Decay times of transitionally dense specularly reflecting meteor trails and potential chemical impact on trail lifetimes

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W. K. Hocking

2016-12-01

Full Text Available Studies of transitionally dense meteor trails using radars which employ specularly reflecting interferometric techniques are used to show that measurable high-temperature chemistry exists at timescales of a few tenths of a second after the formation of these trails. This is a process which is distinct from the ambient-temperature chemistry that is already known to exist at timescales of tens of seconds and longer in long-lived trails. As a consequence, these transitionally dense trails have smaller lifetimes than might be expected if diffusion were the only mechanism for reducing the mean trail electron density. The process has been studied with four SKiYMET radars at latitudes varying from 10 to 75° N, over a period of more than 10 years, 24 h per day. In this paper we present the best parameters to use to represent this behaviour and demonstrate the characteristics of the temporal and latitudinal variability in these parameters. The seasonal, day–night and latitudinal variations correlate reasonably closely with the corresponding variations of ozone in the upper mesosphere. Possible reasons for these effects are discussed, but further investigations of any causative relation are still the subject of ongoing studies.

Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

International Nuclear Information System (INIS)

Zheng, Liu; Weilun, Zhang; Minghong, Jiang; Yaxi, Zhang; Shilian, Liu; Yanxin, Liu; Dexian, Zheng

2012-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy

Associations between sociodemographic characteristics and perceptions of the built environment with the frequency, type, and duration of physical activity among trail users.

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Maslow, Andréa L; Reed, Julian A; Price, Anna E; Hooker, Steven P

2012-01-01

Rail trails are elements of the built environment that support the Task Force on Community Preventive Services' recommendation to create, or enhance access to, places for physical activity (PA). The purpose of this study was to examine the associations between sociodemographic characteristics and perceptions of the built environment with the frequency, type, and duration of PA among users of an urban, paved rail trail segment. Interviewers conducted intercept surveys with 431 rail trail users and analyzed data by using logistic regression to estimate odds ratios between sociodemographic characteristics and perceptions of the built environment on the frequency, type, and duration of PA performed on the trail. Adults who used the trail in the cool months, traveled to the trail by a motorized vehicle, used the trail with others, and had some graduate school education visited the trail less often. Younger adults, men, whites, and those with some graduate school education were more likely to engage in vigorous activities on the trail. Adults who traveled to the trail by a motorized vehicle spent more time engaged in PA on the trail. Our results suggest that the most frequent users of a rail trail for PA are those who use the trail alone and travel to the trail by bicycle or on foot. Trails are an aspect of the built environment that supports active lifestyles, and future studies should evaluate different types of trails among more diverse populations and locations.

TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill

International Nuclear Information System (INIS)

Mohr, Andrea; Yu, Rui; Zwacka, Ralf M.

2015-01-01

TRAIL is a potent and specific inducer of apoptosis in tumour cells and therefore is a possible new cancer treatment. It triggers apoptosis by binding to its cognate, death-inducing receptors, TRAIL-R1 and TRAIL-R2. In order to increase its activity, receptor-specific ligands and agonistic antibodies have been developed and some cancer types, including pancreatic cancer, have been reported to respond preferentially to TRAIL-R1 triggering. The aim of the present study was to examine an array of TRAIL-receptor specific variants on a number of pancreatic cancer cells and test the generality of the concept of TRAIL-R1 preference in these cells. TRAIL-R1 and TRAIL-R2 specific sTRAIL variants were designed and tested on a number of pancreatic cancer cells for their TRAIL-receptor preference. These sTRAIL variants were produced in HEK293 cells and were secreted into the medium. After having measured and normalised the different sTRAIL variant concentrations, they were applied to pancreatic and control cancer cells. Twenty-four hours later apoptosis was measured by DNA hypodiploidy assays. Furthermore, the specificities of the sTRAIL variants were validated in HCT116 cells that were silenced either for TRAIL-R1 or TRAIL-R2. Our results show that some pancreatic cancer cells use TRAIL-R1 to induce cell death, whereas other pancreatic carcinoma cells such as AsPC-1 and BxPC-3 cells trigger apoptosis via TRAIL-R2. This observation extended to cells that were naturally TRAIL-resistant and had to be sensitised by silencing of XIAP (Panc1 cells). The measurement of TRAIL-receptor expression by FACS revealed no correlation between receptor preferences and the relative levels of TRAIL-R1 and TRAIL-R2 on the cellular surface. These results demonstrate that TRAIL-receptor preferences in pancreatic cancer cells are variable and that predictions according to cancer type are difficult and that determining factors to inform the optimal TRAIL-based treatments still have to be identified

Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

Directory of Open Access Journals (Sweden)

Zheng Liu

2012-04-01

Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

Associations between self-reported and objective physical environmental factors and use of a community rail-trail.

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Troped, P J; Saunders, R P; Pate, R R; Reininger, B; Ureda, J R; Thompson, S J

2001-02-01

To effectively promote physical activIty, researchers and policy makers have advocated for greater use of environmental approaches, such as the construction of community paths and trails. However, research on the use of these facilities is limited. In this cross-sectional community study, we examined associations between self-reported and objective physical environmental variables and use of the Minuteman Bikeway (Arlington, MA) in a random sample of 413 adults. Sociodemographic and perceived environmental variables were measured with a mail survey during September 1998. Geographic information system (GIS) data were used to geocode survey respondents' homes and create three objective environmental variables: distance to the Bikeway, steep hill barrier, and a busy street barrier. In logistic models, age and female gender showed statistically significant inverse associations with Bikeway use over the previous 4-week period. Increases in self-reported (OR = 0.65) and GIS distance (OR = 0.57) were associated with decreased likelihood of Bikeway use. Absence of self-reported busy street (OR = 2.01) and GIS steep hill barriers (OR = 1.84) were associated with Bikeway use. Environmental barriers such as travel distance and hilly terrain should be considered when planning community trails. A better understanding of such factors may lead to more effective promotion of trail use. Copyright 2001 American Health Foundation and Academic Press.

Alaska State Trails Program

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Recreation Search DNR State of Alaska Home Menu Parks Home Alaska State Trails Boating Safety Design and Home / Alaska State Trails Alaska State Trails Program Trails in the Spotlight Glacier Lake and Saddle Trails in Kachemak State Park Glacier Lake A Popular route joins the Saddle and Glacier Lake Trails. The

The prosurvival activity of ascites against TRAIL is associated with a shorter disease-free interval in patients with ovarian cancer

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Lane Denis

2010-01-01

associated with shorter disease-free interval. Conclusions The prosurvival activity of ascites against TRAIL is associated with shorter disease-free interval, which may be explained, at least in part, by ascites-induced cisplatin/paclitaxel resistance. Our findings suggest that ascites may contain prosurvival factors that protect against TRAIL and chemotherapy and consequently affect disease progression.

Acceleration of a trailing positron bunch in a plasma wakefield accelerator

International Nuclear Information System (INIS)

Doche, A.; Beekman, C.; Corde, S.

2017-01-01

High gradients of energy gain and high energy efficiency are necessary parameters for compact, cost-efficient and high-energy particle colliders. Plasma Wakefield Accelerators (PWFA) offer both, making them attractive candidates for next-generation colliders. Here in these devices, a charge-density plasma wave is excited by an ultra-relativistic bunch of charged particles (the drive bunch). The energy in the wave can be extracted by a second bunch (the trailing bunch), as this bunch propagates in the wake of the drive bunch. While a trailing electron bunch was accelerated in a plasma with more than a gigaelectronvolt of energy gain, accelerating a trailing positron bunch in a plasma is much more challenging as the plasma response can be asymmetric for positrons and electrons. We report the demonstration of the energy gain by a distinct trailing positron bunch in a plasma wakefield accelerator, spanning nonlinear to quasi-linear regimes, and unveil the beam loading process underlying the accelerator energy efficiency. A positron bunch is used to drive the plasma wake in the experiment, though the quasi-linear wake structure could as easily be formed by an electron bunch or a laser driver. Finally, the results thus mark the first acceleration of a distinct positron bunch in plasma-based particle accelerators.

High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

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Lee Jae-Won

2011-04-01

Full Text Available Abstract Background Tumor recurrence and metastasis develop as a result of tumors' acquisition of anti-apoptotic mechanisms and therefore, it is necessary to develop novel effective therapeutics against metastatic cancers. In this study, we showed the differential TRAIL responsiveness of human prostate adenocarcinoma PC3 and human colon carcinoma KM12 cells and their respective highly metastatic PC3-MM2 and KM12L4A sublines and investigated the mechanism underlying high susceptibility of human metastatic cancer cells to TRAIL. Results PC3-MM2 and KM12L4A cells with high level of c-Myc and DNA-PKcs were more susceptible to TRAIL than their poorly metastatic primary PC3 and KM12 cells, which was associated with down-regulation of c-FLIPL/S and Mcl-1 and up-regulation of the TRAIL receptor DR5 but not DR4 in both metastatic cells. Moreover, high susceptibility of these metastatic cells to TRAIL was resulted from TRAIL-induced potent activation of caspase-8, -9, and -3 in comparison with their primary cells, which led to cleavage and down-regulation of DNA-PKcs. Knockdown of c-Myc gene in TRAIL-treated PC3-MM2 cells prevented the increase of DR5 cell surface expression, caspase activation and DNA-PKcs cleavage and attenuated the apoptotic effects of TRAIL. Moreover, the suppression of DNA-PKcs level with siRNA in the cells induced the up-regulation of DR5 and active caspase-8, -9, and -3. We also found that 4,5-dimethoxy-2-nitrobenzaldehyde (DMNB, a specific inhibitor of DNA-PK, potentiated TRAIL-induced cytotoxicity and apoptosis in relatively TRAIL-insensitive PC3 and KM12 cells and therefore functioned as a TRAIL sensitizer. Conclusion This study showed the positive relationship between c-Myc expression in highly metastatic human prostate and colon cancer cells and susceptibility to TRAIL-induced apoptosis and therefore indicated that TRAIL might be used as an effective therapeutic modality for advanced metastatic cancers overexpressing c-Myc and

Superior Hiking Trail

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Minnesota Department of Natural Resources — Superior Hiking Trail main trail, spurs, and camp spurs for completed trail throughout Cook, Lake, St. Louis and Carlton counties. These data were collected with...

Snails and their trails: the multiple functions of trail-following in gastropods.

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Ng, Terence P T; Saltin, Sara H; Davies, Mark S; Johannesson, Kerstin; Stafford, Richard; Williams, Gray A

2013-08-01

Snails are highly unusual among multicellular animals in that they move on a layer of costly mucus, leaving behind a trail that can be followed and utilized for various purposes by themselves or by other animals. Here we review more than 40 years of experimental and theoretical research to try to understand the ecological and evolutionary rationales for trail-following in gastropods. Data from over 30 genera are currently available, representing a broad taxonomic range living in both aquatic and terrestrial environments. The emerging picture is that the production of mucus trails, which initially was an adaptation to facilitate locomotion and/or habitat extension, has evolved to facilitate a multitude of additional functions. Trail-following supports homing behaviours, and provides simple mechanisms for self-organisation in groups of snails, promoting aggregation and thus relieving desiccation and predation pressures. In gastropods that copulate, trail-following is an important component in mate-searching, either as an alternative, or in addition to the release of water- or air-borne pheromones. In some species, this includes a capacity of males not only to identify trails of conspecifics but also to discriminate between trails laid by females and males. Notably, trail discrimination seems important as a pre-zygotic barrier to mating in some snail species. As production of a mucus trail is the most costly component of snail locomotion, it is also tempting to speculate that evolution has given rise to various ways to compensate for energy losses. Some snails, for example, increase energy intake by eating particles attached to the mucus of trails that they follow, whereas others save energy through reducing the production of their own mucus by moving over previously laid mucus trails. Trail-following to locate a prey item or a mate is also a way to save energy. While the rationale for trail-following in many cases appears clear, the basic mechanisms of trail

Computer simulation of trails on a square lattice. I. Trails at infinite temperature

International Nuclear Information System (INIS)

Lim, H.A.; Meirovitch, H.

1989-01-01

A trail is a random walk on a lattice for which two bonds are not allowed to overlap. However, the chain may cross itself and one may associate with each such intersection an attractive energy epsilon-c. We study trails at infinite temperature T = ∞ (i.e., trails without attractions) on a square lattice using the scanning simulation method. Our results for the radius of gyration and the end-to-end distance strongly suggest (as do previous studies) that the shape exponent is ν = 0.75, similar to that for self-avoiding walks (SAW's). We obtain significantly more accurate estimates than have been obtained before for the entropy exponent γ = 1.350 +- 0.012 and for the effective growth parameter μ = 2.720 58 +- 0.000 20 (95% confidence limit). The persistence length is found to increase with increasing chain length N and the data fit slightly better an exponential function N/sup w/ where w = 0.047 +- 0.009 than a logarithmic one. Guttmann [J. Phys. A 18, 567 (1985)] has shown exactly that trails and SAW's on the hexagonal lattice at T = ∞ have the same exponents. Our results suggest that this is true also for the square lattice

Thigmotaxis Mediates Trail Odour Disruption.

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Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

2017-05-10

Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

International Nuclear Information System (INIS)

Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

2005-01-01

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

Superior Hiking Trail Facilities

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Minnesota Department of Natural Resources — Superior Hiking Trail main trail, spurs, and camp spurs for completed trail throughout Cook, Lake, St. Louis and Carlton counties. These data were collected with...

ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.

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Ralff, Marie D; Kline, Christina L B; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T; Prabhu, Varun V; Oster, Wolfgang; El-Deiry, Wafik S

2017-07-01

Breast cancer is a major cause of cancer-related death. TNF-related apoptosis-inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small-molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here, we show that ONC201 is efficacious against both TNBC and non-TNBC cells ( n = 13). A subset of TNBC and non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8), ONC201 has an antiproliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G 1 phase of the cell cycle. pRb expression is associated with sensitivity to the antiproliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells ( n = 5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset ( n = 2) shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL independent. Our data demonstrate that ONC201 has potent antiproliferative and proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a preclinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Improvement of airfoil trailing edge bluntness noise model

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Wei Jun Zhu

2016-02-01

Full Text Available In this article, airfoil trailing edge bluntness noise is investigated using both computational aero-acoustic and semi-empirical approach. For engineering purposes, one of the most commonly used prediction tools for trailing edge noise are based on semi-empirical approaches, for example, the Brooks, Pope, and Marcolini airfoil noise prediction model developed by Brooks, Pope, and Marcolini (NASA Reference Publication 1218, 1989. It was found in previous study that the Brooks, Pope, and Marcolini model tends to over-predict noise at high frequencies. Furthermore, it was observed that this was caused by a lack in the model to predict accurately noise from blunt trailing edges. For more physical understanding of bluntness noise generation, in this study, we also use an advanced in-house developed high-order computational aero-acoustic technique to investigate the details associated with trailing edge bluntness noise. The results from the numerical model form the basis for an improved Brooks, Pope, and Marcolini trailing edge bluntness noise model.

Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer

International Nuclear Information System (INIS)

Norian, Lyse A.; James, Britnie R.; Griffith, Thomas S.

2011-01-01

Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic

Happy trails: the effect of a media campaign on urban trail use in southern Nevada.

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Clark, Sheila; Bungum, Tim J; Meacham, Mindy; Coker, Lisa

2015-01-01

Many Americans do not meet recommendations for physical activity (PA). Communities are building trail networks to encourage PA, but the relationship between trails and PA is not well understood. We monitored usage of urban trails (N = 10) in Las Vegas, NV, before and after a promotional marketing campaign (October 2011 and April 2012). The media campaign featured print, online, and radio ads, as well as billboards and signage on gas pumps. Data were collected with infrared monitors that were placed on the trails for periods of 7 days. We compared preintervention and postintervention usage rates. Mean usage increased (P trails, significant declines at 2 trails, and no change at 1 trail. Promotional campaigns may be an effective way to increase trail usage and encourage PA.

Certification trails for data structures

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Sullivan, Gregory F.; Masson, Gerald M.

1993-01-01

Certification trails are a recently introduced and promising approach to fault detection and fault tolerance. The applicability of the certification trail technique is significantly generalized. Previously, certification trails had to be customized to each algorithm application; trails appropriate to wide classes of algorithms were developed. These certification trails are based on common data-structure operations such as those carried out using these sets of operations such as those carried out using balanced binary trees and heaps. Any algorithms using these sets of operations can therefore employ the certification trail method to achieve software fault tolerance. To exemplify the scope of the generalization of the certification trail technique provided, constructions of trails for abstract data types such as priority queues and union-find structures are given. These trails are applicable to any data-structure implementation of the abstract data type. It is also shown that these ideals lead naturally to monitors for data-structure operations.

Trail Pheromone Disruption of Argentine Ant Trail Formation and Foraging

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Suckling, D.M.; Peck, R.W.; Stringer, L.D.; Snook, K.; Banko, P.C.

2010-01-01

Trail pheromone disruption of invasive ants is a novel tactic that builds on the development of pheromone-based pest management in other insects. Argentine ant trail pheromone, (Z)-9-hexadecenal, was formulated as a micro-encapsulated sprayable particle and applied against Argentine ant populations in 400 m2 field plots in Hawai'i Volcanoes National Park. A widely dispersed point source strategy for trail pheromone disruption was used. Traffic rates of ants in bioassays of treated filter paper, protected from rainfall and sunlight, indicated the presence of behaviorally significant quantities of pheromone being released from the formulation for up to 59 days. The proportion of plots, under trade wind conditions (2-3 m s-1), with visible trails was reduced for up to 14 days following treatment, and the number of foraging ants at randomly placed tuna-bait cards was similarly reduced. The success of these trail pheromone disruption trials in a natural ecosystem highlights the potential of this method for control of invasive ant species in this and other environments. ?? Springer Science+Business Media, LLC 2010.

Prevalence of Injury in Ultra Trail Running

Directory of Open Access Journals (Sweden)

Malliaropoulos Nikolaos

2015-06-01

Full Text Available Purpose. The purpose of the study was to find the rate of musculoskeletal injuries in ultra-trail runners, investigate the most sensitive anatomical areas, and discover associated predicting factors to aid in the effective prevention and rapid rehabilitation of trail running injuries. Methods. Forty ultra trail runners responded to an epidemiological questionnaire. Results. At least one running injury was reported by 90% of the sample, with a total of 135 injuries were reported (111 overuse injuries, 24 appeared during competing. Lower back pain was the most common source of injury (42.5%. Running in the mountains (p = 0.0004 and following a personalized training schedule (p = 0.0995 were found to be protective factors. Runners involved in physical labor are associated with more injuries (p = 0.058. Higher-level runners are associated with more injuries than lower-level cohorts (p = 0.067, with symptoms most commonly arising in the lower back (p = 0.091, hip joint (p = 0.083, and the plantar surface of the foot (p = 0.054. Experienced runners (> 6 years are at greater risk of developing injuries (p = 0.001, especially in the lower back (p = 0.012, tibia (p = 0.049, and the plantar surface of the foot (p = 0 .028. Double training sessions could cause hip joint injury (p = 0.060. Conclusions. In order to avoid injury, it is recommended to train mostly on mountain trails and have a training program designed by professionals.

Ambient air conditions and variation in urban trail use.

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Holmes, Ann M; Lindsey, Greg; Qiu, Chenchen

2009-11-01

This study examines the effect of air quality and administrative policies on use of urban trails in Indianapolis, IN. Attention is focused on two policy variables: (1) issuance of air pollution advisories and (2) the adoption of Daylight Savings Time. Results suggest that while trail use varies with air quality, current public advisories regarding air pollution may be of limited effectiveness in reducing trail users' exposures to hazardous pollutants. In contrast, the adoption of Daylight Savings Time was associated with a statistically significant increase in traffic levels.

Taking Care of our Trails

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our Trails Obeying Environmental Laws Protecting Wildlife Environmental Sustainability Sustainability Protection » Trails Taking Care of our Trails Continued access and use of Los Alamos National Laboratory trails is contingent upon being good stewards of these federal lands. June 7, 2017 Hikers walk along the

Cohort Profile Update: the TRacking Adolescents' Individual Lives Survey (TRAILS).

Science.gov (United States)

Oldehinkel, Albertine J; Rosmalen, Judith Gm; Buitelaar, Jan K; Hoek, Hans W; Ormel, Johan; Raven, Dennis; Reijneveld, Sijmen A; Veenstra, René; Verhulst, Frank C; Vollebergh, Wilma Am; Hartman, Catharina A

2015-02-01

TRAILS consists of a population cohort (N=2230) and a clinical cohort (N=543), both of which were followed from about age 11 years onwards. To date, the population cohort has been assessed five times over a period of 11 years, with retention rates ranging between 80% and 96%. The clinical cohort has been assessed four times over a period of 8 years, with retention rates ranging between 77% and 85%. Since the IJE published a cohort profile on the TRAILS in 2008, the participants have matured from adolescents into young adults. The focus shifted from parents and school to entry into the labour market and family formation, including offspring. Furthermore, psychiatric diagnostic interviews were administered, the database was linked to a Psychiatric Case Registry, and the availability of genome-wide SNP variations opened the door to genome-wide association studies regarding a wide range of (endo)phenotypes. With some delay, TRAILS data are available to researchers outside the TRAILS consortium without costs; access can be obtained by submitting a publication proposal (see www.trails.nl). © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Trails and physical activity: a review.

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Starnes, Heather A; Troped, Philip J; Klenosky, David B; Doehring, Angela M

2011-11-01

To provide a synthesis of research on trails and physical activity from the public health, leisure sciences, urban planning, and transportation literatures. A search of databases was conducted to identify studies published between 1980 and 2008. 52 studies were identified. The majority were cross-sectional (92%) and published after 1999 (77%). The evidence for the effects of trails on physical activity was mixed among 3 intervention and 5 correlational studies. Correlates of trail use were examined in 13 studies. Several demographic (eg, race, education, income) and environmental factors (eg, land-use mix and distance to trail) were related to trail use. Evidence from 31 descriptive studies identified several facilitators and barriers to trail use. Economic studies (n = 5) examining trails in terms of health or recreational outcomes found trails are cost-effective and produce significant economic benefits. There is a growing body of evidence demonstrating important factors that should be considered in promoting trail use, yet the evidence for positive effects of trails on physical activity is limited. Further research is needed to evaluate the effects of trails on physical activity. In addition, trail studies that include children and youth, older adults, and racial and ethnic minorities are a research priority.

TRAIL-coated lipid-nanoparticles overcome resistance to soluble recombinant TRAIL in non-small cell lung cancer cells

International Nuclear Information System (INIS)

De Miguel, Diego; Gallego-Lleyda, Ana; Erviti-Ardanaz, Sandra; Anel, Alberto; Martinez-Lostao, Luis; Ayuso, José María; Fernández, Luis José; Ochoa, Ignacio; Pazo-Cid, Roberto; Del Agua, Celia

2016-01-01

Purpose. Non-small cell lung cancer (NSCLC) is one the types of cancer with higher prevalence and mortality. Apo2-Ligand/TRAIL is a TNF family member able to induce apoptosis in tumor cells but not in normal cells. It has been tested in clinical trials against different types of human cancer including NSCLC. However, results of clinical trials have shown a limited efficacy of TRAIL-based therapies. Recently we have demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) greatly improved TRAIL cytotoxic ability being capable of killing chemoresistant hematological cancer cells. In the present work we have extended the study to NSCLC. Methods/patients. LUV-TRAIL-induced cytotoxicity was assessed on different NSCLC cell lines with different sensitivity to soluble TRAIL and on primary human tumor cells from three patients suffering from NSCLC cancer. We also tested LUV-TRAIL-cytotoxic ability in combination with several anti-tumor agents. Results. LUV-TRAIL exhibited a greater cytotoxic effect compared to soluble TRAIL both in A549 cells and primary human NSCLC cells. LUV-TRAIL-induced cell death was dependent on caspase-8 and caspase-3 activation. Moreover, combination of LUV-TRAIL with other anti-tumor agents such as flavopiridol, and SNS-032 clearly enhanced LUV-TRAIL-induced cytotoxicity against NSCLC cancer cells. Conclusion. The novel formulation of TRAIL based on displaying it on the surface of lipid nanoparticles greatly increases its anti-tumor activity and has clinical potential in cancer treatment. (paper)

Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

Science.gov (United States)

Yoon, Ji-Yong; Cho, Hyun-Soo; Lee, Jeong-Ju; Lee, Hyo-Jung; Jun, Soo Young; Lee, Jae-Hye; Song, Hyuk-Hwan; Choi, SangHo; Saloura, Vassiliki; Park, Choon Gil; Kim, Cheol-Hee; Kim, Nam-Soon

2016-04-01

TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Trail impacts and trail impact management related to ecotourism visitation at Torres del Paine National Park, Chile

Science.gov (United States)

Farrell, T.A.; Marion, J.L.

2002-01-01

Ecotourism and protected area visitation in Central and South America are largely dependent upon a relatively undisturbed quality of natural resources. However, visitation may impact vegetation, soil, water and wildlife resources, and degrade visitor facilities such as recreation sites and trails. Findings are reported from trail impact research conducted at Torres del Paine National Park in Patagonia, Chile. The frequency and magnitude of selected trail impacts and the relative effect of the amount of use, vegetation type, trail position and trail grade are investigated. Findings differed from previous studies in that amount of use was significantly related to both trail width increases and trail erosion. Management actions to minimize trail impacts are offered.

Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

International Nuclear Information System (INIS)

Marini, Patrizia; Schmid, Angelika; Jendrossek, Verena; Faltin, Heidrun; Daniel, Peter T; Budach, Wilfried; Belka, Claus

2005-01-01

TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor

Global variation of meteor trail plasma turbulence

Directory of Open Access Journals (Sweden)

L. P. Dyrud

2011-12-01

Full Text Available We present the first global simulations on the occurrence of meteor trail plasma irregularities. These results seek to answer the following questions: when a meteoroid disintegrates in the atmosphere, will the resulting trail become plasma turbulent? What are the factors influencing the development of turbulence? and how do these trails vary on a global scale? Understanding meteor trail plasma turbulence is important because turbulent meteor trails are visible as non-specular trails to coherent radars. Turbulence also influences the evolution of specular radar meteor trails; this fact is important for the inference of mesospheric temperatures from the trail diffusion rates, and their usage for meteor burst communication. We provide evidence of the significant effect that neutral atmospheric winds and ionospheric plasma density have on the variability of meteor trail evolution and on the observation of non-specular meteor trails. We demonstrate that trails are far less likely to become and remain turbulent in daylight, explaining several observational trends for non-specular and specular meteor trails.

Blazing the trail: Official Report : Singapore 2010 Youth Olympic Games

OpenAIRE

2012-01-01

The official report of the 1st Youth Olympic Games, “Blazing the trail: Official Report: Singapore 2010 Youth Olympic Games” consisted of one volume, published in French and English. The French version was published only in electronic form

Recreational Trails Reduce the Density of Ground-Dwelling Birds in Protected Areas

Science.gov (United States)

Thompson, Bill

2015-05-01

Recreational disturbance associated with trails has been identified as one of the major factors causing a decline of native biodiversity within protected areas. However, despite the negative impacts that recreation can have on biodiversity, providing public access to nature is critical for the future of the conservation of biodiversity. As such, many protected area managers are looking for tools to help maintain a balance between public access and biodiversity conservation. The objectives of this study were to examine the impacts of recreational trails on forest-dwelling bird communities in eastern North America, identify functional guilds which are particularly sensitive to recreational trails, and derive guidelines for trail design to assist in managing the impacts of recreational trails on forest-dwelling birds. Trails within 24 publicly owned natural areas were mapped, and breeding bird communities were described with the use of point count surveys. The density of forest birds, particularly of those species which nest or forage on the ground, were significantly positively influenced by the amount of trail-free refuge habitat. Although management options to control trail use in non-staffed protected areas are limited, this study suggests that protected area managers could design and maintain a trail network that would minimize impacts on resident wildlife, while providing recreational opportunities for visitors, by designing their trail network to maximize the area of trail-free habitat.

Recreational trails reduce the density of ground-dwelling birds in protected areas.

Science.gov (United States)

Thompson, Bill

2015-05-01

Recreational disturbance associated with trails has been identified as one of the major factors causing a decline of native biodiversity within protected areas. However, despite the negative impacts that recreation can have on biodiversity, providing public access to nature is critical for the future of the conservation of biodiversity. As such, many protected area managers are looking for tools to help maintain a balance between public access and biodiversity conservation. The objectives of this study were to examine the impacts of recreational trails on forest-dwelling bird communities in eastern North America, identify functional guilds which are particularly sensitive to recreational trails, and derive guidelines for trail design to assist in managing the impacts of recreational trails on forest-dwelling birds. Trails within 24 publicly owned natural areas were mapped, and breeding bird communities were described with the use of point count surveys. The density of forest birds, particularly of those species which nest or forage on the ground, were significantly positively influenced by the amount of trail-free refuge habitat. Although management options to control trail use in non-staffed protected areas are limited, this study suggests that protected area managers could design and maintain a trail network that would minimize impacts on resident wildlife, while providing recreational opportunities for visitors, by designing their trail network to maximize the area of trail-free habitat.

COROTATING INTERACTION REGION ASSOCIATED SUPRATHERMAL HELIUM ION ENHANCEMENTS AT 1 AU: EVIDENCE FOR LOCAL ACCELERATION AT THE COMPRESSION REGION TRAILING EDGE

International Nuclear Information System (INIS)

Ebert, R. W.; Dayeh, M. A.; Desai, M. I.; Mason, G. M.

