a general feature and a direct consequence of LV and RV diastolic fluid mechanics. Copyright © 2014 the American Physiological Society.

Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

PubMed

Matsuhara, Hirotada; Yamamoto, Ayumu

2016-01-01

Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Cloud Computing with iPlant Atmosphere.

PubMed

McKay, Sheldon J; Skidmore, Edwin J; LaRose, Christopher J; Mercer, Andre W; Noutsos, Christos

2013-10-15

Cloud Computing refers to distributed computing platforms that use virtualization software to provide easy access to physical computing infrastructure and data storage, typically administered through a Web interface. Cloud-based computing provides access to powerful servers, with specific software and virtual hardware configurations, while eliminating the initial capital cost of expensive computers and reducing the ongoing operating costs of system administration, maintenance contracts, power consumption, and cooling. This eliminates a significant barrier to entry into bioinformatics and high-performance computing for many researchers. This is especially true of free or modestly priced cloud computing services. The iPlant Collaborative offers a free cloud computing service, Atmosphere, which allows users to easily create and use instances on virtual servers preconfigured for their analytical needs. Atmosphere is a self-service, on-demand platform for scientific computing. This unit demonstrates how to set up, access and use cloud computing in Atmosphere. Copyright © 2013 John Wiley & Sons, Inc.

Re-entry simulation chamber for thermo-mechanical characterisation of space materials

NASA Astrophysics Data System (ADS)

Liedtke, Volker

2003-09-01

During re-entry, materials and components are subject to very high thermal and mechanical loads. Any failure may cause loss of mission. Therefore, materials and components have to be tested under most rigid conditions to verify the suitability of the material and to verify the design of the components. The Re-Entry Simulation Chamber (RESiC) at ARC Seibersdorf research (ARCS) allows simulating the high thermal loads as well as complex mechanical load profiles that may occur during a re-entry; additionally, the influence of chemical reactions of materials with gaseous components of the atmosphere can be studied. The high vacuum chamber (better than 1×10-6 mbar) has a diameter of 650 mm and allows a sample height of 500 mm, or 1000 mm with extension flange. The gas dosing system is designed to emulate the increasing atmospheric pressure during the re-entry trajectory of a vehicle. Heating is performed by a 30 kW induction generator that allows a sufficiently rapid heating of larger components; electrically conductive materials such as metals or carbon fibre reinforced ceramics are directly heated, while for electrical insulators, susceptor plates or tubes will be employed. The uniaxial servo-hydraulic testing machine has a maximum load of 70 kN, either static or with a frequency of up to 70 Hz, with any given load profile (sinus, rectangular, triangular, ...). Strain measurements will be done by non-contacting laser speckle system for maximum flexibility and minimum instrumentation time effort (currently under application testing), or by strain gauges. All relevant process parameters are controlled and recorded by microcomputer. The highly sophisticated control software allows a convenient and reliable multi-channel data acquisition, e.g. temperatures at various positions of the test piece, pressure, loads, strains, and any other test data according to customer specifications; the data format is suitable for any further data processing. During the set-up and operation testing, the device has successfully been employed for thermal shock testing, thermal cycling and gas cycling tests, thermomechanical tests and combinations thereof, e.g. sintering or hot-pressing. During the current final test series, the device will be completed, further optimised and shall be fully operational in summer 2003.

X-33 Attitude Control System Design for Ascent, Transition, and Entry Flight Regimes

NASA Technical Reports Server (NTRS)

Hall, Charles E.; Gallaher, Michael W.; Hendrix, Neal D.

1998-01-01

The Vehicle Control Systems Team at Marshall Space Flight Center, Systems Dynamics Laboratory, Guidance and Control Systems Division is designing under a cooperative agreement with Lockheed Martin Skunkworks, the Ascent, Transition, and Entry flight attitude control system for the X-33 experimental vehicle. Ascent flight control begins at liftoff and ends at linear aerospike main engine cutoff (NECO) while Transition and Entry flight control begins at MECO and concludes at the terminal area energy management (TAEM) interface. TAEM occurs at approximately Mach 3.0. This task includes not only the design of the vehicle attitude control systems but also the development of requirements for attitude control system components and subsystems. The X-33 attitude control system design is challenged by a short design cycle, the design environment (Mach 0 to about Mach 15), and the X-33 incremental test philosophy. The X-33 design-to-launch cycle of less than 3 years requires a concurrent design approach while the test philosophy requires design adaptation to vehicle variations that are a function of Mach number and mission profile. The flight attitude control system must deal with the mixing of aerosurfaces, reaction control thrusters, and linear aerospike engine control effectors and handle parasitic effects such as vehicle flexibility and propellant sloshing from the uniquely shaped propellant tanks. The attitude control system design is, as usual, closely linked to many other subsystems and must deal with constraints and requirements from these subsystems.

Kinetics of Neuraminidase Action on Glycoproteins by One- and Two-Dimensional NMR

ERIC Educational Resources Information Center

Barb, Adam W.; Glushka, John N.; Prestegard, James H.

2011-01-01

The surfaces of mammalian cells are coated with complex carbohydrates, many terminated with a negatively charged "N"-acetylneuraminic acid residue. This motif is specifically targeted by pathogens, including influenza viruses and many pathogenic bacteria, to gain entry into the cell. A necessary step in the influenza virus life cycle is the…

Molecular mechanisms involved in the early steps of flavivirus cell entry.

PubMed

Kaufmann, Bärbel; Rossmann, Michael G

2011-01-01

Flaviviruses enter their host cells by receptor-mediated endocytosis, a well-orchestrated process of receptor recognition, penetration and uncoating. Recent findings on these early steps in the life cycle of flaviviruses are the focus of this review. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

STS-1 operational flight profile. Volume 5: Descent, cycle 3

NASA Technical Reports Server (NTRS)

Moore, R.; Baker, A.; Hite, R.; Hochstein, A.; Lyons, J.; Strong, K.

1980-01-01

The trajectory data presented are to be used for orbiter systems and subsystems evalation, flight and mission control center software verification, flight techniques and timeline development, crew training, and evaluation of operational mission suitability. The entry profile is very similar to cycle 2, however, elevon and body flap temperature margins have increased and the elevon schedule was changed. The terminal area energy management (TAEM) profile was completely reshaped to conform with new angle of attack constraints and left hand turn around the heading alignment cylinder. Also, the entry/TAEM interface was adjusted to minimize guidance induced angle of attack transients across the interface. The approach and landing phase was reshaped for a 20 deg glideslope and reduced velocity at touchdown. The definition of the runway threshold was standardized for all landing sites. This results in a shift at Edwards Air Force Base in aim points and touchdown relative to the threshold of 1000 feet. The rollout remains essentially unchanged with the exception of the speedbrake, which is now deployed to 50 percent at touchdown.

mTOR and Neuronal Cell Cycle Re-entry: How Impaired Brain Insulin Signaling Promotes Alzheimer's Disease

PubMed Central

Norambuena, Andrés; Wallrabe, Horst; McMahon, Lloyd; Silva, Antonia; Swanson, Eric; Khan, Shahzad S.; Baerthlein, Daniel; Kodis, Erin; Oddo, Salvatore; Mandell, James W.; Bloom, George S.

2016-01-01

A major obstacle to pre-symptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle re-entry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death. PMID:27693185

Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy.

PubMed

Cabezas-Wallscheid, Nina; Buettner, Florian; Sommerkamp, Pia; Klimmeck, Daniel; Ladel, Luisa; Thalheimer, Frederic B; Pastor-Flores, Daniel; Roma, Leticia P; Renders, Simon; Zeisberger, Petra; Przybylla, Adriana; Schönberger, Katharina; Scognamiglio, Roberta; Altamura, Sandro; Florian, Carolina M; Fawaz, Malak; Vonficht, Dominik; Tesio, Melania; Collier, Paul; Pavlinic, Dinko; Geiger, Hartmut; Schroeder, Timm; Benes, Vladimir; Dick, Tobias P; Rieger, Michael A; Stegle, Oliver; Trumpp, Andreas

2017-05-18

Dormant hematopoietic stem cells (dHSCs) are atop the hematopoietic hierarchy. The molecular identity of dHSCs and the mechanisms regulating their maintenance or exit from dormancy remain uncertain. Here, we use single-cell RNA sequencing (RNA-seq) analysis to show that the transition from dormancy toward cell-cycle entry is a continuous developmental path associated with upregulation of biosynthetic processes rather than a stepwise progression. In addition, low Myc levels and high expression of a retinoic acid program are characteristic for dHSCs. To follow the behavior of dHSCs in situ, a Gprc5c-controlled reporter mouse was established. Treatment with all-trans retinoic acid antagonizes stress-induced activation of dHSCs by restricting protein translation and levels of reactive oxygen species (ROS) and Myc. Mice maintained on a vitamin A-free diet lose HSCs and show a disrupted re-entry into dormancy after exposure to inflammatory stress stimuli. Our results highlight the impact of dietary vitamin A on the regulation of cell-cycle-mediated stem cell plasticity. VIDEO ABSTRACT. Copyright © 2017. Published by Elsevier Inc.

Selecting Cells for Bioartificial Liver Devices and the Importance of a 3D Culture Environment: A Functional Comparison between the HepaRG and C3A Cell Lines.

PubMed

van Wenum, Martien; Adam, Aziza A A; Hakvoort, Theodorus B M; Hendriks, Erik J; Shevchenko, Valery; van Gulik, Thomas M; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

2016-01-01

Recently, the first clinical trials on Bioartificial Livers (BALs) loaded with a proliferative human hepatocyte cell source have started. There are two cell lines that are currently in an advanced state of BAL development; HepaRG and HepG2/C3A. In this study we aimed to compare both cell lines on applicability in BALs and to identify possible strategies for further improvement. We tested both cell lines in monolayer- and BAL cultures on growth characteristics, hepatic differentiation, nitrogen-, carbohydrate-, amino acid- and xenobiotic metabolism. Interestingly, both cell lines adapted the hepatocyte phenotype more closely when cultured in BALs; e.g. monolayer cultures produced lactate, while BAL cultures showed diminished lactate production (C3A) or conversion to elimination (HepaRG), and urea cycle activity increased upon BAL culturing in both cell lines. HepaRG-BALs outperformed C3A-BALs on xenobiotic metabolism, ammonia elimination and lactate elimination, while protein synthesis was comparable. In BAL cultures of both cell lines ammonia elimination correlated positively with glutamine production and glutamate consumption, suggesting ammonia elimination was mainly driven by the balance between glutaminase and glutamine synthetase activity. Both cell lines lacked significant urea cycle activity and both required multiple culture weeks before reaching optimal differentiation in BALs. In conclusion, culturing in BALs enhanced hepatic functionality of both cell lines and from these, the HepaRG cells are the most promising proliferative cell source for BAL application.

Life Cycle Costing: A Working Level Approach

DTIC Science & Technology

1981-06-01

Effects Analysis ( FMEA ) ...... ................ .. 59 Logistics Performance Factors (LPFs) 60 Planning the Use of Life Cycle Cost in the Demonstration...form. Failure Mode and Effects Analysis ( FMEA ). Description. FMEA is a technique that attempts to improve the design of any particular unit. The FMEA ...failure modes and also eliminate extra parts or ones that are used to achieve more performance than is necessary (16:5-14]. Advantages. FMEA forces

Ubiquitin in Influenza Virus Entry and Innate Immunity.

PubMed

Rudnicka, Alina; Yamauchi, Yohei

2016-10-24

Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating. We also discuss the roles of ubiquitin in innate immunity and its implications in the IAV life cycle.

Ubiquitin in Influenza Virus Entry and Innate Immunity

PubMed Central

Rudnicka, Alina; Yamauchi, Yohei

2016-01-01

Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating. We also discuss the roles of ubiquitin in innate immunity and its implications in the IAV life cycle. PMID:27783058

Bipolar Ag-Zn battery

NASA Astrophysics Data System (ADS)

Giltner, L. John

1994-02-01

The silver-zinc (AgZn) battery system has been unique in its ability to safely satisfy high power demand applications with low mass and volume. However, a new generation of defense, aerospace, and commercial applications will impose even higher power demands. These new power demands can be satisfied by the development of a bipolar battery design. In this configuration the power consuming, interelectrode current conductors are eliminated while the current is then conducted via the large cross-section electrode substrate. Negative and positive active materials are applied to opposite sides of a solid silver foil substrate. In addition to reducing the weight and volume required for a specified power level, the output voltage performance is also improved as follows. Reduced weight through: elimination of the plastic cell container; elimination of plate leads and intercell connector; and elimination of internal plate current collector. Increased voltage through: elimination of resistance of current collector; elimination of resistance of plate lead; and elimination of resistance of intercell connector. EPI worked previously on development of a secondary bipolar silver zinc battery. This development demonstrated the electrical capability of the system and manufacturing techniques. One difficulty with this development was mechanical problems with the seals. However, recent improvements in plastics and adhesives should eliminate the major problem of maintaining a seal around the periphery of the bipolar module. The seal problem is not as significant for a primary battery application or for a requirement for only a few discharge cycles. A second difficulty encountered was with activation (introducing electrolyte into the cell) and with venting gas from the cell without loss of electrolyte. During previous work, the following projections for energy density were made from test data for a high power system which demonstrated in excess of 50 discharge/charge cycles. Projected system power = 100 kilowatts; discharge time = 30 seconds; discharge current density = 1.75 amps/sq in.; system weight = 86 lbs (9.7 WH/lb); and system volume = 1071 cu. in. (.78 WH/cu. in.). EPI is currently working on a development program to produce a bipolar silver-zinc battery design for NASA. The potential application would be to power electromechanical actuators for space launch vehicles.

Bipolar Ag-Zn battery

NASA Technical Reports Server (NTRS)

Giltner, L. John

1994-01-01

The silver-zinc (AgZn) battery system has been unique in its ability to safely satisfy high power demand applications with low mass and volume. However, a new generation of defense, aerospace, and commercial applications will impose even higher power demands. These new power demands can be satisfied by the development of a bipolar battery design. In this configuration the power consuming, interelectrode current conductors are eliminated while the current is then conducted via the large cross-section electrode substrate. Negative and positive active materials are applied to opposite sides of a solid silver foil substrate. In addition to reducing the weight and volume required for a specified power level, the output voltage performance is also improved as follows. Reduced weight through: elimination of the plastic cell container; elimination of plate leads and intercell connector; and elimination of internal plate current collector. Increased voltage through: elimination of resistance of current collector; elimination of resistance of plate lead; and elimination of resistance of intercell connector. EPI worked previously on development of a secondary bipolar silver zinc battery. This development demonstrated the electrical capability of the system and manufacturing techniques. One difficulty with this development was mechanical problems with the seals. However, recent improvements in plastics and adhesives should eliminate the major problem of maintaining a seal around the periphery of the bipolar module. The seal problem is not as significant for a primary battery application or for a requirement for only a few discharge cycles. A second difficulty encountered was with activation (introducing electrolyte into the cell) and with venting gas from the cell without loss of electrolyte. During previous work, the following projections for energy density were made from test data for a high power system which demonstrated in excess of 50 discharge/charge cycles. Projected system power = 100 kilowatts; discharge time = 30 seconds; discharge current density = 1.75 amps/sq in.; system weight = 86 lbs (9.7 WH/lb); and system volume = 1071 cu. in. (.78 WH/cu. in.). EPI is currently working on a development program to produce a bipolar silver-zinc battery design for NASA. The potential application would be to power electromechanical actuators for space launch vehicles.

Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression

PubMed Central

Ruijtenberg, Suzan; van den Heuvel, Sander

2016-01-01

ABSTRACT Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue-specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID:26825227

Image Data Compression Having Minimum Perceptual Error

NASA Technical Reports Server (NTRS)

Watson, Andrew B. (Inventor)

1997-01-01

A method is presented for performing color or grayscale image compression that eliminates redundant and invisible image components. The image compression uses a Discrete Cosine Transform (DCT) and each DCT coefficient yielded by the transform is quantized by an entry in a quantization matrix which determines the perceived image quality and the bit rate of the image being compressed. The quantization matrix comprises visual masking by luminance and contrast technique all resulting in a minimum perceptual error for any given bit rate, or minimum bit rate for a given perceptual error.

Regulation of store-operated Ca2+ entry activity by cell cycle dependent up-regulation of Orai2 in brain capillary endothelial cells.

PubMed

Kito, Hiroaki; Yamamura, Hisao; Suzuki, Yoshiaki; Yamamura, Hideto; Ohya, Susumu; Asai, Kiyofumi; Imaizumi, Yuji

2015-04-10

Store-operated Ca(2+) entry (SOCE) via Orai1 and STIM1 complex is supposed to have obligatory roles in the regulation of cellular functions of vascular endothelial cells, while little is known about the contribution of Orai2. Quantitative PCR and Western blot analyses indicated the expression of Orai2 and STIM2, in addition to Orai1 and STIM1 in bovine brain capillary endothelial cell line, t-BBEC117. During the exponential growth of t-BBEC117, the knockdown of Orai1 and STIM1 significantly reduced the SOCE activity, whereas Orai2 and STIM2 siRNAs had no effect. To examine whether endogenous SOCE activity contributes to the regulation of cell cycle progression, t-BBEC117 were synchronized using double thymidine blockage. At the G2/M phase, Ca(2+) influx via SOCE was decreased and Orai2 expression was increased compared to the G0/G1 phase. When Orai2 was knocked down at the G2/M phase, the decrease in SOCE was removed, and cell proliferation was partly attenuated. Taken together, Orai1 significantly contributes to cell proliferation via the functional expression, which is presumably independent of the cell cycle phases. In construct, Orai2 is specifically up-regulated during the G2/M phase, negatively modulates the SOCE activity, and may contribute to the regulation of cell cycle progression in brain capillary endothelial cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

PubMed Central

Londrigan, Sarah L.; Short, Kirsty R.; Ma, Joel; Gillespie, Leah; Rockman, Steven P.; Brooks, Andrew G.

2015-01-01

ABSTRACT Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. PMID:26423941

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.

PubMed

Londrigan, Sarah L; Short, Kirsty R; Ma, Joel; Gillespie, Leah; Rockman, Steven P; Brooks, Andrew G; Reading, Patrick C

2015-12-01

Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Influence of seasonal cycles in Martian atmosphere on entry, descent and landing sequence

NASA Astrophysics Data System (ADS)

Marčeta, Dušan; Šegan, Stevo; Rašuo, Boško

2014-05-01

The phenomena like high eccentricity of Martian orbit, obliquity of the orbital plane and close alignment of the winter solstice and the orbital perihelion, separately or together can significantly alter not only the level of some Martian atmospheric parameters but also the characteristics of its diurnal and seasonal cycle. Considering that entry, descent and landing (EDL) sequence is mainly driven by the density profile of the atmosphere and aerodynamic characteristic of the entry vehicle. We have performed the analysis of the influence of the seasonal cycles of the atmospheric parameters on EDL profiles by using Mars Global Reference Atmospheric Model (Mars-GRAM). Since the height of the deployment of the parachute and the time passed from the deployment to propulsion firing (descent time) are of crucial importance for safe landing and the achievable landing site elevation we paid special attention to the influence of the areocentric longitude of the Sun (Ls) on these variables. We have found that these variables have periodic variability with respect to Ls and can be very well approximated with a sine wave function whose mean value depends only on the landing site elevation while the amplitudes and phases depend only on the landing site latitude. The amplitudes exhibit behavior which is symmetric with respect to the latitude but the symmetry is shifted from the equator to the northern mid-tropics. We have also noticed that the strong temperature inversions which are usual for middle and higher northern latitudes while Mars is around its orbital perihelion significantly alter the descent time without influencing the height of the parachute deployment. At last, we applied our model to determine the dependence of the accessible landing region on Ls and found that this region reaches maximum when Mars is around the orbital perihelion and can vary 50° in latitude throughout the Martian year.

Microgravity can activate signals urging cells to S-phase entry during tissue and organ regeneration in Urodele amphibians exposed to real and simulated microgravity

NASA Astrophysics Data System (ADS)

Grigoryan, E.; Anton, H.-J.; Mitashov, V.

Regenerative response following local injury or tissue removal in urodele amphibians is dependent on cell cycle entry of cells sources for regeneration in the remaining tissue. In a number of our experiments performed aboard biosatellites in orbital flights and fast rotated clinostat we found enhanced proliferative activity and, as a result, regeneration quicker than that in controls. In each investigated case an activity of cell proliferation evaluated by 3H-thymidine radioautography and BrdU assay at the early stages of lens, retina, forelimb and tail regeneration in newts was about 1,2-1,7 fold higher both under conditions of real and physiological weightlessness as compared with controls. Faster S-phase entry under conditions of micro- g was demonstrated by cycling multipotent cells as well as by differentiated postmitotic cells both participated in regeneration. Important, that cycling cells outside areas of regeneration were also found as displayed faster cellular growth. In our papers (1,2,3,4) we offered some hypothesis that could explain mechanisms of low g stimulating effect upon cell growth in regeneration in Urodela. In particular, changes in expression of some growth factors and their receptors, as well as the synthesis of specific range of generalized stress proteins (AGSPs) were proposed. However, in fact, molecular mechanisms of micro- g effect upon cell proliferation are mediated by changes on organismic level induced by micro- g environment. Some of them which are able to trigger off signaling changes on the cellular level that, in turn, evoke cells to grow faster would be represented in our report. 1. Mitashov V. et al. Adv. Space Res. 1996. 17 (6/7): 241-255 2. Anton H.-J. et al. Adv. Space Res. 1996. 17 (6/7): 55-65 3. Grigoryan E. et al. Adv. Space Res. 1998. 22 (2): 293-301 4. Grigoryan E. et al. Adv. Space Res. 2002. 30 (4): 757-764

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

PubMed Central

Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G.; Zhang, Nianshu

2016-01-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding ‘signaling’ proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast. PMID:27923067

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases.

PubMed

Cao, Lu; Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G; Zhang, Nianshu

2016-12-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast.

Radiology reporting: a closed-loop cycle from order entry to results communication.

PubMed

Weiss, David L; Kim, Woojin; Branstetter, Barton F; Prevedello, Luciano M

2014-12-01

With the increasing prevalence of PACS over the past decade, face-to-face image review among health care providers has become a rarity. This change has resulted in increasing dependence on fast and accurate communication in radiology. Turnaround time expectations are now conveyed in minutes rather than hours or even days. Ideal modern radiology communication is a closed-loop cycle with multiple interoperable applications contributing to the final product. The cycle starts with physician order entry, now often performed through the electronic medical record, with clinical decision support to ensure that the most effective imaging study is ordered. Radiology reports are now almost all in electronic format. The majority are produced using speech recognition systems. Optimization of this software use can alleviate some, if not all, of the inherent user inefficiencies in this type of reporting. Integrated third-party software applications that provide data mining capability are extremely helpful in both academic and clinical settings. The closed-loop ends with automated communication of imaging results. Software products for this purpose should facilitate use of levels of alert, automated escalation to providers, and recording of audit trails of reports received. The multiple components of reporting should be completely interoperable with each other, as well as with the PACS, the RIS, and the electronic medical record. This integration will maximize radiologist efficiency and minimize the possibility of communication error. Copyright © 2014. Published by Elsevier Inc.

Mars Pathfinder Atmospheric Entry Navigation Operations

NASA Technical Reports Server (NTRS)

Braun, R. D.; Spencer, D. A.; Kallemeyn, P. H.; Vaughan, R. M.

1997-01-01

On July 4, 1997, after traveling close to 500 million km, the Pathfinder spacecraft successfully completed entry, descent, and landing, coming to rest on the surface of Mars just 27 km from its target point. In the present paper, the atmospheric entry and approach navigation activities required in support of this mission are discussed. In particular, the flight software parameter update and landing site prediction analyses performed by the Pathfinder operations navigation team are described. A suite of simulation tools developed during Pathfinder's design cycle, but extendible to Pathfinder operations, are also presented. Data regarding the accuracy of the primary parachute deployment algorithm is extracted from the Pathfinder flight data, demonstrating that this algorithm performed as predicted. The increased probability of mission success through the software parameter update process is discussed. This paper also demonstrates the importance of modeling atmospheric flight uncertainties in the estimation of an accurate landing site. With these atmospheric effects included, the final landed ellipse prediction differs from the post-flight determined landing site by less then 0.5 km in downtrack.

Progress in Payload Separation Risk Mitigation for a Deployable Venus Heat Shield

NASA Technical Reports Server (NTRS)

Smith, Brandon P.; Yount, Bryan C.; Venkatapathy, Ethiraj; Stern, Eric C.; Prabhu, Dinesh K.; Litton, Daniel K.

2013-01-01

A deployable decelerator known as the Adaptive Deployable Entry and Placement Technology (ADEPT) offers substantial science and mass savings for the Venus In Situ Explorer (VISE) mission. The lander and science payload must be separated from ADEPT during atmospheric entry. This paper presents a trade study of the separation system concept of operations and provides a conceptual design of the baseline: aft-separation with a subsonic parachute. Viability of the separation system depends on the vehicle's dynamic stability characteristics during deceleration from supersonic to subsonic speeds. A trajectory sensitivity study presented shows that pitch damping and Venusian winds drive stability prior to parachute deployment, while entry spin rate is not a driver of stability below Mach 5. Additionally, progress in free-flight CFD techniques capable of computing aerodynamic damping parameters is presented. Exploratory simulations of ADEPT at a constant speed of Mach number of 0.8 suggest the vehicle may have an oscillation limit cycle near 5 angle-of-attack. The proposed separation system conceptual design is thought to be viable.

Remote Imaging of Exploration Flight Test-1 (EFT-1) Entry Heating Risk Reduction

NASA Technical Reports Server (NTRS)

Schuster, David M.; Horvath, Thomas J.; Schwartz, Richard J.

2016-01-01

A Measure of Performance (MOP) identified with an Exploration Flight Test-1 (EFT-1) Multi- Purpose Crew Vehicle (MPCV) Program Flight Test Objective (FTO) (OFT1.091) specified an observation during reentry though external ground-based or airborne assets with thermal detection capabilities. The objective of this FTO was to be met with onboard Developmental Flight Instrumentation (DFI), but the MOP for external observation was intended to provide complementary quantitative data and serve as a risk reduction in the event of anomalous DFI behavior (or failure). Mr. Gavin Mendeck, the Entry, Descent, and Landing (EDL) Phase Engineer for the MPCV Program (Vehicle Integration Office/Systems & Mission Integration) requested a risk-reduction assessment from the NASA Engineering and Safety Center (NESC) to determine whether quantitative imagery could be obtained from remote aerial assets to support the external observation MOP. If so, then a viable path forward was to be determined, risks identified, and an observation pursued. If not, then the MOP for external observation was to be eliminated.

Animal life support transporters for Shuttle/Spacelab

NASA Technical Reports Server (NTRS)

Berry, W. E.; Hunt, S. R.

1978-01-01

Two transporter devices have been developed by the NASA Ames Research Center, primarily for the purpose of stowing small vertebrates and primates in the mid-deck avionics bay of the Shuttle during launch and re-entry. These animals will be used in Life Science Spacelab experiments. Stowage in the mid-deck area will reduce animal exposure to the high noise levels existing in Spacelab during launch; further, the possible exposure of the animals to high temperatures in Spacelab during re-entry and post-landing will be eliminated. The transporters will provide experimenters more timely access to their animals during experiment-critical, pre-launch, and post-landing periods. Rechargeable batteries in the transporters will provide life support system functions for the animals during periods of transfer and during mission phases in which power is temporarily unavailable. The transporters have been successfully designed, fabricated, and tested. Integrated testing of the transporters was performed in the Space Mission Development III (SMD III) Simulation at the NASA Johnson Space Center.

Can utilizing a computerized provider order entry (CPOE) system prevent hospital medical errors and adverse drug events?

PubMed

Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

2014-01-01

Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians' resistance to change.

Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication.

PubMed

Schultz, M J; Tan, A L; Gray, C N; Isern, S; Michael, S F; Frydman, H M; Connor, J H

2018-05-22

Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia w Stri, isolated from Laodelphax striatellus , was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that w Stri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. w Stri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by w Stri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into w Stri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia -infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in w Stri-infected cells. This study's findings increase the potential for application of w Stri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so far failed, making it crucial to explore new ways of limiting the spread of these viruses. Here, we show that introduction of an insect symbiont, Wolbachia w Stri, into mosquito cells is highly effective at reducing yellow fever virus, dengue virus, Zika virus, and Chikungunya virus production. Reduction of virus replication was attributable to decreases in entry and a strong block of virus gene expression at the translational level. These findings expand the potential use of Wolbachia w Stri to block viruses and identify two separate steps for limiting virus replication in mosquitos that could be targeted via microbes or other means as an antiviral strategy. Copyright © 2018 Schultz et al.

Cycle bases to the rescue

NASA Astrophysics Data System (ADS)

Tóbiás, Roland; Furtenbacher, Tibor; Császár, Attila G.

2017-12-01

Cycle bases of graph theory are introduced for the analysis of transition data deposited in line-by-line rovibronic spectroscopic databases. The principal advantage of using cycle bases is that outlier transitions -almost always present in spectroscopic databases built from experimental data originating from many different sources- can be detected and identified straightforwardly and automatically. The data available for six water isotopologues, H216O, H217O, H218O, HD16O, HD17O, and HD18O, in the HITRAN2012 and GEISA2015 databases are used to demonstrate the utility of cycle-basis-based outlier-detection approaches. The spectroscopic databases appear to be sufficiently complete so that the great majority of the entries of the minimum cycle basis have the minimum possible length of four. More than 2000 transition conflicts have been identified for the isotopologue H216O in the HITRAN2012 database, the seven common conflict types are discussed. It is recommended to employ cycle bases, and especially a minimum cycle basis, for the analysis of transitions deposited in high-resolution spectroscopic databases.

Combined cycle plants: Yesterday, today, and tomorrow (review)

NASA Astrophysics Data System (ADS)

Ol'khovskii, G. G.

2016-07-01

Gas turbine plants (GTP) for a long time have been developed by means of increasing the initial gas temperature and improvement of the turbo-machines aerodynamics and the efficiency of the critical components air cooling within the framework of a simple thermodynamic cycle. The application of watercooling systems that were used in experimental turbines and studied approximately 50 years ago revealed the fundamental difficulties that prevented the practical implementation of such systems in the industrial GTPs. The steam cooling researches have developed more substantially. The 300 MW power GTPs with a closedloop steam cooling, connected in parallel with the intermediate steam heating line in the steam cycle of the combined cycle plant (CCP) have been built, tested, and put into operation. The designs and cycle arrangements of such GTPs and entire combined cycle steam plants have become substantially more complicated without significant economic benefits. As a result, the steam cooling of gas turbines has not become widespread. The cycles—complicated by the intermediate air cooling under compression and reheat of the combustion products under expansion and their heat recovery to raise the combustion chamber entry temperature of the air—were used, in particular, in the domestic power GTPs with a moderate (700-800°C) initial gas turbine entry temperature. At the temperatures being reached to date (1300-1450°C), only one company, Alstom, applies in their 240-300 MW GTPs the recycled fuel cycle under expansion of gases in the turbine. Although these GTPs are reliable, there are no significant advantages in terms of their economy. To make a forecast of the further improvement of power GTPs, a brief review and assessment of the water cooling and steam cooling of hot components and complication of the GTP cycle by the recycling of fuel under expansion of gases in the turbine has been made. It is quite likely in the long term to reach the efficiency for the traditional GTPs of approximately 43% and 63% for PGUs at the initial gas temperature of 1600°C and less likely to increase the efficiency of these plants up to 45% and 65% by increasing the gas temperature up to 1700°C or by application of the steam cooling in the recycled fuel cycle.