2012-01-01

We examined the temporal profiles and peak intensities for 73 corotating interaction region (CIR)-associated suprathermal (∼0.1-8 MeV nucleon –1 ) helium (He) ion enhancements identified at STEREO-A, STEREO-B, and/or Advanced Composition Explorer between 2007 and 2010. We found that in most events the peak He intensity times were well organized by the CIR compression region trailing edge, regardless of whether or not a reverse shock was present. Out of these events, 19% had their 0.193 MeV nucleon –1 He intensities peak within 1 hr and 50% within 4.75 hr of the CIR trailing edge, the distribution having a 1σ value of 7.3 hr. Events with a 0.193 MeV nucleon –1 He intensity peak time within 1σ of the CIR trailing edge showed a positive correlation between the ∼0.1 and 0.8 MeV nucleon –1 He peak intensities and magnetic compression ratios in events both with and without a reverse shock. The peak intensities in all other events showed little to moderate correlation between these parameters. Our results provide evidence that some fraction of the CIR-associated –1 He intensity enhancements observed at 1 AU are locally driven. We suggest an extended source for the CIR-associated energetic particles observed at 1 AU where the –1 ions are accelerated locally at or near the CIR trailing edge, the intensities being proportional to the local compression ratio strength, while the >MeV particles are likely accelerated at CIR-driven shocks beyond Earth orbit.

Inhibition of TRAIL-induced apoptosis and forced internalization of TRAIL receptor 1 by adenovirus proteins.

Science.gov (United States)

Tollefson, A E; Toth, K; Doronin, K; Kuppuswamy, M; Doronina, O A; Lichtenstein, D L; Hermiston, T W; Smith, C A; Wold, W S

2001-10-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis through two receptors, TRAIL-R1 (also known as death receptor 4) and TRAIL-R2 (also known as death receptor 5), that are members of the TNF receptor superfamily of death domain-containing receptors. We show that human adenovirus type 5 encodes three proteins, named RID (previously named E3-10.4K/14.5K), E3-14.7K, and E1B-19K, that independently inhibit TRAIL-induced apoptosis of infected human cells. This conclusion was derived from studies using wild-type adenovirus, adenovirus replication-competent mutants that lack one or more of the RID, E3-14.7K, and E1B-19K genes, and adenovirus E1-minus replication-defective vectors that express all E3 genes, RID plus E3-14.7K only, RID only, or E3-14.7K only. RID inhibits TRAIL-induced apoptosis when cells are sensitized to TRAIL either by adenovirus infection or treatment with cycloheximide. RID induces the internalization of TRAIL-R1 from the cell surface, as shown by flow cytometry and indirect immunofluorescence for TRAIL-R1. TRAIL-R1 was internalized in distinct vesicles which are very likely to be endosomes and lysosomes. TRAIL-R1 is degraded, as indicated by the disappearance of the TRAIL-R1 immunofluorescence signal. Degradation was inhibited by bafilomycin A1, a drug that prevents acidification of vesicles and the sorting of receptors from late endosomes to lysosomes, implying that degradation occurs in lysosomes. RID was also shown previously to internalize and degrade another death domain receptor, Fas, and to prevent apoptosis through Fas and the TNF receptor. RID was shown previously to force the internalization and degradation of the epidermal growth factor receptor. E1B-19K was shown previously to block apoptosis through Fas, and both E1B-19K and E3-14.7K were found to prevent apoptosis through the TNF receptor. These findings suggest that the receptors for TRAIL, Fas ligand, and TNF play a role in limiting virus

Comparative efficacy of multimodal digital methods in assessing trail/resource degradation

Science.gov (United States)

Logan O. Park

2014-01-01

Outdoor recreation can cause both positive and negative impacts on associated forest ecosystems. Forest recreation trails localize negative impacts to a controlled spatial extent while providing recreation access beyond developed areas and transportation networks. Current methods for assessing extent and severity of trail and proximal resource degradation require...

The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

International Nuclear Information System (INIS)

Maduro, John H.; Noordhuis, Maartje G.; Hoor, Klaske A. ten; Pras, Elisabeth; Arts, Henriette J.G.; Eijsink, Jasper J.H.; Hollema, Harry; Mom, Constantijne H.; Jong, Steven de; Vries, Elisabeth G.E. de; Bock, Geertruida H. de; Zee, Ate G.J. van der

2009-01-01

Purpose: Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervical cancer and to determine their predictive and prognostic value. Methods and Materials: Tissue microarrays were constructed from tumors of 645 cervical cancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival. Results: Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p ≤0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival. Conclusions: Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervical cancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.

THE ARC TRAIL

African Journals Online (AJOL)

INTRODUCTION. The project, carried out by the 1985 Conservation. Team at Durban Girls1 High School, consisted of three main aims- Awareness, Recreation and conservation, which were incorporated into the naming of the ARC trail. The trail is situated in suburban Durban where it was felt that it was important to ...

Dichotomous scoring of Trails B in patients referred for a dementia evaluation.

Science.gov (United States)

Schmitt, Andrew L; Livingston, Ronald B; Smernoff, Eric N; Waits, Bethany L; Harris, James B; Davis, Kent M

2010-04-01

The Trail Making Test is a popular neuropsychological test and its interpretation has traditionally used time-based scores. This study examined an alternative approach to scoring that is simply based on the examinees' ability to complete the test. If an examinee is able to complete Trails B successfully, they are coded as "completers"; if not, they are coded as "noncompleters." To assess this approach to scoring Trails B, the performance of 97 diagnostically heterogeneous individuals referred for a dementia evaluation was examined. In this sample, 55 individuals successfully completed Trails B and 42 individuals were unable to complete it. Point-biserial correlations indicated a moderate-to-strong association (r(pb)=.73) between the Trails B completion variable and the Total Scale score of the Repeatable Battery for the Assessment of Neurological Status (RBANS), which was larger than the correlation between the Trails B time-based score and the RBANS Total Scale score (r(pb)=.60). As a screen for dementia status, Trails B completion showed a sensitivity of 69% and a specificity of 100% in this sample. These results suggest that dichotomous scoring of Trails B might provide a brief and clinically useful measure of dementia status.

TRAIL death receptors and cancer therapeutics

International Nuclear Information System (INIS)

Huang Ying; Sheikh, M. Saeed

2007-01-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) also known as Apo2L is an apoptotic molecule that belongs to the tumor necrosis factor superfamily of cytokines. It mediates its apoptotic effects via its cognate death receptors including DR4 and DR5. Agonistic monoclonal antibodies have also been developed that selectively activate TRAIL death receptors to mediate apoptosis. Multiple clinically relevant agents also upregulate the expression of TRAIL death receptors, and cooperate with TRAIL as well as DR4 and DR5-specific agonistic antibodies to exhibit tumor cell killing. TRAIL is currently in phase I clinical trials, whereas DR4 and DR5-specific agonistic antibodies have been tested in phase I and II studies. Thus, TRAIL has clearly distinguished itself from the other family members including TNF-alpha and FasL both of which could not make it to the clinic due to their toxic nature. It is therefore, evident that the future of TRAIL-based therapeutic approaches looks brighter

Cohort Profile Update: The TRacking Adolescents’ Individual Lives Survey (TRAILS)

Science.gov (United States)

Oldehinkel, Albertine J; Rosmalen, Judith GM; Buitelaar, Jan K; Hoek, Hans W; Ormel, Johan; Raven, Dennis; Reijneveld, Sijmen A; Veenstra, René; Verhulst, Frank C; Vollebergh, Wilma AM; Hartman, Catharina A

2015-01-01

TRAILS consists of a population cohort (N = 2230) and a clinical cohort (N = 543), both of which were followed from about age 11 years onwards. To date, the population cohort has been assessed five times over a period of 11 years, with retention rates ranging between 80% and 96%. The clinical cohort has been assessed four times over a period of 8 years, with retention rates ranging between 77% and 85%. Since the IJE published a cohort profile on the TRAILS in 2008, the participants have matured from adolescents into young adults. The focus shifted from parents and school to entry into the labour market and family formation, including offspring. Furthermore, psychiatric diagnostic interviews were administered, the database was linked to a Psychiatric Case Registry, and the availability of genome-wide SNP variations opened the door to genome-wide association studies regarding a wide range of (endo)phenotypes. With some delay, TRAILS data are available to researchers outside the TRAILS consortium without costs; access can be obtained by submitting a publication proposal (see www.trails.nl). PMID:25431468

L-DRD4 genotype not associated with sensation seeking, gambling performance and startle reactivity in adolescents: the TRAILS study

NARCIS (Netherlands)

Nederhof, E.; Creemers, H.E.; Huizink, A.C.; Ormel, J.; Oldehinkel, A.J.

2011-01-01

The purpose of the present study was to investigate whether a length polymorphism in the dopamine receptor D4 gene (DRD4) was associated with approach related traits in adolescents. Data were used from TRAILS (TRacking Adolescents’ Individual Lives Survey), a population based cohort of Dutch

Comparing impacts between formal and informal recreational trails.

Science.gov (United States)

Pickering, Catherine Marina; Norman, Patrick

2017-05-15

Globally there are hundreds of thousands of kilometres of recreational trails traversing natural areas of high conservation value: but what are their impacts and do impacts differ among trails? We compared the effects of four common types of recreational trails [(1) narrow and (2) medium width informal bare earth trails and (3) gravel and (4) tarmac/concrete formal trails] on vegetation adjacent to trails in a high conservation value plant community that is popular for mountain biking and hiking in Australia. Plant species composition was recorded in quadrats along the edge of the four types of trails and in control sites away from trails. Vegetation cover, the cover of individual growth forms, and species richness along the edges of all four types of trails were similar to the controls, although the wider trails affected plant composition, with the tarmac and gravel trails favouring different species. With very few comparative studies, more research is required to allow managers and researchers to directly compare differences in the severity and types of impacts on vegetation among trails. In the meantime, limiting damage to vegetation on the edge of hardened trails during construction, use and maintenance is important, and hardening trails may not always be appropriate. Copyright © 2016. Published by Elsevier Ltd.

ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

Science.gov (United States)

Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

2017-01-01

Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The pro-apoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8) ONC201 has an anti-proliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the anti-proliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n=5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n=2) show PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL-independent. Our data demonstrate that ONC201 has potent anti-proliferative and pro-apoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a pre-clinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. PMID:28424227

3-Bromopyruvate enhances TRAIL-induced apoptosis in human nasopharyngeal carcinoma cells through CHOP-dependent upregulation of TRAIL-R2.

Science.gov (United States)

Can, Zhou; Lele, Song; Zhirui, Zhang; Qiong, Pan; Yuzhong, Chen; Lingling, Liu; Surong, Zhao; Yiming, Sun; Pei, Zhang; Chenchen, Jiang; Liu, Hao

2017-08-01

Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC.

Cellular characterisation of Candida tropicalis presenting fluconazole-related trailing growth

Directory of Open Access Journals (Sweden)

Marcos Dornelas-Ribeiro

2012-02-01

Full Text Available We assessed fluconazole susceptibility in 52 Candida tropicalis clinical strains using seven antifungal susceptibility methods, including broth microdilution (BMD [standard M27 A3 (with neutral and acid pH, ATB Fungus 3, Vitek 2 system and flow cytometric analysis] and agar-based methods (disk diffusion and E-test. Trailing growth, detection of cell-associated secreted aspartic proteases (Saps and morphological and ultrastructural traits of these clinical strains were also examined. The ranges of fluconazole 24 h-minimum inhibitory concentration (MIC values were similar among all methods. The essential agreement among the methods used for MIC determinations was excellent and all methods categorised all strains as susceptible, except for one strain that showed a minor error. The presence of the trailing effect was assessed by six methods. Trailing positivity was observed for 86.5-100% of the strains. The exception was the BMD-Ac method where trailing growth was not observed. Morphological and ultrastructural alterations were detected in C. tropicalis trailing cells, including mitochondrial swelling and cell walls with irregular shapes. We tested the production of Saps in 13 C. tropicalis strains expressing trailing growth through flow cytometry. Our results showed that all of the C. tropicalis strains up-regulated surface Sap expression after 24 h or 48 h of exposure to fluconazole, which was not observed in untreated yeast strains. We concluded that C. tropicalis strains expressing trailing growth presented some particular features on both biological and ultrastructural levels.

Existence of spanning and dominating trails and circuits

NARCIS (Netherlands)

Veldman, H.J.

1986-01-01

Let T be a trail of a graph G. T is a spanning trail (S-trail) if T contains all vertices of G. T is a dominating trail (D-trail) if every edge of G is incident with at least one vertex of T. A circuit is a nontrivial closed trail. Sufficient conditions involving lower bounds on the degree-sum of

Estimating the economic value and impacts of recreational trails: a case study of the Virginia creeper rail trail

Science.gov (United States)

J. Michael Bowker; John C. Bergstrom; Joshua Gill

2007-01-01

Many communities are interested in developing and maintaining recreational trails to benefit trail users and as tourist attractions to stimulate economic growth. In this paper, a study is described which estimates the net economic value to trail users and the local economic impacts of the Virginia Creeper Rail Trail in south-western Virginia, USA. The monetary...

Attitudes and intentions of off-highway vehicle riders toward trail use: implications for forest managers

Science.gov (United States)

Kuehn, D.M.; D'Luhosch, P. D.; Luzadis, V.A.; Malmsheimer, R.W.; Schuster, R.M.

2011-01-01

Management of off-highway vehicles (OHV) in public forest areas requires up-to-date information about the attitudes and intentions of OHV riders toward trail use. A survey of 811 members of the New England Trail Riders Association was conducted in fall 2007; 380 questionnaires were completed and returned. Descriptive statistics and regressions were used to identify relationships between OHV rider attitudes, management preferences, and intentions toward two trail use-related behaviors (i.e., illegal use of trails by OHVs and the creation and/or use of unauthorized trails by OHV riders). Results reveal that the average responding association member has a negative attitude toward the two depreciative behaviors, intends to ride OHVs legally, and slightly prefers indirect over direct forms of management. Significant relationships between intentions and both attitudes and management preferences are identified. Policy and management implications and strategies are discussed. ?? 2011 by the Society of American Foresters.

75 FR 32555 - Consolidated Audit Trail

Science.gov (United States)

2010-06-08

... Part II Securities and Exchange Commission 17 CFR Part 242 Consolidated Audit Trail; Proposed Rule... 3235-AK51 Consolidated Audit Trail AGENCY: Securities and Exchange Commission. ACTION: Proposed rule... a consolidated order tracking system, or consolidated audit trail, with respect to the trading of...

Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

Science.gov (United States)

Xu, Ying; Gao, Cheng-Cheng; Pan, Zhen-Guo; Zhou, Chuan-Wen

2018-02-12

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment. Copyright © 2018. Published by Elsevier Inc.

BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis

Directory of Open Access Journals (Sweden)

Christina A. Wicker

2009-01-01

Full Text Available Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12, which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC. BITC is a component of cruciferous vegetables and a cell cycle inhibitor. BxPC3, MiaPaCa2 and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC induced TRAIL sensitization by dual activation of both the extrinsic and intrinsic apoptotic pathways.

Efforts of a Kansas foundation to increase physical activity and improve health by funding community trails, 2012.

Science.gov (United States)

Heinrich, Katie M; Lightner, Joseph; Oestman, Katherine B; Hughey, S Morgan; Kaczynski, Andrew T

2014-11-26

Trails are associated with increased physical activity; however, little is known about the process of building trails by various types of organizations. From 2005 through 2012 the Sunflower Foundation: Health Care for Kansans (Sunflower) funded multiple organizations to construct 70 trails of varying lengths and surfaces in municipalities, schools, and communities across Kansas. The purpose of this study was to assess the process of developing and implementing community trail projects across Kansas with funding from a public foundation. In 2012, we stratified funded organizations by type and conducted proportional random sampling to select 20 key informants from those organizations to participate in structured telephone interviews. Interviews were recorded and transcribed verbatim. Two researchers coded interview transcripts according to issues identified by participants. Issues associated with trail-building identified as important were collaboration among groups, unexpected construction costs, champions for the project, and level of difficulty of construction. Participants indicated that trails facilitated physical activity. Trails were integrated into communities through events such as walking events and other promotional efforts; these efforts were thought to increase trail use. The perceived outcomes of building the trails included providing the community with a physical activity resource, inspiring the community to start additional trail projects, and increasing the physical activity of local residents. Sunflower's funding was instrumental in developing trail projects to provide new physical activity resources across Kansas. Public health practitioners seeking to increase physical activity should seek funding from foundations that focus on health.

77 FR 45721 - Consolidated Audit Trail

Science.gov (United States)

2012-08-01

... maintain a consolidated order tracking system, or consolidated audit trail, with respect to the trading of... With a Consolidated Audit Trail 3. Large Trader Reporting System Rule B. Summary of Proposed Rule 613 C... Authority (``FINRA'') and some of the exchanges currently maintain their own separate audit trail systems...

Heavy water at Trail, British Columbia

International Nuclear Information System (INIS)

Arsenault, J.E.

2006-01-01

Today Canada stands on the threshold of a nuclear renaissance, based on the CANDU reactor family, which depends on heavy water as a moderator and for cooling. Canada has a long history with heavy water, with commercial interests beginning in 1934, a mere two years after its discovery. At one time Canada was the world's largest producer of heavy water. The Second World War stimulated interest in this rather rare substance, such that the worlds largest supply (185 kg) ended up in Canada in 1942 to support nuclear research work at the Montreal Laboratories of the National Research Council. A year later commercial production began at Trail, British Columbia, to support work that later became known as the P-9 project, associated with the Manhattan Project. The Trail plant produced heavy water from 1943 until 1956, when it was shut down. During the war years the project was so secret that Lesslie Thomson, Special Liaison Officer reporting on nuclear matters to C.D. Howe, Minister of Munitions and Supply, was discouraged from visiting Trail operations. Thomson never did visit the Trail facility during the war. In 2005 the remaining large, tall concrete exchange tower was demolished at a cost of about $2.4 million, about the same as it cost to construct the facility about 60 years ago. Thus no physical evidence remains of this historic facility and another important artifact from Canada's nuclear history has disappeared forever. It is planned to place a plaque at the site at some point in the future. (author)

Heavy water at Trail, British Columbia

Energy Technology Data Exchange (ETDEWEB)

Arsenault, J.E. [Ontario (Canada)

2006-09-15

Today Canada stands on the threshold of a nuclear renaissance, based on the CANDU reactor family, which depends on heavy water as a moderator and for cooling. Canada has a long history with heavy water, with commercial interests beginning in 1934, a mere two years after its discovery. At one time Canada was the world's largest producer of heavy water. The Second World War stimulated interest in this rather rare substance, such that the worlds largest supply (185 kg) ended up in Canada in 1942 to support nuclear research work at the Montreal Laboratories of the National Research Council. A year later commercial production began at Trail, British Columbia, to support work that later became known as the P-9 project, associated with the Manhattan Project. The Trail plant produced heavy water from 1943 until 1956, when it was shut down. During the war years the project was so secret that Lesslie Thomson, Special Liaison Officer reporting on nuclear matters to C.D. Howe, Minister of Munitions and Supply, was discouraged from visiting Trail operations. Thomson never did visit the Trail facility during the war. In 2005 the remaining large, tall concrete exchange tower was demolished at a cost of about $2.4 million, about the same as it cost to construct the facility about 60 years ago. Thus no physical evidence remains of this historic facility and another important artifact from Canada's nuclear history has disappeared forever. It is planned to place a plaque at the site at some point in the future. (author)

Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

Directory of Open Access Journals (Sweden)

Ruo-Jing Wei

2018-01-01

Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer (PCa cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPr1, and LNCaP cells were treated with Andrographolide (Andro and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction (PCR and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species (ROS in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.

Differential expression of TRAIL and its receptors relative to calcification in AAA

International Nuclear Information System (INIS)

Liu, Xun; Winrow, Vivienne R.; Horrocks, Michael; Stevens, Cliff R.

2007-01-01

Abdominal aortic aneurysm (AAA) is commonly associated with atherosclerosis. Human AAA tissue displays cells undergoing all stages of apoptosis. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumour cells but not in normal cells. It has death receptors and decoy receptors. An inhibitor of TRAIL, osteoprotegerin (OPG), is involved in osteogenesis and vascular calcification. We investigated TRAIL and its receptors in AAA compared within normal aorta (NA). Both qualitative and quantitative analyses of calcification in AAA walls were determined using Von Kossa staining and pre-operation computer tomography (CT) scans. There was a significant difference in calcification level at different locations in the AAA wall (p < 0.05). Apoptosis was confirmed in AAA by TUNEL assay. A significant difference in TRAIL and its receptor expression was observed between normal aortae and AAA (p < 0.05). Significant differences were also observed between tissues displaying different extents of calcification for TRAIL mRNA (p < 0.05) by RT-PCR examination and OPG protein (p < 0.01) by protein blotting examination. We propose that this pattern of expression of TRAIL and its receptors may contribute to AAA formation and calcification in the AAA wall

Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis

DEFF Research Database (Denmark)

Zhuang, Hongqin; Jiang, Weiwei; Cheng, Wei

2010-01-01

Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) has recently emerged as a cancer therapeutic agent because it preferentially induces apoptosis in human cancer over normal cells. Most tumor cells, including lung cancer cell line A549, unfortunately, are resistant to TRAIL tre...

An analysis of state legislation on community trails.

Science.gov (United States)

Eyler, Amy; Lankford, Tina; Chriqui, Jamie; Evenson, Kelly R; Kruger, Judy; Tompkins, Nancy; Voorhees, Carolyn; Zieff, Susan; Aytur, Semra; Brownson, Ross

2010-03-01

Trails provide opportunities for recreation, transportation and activity. The purpose of this article is to describe state legislation related to community trails, to analyze legislation content, and to evaluate legislation on inclusion of evidence-informed elements. State trail legislation from 2001 to 2008 was identified using online legislative databases. An analysis of evidence-informed elements included in the legislation was conducted. These elements included: funding, liability, accessibility, connectivity, and maintenance. Of the total 991 trail bills, 516 (52.0%) were appropriations bills, of which 167 (32.2%) were enacted. We analyzed 475 (48%) nonappropriation trail bills of which 139 (29.3%) were enacted. The percentage of enactment of appropriations bills decreased over time while enactment of nonappropriations trail bills increased. Over half of the nonappropriations trail bills included at least 1 evidence-informed element, most commonly funding. Few bills contained liability, connectivity, accessibility, or maintenance. There is opportunity for providing evidence-informed information to policy-makers to potentially influence bill content. The number of bills with a funding element demonstrates that fiscal support for trails is an important policy lever that state legislatures may use to support trails. Lastly, trails should be considered in over-all state-level physical activity legislation to provide opportunities for communities to be active.

Allegheny County Blazed Trails Locations

Data.gov (United States)

Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Shows the location of blazed trails in all Allegheny County parks. This is the same data used in the Allegheny County Parks Trails Mobile App, available for Apple...

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

Directory of Open Access Journals (Sweden)

Fernanda Genre

2014-01-01

Full Text Available Objective. TRAIL is a potential biomarker of cardiovascular (CV disease. Ankylosing spondylitis (AS is a chronic inflammatory disease associated with metabolic syndrome (MeS and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

36 CFR 261.55 - National Forest System trails.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false National Forest System trails... PROHIBITIONS Prohibitions in Areas Designated by Order § 261.55 National Forest System trails. When provided by... National Forest System trail: (a) Being on a trail. (b) Using any type of vehicle prohibited by the order...

Tissue distribution of the death ligand TRAIL and its receptors

NARCIS (Netherlands)

Spierings, DC; de Vries, EG; Vellenga, E; van den Heuvel, FA; Koornstra, JJ; Wesseling, J; Hollema, H; de Jong, S

Recombinant human (rh) TNF-related apoptosis-inducing ligand (TRAIL) harbors potential as an anticancer agent. RhTRAIL induces apoptosis via the TRAIL receptors TRAIL-R1 and TRAIL-R2 in tumors and is non-toxic to nonhuman primates. Because limited data are available about TRAIL receptor

Assessing and Predicting Erosion from Off Highway Vehicle Trails in Front-Range Rocky Mountain Watersheds.

Science.gov (United States)

Howard, M. J.; Silins, U.; Anderson, A.

2016-12-01

Off highway vehicle (OHV) trails have the potential to deliver sediment to sensitive headwater streams and increased OHV use is a growing watershed management concern in many Rocky Mountain regions. Predictive tools for estimating erosion and sediment inputs are needed to support assessment and management of erosion from OHV trail networks. The objective of this study was to a) assess erodibility (K factor) and total erosion from OHV trail networks in Rocky Mountain watersheds in south-west Alberta, Canada, and to b) evaluate the applicability of the Universal Soil Loss Equation (USLE) for predicting OHV trail erosion to support erosion management strategies. Measured erosion rates and erodibility (K) from rainfall simulation plots on OHV trails during the summers of 2014 and 2015 were compared to USLE predicted erosion from these same trails. Measured erodibility (K) from 23 rainfall simulation plots was highly variable (0.001-0.273 Mg*ha*hr/ha*MJ*mm) as was total seasonal erosion from 52 large trail sections (0.0595-43.3 Mg/ha) across trail segments of variable slope, stoniness, and trail use intensity. In particular, intensity of trail use had a large effect on both erodibility and total erosion that is not presently captured by erodibility indices (K) derived from soil characteristics. Results of this study suggest that while application of USLE for predicting erosion from OHV trail networks may be useful for initial coarse erosion assessment, a better understanding of the effect of factors such as road/trail use intensity on erodibility is needed to support use of USLE or associated erosion prediction tools for road/trail erosion management.

Distribution, abundance and trail characteristics of acorn worms at Australian continental margins

Science.gov (United States)

Anderson, T. J.; Przeslawski, R.; Tran, M.

2011-04-01

Acorn worms (Enteropneusta), which were previously thought to be a missing link in understanding the evolution of chordates, are an unusual and potentially important component of many deep-sea benthic environments, particularly for nutrient cycling. Very little is known about their distribution, abundance, or behaviour in deep-sea environments around the world, and almost nothing is known about their distribution within Australian waters. In this study, we take advantage of two large-scale deep-sea mapping surveys along the eastern (northern Lord Howe Rise) and western continental margins of Australia to quantify the distribution, abundance and trail-forming behaviour of this highly unusual taxon. This is the first study to quantify the abundance and trail behaviour of acorn worms within Australian waters and provides the first evidence of strong depth-related distributions. Acorn worm densities and trail activity were concentrated between transect-averaged depths of 1600 and 3000 m in both eastern and western continental margins. The shallow limit of their depth distribution was 1600 m. The deeper limit was less well-defined, as individuals were found in small numbers below 3000 down to 4225 m. This distributional pattern may reflect a preference for these depths, possibly due to higher availability of nutrients, rather than a physiological constraint to greater depths. Sediment characteristics alone were poor predictors of acorn worm densities and trail activity. High densities of acorn worms and trails were associated with sandy-mud sediments, but similar sediment characteristics in either shallower or deeper areas did not support similar densities of acorn worms or trails. Trail shapes varied between eastern and western margins, with proportionally more meandering trails recorded in the east, while spiral and meandering trails were both common in the west. Trail shape varied by depth, with spiral-shaped trails dominant in areas of high acorn worm densities

Use of the color trails test as an embedded measure of performance validity.

Science.gov (United States)

Henry, George K; Algina, James

2013-01-01

One hundred personal injury litigants and disability claimants referred for a forensic neuropsychological evaluation were administered both portions of the Color Trails Test (CTT) as part of a more comprehensive battery of standardized tests. Subjects who failed two or more free-standing tests of cognitive performance validity formed the Failed Performance Validity (FPV) group, while subjects who passed all free-standing performance validity measures were assigned to the Passed Performance Validity (PPV) group. A cutscore of ≥45 seconds to complete Color Trails 1 (CT1) was associated with a classification accuracy of 78%, good sensitivity (66%) and high specificity (90%), while a cutscore of ≥84 seconds to complete Color Trails 2 (CT2) was associated with a classification accuracy of 82%, good sensitivity (74%) and high specificity (90%). A CT1 cutscore of ≥58 seconds, and a CT2 cutscore ≥100 seconds was associated with 100% positive predictive power at base rates from 20 to 50%.

Travel to, and use of, twenty-one Michigan trails.

Science.gov (United States)

Price, Anna E; Reed, Julian A; Grost, Lisa; Harvey, Christina; Mantinan, Karah

2013-03-01

This study examined trail use among 857 trail users on 21 trails in Michigan from 2008 to 2011 using a valid and reliable intercept survey. Most of the 857 participants traveled to the trail from their home (92.6%), lived within 15 min of the trails (74.8%), and used active transport to travel to the trails 69.7%. The odds of active transport to the trails were greater among those who had not graduated high school (OR=3.49; 95% CI=1.02, 11.99) and high school graduates (OR=7.432; 95% CI=2.02, 27.30) compared to college graduates. Whites and adults also had greater odds of active transport than non-Whites (OR=3.160, 95% CI: 1.65, 6.05), and older adults (OR=1.75; 95% CI: 1.20, 2.54). The majority of respondents (89.7%) reported using trails for recreational purposes. A significantly greater proportion of females (73.3%) compared to males (64.7%) reported using the trail with others. The findings from this study might enable health and parks and recreation professionals to better promote physical activity on trails. Copyright © 2013 Elsevier Inc. All rights reserved.

Automatic dirt trail analysis in dermoscopy images.