Characterization of the "CCR5" Chemokine Receptor Gene

ERIC Educational Resources Information Center

Thomas, John C.

2004-01-01

The life cycle of retroviruses is an essential topic of modern cell biology instruction. Furthermore, the process of HIV viral entry into the cell is a question of great interest in basic and clinical biology. This paper describes how students can easily recover their own DNA, amplify a portion of the "CCR5" chemokine receptor gene, characterize…

From Data Entry to Evidence-Based Decision-Making: How Data and Analysis Can Drive Improvements in Admissions Policies

ERIC Educational Resources Information Center

Hourigan, Clare

2011-01-01

Academic standards and performance outcomes are a major focus of the current Cycle 2 Australian Universities Quality Agency (AUQA) audits. AUQA has clearly stated that universities will need to provide "evidence of setting, maintaining, and reviewing institutional academic standards and outcomes" (2010, p. 27). To do this, universities…

Mars Science Laboratory Differential Restraint: The Devil is in the Details

NASA Technical Reports Server (NTRS)

Jordan, Elizabeth

2012-01-01

The Differential Restraint, a mechanism used on the Mars Science Laboratory (MSL) rover to maintain symmetry of the mobility system during the launch, cruise, and entry descent and landing phases of the MSL mission, completed nearly three full design cycles before a finalized successful design was achieved. This paper address the lessons learned through these design cycles, including three major design elements that can easily be overlooked during the design process, including, tolerance stack contribution to load path, the possibility of Martian dirt as a failure mode, and the effects of material properties at temperature extremes.

Combined rankine and vapor compression cycles

DOEpatents

Radcliff, Thomas D.; Biederman, Bruce P.; Brasz, Joost J.

2005-04-19

An organic rankine cycle system is combined with a vapor compression cycle system with the turbine generator of the organic rankine cycle generating the power necessary to operate the motor of the refrigerant compressor. The vapor compression cycle is applied with its evaporator cooling the inlet air into a gas turbine, and the organic rankine cycle is applied to receive heat from a gas turbine exhaust to heat its boiler within one embodiment, a common condenser is used for the organic rankine cycle and the vapor compression cycle, with a common refrigerant, R-245a being circulated within both systems. In another embodiment, the turbine driven generator has a common shaft connected to the compressor to thereby eliminate the need for a separate motor to drive the compressor. In another embodiment, an organic rankine cycle system is applied to an internal combustion engine to cool the fluids thereof, and the turbo charged air is cooled first by the organic rankine cycle system and then by an air conditioner prior to passing into the intake of the engine.

Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.

PubMed

Dong, Peng; Maddali, Manoj V; Srimani, Jaydeep K; Thélot, François; Nevins, Joseph R; Mathey-Prevot, Bernard; You, Lingchong

2014-09-01

A body of evidence has shown that the control of E2F transcription factor activity is critical for determining cell cycle entry and cell proliferation. However, an understanding of the precise determinants of this control, including the role of other cell-cycle regulatory activities, has not been clearly defined. Here, recognizing that the contributions of individual regulatory components could be masked by heterogeneity in populations of cells, we model the potential roles of individual components together with the use of an integrated system to follow E2F dynamics at the single-cell level and in real time. These analyses reveal that crossing a threshold amplitude of E2F accumulation determines cell cycle commitment. Importantly, we find that Myc is critical in modulating the amplitude, whereas cyclin D/E activities have little effect on amplitude but do contribute to the modulation of duration of E2F activation, thereby affecting the pace of cell cycle progression.

Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events.

PubMed

Araujo, Ana Rita; Gelens, Lendert; Sheriff, Rahuman S M; Santos, Silvia D M

2016-10-20

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.

PubMed

Mengistu, Meron; Ray, Krishanu; Lewis, George K; DeVico, Anthony L

2015-03-01

The HIV-1 envelope glycoprotein, gp120, undergoes multiple molecular interactions and structural rearrangements during the course of host cell attachment and viral entry, which are being increasingly defined at the atomic level using isolated proteins. In comparison, antigenic markers of these dynamic changes are essentially unknown for single HIV-1 particles bound to target cells. Such markers should indicate how neutralizing and/or non-neutralizing antibodies might interdict infection by either blocking infection or sensitizing host cells for elimination by Fc-mediated effector function. Here we address this deficit by imaging fluorescently labeled CCR5-tropic HIV-1 pseudoviruses using confocal and superresolution microscopy to track the exposure of neutralizing and non-neutralizing epitopes as they appear on single HIV-1 particles bound to target cells. Epitope exposure was followed under conditions permissive or non-permissive for viral entry to delimit changes associated with virion binding from those associated with post-attachment events. We find that a previously unexpected array of gp120 epitopes is exposed rapidly upon target cell binding. This array comprises both neutralizing and non-neutralizing epitopes, the latter being hidden on free virions yet capable of serving as potent targets for Fc-mediated effector function. Under non-permissive conditions for viral entry, both neutralizing and non-neutralizing epitope exposures were relatively static over time for the majority of bound virions. Under entry-permissive conditions, epitope exposure patterns changed over time on subsets of virions that exhibited concurrent variations in virion contents. These studies reveal that bound virions are distinguished by a broad array of both neutralizing and non-neutralizing gp120 epitopes that potentially sensitize a freshly engaged target cell for destruction by Fc-mediated effector function and/or for direct neutralization at a post-binding step. The elucidation of these epitope exposure patterns during viral entry will help clarify antibody-mediated inhibition of HIV-1 as it is measured in vitro and in vivo.

Eliminating Voltage Decay of Lithium-Rich Li 1.14Mn 0.54Ni 0.14Co 0.14O 2 Cathodes by Controlling the Electrochemical Process

DOE PAGES

Wei, Z.; Zhu, Y.; Zhang, W.; ...

2015-03-27

Lithium-rich material owns a particularly high capacity owing to the activation of electrochemical inactive Li 2MnO 3 phase. But at the same time, MnO 2 phase formed after Li 2MnO 3 activation confronts a severe problem of converting to spinel phase, and resulting in voltage decay. To our knowledge, this phenomenon is inherent property of layered manganese oxide materials and can hardly be overcome. Based on this, unlike previous reports, herein we design a method for the first time to accelerate the phase transformation by tuning the charge upper-limit voltage at a high value, so the phase transformation process canmore » be finished in a few cycles. Then material structure remains stable while cycling at a low upper-limit voltage. By this novel method voltage decay is eliminated significantly.« less

Exploring luminescence-based temperature sensing using protein-passivated gold nanoclusters

NASA Astrophysics Data System (ADS)

Chen, Xi; Essner, Jeremy B.; Baker, Gary A.

2014-07-01

We explore the analytical performance and limitations of optically monitoring aqueous-phase temperature using protein-protected gold nanoclusters (AuNCs). Although not reported elsewhere, we find that these bio-passivated AuNCs show pronounced hysteresis upon thermal cycling. This unwanted behaviour can be eliminated by several strategies, including sol-gel coating and thermal denaturation of the biomolecular template, introducing protein-templated AuNC probes as viable nanothermometers.We explore the analytical performance and limitations of optically monitoring aqueous-phase temperature using protein-protected gold nanoclusters (AuNCs). Although not reported elsewhere, we find that these bio-passivated AuNCs show pronounced hysteresis upon thermal cycling. This unwanted behaviour can be eliminated by several strategies, including sol-gel coating and thermal denaturation of the biomolecular template, introducing protein-templated AuNC probes as viable nanothermometers. Electronic supplementary information (ESI) available: Supplemental figures and experimental details. See DOI: 10.1039/c4nr02069c

Efficiency, costs and benefits of AOPs for removal of pharmaceuticals from the water cycle.

PubMed

Tuerk, J; Sayder, B; Boergers, A; Vitz, H; Kiffmeyer, T K; Kabasci, S

2010-01-01

Different advanced oxidation processes (AOP) were developed for the treatment of highly loaded wastewater streams. Optimisation of removal and improvement of efficiency were carried out on a laboratory, semiworks and pilot plant scale. The persistent cytostatic drug cyclophosphamide was selected as a reference substance regarding elimination and evaluation of the various oxidation processes because of its low degradability rate. The investigated processes are cost-efficient and suitable regarding the treatment of wastewater streams since they lead to efficient elimination of antibiotics and antineoplastics. A total reduction of toxicity was proven by means of the umuC-test. However, in order to reduce pharmaceuticals from the water cycle, it must be considered that the input of more than 80 % of the pharmaceuticals entering wastewater treatment systems results from private households. Therefore, advanced technologies should also be installed at wastewater treatment plants.

Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme

PubMed Central

Paskaleva, Elena E; Lin, Xudong; Li, Wen; Cotter, Robin; Klein, Michael T; Roberge, Emily; Yu, Er K; Clark, Bruce; Veille, Jean-Claude; Liu, Yanze; Lee, David Y-W; Canki, Mario

2006-01-01

Background The high rate of HIV-1 mutation and increasing resistance to currently available antiretroviral (ART) therapies highlight the need for new antiviral agents. Products derived from natural sources have been shown to inhibit HIV-1 replication during various stages of the virus life cycle, and therefore represent a potential source of novel therapeutic agents. To expand our arsenal of therapeutics against HIV-1 infection, we investigated aqueous extract from Sargassum fusiforme (S. fusiforme) for ability to inhibit HIV-1 infection in the periphery, in T cells and human macrophages, and for ability to inhibit in the central nervous system (CNS), in microglia and astrocytes. Results S. fusiforme extract blocked HIV-1 infection and replication by over 90% in T cells, human macrophages and microglia, and it also inhibited pseudotyped HIV-1 (VSV/NL4-3) infection in human astrocytes by over 70%. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5)-tropic HIV-1, was dose dependant and long lasting, did not inhibit cell growth or viability, was not toxic to cells, and was comparable to inhibition by the nucleoside analogue 2', 3'-didoxycytidine (ddC). S. fusiforme treatment blocked direct cell-to-cell infection spread. To investigate at which point of the virus life cycle this inhibition occurs, we infected T cells and CD4-negative primary human astrocytes with HIV-1 pseudotyped with envelope glycoprotein of vesicular stomatitis virus (VSV), which bypasses the HIV receptor requirements. Infection by pseudotyped HIV-1 (VSV/NL4-3) was also inhibited in a dose dependant manner, although up to 57% less, as compared to inhibition of native NL4-3, indicating post-entry interferences. Conclusion This is the first report demonstrating S. fusiforme to be a potent inhibitor of highly productive HIV-1 infection and replication in T cells, in primary human macrophages, microglia, and astrocytes. Results with VSV/NL4-3 infection, suggest inhibition of both entry and post-entry events of the virus life cycle. Absence of cytotoxicity and high viability of treated cells also suggest that S. fusiforme is a potential source of novel naturally occurring antiretroviral compounds that inhibit HIV-1 infection and replication at more than one site of the virus life cycle. PMID:16725040

Mixed polyanion glass cathodes: Effect of polyanion content

DOE PAGES

Kercher, Andrew K.; Kolopus, James A.; Sacci, Robert L.; ...

2017-02-18

Mixed polyanion glass cathodes in lithium-ion batteries have very high capacities (200-500 mAh/g), but currently these materials have fundamental problems with 1 st-cycle irreversible loss, cycling efficiency, and capacity fade. It is well established that polyanion substitutions into glasses can dramatically affect their physical properties, but the effect of polyanion content on the electrochemical performance has not been previously established. The proper amount of lithium and borate substitution in copper phosphate/vanadate glasses was shown to nearly eliminate 1 st-cycle irreversible loss and improve cycling efficiency. As a result, Raman and IR spectroscopy were used to identify polyanions that correlated withmore » electrochemical performance changes.« less

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

PubMed Central

Barna, Maria; Pusic, Aya; Zollo, Ornella; Costa, Maria; Kondrashov, Nadya; Rego, Eduardo; Rao, Pulivarthi H; Ruggero, Davide

2008-01-01

The Myc oncogene regulates the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III, and rDNA1,2. An outstanding question is whether and how increasing the cellular protein synthesis capacity can affect the multi-step process leading to cancer. We utilized ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Eμ–Myc/+ transgenic mice to normal levels and show that in this context Myc's oncogenic potential is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a novel paradigm that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation employed to regulate the expression of selective mRNAs. We show that an aberrant increase in cap-dependent translation downstream Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (p58-PITSLRE)3-5, which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Eμ–Myc/+ mice. When accurate translational control is re-established in Eμ–Myc/+ mice, genome instability is suppressed. Our findings reveal how perturbations in translational control provide a highly specific outcome on gene expression, genome stability, and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level. PMID:19011615

Synthesis of betulinic acid derivatives as entry inhibitors against HIV-1 and bevirimat-resistant HIV-1 variants.

PubMed

Dang, Zhao; Qian, Keduo; Ho, Phong; Zhu, Lei; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho

2012-08-15

Betulinic acid derivatives modified at the C28 position are HIV-1entry inhibitors such as compound A43D; however, modified at the C3 position instead of C28 give HIV-1 maturation inhibitor such as bevirimat. Bevirimat exhibited promising pharmacokinetic profiles in clinical trials, but its effectiveness was compromised by the high baseline drug resistance of HIV-1 variants with polymorphism in the putative drug binding site. In an effort to determine whether the viruses with bevirimat resistant polymorphism also altered their sensitivities to the betulinic acid derivatives that inhibit HIV-1 entry, a series of new betulinic acid entry inhibitors were synthesized and tested for their activities against HIV-1 NL4-3 and NL4-3 variants resistant to bevirimat. The results show that the bevirimat resistant viruses were approximately 5- to10-fold more sensitive to three new glutamine ester derivatives (13, 15 and 38) and A43D in an HIV-1 multi-cycle replication assay. In contrast, the wild type NL4-3 and the bevirimat resistant variants were equally sensitive to the HIV-1 RT inhibitor AZT. In addition, these three new compounds markedly improved microsomal stability compared to A43D. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry

PubMed Central

Schäfer, Georgia; Blumenthal, Melissa J.; Katz, Arieh A.

2015-01-01

Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection. PMID:26008702

Characterizing the Anti-HIV Activity of Papuamide A

PubMed Central

Andjelic, Cynthia D; Planelles, Vicente; Barrows, Louis R

2008-01-01

Papuamide A is representative of a class of marine derived cyclic depsipeptides, reported to have cytoprotective activity against HIV-1 in vitro. We show here that papuamide A acts as an entry inhibitor, preventing human immunodeficiency virus infection of host cells and that this inhibition is not specific to R5 or X4 tropic virus. This inhibition of viral entry was determined to not be due to papuamide A binding to CD4 or HIV gp120, the two proteins involved in the cell-virus recognition and binding. Furthermore, papuamide A was able to inhibit HIV pseudotype viruses expressing envelope glycoproteins from vesicular stomatitis virus or amphotropic murine leukemia virus indicating the mechanism of viral entry inhibition is not HIV-1 envelope glycoprotein specific. Time delayed addition studies with the pseudotyped viruses show that papuamide A inhibits viral infection only at the initial stage of the viral life cycle. Additionally, pretreatment studies revealed that the virus, and not the cell, is the target of papuamide A’s action. Together, these results suggest a direct virucidal mechanism of HIV-1 inhibition by papuamide A. We also demonstrate here that the other papuamides (B-D) are able to inhibit viral entry indicating that the free amino moiety of 2,3-diaminobutanoic acid residue is not required for the virucidal activity. PMID:19172193

Nonnative forest insects and pathogens in the United States: Impacts and policy options.

PubMed

Lovett, Gary M; Weiss, Marissa; Liebhold, Andrew M; Holmes, Thomas P; Leung, Brian; Lambert, Kathy Fallon; Orwig, David A; Campbell, Faith T; Rosenthal, Jonathan; McCullough, Deborah G; Wildova, Radka; Ayres, Matthew P; Canham, Charles D; Foster, David R; LaDeau, Shannon L; Weldy, Troy

2016-07-01

We review and synthesize information on invasions of nonnative forest insects and diseases in the United States, including their ecological and economic impacts, pathways of arrival, distribution within the United States, and policy options for reducing future invasions. Nonnative insects have accumulated in United States forests at a rate of ~2.5 per yr over the last 150 yr. Currently the two major pathways of introduction are importation of live plants and wood packing material such as pallets and crates. Introduced insects and diseases occur in forests and cities throughout the United States, and the problem is particularly severe in the Northeast and Upper Midwest. Nonnative forest pests are the only disturbance agent that has effectively eliminated entire tree species or genera from United States forests within decades. The resulting shift in forest structure and species composition alters ecosystem functions such as productivity, nutrient cycling, and wildlife habitat. In urban and suburban areas, loss of trees from streets, yards, and parks affects aesthetics, property values, shading, stormwater runoff, and human health. The economic damage from nonnative pests is not yet fully known, but is likely in the billions of dollars per year, with the majority of this economic burden borne by municipalities and residential property owners. Current policies for preventing introductions are having positive effects but are insufficient to reduce the influx of pests in the face of burgeoning global trade. Options are available to strengthen the defenses against pest arrival and establishment, including measures taken in the exporting country prior to shipment, measures to ensure clean shipments of plants and wood products, inspections at ports of entry, and post-entry measures such as quarantines, surveillance, and eradication programs. Improved data collection procedures for inspections, greater data accessibility, and better reporting would support better evaluation of policy effectiveness. Lack of additional action places the nation, local municipalities, and property owners at high risk of further damaging and costly invasions. Adopting stronger policies to reduce establishments of new forest insects and diseases would shift the major costs of control to the source and alleviate the economic burden now borne by homeowners and municipalities. © 2016 by the Ecological Society of America.

Live-cell imaging visualizes frequent mitotic skipping during senescence-like growth arrest in mammary carcinoma cells exposed to ionizing radiation.

PubMed

Suzuki, Masatoshi; Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi

2012-06-01

Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO(2)-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ß-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp; Yamauchi, Motohiro; Oka, Yasuyoshi

Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% andmore » 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.« less

Holonomic Quantum Control by Coherent Optical Excitation in Diamond.

PubMed

Zhou, Brian B; Jerger, Paul C; Shkolnikov, V O; Heremans, F Joseph; Burkard, Guido; Awschalom, David D

2017-10-06

Although geometric phases in quantum evolution are historically overlooked, their active control now stimulates strategies for constructing robust quantum technologies. Here, we demonstrate arbitrary single-qubit holonomic gates from a single cycle of nonadiabatic evolution, eliminating the need to concatenate two separate cycles. Our method varies the amplitude, phase, and detuning of a two-tone optical field to control the non-Abelian geometric phase acquired by a nitrogen-vacancy center in diamond over a coherent excitation cycle. We demonstrate the enhanced robustness of detuned gates to excited-state decoherence and provide insights for optimizing fast holonomic control in dissipative quantum systems.

Holonomic Quantum Control by Coherent Optical Excitation in Diamond

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

Zhou, Brian B.; Jerger, Paul C.; Shkolnikov, V. O.

Although geometric phases in quantum evolution are historically overlooked, their active control now stimulates strategies for constructing robust quantum technologies. Here, we demonstrate arbitrary singlequbit holonomic gates from a single cycle of nonadiabatic evolution, eliminating the need to concatenate two separate cycles. Our method varies the amplitude, phase, and detuning of a two-tone optical field to control the non-Abelian geometric phase acquired by a nitrogen-vacancy center in diamond over a coherent excitation cycle. We demonstrate the enhanced robustness of detuned gates to excited-state decoherence and provide insights for optimizing fast holonomic control in dissipative quantum systems.

Space and man. [planetary exploration and energy sources

NASA Technical Reports Server (NTRS)

Kolman, E.

1974-01-01

The effects of man's entry into space on changes in economics and technology, politics and law, science, philosophy, and art are considered. A single world economy, extracting from the natural resources of the moon and other cosmic bodies raw materials and energy, will avoid terrestrial limitations and improve society by eliminating the inequalities of economic and social status. However, a spacecraft for interplanetary travel require thermonuclear engines that achieve an escape velocity of 0.1 times the speed of light in order to allow an astronaut stellar expedition corresponding to the active life of a single generation.

Apparatus for measuring charged particle beam

NASA Technical Reports Server (NTRS)

Gregory, D. A.; Stocks, C. D. (Inventor)

1984-01-01

An apparatus to measure the incident charged particle beam flux while effectively eliminating losses to reflection and/or secondary emission of the charged particle beam being measured is described. It comprises a sense cup through which the charged particle beam enters. A sense cone forms the rear wall of the interior chamber with the cone apex adjacent the entry opening. An outer case surrounds the sense cup and is electrically insulated therefrom. Charged particles entering the interior chamber are trapped and are absorbed by the sense cup and cone and travel through a current measuring device to ground.

The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

PubMed

Bouchard-Cannon, Pascale; Mendoza-Viveros, Lucia; Yuen, Andrew; Kærn, Mads; Cheng, Hai-Ying M

2013-11-27

The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Origin of bistability underlying mammalian cell cycle entry

PubMed Central

Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

2011-01-01

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at the lateral semi-circular canal.

PubMed

Salt, Alec N; Hartsock, Jared J; Gill, Ruth M; Piu, Fabrice; Plontke, Stefan K

2012-12-01

Perilymph pharmacokinetics was investigated by a novel approach, in which solutions containing drug or marker were injected from a pipette sealed into the perilymphatic space of the lateral semi-circular canal (LSCC). The cochlear aqueduct provides the outlet for fluid flow so this procedure allows almost the entire perilymph to be exchanged. After wait times of up to 4 h the injection pipette was removed and multiple, sequential samples of perilymph were collected from the LSCC. Fluid efflux at this site results from cerebrospinal fluid (CSF) entry into the basal turn of scala tympani (ST) so the samples allow drug levels from different locations in the ear to be defined. This method allows the rate of elimination of substances from the inner ear to be determined more reliably than with other delivery methods in which drug may only be applied to part of the ear. Results were compared for the markers trimethylphenylammonium (TMPA) and fluorescein and for the drug dexamethasone (Dex). For each substance, the concentration in fluid samples showed a progressive decrease as the delay time between injection and sampling was increased. This is consistent with the elimination of substance from the ear with time. The decline with time was slowest for fluorescein, was fastest for Dex, with TMPA at an intermediate rate. Simulations of the experiments showed that elimination occurred more rapidly from scala tympani (ST) than from scala vestibuli (SV). Calculated elimination half-times from ST averaged 54.1, 24.5 and 22.5 min for fluorescein, TMPA and Dex respectively and from SV 1730, 229 and 111 min respectively. The elimination of Dex from ST occurred considerably faster than previously appreciated. These pharmacokinetic parameters provide an important foundation for understanding of drug treatments of the inner ear.

Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

PubMed

Lee, Tae J; Yao, Guang; Bennett, Dorothy C; Nevins, Joseph R; You, Lingchong

2010-09-21

The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.

Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B.

PubMed

Ren, Dapeng; Fisher, Laura A; Zhao, Jing; Wang, Ling; Williams, Byron C; Goldberg, Michael L; Peng, Aimin

2017-06-16

Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in Xenopus ). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B) as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new cell cycle regulator that functions by governing Gwl dephosphorylation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural mechanisms of DREAM complex assembly and regulation

PubMed Central

Guiley, Keelan Z.; Liban, Tyler J.; Felthousen, Jessica G.; Ramanan, Parameshwaran

2015-01-01

The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52–p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phosphate at nearby S28 to bind the LxCxE cleft of the pocket domain with high affinity. The structure explains the specificity for p107/p130 over Rb in the DREAM complex and how the complex is disrupted by viral oncoproteins. Based on insights from the structure, we addressed how DREAM is disassembled upon cell cycle entry. We found that p130 and B-Myb can both bind the core MuvB complex simultaneously but that cyclin-dependent kinase phosphorylation of p130 weakens its association. Together, our data inform a novel target interface for studying MuvB and p130 function and the design of inhibitors that prevent tumor escape in quiescence. PMID:25917549

POLLUTION PREVENTION AND LIFE CYCLE ASSESSMENT (CHAPTER 15)

EPA Science Inventory

Much has been accomplished internationally to establish industrial Pollution Prevention as an important component in environmental management. It includes approaches that reduce or eliminate the creation of pollutants or wastes at the source. However, the growing recognition th...

Scale Resistant Heat Exchanger for Low Temperature Geothermal Binary Cycle Power Plant

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

Hays, Lance G.

2014-11-18

Phase 1 of the investigation of improvements to low temperature geothermal power systems was completed. The improvements considered were reduction of scaling in heat exchangers and a hermetic turbine generator (eliminating seals, seal system, gearbox, and lube oil system). A scaling test system with several experiments was designed and operated at Coso geothermal resource with brine having a high scaling potential. Several methods were investigated at the brine temperature of 235 ºF. One method, circulation of abradable balls through the brine passages, was found to substantially reduce scale deposits. The test heat exchanger was operated with brine outlet temperatures asmore » low as 125 ºF, which enables increased heat input available to power conversion systems. For advanced low temperature cycles, such as the Variable Phase Cycle (VPC) or Kalina Cycle, the lower brine temperature will result in a 20-30% increase in power production from low temperature resources. A preliminary design of an abradable ball system (ABS) was done for the heat exchanger of the 1 megawatt VPC system at Coso resource. The ABS will be installed and demonstrated in Phase 2 of this project, increasing the power production above that possible with the present 175 ºF brine outlet limit. A hermetic turbine generator (TGH) was designed and manufacturing drawings produced. This unit will use the working fluid (R134a) to lubricate the bearings and cool the generator. The 200 kW turbine directly drives the generator, eliminating a gearbox and lube oil system. Elimination of external seals eliminates the potential of leakage of the refrigerant or hydrocarbon working fluids, resulting in environmental improvement. A similar design has been demonstrated by Energent in an ORC waste heat recovery system. The existing VPC power plant at Coso was modified to enable the “piggyback” demonstration of the TGH. The existing heat exchanger, pumps, and condenser will be operated to provide the required process conditions for the TGH demonstration. Operation of the TGH with and without the ABS system will demonstrate an increase in geothermal resource productivity for the VPC from 1 MW/(million lb) of brine to 1.75 MW/(million lb) of brine, a 75% increase.« less

Eliminating Major Gaps in DoD Data on the Fully-Burdened and Life-Cycle Cost of Military Personnel: Cost Elements Should be Mandated by Policy

DTIC Science & Technology

2013-01-07

Budgetary Assessment as well as private sector companies . Reserve Forces Policy Board Eliminating Major Gaps in DoD Data on the Fully-Burdened and Life...and utilities costs associated with the housing, childcare and recreation facilities found on major bases. This is true whether the reservist is...Notably, the current Under Secretary of Defense Comptroller, the Honorable Robert Hale has said, “the cost of pay and benefits has risen more than 87

Engine for the next-generation launcher

NASA Astrophysics Data System (ADS)

Beichel, Rudi; Grey, Jerry

1995-05-01

The proposed dual-fuel/dual-expansion engine for the Reusable Launch Vehicle (RLV) could solve the vehicle's need for a high-performance, lightweight, low-cost, maintainable engine. The features that make dual-fuel/dual-expansion engine a prime candidate for RLV include oxygen-rich combustion, high-pressure staged-combustion cycle and dual-fuel operation. Cost-reducing, reliability-enhancing innovations such as the elimination of regenerative cooling, elimination of gimbaling and replacement of kerosene-based hydrocarbon fuel by subcooled propane have also made the this type of engine an attractive option.

Solar Sea Power Plants (SSPP): A critical review and survey

NASA Technical Reports Server (NTRS)

Strauss, A. M.

1974-01-01

An overview of technical and economic matters relating to the eventual success or failure of the SSPP concept is presented, with emphasis on the pollution and energy problems which the SSPP would serve to eliminate. Factors discussed include cost, mariculture possibilities, siting, legal limitations, design materials, mooring and anchoring, and the human element involved. Several alternative power systems are considered for incorporation into SSPP design, such as Nitinol power, Claude cycle, and closed cycle engine systems.

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

PubMed

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Consoer et al PFOS dataset

EPA Pesticide Factsheets

This ScienceHub entry was developed for the published paper: Consoer et al., 2016, Toxicokinetics of perfluorooctane sulfonate in rainow trout (Oncorhynchus mykiss), Environ. Toxicol. Chem. 35:717-727. Individual rainbow trout were exposed to PFOS by bolus injection (elimination studies) or by adding PFOS to incoming water (branchial uptake studies). The trout were fitted with indwelling catheters and urinary cannulae to permit periodic collection of blood and urine. Additional sampling was conducted to evaluate PFOS uptake from and elimination to respired water. Data obtained from each fish was evaluated using a clearance-volume pharmacokinetic model. Modeled kinetic parameters were then averaged to develop summary statistics which were used as a basis for interpreting modeled results and making comparisons to a previous study of rainbow trout exposed to perfluorooctanoate (PFOA; Consoer et al., 2014, Aquat. Toxicol. 156:65-73). The results of this study, combined with that of the previous PFOA study, suggest that PFOA is a substrate for renal transporters in fish while glomerular filtration alone may be sufficient to explain the observed renal elimination of PFOS. These findings demonstrate that models developed to predict the bioaccumulation of perfluoroalkyl acids by fish must account for differences in renal clearance of individual compounds.This dataset is associated with the following publication:Consoer, D., A. Hoffman , P. Fitzsimmons , P. Kosia

Efficacy of imidocarb dipropionate in eliminating Theileria equi from experimentally infected horses.

PubMed

Grause, Juanita F; Ueti, Massaro W; Nelson, Jeffrey T; Knowles, Donald P; Kappmeyer, Lowell S; Bunn, Thomas O

2013-06-01

Theileria equi, one of the causative agents of equine piroplasmosis, is endemic in many regions of the world but is considered a 'foreign' animal disease in the USA. In an effort to prevent the importation of T. equi, stringent serological screening of horses is practiced prior to entry to the USA. Current regulatory options available where horses are found to be infected include permanent quarantine with or without chemotherapy, repatriation, or euthanasia. Chemotherapeutics that eliminate infection and subsequently transmission risk are critical in the management of infected horses. In this study, the efficacy of the drug imidocarb dipropionate against experimental T. equi infection was assessed. Of nine horses experimentally inoculated with T. equi isolated from an animal previously imported from Peru, six were treated with imidocarb dipropionate after the resolution of the acute phase of the disease. Elimination of the parasite was demonstrated in 5/6 by nested PCR, blood transfusions to naïve horses, and reversion to seronegative status. The findings support the use of this drug as a potential treatment option in controlling outbreaks of T. equi, and also suggest that 'combination testing' using both serological and PCR detection methods are necessary to demonstrate clearance of infection. Published by Elsevier Ltd.

[The life cycle of Rubella Virus].

PubMed

Sakata, Masafumi; Mori, Yoshio

2014-01-01

Rubella virus (RV), an infectious agent of rubella, is the sole member of the genus Rubivirus in the family of Togaviridae. RV has a positive-stranded sense RNA as a genome. A natural host of RV is limited to human, and rubella is considered to be a childhood disease in general. When woman is infected with RV during early pregnancy, her fetus may develop severe birth defects known as congenital rubella syndrome. In this review, the RV life cycle from the virus entry to budding is illustrated in comparison with those of member viruses of the genus alphavirus in the same family. The multiple functions of the RV capsid protein are also introduced.