Science.gov (United States)

Cheng, Beibei; Joe Stanley, R; Stoecker, William V; Osterwise, Christopher T P; Stricklin, Sherea M; Hinton, Kristen A; Moss, Randy H; Oliviero, Margaret; Rabinovitz, Harold S

2013-02-01

Basal cell carcinoma (BCC) is the most common cancer in the US. Dermatoscopes are devices used by physicians to facilitate the early detection of these cancers based on the identification of skin lesion structures often specific to BCCs. One new lesion structure, referred to as dirt trails, has the appearance of dark gray, brown or black dots and clods of varying sizes distributed in elongated clusters with indistinct borders, often appearing as curvilinear trails. In this research, we explore a dirt trail detection and analysis algorithm for extracting, measuring, and characterizing dirt trails based on size, distribution, and color in dermoscopic skin lesion images. These dirt trails are then used to automatically discriminate BCC from benign skin lesions. For an experimental data set of 35 BCC images with dirt trails and 79 benign lesion images, a neural network-based classifier achieved a 0.902 are under a receiver operating characteristic curve using a leave-one-out approach. Results obtained from this study show that automatic detection of dirt trails in dermoscopic images of BCC is feasible. This is important because of the large number of these skin cancers seen every year and the challenge of discovering these earlier with instrumentation. © 2011 John Wiley & Sons A/S.

Pheromone disruption of Argentine ant trail integrity

Science.gov (United States)

Suckling, D.M.; Peck, R.W.; Manning, L.M.; Stringer, L.D.; Cappadonna, J.; El-Sayed, A. M.

2008-01-01

Disruption of Argentine ant trail following and reduced ability to forage (measured by bait location success) was achieved after presentation of an oversupply of trail pheromone, (Z)-9-hexadecenal. Experiments tested single pheromone point sources and dispersion of a formulation in small field plots. Ant walking behavior was recorded and digitized by using video tracking, before and after presentation of trail pheromone. Ants showed changes in three parameters within seconds of treatment: (1) Ants on trails normally showed a unimodal frequency distribution of walking track angles, but this pattern disappeared after presentation of the trail pheromone; (2) ants showed initial high trail integrity on a range of untreated substrates from painted walls to wooden or concrete floors, but this was significantly reduced following presentation of a point source of pheromone; (3) the number of ants in the pheromone-treated area increased over time, as recruitment apparently exceeded departures. To test trail disruption in small outdoor plots, the trail pheromone was formulated with carnuba wax-coated quartz laboratory sand (1 g quartz sand/0.2 g wax/1 mg pheromone). The pheromone formulation, with a half-life of 30 h, was applied by rotary spreader at four rates (0, 2.5, 7.5, and 25 mg pheromone/m2) to 1- and 4-m2 plots in Volcanoes National Park, Hawaii. Ant counts at bait cards in treated plots were significantly reduced compared to controls on the day of treatment, and there was a significant reduction in ant foraging for 2 days. These results show that trail pheromone disruption of Argentine ants is possible, but a much more durable formulation is needed before nest-level impacts can be expected. ?? 2008 Springer Science+Business Media, LLC.

Potential prognostic significance of decreased serum levels of TRAIL after acute myocardial infarction.

Directory of Open Access Journals (Sweden)

Paola Secchiero

Full Text Available BACKGROUND: Since soluble TRAIL exhibits anti-inflammatory and anti-atherosclerotic activities both in vitro and in animal models, this study was designed to assess the relationship between the serum levels of TRAIL and clinical outcomes in patients with acute myocardial infarction (AMI. METHODOLOGY/PRINCIPAL FINDINGS: Levels of TRAIL were measured by ELISA in serial serum samples obtained from 60 patients admitted for AMI, both during hospitalization and in a follow-up of 12 months, as well as in 60 healthy control subjects. Serum levels of TRAIL were significantly decreased in patients with AMI at baseline (within 24 hours from admission, compared with healthy controls, and showed a significant inverse correlation with a series of negative prognostic markers, such as CK, CK-MB and BNP. TRAIL serum levels progressively increased at discharge, but normalized only at 6-12 months after AMI. Of note, low TRAIL levels at the patient discharge were associated with increased incidence of cardiac death and heart failure in the 12-month follow-up, even after adjustment for demographic and clinical risk parameters (hazard ratio [HR] of 0.93 [95% CI, 0.89 to 0.97]; p = 0.001. CONCLUSIONS/SIGNIFICANCE: Although the number of patients studied was limited, our findings indicate for the first time that circulating TRAIL might represent an important predictor of cardiovascular events, independent of conventional risk markers.

The confining trailing string

CERN Document Server

Kiritsis, E; Nitti, F

2014-01-01

We extend the holographic trailing string picture of a heavy quark to the case of a bulk geometry dual to a confining gauge theory. We compute the classical trailing confining string solution for a static as well as a uniformly moving quark. The trailing string is infinitely extended and approaches a confining horizon, situated at a critical value of the radial coordinate, along one of the space-time directions, breaking boundary rotational invariance. We compute the equations for the fluctuations around the classical solutions, which are used to obtain boundary force correlators controlling the Langevin dynamics of the quark. The imaginary part of the correlators has a non-trivial low-frequency limit, which gives rise to a viscous friction coefficient induced by the confining vacuum. The vacuum correlators are used to define finite-temperature dressed Langevin correlators with an appropriate high-frequency behavior.

Greenway Trails

Data.gov (United States)

Town of Cary, North Carolina — View the Town’s current and proposed greenway system, including connectors and street side trails.A greenway is a linear parcel of land set aside to preserve open...

Radiated sound and turbulent motions in a blunt trailing edge flow field

International Nuclear Information System (INIS)

Shannon, Daniel W.; Morris, Scott C.; Mueller, Thomas J.

2006-01-01

The dipole sound produced by edge scattering of pressure fluctuations at a trailing edge is most often an undesirable effect in turbomachinery and control surface flows. The ability to model the flow mechanisms associated with the production of trailing edge acoustics is important for the quiet design of such devices. The objective of the present research was to experimentally measure flow field and acoustic variables in order to develop an understanding of the mechanisms that generate trailing edge noise. The results of these experiments have provided insight into the causal relationships between the turbulent flow field, unsteady surface pressure, and radiated far field acoustics. Experimental methods used in this paper include particle image velocimetry (PIV), unsteady surface pressures, and far field acoustic pressures. The model investigated had an asymmetric 45 o beveled trailing edge. Reynolds numbers based on chord ranged from 1.2 x 10 6 to 1.9 x 10 6 . It was found that the small-scale turbulent motions in the vicinity of the trailing edge were modulated by a large scale von Karman wake instability. The broadband sound produced by these motions was also found to be dependant on the 'phase' of the wake instability

A mixed-modes approach for estimating hiking on trails through diverse forest landscapes: the case of the Appalachian Trail

Science.gov (United States)

Stanley J. Zarnoch; J.M. Bowker; H. Ken. Cordell

2011-01-01

Many hiking trails traverse the forests and public lands across North America. It has therefore become important for federal management to gain an understanding of total use on these trails. However, there has never been a formal attempt to estimate hiking on these long, backcountry trails. This paper presents an approach that utilizes two survey instruments (exit-site...

Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1beta-dependent stabilization of Snail in tumor cells.

Directory of Open Access Journals (Sweden)

Pawan Kaler

2010-07-01

Full Text Available We recently reported that colon tumor cells stimulate macrophages to release IL-1beta, which in turn inactivates GSK3beta and enhances Wnt signaling in colon cancer cells, generating a self-amplifying loop that promotes the growth of tumor cells.Here we describe that macrophages protect HCT116 and Hke-3 colon cancer cells from TRAIL-induced apoptosis. Inactivation of IL-1beta by neutralizing IL-1beta antibody, or silencing of IL-1beta in macrophages inhibited their ability to counter TRAIL-induced apoptosis. Accordingly, IL-1beta was sufficient to inhibit TRAIL-induced apoptosis. TRAIL-induced collapse of the mitochondrial membrane potential (Delta psi and activation of caspases were prevented by macrophages or by recombinant IL-1beta. Pharmacological inhibition of IL-1beta release from macrophages by vitamin D(3, a potent chemopreventive agent for colorectal cancer, restored the ability of TRAIL to induce apoptosis of tumor cells cultured with macrophages. Macrophages and IL-1beta failed to inhibit TRAIL-induced apoptosis in HCT116 cells expressing dnIkappaB, dnAKT or dnTCF4, confirming that they oppose TRAIL-induced cell death through induction of Wnt signaling in tumor cells. We showed that macrophages and IL-1beta stabilized Snail in tumor cells in an NF-kappaB/Wnt dependent manner and that Snail deficient tumor cells were not protected from TRAIL-induced apoptosis by macrophages or by IL-1beta, demonstrating a crucial role of Snail in the resistance of tumor cells to TRAIL.We have identified a positive feedback loop between tumor cells and macrophages that propagates the growth and promotes the survival of colon cancer cells: tumor cells stimulate macrophages to secrete IL-1beta, which in turn, promotes Wnt signaling and stabilizes Snail in tumor cells, conferring resistance to TRAIL. Vitamin D(3 halts this amplifying loop by interfering with the release of IL-1beta from macrophages. Accordingly, vitamin D(3 sensitizes tumor cells to TRAIL

Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.

Science.gov (United States)

Allen, Joshua E; Krigsfeld, Gabriel; Patel, Luv; Mayes, Patrick A; Dicker, David T; Wu, Gen Sheng; El-Deiry, Wafik S

2015-05-01

We previously reported the identification of ONC201/TIC10, a novel small molecule inducer of the human TRAIL gene that improves efficacy-limiting properties of recombinant TRAIL and is in clinical trials in advanced cancers based on its promising safety and antitumor efficacy in several preclinical models. We performed a high throughput luciferase reporter screen using the NCI Diversity Set II to identify TRAIL-inducing compounds. Small molecule-mediated induction of TRAIL reporter activity was relatively modest and the majority of the hit compounds induced low levels of TRAIL upregulation. Among the candidate TRAIL-inducing compounds, TIC9 and ONC201/TIC10 induced sustained TRAIL upregulation and apoptosis in tumor cells in vitro and in vivo. However, ONC201/TIC10 potentiated tumor cell death while sparing normal cells, unlike TIC9, and lacked genotoxicity in normal fibroblasts. Investigating the effects of TRAIL-inducing compounds on cell signaling pathways revealed that TIC9 and ONC201/TIC10, which are the most potent inducers of cell death, exclusively activate Foxo3a through inactivation of Akt/ERK to upregulate TRAIL and its pro-apoptotic death receptor DR5. These studies reveal the selective activity of ONC201/TIC10 that led to its selection as a lead compound for this novel class of antitumor agents and suggest that ONC201/TIC10 is a unique inducer of the TRAIL pathway through its concomitant regulation of the TRAIL ligand and its death receptor DR5.

Monitoring of recreational trail erosion using terrestrial structure-from-motion approach

Science.gov (United States)

Ewertowski, Marek; Tomczyk, Aleksandra

2017-04-01

Protected natural areas (PNAs) such as national and landscape parks as well as suburban green areas often constitute areas very popular among the visitors. Visitor pressure in PNAs is focused mainly on recreational trails, which facilitate activities such as hiking, cycling, horse riding. Trails prepared for different groups of users are among the most common types of infrastructure in PNAs, facilitating access to these areas. However, high visitor pressure can lead to increases in trail width and an associated increase in soil erosion. In case of extensive protected areas, the performing of regular geodetic monitoring using dGPS or laser scanning is expensive and therefore park managers often face a problem in selecting sites for impact monitoring. However, recent advances in technology enables the development of low-cost alternatives for traditional surveys. Consumer-grade cameras can be used to rapid acquire of photographs. The ground-based photographs can be subsequently processed through the structure-from-motion approach to generate detailed mosaics and digital elevation models of trail surfaces. It is possible to apply such models to study, monitor and quantify processes like soil erosion and vegetation trampling. In this study, we present methodological framework for monitoring of trail impact with the use of structure-from-motion approach and demonstrate its application based on examples from recreational trail located in suburban settings of Poznań. The data were collected on 10-meter long trail segment in June, July and October 2016 capturing the initial condition at the beginning of the months, and then two session pre-, and immediately after intense rainfall event, and the last session after termination of summer season. The total number of images was between 150 and 300 for each of the survey session. Dens point clouds were from 18 to 29 million points and were downsampled to DEM with 1 mm resolution. To detect surface changes, Digital elevation

Nature Trails, Braille Trails, Foot Paths, Fragrance Gardens, Touch Museums for the Blind; Policy Statement.

Science.gov (United States)

American Foundation for the Blind, New York, NY.

The policy statement by the American Foundation for the Blind deals with nature trails, braille trails, foot paths, fragrance gardens, and touch museums for the blind. It is stated that the foundation approves of services such as provision of tape recorded guides and planting of fragrant shrubs which would benefit all users while recognizing…

Airbag Trails

Science.gov (United States)

2004-01-01

This segment of the first color image from the panoramic camera on the Mars Exploration Rover Spirit shows the rover's airbag trails. These depressions in the soil were made when the airbags were deflated and retracted after landing.

Assessing soil erosion on trails: A comparison of techniques

Science.gov (United States)

Mark C. Jewell; William E. Hammitt

2000-01-01

Reports of trail degradation have been increasing in different wildernesses. This impact has become a common concern among managers. Deteriorating tread conditions of trails are increasing, as is concern at protected areas worldwide. In order to make objective and timely trail resource decisions, managers need to have effective and efficient methods of assessing trail...

The Prognostic Significance of The Serum Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL in Childhood Acute Leukemias

Directory of Open Access Journals (Sweden)

Zeliha Haytoglu

2015-12-01

Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002. In patients with high-risk-grade (HRG of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008. In patients with common acute lymphoblastic leukemia antigen(CALLA(- B ALL compared with control group have shown low serum TRAIL levels in CALLA(- B ALL (p=0.004. Children with acute leukemias (ALL, AML who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004. Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL's role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed. [Cukurova Med J 2015; 40(4.000: 774-781

The impact of glide phases on the trackability of hydrodynamic trails in harbour seals (Phoca vitulina).

Science.gov (United States)

Wieskotten, S; Dehnhardt, G; Mauck, B; Miersch, L; Hanke, W

2010-11-01

The mystacial vibrissae of harbour seals (Phoca vitulina) constitute a highly sensitive hydrodynamic receptor system enabling the seals to detect and follow hydrodynamic trails. In the wild, hydrodynamic trails, as generated by swimming fish, consist of cyclic burst-and-glide phases, associated with various differences in the physical parameters of the trail. Here, we investigated the impact of glide phases on the trackability of differently aged hydrodynamic trails in a harbour seal. As fish are not easily trained to swim certain paths with predetermined burst-and-glide phases, the respective hydrodynamic trails were generated using a remote-controlled miniature submarine. Gliding phases in hydrodynamic trails had a negative impact on the trackability when trails were 15 s old. The seal lost the generated trails more often within the transition zones, when the submarine switched from a burst to a glide moving pattern. Hydrodynamic parameter analysis (particle image velocimetry) revealed that the smaller dimensions and faster decay of hydrodynamic trails generated by the gliding submarine are responsible for the impaired success of the seal tracking the gliding phase. Furthermore, the change of gross water flow generated by the submarine from a rearwards-directed stream in the burst phase to a water flow passively dragged behind the submarine during gliding might influence the ability of the seal to follow the trail as this might cause a weaker deflection of the vibrissae. The possible ecological implications of intermittent swimming behaviour in fish for piscivorous predators are discussed.

Possible novel therapy for malignant gliomas with secretable trimeric TRAIL.

Directory of Open Access Journals (Sweden)

Moonsup Jeong

Full Text Available Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI. Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl-1-nitrosourea (BCNU, a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.

Hybrid immersed boundary method for airfoils with a trailing-edge flap

DEFF Research Database (Denmark)

Zhu, Wei Jun; Behrens, Tim; Shen, Wen Zhong

2013-01-01

In this paper, a hybrid immersed boundary technique has been developed for simulating turbulent flows past airfoils with moving trailing-edge flaps. Over the main fixed part of the airfoil, the equations are solved using a standard body-fitted finite volume technique, whereas the moving trailing......-edge flap is simulated using the immersed boundary method on a curvilinear mesh. An existing in-house-developed flow solver is employed to solve the incompressible Reynolds-Averaged Navier-Stokes equations together with the k-ω turbulence model. To achieve consistent wall boundary conditions at the immersed...... boundaries the k-ωturbulence model is modified and adapted to the local conditions associated with the immersed boundary method. The obtained results show that the hybrid approach is an efficient and accurate method for solving turbulent flows past airfoils with a trailing-edge flap and that flow control...

Great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo abelii) follow visual trails to locate hidden food.

Science.gov (United States)

Völter, Christoph J; Call, Josep

2014-05-01

Whether nonhuman primates understand causal relations beyond mere associations is still a matter of debate. We presented all four species of nonhuman great apes (N = 36) with a choice between 2 opaque, upside down cups after displacing them out of sight from their starting positions. Crucially, 1 of them had left a yogurt trail behind it. Great apes spontaneously used the trail to select the yogurt baited cup. Follow-up experiments demonstrated that chimpanzees distinguished trails based on the temporal order of cause and effect by ignoring trails that were already present before the reward was hidden. Additionally, chimpanzees did not select cups based on the amount of yogurt near them but instead preferred cups that signaled the endpoint of the trail. We conclude that apes' choices reveal sensitivity to a causal relation between cause (reward) and effect (trail) including their temporal order. ©2014 APA, all rights reserved.

VT Green Mountain National Forest - Long Trail and Appalachian Trail

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) GMNFTRAILS contains minor Forest Service roads and all trails within the proclamation boundary of the Green Mountain National Forest and many of...

Hydrodynamic trails produced by Daphnia: size and energetics.

Science.gov (United States)

Wickramarathna, Lalith N; Noss, Christian; Lorke, Andreas

2014-01-01

This study focuses on quantifying hydrodynamic trails produced by freely swimming zooplankton. We combined volumetric tracking of swimming trajectories with planar observations of the flow field induced by Daphnia of different size and swimming in different patterns. Spatial extension of the planar flow field along the trajectories was used to interrogate the dimensions (length and volume) and energetics (dissipation rate of kinetic energy and total dissipated power) of the trails. Our findings demonstrate that neither swimming pattern nor size of the organisms affect the trail width or the dissipation rate. However, we found that the trail volume increases with increasing organism size and swimming velocity, more precisely the trail volume is proportional to the third power of Reynolds number. This increase furthermore results in significantly enhanced total dissipated power at higher Reynolds number. The biggest trail volume observed corresponds to about 500 times the body volume of the largest daphnids. Trail-averaged viscous dissipation rate of the swimming daphnids vary in the range of 1.8 x 10(-6) W/kg to 3.4 x 10(-6) W/kg and the observed magnitudes of total dissipated power between 1.3 x 10(-9) W and 1 x 10(-8) W, respectively. Among other zooplankton species, daphnids display the highest total dissipated power in their trails. These findings are discussed in the context of fluid mixing and transport by organisms swimming at intermediate Reynolds numbers.

A Novel Role of IGF1 in Apo2L/TRAIL-Mediated Apoptosis of Ewing Tumor Cells

Directory of Open Access Journals (Sweden)

Frans van Valen

2012-01-01

Full Text Available Insulin-like growth factor 1 (IGF1 reputedly opposes chemotoxicity in Ewing sarcoma family of tumor (ESFT cells. However, the effect of IGF1 on apoptosis induced by apoptosis ligand 2 (Apo2L/tumor necrosis factor (TNF- related apoptosis-inducing ligand (TRAIL remains to be established. We find that opposite to the partial survival effect of short-term IGF1 treatment, long-term IGF1 treatment amplified Apo2L/TRAIL-induced apoptosis in Apo2L/TRAIL-sensitive but not resistant ESFT cell lines. Remarkably, the specific IGF1 receptor (IGF1R antibody α-IR3 was functionally equivalent to IGF1. Short-term IGF1 incubation of cells stimulated survival kinase AKT and increased X-linked inhibitor of apoptosis (XIAP protein which was associated with Apo2L/TRAIL resistance. In contrast, long-term IGF1 incubation resulted in repression of XIAP protein through ceramide (Cer formation derived from de novo synthesis which was associated with Apo2L/TRAIL sensitization. Addition of ceramide synthase (CerS inhibitor fumonisin B1 during long-term IGF1 treatment reduced XIAP repression and Apo2L/TRAIL-induced apoptosis. Noteworthy, the resistance to conventional chemotherapeutic agents was maintained in cells following chronic IGF1 treatment. Overall, the results suggest that chronic IGF1 treatment renders ESFT cells susceptible to Apo2L/TRAIL-induced apoptosis and may have important implications for the biology as well as the clinical management of refractory ESFT.

Aerodynamic Analysis of Trailing Edge Enlarged Wind Turbine Airfoils

DEFF Research Database (Denmark)

Xu, Haoran; Shen, Wen Zhong; Zhu, Wei Jun

2014-01-01

characteristics of blunt trailing edge airfoils are caused by blunt body vortices at low angles of attack, and by the combined effect of separation and blunt body vortices at large angles of attack. With the increase of thickness of blunt trailing edge, the vibration amplitudes of lift and drag curves increase......The aerodynamic performance of blunt trailing edge airfoils generated from the DU- 91-W2-250, DU-97-W-300 and DU-96-W-350 airfoils by enlarging the thickness of trailing edge symmetrically from the location of maximum thickness to chord to the trailing edge were analyzed by using CFD and RFOIL...... methods at a chord Reynolds number of 3 × 106. The goal of this study is to analyze the aerodynamic performance of blunt trailing edge airfoils with different thicknesses of trailing edge and maximum thicknesses to chord. The steady results calculated by the fully turbulent k-ω SST, transitional k-ω SST...

49 CFR 236.776 - Movement, trailing.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Movement, trailing. 236.776 Section 236.776 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Movement, trailing. The movement of a train over the points of a switch which face in the direction in...

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.

Science.gov (United States)

Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

2014-07-17

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke.

Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

International Nuclear Information System (INIS)

Adachi, Takaomi; Sugiyama, Noriyuki; Gondai, Tatsuro; Yagita, Hideo; Yokoyama, Takahiko

2013-01-01

Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI

Study of airfoil trailing edge bluntness noise

DEFF Research Database (Denmark)

Zhu, Wei Jun; Shen, Wen Zhong; Sørensen, Jens Nørkær

2010-01-01

This paper deals with airfoil trailing edge noise with special focus on airfoils with blunt trailing edges. Two methods are employed to calculate airfoil noise: The flow/acoustic splitting method and the semi-empirical method. The flow/acoustic splitting method is derived from compressible Navier...... design or optimization. Calculations from both methods are compared with exist experiments. The airfoil blunt noise is found as a function of trailing edge bluntness, Reynolds number, angle of attack, etc....

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype

OpenAIRE

Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

2014-01-01

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in strok...

30 CFR 75.601 - Short circuit protection of trailing cables.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Short circuit protection of trailing cables. 75... MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Trailing Cables § 75.601 Short circuit protection of trailing cables. [Statutory Provisions] Short circuit protection for trailing cables...

Minnesota Water Trails

Data.gov (United States)

Minnesota Department of Natural Resources — This shapefile describes water trails in the State of Minnesota as designated through legislation and recognized by the Department of Natural Resources. The...

Trailing Vortex-Induced Loads During Close Encounters in Cruise

Science.gov (United States)

Mendenhall, Michael R.; Lesieutre, Daniel J; Kelly, Michael J.

2015-01-01

The trailing vortex induced aerodynamic loads on a Falcon 20G business jet flying in the wake of a DC-8 are predicted to provide a preflight estimate of safe trail distances during flight test measurements in the wake. Static and dynamic loads on the airframe flying in the near wake are shown at a matrix of locations, and the dynamic motion of the Falcon 20G during traverses of the DC-8 primary trailing vortex is simulated. Safe trailing distances for the test flights are determined, and optimum vortex traverse schemes are identified to moderate the motion of the trailing aircraft during close encounters with the vortex wake.

Appalachian National Scenic Trail pilot survey

Science.gov (United States)

Stan Zarnoch; Michael Bowker; Ken Cordell; Matt Owens; Gary T. Green; Allison Ginn

2011-01-01

Visitation statistics on the Appalachian National Scenic Trail (AT) are important for management and Federal Government reporting purposes. However, no survey methodology has been developed to obtain accurate trailwide estimates over linear trails that traverse many hundreds of back-country miles. This research develops a stratified random survey design which utilizes...

Cuticular lipids as trail pheromone in a social wasp.

OpenAIRE

Steinmetz, Inge; Schmolz, Erik; Ruther, Joachim

2003-01-01

We investigated the origin and composition of the chemical trail of the common yellow jacket Vespula vulgaris L. (Vespidae) and found that an artificial trail made from an extract of cuticular lipids from V. vulgaris foragers was biologically as active as a trail laid naturally by the foragers. Chemical analysis of natural trail extracts and the behaviourally active cuticular extracts by coupled gas chromatography-mass spectrometry revealed that the majority of cuticular hydrocarbons were als...

Recreational Trails in the State of Iowa

Data.gov (United States)

Iowa State University GIS Support and Research Facility — This file represents the locations of trails in Iowa. The original trail file was created by the Iowa Department of Transportation (IDOT), and included developed...

Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin

Directory of Open Access Journals (Sweden)

Felley-Bosco Emanuela

2007-10-01

Full Text Available Abstract Background The incidence of malignant pleural mesothelioma (MPM is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1 or TRAIL-R2 has been thought to be a promising cancer therapy. Results We have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab and TRAIL-R2 (Lexatumumab and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine. Conclusion Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.

A Tale of Two Trails: Exploring Different Paths to Success

Science.gov (United States)

Walker, Jennifer G.; Evenson, Kelly R.; Davis, William J.; Bors, Philip; Rodríguez, Daniel A.

2016-01-01

Background This comparative case study investigates 2 successful community trail initiatives, using the Active Living By Design (ALBD) Community Action Model as an analytical framework. The model includes 5 strategies: preparation, promotion, programs, policy, and physical projects. Methods Key stakeholders at 2 sites participated in in-depth interviews (N = 14). Data were analyzed for content using Atlas Ti and grouped according to the 5 strategies. Results Preparation Securing trail resources was challenging, but shared responsibilities facilitated trail development. Promotions The initiatives demonstrated minimal physical activity encouragement strategies. Programs Community stakeholders did not coordinate programmatic opportunities for routine physical activity. Policy Trails’ inclusion in regional greenway master plans contributed to trail funding and development. Policies that were formally institutionalized and enforced led to more consistent trail construction and safer conditions for users. Physical Projects Consistent standards for way finding signage and design safety features enhanced trail usability and safety. Conclusions Communities with different levels of government support contributed unique lessons to inform best practices of trail initiatives. This study revealed a disparity between trail development and use-encouragement strategies, which may limit trails’ impact on physical activity. The ALBD Community Action Model provided a viable framework to structure cross-disciplinary community trail initiatives. PMID:21597125

State Park Trails

Data.gov (United States)

Minnesota Department of Natural Resources — This data set is a collection of ArcView shapefiles (by park) of trails within statutory boundaries of individual MN State Parks, State Recreation Areas and State...

SPAG6 regulates cell apoptosis through the TRAIL signal pathway in myelodysplastic syndromes.

Science.gov (United States)

Li, Xinxin; Yang, Bihui; Wang, Li; Chen, Liping; Luo, Xiaohua; Liu, Lin

2017-05-01

Myelodysplastic syndromes (MDSs) are a group of malignant clone hematopoietic stem-cell diseases, and the evolution and progression of MDS depend on the abnormal apoptosis of bone marrow cells. Our previous studies have indicated that sperm-associated antigen 6 (SPAG6), located in the uniparental disomy regions of myeloid cells, is overexpressed in patients with MDS as compared to controls, and SPAG6 can inhibit apoptosis of SKM-1. However, the concrete mechanism is still unclear. In the present study, it was found that the TNF-related apoptosis-inducing ligand (TRAIL)signal pathway was activated when the expression of SPAG6 was inhibited by SPAG6-shRNA lentivirus in SKM-1 cells. Additionally, the results of flow cytometry, Cell Counting Kit-8 assay and western blot analysis implied that the TRAIL signal pathway could be inhibited by a high expression of SPAG6. However, SPAG6 cannot influence the expression of TRAIL death receptors, except for FADD. Additionally the interaction between FADD and TRAIL death receptors also increased in SKM-1 cells infected with SPAG6-shRNA lentivirus. Thus, our study demonstrates that SPAG6 may regulate apoptosis in SKM-1 through the TRAIL signal pathway, indicating that SPAG6 could be a potential therapeutic target.

Assessing trail conditions in protected areas: Application of a problem-assessment method in Great Smoky Mountains National Park, USA

Science.gov (United States)

Leung, Y.-F.; Marion, J.

1999-01-01

The degradation of trail resources associated with expanding recreation and tourism visitation is a growing management problem in protected areas worldwide. In order to make judicious trail and visitor management decisions, protected area managers need objective and timely information on trail resource conditions. This paper introduces a trail survey method that efficiently characterizes the lineal extent of common trail problems. The method was applied to a large sample of trails within Great Smoky Mountains National Park, a highuse protected area in the USA. The Trail ProblemAssessment Method (TPAM) employs a continuous search for multiple indicators of predefined tread problems, yielding census data documenting the location, occurrence and extent of each problem. The present application employed 23 different indicators in three categories to gather inventory, resource condition, and design and maintenance data of each surveyed trail. Seventy-two backcountry hiking trails (528 km), or 35% of the Park's total trail length, were surveyed. Soil erosion and wet soil were found to be the two most common impacts on a lineal extent basis. Trails with serious tread problems were well distributed throughout the Park, although wet muddy treads tended to be concentrated in areas where horse use was high. The effectiveness of maintenance features installed to divert water from trail treads was also evaluated. Water bars were found to be more effective than drainage dips. The TPAM was able to provide Park managers with objective and quantitative information for use in trail planning, management and maintenance decisions, and is applicable to other protected areas elsewhere with different environmental and impact characteristics.

Beneficial effect of TRAIL on HIV burden, without detectable immune consequences.

Directory of Open Access Journals (Sweden)

Brett D Shepard

2008-08-01

Full Text Available During uncontrolled HIV disease, both TNF-related apoptosis inducing ligand (TRAIL and TRAIL receptor expression are increased. Enhanced TRAIL sensitivity is due to TRAIL receptor up-regulation induced by gp120. As a result of successful antiretroviral therapy TRAIL is down-regulated, and there are fewer TRAIL-sensitive cells. In this setting, we hypothesized that all cells that contain virus, including those productively- and latently-infected, have necessarily been "primed" by gp120 and remain TRAIL-sensitive, whereas uninfected cells remain relatively TRAIL-resistant.We evaluated the immunologic and antiviral effects of TRAIL in peripheral blood lymphocytes collected from HIV-infected patients with suppressed viral replication. The peripheral blood lymphocytes were treated with recombinant TRAIL or an equivalent amount of bovine serum albumin as a negative control. Treated cells were then analyzed by quantitative flow cytometry, ELISPOT for CD4+ and CD8+ T-cell function, and limiting dilution microculture for viral burden. Alterations in the cytokine milieu of treated cells were assessed with a multiplex cytokine assay. Treatment with recombinant TRAIL in vitro reduced viral burden in lymphocytes collected from HIV-infected patients with suppressed viral load. TRAIL treatment did not alter the cytokine milieu of treated cells. Moreover, treatment with recombinant TRAIL had no adverse effect on either the quantity or function of immune cells from HIV-infected patients with suppressed viral replication.TRAIL treatment may be an important adjunct to antiretroviral therapy, even in patients with suppressed viral replication, perhaps by inducing apoptosis in cells with latent HIV reservoirs. The absence of adverse effect on the quantity or function of immune cells from HIV-infected patients suggests that there is not a significant level of "bystander death" in uninfected cells.

Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma.

Science.gov (United States)

Crommentuijn, Matheus H W; Maguire, Casey A; Niers, Johanna M; Vandertop, W Peter; Badr, Christian E; Würdinger, Thomas; Tannous, Bakhos A

2016-04-01

Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. In U87 cells, conditioned medium from AAV2-sTRAIL expressing cells combined with lan C induced 80% cell death. Similarly, lan C sensitized primary GBM spheres to sTRAIL causing over 90% cell death. In mice bearing intracranial U87 tumors treated with AAVrh.8-sTRAIL, administration of lan C caused a decrease in tumor-associated Fluc signal, while tumor size increased within days of stopping the treatment. Another round of lan C treatment re-sensitized GBM tumor to sTRAIL-induced cell death. AAVrh.8-sTRAIL treatment alone and combined with lanatoside C resulted in a significant decrease in tumor growth and longer survival of mice bearing orthotopic invasive GBM brain tumors. In summary, AAV-sTRAIL combined with lanatoside C induced cell death in U87 glioma cells and patient-derived GBM neural spheres in culture and in vivo leading to an increased in overall mice survival. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Trail pheromone of the Argentine ant, Linepithema humile (Mayr (Hymenoptera: Formicidae.

Directory of Open Access Journals (Sweden)

Dong-Hwan Choe

Full Text Available The Argentine ant (Linepithema humile is recognized as one of the world's most damaging invasive species. One reason for the ecological dominance of introduced Argentine ant populations is their ability to dominate food and habitat resources through the rapid mobilization and recruitment of thousands of workers. More than 30 years ago, studies showed that (Z-9-hexadecenal strongly attracted Argentine ant workers in a multi-choice olfactometer, suggesting that (Z-9-hexadecenal might be the trail pheromone, or a component of a trail pheromone mixture. Since then, numerous studies have considered (Z-9-hexadecenal as the key component of the Argentine ant trails. Here, we report the first chemical analyses of the trails laid by living Argentine ants and find that (Z-9-hexadecenal is not present in a detectible quantity. Instead, two iridoids, dolichodial and iridomyrmecin, appear to be the primary chemical constituents of the trails. Laboratory choice tests confirmed that Argentine ants were attracted to artificial trails comprised of these two chemicals significantly more often than control trails. Although (Z-9-hexadecenal was not detected in natural trails, supplementation of artificial dolichodial+iridomyrmecin trails with an extremely low concentraion of (Z-9-hexadecenal did increase the efficacy of the trail-following behavior. In stark contrast with previous dogma, our study suggests that dolichodial and iridomyrmecin are major components of the Argentine ant trail pheromone. (Z-9-hexadecenal may act in an additive manner with these iridoids, but it does not occur in detectable quantities in Argentine ant recruitment trails.

Modeling of Airfoil Trailing Edge Flap with Immersed Boundary Method

DEFF Research Database (Denmark)

Zhu, Wei Jun; Shen, Wen Zhong; Sørensen, Jens Nørkær

2011-01-01

The present work considers incompressible flow over a 2D airfoil with a deformable trailing edge. The aerodynamic characteristics of an airfoil with a trailing edge flap is numerically investigated using computational fluid dynamics. A novel hybrid immersed boundary (IB) technique is applied...... to simulate the moving part of the trailing edge. Over the main fixed part of the airfoil the Navier-Stokes (NS) equations are solved using a standard body-fitted finite volume technique whereas the moving trailing edge flap is simulated with the immersed boundary method on a curvilinear mesh. The obtained...... results show that the hybrid approach is an efficient and accurate method for solving turbulent flows past airfoils with a trailing edge flap and flow control using trailing edge flap is an efficient way to regulate the aerodynamic loading on airfoils....

77 FR 25910 - National Trails System Act and Railroad Rights-of-Way

Science.gov (United States)

2012-05-02

...] National Trails System Act and Railroad Rights-of-Way AGENCY: Surface Transportation Board, DOT. ACTION...) for rail banking and interim trail use under the National Trails System Act (Trails Act). New rules are adopted that require the parties jointly to notify the Board when an interim trail use/rail...

Continental Divide Trail

Data.gov (United States)

Earth Data Analysis Center, University of New Mexico — This shapefile was created to show the proximity of the Continental Divide to the Continental Divide National Scenic Trail in New Mexico. This work was done as part...

Fast and flexible: argentine ants recruit from nearby trails.

Science.gov (United States)

Flanagan, Tatiana P; Pinter-Wollman, Noa M; Moses, Melanie E; Gordon, Deborah M

2013-01-01

Argentine ants (Linepithema humile) live in groups of nests connected by trails to each other and to stable food sources. In a field study, we investigated whether some ants recruit directly from established, persistent trails to food sources, thus accelerating food collection. Our results indicate that Argentine ants recruit nestmates to food directly from persistent trails, and that the exponential increase in the arrival rate of ants at baits is faster than would be possible if recruited ants traveled from distant nests. Once ants find a new food source, they walk back and forth between the bait and sometimes share food by trophallaxis with nestmates on the trail. Recruiting ants from nearby persistent trails creates a dynamic circuit, like those found in other distributed systems, which facilitates a quick response to changes in available resources.

30 CFR 77.600 - Trailing cables; short-circuit protection; disconnecting devices.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cables; short-circuit protection... AREAS OF UNDERGROUND COAL MINES Trailing Cables § 77.600 Trailing cables; short-circuit protection; disconnecting devices. Short-circuit protection for trailing cables shall be provided by an automatic circuit...

36 CFR 212.56 - Identification of designated roads, trails, and areas.

Science.gov (United States)

2010-07-01

... roads, trails, and areas. 212.56 Section 212.56 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.56 Identification of designated roads, trails, and areas. Designated roads, trails, and areas...

Aerodynamic Analysis of Trailing Edge Enlarged Wind Turbine Airfoils

International Nuclear Information System (INIS)

Xu, Haoran; Yang, Hua; Liu, Chao; Shen, Wenzhong; Zhu, Weijun

2014-01-01

The aerodynamic performance of blunt trailing edge airfoils generated from the DU- 91-W2-250, DU-97-W-300 and DU-96-W-350 airfoils by enlarging the thickness of trailing edge symmetrically from the location of maximum thickness to chord to the trailing edge were analyzed by using CFD and RFOIL methods at a chord Reynolds number of 3 × 10 6 . The goal of this study is to analyze the aerodynamic performance of blunt trailing edge airfoils with different thicknesses of trailing edge and maximum thicknesses to chord. The steady results calculated by the fully turbulent k-ω SST, transitional k-ω SST model and RFOIL all show that with the increase of thickness of trailing edge, the linear region of lift is extended and the maximum lift also increases, the increase rate and amount of lift become limited gradually at low angles of attack, while the drag increases dramatically. For thicker airfoils with larger maximum thickness to chord length, the increment of lift is larger than that of relatively thinner airfoils when the thickness of blunt trailing edge is increased from 5% to 10% chord length. But too large lift can cause abrupt stall which is profitless for power output. The transient characteristics of blunt trailing edge airfoils are caused by blunt body vortices at low angles of attack, and by the combined effect of separation and blunt body vortices at large angles of attack. With the increase of thickness of blunt trailing edge, the vibration amplitudes of lift and drag curves increase. The transient calculations over-predict the lift at large angles of attack and drag at all angles of attack than the steady calculations which is likely to be caused by the artificial restriction of the flow in two dimensions

The Tourism Carrying Capacity of Underwater Trails in Isabel Island National Park, Mexico

Science.gov (United States)

Ríos-Jara, Eduardo; Galván-Villa, Cristian Moisés; Rodríguez-Zaragoza, Fabián Alejandro; López-Uriarte, Ernesto; Muñoz-Fernández, Vicente Teófilo

2013-08-01

The popularity of ecotourism in the marine protected areas of Mexico has increased over the last 10 years; in particular there is a large development of a SCUBA diving industry in the Mexican Pacific including Isabel Island. Given the risks associated with human activity in the marine environments around this island, we propose two ecotourism management strategies: (1) the creation and use of underwater trails, and (2) the estimation of the specific tourism carrying capacity (TCC) for each trail. Six underwater trails were selected in sites that presented elements of biological, geological, and scenic interest, using information obtained during field observations. The methodology used to estimate the TCC was based upon the physical and biological conditions of each site, the infrastructure and equipment available, and the characteristics of the service providers and the administrators of the park. Correction factors of the TCC included elements of the quality of the visit and the threat and vulnerability of the marine environment of each trail (e.g., divers' expertise, size and distance between groups of divers, accessibility, wind, coral coverage). The TCC values ranged between 1,252 and 1,642 dives/year/trail, with a total of 8,597 dives/year for all six trails. Although these numbers are higher than the actual number of recreational visitors to the island (~1,000 dives per year), there is a need for adequate preventive management if the diving sites are to maintain their esthetic appeal and biological characteristics. Such management might be initially directed toward using only the sites and the TCC proposed here.

The tourism carrying capacity of underwater trails in Isabel Island National Park, Mexico.

Science.gov (United States)

Ríos-Jara, Eduardo; Galván-Villa, Cristian Moisés; Rodríguez-Zaragoza, Fabián Alejandro; López-Uriarte, Ernesto; Muñoz-Fernández, Vicente Teófilo

2013-08-01

The popularity of ecotourism in the marine protected areas of Mexico has increased over the last 10 years; in particular there is a large development of a SCUBA diving industry in the Mexican Pacific including Isabel Island. Given the risks associated with human activity in the marine environments around this island, we propose two ecotourism management strategies: (1) the creation and use of underwater trails, and (2) the estimation of the specific tourism carrying capacity (TCC) for each trail. Six underwater trails were selected in sites that presented elements of biological, geological, and scenic interest, using information obtained during field observations. The methodology used to estimate the TCC was based upon the physical and biological conditions of each site, the infrastructure and equipment available, and the characteristics of the service providers and the administrators of the park. Correction factors of the TCC included elements of the quality of the visit and the threat and vulnerability of the marine environment of each trail (e.g., divers' expertise, size and distance between groups of divers, accessibility, wind, coral coverage). The TCC values ranged between 1,252 and 1,642 dives/year/trail, with a total of 8,597 dives/year for all six trails. Although these numbers are higher than the actual number of recreational visitors to the island (~1,000 dives per year), there is a need for adequate preventive management if the diving sites are to maintain their esthetic appeal and biological characteristics. Such management might be initially directed toward using only the sites and the TCC proposed here.

LES tests on airfoil trailing edge serration

DEFF Research Database (Denmark)

Zhu, Wei Jun; Shen, Wen Zhong

2016-01-01

In the present study, a large number of acoustic simulations are carried out for a low noise airfoil with different Trailing Edge Serrations (TES). The Ffowcs Williams-Hawkings (FWH) acoustic analogy is used for noise prediction at trailing edge. The acoustic solver is running on the platform...

Certification trails and software design for testability

Science.gov (United States)

Sullivan, Gregory F.; Wilson, Dwight S.; Masson, Gerald M.

1993-01-01

Design techniques which may be applied to make program testing easier were investigated. Methods for modifying a program to generate additional data which we refer to as a certification trail are presented. This additional data is designed to allow the program output to be checked more quickly and effectively. Certification trails were described primarily from a theoretical perspective. A comprehensive attempt to assess experimentally the performance and overall value of the certification trail method is reported. The method was applied to nine fundamental, well-known algorithms for the following problems: convex hull, sorting, huffman tree, shortest path, closest pair, line segment intersection, longest increasing subsequence, skyline, and voronoi diagram. Run-time performance data for each of these problems is given, and selected problems are described in more detail. Our results indicate that there are many cases in which certification trails allow for significantly faster overall program execution time than a 2-version programming approach, and also give further evidence of the breadth of applicability of this method.

Detection of tundra trail damage near Barrow, Alaska using remote imagery

Science.gov (United States)

Hinkel, K. M.; Eisner, W. R.; Kim, C. J.

2017-09-01

In the past several decades, the use of all-terrain vehicles (ATVs) has proliferated in many Arctic communities in North America. One example is the village of Barrow, Alaska. This coastal community has only local roads, so all access to the interior utilizes off-road machines. These 4-wheel vehicles are the primary means of tundra traverse and transport in summer by hunters and berry-pickers, and by village residents accessing summer camps. Traveling cross-country is difficult due to the large number of thermokarst lakes, wetlands, and streams, and tundra trails tend to follow dryer higher ground while avoiding areas of high microrelief such as high-centered ice-wedge polygons. Thus, modern ATV trails tend to follow the margins of drained or partially drained thermokarst lake basins where it is flat and relatively dry, and these trails are heavily used. The deeply-ribbed tires of the heavy and powerful ATVs cause damage by destroying the vegetation and disturbing the underlying organic soil. Exposure of the dark soil enhances summer thaw and leads to local thermokarst of the ice-rich upper permafrost. The damage increases over time as vehicles continue to follow the same track, and sections eventually become unusable; this is especially true where the trail crosses ice-wedge troughs. Deep subsidence in the ponded troughs results in ATV users veering to avoid the wettest area, which leads to a widening of the damaged area. Helicopter surveys, site visits, and collection of ground penetrating radar data were combined with time series analysis of high-resolution aerial and satellite imagery for the period 1955-2014. The analysis reveals that there are 507 km of off-road trails on the Barrow Peninsula. About 50% of the total trail length was developed before 1955 in association with resource extraction, and an additional 40% were formed between 1979 and 2005 by ATVs. Segments of the more modern trail are up to 100 m wide. Damage to the tundra is especially pronounced

Fast and flexible: argentine ants recruit from nearby trails.

Directory of Open Access Journals (Sweden)

Tatiana P Flanagan

Full Text Available Argentine ants (Linepithema humile live in groups of nests connected by trails to each other and to stable food sources. In a field study, we investigated whether some ants recruit directly from established, persistent trails to food sources, thus accelerating food collection. Our results indicate that Argentine ants recruit nestmates to food directly from persistent trails, and that the exponential increase in the arrival rate of ants at baits is faster than would be possible if recruited ants traveled from distant nests. Once ants find a new food source, they walk back and forth between the bait and sometimes share food by trophallaxis with nestmates on the trail. Recruiting ants from nearby persistent trails creates a dynamic circuit, like those found in other distributed systems, which facilitates a quick response to changes in available resources.

How Networks of Informal Trails Cause Landscape Level Damage to Vegetation.

Science.gov (United States)

Barros, Agustina; Marina Pickering, Catherine

2017-07-01

When visitors are not constrained to remain on formal trails, informal trail networks can develop and damage plant communities in protected areas. These networks can form in areas with low growing vegetation, where formal trails are limited, where there is limited regulation and where vegetation is slow to recover once disturbed. To demonstrate the extent of impacts from unregulated recreational use, we assessed damage to alpine vegetation by hikers and pack animals in the highest protected area in the southern Hemisphere: Aconcagua Park, in the Andes. Within the 237 ha area surveyed in the Horcones Valley, over 19 km of trails were found, nearly all of which (94%) were informal. This network of trails resulted in the direct loss of 11.5 ha of vegetation and extensive fragmentation of alpine meadows (21 fragments) and steppe vegetation (68 fragments). When levels of disturbance off these trails were quantified using rapid visual assessments, 81% of 102 randomly located plots showed evidence of disturbance, with the severity of disturbance greatest close to trails. As a result, vegetation in 90% of the Valley has been damaged by visitor use, nearly all of it from unregulated use. These results highlight the extent to which informal trails and trampling off-trail can cause landscape damage to areas of high conservation value, and hence the importance of better regulation of visitor use. The methodology used for off-trail impact assessment can be easily applied or adapted for other popular protected areas where trampling off-trail is also an issue.

Airbag Trails-2

Science.gov (United States)

2004-01-01

This segment of the first color image from the panoramic camera on the Mars Exploration Rover Spirit shows the rover's airbag trails (upper left). These depressions in the soil were made when the airbags were deflated and retracted after landing.

TRAIL: A Novel Therapeutic Agent for Prostate Cancer

National Research Council Canada - National Science Library

Li, Honglin

2002-01-01

This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

TRAIL: A Novel Therapeutic Agent for Prostate Cancer

National Research Council Canada - National Science Library

Li, Honglin

2004-01-01

This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

TRAIL: A Novel Therapeutic Agent for Prostate Cancer

National Research Council Canada - National Science Library

Li, Honglin

2003-01-01

This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

The Global and Local Characters of Mars Perihelion Cloud Trails

Science.gov (United States)

Clancy, R. T.; Wolff, M. J.; Smith, M. D.; Cantor, B. A.; Spiga, A.

2014-12-01

We present the seasonal and spatial distribution of Mars perihelion cloud trails as mapped from Mars Reconnaissance Orbiter (MRO) MARCI (Mars Color Imager) imaging observations in 2 ultraviolet and 3 visible filters. The extended 2007-2013 period of MARCI daily global image maps reveals the widespread distribution of these high altitude clouds, which are somewhat paradoxically associated with specific surface regions. They appear as longitudinally extended (300-700 km) cloud trails with distinct leading plumes of substantial ice cloud optical depths (0.02-0.2) for such high altitudes of occurrence (40-50 km, from cloud surface shadow measurements). These plumes generate small ice particles (Reff~1 to reflect locally elevated mesospheric water ice formation that may impact the global expression of mesospheric water ice aerosols.

Audit trails in an online accountability system

International Nuclear Information System (INIS)

Jamison, C.

1985-01-01

The Safeguards Accountability Network (SAN) is an online computer system that was developed by Rockwell International to track the accounting and processing of nuclear materials from the time it arrives at Rocky Flats Plant through its life cycle. A major contributor to the success of SAN is the use of audit trails. They have proven to be invaluable for the management and safeguarding of these sensitive materials at Rocky Flats. Producing effective audit trails requires the recording of all pertinent transactions and the capability to access and report the information in a timely fashion. This paper discusses the implementation and application of these audit trails on the Rocky Flats SAN system

Quantification of soil losses from tourist trails - use of Digital Elevation Models

Science.gov (United States)

Tomczyk, Aleksandra

2010-05-01

Tourism impacts in protected mountain areas are one of the main concerns for land managers. Impact to environment is most visible at locations of highly concentrated activities like tourist trails, campsites etc. The main indicators of the tourist trail degradation are: vegetation loss (trampling of vegetation cover), change of vegetation type and composition, widening of the trails, muddiness and soil erosion. The last one is especially significant, since it can cause serious transformation of the land surface. Such undesirable changes cannot be repaired without high-cost management activities, and, in some cases they can made the trails difficult and unsafe to use. Scientific understanding of soil erosion related to human impact can be useful for more effective management of the natural protected areas. The aim of this study was to use of digital elevation models (DEMs) to precisely quantify of soil losses from tourist trails. In the study precise elevation data were gathered in several test fields of 4 by 5 m spatial dimension. Measurements were taken in 13 test fields, located in two protected natural areas in south Poland: Gorce National Park and Popradzki Landscape Park. The measuring places were located on trails characterized by different slope, type of vegetation and type of use. Each test field was established by four special marks, firmly dug into the ground. Elevation data were measured with the electronic total station. Irregular elevation points were surveying with essential elements of surrounding terrain surface being included. Moreover, surveys in fixed profile lines were done. For each test field a set of 30 measurements in control points has been collected and these data provide the base for verification of digital elevation models. Average density of the surveying was 70 points per square meter (1000 - 1500 elevation points per each test fields). Surveys in each test field were carried out in August and September of 2008, June 2009 and August

Back in Time on a Mathematics Trail

Science.gov (United States)

Moffett, Pamela

2010-01-01

The recently revised "Northern Ireland Primary Curriculum" recommends that teachers make use of the environment to extend children's understanding of mathematics. One approach to using the environment in mathematics is to take children on a mathematics trail. A mathematics trail uses the resources and features within the environment as a…

Systematic review of the evidence for Trails B cut-off scores in assessing fitness-to-drive.

Science.gov (United States)

Roy, Mononita; Molnar, Frank

2013-01-01

Fitness-to-drive guidelines recommend employing the Trail Making B Test (a.k.a. Trails B), but do not provide guidance regarding cut-off scores. There is ongoing debate regarding the optimal cut-off score on the Trails B test. The objective of this study was to address this controversy by systematically reviewing the evidence for specific Trails B cut-off scores (e.g., cut-offs in both time to completion and number of errors) with respect to fitness-to-drive. Systematic review of all prospective cohort, retrospective cohort, case-control, correlation, and cross-sectional studies reporting the ability of the Trails B to predict driving safety that were published in English-language, peer-reviewed journals. Forty-seven articles were reviewed. None of the articles justified sample sizes via formal calculations. Cut-off scores reported based on research include: 90 seconds, 133 seconds, 147 seconds, 180 seconds, and Trails B cut-offs of 3 minutes or 3 errors (the '3 or 3 rule'). Major methodological limitations of this body of research were uncovered including (1) lack of justification of sample size leaving studies open to Type II error (i.e., false negative findings), and (2) excessive focus on associations rather than clinically useful cut-off scores.

Digital Elevation Models of Differences (DODs): implementation for assessment of soil erosion on recreational trails.

Science.gov (United States)

Tomczyk, A.; Ewertowski, M.

2012-04-01

Introduction: Tourism's negative impact on protected mountain areas is one of the main concerns for land managers. The impact on the natural environment is the most visible at locations of highly concentrated activities such as tourist trails, campsites, etc. The main indicators of the tourist trail degradation are vegetation loss (trampling of vegetation cover), change of vegetation type and composition, trail widening, muddiness and soil erosion. The last one is especially significant, since it can cause serious transformation to the land surface. Such undesirable changes cannot be repaired without high-cost management activities and in some cases they can made the trails difficult and unsafe to use. The scientific understanding of soil erosion in relation to human impact can be useful for a more effective management of protected natural areas (PNAs). The main objectives of this study are: (1) to analyse the spatial aspect of surface changes in microscale; (2) to quantify precisely the short-term rate of soil loss and deposition. Study area and methods: To gather precise and objective elevation data, an electronic total station with microprism were used. Measurements were taken in 12 test fields, located in two protected natural areas in south Poland: the Gorce National Park and Popradzki Landscape Park. The measuring places were located on the trails characterized by different slope, types of vegetation, and types of use. Each of the test fields was established by four special marks, firmly dug into the ground. Five sessions of measurement was carried out for each test field: August/September 2008, June 2009, August/September 2009, June 2010, August/September 2010. Generated DEMs (based on field surveys' results) were subtracted from each other, and thus we obtained a spatial picture of the loss or deposition of soil in each cell of the model, from one survey session to another. The subtraction of DEMs from subsequent time periods (DEMs of Difference - DoDs gave

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Dae-Hee, E-mail: leedneo@gmail.com [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Dong-Wook [Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States); Jung, Chang-Hwa [Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of); Lee, Yong J. [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Park, Daeho, E-mail: daehopark@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

2014-09-15

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.

Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

International Nuclear Information System (INIS)

Lee, Dae-Hee; Kim, Dong-Wook; Jung, Chang-Hwa; Lee, Yong J.; Park, Daeho

2014-01-01

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway

Promoting and developing a trail network across suburban, rural, and urban communities.

Science.gov (United States)

Schasberger, Michele G; Hussa, Carol S; Polgar, Michael F; McMonagle, Julie A; Burke, Sharon J; Gegaris, Andrew J

2009-12-01

The Wyoming Valley Wellness Trails Partnership received an Active Living by Design grant late in 2003 for a project centered on a growing trail network linking urban, suburban, and rural communities in northeast Pennsylvania, a former coal region, in order to increase physical activity among residents. The partnership conducted research, collected information, created promotional documents, worked with partners on events and programs, and participated in trail planning. Local trail organizations continued planning and construction toward developing a trail network. Other partners spearheaded policy change in schools and worksites and worked toward downtown revitalization. The partnership assisted these efforts by providing a forum in which organizations could meet. The partnership became a central resource for information about local parks, trails, and outdoor recreational activities. The partnership increased awareness and use of recreational facilities. Trail partners constructed 22 miles of walking and biking trails. The partnership took advantage of an allied effort that created organizational capacity for wellness in schools and worksites. Messages promoting social and entertainment benefits of physical activity were more successful than those promoting health benefits. The existence of multiple small, independent trail organizations can help advance trail development through concurrent development efforts. Urban, suburban, and rural residents' conceptions of walkability may differ. Trails provide options for recreational and transportation-related physical activity across urban, suburban, and rural landscapes that are supported by all constituents. Trail builders can be strong allies in bringing active living to suburban and rural places.

Hiking trails and tourism impact assessment in protected area: Jiuzhaigou Biosphere Reserve, China.

Science.gov (United States)

Li, Wenjun; Ge, Xiaodong; Liu, Chunyan

2005-09-01

More and more visitors are attracted to protected areas nowadays, which not only bring about economic increase but also seriously adverse impacts on the ecological environment. In protected areas, trails are linkage between visitors and natural ecosystem, so they concentrate most of the adverse impacts caused by visitors. The trampling problems on the trails have been received attentions in the tremendous researches. However, few of them have correlated the environmental impacts to trail spatial patterns. In this project, the trails were selected as assessment objective, the trampling problems trail widening, multiple trail, and root exposure were taken as assessment indicators to assess ecological impacts in the case study area Jiuzhaigou Biosphere Reserve, and two spatial index, connectivity and circularity, were taken to indicate the trail network spatial patterns. The research results showed that the appearing frequency of the trampling problems had inverse correlation with the circularity and connectivity of the trail network, while the problem extent had no correlation with the spatial pattern. Comparing with the pristine trails, the artificial maintenance for the trails such as wooden trails and flagstone trails could prohibit vegetation root from exposure effectively. The research finds will be useful for the future trail design and tourism management.

Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma

NARCIS (Netherlands)

Crommentuijn, Matheus H. W.; Maguire, Casey A.; Niers, Johanna M.; Vandertop, W. Peter; Badr, Christian E.; Würdinger, Thomas; Tannous, Bakhos A.

2016-01-01

Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing

BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL.

Science.gov (United States)

Fu, Yao; Chang, Ye; Chen, Shuang; Li, Yuan; Chen, Yintao; Sun, Guozhe; Yu, Shasha; Ye, Ning; Li, Chao; Sun, Yingxian

2018-05-01

Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL

Assessing the influence of sustainable trail design and maintenance on soil loss

Science.gov (United States)

Marion, Jeff; Wimpey, Jeremy

2017-01-01

Natural-surfaced trail systems are an important infrastructure component providing a means for accessing remote protected natural area destinations. The condition and usability of trails is a critical concern of land managers charged with providing recreational access while preserving natural conditions, and to visitors seeking high quality recreational opportunities and experiences. While an adequate number of trail management publications provide prescriptive guidance for designing, constructing, and maintaining natural-surfaced trails, surprisingly little research has been directed at providing a scientific basis for this guidance. Results from a review of the literature and three scientific studies are presented to model and clarify the influence of factors that substantially influence trail soil loss and that can be manipulated by trail professionals to sustain high traffic while minimizing soil loss over time. Key factors include trail grade, slope alignment angle, tread drainage features, and the amount of rock in tread substrates. A new Trail Sustainability Rating is developed and offered as a tool for evaluating or improving the sustainability of existing or new trails.

Assessing the influence of sustainable trail design and maintenance on soil loss.

Science.gov (United States)

Marion, Jeffrey L; Wimpey, Jeremy

2017-03-15

Natural-surfaced trail systems are an important infrastructure component providing a means for accessing remote protected natural area destinations. The condition and usability of trails is a critical concern of land managers charged with providing recreational access while preserving natural conditions, and to visitors seeking high quality recreational opportunities and experiences. While an adequate number of trail management publications provide prescriptive guidance for designing, constructing, and maintaining natural-surfaced trails, surprisingly little research has been directed at providing a scientific basis for this guidance. Results from a review of the literature and three scientific studies are presented to model and clarify the influence of factors that substantially influence trail soil loss and that can be manipulated by trail professionals to sustain high traffic while minimizing soil loss over time. Key factors include trail grade, slope alignment angle, tread drainage features, and the amount of rock in tread substrates. A new Trail Sustainability Rating is developed and offered as a tool for evaluating or improving the sustainability of existing or new trails. Published by Elsevier Ltd.