The principles of disease elimination and eradication.

PubMed Central

Dowdle, W. R.

1998-01-01

The Dahlem Workshop discussed the hierarchy of possible public health interventions in dealing with infectious diseases, which were defined as control, elimination of disease, elimination of infections, eradication, and extinction. The indicators of eradicability were the availability of effective interventions and practical diagnostic tools and the essential need for humans in the life-cycle of the agent. Since health resources are limited, decisions have to be made as to whether their use for an elimination or eradication programme is preferable to their use elsewhere. The costs and benefits of global eradication programmes concern direct effects on morbidity and mortality and consequent effects on the health care system. The success of any disease eradication initiative depends strongly on the level of societal and political commitment, with a key role for the World Health Assembly. Eradication and ongoing programmes constitute potentially complementary approaches to public health. Elimination and eradication are the ultimate goals of public health, evolving naturally from disease control. The basic question is whether these goals are to be achieved in the present or some future generation. PMID:10063669

Integrin αvβ3 promotes infection by Japanese encephalitis virus.

PubMed

Fan, Wenchun; Qian, Ping; Wang, Dandan; Zhi, Xianwei; Wei, Yanming; Chen, Huanchun; Li, Xiangmin

2017-04-01

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is one of the major causes of viral encephalitis diseases worldwide. The JEV envelope protein facilitates viral entry, and its domain III contains an Arg-Gly-Asp (RGD) motif, that may modulate JEV entry through the RGD-binding integrin. In this study, the roles of integrin αv and β3 on the infection of JEV were evaluated. Reduced expression of integrin αv/β3 by special shRNA confers 2 to 4-fold inhibition of JEV replication in BHK-21 cells. Meanwhile, antibodies specific for integrin αv/β3 displayed ~58% and ~33% inhibition of JEV infectivity and RGD-specific peptides produced ~36% of inhibition. Expression of E protein and JEV RNA loads were clearly increased in CHO cells transfected with cDNA encoding human integrin β3. Moreover, integrin αv mediates JEV infection in viral binding stage of life cycle. Therefore, our study suggested that integrin αv and β3 serve as a host factor associated with JEV entry into the target cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Japanese encephalitis virus invasion of cell: allies and alleys.

PubMed

Nain, Minu; Abdin, Malik Z; Kalia, Manjula; Vrati, Sudhanshu

2016-03-01

The mosquito-borne flavivirus, Japanese encephalitis virus (JEV), is the leading cause of virus-induced encephalitis globally and a major public health concern of several countries in Southeast Asia, with the potential to become a global pathogen. The virus is neurotropic, and the disease ranges from mild fever to severe hemorrhagic and encephalitic manifestations and death. The early steps of the virus life cycle, binding, and entry into the cell are crucial determinants of infection and are potential targets for the development of antiviral therapies. JEV can infect multiple cell types; however, the key receptor molecule(s) still remains elusive. JEV also has the capacity to utilize multiple endocytic pathways for entry into cells of different lineages. This review not only gives a comprehensive update on what is known about the virus attachment and receptor system (allies) and the endocytic pathways (alleys) exploited by the virus to gain entry into the cell and establish infection but also discusses crucial unresolved issues. We also highlight common themes and key differences between JEV and other flaviviruses in these contexts. Copyright © 2015 John Wiley & Sons, Ltd.

Advanced Rigid Ablative TPS

NASA Technical Reports Server (NTRS)

Gasch, Matthew J.

2011-01-01

NASA Exploration Systems Mission Directorate s (ESMD) Entry, Descent, and Landing (EDL) Technology Development Project (TDP) and the NASA Aeronautics Research Mission Directorate s (ARMD) Hypersonics Project are developing new advanced rigid ablators in an effort to substantially increase reliability, decrease mass, and reduce life cycle cost of rigid aeroshell-based entry systems for multiple missions. Advanced Rigid Ablators combine ablation resistant top layers capable of high heat flux entry and enable high-speed EDL with insulating mass-efficient bottom that, insulate the structure and lower the areal weight. These materials may benefit Commercial Orbital Transportation Services (COTS) vendors and may potentially enable new NASA missions for higher velocity returns (e.g. asteroid, Mars). The materials have been thermally tested to 400-450 W/sq cm at the Laser Hardened Materials Evaluation Lab (LHMEL), Hypersonics Materials Evaluation Test System (HyMETS) and in arcjet facilities. Tested materials exhibit much lower backface temperatures and reduced recession over the baseline materials (PICA). Although the EDL project is ending in FY11, NASA in-house development of advanced ablators will continue with a focus on varying resin systems and fiber/resin interactions.

Subsonic Static and Dynamic Aerodynamics of Blunt Entry Vehicles

NASA Technical Reports Server (NTRS)

Mitcheltree, Robert A.; Fremaux, Charles M.; Yates, Leslie A.

1999-01-01

The incompressible subsonic aerodynamics of four entry-vehicle shapes with variable c.g. locations are examined in the Langley 20-Foot Vertical Spin Tunnel. The shapes examined are spherically-blunted cones with half-cone angles of 30, 45, and 60 deg. The nose bluntness varies between 0.25 and 0.5 times the base diameter. The Reynolds number based on model diameter for these tests is near 500,000. Quantitative data on attitude and location are collected using a video-based data acquisition system and reduced with a six deg-of-freedom inverse method. All of the shapes examined suffered from strong dynamic instabilities which could produced limit cycles with sufficient amplitudes to overcome static stability of the configuration. Increasing cone half-angle or nose bluntness increases drag but decreases static and dynamic stability.

Involvement of a Gardos-type potassium channel in head activator-induced mitosis of BON cells.

PubMed

Kayser, S T; Ulrich, H; Schaller, H C

1998-06-01

The human neuroendocrine cell line BON was used to study second messengers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entry into mitosis. HA-induced mitosis is mediated by an inhibitory G protein, the action of which is blocked by pertussis toxin. HA signaling requires inhibition of the cAMP pathway, calcium influx, and hyperpolarization of cells. The latter is a very important and sensitive step involving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with specific inhibitors of this potassium channel. Pharmacology and RNA analysis suggest identity with the recently cloned Gardos-type potassium channel.

Implications of a 20-Hz Booster cycle-rate for Slip-stacking

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

Eldred, Jeffrey; Zwaska, Robert

2014-06-10

We examine the potential impacts to slip-stacking from a change of the Booster cycle-rate from 15- to 20-Hz. We find that changing the Booster cycle-rate to 20-Hz would greatly increase the slip-stacking bucket area, while potentially requiring greater usage of the Recycler momentum aperture and additional power dissipation in the RF cavities. In particular, the losses from RF interference can be reduced by a factor of 4-10 (depending on Booster beam longitudinal parameters). We discuss the aspect ratio and beam emittance requirements for efficient slip-stacking in both cycle-rate cases. Using a different injection scheme can eliminate the need for greatermore » momentum aperture in the Recycler.« less

On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles

PubMed Central

Carvalho, Carlos A.M.; Silva, Jerson L.; Oliveira, Andréa C.

2017-01-01

Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell. PMID:28462045

Partner's Resources and Adjusting Working Hours in the Netherlands: Differences over Time, between Levels of Human Capital, and over the Family Cycle

ERIC Educational Resources Information Center

Verbakel, Ellen

2010-01-01

We study to what extent adjustments in labor market participation, defined as employment entry and exit, and as increases and reductions of weekly working hours, depend on resources of the partner. Moreover, we investigate whether the influence of the partner depends on historical period, human capital, and children. We are especially interested…

An evaluation of voluntary 2-dose varicella vaccination coverage in New York City public schools.

PubMed

Doll, Margaret K; Rosen, Jennifer B; Bialek, Stephanie R; Szeto, Hiram; Zimmerman, Christopher M

2015-05-01

We assessed coverage for 2-dose varicella vaccination, which is not required for school entry, among New York City public school students and examined characteristics associated with receipt of 2 doses. We measured receipt of either at least 1 or 2 doses of varicella vaccine among students aged 4 years and older in a sample of 336 public schools (n = 223 864 students) during the 2010 to 2011 school year. Data came from merged student vaccination records from 2 administrative data systems. We conducted multivariable regression to assess associations of age, gender, race/ethnicity, and school location with 2-dose prevalence. Coverage with at least 1 varicella dose was 96.2% (95% confidence interval [CI] = 96.2%, 96.3%); coverage with at least 2 doses was 64.8% (95% CI = 64.6%, 64.9%). Increasing student age, non-Hispanic White race/ethnicity, and attendance at school in Staten Island were associated with lower 2-dose coverage. A 2-dose varicella vaccine requirement for school entry would likely improve 2-dose coverage, eliminate coverage disparities, and prevent disease.

Dual Stem Loops within the Poliovirus Internal Ribosomal Entry Site Control Neurovirulence

PubMed Central

Gromeier, Matthias; Bossert, Birgit; Arita, Mineo; Nomoto, Akio; Wimmer, Eckard

1999-01-01

In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5′ nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity. PMID:9882296

A hybrid water-splitting cycle using copper sulfate and mixed copper oxides

NASA Technical Reports Server (NTRS)

Schreiber, J. D.; Remick, R. J.; Foh, S. E.; Mazumder, M. M.

1980-01-01

The Institute of Gas Technology has derived and developed a hybrid thermochemical water-splitting cycle based on mixed copper oxides and copper sulfate. Similar to other metal oxide-metal sulfate cycles that use a metal oxide to 'concentrate' electrolytically produced sulfuric acid, this cycle offers the advantage of producing oxygen (to be vented) and sulfur dioxide (to be recycled) in separate steps, thereby eliminating the need of another step to separate these gases. The conceptual process flow-sheet efficiency of the cycle promises to exceed 50%. It has been completely demonstrated in the laboratory with recycled materials. Research in the electrochemical oxidation of sulfur dioxide to produce sulfuric acid and hydrogen performed at IGT indicates that the cell performance goals of 200 mA/sq cm at 0.5 V will be attainable using relatively inexpensive electrode materials.

Life without complex I: proteome analyses of an Arabidopsis mutant lacking the mitochondrial NADH dehydrogenase complex

PubMed Central

Fromm, Steffanie; Senkler, Jennifer; Eubel, Holger; Peterhänsel, Christoph; Braun, Hans-Peter

2016-01-01

The mitochondrial NADH dehydrogenase complex (complex I) is of particular importance for the respiratory chain in mitochondria. It is the major electron entry site for the mitochondrial electron transport chain (mETC) and therefore of great significance for mitochondrial ATP generation. We recently described an Arabidopsis thaliana double-mutant lacking the genes encoding the carbonic anhydrases CA1 and CA2, which both form part of a plant-specific ‘carbonic anhydrase domain’ of mitochondrial complex I. The mutant lacks complex I completely. Here we report extended analyses for systematically characterizing the proteome of the ca1ca2 mutant. Using various proteomic tools, we show that lack of complex I causes reorganization of the cellular respiration system. Reduced electron entry into the respiratory chain at the first segment of the mETC leads to induction of complexes II and IV as well as alternative oxidase. Increased electron entry at later segments of the mETC requires an increase in oxidation of organic substrates. This is reflected by higher abundance of proteins involved in glycolysis, the tricarboxylic acid cycle and branched-chain amino acid catabolism. Proteins involved in the light reaction of photosynthesis, the Calvin cycle, tetrapyrrole biosynthesis, and photorespiration are clearly reduced, contributing to the significant delay in growth and development of the double-mutant. Finally, enzymes involved in defense against reactive oxygen species and stress symptoms are much induced. These together with previously reported insights into the function of plant complex I, which were obtained by analysing other complex I mutants, are integrated in order to comprehensively describe ‘life without complex I’. PMID:27122571

PLC-γ1 Signaling Plays a Subtype-Specific Role in Postbinding Cell Entry of Influenza A Virus

PubMed Central

Zhu, Liqian; Ly, Hinh

2014-01-01

Host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. In this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (PLC-γ1) in mediating cell entry of influenza virus H1N1 but not H3N2 subtype. Both PLC-γ1-specific inhibitor and short hairpin RNA (shRNA) strongly suppress the replication of H1N1 but not H3N2 viruses in cell culture, suggesting that PLC-γ1 plays an important subtype-specific role in the influenza viral life cycle. Further analyses demonstrate that PLC-γ1 activation is required for viral postbinding cell entry. In addition, H1N1, but not H3N2, infection leads to the phosphorylation of PLC-γ1 at Ser 1248 immediately after infection and independent of viral replication. We have further shown that H1N1-induced PLC-γ1 activation is downstream of epidermal growth factor receptor (EGFR) signaling. Interestingly, both H1N1 and H3N2 infections activate EGFR, but only H1N1 infection leads to PLC-γ1 activation. Taking our findings together, we have identified for the first time the subtype-specific interplay of host PLC-γ1 signaling and H1N1 virus that is critical for viral uptake early in the infection. Our study provides novel insights into how virus interacts with the cellular signaling network by demonstrating that viral determinants can regulate how the host signaling pathways function in virally infected cells. PMID:24155396

Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass

PubMed Central

Olson, Aaron K.; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy; Rosiers, Christine Des

2012-01-01

Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-13Carbon(13C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 μg/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-13C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (∼4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, 13C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion. PMID:22180654

TRIIODOTHYRONINE INCREASES MYOCARDIAL FUNCTION AND PYRUVATE ENTRY INTO THE CITRIC ACID CYCLE AFTER REPERFUSION IN A MODEL OF INFANT CARDIOPULMONARY BYPASS

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

Olson, Aaron; Bouchard, Bertrand; Ning, Xue-Han

We utilized a translational model of infant CPB to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)]-pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels (aCAC) and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC ) and anaplerotic carboxylation (PC; ) using 13C-labeled pyruvate and isotopomermore » analysis by gas and liquid chromatography-mass spectrometry and 13C NMR. Neither IR nor IR-Tr modified aCAC. However, compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after CPB while elevating both PDC and PC (~ four-fold). T3 inhibited IR induced reductions in CAC intermediate molar percent enrichment (MPE) and oxaloacetate(citrate)/malate MPE ratio; an index of aspartate entry into the CAC. Conclusions: T3 markedly enhances PC and PDC thereby providing substrate for elevated cardiac function and work after reperfusion. The increases in pyruvate flux occur with preservation of the CAC intermediate pool. Additionally, T3 inhibition of reductions in CAC intermediate MPEs indicates that T3 reduces the reliance on amino acids (AA) for anaplerosis after reperfusion. Thus, AA should be more available for other functions such as protein synthesis.« less

Effect of thermal cycling. Final report, April 1985-January 1987

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

Jacobs, S.F.

The objective of this effort is to evaluate the stability of low expansion Zerodur, developmental Zerodur, ULE, and Cer-Vit as possible substrate materials for high energy laser mirrors. This effort will determine whether there is instability in developmental Zerodur, ULE and Cer-Vit over operating temperatures and coating temperatures (300-475K). Zerodur has already been shown to exhibit instability. Thermal cycling will be investigated as a possible approach to eliminate or reduce hysteresis. The effect of polishing on hysteresis will also be investigated.

Effect of thermal cycling

NASA Astrophysics Data System (ADS)

Jacobs, Stephen F.

1988-05-01

The objective of this effort is to evaluate the stability of low expansion Zerodur, developmental Zerodur, ULE, and Cer-Vit as possible substrate materials for high energy laser mirrors. This effort will determine whether there is instability in developmental Zerodur, ULE and Cer-Vit over operating temperatures and coating temperatures (300 to 475 K). Zerodur has already been shown to exhibit instability. Thermal cycling will be investigated as a possible approach to eliminate or reduce hysteresis. The effect of polishing on hysteresis will also be investigated.

The Endocrine Dyscrasia that Accompanies Menopause and Andropause Induces Aberrant Cell Cycle Signaling that Triggers Cell Cycle Reentry of Post-mitotic Neurons, Neurodysfunction, Neurodegeneration and Cognitive Disease

PubMed Central

Atwood, Craig S.; Bowen, Richard L.

2016-01-01

Sex hormones are the physiological factors that regulate neurogenesis during embryogenesis and continuing through adulthood. These hormones support the formation of brain structures such as dendritic spines, axons and synapses required for the capture of information (memories). Intriguingly, a recent animal study has demonstrated that induction of neurogenesis results in the loss of previously encoded memories in animals (e.g. infantile amnesia). In this connection, much evidence now indicates that Alzheimer’s disease (AD) also involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Since sex hormones control when and how neurons proliferate and differentiate, the endocrine dyscrasia that accompanies menopause and andropause is a key signaling event that impacts neurogenesis and the acquisition, processing, storage and recall of memories. Here we review the biochemical, epidemiological and clinical evidence that alterations in endocrine signaling with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle with neurite retraction that leads to neuron dysfunction and death. When the reproductive axis is in balance, luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the ratio of LH:sex steroids as driving aberrant mitotic events mediated by the upregulation of tumor necrosis factor, amyloid-β precursor protein processing towards the production of mitogenic Aβ, and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive studies also demonstrate the negative consequences of a high LH:sex steroid ratio on human cognitive performance. Prospective epidemiological and clinical evidence in humans supports lowering the ratio of circulating gonadotropins-GnRH to sex steroids in reducing the incidence of AD and halting cognitive decline. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson’s disease. PMID:26188949

A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer

PubMed Central

ZHANG, HAO; ZHOU, LEI; SHI, WEI; SONG, NING; YU, KARU; GU, YUCHUN

2012-01-01

Breast cancer is the most frequent cancer in women. Evidence suggests that the polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) affect breast cancer proliferation, differentiation and prognosis. However, the mechanism still remains unclear. In this study, the expression of transient receptor potential canonical (TRPC)3 was detected throughout the cell cytoplasm and at the cell surface of MCF-7 cells. Ca2+ entry was induced in these cells via activated TRPC3 by either the diacylglycerol analogue (OAG) or by intracellular Ca2+ store depletion. TRPC-mediated Ca2+ entry was inhibited by PUFAs including arachidonic acid (AA) and linolenic acid (LA) but not saturated fatty acids. Overexpression of the PUFA degradation enzyme, cyclooxygenase 2 (COX2), enhanced capacitative Ca2+ entry. In addition, inhibition of COX2 reduced [Ca2+]i. Nevertheless, inhibition of TRPC reduced the cell cycle S phase and cell migration, implicating a functional role for TRP-mediated Ca2+ entry in cell proliferation and invasion. Exogenous PUFA as well as a TRPC3 antagonist consistently attenuated breast cancer cell proliferation and migration, suggesting a mechanism in which PUFA restrains the breast cancer partly via its inhibition of TRPC channels. Additionally, our results also suggest that TRPC3 appears as a new mediator of breast cancer cell migration/invasion and represents a potential target for a new class of anticancer agent. PMID:22692672

Fad24, a Positive Regulator of Adipogenesis, Is Required for S Phase Re-entry of C2C12 Myoblasts Arrested in G0 Phase and Involved in p27(Kip1) Expression at the Protein Level.

PubMed

Ochiai, Natsuki; Nishizuka, Makoto; Osada, Shigehiro; Imagawa, Masayoshi

2016-05-01

Factor for adipocyte differentiation 24 (fad24) is a positive regulator of adipogenesis. We previously found that human fad24 is abundantly expressed in skeletal muscle. However, the function of fad24 in skeletal muscle remains largely unknown. Because skeletal muscle is a highly regenerative tissue, we focused on the function of fad24 in skeletal muscle regeneration. In this paper, we investigated the role of fad24 in the cell cycle re-entry of quiescent C2C12 myoblasts-mimicked satellite cells. The expression levels of fad24 and histone acetyltransferase binding to ORC1 (hbo1), a FAD24-interacting factor, were elevated at the early phase of the regeneration process in response to cardiotoxin-induced muscle injury. The knockdown of fad24 inhibited the proliferation of quiescent myoblasts, whereas fad24 knockdown did not affect differentiation. S phase entry following serum activation is abrogated by fad24 knockdown in quiescent cells. Furthermore, fad24 knockdown cells show a marked accumulation of p27(Kip1) protein. These results suggest that fad24 may have an important role in the S phase re-entry of quiescent C2C12 cells through the regulation of p27(Kip1) at the protein level.

Gluconeogenesis in Leishmania mexicana

PubMed Central

Rodriguez-Contreras, Dayana; Hamilton, Nicklas

2014-01-01

Gluconeogenesis is an active pathway in Leishmania amastigotes and is essential for their survival within the mammalian cells. However, our knowledge about this pathway in trypanosomatids is very limited. We investigated the role of glycerol kinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate phosphate dikinase (PPDK) in gluconeogenesis by generating the respective Leishmania mexicana Δgk, Δpepck, and Δppdk null mutants. Our results demonstrated that indeed GK, PEPCK, and PPDK are key players in the gluconeogenesis pathway in Leishmania, although stage-specific differences in their contribution to this pathway were found. GK participates in the entry of glycerol in promastigotes and amastigotes; PEPCK participates in the entry of aspartate in promastigotes, and PPDK is involved in the entry of alanine in amastigotes. Furthermore, the majority of alanine enters into the pathway via decarboxylation of pyruvate in promastigotes, whereas pathway redundancy is suggested for the entry of aspartate in amastigotes. Interestingly, we also found that l-lactate, an abundant glucogenic precursor in mammals, was used by Leishmania amastigotes to synthesize mannogen, entering the pathway through PPDK. On the basis of these new results, we propose a revision in the current model of gluconeogenesis in Leishmania, emphasizing the differences between amastigotes and promastigotes. This work underlines the importance of studying the trypanosomatid intracellular life cycle stages to gain a better understanding of the pathologies caused in humans. PMID:25288791

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor.

PubMed

Cui, Qinghua; Du, Ruikun; Anantpadma, Manu; Schafer, Adam; Hou, Lin; Tian, Jingzhen; Davey, Robert A; Cheng, Han; Rong, Lijun

2018-03-27

The recent 2014-2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor

PubMed Central

Cui, Qinghua; Du, Ruikun; Anantpadma, Manu; Schafer, Adam; Hou, Lin; Tian, Jingzhen; Cheng, Han; Rong, Lijun

2018-01-01

The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment. PMID:29584652

Enhancing hair follicle regeneration by nonablative fractional laser: Assessment of irradiation parameters and tissue response.

PubMed

Wu, Yueh-Feng; Wang, Shiou-Han; Wu, Pei-Shan; Fan, Sabrina Mai-Yi; Chiu, Hsien-Yi; Tsai, Tsung-Hua; Lin, Sung-Jan

2015-04-01

Identification of methods to enhance anagen entry can be helpful for alopecia. Recently, nonablative laser has been proposed as a potential treatment for alopecia. However, how the laser parameters affect stem cell activity, hair cycles and the associated side effects have not been well characterized. Here we examine the effects of irradiation parameters of 1,550-nm fractional laser on hair cycles. The dorsal skin of eight-week-old female C57BL/6 mice with hair follicles in synchronized telogen was shaved and irradiated with a 1,550-nm fractional erbium-glass laser (Fraxel RE:STORE (SR1500) Laser System, Solta Medical, U.S.A.) with varied beam energies (5-35 mJ) and beam densities (500-3500 microthermal zones/cm(2) ). The cutaneous changes were evaluated both grossly and histologically. Hair follicle stem cell activity was detected by BrdU incorporation and changes in gene expression were quantified by real-time PCR. Direct thermal injury to hair follicles could be observed early after irradiation, especially at higher beam energy. Anagen induction in the irradiated skin showed an all-or-non change. Anagen induction and ulcer formation were affected by the combination of beam energy and density. The lowest beam energy of 5 mJ failed to promote anagen entry at all beam densities tested. As beam energy increased from 10 mJ to 35 mJ, we found a decreasing trend of beam density that could induce anagen entry within 7-9 days with activation of hair follicle stem cells. Beam density above the pro-regeneration density could lead to ulcers and scarring followed by anagen entry in adjacent skin. Analysis of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, revealed that transient moderate inflammation was associated with anagen induction and intense prolonged inflammation preceded ulcer formation. To avoid side effects of hair follicle injury and scarring, appropriate combination of beam energy and density is required. Parameters outside the therapeutic window can result in either no anagen promotion or ulcer formation. © 2015 Wiley Periodicals, Inc.

Structured physician order entry for trauma CT: value in improving clinical information transfer and billing efficiency.

PubMed

Wortman, Jeremy R; Goud, Asha; Raja, Ali S; Marchello, Dana; Sodickson, Aaron

2014-12-01

The purpose of this study was to measure the effects of use of a structured physician order entry system for trauma CT on the communication of clinical information and on coding practices and reimbursement efficiency. This study was conducted between April 1, 2011, and January 14, 2013, at a level I trauma center with 59,000 annual emergency department visits. On March 29, 2012, a structured order entry system was implemented for head through pelvis trauma CT, so-called pan-scan CT. This study compared the following factors before and after implementation: communication of clinical signs and symptoms and mechanism of injury, primary International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code category, success of reimbursement, and time required for successful reimbursement for the examination. Chi-square statistics were used to compare all categoric variables before and after the intervention, and the Wilcoxon rank sum test was used to compare billing cycle times. A total of 457 patients underwent pan-scan CT in 2734 distinct examinations. After the intervention, there was a 62% absolute increase in requisitions containing clinical signs or symptoms (from 0.4% to 63%, p<0.0001) and a 99% absolute increase in requisitions providing mechanism of injury (from 0.4% to 99%, p<0.0001). There was a 19% absolute increase in primary ICD-9-CM codes representing clinical signs or symptoms (from 2.9% to 21.8%, p<0.0001), and a 7% absolute increase in reimbursement success for examinations submitted to insurance carriers (from 83.0% to 89.7%, p<0.0001). For reimbursed studies, there was a 14.7-day reduction in mean billing cycle time (from 68.4 days to 53.7 days, p=0.008). Implementation of structured physician order entry for trauma CT was associated with significant improvement in the communication of clinical history to radiologists. The improvement was also associated with changes in coding practices, greater billing efficiency, and an increase in reimbursement success.

Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses

PubMed Central

Cline, Troy; Baranovich, Tatiana; Govorkova, Elena A.; Schultz-Cherry, Stacey

2014-01-01

ABSTRACT Viruses modulate cellular signaling pathways at almost every step of the infection cycle. Cellular signaling pathways activated at later times of influenza infection have previously been investigated; however, early influenza virus-host cell interactions remain understudied. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates phosphatidylinositol 3-kinase (PI3K) activation and actin reorganization, two critical processes during influenza A virus (IAV) infection in most cell types. Using 6 influenza A virus strains (A/Puerto Rico/8/1934, A/Aichi/2/1968 × A/Puerto Rico/8/1934 reassortant [X-31], A/California/04/2009, mouse-adapted A/California/04/2009, A/WSN/1933, and A/New Caledonia/20/1999), we examined the role of FAK during IAV entry. We found that influenza virus attachment induced PI3K-dependent FAK-Y397 phosphorylation. Pharmacological FAK inhibition or expression of a kinase-dead mutant of FAK led to disruption of the actin meshwork that resulted in sequestration of IAV at the cell periphery and reduced virion localization to early endosomes. Additionally, FAK inhibition impeded viral RNA replication at later times of infection and ultimately resulted in significantly reduced viral titers in both A549 and differentiated normal human bronchial epithelial (NHBE) cells. Although not all tested strains activated FAK, all of them exhibited a reduction in viral replication in response to inhibition of FAK signaling. These findings highlight novel biphasic roles of FAK activation during IAV infection and indicate that FAK serves as a central link between receptor-mediated PI3K activation and actin reorganization during IAV infection. IMPORTANCE We found that FAK links early activation of PI3K and actin reorganization, thereby regulating influenza virus entry. Surprisingly, we also found that FAK can regulate viral RNA replication independently of its role in entry. Our study addresses a knowledge gap in the understanding of signaling events triggered by influenza virus that mediate its internalization and initiation of the infection cycle. Understanding of these fundamental molecular events will be necessary to identify novel host targets, such as FAK, and development of future anti-influenza virus therapeutics. PMID:24696469

Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch

PubMed Central

Seidel, Hannah S; Kimble, Judith

2015-01-01

Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells—including germline stem cells—become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions—GLP-1/Notch signaling—becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance. DOI: http://dx.doi.org/10.7554/eLife.10832.001 PMID:26551561

Three-dimensional visualization of gammaherpesvirus life cycle in host cells by electron tomography.

PubMed

Peng, Li; Ryazantsev, Sergey; Sun, Ren; Zhou, Z Hong

2010-01-13

Gammaherpesviruses are etiologically associated with human tumors. A three-dimensional (3D) examination of their life cycle in the host is lacking, significantly limiting our understanding of the structural and molecular basis of virus-host interactions. Here, we report the first 3D visualization of key stages of the murine gammaherpesvirus 68 life cycle in NIH 3T3 cells, including viral attachment, entry, assembly, and egress, by dual-axis electron tomography. In particular, we revealed the transient processes of incoming capsids injecting viral DNA through nuclear pore complexes and nascent DNA being packaged into progeny capsids in vivo as a spool coaxial with the putative portal vertex. We discovered that intranuclear invagination of both nuclear membranes is involved in nuclear egress of herpesvirus capsids. Taken together, our results provide the structural basis for a detailed mechanistic description of gammaherpesvirus life cycle and also demonstrate the advantage of electron tomography in dissecting complex cellular processes of viral infection.

A wireless mobile health-related quality of life assessment.

PubMed

Wu, Cai; Volk, Robert J; Steinbauer, Jeffrey R; Kuo, Grace M; Smith, J Scott

2003-01-01

Self-administered waiting room questionnaires are popular tools for gathering health information from patients, but they require optical scanning or manual data entry to obtain survey results. The application described here eliminates those extra steps by inputting the results into a remote database directly through wireless connection, and the assessment can be finished easily anywhere in the clinic through a mobile platform. A measure of health-related quality of life, the SF-8 Health Survey, was used in developing this application for using in the clinical setting. It has only eight questions measuring each of the eight domains of health in the longer SF-36 Health Survey.

Image data compression having minimum perceptual error

NASA Technical Reports Server (NTRS)

Watson, Andrew B. (Inventor)

1995-01-01

A method for performing image compression that eliminates redundant and invisible image components is described. The image compression uses a Discrete Cosine Transform (DCT) and each DCT coefficient yielded by the transform is quantized by an entry in a quantization matrix which determines the perceived image quality and the bit rate of the image being compressed. The present invention adapts or customizes the quantization matrix to the image being compressed. The quantization matrix comprises visual masking by luminance and contrast techniques and by an error pooling technique all resulting in a minimum perceptual error for any given bit rate, or minimum bit rate for a given perceptual error.

Image-adapted visually weighted quantization matrices for digital image compression

NASA Technical Reports Server (NTRS)

Watson, Andrew B. (Inventor)

1994-01-01

A method for performing image compression that eliminates redundant and invisible image components is presented. The image compression uses a Discrete Cosine Transform (DCT) and each DCT coefficient yielded by the transform is quantized by an entry in a quantization matrix which determines the perceived image quality and the bit rate of the image being compressed. The present invention adapts or customizes the quantization matrix to the image being compressed. The quantization matrix comprises visual masking by luminance and contrast techniques and by an error pooling technique all resulting in a minimum perceptual error for any given bit rate, or minimum bit rate for a given perceptual error.

Estimation of Soil-Water Characteristic Curves in Multiple-Cycles Using Membrane and TDR System

PubMed Central

Hong, Won-Taek; Jung, Young-Seok; Kang, Seonghun; Lee, Jong-Sub

2016-01-01

The objective of this study is to estimate multiple-cycles of the soil-water characteristic curve (SWCC) using an innovative volumetric pressure plate extractor (VPPE), which is incorporated with a membrane and time domain reflectometry (TDR). The pressure cell includes the membrane to reduce the experimental time and the TDR probe to automatically estimate the volumetric water content. For the estimation of SWCC using the VPPE system, four specimens with different grain size and void ratio are prepared. The volumetric water contents of the specimens according to the matric suction are measured by the burette system and are estimated in the TDR system during five cycles of SWCC tests. The volumetric water contents estimated by the TDR system are almost identical to those determined by the burette system. The experimental time significantly decreases with the new VPPE. The hysteresis in the SWCC is largest in the first cycle and is nearly identical after 1.5 cycles. As the initial void ratio decreases, the air entry value increases. This study suggests that the new VPPE may effectively estimate multiple-cycles of the SWCC of unsaturated soils. PMID:28774139

Early induction of c-Myc is associated with neuronal cell death.

PubMed

Lee, Hyun-Pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2011-11-14

Neuronal cell cycle activation has been implicated in neurodegenerative diseases such as Alzheimer's disease, while the initiating mechanism of cell cycle activation remains to be determined. Interestingly, our previous studies have shown that cell cycle activation by c-Myc (Myc) leads to neuronal cell death which suggests Myc might be a key regulator of cell cycle re-entry mediated neuronal cell death. However, the pattern of Myc expression in the process of neuronal cell death has not been addressed. To this end, we examined Myc induction by the neurotoxic agents camptothecin and amyloid-β peptide in a differentiated SH-SY5Y neuronal cell culture model. Myc expression was found to be significantly increased following either treatment and importantly, the induction of Myc preceded neuronal cell death suggesting it is an early event of neuronal cell death. Since ectopic expression of Myc in neurons causes the cell cycle activation and neurodegeneration in vivo, the current data suggest that induction of Myc by neurotoxic agents or other disease factors might be a key mediator in cell cycle activation and consequent cell death that is a feature of neurodegenerative diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Environmentally friendly tool to control mosquito populations without risk of insecticide resistance: the Lehmann’s funnel entry trap

PubMed Central

2013-01-01

Background Current malaria control strategies have cut down the malaria burden in many endemic areas, however the emergence and rapid spread of insecticide and drug resistance undermine the success of these efforts. There is growing concern that malaria eradication will not be achieved without the introduction of novel control tools. One approach that has been developed in the last few years is based on house screening to reduce indoor mosquito vector densities and consequently decrease malaria transmission. Here screening and trapping were combined in one tool to control mosquito populations. The trap does not require an insecticide or even an attractant, yet it effectively collects incoming resistant and susceptible mosquitoes and kills them. Results Performance of the funnel entry trap was tested in low and high malaria vector density areas. An overall reduction of 70 to 80% of mosquito density was seen in both. Species and molecular forms of Anopheles gambiae identification indicated no variation in the number of Anopheles arabiensis and the molecular forms of An. gambiae between houses and traps. Mosquitoes collected in the traps and in houses were highly resistant to pyrethroids (0.9 kdr-based mechanism). Conclusion There is a global consensus that new intervention tools are needed to cross the last miles in malaria elimination/eradication. The funnel entry trap showed excellent promise in suppressing mosquito densities even in area of high insecticide resistance. It requires no chemicals and is self-operated. PMID:23758904

Decompression Sickness During Simulated Low Pressure Exposure is Increased with Mild Ambulation Exercise

NASA Technical Reports Server (NTRS)

Pollock, N. W.; Natoli, M. J.; Martina, S. D.; Conkin, J.; Wessel, J. H., III; Gernhardt, M. L.

2016-01-01

Musculoskeletal activity accelerates inert gas elimination during oxygen breathing prior to decompression (prebreathe), but may also promote bubble formation (nucleation) and increase the risk of decompression sickness (DCS). The timing, pattern and intensity of musculoskeletal activity are likely critical to the net effect. The NASA Prebreathe Reduction Program (PRP) combined oxygen prebreathe and exercise preceding a 4.3 psia exposure in non-ambulatory subjects (a microgravity analog) to produce two protocols now used by astronauts preparing for extravehicular activity - one employing cycling and non-cycling exercise (CEVIS: 'cycle ergometer vibration isolation system') and one relying on non-cycling exercise only (ISLE: 'in-suit light exercise'). Current efforts investigate whether light exercise normal to 1 G environments increases the risk of DCS over microgravity simulation.

Enhanced electrohydrodynamic force generation in a two-stroke cycle dielectric-barrier-discharge plasma actuator

NASA Astrophysics Data System (ADS)

Sato, Shintaro; Takahashi, Masayuki; Ohnishi, Naofumi

2017-05-01

An approach for electrohydrodynamic (EHD) force production is proposed with a focus on a charge cycle on a dielectric surface. The cycle, consisting of positive-charging and neutralizing strokes, is completely different from the conventional methodology, which involves a negative-charging stroke, in that the dielectric surface charge is constantly positive. The two-stroke charge cycle is realized by applying a DC voltage combined with repetitive pulses. Simulation results indicate that the negative pulse eliminates the surface charge accumulated during constant voltage phase, resulting in repetitive EHD force generation. The time-averaged EHD force increases almost linearly with increasing repetitive pulse frequency and becomes one order of magnitude larger than that driven by the sinusoidal voltage, which has the same peak-to-peak voltage.

Prebiotic chemistry in clouds

NASA Technical Reports Server (NTRS)

Oberbeck, Verne R.; Marshall, John; Shen, Thomas

1991-01-01

The chemical evolution hypothesis of Woese (1979), according to which prebiotic reactions occurred rapidly in droplets in giant atmospheric reflux columns was criticized by Scherer (1985). This paper proposes a mechanism for prebiotic chemistry in clouds that answers Scherer's concerns and supports Woese's hypothesis. According to this mechanism, rapid prebiotic chemical evolution was facilitated on the primordial earth by cycles of condensation and evaporation of cloud drops containing clay condensation nuclei and nonvolatile monomers. For example, amino acids supplied by, or synthesized during entry of meteorites, comets, and interplanetary dust, would have been scavenged by cloud drops containing clay condensation nuclei and would be polymerized within cloud systems during cycles of condensation, freezing, melting, and evaporation of cloud drops.

Space Industry Study Industrial College of the Armed Forces National Defense University

DTIC Science & Technology

2002-06-01

information technologies , especially fiber, cable, and cellular communications, which forced space systems away from old market roles and denied entry to... technologies fill market niches. As technology matures, small satellites have been viewed a partial solution to this cycle, enabling faster programs...years, the largely unforeseen growth in the internet has proven a valuable new market for satellite service providers. And over the past few years

FM dyes enter via a store-operated calcium channel and modify calcium signaling of cultured astrocytes

PubMed Central

Li, Dongdong; Hérault, Karine; Oheim, Martin; Ropert, Nicole

2009-01-01

The amphiphilic fluorescent styryl pyridinium dyes FM1-43 and FM4-64 are used to probe activity-dependent synaptic vesicle cycling in neurons. Cultured astrocytes can internalize FM1-43 and FM4-64 inside vesicles but their uptake is insensitive to the elevation of cytosolic calcium (Ca2+) concentration and the underlying mechanism remains unclear. Here we used total internal reflection fluorescence microscopy and pharmacological tools to study the mechanisms of FM4-64 uptake into cultured astrocytes from mouse neocortex. Our data show that: (i) endocytosis is not a major route for FM4-64 uptake into astrocytes; (ii) FM4-64 enters astrocytes through an aqueous pore and strongly affects Ca2+ homeostasis; (iii) partitioning of FM4-64 into the outer leaflet of the plasma membrane results in a facilitation of store-operated Ca2+ entry (SOCE) channel gating; (iv) FM4-64 permeates and competes with Ca2+ for entry through a SOCE channel; (v) intracellular FM4-64 mobilizes Ca2+ from the endoplasmic reticulum stores, conveying a positive feedback to activate SOCE and to sustain dye uptake into astrocytes. Our study demonstrates that FM dyes are not markers of cycling vesicles in astrocytes and calls for a careful interpretation of FM fluorescence. PMID:20007370

Recent advances in understanding of meiosis initiation and the apomictic pathway in plants.

PubMed

Wang, Chung-Ju R; Tseng, Ching-Chih

2014-01-01

Meiosis, a specialized cell division to produce haploid cells, marks the transition from a sporophytic to a gametophytic generation in the life cycle of plants. In angiosperms, meiosis takes place in sporogenous cells that develop de novo from somatic cells in anthers or ovules. A successful transition from the mitotic cycle to the meiotic program in sporogenous cells is crucial for sexual reproduction. By contrast, when meiosis is bypassed or a mitosis-like division occurs to produce unreduced cells, followed by the development of an embryo sac, clonal seeds can be produced by apomixis, an asexual reproduction pathway found in 400 species of flowering plants. An understanding of the regulation of entry into meiosis and molecular mechanisms of apomictic pathway will provide vital insight into reproduction for plant breeding. Recent findings suggest that AM1/SWI1 may be the key gene for entry into meiosis, and increasing evidence has shown that the apomictic pathway is epigenetically controlled. However, the mechanism for the initiation of meiosis during sexual reproduction or for its omission in the apomictic pathway still remains largely unknown. Here we review the current understanding of meiosis initiation and the apomictic pathway and raised several questions that are awaiting further investigation.

Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice.

PubMed

Iismaa, Siiri E; Li, Ming; Kesteven, Scott; Wu, Jianxin; Chan, Andrea Y; Holman, Sara R; Calvert, John W; Haq, Ahtesham Ul; Nicks, Amy M; Naqvi, Nawazish; Husain, Ahsan; Feneley, Michael P; Graham, Robert M

2018-04-17

We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W v mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture.

Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus.

PubMed

Phongphaew, Wallaya; Kobayashi, Shintaro; Sasaki, Michihito; Carr, Michael; Hall, William W; Orba, Yasuko; Sawa, Hirofumi

2017-01-15

Valosin-containing protein (VCP) is classified as a member of the type II AAA + ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown. It could be shown that the inhibition of endogenous VCP expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused a significant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that VCP may play a role in early steps either the binding or entry steps of the WNV life cycle. Using WNV virus like particles and WNV-DNA-based replicon, it could be demonstrated that perturbation of VCP expression decreased levels of newly synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replication of the WNV life cycle. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlling the response to DNA damage by the APC/C-Cdh1.

PubMed

de Boer, H Rudolf; Guerrero Llobet, S; van Vugt, Marcel A T M

2016-03-01

Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage.

Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

PubMed

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-07-05

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

Complex Virus–Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview

PubMed Central

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-01-01

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV–host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus–host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding. PMID:28678154

Optimizing product life cycle processes in design phase

NASA Astrophysics Data System (ADS)

Faneye, Ola. B.; Anderl, Reiner

2002-02-01

Life cycle concepts do not only serve as basis in assisting product developers understand the dependencies between products and their life cycles, they also help in identifying potential opportunities for improvement in products. Common traditional concepts focus mainly on energy and material flow across life phases, necessitating the availability of metrics derived from a reference product. Knowledge of life cycle processes won from an existing product is directly reused in its redesign. Depending on sales volume nevertheless, the environmental impact before product optimization can be substantial. With modern information technologies today, computer-aided life cycle methodologies can be applied well before product use. On the basis of a virtual prototype, life cycle processes are analyzed and optimized, using simulation techniques. This preventive approach does not only help in minimizing (or even eliminating) environmental burdens caused by product, costs incurred due to changes in real product can also be avoided. The paper highlights the relationship between product and life cycle and presents a computer-based methodology for optimizing the product life cycle during design, as presented by SFB 392: Design for Environment - Methods and Tools at Technical University, Darmstadt.

Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria.

PubMed

Su, Yu-Bin; Peng, Bo; Li, Hui; Cheng, Zhi-Xue; Zhang, Tian-Tuo; Zhu, Jia-Xin; Li, Dan; Li, Min-Yi; Ye, Jin-Zhou; Du, Chao-Chao; Zhang, Song; Zhao, Xian-Liang; Yang, Man-Jun; Peng, Xuan-Xian

2018-02-13

The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in Escherichia coli and Edwardsiella tarda These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.

A Modified Through-Flow Wave Rotor Cycle with Combustor Bypass Ducts

NASA Technical Reports Server (NTRS)

Paxson Daniel E.; Nalim, M. Razi

1998-01-01

A wave rotor cycle is described which avoids the inherent problem of combustor exhaust gas recirculation (EGR) found in four-port, through-flow wave rotor cycles currently under consideration for topping gas turbine engines. The recirculated hot gas is eliminated by the judicious placement of a bypass duct which transfers gas from one end of the rotor to the other. The resulting cycle, when analyzed numerically, yields an absolute mean rotor temperature 18% below the already impressive value of the conventional four-port cycle (approximately the turbine inlet temperature). The absolute temperature of the gas leading to the combustor is also reduced from the conventional four-port design by 22%. The overall design point pressure ratio of this new bypass cycle is approximately the same as the conventional four-port cycle. This paper will describe the EGR problem and the bypass cycle solution including relevant wave diagrams. Performance estimates of design and off-design operation of a specific wave rotor will be presented. The results were obtained using a one-dimensional numerical simulation and design code.

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability.

PubMed

Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Fernández-López, José-Antonio; Romero, María del Mar; Alemany, Marià; Remesar, Xavier

2014-01-01

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NO x ; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NO(x) and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

PubMed Central

Sabater, David; Arriarán, Sofía; Fernández-López, José-Antonio; Romero, María del Mar; Remesar, Xavier

2014-01-01

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids. We analyzed whether reduced urea excretion was a consequence of higher NOx; (nitrite, nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion. There were no differences in plasma nitrate or nitrite. NOx and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithine when compared with controls, whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability. PMID:24707502

Use of vacuum-steam-vacuum and ionizing radiation to eliminate Listeria innocua from ham.

PubMed

Sommers, Christopher; Kozempel, Michael; Fan, Xuetong; Radewonuk, E Richard

2002-12-01

Listeria spp. are a frequent postprocess contaminant of ready-to-eat (RTE) meat products, including ham. Vacuum-steam-vacuum (VSV) technology has been used successfully to eliminate Listeria innocua from hot dogs. Ionizing radiation can eliminate Listeria spp. from RTE meats. However, the excessive application of either technology can cause changes in product quality, including structural changes, changes in cure color (redness), and lipid oxidation. In this study, two cycles of VSV were combined with 2.0 kGy of ionizing radiation to obtain 4.40- and 4.85-log10 reductions of L. innocua on ham meat and skin, respectively. The use of both treatments resulted in an additive, as opposed to synergistic, reduction of L. innocua on ham. The combination treatment did not cause statistically significant changes in product structure, color (redness), or lipid oxidation.

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

PubMed Central

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

PubMed

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells.

PubMed

Liu, Chun-Chun; Zhang, Yun-Na; Li, Zhao-Yao; Hou, Jin-Xiu; Zhou, Jing; Kan, Lin; Zhou, Bin; Chen, Pu-Yan

2017-10-01

During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses. IMPORTANCE Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that requires Rab5 and Rab11. Our work provides a detailed picture of the entry of JEV into BHK-21 cells and the cellular events that follow. Copyright © 2017 American Society for Microbiology.

40 CFR 129.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Discharge Elimination System established by section 402 of the Act and implemented in regulations in 40 CFR... time exceeding 96 hours and continuing at least through one reproductive cycle; and will not result in a significant risk of adverse health effects in a large human population based on available...

40 CFR 129.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Discharge Elimination System established by section 402 of the Act and implemented in regulations in 40 CFR... time exceeding 96 hours and continuing at least through one reproductive cycle; and will not result in a significant risk of adverse health effects in a large human population based on available...

40 CFR 129.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Discharge Elimination System established by section 402 of the Act and implemented in regulations in 40 CFR... time exceeding 96 hours and continuing at least through one reproductive cycle; and will not result in a significant risk of adverse health effects in a large human population based on available...

40 CFR 129.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Discharge Elimination System established by section 402 of the Act and implemented in regulations in 40 CFR... time exceeding 96 hours and continuing at least through one reproductive cycle; and will not result in a significant risk of adverse health effects in a large human population based on available...

40 CFR 129.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Discharge Elimination System established by section 402 of the Act and implemented in regulations in 40 CFR... time exceeding 96 hours and continuing at least through one reproductive cycle; and will not result in a significant risk of adverse health effects in a large human population based on available...

Earth Return Aerocapture for the TransHab/Ellipsled Vehicle

NASA Technical Reports Server (NTRS)

Muth, W. D.; Hoffmann, C.; Lyne, J. E.

2000-01-01

The current architecture being considered by NASA for a human Mars mission involves the use of an aerocapture procedure at Mars arrival and possibly upon Earth return. This technique would be used to decelerate the vehicles and insert them into their desired target orbits, thereby eliminating the need for propulsive orbital insertions. The crew may make the interplanetary journey in a large, inflatable habitat known as the TransHab. It has been proposed that upon Earth return, this habitat be captured into orbit for use on subsequent missions. In this case, the TransHab would be complimented with an aeroshell, which would protect it from heating during the atmospheric entry and provide the vehicle with aerodynamic lift. The aeroshell has been dubbed the "Ellipsled" because of its characteristic shape. This paper reports the results of a preliminary study of the aerocapture of the TransHab/Ellipsled vehicle upon Earth return. Undershoot and overshoot boundaries have been determined for a range of entry velocities, and the effects of variations in the atmospheric density profile, the vehicle deceleration limit, the maximum vehicle roll rate, the target orbit, and the vehicle ballistic coefficient have been examined. A simple, 180 degree roll maneuver was implemented in the undershoot trajectories to target the desired 407 km circular Earth orbit. A three-roll sequence was developed to target not only a specific orbital energy, but also a particular inclination, thereby decreasing propulsive inclination changes and post-aerocapture delta-V requirements. Results show that the TransHab/Ellipsled vehicle has a nominal corridor width of at least 0.7 degrees for entry speeds up to 14.0 km/s. Most trajectories were simulated using continuum flow aerodynamics, but the impact of high-altitude viscous effects was evaluated and found to be minimal. In addition, entry corridor comparisons have been made between the TransHab/Ellipsled and a modified Apollo capsule which is also being considered as the crew return vehicle; because of its slightly higher lift-to-drag ratio, the TransHab has a modest advantage with regard to corridor width. Stagnation-point heating rates and integrated heat loads were determined for a range of vehicle ballistic coefficients and entry velocities.

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

PubMed Central

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M.; Whitmire, Jason K.; Maury, Wendy

2017-01-01

ABSTRACT Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. PMID:28874468

Technical and economic feasibility study of solar/fossil hybrid power systems

NASA Technical Reports Server (NTRS)

Bloomfield, H. S.; Calogeras, J. E.

1977-01-01

Results show that new hybrid systems utilizing fossil fuel augmentation of solar energy can provide significant capital and energy cost benefits when compared with solar thermal systems requiring thermal storage. These benefits accrue from a reduction of solar collection area that results from both the use of highly efficient gas and combined cycle energy conversion subsystems and elimination of the requirement for long-term energy storage subsystems. Technical feasibility and fuel savings benefits of solar hybrid retrofit to existing fossil-fired, gas and vapor cycle powerplants was confirmed; however, economic viability of steam cycle retrofit was found to be dependent on the thermodynamic and operational characteristics of the existing powerplant.

Breaking the Intergenerational Cycle of Disadvantage: The Three Generation Approach

PubMed Central

Johnson, Sara B.; Goodman, Elizabeth

2016-01-01

Health disparities in the United States related to socioeconomic status are persistent and pervasive. This review highlights how social disadvantage, particularly low socioeconomic status and the health burden it brings, is passed from 1 generation to the next. First, we review current frameworks for understanding the intergenerational transmission of health disparities and provide 4 illustrative examples relevant to child health, development, and well-being. Second, the leading strategy to break the cycle of poverty in young families in the United States, the 2-generation approach, is reviewed. Finally, we propose a new 3-generation approach that must combine with the 2-generation approach to interrupt the intergenerational cycle of disadvantage and eliminate health disparities. PMID:27244844

Cyclin C influences the timing of mitosis in fission yeast

PubMed Central

Banyai, Gabor; Szilagyi, Zsolt; Baraznenok, Vera; Khorosjutina, Olga; Gustafsson, Claes M.

2017-01-01

The multiprotein Mediator complex is required for the regulated transcription of nearly all RNA polymerase II–dependent genes. Mediator contains the Cdk8 regulatory subcomplex, which directs periodic transcription and influences cell cycle progression in fission yeast. Here we investigate the role of CycC, the cognate cyclin partner of Cdk8, in cell cycle control. Previous reports suggested that CycC interacts with other cellular Cdks, but a fusion of CycC to Cdk8 reported here did not cause any obvious cell cycle phenotypes. We find that Cdk8 and CycC interactions are stabilized within the Mediator complex and the activity of Cdk8-CycC is regulated by other Mediator components. Analysis of a mutant yeast strain reveals that CycC, together with Cdk8, primarily affects M-phase progression but mutations that release Cdk8 from CycC control also affect timing of entry into S phase. PMID:28515143

VDAC3 and Mps1 negatively regulate ciliogenesis.

PubMed

Majumder, Shubhra; Fisk, Harold A

2013-03-01

Centrosomes serve to organize new centrioles in cycling cells, whereas in quiescent cells they assemble primary cilia. We have recently shown that the mitochondrial porin VDAC3 is also a centrosomal protein that is predominantly associated with the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes. Here, we show that depletion of VDAC3 causes inappropriate ciliogenesis in cycling cells, while expression of GFP-VDAC3 suppresses ciliogenesis in quiescent cells. Mps1 also negatively regulates ciliogenesis, and the inappropriate ciliogenesis caused by VDAC3 depletion can be bypassed by targeting Mps1 to centrosomes independently of VDAC3. Thus, our data show that a VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry and suppresses cilia assembly in proliferating cells. Our data also suggests that VDAC3 might be a link between mitochondrial dysfunction and ciliopathies in mammalian cells.

Design of production process main shaft process with lean manufacturing to improve productivity

NASA Astrophysics Data System (ADS)

Siregar, I.; Nasution, A. A.; Andayani, U.; Anizar; Syahputri, K.

2018-02-01

This object research is one of manufacturing companies that produce oil palm machinery parts. In the production process there is delay in the completion of the Main shaft order. Delays in the completion of the order indicate the low productivity of the company in terms of resource utilization. This study aimed to obtain a draft improvement of production processes that can improve productivity by identifying and eliminating activities that do not add value (non-value added activity). One approach that can be used to reduce and eliminate non-value added activity is Lean Manufacturing. This study focuses on the identification of non-value added activity with value stream mapping analysis tools, while the elimination of non-value added activity is done with tools 5 whys and implementation of pull demand system. Based on the research known that non-value added activity on the production process of the main shaft is 9,509.51 minutes of total lead time 10,804.59 minutes. This shows the level of efficiency (Process Cycle Efficiency) in the production process of the main shaft is still very low by 11.89%. Estimation results of improvement showed a decrease in total lead time became 4,355.08 minutes and greater process cycle efficiency that is equal to 29.73%, which indicates that the process was nearing the concept of lean production.

Low Cost Entry, Descent, and Landing (EDL) Instrumentation for Planetary Missions

NASA Technical Reports Server (NTRS)

Hwang, H. H.; Munk, M. M.; Dillman, R. A.; Mahzari, M.; Swanson, G. T.; White, T. R.

2016-01-01

Missions that involve traversing through a planetary atmosphere are unique opportunities that require elements of entry, descent, and landing (EDL). Many aspects of the EDL sequence are qualified using analysis and simulation due to the inability to conduct appropriate ground tests, however validating flight data are often lacking, especially for missions not involving Earth re-entry. NASA has made strategic decisions to collect EDL flight data in order to improve future mission designs. For example, MEDLI1 and EFT-1 gathered hypersonic pressure and in-depth temperature data in the thermal protection system (TPS). However, the ability to collect EDL flight data from the smaller competed missions, such as Discovery and New Frontiers, has been limited in part due to the Principal Investigator-managed cost-caps (PIMCC). The recent NASA decision to consider EDL instrumentation earlier in the mission design cycle led to the inclusion of a requirement in the Discovery 2014 Announcement of Opportunity which requires all missions that involve EDL to include an Engineering Science Investigation (ESI).2 The ESI would involve sensors for aerothermal environment and TPS; atmosphere, aerodynamics, and flight dynamics; atmospheric decelerator; and/or vehicle structure.3 The ESI activity would be funded outside of the PIMCC.

Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages

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

Arcangeletti, Maria-Cristina, E-mail: mariacristina.arcangeletti@unipr.it; Germini, Diego; Rodighiero, Isabella

2013-05-25

Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promotingmore » cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle. - Highlights: ► We studied HCMV infection impact on THP-1 macrophage cell cycle. ► We analysed the role played by Toll-like receptor (TLR) 4 upon HCMV infection. ► HCMV pushes THP-1 macrophages (i.e. resting cells) to re-enter the cell cycle. ► TLR4 pathway inhibition strongly affects the effectiveness of HCMV replication. ► TLR4 pathway inhibition significantly decreases HCMV-induced cell cycle re-entry.« less

A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination

PubMed Central

Stringer, Daniel K.

2011-01-01

ESCRTs (endosomal sorting complexes required for transport) bind and sequester ubiquitinated membrane proteins and usher them into multivesicular bodies (MVBs). As Ubiquitin (Ub)-binding proteins, ESCRTs themselves become ubiquitinated. However, it is unclear whether this regulates a critical aspect of their function or is a nonspecific consequence of their association with the Ub system. We investigated whether ubiquitination of the ESCRTs was required for their ability to sort cargo into the MVB lumen. Although we found that Rsp5 was the main Ub ligase responsible for ubiquitination of ESCRT-0, elimination of Rsp5 or elimination of the ubiquitinatable lysines within ESCRT-0 did not affect MVB sorting. Moreover, by fusing the catalytic domain of deubiquitinating peptidases onto ESCRTs, we could block ESCRT ubiquitination and the sorting of proteins that undergo Rsp5-dependent ubiquitination. Yet, proteins fused to a single Ub moiety were efficiently delivered to the MVB lumen, which strongly indicates that a single Ub is sufficient in sorting MVBs in the absence of ESCRT ubiquitination. PMID:21242292

Pre-exposure to 50 Hz-electromagnetic fields enhanced the antiproliferative efficacy of 5-fluorouracil in breast cancer MCF-7 cells

PubMed Central

Chen, Sha; Sun, Xiongshan; Guan, Xiao; Yang, Yao; Peng, Bingjie; Pan, Xiaodong; Li, Jinfang; Yi, Weijing; Li, Peng; Zhang, Hongwei; Feng, Dongfang; Chen, An; Li, Xiaohui; Yin, Zuoming

2018-01-01

Resistance to 5-fluorouracil (5-FU) and its induced immune suppression have prevented its extensive application in the clinical treatment of breast cancer. In this study, the combined effect of 50 Hz-EMFs and 5-FU in the treatment of breast cancer was explored. MCF-7 and MCF10A cells were pre-exposed to 50 Hz-EMFs for 0, 2, 4, 8 and 12 h and then treated with different concentrations of 5-FU for 24 h; cell viability was analyzed by MTT assay and flow cytometry. After pre-exposure to 50 Hz-EMFs for 12 h, apoptosis and cell cycle distribution in MCF-7 and MCF10A cells were detected via flow cytometry and DNA synthesis was measured by EdU incorporation assay. Apoptosis-related and cell cycle-related gene and protein expression levels were monitored by qPCR and western blotting. Pre-exposure to 50 Hz-EMFs for 12 h enhanced the antiproliferative effect of 5-FU in breast cancer cell line MCF-7 in a dose-dependent manner but not in normal human breast epithelial cell line MCF10A. Exposure to 50 Hz-EMFs had no effect on apoptosis and P53 expression of MCF-7 and MCF10A cells, whereas it promoted DNA synthesis, induced entry of MCF-7 cells into the S phase of cell cycle, and upregulated the expression levels of cell cycle-related proteins Cyclin D1 and Cyclin E. Considering the pharmacological mechanisms of 5-FU in specifically disrupting DNA synthesis, this enhanced inhibitory effect might have resulted from the specific sensitivity of MCF7 cells in active S phase to 5-FU. Our findings demonstrate the enhanced cytotoxic activity of 5-FU on MCF7 cells through promoting entry into the S phase of the cell cycle via exposure to 50 Hz-EMFs, which provides a novel method of cancer treatment based on the combinatorial use of 50 Hz-EMFs and chemotherapy. PMID:29617363

DYRK1A Is a Regulator of S-Phase Entry in Hepatic Progenitor Cells.

PubMed

Kruitwagen, Hedwig S; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda J; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

2018-01-15

Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage, HPC proliferation is triggered by external activation mechanisms from their niche. Although several important proproliferative mechanisms have been described, it is not known which key intracellular regulators govern the switch between HPC quiescence and active cell cycle. We performed a high-throughput kinome small interfering RNA (siRNA) screen in HepaRG cells, a HPC-like cell line, and evaluated the effect on proliferation with a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. One hit increased the percentage of EdU-positive cells after knockdown: dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A). Although upon DYRK1A silencing, the percentage of EdU- and phosphorylated histone H3 (pH3)-positive cells was increased, and total cell numbers were not increased, possibly through a subsequent delay in cell cycle progression. This phenotype was confirmed with chemical inhibition of DYRK1A using harmine and with primary HPCs cultured as liver organoids. DYRK1A inhibition impaired Dimerization Partner, RB-like, E2F, and multivulva class B (DREAM) complex formation in HPCs and abolished its transcriptional repression on cell cycle progression. To further analyze DYRK1A function in HPC proliferation, liver organoid cultures were established from mBACtgDyrk1A mice, which harbor one extra copy of the murine Dyrk1a gene (Dyrk+++). Dyrk+++ organoids had both a reduced percentage of EdU-positive cells and reduced proliferation compared with wild-type organoids. This study provides evidence for an essential role of DYRK1A as balanced regulator of S-phase entry in HPCs. An exact gene dosage is crucial, as both DYRK1A deficiency and overexpression affect HPC cell cycle progression.