36 CFR 261.12 - National Forest System roads and trails.

Science.gov (United States)

2010-07-01

... and trails. 261.12 Section 261.12 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROHIBITIONS General Prohibitions § 261.12 National Forest System roads and trails. The following... by a sign. (c) Damaging and leaving in a damaged condition any such road, trail, or segment thereof...

Molecular requirements for the combined effects of TRAIL and ionising radiation

International Nuclear Information System (INIS)

Marini, Patrizia; Jendrossek, Verena; Durand, Elise; Gruber, Charlotte; Budach, Wilfried; Belka, Claus

2003-01-01

Background and purpose: Previously it was shown that combination of death ligand TRAIL and irradiation strongly increases cell kill in several human tumour cell lines. Since Bcl-2 overexpression did not strongly interfere with the efficacy, components of the mitochondrial death pathway are not required for an effective combined treatment. In the present study the minimal molecular prerequisites for the efficacy of a combined treatment were determined. Materials and methods: Apoptosis induction in control, caspase-8 and FADD negative Jurkat cells, BJAB control and FADD-DN cells was analysed by FACS. Activation of caspase-8, -10 and -3 and cleavage of PARP was determined by immunoblotting. TRAIL receptors were activated using recombinant human TRAIL. Surface expression of TRAIL receptors DR4 and DR5 was analysed by FACS. Results: Jurkat T-cells express the agonistic DR5 receptor but not DR4. Presence of FADD was found to be essential for TRAIL induced apoptosis. Caspase-8 negative cells show very low rates of apoptosis after prolonged stimulation with TRAIL. No combined effects of TRAIL with irradiation could be found in FADD-DN over expressing and FADD deficient cells. However, the combination of TRAIL and irradiation clearly lead to a combined effect in caspase-8 negative Jurkat cells, albeit with reduced death rates. In these cells activation of the alternative initiator caspase-10 could be detected after combined treatment. Conclusion: Our data show that a combined therapy with TRAIL and irradiation will only be effective in cells expressing at least one agonistic TRAIL receptor, FADD and caspase-8 or caspase-10

36 CFR 212.51 - Designation of roads, trails, and areas.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Designation of roads, trails... AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.51 Designation of roads, trails, and areas. (a) General. Motor vehicle use on National Forest System roads, on...

Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression

International Nuclear Information System (INIS)

Ivanov, Vladimir N.; Hei, Tom K.

2006-01-01

AP-1/cJun, NF-κB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-κB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malignant melanoma is highly refractory to conventional radio- and chemotherapy. In the present study, we observed strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas. Arsenite treatment upregulated surface levels of death receptors, TRAIL-R1 and TRAIL-R2, through increased translocation of these proteins from cytoplasm to the cell surface. Furthermore, activation of cJun and suppression of NF-κB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression (which encodes one of the main anti-apoptotic proteins in melanomas) followed by cFLIP protein degradation and, finally, by acceleration of TRAIL-induced apoptosis. Direct suppression of cFLIP expression by cFLIP RNAi also accelerated TRAIL-induced apoptosis in these melanomas, while COX-2 suppression substantially increased levels of both TRAIL-induced and arsenite-induced apoptosis. In contrast, overexpression of permanently active AKTmyr inhibited TRAIL-mediated apoptosis via downregulation of TRAIL-R1 levels. Finally, AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment

Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium.

Science.gov (United States)

Karmakar, Utpal K; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

2015-08-01

The ability of TRAIL to selectively induce apoptosis in cancer cells while sparing normal cells makes it an attractive target for the development of new cancer therapy. In search of bioactive natural products for overcoming TRAIL-resistance from natural resources, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionations of the extract of Xanthium strumarium led to the isolation of five sesquiterpene compounds (1-5). 11α,13-dihydroxanthinin (2) and 11α,13-dihydroxanthuminol (3) were first isolated from natural resources and xanthinosin (1), desacetylxanthanol (4), and lasidiol p-methoxybenzoate (5) were known compounds. All compounds (1-5) showed potent TRAIL-resistance overcoming activity at 8, 20, 20, 16, and 16 μM, respectively, in TRAIL-resistant AGS cells. Compounds 1 and 5 enhanced the levels of apoptosis inducing proteins DR4, DR5, p53, CHOP, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant AGS cells in a dose-dependent manner. Compound 1 also enhanced the levels of DR4 and DR5 proteins in a time-dependent manner. Thus, compounds 1 and 5 were found to induce both extrinsic and intrinsic apoptotic cell death. Compound 1 also exhibit TRAIL-resistance overcoming activity in DLD1, DU145, HeLa, and MCF7 cells but did not decrease viability in non-cancer HEK293 cells up to 8 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

76 FR 8992 - National Trails System Act and Railroad Rights-of-Way

Science.gov (United States)

2011-02-16

...] National Trails System Act and Railroad Rights-of-Way AGENCY: Surface Transportation Board, DOT. ACTION... procedures regarding the use of railroad rights-of-way for railbanking and interim trail use under the National Trails System Act (Trails Act). DATES: Comments are due by April 12, 2011; replies are due by May...

Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists

Science.gov (United States)

Urso, Loredana; Biasini, Lorena; Zago, Giulia; Calabrese, Fiorella; Conte, Pier Franco; Ciminale, Vincenzo; Pasello, Giulia

2017-01-01

Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL. In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs. In vivo studies were conducted on a sarcomatoid MPM mouse model. In all the cell lines tested (with the exception of ZL55, which carries a biallelic loss-of-function mutation of p53), Nutlin 3a enhanced p21, MDM2 and DR5 expression, and decreased survivin expression. These changes were associated to cell cycle arrest but not to a significant induction of apoptosis. A synergistic pro-apoptotic effect was obtained through the association of rhTRAIL in all the cell lines harboring functional p53. This synergistic interaction of MDM2 inhibitor and TRAIL agonist was confirmed using a mouse preclinical model. Our results suggest that the combined targeting of MDM2 and TRAIL might provide a novel therapeutic option for treatment of MPM patients, particularly in the case of sarcomatoid MPM with MDM2 overexpression and functional inactivation of wild-type p53. PMID:28562336

The dynamics of foraging trails in the tropical arboreal ant Cephalotes goniodontus.

Directory of Open Access Journals (Sweden)

Deborah M Gordon

Full Text Available The foraging behavior of the arboreal turtle ant, Cephalotes goniodontus, was studied in the tropical dry forest of western Mexico. The ants collected mostly plant-derived food, including nectar and fluids collected from the edges of wounds on leaves, as well as caterpillar frass and lichen. Foraging trails are on small pieces of ephemeral vegetation, and persist in exactly the same place for 4-8 days, indicating that food sources may be used until they are depleted. The species is polydomous, occupying many nests which are abandoned cavities or ends of broken branches in dead wood. Foraging trails extend from trees with nests to trees with food sources. Observations of marked individuals show that each trail is travelled by a distinct group of foragers. This makes the entire foraging circuit more resilient if a path becomes impassable, since foraging in one trail can continue while a different group of ants forms a new trail. The colony's trails move around the forest from month to month; from one year to the next, only one colony out of five was found in the same location. There is continual searching in the vicinity of trails: ants recruited to bait within 3 bifurcations of a main foraging trail within 4 hours. When bait was offered on one trail, to which ants recruited, foraging activity increased on a different trail, with no bait, connected to the same nest. This suggests that the allocation of foragers to different trails is regulated by interactions at the nest.

The dynamics of foraging trails in the tropical arboreal ant Cephalotes goniodontus.

Science.gov (United States)

Gordon, Deborah M

2012-01-01

The foraging behavior of the arboreal turtle ant, Cephalotes goniodontus, was studied in the tropical dry forest of western Mexico. The ants collected mostly plant-derived food, including nectar and fluids collected from the edges of wounds on leaves, as well as caterpillar frass and lichen. Foraging trails are on small pieces of ephemeral vegetation, and persist in exactly the same place for 4-8 days, indicating that food sources may be used until they are depleted. The species is polydomous, occupying many nests which are abandoned cavities or ends of broken branches in dead wood. Foraging trails extend from trees with nests to trees with food sources. Observations of marked individuals show that each trail is travelled by a distinct group of foragers. This makes the entire foraging circuit more resilient if a path becomes impassable, since foraging in one trail can continue while a different group of ants forms a new trail. The colony's trails move around the forest from month to month; from one year to the next, only one colony out of five was found in the same location. There is continual searching in the vicinity of trails: ants recruited to bait within 3 bifurcations of a main foraging trail within 4 hours. When bait was offered on one trail, to which ants recruited, foraging activity increased on a different trail, with no bait, connected to the same nest. This suggests that the allocation of foragers to different trails is regulated by interactions at the nest.

Ambient Air Conditions and Variation in Urban Trail Use

OpenAIRE

Holmes, Ann M.; Lindsey, Greg; Qiu, Chenchen

2009-01-01

This study examines the effect of air quality and administrative policies on use of urban trails in Indianapolis, IN. Attention is focused on two policy variables: (1) issuance of air pollution advisories and (2) the adoption of Daylight Savings Time. Results suggest that while trail use varies with air quality, current public advisories regarding air pollution may be of limited effectiveness in reducing trail users’ exposures to hazardous pollutants. In contrast, the adoption of Daylight Sav...

30 CFR 75.600 - Trailing cables; flame resistance.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cables; flame resistance. 75.600 Section 75.600 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... cables; flame resistance. [Statutory Provisions] Trailing cables used in coal mines shall meet the...

A new concept in trail grooming. `The KRC groomer`

Energy Technology Data Exchange (ETDEWEB)

Alger, R G [Michigan Technological Univ., Houghton, MI (United States)

1994-12-31

A groomer developed for maintaining snow roads in Arctic regions was described. The KRC groomer was initially designed for use on snowmobile trails. The device resulted from research into the problem of mogul formation on trails and how to improve on present techniques to make trail surfaces more durable. Studies were conducted both in the laboratory and in the field in an attempt to better understand this bump formation. The device and studies of its design were discussed. 9 figs., 7 refs.

Home | Trails of Hope: Overland Diaries and Letters, 1846-1869 | Digital

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Collections | HBLL BYU Harold B. Lee Library Collections Trails of Hope: Overland Diaries and Mormons--Religious Life Religious Life Women Browse Search Browse all Maps Interactive Maps These maps illustrations. Search Browse all Photographs and Illustrations Search Browse all Trail Guides Trails of Hope

30 CFR 77.804 - High-voltage trailing cables; minimum design requirements.

Science.gov (United States)

2010-07-01

... OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.804 High-voltage trailing cables; minimum design requirements. (a) High-voltage trailing cables used in resistance grounded systems shall be... 30 Mineral Resources 1 2010-07-01 2010-07-01 false High-voltage trailing cables; minimum design...

TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis

International Nuclear Information System (INIS)

Polek, Tara C.; Talpaz, Moshe; Spivak-Kroizman, Taly R.

2006-01-01

Ste20-related proline-alanine-rich kinase (SPAK) has been linked to various cellular processes, including proliferation, differentiation, and ion transport regulation. Recently, we showed that SPAK mediates signaling by the TNF receptor, RELT. The presence of a caspase cleavage site in SPAK prompted us to study its involvement in apoptotic signaling induced by another TNF member, TRAIL. We show that TRAIL stimulated caspase 3-like proteases that cleaved SPAK at two distinct sites. Cleavage had little effect on the activity of SPAK but removed its substrate-binding domain. In addition, TRAIL reduced the activity of SPAK in HeLa cells in a caspase-independent manner. Thus, TRAIL inhibited SPAK by two mechanisms: activation of caspases, which removed its substrate-binding domain, and caspase-independent down-regulation of SPAK activity. Furthermore, reducing the amount of SPAK by siRNA increased the sensitivity of HeLa cells to TRAIL-induced apoptosis. Thus, TRAIL down-regulation of SPAK is an important event that enhances its apoptotic effects

Neutrophil trails guide influenza-specific CD8⁺ T cells in the airways.

Science.gov (United States)

Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J; Kim, Minsoo

2015-09-04

During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8(+) T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8(+) T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8(+) T cell migration and localization in influenza-infected tissues. Copyright © 2015, American Association for the Advancement of Science.

Trail marking by caterpillars of the silverspot butterfly Dione juno huascuma.

Science.gov (United States)

Pescador-Rubio, Alfonso; Stanford-Camargo, Sergio G; Páez-Gerardo, Luis E; Ramírez-Reyes, Alberto J; Ibarra-Jiménez, René A; Fitzgerald, Terrence D

2011-01-01

A pheromone is implicated in the trail marking behavior of caterpillars of the nymphalid silverspot butterfly, Dione juno huascuma (Reakirt) (Lepidoptera: Heliconiinae) that feed gregariously on Passiflora (Malpighiales: Passifloraceae) vines in Mexico. Although they mark pathways leading from one feeding site to another with silk, this study shows that the silk was neither adequate nor necessary to elicit trail following behavior. Caterpillars marked trails with a long-lived pheromone that was deposited when they brushed the ventral surfaces of the tips of their abdomens along branch pathways. The caterpillars distinguished between pathways deposited by different numbers of siblings and between trails of different ages. Caterpillars also preferentially followed the trails of conspecifics over those of another nymphalid, Nymphalis antiopa L., the mourning cloak butterfly.

The emphysematous lung is abnormally sensitive to TRAIL-mediated apoptosis

Directory of Open Access Journals (Sweden)

Milot Julie

2011-08-01

Full Text Available Abstract Background Alveolar apoptosis is increased in the emphysematous lung. However, mechanisms involved are not fully understood. Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax/Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation. Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis. Methodology A549 cells were exposed to rTRAIL, cigarette smoke extract, and/or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment. In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours. Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates. Results Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis. Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects. Significance of the study Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress. This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation.

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

Science.gov (United States)

Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

2017-11-15

Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell

Indicators and protocols for monitoring impacts of formal and informal trails in protected areas

Science.gov (United States)

Marion, Jeffrey L.; Leung, Yu-Fai

2011-01-01

Trails are a common recreation infrastructure in protected areas and their conditions affect the quality of natural resources and visitor experiences. Various trail impact indicators and assessment protocols have been developed in support of monitoring programs, which are often used for management decision-making or as part of visitor capacity management frameworks. This paper reviews common indicators and assessment protocols for three types of trails, surfaced formal trails, unsurfaced formal trails, and informal (visitor-created) trails. Monitoring methods and selected data from three U.S. National Park Service units are presented to illustrate some common trail impact indicators and assessment options.

Equivalence of the Color Trails Test and Trail Making Test in nonnative English-speakers.

Science.gov (United States)

Dugbartey, A T; Townes, B D; Mahurin, R K

2000-07-01

The Color Trails Test (CTT) has been described as a culture-fair test of visual attention, graphomotor sequencing, and effortful executive processing abilities relative to the Trail Making Test (TMT). In this study, the equivalence of the TMT and the CTT among a group of 64 bilingual Turkish university students was examined. No difference in performance on the CTT-1 and TMT Part A was found, suggesting functionally equivalent performance across both tasks. In contrast, the statistically significant differences in performance on CTT-2 and TMT Part B, as well as the interference indices for both tests, were interpreted as providing evidence for task nonequivalence of the CTT-2 and TMT Part B. Results have implications for both psychometric test development and clinical cultural neuropsychology.

The interplay between scent trails and group-mass recruitment systems in ants.

Science.gov (United States)

Planqué, Robert; van den Berg, Jan Bouwe; Franks, Nigel R

2013-10-01

Large ant colonies invariably use effective scent trails to guide copious ant numbers to food sources. The success of mass recruitment hinges on the involvement of many colony members to lay powerful trails. However, many ant colonies start off as single queens. How do these same colonies forage efficiently when small, thereby overcoming the hurdles to grow large? In this paper, we study the case of combined group and mass recruitment displayed by some ant species. Using mathematical models, we explore to what extent early group recruitment may aid deployment of scent trails, making such trails available at much smaller colony sizes. We show that a competition between group and mass recruitment may cause oscillatory behaviour mediated by scent trails. This results in a further reduction of colony size to establish trails successfully.

Leading and Trailing Anvil Clouds of West African Squall Lines

Science.gov (United States)

Centrone, Jasmine; Houze, Robert A.

2011-01-01

The anvil clouds of tropical squall-line systems over West Africa have been examined using cloud radar data and divided into those that appear ahead of the leading convective line and those on the trailing side of the system. The leading anvils are generally higher in altitude than the trailing anvil, likely because the hydrometeors in the leading anvil are directly connected to the convective updraft, while the trailing anvil generally extends out of the lower-topped stratiform precipitation region. When the anvils are subdivided into thick, medium, and thin portions, the thick leading anvil is seen to have systematically higher reflectivity than the thick trailing anvil, suggesting that the leading anvil contains numerous larger ice particles owing to its direct connection to the convective region. As the leading anvil ages and thins, it retains its top. The leading anvil appears to add hydrometeors at the highest altitudes, while the trailing anvil is able to moisten a deep layer of the atmosphere.

BCDC Bay Trail Alignment 2009

Data.gov (United States)

California Natural Resource Agency — The Bay Trail provides easily accessible recreational opportunities for outdoor enthusiasts, including hikers, joggers, bicyclists and skaters. It also offers a...

ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

OpenAIRE

Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

2017-01-01

Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell...

IMPROVED TUMOR CELL KILLING BY TRAIL REQUIRES SELECTIVE AND HIGH AFFINITY RECEPTOR ACTIVATION

NARCIS (Netherlands)

Szegezdi, Eva; van der Sloot, Almer M.; Alessandro, Natoni; Mahalingam, Devalingam; Cool, Robbert H.; Munoz, Ines G.; Montoya, Guillermo; Quax, Wim J.; Luis Serrano, Steven de Jong; Samali, Afshin; Wallach, D; Kovalenko, A; Feldman, M

2011-01-01

Apoptosis can be activated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a wide range of tumor cells, but not in non-transformed cells. TRAIL interaction with receptors DR4 or DR5 induces apoptosis, whereas DcR1, DcR2 and osteoprotegerin are decoy receptors for TRAIL. TRAIL

Access Control Based on Trail Inference

Directory of Open Access Journals (Sweden)

ALBARELO, P. C.

2015-06-01

Full Text Available Professionals are constantly seeking qualification and consequently increasing their knowledge in their area of expertise. Thus, it is interesting to develop a computer system that knows its users and their work history. Using this information, even in the case of professional role change, the system could allow the renewed authorization for activities, based on previously authorized use. This article proposes a model for user access control that is embedded in a context-aware environment. The model applies the concept of trails to manage access control, recording activities usage in contexts and applying this history as a criterion to grant new accesses. Despite the fact that previous related research works consider contexts, none of them uses the concept of trails. Hence, the main contribution of this work is the use of a new access control criterion, namely, the history of previous accesses (trails. A prototype was implemented and applied in an evaluation based on scenarios. The results demonstrate the feasibility of the proposal, allowing for access control systems to use an alternative way to support access rights.

Experimental investigation of airfoil trailing edge heat transfer and aerodynamic losses

Energy Technology Data Exchange (ETDEWEB)

Brundage, A.L. [Sandia National Laboratories, Albuquerque, NM 87185 (United States); Plesniak, M.W.; Lawless, P.B. [School of Mechanical Engineering, Maurice J. Zucrow Laboratories, Purdue University, West Lafayette, IN 47907 (United States); Ramadhyani, S. [132 Cecil Street SE, Minneapolis, MN 55414 (United States)

2007-01-15

Modern gas turbine development is being driven by the often-incompatible goals of increased efficiency, better durability, and reduced emissions. High turbine inlet temperatures and ineffective cooling at the trailing edge of a first-stage stator vane lead to corrosion, oxidation, and thermal fatigue. Observations of this region in engines frequently reveal burn marks, cracks, and buckling. Fundamental studies of the importance of trailing edge heat transfer to the design of an optimal cooling scheme are scarce. An experimental study of an actively cooled trailing edge configuration, in which coolant is injected through a slot, is performed. Trailing edge heat transfer and aerodynamic measurements are reported. An optimum balance between maximizing blade row aerodynamic efficiency and improving thermal protection at the trailing edge is estimated to be achieved when blowing ratios are in the range between 2.1% and 2.8%. The thermal phenomena at the trailing edge are dominated by injection slot heat transfer and flow physics. These measured trends are generally applicable over a wide range of gas turbine applications. (author)

The role of trails in the creation of tourist space

OpenAIRE

MacLeod, Nicola

2017-01-01

Trails and routes are increasingly ubiquitous features within the tourism landscape and although their role and usefulness as applied tourism products has been analysed, they remain under-theorised within the academic literature. This article addresses this gap by exploring the role of trails within the socio-cultural construction of space. In particular, the potential function of trails in creating themed, static spaces is analysed and the concept of museumisation is employed to further illu...

The influence of snowmobile trails on coyote movements during winter in high-elevation landscapes.

Directory of Open Access Journals (Sweden)

Eric M Gese

Full Text Available Competition between sympatric carnivores has long been of interest to ecologists. Increased understanding of these interactions can be useful for conservation planning. Increased snowmobile traffic on public lands and in habitats used by Canada lynx (Lynx canadensis remains controversial due to the concern of coyote (Canis latrans use of snowmobile trails and potential competition with lynx. Determining the variables influencing coyote use of snowmobile trails has been a priority for managers attempting to conserve lynx and their critical habitat. During 2 winters in northwest Wyoming, we backtracked coyotes for 265 km to determine how varying snow characteristics influenced coyote movements; 278 km of random backtracking was conducted simultaneously for comparison. Despite deep snow (>1 m deep, radio-collared coyotes persisted at high elevations (>2,500 m year-round. All coyotes used snowmobile trails for some portion of their travel. Coyotes used snowmobile trails for 35% of their travel distance (random: 13% for a mean distance of 149 m (random: 59 m. Coyote use of snowmobile trails increased as snow depth and penetrability off trails increased. Essentially, snow characteristics were most influential on how much time coyotes spent on snowmobile trails. In the early months of winter, snow depth was low, yet the snow column remained dry and the coyotes traveled off trails. As winter progressed and snow depth increased and snow penetrability increased, coyotes spent more travel distance on snowmobile trails. As spring approached, the snow depth remained high but penetrability decreased, hence coyotes traveled less on snowmobile trails because the snow column off trail was more supportive. Additionally, coyotes traveled closer to snowmobile trails than randomly expected and selected shallower snow when traveling off trails. Coyotes also preferred using snowmobile trails to access ungulate kills. Snow compaction from winter recreation influenced

The influence of snowmobile trails on coyote movements during winter in high-elevation landscapes.

Science.gov (United States)

Gese, Eric M; Dowd, Jennifer L B; Aubry, Lise M

2013-01-01

Competition between sympatric carnivores has long been of interest to ecologists. Increased understanding of these interactions can be useful for conservation planning. Increased snowmobile traffic on public lands and in habitats used by Canada lynx (Lynx canadensis) remains controversial due to the concern of coyote (Canis latrans) use of snowmobile trails and potential competition with lynx. Determining the variables influencing coyote use of snowmobile trails has been a priority for managers attempting to conserve lynx and their critical habitat. During 2 winters in northwest Wyoming, we backtracked coyotes for 265 km to determine how varying snow characteristics influenced coyote movements; 278 km of random backtracking was conducted simultaneously for comparison. Despite deep snow (>1 m deep), radio-collared coyotes persisted at high elevations (>2,500 m) year-round. All coyotes used snowmobile trails for some portion of their travel. Coyotes used snowmobile trails for 35% of their travel distance (random: 13%) for a mean distance of 149 m (random: 59 m). Coyote use of snowmobile trails increased as snow depth and penetrability off trails increased. Essentially, snow characteristics were most influential on how much time coyotes spent on snowmobile trails. In the early months of winter, snow depth was low, yet the snow column remained dry and the coyotes traveled off trails. As winter progressed and snow depth increased and snow penetrability increased, coyotes spent more travel distance on snowmobile trails. As spring approached, the snow depth remained high but penetrability decreased, hence coyotes traveled less on snowmobile trails because the snow column off trail was more supportive. Additionally, coyotes traveled closer to snowmobile trails than randomly expected and selected shallower snow when traveling off trails. Coyotes also preferred using snowmobile trails to access ungulate kills. Snow compaction from winter recreation influenced coyote

Validation of Walking Trails for the Urban Training™ of Chronic Obstructive Pulmonary Disease Patients.

Directory of Open Access Journals (Sweden)

Ane Arbillaga-Etxarri

Full Text Available Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD are needed. We designed urban trails of different intensities (low, moderate and high in different types of public spaces (boulevard, beach and park. We aimed to validate the trails' design by assessing the physiological response to unsupervised walking trails of: (1 different intensities in COPD patients, and (2 same intensity from different public spaces in healthy adults.On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces. We measured physiological response and energy expenditure using a gas analyzer. We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD peak V̇O2 15.9 (3.5, 17.4 (4.7, and 17.7 (4.4 mL/min/kg (p-trend = 0.02, and MET-min 60 (23, 64 (26, 72 (31 (p-trend<0.01 in low, moderate and high intensity trails, respectively. In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails' intensity and did not change across trails of the same intensity in different public space. Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community.

Female Sex Pheromone in Trails of the Minute Pirate Bug, Orius minutus (L).

Science.gov (United States)

Maeda, Taro; Fujiwara-Tsujii, Nao; Yasui, Hiroe; Matsuyama, Shigeru

2016-05-01

Orius minutus (L.) (Heteroptera: Anthocoridae) is a natural enemy of agricultural pests such as thrips, aphids, and various newly hatched insect juveniles. In this study, we conducted 1) behavioral assays for evidence of contact sex pheromone activity in trails of O. minutus, and 2) chemical analysis to identify the essential chemical components of the trails. Males showed arrestment to trails of mature virgin females but not to trails from either conspecific nymphs or immature females. Females also showed arrestment to trails from conspecific males, although the response was weaker than that exhibited by males. The activity of female trails lasted for at least 46 h after deposition. Males showed a response irrespective of mating experience. Following confirmation that a contact sex pheromone was present in the trails of female O. minutus, we used a bioassay-driven approach to isolate the active chemicals. After fractionation on silica gel, the n-hexane fraction was found to be biologically active to males. A major compound in the active fraction was (Z)-9-nonacosene; this compound was found only in trail extracts of mature virgin females. Synthetic (Z)-9-nonacosene arrested O. minutus males, indicating that it is the major active component of the contact sex pheromone in the trails of female O. minutus.

Sediment pathways in a tropical forest: effects of logging roads and skid trails

Science.gov (United States)

Sidle, Roy C.; Sasaki, Shozo; Otsuki, Mieko; Noguchi, Shoji; Rahim Nik, Abdul

2004-03-01

Significant erosion occurred from recently constructed forest logging roads and skid trails in a small headwater catchment in Peninsular Malaysia. Soil loss was estimated by measuring dimensions of all significant rills and gullies along the road, as well as by measuring height of preserved soil pedestals in sidecast and fill material and on skid trails. Estimates of surface erosion from logging roads and skid trails were 272 +/- 20 t ha-1 year-1 and 275 +/- 20 t ha-1 year-1 respectively. However, owing to lack of connectivity of skid trails to the stream, much of the sediment mobilized on skid trails was stored either on adjacent hillslopes or the trails themselves, rather than being transported to the stream system, as was the case for the road. Steeper skid trails (>20% gradient) had slightly higher erosion rates (320 +/- 24 t ha-1 year-1) than trails with gentler gradients (245-264 t ha-1 year-1). Some 60% of the soil loss on logging roads comes from erosion of the running surface. Disturbed cut and fill material along the road supplied the remaining 40% of the soil loss from roads. Roads and skid trails had no designed drainage systems; runoff discharged onto the hillslope at 25 major discharge nodes from the logging road (690 m total length) and at 34 nodes from skid trails (2300 m). Sediment pathways were either fully or moderately connected to headwater channels at 64% of the logging road nodes, but at only 26% of the nodes emanating from skid trails. A detailed sediment budget revealed that 78% of the soil loss from the road system (including log landings) was delivered to the stream in the first 16 months after logging began. Most (90%) of the deposition from skid trails occurred below just three discharge nodes. Runoff from and onto skid trails often exacerbated the sediment connectivity to channels. Clearly, sediment discharge from logging roads was more highly connected to the stream than discharge from skid trails. Once in the channel, much of this

Estimating soil erosion on hiking trails in the Sierra Mariola Natural Park in southern Spain

Science.gov (United States)

Magdalena Warter, Maria; Peeters, Mattias; Kuppen, Emiel; Blok, Kas; Dilly, Lina

2017-04-01

Natural parks and protected natural areas provide excellent recreational opportunities for outdoor activities through the richness of the natural environment and the abundance of walking trails. Hiking, mountain biking and running have rapidly gained popularity over recent years increasing concerns about the erosion and degradation of hiking trails caused by (over)use. This is also the case in the Sierra Mariola Natural Park in southeast Spain, which is a popular destination for tourists due to its diverse fauna and flora. The increasing number of tourists together with the negative impacts of climate change necessitates a better understanding of the key soil erosion processes impacting hiking trails. There are 4 scenic trail routes in the Natural Park amounting to 21 km plus an additional network of unofficial trails. Apart from the heavy touristic traffic on the trails there are large trail running events with up to 1000 participants becoming increasingly popular, however local park authorities have voiced concerns about the impacts of these activities on the trails. Despite the popularity of walking trails around the world, there is a paucity of research exploring soil erosion from these features. Therefore, the aims of this study are: 1) to ascertain the amount of erosion that occurs on trails in the Sierra Mariola Natural Park, and 2) determine the key factors that influence soil erosion. Some 100 km of trails were evaluated (both official and unmarked trails), with route segments ranging between 2 and 10 km. A trail classification system was developed to group trail segments based on their surface characteristics (bedrock, gravel, mixed sediment, soil or man-made) and specific erosion features (rills, ditch-shaped, tilted). For each class, the average erosion rate was calculated which ranged from 262 t/ha for soil-based trails to 2006 t/ha for heavily eroded, ditch-shaped trails. The spatial distribution of the different erosion rates and trail types were

Experimental Investigation of Aerodynamic Performance of Airfoils Fitted with Morphing Trailing Edges

OpenAIRE

Ai, Qing; Kamliya Jawahar, Hasan; Azarpeyvand, Mahdi

2016-01-01

The aerodynamic performance and wake development of a NACA 0012 airfoil fitted with morphing trailing edges were studied using experimental and computational techniques. The NACA 0012 airfoil was tested with morphing trailing edges having various camber profiles with the same trailing edge tip deflection. The aerodynamic force measurements for the airfoil were carried out for a wide range of chord-based Reynolds number and angles of attack with trailing edge deflection angle of β= 5◦ and 10◦....