Regulation of store-operated Ca{sup 2+} entry activity by cell cycle dependent up-regulation of Orai2 in brain capillary endothelial cells

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

Kito, Hiroaki; Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto; Yamamura, Hisao

2015-04-10

Store-operated Ca{sup 2+} entry (SOCE) via Orai1 and STIM1 complex is supposed to have obligatory roles in the regulation of cellular functions of vascular endothelial cells, while little is known about the contribution of Orai2. Quantitative PCR and Western blot analyses indicated the expression of Orai2 and STIM2, in addition to Orai1 and STIM1 in bovine brain capillary endothelial cell line, t-BBEC117. During the exponential growth of t-BBEC117, the knockdown of Orai1 and STIM1 significantly reduced the SOCE activity, whereas Orai2 and STIM2 siRNAs had no effect. To examine whether endogenous SOCE activity contributes to the regulation of cell cyclemore » progression, t-BBEC117 were synchronized using double thymidine blockage. At the G2/M phase, Ca{sup 2+} influx via SOCE was decreased and Orai2 expression was increased compared to the G0/G1 phase. When Orai2 was knocked down at the G2/M phase, the decrease in SOCE was removed, and cell proliferation was partly attenuated. Taken together, Orai1 significantly contributes to cell proliferation via the functional expression, which is presumably independent of the cell cycle phases. In construct, Orai2 is specifically up-regulated during the G2/M phase, negatively modulates the SOCE activity, and may contribute to the regulation of cell cycle progression in brain capillary endothelial cells. - Highlights: • Orai1 is essential for SOCE activity in brain capillary endothelial cells (BCECs). • Cell cycle independent expression of Orai1 regulated SOCE and cell proliferation. • Orai2 was up-regulated only at G2/M phase and this consequently reduced SOCE. • Orai2 as well as Orai1 is a key player controlling SOCE and proliferation in BCECs.« less

Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1).

PubMed

Yamaguchi, Koushi; Honda, Mitsuo; Ikigai, Hajime; Hara, Yukihiko; Shimamura, Tadakatsu

2002-01-01

Epigallocatechin gallate (EGCg), the major tea catechin, is known as a potent anti-bacterial agent. In addition, anti-tumor promoting, anti-inflammatory, anti-oxidative and antiviral activities have been reported. In the present study, we investigated possible anti-human immunodeficiency virus type-1 (HIV-1) activity of EGCg and its mechanisms of action in the viral life cycle. EGCg impinges on each step of the HIV life cycle. Thus, destruction of the viral particles, viral attachment to cells, post-adsorption entry into cells, reverse transcription (RT), viral production from chronically-infected cells, and the level of expression of viral mRNA, were analyzed using T-lymphoid (H9) and monocytoid (THP-1) cell systems, and antiviral protease activity was measured using a cell-free assay. Inhibitory effects of EGCg on specific binding of the virions to the cellular surfaces and changes in the steady state viral regulation (mRNA expression) due to EGCg were not observed. However, EGCg had a destructive effect on the viral particles, and post-adsorption entry and RT in acutely infected monocytoid cells were significantly inhibited at concentrations of EGCg greater than 1 microM, and protease kinetics were suppressed at a concentration higher than 10 microM in the cell-free study. Viral production by THP-1 cells chronically-infected with HIV-1 was also inhibited in a dose-dependent manner and the inhibitory effect was enhanced by liposome modification of EGCg. As expected, increased viral mRNA production was observed in lipopolysaccharide (LPS)-activated chronically HIV-1-infected cells. This production was significantly inhibited by EGCg treatment of THP-1 cells. In contrast, production of HIV-1 viral mRNA in unstimulated or LPS-stimulated T-lymphoid cells (H9) was not inhibited by EGCg. Anti-HIV viral activity of EGCg may thus result from an interaction with several steps in the HIV-1 life cycle.

Prelithiation of silicon-carbon nanotube anodes for lithium ion batteries by stabilized lithium metal powder (SLMP).

PubMed

Forney, Michael W; Ganter, Matthew J; Staub, Jason W; Ridgley, Richard D; Landi, Brian J

2013-09-11

Stabilized lithium metal powder (SLMP) has been applied during battery assembly to effectively prelithiate high capacity (1500-2500 mAh/g) silicon-carbon nanotube (Si-CNT) anodes, eliminating the 20-40% first cycle irreversible capacity loss. Pressure-activation of SLMP is shown to enhance prelithiation and enable capacity matching between Si-CNT anodes and lithium nickel cobalt aluminum oxide (NCA) cathodes in full batteries with minimal added mass. The prelithiation approach enables high energy density NCA/Si-CNT batteries achieving >1000 cycles at 20% depth-of-discharge.

Optical and X-ray radiation from fast pulsars - Effects of duty cycle and spectral shape

NASA Technical Reports Server (NTRS)

Pacini, F.; Salvati, M.

1987-01-01

The optical luminosity of PSR 0540 is considerably stronger than what one would have predicted in a simple model developed earlier where the pulses are synchrotron radiation by secondary electrons near the light cylinder. This discrepancy can be eliminated if one incorporates into the model the effects of the large duty cycle and the spectral properties of PSR 0540. It is also shown that the same model can provide a reasonable fit to the observed X-ray fluxes from fast pulsars.

ON IMPROVING THE ECONOMIC STATUS OF THE NEGRO.

ERIC Educational Resources Information Center

TOBIN, JAMES

EFFORTS TO ELIMINATE NEGRO POVERTY MUST BE UNDERTAKEN WITHIN A FAVORABLE OVERALL ECONOMIC CLIMATE, AND THE CURRENT CLIMATE IS NOT FAVORABLE BECAUSE MANPOWER AND PLANT CAPACITY ARE NOT FULLY UTILIZED. SUCH FACTORS AS LIMITED JOBS, EXAGGERATED JOB REQUIREMENTS, LOWER EARNING CAPACITY, DURATION OF UNEMPLOYMENT, FLUCTUATIONS OF THE BUSINESS CYCLE, AND…

Ending the Tech Refresh Nightmare

ERIC Educational Resources Information Center

Demski, Jennifer

2010-01-01

As higher education budgets tighten in the ongoing recession, colleges and universities have found themselves questioning, lengthening, and even eliminating tech refresh cycles. Yet how deep an institution cuts into its refresh program can compromise its ability to provide an up-to-date and competitive computing environment for students and a…

THE IMPORTANCE OF EMISSIONS SPECIATION TO THE ATMOSPHERIC TRANSPORT AND DEPOSITION OF MERCURY

EPA Science Inventory

The atmospheric pathway of the global mercury cycle is believed to be the main source of mercury contamination to aquatic eco-systems throughout the United States and in most other nations where direct disposal of mercury to water has been largely eliminated. Although the spatia...

40 CFR 51.357 - Test procedures and standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... invalid test condition, unsafe conditions, fast pass/fail algorithms, or, in the case of the on-board... using approved fast pass or fast fail algorithms and multiple pass/fail algorithms may be used during the test cycle to eliminate false failures. The transient test procedure, including algorithms and...

40 CFR 51.357 - Test procedures and standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... invalid test condition, unsafe conditions, fast pass/fail algorithms, or, in the case of the on-board... using approved fast pass or fast fail algorithms and multiple pass/fail algorithms may be used during the test cycle to eliminate false failures. The transient test procedure, including algorithms and...

40 CFR 51.357 - Test procedures and standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... invalid test condition, unsafe conditions, fast pass/fail algorithms, or, in the case of the on-board... using approved fast pass or fast fail algorithms and multiple pass/fail algorithms may be used during the test cycle to eliminate false failures. The transient test procedure, including algorithms and...

40 CFR 51.357 - Test procedures and standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... invalid test condition, unsafe conditions, fast pass/fail algorithms, or, in the case of the on-board... using approved fast pass or fast fail algorithms and multiple pass/fail algorithms may be used during the test cycle to eliminate false failures. The transient test procedure, including algorithms and...

Community Response to a Public Health Threat-VEE

ERIC Educational Resources Information Center

McDonald, John L.; Vuturo, Anthony F.

1975-01-01

After identifying the mosquito as the Venezuelan equine encephalitis vector, health officials worked with the community to eliminate mosquito breeding sites. By educating the public first, cooperation was received in opening drainage areas and stocking water collection areas with mosquito eating fish to interrupt the host-vector-recipient cycle.…

Imaging single cells in a beam of live cyanobacteria with an X-ray laser (CXIDB ID 26)

DOE Data Explorer

Schot, Gijs, vander

2015-02-10

This entry contains ten diffraction patterns, and reconstructions images, of individual living Cyanobium gracile cells, imaged using 517 eV X-rays from the LCLS XFEL. The Hawk software package was used for phasing. The Uppsala aerosol injector was used for sample injection, assuring very low noise levels. The cells come from various stages of the cell cycle, and were imaged in random orientations.

Enhanced lithium ion battery cycling of silicon nanowire anodes by template growth to eliminate silicon underlayer islands.

PubMed

Cho, Jeong-Hyun; Picraux, S Tom

2013-01-01

It is well-known that one-dimensional nanostructures reduce pulverization of silicon (Si)-based anode materials during Li ion cycling because they allow lateral relaxation. However, even with improved designs, Si nanowire-based structures still exhibit limited cycling stability for extended numbers of cycles, with the specific capacity retention with cycling not showing significant improvements over commercial carbon-based anode materials. We have found that one important reason for the lack of long cycling stability can be the presence of milli- and microscale Si islands which typically form under nanowire arrays during their growth. Stress buildup in these Si island underlayers with cycling results in cracking, and the loss of specific capacity for Si nanowire anodes, due to progressive loss of contact with current collectors. We show that the formation of these parasitic Si islands for Si nanowires grown directly on metal current collectors can be avoided by growth through anodized aluminum oxide templates containing a high density of sub-100 nm nanopores. Using this template approach we demonstrate significantly enhanced cycling stability for Si nanowire-based lithium-ion battery anodes, with retentions of more than ~1000 mA·h/g discharge capacity over 1100 cycles.

Gluconeogenesis in Leishmania mexicana: contribution of glycerol kinase, phosphoenolpyruvate carboxykinase, and pyruvate phosphate dikinase.

PubMed

Rodriguez-Contreras, Dayana; Hamilton, Nicklas

2014-11-21

Gluconeogenesis is an active pathway in Leishmania amastigotes and is essential for their survival within the mammalian cells. However, our knowledge about this pathway in trypanosomatids is very limited. We investigated the role of glycerol kinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate phosphate dikinase (PPDK) in gluconeogenesis by generating the respective Leishmania mexicana Δgk, Δpepck, and Δppdk null mutants. Our results demonstrated that indeed GK, PEPCK, and PPDK are key players in the gluconeogenesis pathway in Leishmania, although stage-specific differences in their contribution to this pathway were found. GK participates in the entry of glycerol in promastigotes and amastigotes; PEPCK participates in the entry of aspartate in promastigotes, and PPDK is involved in the entry of alanine in amastigotes. Furthermore, the majority of alanine enters into the pathway via decarboxylation of pyruvate in promastigotes, whereas pathway redundancy is suggested for the entry of aspartate in amastigotes. Interestingly, we also found that l-lactate, an abundant glucogenic precursor in mammals, was used by Leishmania amastigotes to synthesize mannogen, entering the pathway through PPDK. On the basis of these new results, we propose a revision in the current model of gluconeogenesis in Leishmania, emphasizing the differences between amastigotes and promastigotes. This work underlines the importance of studying the trypanosomatid intracellular life cycle stages to gain a better understanding of the pathologies caused in humans. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis.

PubMed Central

Percy, N; Belsham, G J; Brangwyn, J K; Sullivan, M; Stone, D M; Almond, J W

1992-01-01

A series of genetic deletions based partly on two RNA secondary structure models (M. A. Skinner, V. R. Racaniello, G. Dunn, J. Cooper, P. D. Minor, and J. W. Almond, J. Mol. Biol. 207:379-392, 1989; E. V. Pilipenko, V. M. Blinov, L. I. Romanova, A. N. Sinyakov, S. V. Maslova, and V. I. Agol, Virology 168:201-209, 1989) was made in the cDNA encoding the 5' noncoding region (5' NCR) of the poliovirus genome in order to study the sequences that direct the internal entry of ribosomes. The modified cDNAs were placed between two open reading frames in a single transcriptional unit and used to transfect cells in culture. Internal entry of ribosomes was detected by measuring translation from the second open reading frame in the bicistronic mRNA. When assayed alone, a large proportion of the poliovirus 5' NCR superstructure including several well-defined stem-loops was required for ribosome entry and efficient translation. However, in cells cotransfected with a complete infectious poliovirus cDNA, the requirement for the stem-loops in this large superstructure was reduced. The results suggest that virus infection modifies the cellular translational machinery, so that shortened forms of the 5' NCR are sufficient for cap-independent translation, and that the internal entry of ribosomes occurs by two distinct modes during the virus replication cycle. Images PMID:1310772

Integrated systems analysis of persistent polar pollutants in the water cycle.

PubMed

van der Voet, E; Nikolic, I; Huppes, G; Kleijn, R

2004-01-01

Persistent polar pollutants (P3) are difficult to degrade in standard waste water treatment plants. As a result, they end up in the effluent and are emitted to the surface water. In some areas, this problem is aggravated through "closed loop recycling", causing concentrations of P3 in surface water to build up over time. This could cause violation of (future) EU regulations. In the P-THREE project, various alternative waste water treatment techniques are investigated regarding their effectiveness in eliminating these substances, especially membrane bioreactor treatment and advanced oxidation processes, MBR and AOP. The integrated systems analysis which is the subject of this paper assesses these techniques in a broader systems context: (1) the life-cycle of the P3, (2) the life cycle of the WWTPs, and (3) the WWTP life cycle costs.

Effect of high-pressure H{sub 2}O treatment on elimination of interfacial GeO{sub X} layer between ZrO{sub 2} and Ge stack

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

Huang, Chen-Shuo; Liu, Po-Tsun

2011-08-22

This investigation demonstrates the effect of high-pressure H{sub 2}O treatment on the elimination of the interfacial germanium suboxide (GeO{sub X}) layer between ZrO{sub 2} and Ge. The formation of GeO{sub X} interlayer increases the gate-leakage current and worsen the controllability of the gate during deposition or thermal cycles. X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy reveal that high-pressure H{sub 2}O treatment eliminates the interfacial GeO{sub X} layer. The physical mechanism involves the oxidation of non-oxidized Zr with H{sub 2}O and the reduction of GeO{sub X} by H{sub 2}. Treatment with H{sub 2}O reduces the gate-leakage current of a ZrO{submore » 2}/Ge capacitor by a factor of 1000.« less

Dependence of Ca outflow and depression of frog myocardium contraction on ryodipine concentration.

PubMed

Narusevicius, E; Gendviliene, V; Macianskiene, R; Hmelj-Dunai, G; Velena, A; Duburs, G

1988-02-01

The effect of ryodipine on calcium outflow from tissues, on contraction force, the duration of action potentials and the relaxation phase time-constant in the contraction cycles of myocardial strips was studied using frog heart preparations. It was found that calcium outflow (delta Ca) as a function on ryodipine concentration can be represented as: (formula; see text) A linear correlation exists between Ca2+, contraction blocking and the shortening of the action potential in the presence of various ryodipine concentrations. Ryodipine (10(-5) mol/l) decreased the relaxation time-constant by about 20% as compared to controls. It was concluded that calcium outflow from myocardial tissues in response to ryodipine is due to blockade of calcium entry into the cells and their output through the Na+--Ca2+ exchange system. Frog heart myocardial contractions are essentially under the control of calcium entry through sarcolemmal calcium channels.

A Computational Intelligence (CI) Approach to the Precision Mars Lander Problem

NASA Technical Reports Server (NTRS)

Birge, Brian; Walberg, Gerald

2002-01-01

A Mars precision landing requires a landed footprint of no more than 100 meters. Obstacles to reducing the landed footprint include trajectory dispersions due to initial atmospheric entry conditions such as entry angle, parachute deployment height, environment parameters such as wind, atmospheric density, parachute deployment dynamics, unavoidable injection error or propagated error from launch, etc. Computational Intelligence (CI) techniques such as Artificial Neural Nets and Particle Swarm Optimization have been shown to have great success with other control problems. The research period extended previous work on investigating applicability of the computational intelligent approaches. The focus of this investigation was on Particle Swarm Optimization and basic Neural Net architectures. The research investigating these issues was performed for the grant cycle from 5/15/01 to 5/15/02. Matlab 5.1 and 6.0 along with NASA's POST were the primary computational tools.

Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator

PubMed Central

Huang, Jiaoyan; Yan, Wenzhong; Wang, Jinglan; Su, Dan; Ni, Cheng; Li, Jian; Rao, Zihe; Liu, Lei; Lou, Zhiyong

2014-01-01

Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection. PMID:25275585

Alternative Ways to Think about Cellular Internal Ribosome Entry*

PubMed Central

Gilbert, Wendy V.

2010-01-01

Internal ribosome entry sites (IRESs) are specialized mRNA elements that allow recruitment of eukaryotic ribosomes to naturally uncapped mRNAs or to capped mRNAs under conditions in which cap-dependent translation is inhibited. Putative cellular IRESs have been proposed to play crucial roles in stress responses, development, apoptosis, cell cycle control, and neuronal function. However, most of the evidence for cellular IRES activity rests on bicistronic reporter assays, the reliability of which has been questioned. Here, the mechanisms underlying cap-independent translation of cellular mRNAs and the contributions of such translation to cellular protein synthesis are discussed. I suggest that the division of cellular mRNAs into mutually exclusive categories of “cap-dependent” and “IRES-dependent” should be reconsidered and that the implications of cellular IRES activity need to be incorporated into our models of cap-dependent initiation. PMID:20576611

Superior Cardiac Function Via Anaplerotic Pyruvate in the Immature Swine Heart After Cardiopulmonary Bypass and Reperfusion

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

Olson, Aaron; Hyyti, Outi M.; Cohen, Gordon A.

2008-12-01

Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the citric acid cycle (CAC) via carboxylation are linked to stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2]-13C-pyruvate (to achieve a final concentration of 8 mM) was given for 35 minutes starting either during weaning (Group I), after discontinuation (Group II) or without (Control) CPB. Hemodynamic data was collected. 13C NMRmore » spectroscopy was used to determine the fraction of pyruvate entering the CAC via pyruvate carboxylation (PC) to total CAC entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment.« less

BmNHR96 participate BV entry of BmN-SWU1 cells via affecting the cellular cholesterol level.

PubMed

Dong, Xiao-Long; Liu, Tai-Hang; Wang, Wei; Pan, Cai-Xia; Du, Guo-Yu; Wu, Yun-Fei; Pan, Min-Hui; Lu, Cheng

2017-01-22

B.mori nucleopolyhedrovirus (BmNPV), which produces BV and ODV two virion phenotypes in its life cycle, caused the amount of economic loss in sericulture. But the mechanism of its infection was still unclear. In this study we characterized B.mori nuclear hormone receptor 96 (BmNHR96) as a NHR96 family member, which was localized in the nucleus. We also found BmNHR96 over-expression could enhance the entry of BV as well as cellular cholesterol level. Furthermore, we validated that BmNHR96 increased membrane fusion mediated by GP64, which could probably promote BV-infection. In summary, our study suggested that BmNHR96 plays an important role in BV infection and this function probably actualized by affecting cellular cholesterol level, and our results provided insights to the mechanisms of BV-infection of B.mori. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of repeated photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm: an in vitro study.

PubMed

Prażmo, Ewa Joanna; Godlewska, Renata Alicja; Mielczarek, Agnieszka Beata

2017-04-01

The study aimed to investigate the effectiveness of photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm and to analyse how a repeated light irradiation, replenishment of oxygen and photosensitiser affect the results of the photodynamic disinfecting protocol. After chemomechanical preparation, 46 single-rooted human teeth were infected with a clinical strain of E. faecalis and incubated for a week in microaerobic conditions. The experimental procedures included groups of single application of photodynamic therapy, two cycles of PDT, irrigation with 5.25% NaOCl solution and negative and positive control. The number of residing bacterial colonies in the root canals was determined based on the CFU/ml method. In the group of preparations irrigated with NaOCl, bacterial colonies were not observed. A single PDT eliminated 45% of the initial CFU/ml. Repeated PDT eradicated 95% of the intracanal bacterial biofilm. Photodynamic therapy has a high potential for the elimination of E. faecalis biofilm. There is a safe therapeutic window where photoinduced disinfection can be used as an adjuvant to conventional endodontic treatment, which remains the most effective.

Global Water Cycle Diagrams Minimize Human Influence and Over-represent Water Security

NASA Astrophysics Data System (ADS)

Abbott, B. W.; Bishop, K.; Zarnetske, J. P.; Minaudo, C.; Chapin, F. S., III; Plont, S.; Marçais, J.; Ellison, D.; Roy Chowdhury, S.; Kolbe, T.; Ursache, O.; Hampton, T. B.; GU, S.; Chapin, M.; Krause, S.; Henderson, K. D.; Hannah, D. M.; Pinay, G.

2017-12-01

The diagram of the global water cycle is the central icon of hydrology, and for many people, the point of entry to thinking about key scientific concepts such as conservation of mass, teleconnections, and human dependence on ecological systems. Because humans now dominate critical components of the hydrosphere, improving our understanding of the global water cycle has graduated from an academic exercise to an urgent priority. To assess how the water cycle is conceptualized by researchers and the general public, we analyzed 455 water cycle diagrams from textbooks, scientific articles, and online image searches performed in different languages. Only 15% of diagrams integrated human activity into the water cycle and 77% showed no sign of humans whatsoever, although representation of humans varied substantially by region (lowest in China, N. America, and Australia; highest in Western Europe). The abundance and accessibility of freshwater resources were overrepresented, with 98% of diagrams omitting water pollution and climate change, and over 90% of diagrams making no distinction for saline groundwater and lakes. Oceanic aspects of the water cycle (i.e. ocean size, circulation, and precipitation) and related teleconnections were nearly always underrepresented. These patterns held across disciplinary boundaries and through time. We explore the historical and contemporary reasons for some of these biases and present a revised version of the global water cycle based on research from natural and social sciences. We conclude that current depictions of the global water cycle convey a false sense of water security and that reintegrating humans into water cycle diagrams is an important first step towards understanding and sustaining the hydrosocial cycle.

Cost implications of implementation of pathogen-inactivated platelets

PubMed Central

McCullough, Jeffrey; Goldfinger, Dennis; Gorlin, Jed; Riley, William J; Sandhu, Harpreet; Stowell, Christopher; Ward, Dawn; Clay, Mary; Pulkrabek, Shelley; Chrebtow, Vera; Stassinopoulos, Adonis

2015-01-01

BACKGROUND Pathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact. STUDY DESIGN AND METHODS Cost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing 1) special requests and 2) test results, 3) quality control and proficiency testing, 4) equipment acquisition and maintenance, 5) replacement of units lost to positive tests, 6) seasonal or geographic testing, and 7) health department interactions. RESULTS All costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage. CONCLUSIONS While PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing. PMID:25989465

Decreasing the Preincision Time for Pulmonary Lobectomy: The Process of Lean and Value Stream Mapping.

PubMed

Cerfolio, Robert James; Steenwyk, Brad L; Watson, Caroline; Sparrow, James; Belopolsky, Victoria; Townsley, Matthew; Lyerly, Ralph; Downing, Michelle; Bryant, Ayesha; Gurley, William Quinton; Henling, Colleen; Crawford, Jack; Gayeski, Thomas E

2016-03-01

Our objective was to evaluate our results after the implementation of lean (the elimination of wasteful parts of a process). After meetings with our anesthesiologists, we standardized our "in the operating room-to-skin incision protocols" before pulmonary lobectomy. Patients were divided into consecutive cohorts of 300 lobectomy patients. Several protocols were slowly adopted and outcomes were evaluated. One surgeon performed 2,206 pulmonary lobectomies, of which 84% were for cancer. Protocols for lateral decubitus positioning changed over time. We eliminated axillary rolls, arm boards, and beanbags. Monitoring devices were slowly eliminated. Central catheters decreased from 75% to 0% of patients, epidurals from 84% to 3%, arterial catheters from 93% to 4%, and finally, Foley catheters were reduced from 99% to 11% (p ≤ 0.001 for all). A protocol for the insertion of double-lumen endotracheal tubes was established and times decreased (mean, 14 minutes to 1 minute; p = 0.001). After all changes were made, the time between operating room entry and incision decreased from a mean of 64 minutes to 37 minutes (p < 0.001). Outcomes improved, mortality decreased from 3.2% to 0.26% (p = 0.015), and major morbidity decreased from 15.2% to 5.3% (p = 0.042). Lean and value stream mapping can be safely applied to the clinical algorithms of high-risk patient care. We demonstrate that elimination of non-value-added steps can safely decrease preincision time without increasing patient risk in patients who undergo pulmonary lobectomy. Selected centers may be able to adopt some of these lean-driven protocols. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cost implications of implementation of pathogen-inactivated platelets.

PubMed

McCullough, Jeffrey; Goldfinger, Dennis; Gorlin, Jed; Riley, William J; Sandhu, Harpreet; Stowell, Christopher; Ward, Dawn; Clay, Mary; Pulkrabek, Shelley; Chrebtow, Vera; Stassinopoulos, Adonis

2015-10-01

Pathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact. Cost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing (1) special requests and (2) test results, (3) quality control and proficiency testing, (4) equipment acquisition and maintenance, (5) replacement of units lost to positive tests, (6) seasonal or geographic testing, and (7) health department interactions. All costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage. While PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing. © 2015 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

DREAMs make plant cells to cycle or to become quiescent.

PubMed

Magyar, Zoltán; Bögre, László; Ito, Masaki

2016-12-01

Cell cycle phase specific oscillation of gene transcription has long been recognized as an underlying principle for ordered processes during cell proliferation. The G1/S-specific and G2/M-specific cohorts of genes in plants are regulated by the E2F and the MYB3R transcription factors. Mutant analysis suggests that activator E2F functions might not be fully required for cell cycle entry. In contrast, the two activator-type MYB3Rs are part of positive feedback loops to drive the burst of mitotic gene expression, which is necessary at least to accomplish cytokinesis. Repressor MYB3Rs act outside the mitotic time window during cell cycle progression, and are important for the shutdown of mitotic genes to impose quiescence in mature organs. The two distinct classes of E2Fs and MYB3Rs together with the RETINOBLATOMA RELATED are part of multiprotein complexes that may be evolutionary related to what is known as DREAM complex in animals. In plants, there are multiple such complexes with distinct compositions and functions that may be involved in the coordinated cell cycle and developmental regulation of E2F targets and mitotic genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cyclin B in mouse oocytes and embryos: importance for human reproduction and aneuploidy.

PubMed

Polański, Zbigniew; Homer, Hayden; Kubiak, Jacek Z

2012-01-01

Oocyte maturation and early embryo development require precise coordination between cell cycle progression and the developmental programme. Cyclin B plays a major role in this process: its accumulation and degradation is critical for driving the cell cycle through activation and inactivation of the major cell cycle kinase, CDK1. CDK1 activation is required for M-phase entry whereas its inactivation leads to exit from M-phase. The tempo of oocyte meiotic and embryonic mitotic divisions is set by the rate of cyclin B accumulation and the timing of its destruction. By controlling when cyclin B destruction is triggered and by co-ordinating this with the completion of chromosome alignment, the spindle assembly checkpoint (SAC) is a critical quality control system important for averting aneuploidy and for building in the flexibility required to better integrate cell cycle progression with development. In this review we focus on cyclin B metabolism in mouse oocytes and embryos and illustrate how the cell cycle-powered clock (in fact cyclin B-powered clock) controls oocyte maturation and early embryo development, thereby providing important insight into human reproduction and potential causes of Down syndrome.

An Evaluation of Voluntary 2-Dose Varicella Vaccination Coverage in New York City Public Schools

PubMed Central

Rosen, Jennifer B.; Bialek, Stephanie R.; Szeto, Hiram; Zimmerman, Christopher M.

2015-01-01

Objectives. We assessed coverage for 2-dose varicella vaccination, which is not required for school entry, among New York City public school students and examined characteristics associated with receipt of 2 doses. Methods. We measured receipt of either at least 1 or 2 doses of varicella vaccine among students aged 4 years and older in a sample of 336 public schools (n = 223 864 students) during the 2010 to 2011 school year. Data came from merged student vaccination records from 2 administrative data systems. We conducted multivariable regression to assess associations of age, gender, race/ethnicity, and school location with 2-dose prevalence. Results. Coverage with at least 1 varicella dose was 96.2% (95% confidence interval [CI] = 96.2%, 96.3%); coverage with at least 2 doses was 64.8% (95% CI = 64.6%, 64.9%). Increasing student age, non-Hispanic White race/ethnicity, and attendance at school in Staten Island were associated with lower 2-dose coverage. Conclusions. A 2-dose varicella vaccine requirement for school entry would likely improve 2-dose coverage, eliminate coverage disparities, and prevent disease. PMID:25521904

Memory load as a cognitive antidote to performance decrements in data entry.

PubMed

Chapman, Mary J; Healy, Alice F; Kole, James A

2016-10-01

In two experiments, subjects trained in data entry, typing one 4-digit number at a time. At training, subjects either typed the numbers immediately after they appeared (immediate) or typed the previous number from memory while viewing the next number (delayed). In Experiment 2 stimulus presentation time was limited and either nothing or a space (gap) was inserted between the second and third digits. In both experiments after training, all subjects completed a test with no gap and typed numbers immediately. Training with a memory load improved speed across training blocks (Experiment 1) and eliminated the decline in accuracy across training blocks (Experiment 2), thus serving as a cognitive antidote to performance decrements. An analysis of each keystroke revealed different underlying processes and strategies for the two training conditions, including when encoding took place. Chunking (in which the first and last two digits are treated separately) was more evident in the immediate than in the delayed condition and was exaggerated with a gap, even at test when there was no gap. These results suggest that such two-digit chunking is due to stimulus encoding and motor planning processes as well as memory, and those processes transferred from training to testing.

Detecting and Preventing Sybil Attacks in Wireless Sensor Networks Using Message Authentication and Passing Method.

PubMed

Dhamodharan, Udaya Suriya Raj Kumar; Vayanaperumal, Rajamani

2015-01-01

Wireless sensor networks are highly indispensable for securing network protection. Highly critical attacks of various kinds have been documented in wireless sensor network till now by many researchers. The Sybil attack is a massive destructive attack against the sensor network where numerous genuine identities with forged identities are used for getting an illegal entry into a network. Discerning the Sybil attack, sinkhole, and wormhole attack while multicasting is a tremendous job in wireless sensor network. Basically a Sybil attack means a node which pretends its identity to other nodes. Communication to an illegal node results in data loss and becomes dangerous in the network. The existing method Random Password Comparison has only a scheme which just verifies the node identities by analyzing the neighbors. A survey was done on a Sybil attack with the objective of resolving this problem. The survey has proposed a combined CAM-PVM (compare and match-position verification method) with MAP (message authentication and passing) for detecting, eliminating, and eventually preventing the entry of Sybil nodes in the network. We propose a scheme of assuring security for wireless sensor network, to deal with attacks of these kinds in unicasting and multicasting.

Detecting and Preventing Sybil Attacks in Wireless Sensor Networks Using Message Authentication and Passing Method

PubMed Central

Dhamodharan, Udaya Suriya Raj Kumar; Vayanaperumal, Rajamani

2015-01-01

Wireless sensor networks are highly indispensable for securing network protection. Highly critical attacks of various kinds have been documented in wireless sensor network till now by many researchers. The Sybil attack is a massive destructive attack against the sensor network where numerous genuine identities with forged identities are used for getting an illegal entry into a network. Discerning the Sybil attack, sinkhole, and wormhole attack while multicasting is a tremendous job in wireless sensor network. Basically a Sybil attack means a node which pretends its identity to other nodes. Communication to an illegal node results in data loss and becomes dangerous in the network. The existing method Random Password Comparison has only a scheme which just verifies the node identities by analyzing the neighbors. A survey was done on a Sybil attack with the objective of resolving this problem. The survey has proposed a combined CAM-PVM (compare and match-position verification method) with MAP (message authentication and passing) for detecting, eliminating, and eventually preventing the entry of Sybil nodes in the network. We propose a scheme of assuring security for wireless sensor network, to deal with attacks of these kinds in unicasting and multicasting. PMID:26236773

El Camino Hospital: using health information technology to promote patient safety.

PubMed

Bukunt, Susan; Hunter, Christine; Perkins, Sharon; Russell, Diana; Domanico, Lee

2005-10-01

El Camino Hospital is a leader in the use of health information technology to promote patient safety, including bar coding, computerized order entry, electronic medical records, and wireless communications. Each year, El Camino Hospital's board of directors sets performance expectations for the chief executive officer, which are tied to achievement of local, regional, and national safety and quality standards, including the six Institute of Medicine quality dimensions. He then determines a set of explicit quality goals and measurable actions, which serve as guidelines for the overall hospital. The goals and progress reports are widely shared with employees, medical staff, patients and families, and the public. For safety, for example, the medication error reduction team tracks and reviews medication error rates. The hospital has virtually eliminated transcription errors through its 100% use of computerized physician order entry. Clinical pathways and standard order sets have reduced practice variation, providing a safer environment. Many projects focused on timeliness, such as emergency department wait time, lab turnaround time, and pneumonia time to initial antibiotic. Results have been mixed, with projects most successful when a link was established with patient outcomes, such as in reducing time to percutaneous transluminal coronary angioplasty for patients with acute myocardial infarction.

Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.

PubMed

Sugden, M C; Lall, H S; Harris, R A; Holness, M J

2000-11-01

The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.

Levels of Ycg1 Limit Condensin Function during the Cell Cycle

PubMed Central

Arsenault, Heather E.; Benanti, Jennifer A.

2016-01-01

During mitosis chromosomes are condensed to facilitate their segregation, through a process mediated by the condensin complex. Although several factors that promote maximal condensin activity during mitosis have been identified, the mechanisms that downregulate condensin activity during interphase are largely unknown. Here, we demonstrate that Ycg1, the Cap-G subunit of budding yeast condensin, is cell cycle-regulated with levels peaking in mitosis and decreasing as cells enter G1 phase. This cyclical expression pattern is established by a combination of cell cycle-regulated transcription and constitutive degradation. Interestingly, overexpression of YCG1 and mutations that stabilize Ycg1 each result in delayed cell-cycle entry and an overall proliferation defect. Overexpression of no other condensin subunit impacts the cell cycle, suggesting that Ycg1 is limiting for condensin complex formation. Consistent with this possibility, we find that levels of intact condensin complex are reduced in G1 phase compared to mitosis, and that increased Ycg1 expression leads to increases in both levels of condensin complex and binding to chromatin in G1. Together, these results demonstrate that Ycg1 levels limit condensin function in interphase cells, and suggest that the association of condensin with chromosomes must be reduced following mitosis to enable efficient progression through the cell cycle. PMID:27463097

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions.

PubMed

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M; Whitmire, Jason K; Maury, Wendy; Lemon, Stanley M

2017-09-05

Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1 -/- Ifnar1 -/- and Tim4 -/- Ifnar1 -/- double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1 -/- mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1 -/- Ifnar1 -/- mice compared to Ifnar1 -/- mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. IMPORTANCE T cell immunoglobulin and mucin-containing domain protein 1 (TIM1) was reported more than 2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as "hepatitis A virus cellular receptor 1" (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors. Copyright © 2017 Das et al.

Rapid one-step recombinational cloning

PubMed Central

Fu, Changlin; Wehr, Daniel R.; Edwards, Janice; Hauge, Brian

2008-01-01

As an increasing number of genes and open reading frames of unknown function are discovered, expression of the encoded proteins is critical toward establishing function. Accordingly, there is an increased need for highly efficient, high-fidelity methods for directional cloning. Among the available methods, site-specific recombination-based cloning techniques, which eliminate the use of restriction endonucleases and ligase, have been widely used for high-throughput (HTP) procedures. We have developed a recombination cloning method, which uses truncated recombination sites to clone PCR products directly into destination/expression vectors, thereby bypassing the requirement for first producing an entry clone. Cloning efficiencies in excess of 80% are obtained providing a highly efficient method for directional HTP cloning. PMID:18424799

Transforming the back office with a single keystroke.

PubMed

Kaplan, Charles

2011-09-01

Intelligent data capture is an application that can provide electronic access to data contained in any type of document, including clinical records and financial documents, thereby reducing or eliminating the need for manual data entry. Before implementing this technology, however, healthcare leaders should: Evaluate technology in the context of a business case to ensure a measurable ROI. Communicate with employees throughout the process so they are prepared for and embrace the inevitable changes that will come with automation. Implement the solution in phases, focusing on those document types that can deliver for a safer, less disruptive approach. Achieve maximum benefit to the organization by reengineering business processes to fully leverage technology rather than simply automating existing manual processes.

Pi-CO₂ aqueous post-combustion CO₂ capture: Proof of concept through thermodynamic, hydrodynamic, and gas-lift pump modeling

DOE PAGES

Blount, G.; Gorensek, M.; Hamm, L.; ...

2014-12-31

Partnering in Innovation, Inc. (Pi-Innovation) introduces an aqueous post-combustion carbon dioxide (CO₂) capture system (Pi-CO₂) that offers high market value by directly addressing the primary constraints limiting beneficial re-use markets (lowering parasitic energy costs, reducing delivered cost of capture, eliminating the need for special solvents, etc.). A highly experienced team has completed initial design, modeling, manufacturing verification, and financial analysis for commercial market entry. Coupled thermodynamic and thermal-hydraulic mass transfer modeling results fully support proof of concept. Pi-CO₂ has the potential to lower total cost and risk to levels sufficient to stimulate global demand for CO₂ from local industrial sources.

Experimental analysis of IMEP in a rotary combustion engine

NASA Technical Reports Server (NTRS)

Schock, H. J.; Rice, W. J.; Meng, P. R.

1981-01-01

A real time indicated mean effective pressure measurement system is described which is used to judge proposed improvements in cycle efficiency of a rotary combustion engine. This is the first self-contained instrument that is capable of making real time measurements of IMEP in a rotary engine. Previous methods used require data recording and later processing using a digital computer. The unique features of this instrumentation include its ability to measure IMEP on a cycle by cycle, real time basis and the elimination of the need to differentiate volume function in real time. Measurements at two engine speeds (2000 and 3000 rpm) and a full range of loads are presented, although the instrument was designed to operate to speeds of 9000 rpm.

The origin of intermediary metabolism

NASA Technical Reports Server (NTRS)

Morowitz, H. J.; Kostelnik, J. D.; Yang, J.; Cody, G. D.

2000-01-01

The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique.

Molecular identification of PpHDAC1, the first histone deacetylase fron the slime mold Physarum polycephalum.

PubMed

Brandtner, Eva-Maria; Lechner, Thomas; Loidl, Peter; Lusser, Alexandra

2002-01-01

The dynamic state of post-translational acetylation of eukaryotic histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs have been shown to be components of various regulatory protein complexes in the cell. Their enzymatic activities, intracellular localization and substrate specificities are regulated in a complex, cell cycle related manner. In the myxomycete Physarum polycephalum multiple HATs and HDACs can be distinguished in biochemical terms and they exhibit dynamic activity patterns depending on the cell cycle stage. Here we report on the cloning of the first P. polycephalum HDAC (PpHDAC1) related to the S. cerevisiae Rpd3 protein. The expression pattern of PpHDAC1 mRNA was analysed at different time points of the cell cycle and found to be largely constant. Treatment of macroplasmodia with the HDAC inhibitor trichostatin A at several cell cycle stages resulted in a significant delay in entry into mitosis of treated versus untreated plasmodia. No effect of TSA treatment could be observed on PpHDAC1 expression itself.

Entry, Descent, and Landing for Human Mars Missions

NASA Technical Reports Server (NTRS)

Munk, Michelle M.; DwyerCianciolo, Alicia M.

2012-01-01

One of the most challenging aspects of a human mission to Mars is landing safely on the Martian surface. Mars has such low atmospheric density that decelerating large masses (tens of metric tons) requires methods that have not yet been demonstrated, and are not yet planned in future Mars missions. To identify the most promising options for Mars entry, descent, and landing, and to plan development of the needed technologies, NASA's Human Architecture Team (HAT) has refined candidate methods for emplacing needed elements of the human Mars exploration architecture (such as ascent vehicles and habitats) on the Mars surface. This paper explains the detailed, optimized simulations that have been developed to define the mass needed at Mars arrival to accomplish the entry, descent, and landing functions. Based on previous work, technology options for hypersonic deceleration include rigid, mid-L/D (lift-to-drag ratio) aeroshells, and inflatable aerodynamic decelerators (IADs). The hypersonic IADs, or HIADs, are about 20% less massive than the rigid vehicles, but both have their technology development challenges. For the supersonic regime, supersonic retropropulsion (SRP) is an attractive option, since a propulsive stage must be carried for terminal descent and can be ignited at higher speeds. The use of SRP eliminates the need for an additional deceleration system, but SRP is at a low Technology Readiness Level (TRL) in that the interacting plumes are not well-characterized, and their effect on vehicle stability has not been studied, to date. These architecture-level assessments have been used to define the key performance parameters and a technology development strategy for achieving the challenging mission of landing large payloads on Mars.

A Microbial Avenue to Cell Cycle Control in the Plant Superkingdom[C][W][OPEN

PubMed Central

Tulin, Frej; Cross, Frederick R.

2014-01-01

Research in yeast and animals has resulted in a well-supported consensus model for eukaryotic cell cycle control. The fit of this model to early diverging eukaryotes, such as the plant kingdom, remains unclear. Using the green alga Chlamydomonas reinhardtii, we developed an efficient pipeline, incorporating robotics, semiautomated image analysis, and deep sequencing, to molecularly identify >50 genes, mostly conserved in higher plants, specifically required for cell division but not cell growth. Mutated genes include the cyclin-dependent kinases CDKA (resembling yeast and animal Cdk1) and the plant-specific CDKB. The Chlamydomonas cell cycle consists of a long G1 during which cells can grow >10-fold, followed by multiple rapid cycles of DNA replication and segregation. CDKA and CDKB execute nonoverlapping functions: CDKA promotes transition between G1 and entry into the division cycle, while CDKB is essential specifically for spindle formation and nuclear division, but not for DNA replication, once CDKA-dependent initiation has occurred. The anaphase-promoting complex is required for similar steps in the Chlamydomonas cell cycle as in Opisthokonts; however, the spindle assembly checkpoint, which targets the APC in Opisthokonts, appears severely attenuated in Chlamydomonas, based on analysis of mutants affecting microtubule function. This approach allows unbiased integration of the consensus cell cycle control model with innovations specific to the plant lineage. PMID:25336509

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.

PubMed

Wani, Willayat Yousuf; Kandimalla, Ramesh J L; Sharma, Deep Raj; Kaushal, Alka; Ruban, Anand; Sunkaria, Aditya; Vallamkondu, Jayalakshmi; Chiarugi, Alberto; Reddy, P Hemachandra; Gill, Kiran Dip

2017-07-01

In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G 0 /G 1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Bacteria/virus filter membrane

NASA Technical Reports Server (NTRS)

Lysaght, M. S.; Goodwin, F.; Roebelen, G.

1977-01-01

Hollow acrylate fiber membrane that filters bacterial and viral organisms can be used with closed-cycle life-support systems for underwater habitations or laboratories. Membrane also has applications in fields of medicine, gnotobiotics, pharmaceutical production, and industries and research facilities that require sterile water. Device eliminates need for strong chemicals or sterilizing agents, thereby reducing costs.

Method for eliminating artifacts in CCD imagers

DOEpatents

Turko, B.T.; Yates, G.J.

1992-06-09

An electronic method for eliminating artifacts in a video camera employing a charge coupled device (CCD) as an image sensor is disclosed. The method comprises the step of initializing the camera prior to normal read out and includes a first dump cycle period for transferring radiation generated charge into the horizontal register while the decaying image on the phosphor being imaged is being integrated in the photosites, and a second dump cycle period, occurring after the phosphor image has decayed, for rapidly dumping unwanted smear charge which has been generated in the vertical registers. Image charge is then transferred from the photosites and to the vertical registers and read out in conventional fashion. The inventive method allows the video camera to be used in environments having high ionizing radiation content, and to capture images of events of very short duration and occurring either within or outside the normal visual wavelength spectrum. Resultant images are free from ghost, smear and smear phenomena caused by insufficient opacity of the registers and, and are also free from random damage caused by ionization charges which exceed the charge limit capacity of the photosites. 3 figs.

Applying the Principles of Lean Production to Gastrointestinal Biopsy Handling: From the Factory Floor to the Anatomic Pathology Laboratory.

PubMed

Sugianto, Jessica Z; Stewart, Brian; Ambruzs, Josephine M; Arista, Amanda; Park, Jason Y; Cope-Yokoyama, Sandy; Luu, Hung S

2015-01-01

To implement Lean principles to accommodate expanding volumes of gastrointestinal biopsies and to improve laboratory processes overall. Our continuous improvement (kaizen) project analyzed the current state for gastrointestinal biopsy handling using value-stream mapping for specimens obtained at a 487-bed tertiary care pediatric hospital in Dallas, Texas. We identified non-value-added time within the workflow process, from receipt of the specimen in the histology laboratory to the delivery of slides and paperwork to the pathologist. To eliminate non-value-added steps, we implemented the changes depicted in a revised-state value-stream map. Current-state value-stream mapping identified a total specimen processing time of 507 minutes, of which 358 minutes were non-value-added. This translated to a process cycle efficiency of 29%. Implementation of a revised-state value stream resulted in a total process time reduction to 238 minutes, of which 89 minutes were non-value-added, and an improved process cycle efficiency of 63%. Lean production principles of continuous improvement and waste elimination can be successfully implemented within the clinical laboratory.

The study of operating an air conditioning system using Maisotsenko-Cycle

NASA Astrophysics Data System (ADS)

Khan, Mohammad S.; Tahan, Sami; Toufic El-Achkar, Mohamad; Abou Jamus, Saleh

2018-03-01

The project aims to design and build an air conditioning system that runs on the Maisotsenko cycle. The system is required to condition and cool down ambient air for a small residential space with the reduction in the use of electricity and eliminating the use of commercial refrigerants. This project can operate at its optimum performance in remote areas like oil diggers and other projects that run in the desert or any site that would not have a very high relative humidity level. The Maisotsenko cycle is known as the thermodynamic concept that captures energy from the air by using the psychometric renewable energy available in the latent heat in water evaporating in air. The heat and mass exchanger design was based on choosing a material that would-be water resistant and breathable, which was found to be layers of cardboard placed on top of each other and thus creating channels for air to pass through. Aiming for this design eliminates any high power electrical equipment such as compressors, condensers and evaporators that would be used in an AC system with the exception of a 600 W blower and a 10 W fan, thus making it a more environmentally friendly project. Moreover, the project is limited by the ambient temperature and humidity, as the model operates at an optimum when the relative humidity is lower.

Evaluation of a pulsed xenon ultraviolet disinfection system to decrease bacterial contamination in operating rooms.

PubMed

El Haddad, Lynn; Ghantoji, Shashank S; Stibich, Mark; Fleming, Jason B; Segal, Cindy; Ware, Kathy M; Chemaly, Roy F

2017-10-10

Environmental cleanliness is one of the contributing factors for surgical site infections in the operating rooms (ORs). To decrease environmental contamination, pulsed xenon ultraviolet (PX-UV), an easy and safe no-touch disinfection system, is employed in several hospital environments. The positive effect of this technology on environmental decontamination has been observed in patient rooms and ORs during the end-of-day cleaning but so far, no study explored its feasibility between surgical cases in the OR. In this study, 5 high-touch surfaces in 30 ORs were sampled after manual cleaning and after PX-UV intervention mimicking between-case cleaning to avoid the disruption of the ORs' normal flow. The efficacy of a 1-min, 2-min, and 8-min cycle were tested by measuring the surfaces' contaminants by quantitative cultures using Tryptic Soy Agar contact plates. We showed that combining standard between-case manual cleaning of surfaces with a 2-min cycle of disinfection using a portable xenon pulsed ultraviolet light germicidal device eliminated at least 70% more bacterial load after manual cleaning. This study showed the proof of efficacy of a 2-min cycle of PX-UV in ORs in eliminating bacterial contaminants. This method will allow a short time for room turnover and a potential reduction of pathogen transmission to patients and possibly surgical site infections.

Proceedings of the Annual Conference on Environmental Toxicology (8th) held at Dayton, OH, 4-6 October 1977

DTIC Science & Technology

1977-12-01

generated citrate to the cyto- plasmic fatty acid synthesizing system (Kirsten et al., 1971). As shown in Table 1 , preincubation of mitochondria ( 1 mg...fatty acid bio- synthesis is independent from aconitase in terms of metabolic pathways. 127 TABLE 1 . INHIBITION OF MITOCHONDRIAL CITRATE ENTRY AND... carboxylic acid substrates of the Krebs 132 cycle enzymes revealed that none of them formed covalent adducts with membrane proteins. It was therefore

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

PubMed

Koenigsmann, M; Casper, J; Kahl, C; Basara, N; Sayer, H G; Behre, G; Theurich, S; Christopeit, M; Mohren, M; Reichle, A; Metzner, B; Ganser, A; Stadler, M; Uharek, L; Balleisen, L; Hinke, A; Hinke, R; Niederwieser, D

2014-03-01

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

Anticonvulsants and suicide attempts in bipolar I disorders.

PubMed

Bellivier, F; Belzeaux, R; Scott, J; Courtet, P; Golmard, J-L; Azorin, J-M

2017-05-01

To identify risk factors for suicide attempts (SA) in individuals commencing treatment for a manic or mixed episode. A total of 3390 manic or mixed cases with bipolar disorder (BD) type I recruited from 14 European countries were included in a prospective, 2-year observational study. Poisson regression models were used to identify individual and treatment factors associated with new SA events. Two multivariate models were built, stratified for the presence or absence of prior SA. A total of 302 SA were recorded prospectively; the peak incidence was 0-12 weeks after commencing treatment. In cases with a prior history of SA, risk of SA repetition was associated with younger age of first manic episode (P = 0.03), rapid cycling (P < 0.001), history of alcohol and/or substance use disorder (P < 0.001), number of psychotropic drugs prescribed (P < 0.001) and initiation of an anticonvulsant at study entry (P < 0.001). In cases with no previous SA, the first SA event was associated with rapid cycling (P = 0.02), lifetime history of alcohol use disorder (P = 0.02) and initiation of an anticonvulsant at study entry (P = 0.002). The introduction of anticonvulsants for a recent-onset manic or mixed episode may be associated with an increased risk of SA. Further BD studies must determine whether this link is causal. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Coordinate regulation of the mother centriole component nlp by nek2 and plk1 protein kinases.

PubMed

Rapley, Joseph; Baxter, Joanne E; Blot, Joelle; Wattam, Samantha L; Casenghi, Martina; Meraldi, Patrick; Nigg, Erich A; Fry, Andrew M

2005-02-01

Mitotic entry requires a major reorganization of the microtubule cytoskeleton. Nlp, a centrosomal protein that binds gamma-tubulin, is a G(2)/M target of the Plk1 protein kinase. Here, we show that human Nlp and its Xenopus homologue, X-Nlp, are also phosphorylated by the cell cycle-regulated Nek2 kinase. X-Nlp is a 213-kDa mother centriole-specific protein, implicating it in microtubule anchoring. Although constant in abundance throughout the cell cycle, it is displaced from centrosomes upon mitotic entry. Overexpression of active Nek2 or Plk1 causes premature displacement of Nlp from interphase centrosomes. Active Nek2 is also capable of phosphorylating and displacing a mutant form of Nlp that lacks Plk1 phosphorylation sites. Importantly, kinase-inactive Nek2 interferes with Plk1-induced displacement of Nlp from interphase centrosomes and displacement of endogenous Nlp from mitotic spindle poles, while active Nek2 stimulates Plk1 phosphorylation of Nlp in vitro. Unlike Plk1, Nek2 does not prevent association of Nlp with gamma-tubulin. Together, these results provide the first example of a protein involved in microtubule organization that is coordinately regulated at the G(2)/M transition by two centrosomal kinases. We also propose that phosphorylation by Nek2 may prime Nlp for phosphorylation by Plk1.

Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection.

PubMed

Van der Gucht, Winke; Leemans, Annelies; De Schryver, Marjorie; Heykers, Annick; Caljon, Guy; Maes, Louis; Cos, Paul; Delputte, Peter L

2017-08-17

Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3-2 and A2000/3-4, suggesting that this is a general feature of RSV. RSV infection can be inhibited by broad serine protease inhibitors, AEBSF and TPCK. We confirmed that AEBSF inhibition is independent of the cell line used or RSV strain. The time point at which treatment with the inhibitor was most potent, was found to coincide with the expected moment of entry of the virion with the host cell.

Supercharged two-cycle engines employing novel single element reciprocating shuttle inlet valve mechanisms and with a variable compression ratio

NASA Technical Reports Server (NTRS)

Wiesen, Bernard (Inventor)

2008-01-01

This invention relates to novel reciprocating shuttle inlet valves, effective with every type of two-cycle engine, from small high-speed single cylinder model engines, to large low-speed multiple cylinder engines, employing spark or compression ignition. Also permitting the elimination of out-of-phase piston arrangements to control scavenging and supercharging of opposed-piston engines. The reciprocating shuttle inlet valve (32) and its operating mechanism (34) is constructed as a single and simple uncomplicated member, in combination with the lost-motion abutments, (46) and (48), formed in a piston skirt, obviating the need for any complex mechanisms or auxiliary drives, unaffected by heat, friction, wear or inertial forces. The reciprocating shuttle inlet valve retains the simplicity and advantages of two-cycle engines, while permitting an increase in volumetric efficiency and performance, thereby increasing the range of usefulness of two-cycle engines into many areas that are now dominated by the four-cycle engine.

Evaluation of the microbicidal efficacy of Steris System I for digestive endoscopes using GERMANDE and ASTM validation protocols.

PubMed

Duc, D L; Ribiollet, A; Dode, X; Ducel, G; Marchetti, B; Calop, J

2001-06-01

In the light of more and more invasive procedures being carried out in digestive endoscopy using sterile devices, it appears necessary to put in place a process of endoscope reprocessing capable of ensuring the complete elimination of micro-organisms contaminating the device. We undertook a study of the microbial efficacy of STERIS SYSTEM 1 (SS1) which purports to achieve this objective. The channels of a gastroscope and a colonoscope were contaminated with suspensions of Pseudomonas aeruginosa, Aspergillus niger and Bacillus subtilis spores. Two procedures were then followed: (1) manual washing only, and (2) treatment in SS1 without prewashing. Recoveries of organisms were made from each channel according to a standard methodology to discover any survivors. Contamination controls we re assessed to measure the logarithmic reduction between the initial contamination and that recovered from the channels. Six cycles per micro-organisms, per type of endoscope, and per type of procedure were carried out. From an initial contamination leve l of 10(6) micro-organisms per endoscope, no micro-organisms were recovered in 35 of the 36 cycles with the SS1. In one cycle with the colonoscope, three B. subtilis organisms were recovered from the channels. Washing only gave microbial reductions which varied according to the micro-organism tested. The maximum reduction with washing alone was by a factor of 10(3 +/- 0.1)for B. subtilis and the minimum reduction factor was 10(3 +/- 0.3)for P. aeruginosa. Considering the results obtained with SS1 without prewashing and the efficacy obtained from washing only, the washing step offers an additional antimicrobial assurance reduction factor of between 10 and 103.1. This study shows that SS1, integrated into an overall reprocessing procedure for digestive endoscopes, is capable of delivering the complete elimination of contaminating micro-organisms in a reduced time and eliminates the toxic risk of reprocessing associated with aldehyde based disinfectants. Copyright 2001 The Hospital Infection Society.

Synthesis and characterization of carbazolide-based iridium PNP pincer complexes. Mechanistic and computational investigation of alkene hydrogenation: evidence for an Ir(III)/Ir(V)/Ir(III) catalytic cycle.

PubMed

Cheng, Chen; Kim, Bong Gon; Guironnet, Damien; Brookhart, Maurice; Guan, Changjian; Wang, David Y; Krogh-Jespersen, Karsten; Goldman, Alan S

2014-05-07

New carbazolide-based iridium pincer complexes ((carb)PNP)Ir(C2H4), 3a, and ((carb)PNP)Ir(H)2, 3b, have been prepared and characterized. The dihydride, 3b, reacts with ethylene to yield the cis-dihydride ethylene complex cis-((carb)PNP)Ir(C2H4)(H)2. Under ethylene this complex reacts slowly at 70 °C to yield ethane and the ethylene complex, 3a. Kinetic analysis establishes that the reaction rate is dependent on ethylene concentration and labeling studies show reversible migratory insertion to form an ethyl hydride complex prior to formation of 3a. Exposure of cis-((carb)PNP)Ir(C2H4)(H)2 to hydrogen results in very rapid formation of ethane and dihydride, 3b. DFT analysis suggests that ethane elimination from the ethyl hydride complex is assisted by ethylene through formation of ((carb)PNP)Ir(H)(Et)(C2H4) and by H2 through formation of ((carb)PNP)Ir(H)(Et)(H2). Elimination of ethane from Ir(III) complex ((carb)PNP)Ir(H)(Et)(H2) is calculated to proceed through an Ir(V) complex ((carb)PNP)Ir(H)3(Et) which reductively eliminates ethane with a very low barrier to return to the Ir(III) dihydride, 3b. Under catalytic hydrogenation conditions (C2H4/H2), cis-((carb)PNP)Ir(C2H4)(H)2 is the catalyst resting state, and the catalysis proceeds via an Ir(III)/Ir(V)/Ir(III) cycle. This is in sharp contrast to isoelectronic (PCP)Ir systems in which hydrogenation proceeds through an Ir(III)/Ir(I)/Ir(III) cycle. The basis for this remarkable difference is discussed.

Development of 0.5-5 W, 10K Reverse Brayton Cycle Cryocoolers - Phase II Final Report

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

Doty, F. D.; Boman, A.; Arnold, S.

2001-10-15

Miniature cryocoolers for the 8-30 K range are needed to provide 0.5-5 w of cooling to high sensitivity detectors (for long-wave-length IR, magnetism, mm-wave, X-ray, dark matter, and possibly y-ray detection) while maintaining low mass, ultra-low vibration, and good efficiency. This project presents a new approach to eliminating the problems normally encountered in efforts to build low-vibration, fieldable, miniature cryocoolers. Using the reverse Brayton Cycle (RBC), the approach applies and expands on existing spinner technology previously used only in Nuclear Magnetic Resonance (NMR) probes.

Urea cycle disorder--argininosuccinic lyase deficiency.

PubMed

Mehta, Neeta; Kirk, Pia Chatterjee; Holder, Ray; Precheur, Harry V

2012-01-01

An increased level of ammonia in the bloodstream, or hyperammonemia, is a symptom associated with metabolic disorders referred to as inborn errors of metabolism. Urea cycle disorder is a congenital abnormality or absence of one of the six enzymes involved in the elimination of ammonia. Administration of certain medications, high protein diet, excessive exercise, surgical procedures, or trauma can precipitate symptoms of mental confusion, seizure-like activity, and ataxia. This paper reviews the literature with insight into current treatment and management options of the disorder and modification of treatment for the dental patient. © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Liquefaction process for solid carbonaceous materials containing alkaline earth metal humates

DOEpatents

Epperly, William R.; Deane, Barry C.; Brunson, Roy J.

1982-01-01

An improved liquefaction process wherein wall scale and particulate agglomeration during the liquefaction of solid carbonaceous materials containing alkaline earth metal humates is reduced and/or eliminated by subjecting the solid carbonaceous materials to controlled cyclic cavitation during liquefaction. It is important that the solid carbonaceous material be slurried in a suitable solvent or diluent during liquefaction. The cyclic cavitation may be imparted via pressure cycling, cyclic agitation and the like. When pressure cycling or the like is employed an amplitude equivalent to at least 25 psia is required to effectively remove scale from the liquefaction vessel walls.

Successful Solutions to SSME/AT Development Turbine Blade Distress

NASA Technical Reports Server (NTRS)

Montgomery, Stuart K.

1999-01-01

As part of the High-Pressure Fuel Turbopump/Alternate Turbopump (HPFTP/AT) turbine blade development program, unique turbine blade design features were implemented to address 2nd stage turbine blade high cycle fatigue distress and improve turbine robustness. Features included the addition of platform featherseal dampers, asymmetric blade tip seal segments, gold plating of the blade attachments, and airfoil tip trailing edge modifications. Development testing shows these features have eliminated turbine blade high cycle fatigue distress and consequently these features are currently planned for incorporation to the flight configuration. Certification testing will begin in 1999. This presentation summarizes these features.

NONO couples the circadian clock to the cell cycle.

PubMed

Kowalska, Elzbieta; Ripperger, Juergen A; Hoegger, Dominik C; Bruegger, Pascal; Buch, Thorsten; Birchler, Thomas; Mueller, Anke; Albrecht, Urs; Contaldo, Claudio; Brown, Steven A

2013-01-29

Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. In vivo, lack of NONO resulted in defective wound repair. Because wound healing defects were also seen in multiple circadian clock-deficient mouse lines, our results therefore suggest that coupling of the cell cycle to the circadian clock via NONO may be useful to segregate in temporal fashion cell proliferation from tissue organization.

Health information system strengthening and malaria elimination in Papua New Guinea.

PubMed

Rosewell, Alexander; Makita, Leo; Muscatello, David; John, Lucy Ninmongo; Bieb, Sibauk; Hutton, Ross; Ramamurthy, Sundar; Shearman, Phil

2017-07-05

The objective of the study was to describe an m-health initiative to strengthen malaria surveillance in a 184-health facility, multi-province, project aimed at strengthening the National Health Information System (NHIS) in a country with fragmented malaria surveillance, striving towards enhanced control, pre-elimination. A remote-loading mobile application and secure online platform for health professionals was created to interface with the new system (eNHIS). A case-based malaria testing register was developed and integrated geo-coded households, villages and health facilities. A malaria programme management dashboard was created, with village-level malaria mapping tools, and statistical algorithms to identify malaria outbreaks. Since its inception in 2015, 160,750 malaria testing records, including village of residence, have been reported to the eNHIS. These case-based, geo-coded malaria data are 100% complete, with a median data entry delay of 9 days from the date of testing. The system maps malaria to the village level in near real-time as well as the availability of treatment and diagnostics to health facility level. Data aggregation, analysis, outbreak detection, and reporting are automated. The study demonstrates that using mobile technologies and GIS in the capture and reporting of NHIS data in Papua New Guinea provides timely, high quality, geo-coded, case-based malaria data required for malaria elimination. The health systems strengthening approach of integrating malaria information management into the eNHIS optimizes sustainability and provides enormous flexibility to cater for future malaria programme needs.

Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry

PubMed Central

Aydin, Halil; Cook, Jonathan D.