Is the color trails culture free?

Science.gov (United States)

Fasfous, Ahmed F; Puente, Antonio E; Pérez-Marfil, María Nieves; Cruz-Quintana, Francisco; Peralta-Ramirez, Isabel; Pérez-García, Miguel

2013-11-01

Increasingly clinical neuropsychology has been addressing the effects of culture on neuropsychological functioning. However, that focus has been on comparing performance on standardized tests across two or more groups, often Hispanic. In this study, Arabic children were tested in Morocco using a "culture-free test," Children's Color Trails. Children of different ages and living in rural and urban centers were tested. The results suggest that the Color Trails Test scores from Arab children differed from U.S. norms available. Furthermore, the location of testing and the age of the child were of significance. The role of culture-specific tests was considered.

Validation of Walking Trails for the Urban Training™ of Chronic Obstructive Pulmonary Disease Patients.

Science.gov (United States)

Arbillaga-Etxarri, Ane; Torrent-Pallicer, Jaume; Gimeno-Santos, Elena; Barberan-Garcia, Anael; Delgado, Anna; Balcells, Eva; Rodríguez, Diego A; Vilaró, Jordi; Vall-Casas, Pere; Irurtia, Alfredo; Rodriguez-Roisin, Robert; Garcia-Aymerich, Judith

2016-01-01

Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed. We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park). We aimed to validate the trails' design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults. On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces. We measured physiological response and energy expenditure using a gas analyzer. We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression. In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V̇O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trendtrails, respectively. In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces. We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails' intensity and did not change across trails of the same intensity in different public space. Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community.

Accurate Natural Trail Detection Using a Combination of a Deep Neural Network and Dynamic Programming.

Science.gov (United States)

Adhikari, Shyam Prasad; Yang, Changju; Slot, Krzysztof; Kim, Hyongsuk

2018-01-10

This paper presents a vision sensor-based solution to the challenging problem of detecting and following trails in highly unstructured natural environments like forests, rural areas and mountains, using a combination of a deep neural network and dynamic programming. The deep neural network (DNN) concept has recently emerged as a very effective tool for processing vision sensor signals. A patch-based DNN is trained with supervised data to classify fixed-size image patches into "trail" and "non-trail" categories, and reshaped to a fully convolutional architecture to produce trail segmentation map for arbitrary-sized input images. As trail and non-trail patches do not exhibit clearly defined shapes or forms, the patch-based classifier is prone to misclassification, and produces sub-optimal trail segmentation maps. Dynamic programming is introduced to find an optimal trail on the sub-optimal DNN output map. Experimental results showing accurate trail detection for real-world trail datasets captured with a head mounted vision system are presented.

Go West: Imagining the Oregon Trail. [Lesson Plan].

Science.gov (United States)

National Endowment for the Humanities (NFAH), Washington, DC.

In this lesson plan, students in grades 3-5 compare imagined travel experiences of their own with the actual experiences of 19th-century pioneers on the Oregon Trail. After the 4 lessons students will have: (1) learned about the pioneer experience on the Oregon Trail; (2) compared and contrasted modern-day travel experiences with those of the 19th…

30 CFR 75.907 - Design of trailing cables for medium-voltage circuits.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Design of trailing cables for medium-voltage... Medium-Voltage Alternating Current Circuits § 75.907 Design of trailing cables for medium-voltage circuits. [Statutory Provisions] Trailing cables for medium-voltage circuits shall include grounding...

Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

Directory of Open Access Journals (Sweden)

Margherita Iaboni

2016-01-01

Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a promising antitumor agent for its remarkable ability to selectively induce apoptosis in cancer cells, without affecting the viability of healthy bystander cells. The TRAIL tumor suppressor pathway is deregulated in many human malignancies including lung cancer. In human non-small cell lung cancer (NSCLC cells, sensitization to TRAIL therapy can be restored by increasing the expression levels of the tumor suppressor microRNA-212 (miR-212 leading to inhibition of the anti-apoptotic protein PED/PEA-15 implicated in treatment resistance. In this study, we exploited a previously described RNA aptamer inhibitor of the tyrosine kinase receptor Axl (GL21.T expressed on lung cancer cells, as a means to deliver miR-212 into human NSCLC cells expressing Axl. We demonstrate efficient delivery of miR-212 following conjugation of the miR to GL21.T (GL21.T-miR212 chimera. We show that the chimera downregulates PED and restores TRAIL-mediate cytotoxicity in cancer cells. Importantly, treatment of Axl+ lung cancer cells with the chimera resulted in (i an increase in caspase activation and (ii a reduction of cell viability in combination with TRAIL therapy. In conclusion, we demonstrate that the GL21.T-miR212 chimera can be employed as an adjuvant to TRAIL therapy for the treatment of lung cancer.

Trail Crews: Developing a Service Component to Your Program.

Science.gov (United States)

Boehringer, Brad; Merrill, Kurt

Through wilderness stewardship programs, service projects, or trail crews, college outdoor programs can help land management agencies with their maintenance needs and provide student participants with rewarding service learning opportunities. Trail crews are usually composed of volunteer outdoor enthusiasts who take part in a multitude of…

Heat Transfer and Friction Studies in a Tilted and Rib-Roughened Trailing-Edge Cooling Cavity with and without the Trailing-Edge Cooling Holes

Directory of Open Access Journals (Sweden)

M. E. Taslim

2014-01-01

Full Text Available Local and average heat transfer coefficients and friction factors were measured in a test section simulating the trailing-edge cooling cavity of a turbine airfoil. The test rig with a trapezoidal cross-sectional area was rib-roughened on two opposite sides of the trapezoid (airfoil pressure and suction sides with tapered ribs to conform to the cooling cavity shape and had a 22-degree tilt in the flow direction upstream of the ribs that affected the heat transfer coefficients on the two rib-roughened surfaces. The radial cooling flow traveled from the airfoil root to the tip while exiting through 22 cooling holes along the airfoil trailing-edge. Two rib geometries, with and without the presence of the trailing-edge cooling holes, were examined. The numerical model contained the entire trailing-edge channel, ribs, and trailing-edge cooling holes to simulate exactly the tested geometry. A pressure-correction based, multiblock, multigrid, unstructured/adaptive commercial software was used in this investigation. Realizable k-ε turbulence model in conjunction with enhanced wall treatment approach for the near wall regions was used for turbulence closure. The applied thermal boundary conditions to the CFD models matched the test boundary conditions. Comparisons are made between the experimental and numerical results.

Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Geel, Tessa M. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Meiss, Gregor [Institute of Biochemistry, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Gun, Bernardina T. van der; Kroesen, Bart Jan; Leij, Lou F. de [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Zaremba, Mindaugas; Silanskas, Arunas [Institute of Biotechnology, Vilnius LT-02241 (Lithuania); Kokkinidis, Michael [IMBB/FORTH and University of Crete/Department of Biology, GR-71409 Heraklion/Crete (Greece); Pingoud, Alfred [Institute of Biochemistry, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Ruiters, Marcel H. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Synvolux therapeutics, Groningen (Netherlands); McLaughlin, Pamela M. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Rots, Marianne G., E-mail: m.g.rots@med.umcg.nl [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands)

2009-09-10

TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restriction endonucleases to directly digest DNA in vivo, thereby circumventing the caspase cascade. For this purpose, we delivered enzymatically active endonucleases via the cationic amphiphilic lipid SAINT-18{sup Registered-Sign }:DOPE to both TRAIL-sensitive and insensitive ovarian carcinoma cells (OVCAR and SKOV-3, respectively). Functional nuclear localization after delivery of various endonucleases (BfiI, PvuII and NucA) was indicated by confocal microscopy and genomic cleavage analysis. For PvuII, analysis of mitochondrial damage demonstrated extensive apoptosis both in SKOV-3 and OVCAR. This study clearly demonstrates that cellular delivery of restriction endonucleases holds promise to serve as a novel therapeutic tool for the treatment of resistant ovarian carcinomas.

Initiation of trailing edge failure in full-scale wind turbine blade test

DEFF Research Database (Denmark)

Haselbach, Philipp Ulrich; Branner, Kim

2016-01-01

non-linear buckling effect of the trailing edge under combined loading, and how it affects the ultimate strength of a blade in a trailing-edge failure dominated load direction were investigated. The study details the interaction between trailing edge buckling on damage onset and sandwich panel failure...

Statistics of semiflexible self-avoiding trails on a family of two-dimensional compact fractals

International Nuclear Information System (INIS)

Živić, I; Elezović-Hadžić, S; Milošević, S

2011-01-01

We have applied the exact and Monte Carlo renormalization group (MCRG) method to study the statistics of semiflexible self-avoiding trails (SATs) on the family of plane-filling (PF) fractals. Each fractal of the family is compact, that is, the fractal dimension d f is equal to 2 for all members of the PF family, which are enumerated by an odd integer b, 3≤b<∞. Varying values of the stiffness parameter s of trails from 1 to 0 (so that when s decreases the trail stiffness increases) we calculate exactly (for 3 ≤ b ≤ 7) and through the MCRG approach (for b ≤ 201) the sets of the critical exponents ν (associated with the mean squared end-to-end distances of SATs) and γ (associated with the total number of different SATs). Our results show that critical exponents are stiffness dependent functions, so that ν(s) is a monotonically decreasing function of s, for each studied b, whereas γ(s) displays a non-monotonic behavior for some values of b. On the other hand, by fixing the stiffness parameter s, our results show clearly that for highly flexible trails (with s = 1 and 0.9) ν is a non-monotonic function of b, while for stiffer SATs (with s ≤ 0.7) ν monotonically decreases with b. We also show that γ(b) increases with increasing b, independently of s. Finally, we compare the obtained SAT data with those obtained for the semiflexible self-avoiding walk (SAW) model on the same fractal family, and for both models we discuss behavior of the studied exponents in the fractal-to-Euclidean crossover region b→∞

Expression and significance of TRAIL and NF-kB in osteosarcoma

International Nuclear Information System (INIS)

Du Xiumin; You Murong; Qi Falian; Hu Chengjin

2005-01-01

To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

Municipal investment in off-road trails and changes in bicycle commuting in Minneapolis, Minnesota over 10 years: a longitudinal repeated cross-sectional study.

Science.gov (United States)

Hirsch, Jana A; Meyer, Katie A; Peterson, Marc; Zhang, Le; Rodriguez, Daniel A; Gordon-Larsen, Penny

2017-02-13

We studied the effect of key development and expansion of an off-road multipurpose trail system in Minneapolis, Minnesota between 2000 and 2007 to understand whether infrastructure investments are associated with increases in commuting by bicycle. We used repeated measures regression on tract-level (N = 116 tracts) data to examine changes in bicycle commuting between 2000 and 2008-2012. We investigated: 1) trail proximity measured as distance from the trail system and 2) trail potential use measured as the proportion of commuting trips to destinations that might traverse the trail system. All analyses (performed 2015-2016) adjusted for tract-level sociodemographic covariates and contemporaneous cycling infrastructure changes (e.g., bicycle lanes). Tracts that were both closer to the new trail system and had a higher proportion of trips to destinations across the trail system experienced greater 10-year increases in commuting by bicycle. Proximity to off-road infrastructure and travel patterns are relevant to increased bicycle commuting, an important contributor to overall physical activity. Municipal investment in bicycle facilities, especially off-road trails that connect a city's population and its employment centers, is likely to lead to increases in commuting by bicycle.

36 CFR 212.55 - Criteria for designation of roads, trails, and areas.

Science.gov (United States)

2010-07-01

... roads, trails, and areas. 212.55 Section 212.55 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.55 Criteria for designation of roads, trails, and areas. (a) General criteria for designation of...

Model predictive control of trailing edge flaps on a wind turbine blade

Energy Technology Data Exchange (ETDEWEB)

Castaignet, D.B.

2011-11-15

Trailing edge flaps on wind turbine blades have been investigated for several years. Aero-servoelastic simulations carried out with different simulation tools, trailing edge flaps configurations and controller designs proved that trailing edge flaps are a suitable solution for reducing some of the wind turbine fatigue and extreme loads. This potential was confirmed with wind tunnel tests made on blade sections with trailing edge flaps and on a scaled two-bladed wind turbine in a wind tunnel. The work presented in this thesis includes a full-scale test run on a Vestas V27 wind turbine equipped with three trailing edge flaps on one blade, located on DTU's Risoe Campus in Roskilde, Denmark. This thesis is divided into three parts: the controller design, results from simulations, and results from the experiments. The trailing edge flaps controller designed for this project is based on a frequency-weighted model predictive control, tuned in order to target only the flapwise blade root loads at the frequencies contributing the most to blade root fatigue damage (the 1P, 2P and 3P frequencies), and to avoid unnecessary wear and tear of the actuators at high frequencies. A disturbance model consisting in periodic disturbances at the rotor speed harmonic frequencies and a quasi-steady input disturbance is aggregated to an analytical model of a spinning blade with trailing edge flaps. Simulations on a multi-megawatt wind turbine show the potential of the trailing edge flaps to reduce the flapwise blade root fatigue loads by 23%, but also the main shaft and the tower fatigue loads by up to 32%. Extreme loads during normal production also benefit from the trailing edge flaps. At last, the same controller was run on the Vestas V27 wind turbine located at the Risoe Campus of the Technical University of Denmark, in Roskilde, Denmark. One blade of the turbine was equipped with three independent trailing edge flaps. In spite of the failure of several sensors and actuators, the

Path Tortuosity and the Permeability of Roads and Trails to Wolf Movement

Directory of Open Access Journals (Sweden)

Jesse Whittington

2004-06-01

Full Text Available Few studies have examined the effects of human development on fine-scale movement behavior, yet understanding animal movement through increasingly human-dominated landscapes is essential for the persistence of many wild populations, especially wary species. In mountainous areas, roads and trails may be particularly deserving of study because they are concentrated in the valley bottoms where they can impede animal movement both across and between valleys. In this study, we tracked wolf (Canis lupus movement in the snow for two winters in Jasper National Park, Alberta, Canada to examine how wolves navigate through or around human-use features. We quantified the effects of human development and topography on the tortuosity of wolf paths and then tested the permeability of roads, trails, and a railway line to wolf movement by comparing the frequency with which actual wolf paths and a null model of random paths crossed these features. Wolf path tortuosity increased near high-use trails, within areas of high-trail and road density, near predation sites, and in rugged terrain. Wolves crossed all roads, trails, and the railway line 9.7% less often than expected, but avoided crossing high-use roads more than low-use trails. Surprisingly, trails affected movement behavior of wolves equally, if not more, than roads. These results suggest that although roads and trails in this study were not absolute barriers to wolf movement, they altered wolf movements across their territories.

Tarague Interpretive Trail Mitigation Plan

National Research Council Canada - National Science Library

Welch, David

2001-01-01

...), International Archaeological Research Institute, Inc. (lARfI) has prepared a mitigation plan for development of an interpretive trail at Tarague Beach, located on the north coast of the island of Guam (Fig. 1...

Differences in the impacts of formal and informal recreational trails on urban forest loss and tree structure.

Science.gov (United States)

Ballantyne, Mark; Pickering, Catherine Marina

2015-08-15

Recreational trails are one of the most common types of infrastructure used for nature-based activities such as hiking and mountain biking worldwide. Depending on their design, location, construction, maintenance and use, these trails differ in their environmental impacts. There are few studies, however, comparing the impacts of different trail types including between formal management-created trails and informal visitor-created trails. Although both types of trails can be found in remote natural areas, dense networks of them often occur in forests close to cities where they experience intense visitor use. To assess the relative impacts of different recreational trails in urban forests, we compared the condition of the trail surface, loss of forest strata and changes in tree structure caused by seven types of trails (total network 46.1 km) traversing 17 remnants of an endangered urban forest in Australia. After mapping and classifying all trails, we assessed their impact on the forest condition at 125 sites (15 sites per trail type, plus 15 control sites within undisturbed forest). On the trail sites, the condition of the trail surface, distance from the trail edge to four forest strata (litter, understory, midstorey and tree cover) and structure of the tree-line were assessed. Informal trails generally had poorer surface conditions and were poorly-designed and located. Per site, formal and informal trails resulted in similar loss of forest strata, with wider trails resulting in greater loss of forest. Because there were more informal trails, however, they accounted for the greatest cumulative forest loss. Structural impacts varied, with the widest informal trails and all formal hardened trails resulting in similar reductions in canopy cover and tree density but an increase in saplings. These structural impacts are likely a function of the unregulated and intense use of large informal trails, and disturbance from the construction and maintenance of formal trails

Combinatorial treatment with anacardic acid followed by TRAIL augments induction of apoptosis in TRAIL resistant cancer cells by the regulation of p53, MAPK and NFκβ pathways.

Science.gov (United States)

Harsha Raj, M; Yashaswini, B; Rössler, Jochen; Salimath, Bharathi P

2016-05-01

TRAIL, an apoptosis inducing cytokine currently in phase II clinical trial, was investigated for its capability to induce apoptosis in six different human tumor cell lines out of which three cell lines showed resistance to TRAIL induced apoptosis. To investigate whether Anacardic acid (A1) an active component of Anacardium occidentale can sensitize the resistant cell lines to TRAIL induced apoptosis, we treated the resistant cells with suboptimal concentration of A1 and showed that it is a potent enhancer of TRAIL induced apoptosis which up-regulates the expression of both DR4 and DR5 receptors, which has been observed in the cellular, protein and mRNA levels. The death receptors upregulation consequent to A1 treatment was corroborated by the activation of p53 as well as phosphorylation of p38 and JNK MAP kinases and concomitant inactivation of NFκβ and ERK signaling cascades. Also, A1 modulated the expression of key apoptotic players like Bax, Bcl-2 and CAD along with the abatement of tumor angiogenesis in vivo in EAT mouse model. Thus, post A1 treatment the TRAIL resistant cells turned into TRAIL sensitive cells. Hence our results demonstrate that A1 can synergize TRAIL induced apoptosis through the upregulation of death receptors and downregulation of anti-apoptotic proteins in cancer context.

Universality of collapsing two-dimensional self-avoiding trails

International Nuclear Information System (INIS)

Foster, D P

2009-01-01

Results of a numerically exact transfer matrix calculation for the model of interacting self-avoiding trails are presented. The results lead to the conclusion that at the collapse transition, self-avoiding trails are in the same universality class as the O(n = 0) model of Bloete and Nienhuis (or vertex-interacting self-avoiding walk), which has thermal exponent ν = 12/23, contrary to previous conjectures. (fast track communication)

The influence of use-related, environmental, and managerial factors on soil loss from recreational trails

Science.gov (United States)

Olive, Nathaniel D.; Marion, Jeffrey L.

2009-01-01

Recreational uses of unsurfaced trails inevitably result in their degradation, with the type and extent of resource impact influenced by factors such as soil texture, topography, climate, trail design and maintenance, and type and amount of use. Of particular concern, the loss of soil through erosion is generally considered a significant and irreversible form of trail impact. This research investigated the influence of several use-related, environmental, and managerial factors on soil loss on recreational trails and roads at Big South Fork National River and Recreation Area, a unit of the U.S. National Park Service. Regression modeling revealed that trail position, trail slope alignment angle, grade, water drainage, and type of use are significant determinants of soil loss. The introduction of individual and groups of variables into a series of regression models provides improved understanding and insights regarding the relative influence of these variables, informing the selection of more effective trail management actions. Study results suggest that trail erosion can be minimized by avoiding “fall-line” alignments, steep grades, and valley-bottom alignments near streams, installing and maintaining adequate densities of tread drainage features, applying gravel to harden treads, and reducing horse and all-terrain vehicle use or restricting them to more resistant routes.This research also sought to develop a more efficient Variable Cross-Sectional Area method for assessing soil loss on trails. This method permitted incorporation of CSA measures in a representative sampling scheme applied to a large (24%) sample of the park's 526 km trail system. The variety of soil loss measures derived from the Variable CSA method, including extrapolated trail-wide soil loss estimates, permit an objective quantification of soil erosion on recreational trails and roads. Such data support relational analyses to increase understanding of trail degradation, and long

The influence of use-related, environmental, and managerial factors on soil loss from recreational trails.

Science.gov (United States)

Olive, Nathaniel D; Marion, Jeffrey L

2009-03-01

Recreational uses of unsurfaced trails inevitably result in their degradation, with the type and extent of resource impact influenced by factors such as soil texture, topography, climate, trail design and maintenance, and type and amount of use. Of particular concern, the loss of soil through erosion is generally considered a significant and irreversible form of trail impact. This research investigated the influence of several use-related, environmental, and managerial factors on soil loss on recreational trails and roads at Big South Fork National River and Recreation Area, a unit of the U.S. National Park Service. Regression modeling revealed that trail position, trail slope alignment angle, grade, water drainage, and type of use are significant determinants of soil loss. The introduction of individual and groups of variables into a series of regression models provides improved understanding and insights regarding the relative influence of these variables, informing the selection of more effective trail management actions. Study results suggest that trail erosion can be minimized by avoiding "fall-line" alignments, steep grades, and valley-bottom alignments near streams, installing and maintaining adequate densities of tread drainage features, applying gravel to harden treads, and reducing horse and all-terrain vehicle use or restricting them to more resistant routes. This research also sought to develop a more efficient Variable Cross-Sectional Area method for assessing soil loss on trails. This method permitted incorporation of CSA measures in a representative sampling scheme applied to a large (24%) sample of the park's 526 km trail system. The variety of soil loss measures derived from the Variable CSA method, including extrapolated trail-wide soil loss estimates, permit an objective quantification of soil erosion on recreational trails and roads. Such data support relational analyses to increase understanding of trail degradation, and long-term monitoring of

CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

Science.gov (United States)

Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

2018-02-23

Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

Recreational trails as corridors for alien plants in the Rocky Mountains, USA

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Wells, Floye H.; Lauenroth, William K.; Bradford, John B.

2012-01-01

Alien plant species often use areas of heavy human activity for habitat and dispersal. Roads and utility corridors have been shown to harbor more alien species than the surrounding vegetation and are therefore believed to contribute to alien plant persistence and spread. Recreational trails represent another corridor that could harbor alien species and aid their spread. Effective management of invasive species requires understanding how alien plants are distributed at trailheads and trails and how their dispersal may be influenced by native vegetation. Our overall goal was to investigate the distribution of alien plants at trailheads and trails in the Rocky Mountains of Colorado. At trailheads, we found that although the number of alien species was less than the number of native species, alien plant cover ( x̄=50%) did not differ from native plant cover, and we observed a large number of alien seedlings in the soil seed bank, suggesting that alien plants are a large component of trailhead communities and will continue to be so in the future. Along trails, we found higher alien species richness and cover on trail (as opposed to 4 m from the trail) in 3 out of 4 vegetation types, and we observed higher alien richness and cover in meadows than in other vegetation types. Plant communities at both trailheads and trails, as well as seed banks at trailheads, contain substantial diversity and abundance of alien plants. These results suggest that recreational trails in the Rocky Mountains of Colorado may function as corridors that facilitate the spread of alien species into wildlands. Our results suggest that control of alien plants should begin at trailheads where there are large numbers of aliens and that control efforts on trails should be prioritized by vegetation type.

Effect of a serrated trailing edge on sound radiation from nearby quadrupoles.

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Karimi, Mahmoud; Croaker, Paul; Kinns, Roger; Kessissoglou, Nicole

2017-05-01

A periodic boundary element technique is implemented to study the noise reduction capability of a plate with a serrated trailing edge under quadrupole excitation. It is assumed for this purpose that the quadrupole source tensor is independent of the trailing edge configuration and that the effect of the trailing edge shape is to modify sound radiation from prescribed boundary layer sources. The flat plate is modelled as a continuous structure with a finite repetition of small spanwise segments. The matrix equation formulated by the periodic boundary element method for this 3D acoustic scattering problem is represented as a block Toeplitz matrix. The discrete Fourier transform is employed in an iterative algorithm to solve the block Toeplitz system. The noise reduction mechanism for a serrated trailing edge in the near field is investigated by comparing contour plots obtained from each component of the quadrupole for unserrated and serrated trailing edge plate models. The noise reduction due to the serrated trailing edge is also examined as a function of the source location.

Estimating Soil Displacement from Timber Extraction Trails in Steep Terrain: Application of an Unmanned Aircraft for 3D Modelling

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Marek Pierzchała

2014-06-01

Full Text Available Skid trails constructed for timber extraction in steep terrain constitute a serious environmental concern if not well planned, executed and ameliorated. Carrying out post-harvest surveys in monitoring constructed trails in such terrain is an onerous task for forest administrators, as hundreds of meters need to be surveyed per site, and the quantification of parameters and volumes is largely based on assumptions of trail symmetry and terrain uniformity. In this study, aerial imagery captured from a multi-rotor Unmanned Aerial Vehicle was used in generating a detailed post-harvest terrain model which included all skid trails. This was then compared with an Airborne Laser Scanning derived pre-harvest terrain model and the dimensions, slopes and cut-and-fill volumes associated with the skid trails were determined. The overall skid trail length was 954 m, or 381 m·ha−1 with segments varying from 40–60 m, inclinations from 3.9% to 9.6%, and cut volumes, from 1.7 to 3.7 m3 per running meter. The methods used in this work can be used in rapidly assessing the extent of disturbance and erosion risk on a wide range of sites. The multi-rotor Unmanned Aerial Vehicle (UAV was found to be highly suited to the task, given the relatively small size of harvested stands, their shape and their location in the mountainous terrain.

Photography of a lithium vapor trail during the daytime.

Science.gov (United States)

Bedinger, J. F.

1973-01-01

Barium and lithium vapors were released from sounding rockets in the thermosphere and observed from aboard a jet aircraft at an altitude of 40,000 ft. The purpose of the releases was to demonstrate the feasibility of an all-weather technique for observing chemical releases and to evaluate methods of observing daytime releases. The selected flight plan of the aircraft allowed a series of observations of the trail from two different straight line paths. Data were recorded photographically. The reduction in sky brightness at the 40,000-ft altitude as compared to the ground allows the use of a filter with a 10-A bandwidth for trail photography in the daytime. These photographs verified the calculation of the usable angular field of the narrow-band filters. Photographs of a 45-min-old trail of lithium vapor were obtained up to 20 min after sunrise at the aircraft. It is concluded that now vapor trail observations may be made during the daytime without regard to weather and logistic restrictions.

Novel targets for sensitizing breast cancer cells to TRAIL-induced apoptosis with siRNA delivery.

Science.gov (United States)

Thapa, Bindu; Bahadur Kc, Remant; Uludağ, Hasan

2018-02-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in variety of cancer cells without affecting most normal cells, which makes it a promising agent for cancer therapy. However, TRAIL therapy is clinically not effective due to resistance induction. To identify novel regulators of TRAIL that can aid in therapy, protein targets whose silencing sensitized breast cancer cells against TRAIL were screened with an siRNA library against 446 human apoptosis-related proteins in MDA-231 cells. Using a cationic lipopolymer (PEI-αLA) for delivery of library members, 16 siRNAs were identified that sensitized the TRAIL-induced death in MDA-231 cells. The siRNAs targeting BCL2L12 and SOD1 were further evaluated based on the novelty and their ability to sensitize TRAIL induced cell death. Silencing both targets sensitized TRAIL-mediated cell death in MDA-231 cells as well as TRAIL resistant breast cancer cells, MCF-7. Combination of TRAIL and siRNA silencing BCL2L12 had no effect in normal human umbilical vein cells and human bone marrow stromal cell. The silencing of BCL2L12 and SOD1 enhanced TRAIL-mediated apoptosis in MDA-231 cells via synergistically activating capsase-3 activity. Hence, here we report siRNAs targeting BCL2L12 and SOD1 as a novel regulator of TRAIL-induced cell death in breast cancer cells, providing a new approach for enhancing TRAIL therapy for breast cancer. The combination of siRNA targeting BCL2L12 and TRAIL can be a highly effective synergistic pair in breast cancer cells with minimal effect on the non-transformed cells. © 2017 UICC.

Aerodynamic behavior of an airfoil with morphing trailing edge for wind turbine applications

Science.gov (United States)

Wolff, T.; Ernst, B.; Seume, J. R.

2014-06-01

The length of wind turbine rotor blades has been increased during the last decades. Higher stresses arise especially at the blade root because of the longer lever arm. One way to reduce unsteady blade-root stresses caused by turbulence, gusts, or wind shear is to actively control the lift in the blade tip region. One promising method involves airfoils with morphing trailing edges to control the lift and consequently the loads acting on the blade. In the present study, the steady and unsteady behavior of an airfoil with a morphing trailing edge is investigated. Two-dimensional Reynolds-Averaged Navier-Stokes (RANS) simulations are performed for a typical thin wind turbine airfoil with a morphing trailing edge. Steady-state simulations are used to design optimal geometry, size, and deflection angles of the morphing trailing edge. The resulting steady aerodynamic coefficients are then analyzed at different angles of attack in order to determine the effectiveness of the morphing trailing edge. In order to investigate the unsteady aerodynamic behavior of the optimal morphing trailing edge, time- resolved RANS-simulations are performed using a deformable grid. In order to analyze the phase shift between the variable trailing edge deflection and the dynamic lift coefficient, the trailing edge is deflected at four different reduced frequencies for each different angle of attack. As expected, a phase shift between the deflection and the lift occurs. While deflecting the trailing edge at angles of attack near stall, additionally an overshoot above and beyond the steady lift coefficient is observed and evaluated.

Aerodynamic behavior of an airfoil with morphing trailing edge for wind turbine applications

International Nuclear Information System (INIS)

Wolff, T; Ernst, B; Seume, J R

2014-01-01

The length of wind turbine rotor blades has been increased during the last decades. Higher stresses arise especially at the blade root because of the longer lever arm. One way to reduce unsteady blade-root stresses caused by turbulence, gusts, or wind shear is to actively control the lift in the blade tip region. One promising method involves airfoils with morphing trailing edges to control the lift and consequently the loads acting on the blade. In the present study, the steady and unsteady behavior of an airfoil with a morphing trailing edge is investigated. Two-dimensional Reynolds-Averaged Navier-Stokes (RANS) simulations are performed for a typical thin wind turbine airfoil with a morphing trailing edge. Steady-state simulations are used to design optimal geometry, size, and deflection angles of the morphing trailing edge. The resulting steady aerodynamic coefficients are then analyzed at different angles of attack in order to determine the effectiveness of the morphing trailing edge. In order to investigate the unsteady aerodynamic behavior of the optimal morphing trailing edge, time- resolved RANS-simulations are performed using a deformable grid. In order to analyze the phase shift between the variable trailing edge deflection and the dynamic lift coefficient, the trailing edge is deflected at four different reduced frequencies for each different angle of attack. As expected, a phase shift between the deflection and the lift occurs. While deflecting the trailing edge at angles of attack near stall, additionally an overshoot above and beyond the steady lift coefficient is observed and evaluated

Geomorphological hazard and tourist vulnerability along Portofino Park trails (Italy)

Science.gov (United States)

Brandolini, P.; Faccini, F.; Piccazzo, M.

2006-06-01

The many trails existing in the coastal area of Portofino Promontory are used by tourists for trekking or as pathways to small villages and beaches. The aim of this paper is to define geomorphological hazard and tourist vulnerability in this area, within the framework of the management and planning of hiking activities in Portofino Natural Park. In particular, processes triggered by gravity, running waters and wave motion, affecting the slopes and the cliff, are considered. The typology of the trails and trail maintenance are also taken into account in relation to weather conditions that can make the excursion routes dangerous for tourists. In conclusion, an operative model is applied for the definition of possible risk scenarios. This model is founded on an inventory and the quantification of geomorphological hazards and tourist vulnerability, in comparison with trail rescue data. The model can be applied to other environments and tourist areas.

Gefitinib upregulates death receptor 5 expression to mediate rmhTRAIL-induced apoptosis in Gefitinib-sensitive NSCLC cell line

Directory of Open Access Journals (Sweden)

Yan D

2015-07-01

synergistically interact to inhibit cell proliferation, and apoptosis assessment demonstrated that associations of drug increased the apoptotic index. rmhTRAIL when used alone downregulated DR5 and upregulated BAX, FLIP, and cleaved-caspase3 proteins expressions. However, results obtained in Western blot analyses demonstrated that the combined treatment-induced cell apoptosis was achieved involving upregulated DR5, cleaved-caspase3, and BAX proteins expression and downregulated FLIP protein expression. Moreover, quantitative polymerase chain reaction showed that gefitinib modulated the expression of targets related to rmhTRAIL activity.Conclusion: These results indicate that epidermal growth factor receptor inhibitors enhance rmhTRAIL antitumor activity in the gefitinib-responsive PC9 cell line, and upregulated DR5 expression plays a critical role in activating caspase-signaling apoptotic pathway.Keywords: gefitinib, rmhTRAIL, apoptosis, DR5

Vortex coupling in trailing vortex-wing interactions

Science.gov (United States)

Chen, C.; Wang, Z.; Gursul, I.

2018-03-01

The interaction of trailing vortices of an upstream wing with rigid and flexible downstream wings has been investigated experimentally in a wind tunnel, using particle image velocimetry, hot-wire, force, and deformation measurements. Counter-rotating upstream vortices exhibit increased meandering when they are close to the tip of the downstream wing. The upstream vortex forms a pair with the vortex shed from the downstream wing and then exhibits large displacements around the wing tip. This coupled motion of the pair has been found to cause large lift fluctuations on the downstream wing. The meandering of the vortex pair occurs at the natural meandering frequency of the isolated vortex, with a low Strouhal number, and is not affected by the frequency of the large-amplitude wing oscillations if the downstream wing is flexible. The displacement of the leading vortex is larger than that of the trailing vortex; however, it causes highly correlated variations of the core radius, core vorticity, and circulation of the trailing vortex with the coupled meandering motion. In contrast, co-rotating vortices do not exhibit any increased meandering.

Errors on the Trail Making Test Are Associated with Right Hemispheric Frontal Lobe Damage in Stroke Patients

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Bruno Kopp

2015-01-01

Full Text Available Measures of performance on the Trail Making Test (TMT are among the most popular neuropsychological assessment techniques. Completion time on TMT-A is considered to provide a measure of processing speed, whereas completion time on TMT-B is considered to constitute a behavioral measure of the ability to shift between cognitive sets (cognitive flexibility, commonly attributed to the frontal lobes. However, empirical evidence linking performance on the TMT-B to localized frontal lesions is mostly lacking. Here, we examined the association of frontal lesions following stroke with TMT-B performance measures (i.e., completion time and completion accuracy measures using voxel-based lesion-behavior mapping, with a focus on right hemispheric frontal lobe lesions. Our results suggest that the number of errors, but not completion time on the TMT-B, is associated with right hemispheric frontal lesions. This finding contradicts common clinical practice—the use of completion time on the TMT-B to measure cognitive flexibility, and it underscores the need for additional research on the association between cognitive flexibility and the frontal lobes. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether our observation is specific for right frontal lesions.

Tracking Online Trails

Science.gov (United States)

Qi, Man; Edgar-Nevill, Denis; Wang, Yongquan; Xu, Rongsheng

Traceability is a key to the investigation of the internet criminal and a cornerstone of internet research. It is impossible to prevent all internet misuse but may be possible to identify and trace the users, and then take appropriate action. This paper presents the value of traceability within the email/-newsposting utilities, the technologies being using to hide identities, the difficulties in locating the traceable data and the challenges in tracking online trails.

Dynamics of foraging trails in the Neotropical termite Velocitermes heteropterus (Isoptera: Termitidae).

Science.gov (United States)

Haifig, Ives; Jost, Christian; Fourcassié, Vincent; Zana, Yossi; Costa-Leonardo, Ana Maria

2015-09-01

Foraging behavior in termites varies with the feeding habits of each species but often occurs through the formation of well-defined trails that connect the nest to food sources in species that build structured nests. We studied the formation of foraging trails and the change in caste ratio during foraging in the termite Velocitermes heteropterus. This species is widespread in Cerrado vegetation where it builds epigeal nests and forages in open-air at night. Our aim was to understand the processes involved in the formation of foraging trails, from the exploration of new unmarked areas to the recruitment of individuals to food and the stabilization of traffic on the trails, as well as the participation of the different castes during these processes. Foraging trails were videotaped in the laboratory and the videos were then analyzed both manually and automatically to assess the flow of individuals and the caste ratio on the trails as well as to examine the spatial organization of traffic over time. Foraging trails were composed of minor workers, major workers, and soldiers. The flow of individuals on the trails gradually increased from the beginning of the exploration of new areas up to the discovery of the food. The caste ratio remained constant throughout the foraging excursion: major workers, minor workers and soldiers forage in a ratio of 8:1:1, respectively. The speed of individuals was significantly different among castes, with major workers and soldiers being significantly faster than minor workers. Overall, our results show that foraging excursions in V. heteropterus may be divided in three different phases, characterized by individual speeds, differential flows and lane segregation. Copyright © 2015 Elsevier B.V. All rights reserved.

Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression

International Nuclear Information System (INIS)

Ivanov, Vladimir N.; Partridge, Michael A.; Johnson, Geoffrey E.; Huang, Sarah X.L.; Zhou, Hongning; Hei, Tom K.

2008-01-01

Although many human melanomas express the death receptors TRAIL-R2/DR5 or TRAIL-R1/DR4 on cell surface, they often exhibit resistance to exogenous TRAIL. One of the main contributors to TRAIL-resistance of melanoma cells is upregulation of transcription factors STAT3 and NF-κB that control the expression of antiapoptotic genes, including cFLIP and Bcl-xL. On the other hand, the JNK-cJun pathway is involved in the negative regulation of cFLIP (a caspase-8 inhibitor) expression. Our observations indicated that resveratrol, a polyphenolic phytoalexin, decreased STAT3 and NF-κB activation, while activating JNK-cJun that finally suppressed expression of cFLIP and Bcl-xL proteins and increased sensitivity to exogenous TRAIL in DR5-positive melanomas. Interestingly, resveratrol did not increase surface expression of DR5 in human melanomas, while γ-irradiation or sodium arsenite treatment substantially upregulated DR5 expression. Hence, an initial increase in DR5 surface expression (either by γ-irradiation or arsenite), and subsequent downregulation of antiapoptotic cFLIP and Bcl-xL (by resveratrol), appear to constitute an efficient approach to reactivate apoptotic death pathways in TRAIL-resistant human melanomas. In spite of partial suppression of mitochondrial function and the mitochondrial death pathway, melanoma cells still retain the potential to undergo the DR5-mediated, caspase-8-dependent death pathway that could be accelerated by either an increase in DR5 surface expression or suppression of cFLIP. Taken together, these results suggest that resveratrol, in combination with TRAIL, may have a significant efficacy in the treatment of human melanomas

Pupil initiatives in urban nature trail development: PMB MOSS and ...

African Journals Online (AJOL)

A brief background to Greenbelt and urban nature trail development in Pietermaritzburg is provided. Negotiations and procedures initiated by standard 9 pupils in stimulating authorities and the public to recognise the need for urban trail development and metropolitan open space (MOSS) are outlined. long-term ...

77 FR 32178 - Notification of Trails Act Agreement/Substitute Sponsorship

Science.gov (United States)

2012-05-31

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [STB Ex Parte No. 702] Notification of Trails Act Agreement/Substitute Sponsorship AGENCY: Surface Transportation Board. ACTION: Notice of OMB... Trails System Act and Railroad Rights-of-Way, STB Ex Parte No. 702 (STB served Apr. 30, 2012) (77 FR...

Students’ Use of Knowledge Resources in Environmental Interaction on an Outdoor Learning Trail

NARCIS (Netherlands)

Tan, Esther; So, Hyo-Jeong

2016-01-01

This study examined how students leveraged different types of knowledge resources on an outdoor learning trail. We positioned the learning trail as an integral part of the curriculum with a pre- and post-trail phase to scaffold and to support students’ meaning-making process. The study was conducted

Numerical analysis of the impact of permeability on trailing-edge noise

Science.gov (United States)

Koh, Seong Ryong; Meinke, Matthias; Schröder, Wolfgang

2018-05-01

The impact of porous surfaces on the near-wall turbulent structures and the generated trailing-edge noise is analyzed for several trailing-edge shapes of finite thickness using a high resolution large-eddy simulation (LES)/computational aeroacoustics (CAA) method. The porous surface of the trailing edge is defined by the porosity and the viscous permeability determined by the solution of a turbulent flat plate boundary layer at a Reynolds number 1280 based on the displacement thickness in the inflow cross section. The volume-averaged approach for the homogeneous porous medium shows that the porous impedance scales linearly with the porosity and exponentially with the mean structure size of a porous medium. The drag induced by the porous surface changes the friction velocity and the permeability Reynolds number ReK which determines the porous impedance Rs scaled by ReK-2/3. The trailing-edge noise is analyzed for three solid and three porous trailing edges. The effect of a finite span is investigated by the spanwise correlation model based on the measured coherence distribution. The acoustic prediction shows a good agreement with measurements of the broadband spectrum and the strong tone generated by a finite trailing-edge thickness. The pressure gradient inside the porous media is redistributed by the Darcy drag defined by the viscous permeability and the porosity. The mean pressure increases in the upstream direction inside the porous medium such that the flow acceleration involved in the acoustic generation is reduced inside the porous medium. The noise reduction by a porous medium reaches 11 dB for the trailing-edge shape which possesses a sharp corner for the solid surface. The porous surface applied to a semi-circular trailing edge achieves a 4 dB noise reduction. The directivity pattern for individual components of the acoustic spectrum shows that the massive noise reduction is determined at the tone. Enhanced wave diffraction by the thick flat plate changes

Geomorphological hazard and tourist vulnerability along Portofino Park trails (Italy

Directory of Open Access Journals (Sweden)

P. Brandolini

2006-01-01

Full Text Available The many trails existing in the coastal area of Portofino Promontory are used by tourists for trekking or as pathways to small villages and beaches. The aim of this paper is to define geomorphological hazard and tourist vulnerability in this area, within the framework of the management and planning of hiking activities in Portofino Natural Park. In particular, processes triggered by gravity, running waters and wave motion, affecting the slopes and the cliff, are considered. The typology of the trails and trail maintenance are also taken into account in relation to weather conditions that can make the excursion routes dangerous for tourists. In conclusion, an operative model is applied for the definition of possible risk scenarios. This model is founded on an inventory and the quantification of geomorphological hazards and tourist vulnerability, in comparison with trail rescue data. The model can be applied to other environments and tourist areas.

Doxorubicin potentiates TRAIL cytotoxicity and apoptosis and can overcome TRAIL-resistance in rhabdomyosarcoma cells

NARCIS (Netherlands)

Komdeur, R; Meijer, C; Van Zweeden, M; De Jong, S; Wesseling, J; Hoekstra, HJ; van der Graaf, WTA

Doxorubicin (DOX) and ifosfamide (IFO) are the most active single agents in soft tissue sarcomas (STS). Tumour necrosis factor-alpha (TNF-alpha) is used for STS in the setting of isolated limb perfusions. Like TNF-alpha, TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis. In contrast to

TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages

International Nuclear Information System (INIS)

Yuan, Bao-Zhu; Chapman, Joshua; Ding, Min; Wang, Junzhi; Jiang, Binghua; Rojanasakul, Yon; Reynolds, Steven H

2013-01-01

Malignant pleural mesothelioma (MPM) is an aggressive malignancy closely associated with asbestos exposure and extremely resistant to current treatments. It exhibits a steady increase in incidence, thus necessitating an urgent development of effective new treatments. Proteasome inhibitors (PIs) and TNFα-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents. To develop effective new treatments, the proapoptotic effects of PIs, MG132 or Bortezomib, and TRAIL were investigated in MPM cell lines NCI-H2052, NCI-H2452 and NCI-H28, which represent three major histological types of human MPM. Treatment with 0.5-1 μM MG132 alone or 30 ng/mL Bortezomib alone induced a limited apoptosis in MPM cells associated with the elevated Mcl-1 protein level and hyperactive PI3K/Akt signaling. However, whereas 10–20 ng/ml TRAIL alone induced a limited apoptosis as well, TRAIL and PI combination triggered a robust apoptosis in all three MPM cell lines. The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells. The combinatorial treatment using TRAIL and PI may represent an effective new treatment for MPMs

Trail communication regulated by two trail pheromone components in the fungus-growing termite Odontotermes formosanus (Shiraki).

Science.gov (United States)

Wen, Ping; Ji, Bao-Zhong; Sillam-Dussès, David

2014-01-01

The eusocial termites are well accomplished in chemical communication, but how they achieve the communication using trace amount of no more than two pheromone components is mostly unknown. In this study, the foraging process and trail pheromones of the fungus-growing termite Odontotermes formosanus (Shiraki) were systematically studied and monitored in real-time using a combination of techniques, including video analysis, solid-phase microextraction, gas chromatography coupled with either mass spectrometry or an electroantennographic detector, and bioassays. The trail pheromone components in foraging workers were (3Z)-dodec-3-en-1-ol and (3Z,6Z)-dodeca-3,6-dien-1-ol secreted by their sternal glands. Interestingly, ratio of the two components changed according to the behaviors that the termites were displaying. This situation only occurs in termites whereas ratios of pheromone components are fixed and species-specific for other insect cuticular glands. Moreover, in bioassays, the active thresholds of the two components ranged from 1 fg/cm to 10 pg/cm according to the behavioral contexts or the pheromonal exposure of tested workers. The two components did not act in synergy. (3Z)-Dodec-3-en-1-ol induced orientation behavior of termites that explore their environment, whereas (3Z,6Z)-dodeca-3,6-dien-1-ol had both an orientation effect and a recruitment effect when food was discovered. The trail pheromone of O. formosanus was regulated both quantitatively by the increasing number of workers involved in the early phases of foraging process, and qualitatively by the change in ratio of the two pheromone components on sternal glandular cuticle in the food-collecting workers. In bioassays, the responses of workers to the pheromone were also affected by the variation in pheromone concentration and component ratio in the microenvironment. Thus, this termite could exchange more information with nestmates using the traces of the two trail pheromone components that can be easily

Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL but not its receptors during oral cancer progression

Directory of Open Access Journals (Sweden)

Muller Susan

2007-06-01

Full Text Available Abstract Background TRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell-death-inducing (DR4 and DR5 and two decoy (DcR1, and DcR2 receptors. Here, we compare the expression levels of TRAIL and its receptors in normal oral mucosa (NOM, oral premalignancies (OPM, and primary and metastatic oral squamous cell carcinomas (OSCC in order to characterize the changes in their expression patterns during OSCC initiation and progression. Methods DNA microarray, immunoblotting and immunohistochemical analyses were used to examine the expression levels of TRAIL and its receptors in oral epithelial cell lines and in archival tissues of NOM, OPM, primary and metastatic OSCC. Apoptotic rates of tumor cells and tumor-infiltrating lymphocytes (TIL in OSCC specimens were determined by cleaved caspase 3 immunohistochemistry. Results Normal oral epithelia constitutively expressed TRAIL, but expression was progressively lost in OPM and OSCC. Reduction in DcR2 expression levels was noted frequently in OPM and OSCC compared to respective patient-matched uninvolved oral mucosa. OSCC frequently expressed DR4, DR5 and DcR1 but less frequently DcR2. Expression levels of DR4, DR5 and DcR1 receptors were not significantly altered in OPM, primary OSCC and metastatic OSCC compared to patient-matched normal oral mucosa. Expression of proapoptotic TRAIL-receptors DR4 and DR5 in OSCC seemed to depend, at least in part, on whether or not these receptors were expressed in their parental oral epithelia. High DR5 expression in primary OSCC correlated significantly with larger tumor size. There was no significant association between TRAIL-R expression and OSSC histology grade, nodal status or apoptosis rates of tumor cells and TIL. Conclusion Loss of TRAIL expression is an early event during oral

Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not its receptors during oral cancer progression

International Nuclear Information System (INIS)

Vigneswaran, Nadarajah; Baucum, Darryl C; Wu, Jean; Lou, Yahuan; Bouquot, Jerry; Muller, Susan; Zacharias, Wolfgang

2007-01-01

TRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell-death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Here, we compare the expression levels of TRAIL and its receptors in normal oral mucosa (NOM), oral premalignancies (OPM), and primary and metastatic oral squamous cell carcinomas (OSCC) in order to characterize the changes in their expression patterns during OSCC initiation and progression. DNA microarray, immunoblotting and immunohistochemical analyses were used to examine the expression levels of TRAIL and its receptors in oral epithelial cell lines and in archival tissues of NOM, OPM, primary and metastatic OSCC. Apoptotic rates of tumor cells and tumor-infiltrating lymphocytes (TIL) in OSCC specimens were determined by cleaved caspase 3 immunohistochemistry. Normal oral epithelia constitutively expressed TRAIL, but expression was progressively lost in OPM and OSCC. Reduction in DcR2 expression levels was noted frequently in OPM and OSCC compared to respective patient-matched uninvolved oral mucosa. OSCC frequently expressed DR4, DR5 and DcR1 but less frequently DcR2. Expression levels of DR4, DR5 and DcR1 receptors were not significantly altered in OPM, primary OSCC and metastatic OSCC compared to patient-matched normal oral mucosa. Expression of proapoptotic TRAIL-receptors DR4 and DR5 in OSCC seemed to depend, at least in part, on whether or not these receptors were expressed in their parental oral epithelia. High DR5 expression in primary OSCC correlated significantly with larger tumor size. There was no significant association between TRAIL-R expression and OSSC histology grade, nodal status or apoptosis rates of tumor cells and TIL. Loss of TRAIL expression is an early event during oral carcinogenesis and may be involved in dysregulation of apoptosis and

Analysis of the impact of recreational trail usage for prioritising management decisions: a regression tree approach

Science.gov (United States)

Tomczyk, Aleksandra; Ewertowski, Marek; White, Piran; Kasprzak, Leszek

2016-04-01

The dual role of many Protected Natural Areas in providing benefits for both conservation and recreation poses challenges for management. Although recreation-based damage to ecosystems can occur very quickly, restoration can take many years. The protection of conservation interests at the same as providing for recreation requires decisions to be made about how to prioritise and direct management actions. Trails are commonly used to divert visitors from the most important areas of a site, but high visitor pressure can lead to increases in trail width and a concomitant increase in soil erosion. Here we use detailed field data on condition of recreational trails in Gorce National Park, Poland, as the basis for a regression tree analysis to determine the factors influencing trail deterioration, and link specific trail impacts with environmental, use related and managerial factors. We distinguished 12 types of trails, characterised by four levels of degradation: (1) trails with an acceptable level of degradation; (2) threatened trails; (3) damaged trails; and (4) heavily damaged trails. Damaged trails were the most vulnerable of all trails and should be prioritised for appropriate conservation and restoration. We also proposed five types of monitoring of recreational trail conditions: (1) rapid inventory of negative impacts; (2) monitoring visitor numbers and variation in type of use; (3) change-oriented monitoring focusing on sections of trail which were subjected to changes in type or level of use or subjected to extreme weather events; (4) monitoring of dynamics of trail conditions; and (5) full assessment of trail conditions, to be carried out every 10-15 years. The application of the proposed framework can enhance the ability of Park managers to prioritise their trail management activities, enhancing trail conditions and visitor safety, while minimising adverse impacts on the conservation value of the ecosystem. A.M.T. was supported by the Polish Ministry of

Minnesota State Park Trails and Roads

Data.gov (United States)

Minnesota Department of Natural Resources — This shapefile covers the trails in the State of Minnesota Parks, Recreation Areas, and Waysides as designated through legislation and recognized by the Department...

Model predictive control of trailing edge flaps on a wind turbine blade

DEFF Research Database (Denmark)

Castaignet, Damien Bruno

of the wind turbine fatigue and extreme loads. This potential was confirmed with wind tunnel tests made on blade sections with trailing edge flaps and on a scaled two-bladed wind turbine in a wind tunnel. The work presented in this thesis includes a full-scale test run on a Vestas V27 wind turbine equipped...... fatigue loads by 23%, but also the main shaft and the tower fatigue loads by up to 32%. Extreme loads during normal production also benefit from the trailing edge flaps. At last, the same controller was run on the Vestas V27 wind turbine located at the Risø Campus of the Technical University of Denmark......Trailing edge flaps on wind turbine blades have been investigated for several years. Aero-servoelastic simulations carried out with different simulation tools, trailing edge flaps configurations and controller designs proved that trailing edge flaps are a suitable solution for reducing some...

VT Green Mountain National Forest - Trails

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) GMNFTRAILS contains minor Forest Service roads and all trails within the proclamation boundary of the Green Mountain National Forest and many of...

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

International Nuclear Information System (INIS)

Levina, Vera; Marrangoni, Adele M.; DeMarco, Richard; Gorelik, Elieser; Lokshin, Anna E.

2008-01-01

TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines. TRAIL at low concentrations preferentially induced cell proliferation. At 100 ng/ml, apoptotic death was readily observed, however surviving cells acquired higher proliferative capacity. TRAIL-stimulated production of several cytokines, IL-8, RANTES, MCP-1 and bFGF, and activation of caspases 1 and 8 was essential for this effect. Antibodies to IL-8, RANTES, and bFGF blocked TRAIL-induced cell proliferation and further stimulated apoptosis. For the first time, we report that high TRAIL concentrations induced cell senescence as determined by the altered morphology and expression of several senescence markers: SA-β-gal, p21 Waf1/Cip1 , p16 INK4a , and HMGA. Caspase 9 inhibition protected TRAIL-treated cells from senescence, whereas inhibition of caspases 1 and 8 increased the yield of SLP cells. In conclusion, in cultured human carcinoma cells, TRAIL therapy results in three functional outcomes, apoptosis, proliferation and senescence. TRAIL-induced proapoptotic and prosurvival responses correlate with the strength of signaling. TRAIL-induced cytokine production is responsible for its proliferative and prosurvival effects

COLLISIONLESS ELECTRON–ION SHOCKS IN RELATIVISTIC UNMAGNETIZED JET–AMBIENT INTERACTIONS: NON-THERMAL ELECTRON INJECTION BY DOUBLE LAYER

International Nuclear Information System (INIS)

Ardaneh, Kazem; Cai, Dongsheng; Nishikawa, Ken-Ichi

2016-01-01

The course of non-thermal electron ejection in relativistic unmagnetized electron–ion shocks is investigated by performing self-consistent particle-in-cell simulations. The shocks are excited through the injection of a relativistic jet into ambient plasma, leading to two distinct shocks (referred to as the trailing shock and leading shock) and a contact discontinuity. The Weibel-like instabilities heat the electrons up to approximately half of the ion kinetic energy. The double layers formed in the trailing and leading edges then accelerate the electrons up to the ion kinetic energy. The electron distribution function in the leading edge shows a clear, non-thermal power-law tail which contains ∼1% of electrons and ∼8% of the electron energy. Its power-law index is −2.6. The acceleration efficiency is ∼23% by number and ∼50% by energy, and the power-law index is −1.8 for the electron distribution function in the trailing edge. The effect of the dimensionality is examined by comparing the results of three-dimensional simulations with those of two-dimensional simulations. The comparison demonstrates that electron acceleration is more efficient in two dimensions.

Effect of Wavy Trailing Edge on 100meter Flatback Wind Turbine Blade

International Nuclear Information System (INIS)

Yang, SJ; Baeder, J D

2016-01-01

The flatback trailing edge design for modern 100meter wind turbine blade has been developed and proposed to make wind turbine blade to be slender and lighter. On the other hand, it will increase aerodynamic drag; consequently the increased drag diminishes turbine power generation. Thus, an aerodynamic drag reducing technique should be accompanied with the flatback trailing edge in order to prevent loss of turbine power generation. In this work, a drag mitigation design, span-wise wavy trailing edge blade, has been applied to a modern 100meter blade. The span-wise trailing edge acts as a vortex generator, and breaks up the strong span-wise coherent trailing edge vortex structure at the flatback airfoil trailing edge which is a major source of large drag. Three-dimensional unsteady Computational Fluid Dynamics (CFD) simulations have been performed for real scale wind turbine blade geometries. Delayed Detached Eddy Simulation (DDES) with the modified laminar-turbulent transition model has been applied to obtain accurate flow field predictions. Graphical Processor Unit (GPU)-accelerated computation has been conducted to reduce computational costs of the real scale wind turbine blade simulations. To verify the structural reliability of the wavy modification of the blade a simple Eigen buckling analysis has been performed in the current study. (paper)

The impacts of trail infrastructure on vegetation and soils: Current literature and future directions.