2014-01-01

Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion. PMID:24131724

Investigations of Control Surface Seals for Re-entry Vehicles

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Curry, Donald M.; DeMange, Jeffrey J.; Rivers, H. Kevin; Hsu, Su-Yuen

2002-01-01

Re-entry vehicles generally require control surfaces (e.g., rudders, body flaps) to steer them during flight. Control surface seals are installed along hinge lines and where control surface edges move close to the vehicle body. These seals must operate at high temperatures and limit heat transfer to underlying structures to prevent them from overheating and causing possible loss of vehicle structural integrity. This paper presents results for thermal analyses and mechanical testing conducted on the baseline rudder/fin seal design for the X-38 re-entry vehicle. Exposure of the seals in a compressed state at the predicted peak seal temperature of 1900 F resulted in loss of seal resiliency. The vertical Inconel rudder/fin rub surface was re-designed to account for this loss of resiliency. Room temperature compression tests revealed that seal unit loads and contact pressures were below limits set to protect Shuttle thermal tiles on the horizontal sealing surface. The seals survived an ambient temperature 1000 cycle scrub test over sanded Shuttle tiles and were able to disengage and re-engage the tile edges during testing. Arc jet tests confirmed the need for seals in the rudder/fin gap location because a single seal caused a large temperature drop (delta T = 1710 F) in the gap.

AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling.

PubMed

Chen, Jian; Yang, Yi-Feng; Yang, Yu; Zou, Peng; Chen, Jun; He, Yongquan; Shui, Sai-Lan; Cui, Yan-Ru; Bai, Ru; Liang, Ya-Jun; Hu, Yunwen; Jiang, Biao; Lu, Lu; Zhang, Xiaoyan; Liu, Jia; Xu, Jianqing

2018-03-01

Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barré syndrome 1,2 . While progress has been made in understanding the causal link between ZIKV infection and microcephaly 3-9 , the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV 10-22 . Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor α chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

PubMed

Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

2015-09-14

The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Urea metabolism in beef steers fed tall fescue, orchardgrass, or gamagrass hays.

PubMed

Huntington, G B; Magee, K; Matthews, A; Poore, M; Burns, J

2009-04-01

Two experiments were conducted to assess effects of endophyte treatments (Exp. 1), forage species (Exp. 2), and supplementation (Exp. 2) on urea production, excretion, and recycling in beef steers. Infusion of (15,15)N-urea and enrichment of urea in urine samples were used to calculate urea-N entry and recycling to the gut. Acceptably stable enrichment of (15)N-urea in urine was obtained after 50 h of intrajugular infusion of (15,15)N-urea, indicating that valid data on urea metabolism can be obtained from steers fed forages twice daily. After adjustment by covariance for differences in N intake among treatments in Exp. 1, steers fed endophyte-infected tall fescue had less (P<0.10) urea-N entry, recycling to the gut, and return of recycled urea-N to the ornithine cycle than those fed endophyte-free or novel endophyte-infected tall fescue. However, urea-N urinary excretion or return to the gut was similar among endophyte treatments when expressed as a proportion of urea-N entry. Urea-N entry and return to the gut in Exp. 2 was similar in steers fed gamagrass or orchardgrass hay after adjustment by covariance for differences in N intake. Less (P<0.01) urinary excretion, expressed as grams per day or as a proportion of urea-N entry, with gamagrass than with orchardgrass was associated with faster in vitro NDF-N digestion with gamagrass. Supplementation of gamagrass or orchardgrass with 1.76 kg/d of readily fermentable fiber and starch decreased urea entry (P<0.06) and urinary excretion of urea (P<0.01). Interactions between hay source and supplement reflected a greater response to supplementation for steers fed orchardgrass than for those fed gamagrass. After adjustment for differences among treatments in N supply, results of both experiments support the concept of improved N use in response to increased carbohydrate fermentability in the rumen, due either to inherent differences in forage fiber or to supplementation with readily fermentable carbohydrate (starch or fiber). Closer coordination of ruminal fermentation of carbohydrate and N sources provided greater and more efficient capture of dietary N as tissue protein in forage-fed steers.

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts

PubMed Central

Hansen, Brian J.; Zhao, Jichao; Csepe, Thomas A.; Moore, Brandon T.; Li, Ning; Jayne, Laura A.; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A.; Simonetti, Orlando P.; Higgins, Robert S.D.; Kilic, Ahmet; Mohler, Peter J.; Janssen, Paul M.L.; Weiss, Raul; Hummel, John D.; Fedorov, Vadim V.

2015-01-01

Aims The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial–epicardial (Endo–Epi) mapping coupled with high-resolution 3D structural imaging. Methods and results Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43–72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo–Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7–6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30–100 µM) perfusion. Dual-sided sub-Endo–sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or ‘breakthrough’ patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Conclusions Integrated 3D structural–functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. PMID:26059724

Turboexpanders for OTEC power plants

NASA Astrophysics Data System (ADS)

Holm, J.

1981-12-01

Centripetal (radial inflow) turboexpanders are well adapted to energy conservation schemes. A mini OTEC demonstration program, completed in 1979, uses a closed ammonia cycle to drive a 50 kw turboexpander generator unit. The turboexpander, which incorporates mechanical designs of low temperature and high speed machinery, has very high levels of reliability and efficiency. Stiff shaft designs have eliminated shaft and bearing criticals in the entire operating range. Rotor resonance problems are almost totally eliminated, and thrust bearing problems can be accurately monitored and controlled. Condensing streams and dust in gas can also be handled without erosion. Designs for radial inflow turboexpanders in sizes up to 70 MWe are presently available for use in OTEC and other power plants.

Effects of thermal cycling on graphie-fiber-reinforced 6061 aluminum

NASA Technical Reports Server (NTRS)

Dries, G. A.; Tompkins, S. S.

1986-01-01

Graphite-reinforced aluminum alloy metal-matrix composites are among materials being considered for structural components in dimensionally stable space structures. This application requires materials with low values of thermal expansions and high specific stiffnesses. They must remain stable during exposures to the space environment for periods extending to 20 years. The effects of thermal cycling on the thermal expansion behavior and mechanical properties of Thornel P100 graphite 6061 aluminum composites, as fabricated and after thermal processing to eliminate thermal strain hysteresis, have been investigated. Two groups of composites were studied: one was fabricated by hot roll bonding and the other by diffusion bonding. Processing significantly reduced strain hysteresis during thermal cycling in both groups and improved the ultimate tensile strength and modulus in the diffusion-bonded composites. Thermal cycling stabilized the as-fabricated composites by reducing the residual fabrication stress and increased the matrix strength by metallurgical aging. Thermal expansion behavior of both groups after processing was insensitive to thermal cycling. Data scatter was too large to determine effects of thermal cycling on the mechanical properties. The primary effects of processing and thermal cycling can be attributed to changes in the metallurgical condition and stress state of the matrix.

Prospects for Accelerator Technology

NASA Astrophysics Data System (ADS)

Todd, Alan

2011-02-01

Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal.

PubMed

McNeill, Brian; Mazerolle, Chantal; Bassett, Erin A; Mears, Alan J; Ringuette, Randy; Lagali, Pamela; Picketts, David J; Paes, Kim; Rice, Dennis; Wallace, Valerie A

2013-03-01

Norrie disease (ND) is a congenital disorder characterized by retinal hypovascularization and cognitive delay. ND has been linked to mutations in 'Norrie Disease Protein' (Ndp), which encodes the secreted protein Norrin. Norrin functions as a secreted angiogenic factor, although its role in neural development has not been assessed. Here, we show that Ndp expression is initiated in retinal progenitors in response to Hedgehog (Hh) signaling, which induces Gli2 binding to the Ndp promoter. Using a combination of genetic epistasis and acute RNAi-knockdown approaches, we show that Ndp is required downstream of Hh activation to induce retinal progenitor proliferation in the retina. Strikingly, Ndp regulates the rate of cell-cycle re-entry and not cell-cycle kinetics, thereby uncoupling the self-renewal and cell-cycle progression functions of Hh. Taken together, we have uncovered a cell autonomous function for Ndp in retinal progenitor proliferation that is independent of its function in the retinal vasculature, which could explain the neural defects associated with ND.

Staying alive: Vibrio cholerae’s cycle of environmental survival, transmission, and dissemination

PubMed Central

Jones, Christopher J.; Yildiz, Fitnat H.

2015-01-01

Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide (1). Increasingly, the crucial role of non-host environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, as these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen, Vibrio cholerae, to describe recent advances in our understanding of how pathogens survive between hosts and highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry and exit from human hosts. PMID:27227302

An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.

PubMed

van Brabant, A J; Buchanan, C D; Charboneau, E; Fangman, W L; Brewer, B J

2001-04-01

Checkpoint controls coordinate entry into mitosis with the completion of DNA replication. Depletion of nucleotide precursors by treatment with the drug hydroxyurea triggers such a checkpoint response. However, it is not clear whether the signal for this hydroxyurea-induced checkpoint pathway is the presence of unreplicated DNA, or rather the persistence of single-stranded or damaged DNA. In a yeast artificial chromosome (YAC) we have engineered an approximately 170 kb region lacking efficient replication origins that allows us to explore the specific effects of unreplicated DNA on cell cycle progression. Replication of this YAC extends the length of S phase and causes cells to engage an S/M checkpoint. In the absence of Rad9 the YAC becomes unstable, undergoing deletions within the origin-free region.

Design of an efficient electrolyte circulation system for the lead-acid battery

NASA Astrophysics Data System (ADS)

Thuerk, D.

The design and operation of an electrolyte circulation system are described. Application of lead acid batteries to electric vehicle and other repetitive deep cycle services produces a nondesirable state in the battery cells, electrolyte stratification. This stratification is the result of acid and water generation at the electrodes during cycling. With continued cycling, the extent of the stratification increases and prevents complete charging with low percentages of overcharge. Ultimately this results in extremely short life for the battery system. The stratification problem was overcome by substantially overcharging the battery. This abusive overcharge produces gassing rates sufficient to mix the electrolyte during the end portion of the charge. Overcharge, even though it is required to eliminate stratification, produces the undesirable results related to high voltage and gassing rates.

Reducing Proliferation Rick Through Multinational Fuel Cycle Facilities

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

Amanda Rynes

2010-11-01

With the prospect of rapid expansion of the nuclear energy industry and the ongoing concern over weapons proliferation, there is a growing need for a viable alternative to traditional nation-based fuel production facilities. While some in the international community remain apprehensive, the advantages of multinational fuel cycle facilities are becoming increasingly apparent, with states on both sides of the supply chain able to garner the security and financial benefits of such facilities. Proliferation risk is minimized by eliminating the need of states to establish indigenous fuel production capabilities and the concept's structure provides an additional internationally monitored barrier against themore » misuse or diversion of nuclear materials. This article gives a brief description of the arguments for and against the implementation of a complete multinational fuel cycle.« less

Lean-Six Sigma: tools for rapid cycle cost reduction.

PubMed

Caldwell, Chip

2006-10-01

Organizational costs can be grouped as process cost, cost of quality, and cost of poor quality. Providers should train managers in the theory and application of Lean-Six Sigma, including the seven categories of waste and how to remove them. Healthcare financial executives should work with managers in eliminating waste to improve service and reduce costs.

40 CFR 125.84 - As an owner or operator of a new facility, what must I do to comply with this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS CRITERIA AND STANDARDS FOR THE NATIONAL POLLUTANT DISCHARGE ELIMINATION SYSTEM Requirements Applicable to Cooling Water Intake Structures for New Facilities... that which can be attained by a closed-cycle recirculating cooling water system; (2) You must design...

10.2 Thermal-Structural Testing

NASA Technical Reports Server (NTRS)

Hudson, Larry D.

2008-01-01

Objective: Test a C/SiC Ruddervator Subcomponent under relevant thermal, mechanical & dynamic loading a) Thermal-structural mission cycling for re-entry and hypersonic cruise conditions; b) High-temperature modal survey to study the effect of heating on mode shapes, natural frequencies and damping. Supports NASA ARMD Hypersonics Material & Structures Program. Partners: NASA Dryden / Langley / Glenn, Lockheed-Martin, Materials Research & Design, GE CCP Test Phases - Phase 1: Acoustic-Vibration Testing (LaRC) completed - Phase 2: Thermal-Mechanical Testing (DFRC) in assembly - Phase 3: Mechanical Testing (DFRC) in assembly

Electron Microscopy of Ebola Virus-Infected Cells.

PubMed

Noda, Takeshi

2017-01-01

Ebola virus (EBOV) replicates in host cells, where both viral and cellular components show morphological changes during the process of viral replication from entry to budding. These steps in the replication cycle can be studied using electron microscopy (EM), including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), which is one of the most useful methods for visualizing EBOV particles and EBOV-infected cells at the ultrastructural level. This chapter describes conventional methods for EM sample preparation of cultured cells infected with EBOV.

Federal policy on criminal offenders who have substance use disorders: how can we maximize public health and public safety?

PubMed

Humphreys, Keith

2012-01-01

The Obama Administration is striving to promote both public health and public safety by improving the public policy response to criminal offenders who have substance use disorders. This includes supporting drug courts, evidence-based probation and parole programs, addiction treatment and re-entry programs. Scientists and clinicians in the addiction field have a critical role to play in this much-needed effort to break the cycle of addiction, crime and incarceration.

Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance

DTIC Science & Technology

2007-05-01

the body: the seed and soil hypothesis, which states : “when a plant goes to seed, its seeds are carried in all directions; but they can only grow if...complete and complex model of breast cancer bone metastasis. Solid black lines indicate established interactions within the vicious cycle. Dotted gray...967–971. 21. Leonard, J. T., & Roy, K. (2006). The HIV entry inhibitors revisited. Current Medicinal Chemistry , 13, 911–934. 22. Harms, J. F., Welch, D

Helicopter Reliability and Maintainability Trends during Development and Production.

DTIC Science & Technology

1981-07-01

engine entry (the T-53) showed improvement in successive models. For helicopters, we have mixed results: some improved (YUH-60A, CH-47, UH-lD, AH-IG...understand the linkage between R&M program goals and life cycle costs, however, it is necessary to understand-- (1) what resource levels are required during...attributes of the system; (3) how those field attributes affect the cost of owner- ship of the system; and (4) whether or not, and at what cost, R&M values

Risk assessment of the entry of canine-rabies into Papua New Guinea via sea and land routes.

PubMed

Brookes, Victoria J; Keponge-Yombo, Andy; Thomson, David; Ward, Michael P

2017-09-15

Canine-rabies is endemic in parts of Indonesia and continues to spread eastwards through the Indonesian archipelago. Papua New Guinea (PNG) has a land border with Papua Province, Indonesia, as well as logging and fishing industry connections throughout Asia. PNG has a Human Development Index of 0.505; therefore, an incursion of canine-rabies could have devastating impacts on human (7.5 million) and animal populations. Given the known difficulties of rabies elimination in resource-scarce environments, an incursion of rabies into PNG would also likely compromise the campaign for global elimination of rabies. A previous qualitative study to determine routes for detailed risk assessment identified logging, fishing and three land-routes (unregulated crossers ["shopper-crossers"], traditional border crossers and illegal hunters) as potential high risk routes for entry of rabies-infected dogs into PNG. The objective of the current study was to quantify and compare the probability of entry of a rabies-infected dog via these routes into PNG and to identify the highest risk provinces and border districts to target rabies prevention and control activities. Online questionnaires were used to elicit expert-opinion about quantitative model parameter values. A quantitative, stochastic model was then used to assess risk, and parameters with the greatest influence on the estimated mean number of rabies-infected dogs introduced/year were identified via global sensitivity analysis (Sobol method). Eight questionnaires - including 7 online - were implemented and >220 empirical distributions were parameterised using >2900 expert-opinions. The highest risk provinces for combined sea routes were West Sepik, Madang and Western Province, driven by the number of vessels and the probability of bringing dogs. The highest risk border districts for combined land routes were Vanimo-Green River and South Fly, driven by the number of people crossing the border and the number of dogs (with hunters). Overall, the risk posed by land routes was much higher than the risk of rabies introduction by sea routes. This study provides a foundation to develop targeted border control measures, surveillance and response strategies for canine-rabies for the highest risk routes and regions in PNG. Sensitivity analysis using the Sobol method played a key role in this study and directed further data collection to refine risk estimates. The ease of expert-elicitation using online methods demonstrates the feasibility of using such methods for animal and human disease surveillance in PNG. Copyright © 2017 Elsevier B.V. All rights reserved.

Fusion energy from the Moon for the twenty-first century

NASA Technical Reports Server (NTRS)

Kulcinski, G. L.; Cameron, E. N.; Santarius, J. F.; Sviatoslavsky, I. N.; Wittenberg, L. J.; Schmitt, Harrison H.

1992-01-01

It is shown in this paper that the D-He-3 fusion fuel cycle is not only credible from a physics standpoint, but that its breakeven and ignition characteristics could be developed on roughly the same time schedule as the DT cycle. It was also shown that the extremely low fraction of power in neutrons, the lack of significant radioactivity in the reactants, and the potential for very high conversion efficiencies, can result in definite advantages for the D-He-3 cycle with respect to DT fusion and fission reactors in the twenty-first century. More specifically, the D-He-3 cycle can accomplish the following: (1) eliminate the need for deep geologic waste burial facilities and the wastes can qualify for Class A, near-surface land burial; (2) allow 'inherently safe' reactors to be built that, under the worst conceivable accident, cannot cause a civilian fatality or result in a significant (greater than 100 mrem) exposure to a member of the public; (3) reduce the radiation damage levels to a point where no scheduled replacement of reactor structural components is required, i.e., full reactor lifetimes (approximately 30 FPY) can be credibly claimed; (4) increase the reliability and availability of fusion reactors compared to DT systems because of the greatly reduced radioactivity, the low neutron damage, and the elimination of T breeding; and (5) greatly reduce the capital costs of fusion power plants (compared to DT systems) by as much as 50 percent and present the potential for a significant reduction on the COE. The concepts presented in this paper tie together two of the most ambitious high-technology endeavors of the twentieth century: the development of controlled thermonuclear fusion for civilian power applications and the utilization of outer space for the benefit of mankind on Earth.

Fusion energy from the Moon for the twenty-first century

NASA Astrophysics Data System (ADS)

Kulcinski, G. L.; Cameron, E. N.; Santarius, J. F.; Sviatoslavsky, I. N.; Wittenberg, L. J.; Schmitt, Harrison H.

1992-09-01

It is shown in this paper that the D-He-3 fusion fuel cycle is not only credible from a physics standpoint, but that its breakeven and ignition characteristics could be developed on roughly the same time schedule as the DT cycle. It was also shown that the extremely low fraction of power in neutrons, the lack of significant radioactivity in the reactants, and the potential for very high conversion efficiencies, can result in definite advantages for the D-He-3 cycle with respect to DT fusion and fission reactors in the twenty-first century. More specifically, the D-He-3 cycle can accomplish the following: (1) eliminate the need for deep geologic waste burial facilities and the wastes can qualify for Class A, near-surface land burial; (2) allow 'inherently safe' reactors to be built that, under the worst conceivable accident, cannot cause a civilian fatality or result in a significant (greater than 100 mrem) exposure to a member of the public; (3) reduce the radiation damage levels to a point where no scheduled replacement of reactor structural components is required, i.e., full reactor lifetimes (approximately 30 FPY) can be credibly claimed; (4) increase the reliability and availability of fusion reactors compared to DT systems because of the greatly reduced radioactivity, the low neutron damage, and the elimination of T breeding; and (5) greatly reduce the capital costs of fusion power plants (compared to DT systems) by as much as 50 percent and present the potential for a significant reduction on the COE. The concepts presented in this paper tie together two of the most ambitious high-technology endeavors of the twentieth century: the development of controlled thermonuclear fusion for civilian power applications and the utilization of outer space for the benefit of mankind on Earth.

Vendors unveil one-step fugitive emissions monitoring, management

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

Walter, M.

1995-04-01

An alliance of manufacturers has developed a ``single-source solution`` for fugitive emissions monitoring. The LeakTracker{trademark} system combines barcode scans, and vapor detection and data collection capabilities to help companies comply with leak detection and repair requirements as mandated by the Environmental Protection Agency`s Method 21 guidelines. LeakTracker doubles productivity and helps eliminate human-error factors associated with fugitive emissions monitoring. Two-person teams, clipboard-and-pencil data entry, and manual data transcription are eliminated. By automating the process and integrating all components, a technician can monitor 500 points daily following Method 21 guidelines, compared to about 250 readings per day using other systems. LeakTrackermore » includes a handheld workstation, sampling probe and laser-scan barcode reader that fit in a vest worn by a field technician. The technician points the workstation toward a barcode tag and pulls the trigger, which initiates a barcode read and automatically records the time, date and location. While the detachable probe ``sniffs`` for emissions, an analyzer interface module converts the gas detection signal from analog to digital format, allowing data to be recorded by the workstation. LeakTracker has an accuracy rate of 1 part per million.« less

The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control.

PubMed

Bukh, Jens

2016-10-01

The discovery of hepatitis C virus (HCV) in 1989 permitted basic research to unravel critical components of a complex life cycle for this important human pathogen. HCV is a highly divergent group of viruses classified in 7 major genotypes and a great number of subtypes, and circulating in infected individuals as a continuously evolving quasispecies destined to escape host immune responses and applied antivirals. Despite the inability to culture patient viruses directly in the laboratory, efforts to define the infectious genome of HCV resulted in development of experimental recombinant in vivo and in vitro systems, including replicons and infectious cultures in human hepatoma cell lines. And HCV has become a model virus defining new paradigms in virology, immunology and biology. For example, HCV research discovered that a virus could be completely dependent on microRNA for its replication since microRNA-122 is critical for the HCV life cycle. A number of other host molecules critical for HCV entry and replication have been identified. Thus, basic HCV research revealed important molecules for development of host targeting agents (HTA). The identification and characterization of HCV encoded proteins and their functional units contributed to the development of highly effective direct acting antivirals (DAA) against the NS3 protease, NS5A and the NS5B polymerase. In combination, these inhibitors have since 2014 permitted interferon-free therapy with cure rates above 90% among patients with chronic HCV infection; however, viral resistance represents a challenge. Worldwide control of HCV will most likely require the development of a prophylactic vaccine, and numerous candidates have been pursued. Research characterizing features critical for antibody-based virus neutralization and T cell based virus elimination from infected cells is essential for this effort. If the world community promotes an ambitious approach by applying current DAA broadly, continues to develop alternative viral- and host- targeted antivirals to combat resistant variants, and invests in the development of a vaccine, it would be possible to eradicate HCV. This would prevent about 500 thousand deaths annually. However, given the nature of HCV, the millions of new infections annually, a high chronicity rate, and with over 150 million individuals with chronic infection (which are frequently unidentified), this effort remains a major challenge for basic researchers, clinicians and communities. Copyright © 2016. Published by Elsevier B.V.

A new global strategy for the elimination of schistosomiasis.

PubMed

Ross, Allen G P; Chau, Thao N; Inobaya, Marianette T; Olveda, Remigio M; Li, Yuesheng; Harn, Donald A

2017-01-01

Mass drug administration utilising a single oral dose of 40mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the global control and elimination of schistosomiasis. However, this strategy is failing primarily because the drugs are not getting to the people who need them the most. The current global coverage is 20%, the drug compliance rate is less than 50%, and the drug efficacy is approximately 50%. Thus in reality, only about 5% of the reservoir human population is actually receiving intermittent chemotherapy. Despite claims that more of the drug will soon be made available the current strategy is inherently flawed and will not lead to disease elimination. We discuss the many practical issues related to this global strategy, and advocate for an integrated control strategy targeting the life cycle and the most at-risk. Moreover, we discuss how an integrated control package for schistosomiasis should fit within a larger integrated health package for rural and remote villages in the developing world. A holistic health system approach is required to achieve sustainable control and ultimately disease elimination. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Branched GAX cycle gas fired heat pump

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

Erickson, D.C.; Anand, G.; Papar, R.A.

1996-12-31

GAX absorption heat pump cycles are characterized by the Generator Absorber Heat eXchange (GAX) between the high temperature end of the absorber and the low temperature end of the generator. The improved thermodynamic performance of the basic GAX cycle coupled with its mechanical simplicity has attracted substantial interest in using this cycle for gas-cooling. However, to be competitive in a cooling dominated market, the cycle has to achieve high cooling performance and also low installed cost. The Branched GAX (BGAX) cycle promises higher cooling performance using similar components as the basic GAX cycle and an additional solution pump. By increasingmore » the solution flow rate at the hot end of the absorber, the BGAX cycle makes more complete use of the temperature overlap. As a result, less external heat is supplied and higher COPs are obtained. A breadboard prototype of the BGAX cycle has been developed and is now operating. A novel thermosyphon cooled absorber eliminates the need for the outdoor hydronic loop, and reduces cost by 10%. Other component improvements yield another 10% cost reduction. The breadboard prototype has operated for more than 200 hours. Gas cooling COP = 0.87 has been consistently achieved at 30.6 C (87 F) ambient conditions. At the 35 C (95 F) ambient capacity rating condition, a cooling load of 4.5 refrigeration tons was achieved at a cycle COP = 0.95.« less

An improved turbine disk design to increase reliability of aircraft jet engines

NASA Technical Reports Server (NTRS)

Barack, W. N.; Domas, P. A.

1976-01-01

An analytical study was performed on a novel disk design to replace the existing high-pressure turbine, stage 1 disk on the CF6-50 turbofan engine. Preliminary studies were conducted on seven candidate disk design concepts. An integral multidisk design with bore entry of the turbine blade cooling air was selected as the improved disk design. This disk has the unique feature of being redundant such that if one portion of the disk would fail, the remaining portion would prevent the release of large disk fragments from the turbine system. Low cycle fatigue lives, initial defect propagation lives, burst speed, and the kinetic energies of probable disk fragment configurations were calculated, and comparisons were made with the existing disk, both in its current material, IN 718, and with the substitution of an advanced alloy, Rene 95. The design for redundancy approach which necessitated the addition of approximately 44.5 kg (98 lb) to the design disk substantially improved the life of the disk. The life to crack initiation was increased from 30,000 cycles to more than 100,000 cycles. The cycles to failure from initial defect propagation were increased from 380 cycles to 1564 cycles. Burst speed was increased from 126 percent overspeed to 149 percent overspeed. Additionally, the maximum fragment energies associated with a failure were decreased by an order of magnitude.

S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.

PubMed

Ye, Weizhen; Blain, Stacy W

2010-08-01

A major phenotype seen in neurodegenerative disorders is the selective loss of neurons due to apoptotic death and evidence suggests that inappropriate re-activation of cell cycle proteins in post-mitotic neurons may be responsible. To investigate whether reactivation of the G1 cell cycle proteins and S phase entry was linked with apoptosis, we examined homocysteine-induced neuronal cell death in a rat cortical neuron tissue culture system. Hyperhomocysteinaemia is a physiological risk factor for a variety of neurodegenerative diseases, including Alzheimer's disease. We found that in response to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nucleus, and p27 levels decreased. Both cyclin-dependent kinases 4 and 2 regained catalytic activity, the G1 gatekeeper retinoblastoma protein was phosphorylated and DNA synthesis was detected, suggesting transit into S phase. Double-labelling immunofluorescence showed a 95% co-localization of anti-bromodeoxyuridine labelling with apoptotic markers, demonstrating that those cells that entered S phase eventually died. Neurons could be protected from homocysteine-induced death by methods that inhibited G1 phase progression, including down-regulation of cyclin D1 expression, inhibition of cyclin-dependent kinases 4 or 2 activity by small molecule inhibitors, or use of the c-Abl kinase inhibitor, Gleevec, which blocked cyclin D and cyclin-dependent kinase 4 nuclear translocation. However, blocking cell cycle progression post G1, using DNA replication inhibitors, did not prevent apoptosis, suggesting that death was not preventable post the G1-S phase checkpoint. While homocysteine treatment caused DNA damage and activated the DNA damage response, its mechanism of action was distinct from that of more traditional DNA damaging agents, such as camptothecin, as it was p53-independent. Likewise, inhibition of the DNA damage sensors, ataxia-telangiectasia mutant and ataxia telangiectasia and Rad3 related proteins, did not rescue apoptosis and in fact exacerbated death, suggesting that the DNA damage response might normally function neuroprotectively to block S phase-dependent apoptosis induction. As cell cycle events appear to be maintained in vivo in affected neurons for weeks to years before apoptosis is observed, activation of the DNA damage response might be able to hold cell cycle-induced death in check.

Recovery from the DNA Replication Checkpoint

PubMed Central

Chaudhury, Indrajit; Koepp, Deanna M.

2016-01-01

Checkpoint recovery is integral to a successful checkpoint response. Checkpoint pathways monitor progress during cell division so that in the event of an error, the checkpoint is activated to block the cell cycle and activate repair pathways. Intrinsic to this process is that once repair has been achieved, the checkpoint signaling pathway is inactivated and cell cycle progression resumes. We use the term “checkpoint recovery” to describe the pathways responsible for the inactivation of checkpoint signaling and cell cycle re-entry after the initial stress has been alleviated. The DNA replication or S-phase checkpoint monitors the integrity of DNA synthesis. When replication stress is encountered, replication forks are stalled, and the checkpoint signaling pathway is activated. Central to recovery from the S-phase checkpoint is the restart of stalled replication forks. If checkpoint recovery fails, stalled forks may become unstable and lead to DNA breaks or unusual DNA structures that are difficult to resolve, causing genomic instability. Alternatively, if cell cycle resumption mechanisms become uncoupled from checkpoint inactivation, cells with under-replicated DNA might proceed through the cell cycle, also diminishing genomic stability. In this review, we discuss the molecular mechanisms that contribute to inactivation of the S-phase checkpoint signaling pathway and the restart of replication forks during recovery from replication stress. PMID:27801838

The Notch pathway regulates the Second Mitotic Wave cell cycle independently of bHLH proteins.

PubMed

Bhattacharya, Abhishek; Li, Ke; Quiquand, Manon; Rimesso, Gerard; Baker, Nicholas E

2017-11-15

Notch regulates both neurogenesis and cell cycle activity to coordinate precursor cell generation in the differentiating Drosophila eye. Mosaic analysis with mitotic clones mutant for Notch components was used to identify the pathway of Notch signaling that regulates the cell cycle in the Second Mitotic Wave. Although S phase entry depends on Notch signaling and on the transcription factor Su(H), the transcriptional co-activator Mam and the bHLH repressor genes of the E(spl)-Complex were not essential, although these are Su(H) coactivators and targets during the regulation of neurogenesis. The Second Mitotic Wave showed little dependence on ubiquitin ligases neuralized or mindbomb, and although the ligand Delta is required non-autonomously, partial cell cycle activity occurred in the absence of known Notch ligands. We found that myc was not essential for the Second Mitotic Wave. The Second Mitotic Wave did not require the HLH protein Extra macrochaetae, and the bHLH protein Daughterless was required only cell-nonautonomously. Similar cell cycle phenotypes for Daughterless and Atonal were consistent with requirement for neuronal differentiation to stimulate Delta expression, affecting Notch activity in the Second Mitotic Wave indirectly. Therefore Notch signaling acts to regulate the Second Mitotic Wave without activating bHLH gene targets. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Abercrombie, Robert K; Buckner Jr, Dooley; Newton, David D

The Oak Ridge National Laboratory (ORNL) Weigh-In-Motion (WIM) system provides a portable and/or semi-portable means of accurately weighing vehicles and its cargo as each vehicle crosses the scales (while in motion), and determining (1) axle weights and (2) axle spacing for vehicles (for determination of Bridge Formula compliance), (3) total vehicle/cargo weight and (4) longitudinal center of gravity (for safety considerations). The WIM system can also weigh the above statically. Because of the automated nature of the WIM system, it eliminates the introduction of human errors caused by manual computations and data entry, adverse weather conditions, and stress. Individual vehiclesmore » can be weighed continuously at low speeds (approximately 3-10 mph) and at intervals of less than one minute. The ORNL WIM system operates and is integrated into the Bethel Jacobs Company Transportation Management and Information System (TMIS, a Radio-Frequency Identification [RFID] enabled information system). The integrated process is as follows: Truck Identification Number and Tare Weight are programmed into a RFID Tag. Handheld RFID devices interact with the RFID Tag, and Electronic Shipping Document is written to the RFID Tag. The RFID tag read by an RFID tower identifies the vehicle and its associated cargo, the specific manifest of radioactive debris for the uniquely identified vehicle. The weight of the cargo (in this case waste debris) is calculated from total vehicle weight information supplied from WIM to TMIS and is further processed into the Information System and kept for historical and archival purposes. The assembled data is the further process in downstream information systems where waste coordination activities at the Y-12 Environmental Management Waste Management Facility (EMWMF) are written to RFID Tag. All cycle time information is monitored by Transportation Operations and Security personnel.« less

Molecular insight into bacterial cleavage of oceanic dimethylsulfoniopropionate into dimethyl sulfide

PubMed Central

Li, Chun-Yang; Wei, Tian-Di; Zhang, Sheng-Hui; Chen, Xiu-Lan; Gao, Xiang; Wang, Peng; Xie, Bin-Bin; Su, Hai-Nan; Qin, Qi-Long; Zhang, Xi-Ying; Yu, Juan; Zhang, Hong-Hai; Zhou, Bai-Cheng; Yang, Gui-Peng; Zhang, Yu-Zhong

2014-01-01

The microbial cleavage of dimethylsulfoniopropionate (DMSP) generates volatile DMS through the action of DMSP lyases and is important in the global sulfur and carbon cycles. When released into the atmosphere from the oceans, DMS is oxidized, forming cloud condensation nuclei that may influence weather and climate. Six different DMSP lyase genes are found in taxonomically diverse microorganisms, and dddQ is among the most abundant in marine metagenomes. Here, we examine the molecular mechanism of DMSP cleavage by the DMSP lyase, DddQ, from Ruegeria lacuscaerulensis ITI_1157. The structures of DddQ bound to an inhibitory molecule 2-(N-morpholino)ethanesulfonic acid and of DddQ inactivated by a Tyr131Ala mutation and bound to DMSP were solved. DddQ adopts a β-barrel fold structure and contains a Zn2+ ion and six highly conserved hydrophilic residues (Tyr120, His123, His125, Glu129, Tyr131, and His163) in the active site. Mutational and biochemical analyses indicate that these hydrophilic residues are essential to catalysis. In particular, Tyr131 undergoes a conformational change during catalysis, acting as a base to initiate the β-elimination reaction in DMSP lysis. Moreover, structural analyses and molecular dynamics simulations indicate that two loops over the substrate-binding pocket of DddQ can alternate between “open” and “closed” states, serving as a gate for DMSP entry. We also propose a molecular mechanism for DMS production through DMSP cleavage. Our study provides important insight into the mechanism involved in the conversion of DMSP into DMS, which should lead to a better understanding of this globally important biogeochemical reaction. PMID:24395783

The Large Marseillevirus Explores Different Entry Pathways by Forming Giant Infectious Vesicles.

PubMed

Arantes, Thalita Souza; Rodrigues, Rodrigo Araújo Lima; Dos Santos Silva, Ludmila Karen; Oliveira, Graziele Pereira; de Souza, Helton Luís; Khalil, Jacques Y B; de Oliveira, Danilo Bretas; Torres, Alice Abreu; da Silva, Luis Lamberti; Colson, Philippe; Kroon, Erna Geessien; da Fonseca, Flávio Guimarães; Bonjardim, Cláudio Antônio; La Scola, Bernard; Abrahão, Jônatas Santos

2016-06-01

Triggering the amoebal phagocytosis process is a sine qua non condition for most giant viruses to initiate their replication cycle and consequently to promote their progeny formation. It is well known that the amoebal phagocytosis process requires the recognition of particles of >500 nm, and most amoebal giant viruses meet this requirement, such as mimivirus, pandoravirus, pithovirus, and mollivirus. However, in the context of the discovery of amoebal giant viruses in the last decade, Marseillevirus marseillevirus (MsV) has drawn our attention, because despite its ability to successfully replicate in Acanthamoeba, remarkably it does not fulfill the >500-nm condition, since it presents an ∼250-nm icosahedrally shaped capsid. We deeply investigated the MsV cycle by using a set of methods, including virological, molecular, and microscopic (immunofluorescence, scanning electron microscopy, and transmission electron microscopy) assays. Our results revealed that MsV is able to form giant vesicles containing dozens to thousands of viral particles wrapped by membranes derived from amoebal endoplasmic reticulum. Remarkably, our results strongly suggested that these giant vesicles are able to stimulate amoebal phagocytosis and to trigger the MsV replication cycle by an acidification-independent process. Also, we observed that MsV entry may occur by the phagocytosis of grouped particles (without surrounding membranes) and by an endosome-stimulated pathway triggered by single particles. Taken together, not only do our data deeply describe the main features of MsV replication cycle, but this is the first time, to our knowledge, that the formation of giant infective vesicles related to a DNA virus has been described. Triggering the amoebal phagocytosis process is a sine qua non condition required by most giant viruses to initiate their replication cycle. This process requires the recognition of particles of >500 nm, and many giant viruses meet this requirement. However, MsV is unusual, as despite having particles of ∼250 nm it is able to replicate in Acanthamoeba Our results revealed that MsV is able to form giant vesicles, containing dozens to thousands of viral particles, wrapped in membranes derived from amoebal endoplasmic reticulum. Remarkably, our results strongly suggest that these giant vesicles are able to stimulate phagocytosis using an acidification-independent process. Our work not only describes the main features of the MsV replication cycle but also describes, for the first time to our knowledge, the formation of huge infective vesicles in a large DNA viruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Sustainable Management of Subterranean Termite Populations (Isoptera: Rhinotermitidae) in Armstrong Park, New Orleans, With Durable Baits.

PubMed

Su, Nan-Yao; Guidry, Eric; Cottone, Carrie

2016-03-27

Durable baits, Recruit HD, were installed in 45 Sentricon stations between September 2010 and July 2014 in the 32-acre Armstrong Park, New Orleans. After eliminating all detectable termite colonies in the Park, 6-12 mo elapsed before new activity was detected. Newly invading termite colonies were usually found near the Park border or were smaller colonies that originated from recently paired alates. After colony elimination, Recruit HD baits were left in the stations to intercept newly invading colonies of subterranean termites, leading to their elimination, and multiple cycles of such interception and elimination events were recorded. Because the presence of Recruit HD baits continues to eliminate incoming colonies with little effort in maintaining and resupplying baits in the target areas, the bait system offers an economically sustainable option for managing subterranean termite populations in a large area. The 32-acre Armstrong Park is a manageable size to carry out an area-wide (AW) project. If the number of such AW projects is gradually increased over time in selected metro areas of New Orleans, we predict that we may be able to turn the tide against the ever-increasing populations ofC. formosanusin the entire city. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex

PubMed Central

Yang, Guang; Gan, Wen-Biao

2012-01-01

Sleep is maximal during early postnatal life when rapid and extensive synapse remodeling occurs. It remains unknown whether and how sleep affects synapse development and plasticity. Using transcranial two-photon microscopy, we examined the formation and elimination of fluorescently-labeled dendritic spines and filopodia of layer 5 pyramidal neurons in the barrel cortex of 3-week old mice during wakefulness and sleep. We observed high turnover of dendritic protrusions over 2 hours in both wake and sleep states. The formation rate of dendritic spines or filopodia over 2 hours was comparable between the two states. The elimination rate of dendritic spines or filopodia was lower during 2-hour wakefulness than during 2-hour sleep. Similar results were observed on dendritic protrusion dynamics over 12-hour light/dark cycle when mice spent more time asleep or awake. The substantial remodeling of dendritic protrusions during the sleep state supports the notion that sleep plays an important role in the development and plasticity of synaptic connections in the mouse cortex. PMID:22058046

Transmission-blocking interventions eliminate malaria from laboratory populations

PubMed Central

Blagborough, A. M.; Churcher, T. S.; Upton, L. M.; Ghani, A. C.; Gething, P. W.; Sinden, R. E.

2013-01-01

Transmission-blocking interventions aim to reduce the prevalence of infection in endemic communities by targeting Plasmodium within the insect host. Although many studies have reported the successful reduction of infection in the mosquito vector, direct evidence that there is an onward reduction in infection in the vertebrate host is lacking. Here we report the first experiments using a population, transmission-based study of Plasmodium berghei in Anopheles stephensi to assess the impact of a transmission-blocking drug upon both insect and host populations over multiple transmission cycles. We demonstrate that the selected transmission-blocking intervention, which inhibits transmission from vertebrate to insect by only 32%, reduces the basic reproduction number of the parasite by 20%, and in our model system can eliminate Plasmodium from mosquito and mouse populations at low transmission intensities. These findings clearly demonstrate that use of transmission-blocking interventions alone can eliminate Plasmodium from a vertebrate population, and have significant implications for the future design and implementation of transmission-blocking interventions within the field. PMID:23652000

The value of atorvastatin over the product life cycle in the United States.

PubMed

Grabner, Michael; Johnson, Wallace; Abdulhalim, Abdulla M; Kuznik, Andreas; Mullins, C Daniel

2011-10-01

US health care reform mandates the reduction of wasteful health care spending while maintaining quality of care. Introducing new drugs into crowded therapeutic classes may be viewed as offering "me-too" (new drugs with a similar mechanism of action compared to existing drugs) drugs without incremental benefit. This article presents an analysis of the incremental costs and benefits of atorvastatin, a lipid-lowering agent. This analysis models the cost-effectiveness of atorvastatin over the product life cycle. The yearly cost-effectiveness of atorvastatin compared to simvastatin was modeled from 1997 to 2030 from the point of view of a US third-party payer. Estimates for incremental costs (in US $) and effects (in quality-adjusted life-years [QALYs]) for the primary and secondary prevention of cardiovascular events were taken from previously published literature and adjusted for changes in drug prices over time. Estimates of total statin use were derived using the National Health and Nutrition Examination Survey. Sensitivity analyses were conducted to examine variations in study parameters, including drug prices, indications, and discount rates. Assuming increasing statin use over time (with a mean of 1.07 million new users per year) and a 3% discount rate, the cumulative incremental cost-effectiveness ratio (ICER) of atorvastatin versus simvastatin ranged from cost-savings at release to a maximum of $45,066/QALY after 6 years of generic simvastatin use in 2012. Over the full modeled life cycle (1997-2030), the cumulative ICER of atorvastatin was $20,331/QALY. The incremental value of atorvastatin to US payers (after subtracting costs) was estimated at $44.57 to $194.78 billion, depending on willingness to pay. Findings from the sensitivity analyses were similar. A hypothetical situation in which atorvastatin did not exist was associated with a reduction in total expenditures but also a loss of QALYs gained. The cumulative ICER of atorvastatin varied across the product life cycle, increasing during the period between generic simvastatin entry and generic atorvastatin entry, and decreasing thereafter. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat.

PubMed Central

Barrand, M. A.; Callingham, B. A.; Dobbin, P.; Hider, R. C.

1991-01-01

1. The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2. The rates of elimination of 59Fe and of tritium from the plasma and their ultimate fate were very different. The half life for 59Fe in the plasma was around 70 min and 59Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12 min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine. 3. Entry of 59Fe and of tritium into the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol was also very different. At low doses of ferric maltol (containing 100 micrograms elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in 59Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of 59Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59Fe prevented further entry of iron at high dose into the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364845

Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops.

PubMed

Kolchinsky, P; Kiprilov, E; Bartley, P; Rubinstein, R; Sodroski, J

2001-04-01

The gp120 envelope glycoprotein of primary human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and the CCR5 chemokine receptor on the target cell. Previously, we adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for CD4-independent replication were limited to the V2 loop-V1/V2 stem. Here we show that elimination of a single glycosylation site at asparagine 197 in the V1/V2 stem is sufficient for CD4-independent gp120 binding to CCR5 and for HIV-1 entry into CD4-negative cells expressing CCR5. Deletion of the V1/V2 loops also allowed CD4-independent viral entry and gp120 binding to CCR5. The binding of the wild-type ADA gp120 to CCR5 was less dependent upon CD4 at 4 degrees C than at 37 degrees C. In the absence of the V1/V2 loops, neither removal of the N-linked carbohydrate at asparagine 197 nor lowering of the temperature increased the CD4-independent phenotypes. A CCR5-binding conformation of gp120, achieved by CD4 interaction or by modification of temperature, glycosylation, or variable loops, was preferentially recognized by the monoclonal antibody 48d. These results suggest that the CCR5-binding region of gp120 is occluded by the V1/V2 variable loops, the position of which can be modulated by temperature, CD4 binding, or an N-linked glycan in the V1/V2 stem.

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Sludge batch 9 simulant runs using the nitric-glycolic acid flowsheet

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

Lambert, D. P.; Williams, M. S.; Brandenburg, C. H.

Testing was completed to develop a Sludge Batch 9 (SB9) nitric-glycolic acid chemical process flowsheet for the Defense Waste Processing Facility’s (DWPF) Chemical Process Cell (CPC). CPC simulations were completed using SB9 sludge simulant, Strip Effluent Feed Tank (SEFT) simulant and Precipitate Reactor Feed Tank (PRFT) simulant. Ten sludge-only Sludge Receipt and Adjustment Tank (SRAT) cycles and four SRAT/Slurry Mix Evaporator (SME) cycles, and one actual SB9 sludge (SRAT/SME cycle) were completed. As has been demonstrated in over 100 simulations, the replacement of formic acid with glycolic acid virtually eliminates the CPC’s largest flammability hazards, hydrogen and ammonia. Recommended processingmore » conditions are summarized in section 3.5.1. Testing demonstrated that the interim chemistry and Reduction/Oxidation (REDOX) equations are sufficient to predict the composition of DWPF SRAT product and SME product. Additional reports will finalize the chemistry and REDOX equations. Additional testing developed an antifoam strategy to minimize the hexamethyldisiloxane (HMDSO) peak at boiling, while controlling foam based on testing with simulant and actual waste. Implementation of the nitric-glycolic acid flowsheet in DWPF is recommended. This flowsheet not only eliminates the hydrogen and ammonia hazards but will lead to shorter processing times, higher elemental mercury recovery, and more concentrated SRAT and SME products. The steady pH profile is expected to provide flexibility in processing the high volume of strip effluent expected once the Salt Waste Processing Facility starts up.« less

Blind, olfactory bulbectomized female rats do not have daily luteinizing hormone surges.

PubMed

Pieper, D R; Mortiere, M R

1985-03-15

Previous studies from other laboratories have shown that female hamsters on short photoperiod become acyclic and have daily LH surges. These effects are eliminated if the animals are pinealectomized (PX) before being placed on the short photoperiod. Reiter and colleagues have shown that pre-pubertally blinded (BL) and olfactory bulbectomized (BX) female rats also have irregular estrous cycles, and this effect is also eliminated by PX [Endocr. Rev., 1 (1983) 109]. The main question addressed by the present study was whether the BL + BX rats also have daily LH surges. Twenty-five-day-old female Sprague-Dawley rats were divided into 5 groups: LD 14:10 sham (control); BL + BX; BL + BX + PX; LD 6:18 sham; and LD 6:18 BX. Ten weeks following surgery, all animals were sampled (0.5 ml) every 5 h for 2 days from an indwelling atrial catheter. Daily vaginal smears indicated that the BL + BX group were in estrus much less frequently than controls (15.8 +/- 1.8 vs 27.3 +/- 1.5% of days cornified cells, 10 rats/group smeared for more than 23 days each) and in general had longer, irregular cycles. The other 3 groups all had smear patterns similar to controls. All 5 groups had LH surges on the day of proestrus (greater than 200 ng/ml maximum value), but no group had LH surges on 2 sequential days or an LH surge on any other day of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

New generation of plasma-sprayed mullite coatings on silicon carbide

NASA Technical Reports Server (NTRS)

Lee, Kang N.; Miller, Robert A.; Jacobson, Nathan S.

1995-01-01

Mullite is promising as a protective coating for silicon-based ceramics in aggressive high-temperature environments. Conventionally plasma-sprayed mullite on SiC tends to crack and debond on thermal cycling. It is shown that this behavior is due to the presence of amorphous mullite in the conventionally sprayed mullite. Heating the SiC substrate during the plasma spraying eliminated the amorphous phase and produced coatings with dramatically improved properties. The new coating exhibits excellent adherence and crack resistance under thermal cycling between room temperature and 1000 to 1400 C. Preliminary tests showed good resistance to Na2CO3-induced hot corrosion.

Adding the Third Dimension to Virus Life Cycles: Three-Dimensional Reconstruction of Icosahedral Viruses from Cryo-Electron Micrographs

PubMed Central

Baker, T. S.; Olson, N. H.; Fuller, S. D.

1999-01-01

Viruses are cellular parasites. The linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. A deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. Here we review the use of cryo-electron microscopy for the determination of the structures of a number of icosahedral viruses. These studies span more than 20 virus families. Representative examples illustrate the use of moderate- to low-resolution (7- to 35-Å) structural analyses to illuminate functional aspects of viral life cycles including host recognition, viral attachment, entry, genome release, viral transcription, translation, proassembly, maturation, release, and transmission, as well as mechanisms of host defense. The success of cryo-electron microscopy in combination with three-dimensional image reconstruction for icosahedral viruses provides a firm foundation for future explorations of more-complex viral pathogens, including the vast number that are nonspherical or nonsymmetrical. PMID:10585969

Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

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

Busk, Peter K.; Hinrichsen, Rebecca; Bartkova, Jirina

2005-03-10

The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21{sup Waf1/Cip1} and p27{sup Kip1}. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic undermore » such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27{sup Kip1}. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2.« less

Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points

PubMed Central

Miga, Karen H.; Sekulic, Nikolina; Soni, Gautam V.; Kim, Dong Hyun; Wong, Adeline K.; Lee, Ah Young; Nguyen, Kristen; Dekker, Cees; Ren, Bing; Black, Ben E.

2017-01-01

Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat–containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1–containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2–4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit. CENP-A chromatin is shown to contain equimolar amounts of CENP-A and histones H2A, H2B, and H4, with no H3. Solid-state nanopore analyses show it to be nucleosomal in size. Thus, in contrast to models for hemisomes that briefly transition to octameric nucleosomes at specific cell cycle points or heterotypic nucleosomes containing both CENP-A and histone H3, human CENP-A chromatin complexes are octameric nucleosomes with two molecules of CENP-A at all cell cycle phases. PMID:28235947

Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation.

PubMed

Michael, Sushama; Travé, Gilles; Ramu, Chenna; Chica, Claudia; Gibson, Toby J

2008-02-15

KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C complex. While annotating the Eukaryotic Linear Motif resource (ELM, http://elm.eu.org/), we found that KEN motifs were significantly enriched in human protein entries with cell cycle keywords in the UniProt/Swiss-Prot database-implying that KEN-boxes might be more common than reported. Matches to short linear motifs in protein database searches are not, per se, significant. KEN-box enrichment with cell cycle Gene Ontology terms suggests that collectively these motifs are functional but does not prove that any given instance is so. Candidates were surveyed for native disorder prediction using GlobPlot and IUPred and for motif conservation in homologues. Among >25 strong new candidates, the most notable are human HIPK2, CHFR, CDC27, Dab2, Upf2, kinesin Eg5, DNA Topoisomerase 1 and yeast Cdc5 and Swi5. A similar number of weaker candidates were present. These proteins have yet to be tested for APC/C targeted destruction, providing potential new avenues of research.

Analysis of Effectiveness of Phoenix Entry Reaction Control System

NASA Technical Reports Server (NTRS)

Dyakonov, Artem A.; Glass, Christopher E.; Desai, Prasun, N.; VanNorman, John W.

2008-01-01

Interaction between the external flowfield and the reaction control system (RCS) thruster plumes of the Phoenix capsule during entry has been investigated. The analysis covered rarefied, transitional, hypersonic and supersonic flight regimes. Performance of pitch, yaw and roll control authority channels was evaluated, with specific emphasis on the yaw channel due to its low nominal yaw control authority. Because Phoenix had already been constructed and its RCS could not be modified before flight, an assessment of RCS efficacy along the trajectory was needed to determine possible issues and to make necessary software changes. Effectiveness of the system at various regimes was evaluated using a hybrid DSMC-CFD technique, based on DSMC Analysis Code (DAC) code and General Aerodynamic Simulation Program (GASP), the LAURA (Langley Aerothermal Upwind Relaxation Algorithm) code, and the FUN3D (Fully Unstructured 3D) code. Results of the analysis at hypersonic and supersonic conditions suggest a significant aero-RCS interference which reduced the efficacy of the thrusters and could likely produce control reversal. Very little aero-RCS interference was predicted in rarefied and transitional regimes. A recommendation was made to the project to widen controller system deadbands to minimize (if not eliminate) the use of RCS thrusters through hypersonic and supersonic flight regimes, where their performance would be uncertain.

Entry, Descent, and Landing Guidance and Control Approaches to Satisfy Mars Human Mission Landing Criteria

NASA Technical Reports Server (NTRS)

Dwyer Cianciolo, Alicia; Powell, Richard W.

2017-01-01

Precision landing on Mars is a challenge. All Mars lander missions prior to the 2012 Mars Science Laboratory (MSL) had landing location uncertainty ellipses on the order of hundreds of kilometers. Sending humans to the surface of Mars will likely require multiple landers delivered in close proximity, which will in turn require orders of magnitude improvement in landing accuracy. MSL was the first Mars mission to use an Apollo-derived bank angle guidance to reduce the size of the landing ellipse. It utilized commanded bank angle magnitude to control total range and bank angle reversals to control cross range. A shortcoming of this bank angle guidance is that the open loop phase of flight created by use of bank reversals increases targeting errors. This paper presents a comparison of entry, descent and landing performance for a vehicle with a low lift-to-drag ratio using both bank angle control and an alternative guidance called Direct Force Control (DFC). DFC eliminates the open loop flight errors by directly controlling two forces independently, lift and side force. This permits independent control of down range and cross range. Performance results, evaluated using the Program to Optimize Simulated Trajectories (POST2), including propellant use and landing accuracy, are presented.

Histopathological changes induced by malathion in the gills of bluegill Lepomis macrochirus

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

Richmonds, C.; Dutta, H.M.

1989-07-01

Malathion is a widely used broad spectrum organophosphorus insecticide. Its wide use provides many occasions for its entry into aquatic environments. The presence of this chemical in the aquatic environment would adversely affect many non-target species like fish. About 50 to 90% of the absorbed malathion can be eliminated in one to three days by the fish. About 25% of malathion remained in river water after 2 wk, and 10% remained after 4 wk from the time of its entry. Respiratory distress is one of the early symptoms of pesticide poisoning. These toxicants appear to cause a loss of adhesionmore » between the epithelial cells and the underlying pillar cell system, accompanied by a collapse of the structural integrity of the secondary lamellae. Gills are important in respiration as well as osmoregulation of the fish. Therefore it was decided to study the effects of malathion on the gills of bluegill sunfish, Lepomis macrochirus. Bluegills were selected for this study due to the following reasons: (1) Bluegills are more sensitive to malathion when compared to fathead minnows and goldfish. (2) They are important both as edible and game fish. (3) They are easily available and easy to maintain in the laboratory.« less

Aerodynamic Characteristics and Control Effectiveness of the HL-20 Lifting Body Configuration at Mach 10 in Air

NASA Technical Reports Server (NTRS)

Scallion, William I.

1999-01-01

A 0.0196-scale model of the HL-20 lifting-body, one of several configurations proposed for future crewed spacecraft, was tested in the Langley 31-Inch Mach 10 Tunnel. The purpose of the tests was to determine the effectiveness of fin-mounted elevons, a lower surface flush-mounted body flap, and a flush-mounted yaw controller at hypersonic speeds. The nominal angle-of-attack range, representative of hypersonic entry, was 2 deg to 41 deg, the sideslip angles were 0 deg, 2 deg, and -2 deg, and the test Reynolds number was 1.06 x 10 E6 based on model reference length. The aerodynamic, longitudinal, and lateral control effectiveness along with surface oil flow visualizations are presented and discussed. The configuration was longitudinally and laterally stable at the nominal center of gravity. The primary longitudinal control, the fin-mounted elevons, could not trim the model to the desired entry angle of attack of 30 deg. The lower surface body flaps were effective for roll control and the associated adverse yawing moment was eliminated by skewing the body flap hinge lines. A yaw controller, flush-mounted on the lower surface, was also effective, and the associated small rolling moment was favorable.

Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit.

PubMed

Puvvula, Pavan Kumar; Desetty, Rohini Devi; Pineau, Pascal; Marchio, Agnés; Moon, Anne; Dejean, Anne; Bischof, Oliver

2014-11-19

Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A (SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence. In proliferating cells, SAFA and PANDA recruit PRC complexes to repress the transcription of senescence-promoting genes. Conversely, the loss of SAFA-PANDA-PRC interactions allows expression of the senescence programme. Accordingly, we find that depleting either SAFA or PANDA in proliferating cells induces senescence. However, in senescent cells where PANDA sequesters transcription factor NF-YA and limits the expression of NF-YA-E2F-coregulated proliferation-promoting genes, PANDA depletion leads to an exit from senescence. Together, our results demonstrate that PANDA confines cells to their existing proliferative state and that modulating its level of expression can cause entry or exit from senescence.

Proceedings of the 1994 international meeting on reduced enrichment for research and test reactors

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

NONE

1997-08-01

This meeting brought together participants in the international effort to minimize and eventually eliminate the use of highly enriched uranium in civilian nuclear programs. Papers cover the following topics: National programs; fuel cycle; nuclear fuels; analyses; advanced reactors; and reactor conversions. Selected papers have been indexed separately for inclusion to the Energy Science and Technology Database.

Response of black ash wetland gaseous soil carbon fluxes to a simulated emerald ash borer infestation

Treesearch

Matthew Van Grinsven; Joseph Shannon; Nicholas Bolton; Joshua Davis; Nam Noh; Joseph Wagenbrenner; Randall Kolka; Thomas Pypker

2018-01-01

The rapid and extensive expansion of emerald ash borer (EAB) in North America since 2002 may eliminate most existing ash stands, likely affecting critical ecosystem services associated with water and carbon cycling. To our knowledge, no studies have evaluated the coupled response of black ash (Fraxinus nigra Marsh.) wetland water tables, soil...

10 CFR Appendix C to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Dishwashers

Code of Federal Regulations, 2011 CFR

2011-01-01

... electrically heated, gas-heated, or oil-heated water. The water consumption for the sensor normal cycle, V, is.... 1.16Truncated sensor heavy response means the sensor heavy response interrupted to eliminate the power-dry feature after the termination of the last rinse operation. 1.17Truncated sensor light response...

10 CFR Appendix C to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Dishwashers

Code of Federal Regulations, 2010 CFR

2010-01-01

... electrically heated, gas-heated, or oil-heated water. The water consumption for the sensor normal cycle, V, is.... 1.16Truncated sensor heavy response means the sensor heavy response interrupted to eliminate the power-dry feature after the termination of the last rinse operation. 1.17Truncated sensor light response...

Involvement of cell proliferation in the process of follicular atresia in the guinea pig.

PubMed

Wang, Wei; Liu, Honglin; Ding, Wei; Gong, Yan; Chen, Jingwei; Hutz, Reinhold J; Mao, Dagan; Shi, Fangxiong

2010-08-01

Cell morphology and proliferation was investigated in the atretic follicles during estrous cycles in the guinea pig. Ovarian samples on days 1, 4, 8, 12 and 16 of the estrous cycle in the guinea pig were taken in the morning for histologic staining with hematoxylin and eosin (HE), and immunohistochemical staining of the protein proliferating cell nuclear antigen (PCNA). The results indicated that the granulosa cells degenerated and eliminated first in atretic follicles, while the fibroblast-like cells appeared in the innermost layer of theca interna cells. When the fibroblast-like cells migrated to the antrum, they proliferated and formed a new tissue in peripheral to the zona pellucida of the oocyte. Our results also revealed that the orientation of the theca interna cell arrangement changed twice during the process of atresia, and the loose connective tissue in the antrum was critical for follicular atresia. Therefore, follicular atresia was not a simple process of cell death and elimination, but coexisted with cell proliferation. To our knowledge, we have for the first time confirmed cell proliferation and the presence of new tissue in atretic follicles in guinea pigs. Copyright 2010 Elsevier Ltd. All rights reserved.

A Reversible Thermally Driven Pump for Use in a Sub-Kelvin Magnetic Refrigerator

NASA Technical Reports Server (NTRS)

Miller, Franklin K.

2012-01-01

A document describes a continuous magnetic refrigerator that is suited for cooling astrophysics detectors. This refrigerator has the potential to provide efficient, continuous cooling to temperatures below 50 mK for detectors, and has the benefits over existing magnetic coolers of reduced mass because of faster cycle times, the ability to pump the cooled fluid to remote cooling locations away from the magnetic field created by the superconducting magnet, elimination of the added complexity and mass of heat switches, and elimination of the need for a thermal bus and single crystal paramagnetic materials due to the good thermal contact between the fluid and the paramagnetic material. A reliable, thermodynamically efficient pump that will work at 1.8 K was needed to enable development of the new magnetic refrigerator. The pump consists of two canisters packed with pieces of gadolinium gallium garnet (GGG). The canisters are connected by a superleak (a porous piece of VYCOR glass). A superconducting magnetic coil surrounds each of the canisters. The configuration enables driving of cyclic thermodynamic cycles (such as the sub-Kelvin Active Magnetic Regenerative Refrigerator) without using pistons or moving parts.

Method for eliminating artifacts in CCD imagers

DOEpatents

Turko, Bojan T.; Yates, George J.

1992-01-01

An electronic method for eliminating artifacts in a video camera (10) employing a charge coupled device (CCD) (12) as an image sensor. The method comprises the step of initializing the camera (10) prior to normal read out and includes a first dump cycle period (76) for transferring radiation generated charge into the horizontal register (28) while the decaying image on the phosphor (39) being imaged is being integrated in the photosites, and a second dump cycle period (78), occurring after the phosphor (39) image has decayed, for rapidly dumping unwanted smear charge which has been generated in the vertical registers (32). Image charge is then transferred from the photosites (36) and (38) to the vertical registers (32) and read out in conventional fashion. The inventive method allows the video camera (10) to be used in environments having high ionizing radiation content, and to capture images of events of very short duration and occurring either within or outside the normal visual wavelength spectrum. Resultant images are free from ghost, smear and smear phenomena caused by insufficient opacity of the registers (28) and (32), and are also free from random damage caused by ionization charges which exceed the charge limit capacity of the photosites (36) and (37).