Science.gov (United States)

Ballantyne, Mark; Pickering, Catherine Marina

2015-12-01

Reflecting the popularity of nature-based activities such as hiking and mountain biking, there are thousands of kilometres of recreational trails worldwide traversing a range of natural areas. These trails have environmental impacts on soils and vegetation, but where has there been research, what impacts have been found and how were they measured? Using a systematic quantitative literature review methodology, we assessed the impacts of trails on vegetation and soils, highlighting what is known, but also key knowledge gaps. Of the 59 original research papers identified on this topic that have been published in English language peer-reviewed academic journals, most were for research conducted in protected areas (71%), with few from developing countries (17%) or threatened ecosystems (14%). The research is concentrated in a few habitats and biodiversity hotspots, mainly temperate woodland, alpine grassland and Mediterranean habitats, often in the USA (32%) or Australia (20%). Most examined formal trails, with just 15% examining informal trails and 11% assessing both types. Nearly all papers report the results of observational surveys (90%), collecting quantitative data (66%) with 24% using geographic information systems. There was an emphasis on assessing trail impacts at a local scale, either on the trail itself and/or over short gradients away from the trail edge. Many assessed changes in composition and to some degree, structure, of vegetation and soils with the most common impacts documented including reduced vegetation cover, changes in plant species composition, trail widening, soil loss and soil compaction. There were 14 papers assessing how these local impacts can accumulate at the landscape scale. Few papers assessed differences in impacts among trails (7 papers), changes in impacts over time (4), species-specific responses (3) and only one assessed effects on plant community functioning. This review provides evidence that there are key research gaps

Validation of Walking Trails for the Urban TrainingTM of Chronic Obstructive Pulmonary Disease Patients

Science.gov (United States)

Arbillaga-Etxarri, Ane; Torrent-Pallicer, Jaume; Gimeno-Santos, Elena; Barberan-Garcia, Anael; Delgado, Anna; Balcells, Eva; Rodríguez, Diego A.; Vilaró, Jordi; Vall-Casas, Pere; Irurtia, Alfredo; Rodriguez-Roisin, Robert; Garcia-Aymerich, Judith

2016-01-01

Purpose Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed. We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park). We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults. Methods On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces. We measured physiological response and energy expenditure using a gas analyzer. We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression. Results In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V˙O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trendtrails, respectively. In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces. Conclusions We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space. Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community. PMID:26766184

Discussion on "The Trail" from the Perspective of Christianism Theology

Science.gov (United States)

Wang, Jing

2008-01-01

Kafka is a writer of strong religious complex. In "The Trail," he illustrates his religious thoughts by probing into the alienation of modern human beings from the God and also shows his pursuit and befuddlement of beliefs. This paper analyzes the crimes and punishment in "The Trail" through three parts, the accusation of…

Comprehensive Trail Making Test Performance in Children and Adolescents with Traumatic Brain Injury

Science.gov (United States)

Allen, Daniel N.; Thaler, Nicholas S.; Ringdahl, Erik N.; Barney, Sally J.; Mayfield, Joan

2012-01-01

The sensitivity of the Trail Making Test to brain damage has been well-established over many years, making it one of the most commonly used tests in clinical neuropsychological evaluations. The current study examined the validity of scores from a newer version of the Trail Making Test, the Comprehensive Trail Making Test (CTMT), in children and…

MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1

Directory of Open Access Journals (Sweden)

Lin Fan

2017-04-01

Full Text Available Aim: Osteosarcoma (OS is an aggressive bone malignancy that affects rapidly growing bones and is associated with a poor prognosis. Our previous study showed that cytochrome c1 (CYC1, a subunit of the cytochrome bc1 complex (complex III of the mitochondrial electron chain, is overexpressed in human OS tissues and cell lines and its silencing induces apoptosis in vitro and inhibits tumor growth in vivo. Here, we investigated the mechanism underlying the modulation of CYC1 expression in OS and its role in the resistance of OS to apoptosis. Methods: qRT-PCR, luciferase reporter assay, western blotting, fow cytometry, and animal experiments were performed in this study. Results: MicroRNA (miR-661 was identified as a downregulated miRNA in OS tissues and cells and shown to directly target CYC1. Ectopically expressed miR-661 inhibited OS cell growth, promoted apoptosis, and reduced the activity of mitochondrial complex III. miR-661 overexpression enhanced TRAIL or STS induced apoptosis and promoted the release of cytochrome c into the cytosol, which induced caspase-9 activation, and these effects were abolished by a caspase-3 inhibitor. Overexpression of CYC1 rescued the effects of miR-661 on sensitizing OS cells to TRAIL or STS induced apoptosis, indicating that the antitumor effect of miR-661 is mediated by the downregulation of CYC1. In vivo, miR-661 overexpression sensitized tumors to TRAIL or STS induced apoptosis in a xenograft mouse model, and these effects were attenuated by co-expression of CYC1. Conclusion: Taken together, our results indicate that miR-661 plays a tumor suppressor role in OS mediated by the downregulation of CYC1, suggesting a potential mechanism underlying cell death resistance in OS.

Reusable Reinforcement Learning via Shallow Trails.

Science.gov (United States)

Yu, Yang; Chen, Shi-Yong; Da, Qing; Zhou, Zhi-Hua

2018-06-01

Reinforcement learning has shown great success in helping learning agents accomplish tasks autonomously from environment interactions. Meanwhile in many real-world applications, an agent needs to accomplish not only a fixed task but also a range of tasks. For this goal, an agent can learn a metapolicy over a set of training tasks that are drawn from an underlying distribution. By maximizing the total reward summed over all the training tasks, the metapolicy can then be reused in accomplishing test tasks from the same distribution. However, in practice, we face two major obstacles to train and reuse metapolicies well. First, how to identify tasks that are unrelated or even opposite with each other, in order to avoid their mutual interference in the training. Second, how to characterize task features, according to which a metapolicy can be reused. In this paper, we propose the MetA-Policy LEarning (MAPLE) approach that overcomes the two difficulties by introducing the shallow trail. It probes a task by running a roughly trained policy. Using the rewards of the shallow trail, MAPLE automatically groups similar tasks. Moreover, when the task parameters are unknown, the rewards of the shallow trail also serve as task features. Empirical studies on several controlling tasks verify that MAPLE can train metapolicies well and receives high reward on test tasks.

77 FR 1723 - Notice of Availability, Potomac Heritage National Scenic Trail

Science.gov (United States)

2012-01-11

... Availability of a ``Foundation for Planning, Administration, Management and Interpretation of Potomac Heritage... the availability of a ``Foundation for Planning, Administration, Management and Interpretation of... planned Trail segments for non-motorized travel. Communities have invested in the Trail concept for a...

Improvement of airfoil trailing edge bluntness noise model

DEFF Research Database (Denmark)

Zhu, Wei Jun; Shen, Wen Zhong; Sørensen, Jens Nørkær

2016-01-01

In this article, airfoil trailing edge bluntness noise is investigated using both computational aero-acoustic and semi-empirical approach. For engineering purposes, one of the most commonly used prediction tools for trailing edge noise are based on semi-empirical approaches, for example, the Brooks......, Pope, and Marcolini airfoil noise prediction model developed by Brooks, Pope, and Marcolini (NASA Reference Publication 1218, 1989). It was found in previous study that the Brooks, Pope, and Marcolini model tends to over-predict noise at high frequencies. Furthermore, it was observed...

TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

International Nuclear Information System (INIS)

Voigt, Susann; Kalthoff, Holger; Adam, Dieter; Philipp, Stephan; Davarnia, Parvin; Winoto-Morbach, Supandi; Röder, Christian; Arenz, Christoph; Trauzold, Anna; Kabelitz, Dieter; Schütze, Stefan

2014-01-01

The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of tumor cells, and that this treatment may

30 CFR 77.601 - Trailing cables or portable cables; temporary splices.

Science.gov (United States)

2010-07-01

... LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Trailing Cables § 77.601 Trailing cables or portable cables; temporary... or splices that heat or spark under load shall not be used. ...

76 FR 35468 - Star-Spangled Banner National Historic Trail Advisory Council

Science.gov (United States)

2011-06-17

... DEPARTMENT OF THE INTERIOR National Park Service Star-Spangled Banner National Historic Trail... the Advisory Committee on the Star-Spangled Banner National Historic Trail will hold a meeting... Council is John Maounis, Superintendent, Chesapeake Bay Office, telephone: (410) 260-2471. DATES: The Star...

Modulation of TRAIL resistance in colon carcinoma cells : Different contributions of DR4 and DR5

NARCIS (Netherlands)

van Geelen, Caroline M. M.; Pennarun, Bodvael; Le, Phuong T. K.; de Vries, Elisabeth G. E.; de Jong, Steven

2011-01-01

Background: rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells

International Nuclear Information System (INIS)

Marrero, María Teresa; Estévez, Sara; Negrín, Gledy; Quintana, José; López, Mariana; Pérez, Francisco J.; Triana, Jorge; León, Francisco; Estévez, Francisco

2012-01-01

Highlights: ► Ayanin diacetate as apoptotic inducer in leukemia cells. ► Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x L . ► The intrinsic and the extrinsic pathways are involved in the mechanism of action. ► Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G 2 -M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x L . Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

Influence of Cattle Trails on Runoff Quantity and Quality.

Science.gov (United States)

Miller, Jim J; Curtis, Tony; Chanasyk, David S; Willms, Walter D

2017-03-01

Cattle trails in grazed pastures close to rivers may adversely affect surface water quality of the adjacent river by directing runoff to it. The objective of this 3-yr study (2013-2015) in southern Alberta, Canada, was to determine if cattle trails significantly increased the risk of runoff and contaminants (sediment, nutrients) compared with the adjacent grazed pasture (control). A portable rainfall simulator was used to generate artificial rainfall (140 mm h) and runoff. The runoff properties measured were time to runoff and initial abstraction (infiltration), total runoff depth and average runoff rates, as well as concentrations and mass loads of sediment, N, and P fractions. Cattle trails significantly ( ≤ 0.10) decreased time to runoff and initial abstraction (26-32%) in the 2 yr measured and increased total runoff depth, runoff coefficients, and average runoff rates (21-51%) in 2 of 3 yr. Concentrations of sediment, N, and P fractions in runoff were not significantly greater for cattle trails than for control areas. However, mass loads of total suspended solids (57-85% increase), NH-N (31-90%), and dissolved reactive P (DRP) (30-92%) were significantly greater because of increased runoff volumes. Overall, runoff quantity and loads of sediment, NH-N, and DRP were greater for cattle trails compared with the adjacent grazed pasture, and hydrologic connection with cattle-access sites on the riverbank suggests that this could adversely affect water quality in the adjacent river. Extrapolation of the study results should be tempered by the specific conditions represented by this rainfall simulation study. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Effects of the built environment on childhood obesity: the case of urban recreational trails and crime.

Science.gov (United States)

Sandy, Robert; Tchernis, Rusty; Wilson, Jeffrey; Liu, Gilbert; Zhou, Xilin

2013-01-01

We study the effects of urban environment on childhood obesity by concentrating on the effects of walking trails and crime close to children's homes on their BMI and obesity status. We use a unique dataset, which combines information on recreational trails in Indianapolis with data on violent crimes and anthropomorphic and diagnostic data from children's clinic visits between 1996 and 2005. We find that having a trail near a home reduces children's weight. However, the effect depends on the amount of nearby violent crimes. Significant reductions occur only in low crime areas and trails could have opposite effects on weight in high crime areas. These effects are primarily among boys, older children, and children who live in higher income neighborhoods. Evaluated at the mean length of trails this effect for older children in no crime areas would be a reduction of 2 lb of the body weight. Falsification tests using planned trails instead of existing trails, show that trails are more likely to be located in areas with heavier children, suggesting that our results on effects of trails represent a lower bound. Published by Elsevier B.V.

Audit Trail Management System in Community Health Care Information Network.

Science.gov (United States)

Nakamura, Naoki; Nakayama, Masaharu; Nakaya, Jun; Tominaga, Teiji; Suganuma, Takuo; Shiratori, Norio

2015-01-01

After the Great East Japan Earthquake we constructed a community health care information network system. Focusing on the authentication server and portal server capable of SAML&ID-WSF, we proposed an audit trail management system to look over audit events in a comprehensive manner. Through implementation and experimentation, we verified the effectiveness of our proposed audit trail management system.

Skipping on uneven ground: trailing leg adjustments simplify control and enhance robustness.

Science.gov (United States)

Müller, Roy; Andrada, Emanuel

2018-01-01

It is known that humans intentionally choose skipping in special situations, e.g. when descending stairs or when moving in environments with lower gravity than on Earth. Although those situations involve uneven locomotion, the dynamics of human skipping on uneven ground have not yet been addressed. To find the reasons that may motivate this gait, we combined experimental data on humans with numerical simulations on a bipedal spring-loaded inverted pendulum model (BSLIP). To drive the model, the following parameters were estimated from nine subjects skipping across a single drop in ground level: leg lengths at touchdown, leg stiffness of both legs, aperture angle between legs, trailing leg angle at touchdown (leg landing first after flight phase), and trailing leg retraction speed. We found that leg adjustments in humans occur mostly in the trailing leg (low to moderate leg retraction during swing phase, reduced trailing leg stiffness, and flatter trailing leg angle at lowered touchdown). When transferring these leg adjustments to the BSLIP model, the capacity of the model to cope with sudden-drop perturbations increased.

Use Deflected Trailing Edge to Improve the Aerodynamic Performance and Develop Low Solidity LPT Cascade

Science.gov (United States)

Chao, Li; Peigang, Yan; Xiangfeng, Wang; Wanjin, Han; Qingchao, Wang

2017-08-01

This paper investigates the feasibility of improving the aerodynamic performance of low pressure turbine (LPT) blade cascades and developing low solidity LPT blade cascades through deflected trailing edge. A deflected trailing edge improved aerodynamic performance of both LPT blade cascades and low solidity LPT blade cascades. For standard solidity LPT cascades, deflecting the trailing edge can decrease the energy loss coefficient by 20.61 % for a Reynolds number (Re) of 25,000 and freestream turbulence intensities (FSTI) of 1 %. For a low solidity LPT cascade, aerodynamic performance was also improved by deflecting the trailing edge. Solidity of the LPT cascade can be reduced by 12.5 % for blades with a deflected trailing edge without a drop in efficiency. Here, the flow control mechanism surrounding a deflected trailing edge was also revealed.

Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

Science.gov (United States)

Bolkun, Lukasz; Lemancewicz, Dorota; Piszcz, Jaroslaw; Moniuszko, Marcin; Bolkun-Skornicka, Urszula; Szkiladz, Malgorzata; Jablonska, Ewa; Kloczko, Janusz; Dzieciol, Janusz

2015-12-01

Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.

Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells.

Science.gov (United States)

Ouyang, Wen; Yang, Chunxu; Zhang, Simin; Liu, Yu; Yang, Bo; Zhang, Junhong; Zhou, Fuxiang; Zhou, Yunfeng; Xie, Conghua

2013-02-01

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a major limitation for its clinical use. The mechanisms of TRAIL resistance have been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that contribute to the development of acquired resistance during treatment with TRAIL. In this study, we established H460R, an isogenic cell line with acquired TRAIL resistance, from the TRAIL‑sensitive human lung cancer cell line H460 to investigate the mechanisms of acquired resistance. The acquired TRAIL‑resistant H460R cells remained sensitive to cisplatin. The mRNA and protein expression levels of death receptor 4 (DR4) and death receptor 5 (DR5) were not altered in either of the TRAIL-treated cell lines. Nevertheless, tests in which the DR4 or DR5 gene was overexpressed or silenced suggest that death receptor expression is necessary but not sufficient for TRAIL‑induced apoptosis. Compared with parental TRAIL-sensitive H460 cells, H460R cells showed a decreased TRAIL-induced translocation of DR4/DR5 into lipid rafts. Further studies showed that nystatin partially prevented lipid raft aggregation and DR4 and DR5 clustering and reduced apoptosis in H460 cells again. Analysis of apoptotic molecules showed that more pro-caspase-8, FADD, caspase-3 and Bid, but less cFLIP in H460 cells than in H460R cells. Our findings suggest that the lack of death receptor redistribution negatively impacts DISC assembly in lipid rafts, which at least partially leads to the development of acquired resistance to TRAIL in H460R cells.

A novel combination of TRAIL and doxorubicin enhances antitumor effect based on passive tumor-targeting of liposomes

International Nuclear Information System (INIS)

Guo Liangran; Fan Li; Ren Jinfeng; Pang Zhiqing; Ren Yulong; Li Jingwei; Jiang Xinguo; Wen Ziyi

2011-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel anticancer agent for non-small cell lung cancer (NSCLC). However, approximately half of NSCLC cell lines are highly resistant to TRAIL. Doxorubicin (DOX) can sensitize NSCLC cells to TRAIL-induced apoptosis, indicating the possibility of combination therapy. Unfortunately, the therapeutic effect of a DOX and TRAIL combination is limited by multiple factors including the short serum half-life of TRAIL, poor compliance and application difficulty in the clinic, chronic DOX-induced cardiac toxicity, and the multidrug resistance (MDR) property of NSCLC cells. To solve such problems, we developed the combination of TRAIL liposomes (TRAIL-LP) and DOX liposomes (DOX-LP). An in vitro cytotoxicity study indicated that DOX-LP sensitized the NSCLC cell line A-549 to TRAIL-LP-induced apoptosis. Furthermore, this combination therapy of TRAIL-LP and DOX-LP displayed a stronger antitumor effect on NSCLC in xenografted mice when compared with free drugs or liposomal drugs alone. Therefore, the TRAIL-LP and DOX-LP combination therapy has excellent potential to become a new therapeutic approach for patients with advanced NSCLC.

Elastically Deformable Side-Edge Link for Trailing-Edge Flap Aeroacoustic Noise Reduction

Science.gov (United States)

Khorrami, Mehdi R. (Inventor); Lockard, David P. (Inventor); Moore, James B. (Inventor); Su, Ji (Inventor); Turner, Travis L. (Inventor); Lin, John C. (Inventor); Taminger, Karen M. (Inventor); Kahng, Seun K. (Inventor); Verden, Scott A. (Inventor)

2014-01-01

A system is provided for reducing aeroacoustic noise generated by an aircraft having wings equipped with trailing-edge flaps. The system includes a plurality of elastically deformable structures. Each structure is coupled to and along one of the side edges of one of the trailing-edge flaps, and is coupled to a portion of one of the wings that is adjacent to the one of the side edges. The structures elastically deform when the trailing-edge flaps are deployed away from the wings.

Runoff and sediment yield from rural roads, trails and settlements in the upper Konto catchment, East Java, Indonesia

Science.gov (United States)

Rijsdijk, Anton; Sampurno Bruijnzeel, L. A.; Sutoto, C. Kukuh

2007-06-01

The potential importance of roads and settlements for the generation of storm runoff and sediment in tropical steeplands is increasingly recognised but rarely quantified. This paper presents runoff and sediment yield data for a cobbled and an unpaved road section, two large unbounded settlement plots, and several trails draining residential areas or terraced fields in a volcanic upland catchment in East Java. In addition, the sediment yield of major landslides associated with roads was quantified. The unpaved road section exhibited an average runoff coefficient of about 65% and yielded about 7 kg m - 2 yr - 1 of sediment. Both the runoff coefficient and the sediment yield for the cobbled road section (plus adjacent yards) were lower (38% and 1.9 kg m - 2 yr - 1 ). Sediment output from a 4160-m 2 hillside plot including a network of trails draining terraced fields (for which runoff and sediment outputs were shown to be negligible) was similar to that for the cobbled road (2-3 kg m - 2 yr - 1 depending on rainfall). However, a much higher value was obtained when the overall soil loss from the plot was expressed per square metre of trail surface area (ca. 42 kg m - 2 yr - 1 ) whereas the associated trail runoff coefficient was about 70%. The results obtained for several trails and large unbounded plots draining residential areas at two locations were less extreme (runoff coefficients of 24-43%; soil loss 1.3-3.5 kg m - 2 yr - 1 ). Landsliding occurred mainly at the end of the rainy season (March) and was estimated to have contributed ca. 2365 m 3 of sediment to the main road network during the 1988/89 wet season vs. ca. 905 m 3 in 1989/90 and only ca. 150 m 3 in 2000/01. It is concluded that, despite their relatively small areal extent (5% in the study area), rural roads, trails and settlements are significant producers of runoff and sediment at the catchment scale and should be included in watershed management programmes designed to reduce catchment sediment yields

Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer.

Science.gov (United States)

Min, Sun Young; Byeon, Hyeong Jun; Lee, Changkyu; Seo, Jisoo; Lee, Eun Seong; Shin, Beom Soo; Choi, Han-Gon; Lee, Kang Choon; Youn, Yu Seok

2015-10-15

Nanoparticle albumin-bound (nab™) technology is an effective way of delivering hydrophobic chemotherapeutics. We developed a one-pot/one-step formulation of paclitaxel (PTX)-bound albumin nanoparticles with embedded tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/PTX HSA-NP) for the treatment of pancreatic cancer. TRAIL/PTX HSA-NPs were fabricated using a high-pressure homogenizer at a TRAIL feeding ratio of 0.2%, 1.0%, and 2.0%. TRAIL/PTX HSA-NPs were spherical and became larger in size (170-230 nm) with increasing TRAIL amount (0.2-2.0%). The loading efficiencies of PTX were in the range of ∼86.4% and significantly low at 2.0% TRAIL (60.4%). Specifically, the inhibitory concentrations (IC50) of TRAIL (1.0 or 2.0%)/PTX HSA-NPs were >20-fold lower than that of plain PTX-HSA NP (0.032±0.06, 0.022±0.005, and 0.96±0.15 ng/ml, respectively) in pancreatic Mia Paca-2 cells. Considering TRAIL loading, bioactivity, and particle size, TRAIL(1.0%)/PTX HSA-NPs were determined as the optimal candidate for further studies. TRAIL(1.0%)/PTX HSA-NPs displayed substantially greater apoptotic activity than plain PTX HSA-NP in both FACS and TUNEL analysis. The loaded PTX and TRAIL were gradually released from the TRAIL(1.0%)/PTX HSA-NPs until ∼24 h, which is considered to be a sufficient time for delivery to the tumor tissue. TRAIL(1.0%)/PTX HSA-NP displayed markedly more antitumor efficacy than plain PTX HSA-NP in Mia Paca-2 cell-xenografted mice in terms of tumor volume (size) and weight (213.9 mm(3) and 0.18 g vs. 1126.8 mm(3) and 0.80 g, respectively). These improved in vitro and in vivo performances were due to the combined synergistic effects of PTX and TRAIL. We believe that this TRAIL/PTX HSA-NP would have potential as a novel apoptosis-based anticancer agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Fascaplysin sensitizes cells to TRAIL-induced apoptosis through upregulating DR5 expression

Science.gov (United States)

Wang, Feng; Chen, Haimin; Yan, Xiaojun; Zheng, Yanling

2013-05-01

This study investigated the molecular mechanism of anti-tumor effect of fascaplysin, a nitrogenous red pigment firstly isolated from a marine sponge. Microarray analysis show that the TNF and TNF receptor superfamily in human umbilical vein endothelial cells (HUVEC) and human hepatocarcinoma cells (BEL-7402) were significantly regulated by fascaplysin. Western Blot results reveal that fascaplysin increased the expression of cleaved caspase-9, active caspase-3, and decreased the level of procaspase-8 and Bid. Flow cytometry and cytotoxicity tests indicate that fascaplysin sensitized cells to tumor necrosis-related apoptosisinducing ligand-(TRAIL) induced apoptosis, which was markedly blocked by TRAIL R2/Fc chimera, a dominant negative form of TRAIL receptor DR5. Therefore, our results demonstrate that fascaplysin promotes apoptosis through the activation of TRAIL signaling pathway by upregulating DR5 expression.

A chimeric antigen receptor for TRAIL-receptor 1 induces apoptosis in various types of tumor cells.

Science.gov (United States)

Kobayashi, Eiji; Kishi, Hiroyuki; Ozawa, Tatsuhiko; Hamana, Hiroshi; Nakagawa, Hidetoshi; Jin, Aishun; Lin, Zhezhu; Muraguchi, Atsushi

2014-10-31

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its associated receptors (TRAIL-R/TR) are attractive targets for cancer therapy because TRAIL induces apoptosis in tumor cells through TR while having little cytotoxicity on normal cells. Therefore, many agonistic monoclonal antibodies (mAbs) specific for TR have been produced, and these induce apoptosis in multiple tumor cell types. However, some TR-expressing tumor cells are resistant to TR-specific mAb-induced apoptosis. In this study, we constructed a chimeric antigen receptor (CAR) of a TRAIL-receptor 1 (TR1)-specific single chain variable fragment (scFv) antibody (TR1-scFv-CAR) and expressed it on a Jurkat T cell line, the KHYG-1 NK cell line, and human peripheral blood lymphocytes (PBLs). We found that the TR1-scFv-CAR-expressing Jurkat cells killed target cells via TR1-mediated apoptosis, whereas TR1-scFv-CAR-expressing KHYG-1 cells and PBLs killed target cells not only via TR1-mediated apoptosis but also via CAR signal-induced cytolysis, resulting in cytotoxicity on a broader range if target cells than with TR1-scFv-CAR-expressing Jurkat cells. The results suggest that TR1-scFv-CAR could be a new candidate for cancer gene therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Frequency-Weighted Model Predictive Control of Trailing Edge Flaps on a Wind Turbine Blade

DEFF Research Database (Denmark)

Castaignet, Damien; Couchman, Ian; Poulsen, Niels Kjølstad

2013-01-01

flapwise blade root moment and trailing edge flap deflection. Frequency-weighted MPC is chosen for its ability to handle constraints on the trailing edge flaps deflection, and to target at loads with given frequencies only. The controller is first tested in servo-aeroelastic simulations, before being......This paper presents the load reduction achieved with trailing edge flaps during a full-scale test on a Vestas V27 wind turbine. The trailing edge flap controller is a frequency-weighted linear model predictive control (MPC) where the quadratic cost consists of costs on the zero-phase filtered...

Numerical Investigation of Flow Control Feasibility with a Trailing Edge Flap

International Nuclear Information System (INIS)

Zhu, W J; Shen, W Z; Sørensen, J N

2014-01-01

This paper concerns a numerical study of employing an adaptive trailing edge flap to control the lift of an airfoil subject to unsteady inflow conditions. The periodically varying inflow is generated by two oscillating airfoils, which are located upstream of the controlled airfoil. To establish the control system, a standard PID controller is implemented in a finite volume based incompressible flow solver. An immersed boundary method is applied to treat the problem of simulating a deformable airfoil trailing edge. The flow field is solved using a 2D Reynolds averaged Navier-Stokes finite volume solver. In order to more accurately simulate wall bounded flows around the immersed boundary, a modified boundary condition is introduced in the k- ω turbulence model. As an example, turbulent flow over a NACA 64418 airfoil with a deformable trailing edge is investigated. Results from numerical simulations are convincing and may give some highlights for practical implementations of trailing edge flap to a wind turbine rotor blade

Use and users of the Appalachian Trail: a geographic study

Science.gov (United States)

Robert E. Manning; William Valliere; Jim Bacon; Alan Graefe; Gerard Kyle; Rita Hennessy

2001-01-01

The Appalachian National Scenic Trail (AT) is a public footpath that spans 2,160 miles of Appalachian Mountain ridgelines from Maine to Georgia. This paper describes the first comprehensive study of recreational use and users of the AT. The primary study method was a survey of visitors to the AT. The Trail was divided into 22 relatively homogeneous sections within four...

Audit trails in an online accountability system

International Nuclear Information System (INIS)

Jamison, C.

1985-01-01

The Safeguards Accountability Network (SAN) is an online computer system that was developed by Rockwell International to track the accounting and processing of nuclear materials from the time it arrives at Rocky Flats Plant through its life cycle. A major contributor to the success of SAN is the use of audit trails. They have proven to be invaluable for the management and safeguarding of these sensitive materials at Rocky Flats. Producing effective audit trails requires the recording of all pertinent transactions and the capability to access and report the information in a timely fashion. This paper discusses the implementation and application of these audit trials on the Rocky Flats SAN system. 1 fig

Exploring visitor acceptability for hardening trails to sustain visitation and minimize impacts

Science.gov (United States)

Cahill, K.L.; Marion, J.L.; Lawson, S.R.

2008-01-01

Protected natural area managers are challenged to provide high quality recreation opportunities and ensure the protection of resources from impacts associated with visitation. Development of visitor use facilities and application of site hardening practices are commonly applied tools for achieving these competing management objectives. This study applies stated choice analysis to examine visitor opinions on acceptability when they are asked to make tradeoffs among competing social, resource and management attributes in backcountry and frontcountry settings of Acadia National Park. This study demonstrates that asking visitors about recreation setting attributes uni-dimensionally, a common approach, can yield less informative responses. Analyses that considered direct tradeoffs revealed more divergent opinions on acceptability for setting attributes than a unidimensional approach. Findings revealed that visitors to an accessible and popular attraction feature supported trail development options to protect resource conditions with unrestricted visitor access. In contrast, visitors to a remote undeveloped island expressed stronger support for no or limited trail development and access restrictions to protect resource conditions.

78 FR 76176 - Notice of Availability of the Record of Decision for the Final Trail Management Plan...

Science.gov (United States)

2013-12-16

... paddling; and improved parking facilities. Alternative 2A emphasized the importance of enhancing the... 1, the no-action alternative, the trails, authorized uses, and facilities addressed in this Plan/EIS... system, adoption of the Sustainable Trail Guidelines, and the consideration of trail facilities. Trail...

Carving a New Assessment Trail

Science.gov (United States)

Morriston, Terry

2007-01-01

TRAILS (Tool for Real-Time Assessment of Information Literacy Skills), is a free online test of student information-handling skills. It was formulated by the Institute for Library and Information Literacy Education and Kent State University Libraries. Based on the Ohio Academic Content Standards and the philosophy of Information Power, it assesses…

Impacts of informal trails on vegetation and soils in the highest protected area in the Southern Hemisphere.

Science.gov (United States)

Barros, Agustina; Gonnet, Jorge; Pickering, Catherine

2013-09-30

There is limited recreation ecology research in South America, especially studies looking at informal trails. Impacts of informal trails formed by hikers and pack animals on vegetation and soils were assessed for the highest protected area in the Southern Hemisphere, Aconcagua Provincial Park. The number of braided trails, their width and depth were surveyed at 30 sites along the main access route to Mt Aconcagua (6962 m a.s.l.). Species composition, richness and cover were also measured on control and trail transects. A total of 3.3 ha of alpine meadows and 13.4 ha of alpine steppe were disturbed by trails. Trails through meadows resulted in greater soil loss, more exposed soil and rock and less vegetation than trails through steppe vegetation. Trampling also affected the composition of meadow and steppe vegetation with declines in sedges, herbs, grasses and shrubs on trails. These results highlight how visitor use can result in substantial cumulative damage to areas of high conservation value in the Andes. With unregulated use of trails and increasing visitation, park agencies need to limit the further spread of informal trails and improve the conservation of plant communities in Aconcagua Provincial Park and other popular parks in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Managing outdoor recreation conflict on the Squamish, British Columbia Trail Network

Science.gov (United States)

Ana Elia Ramón Hidalgo; Howard. Harshaw

2012-01-01

Recreationists with high expectations of satisfaction from outdoor recreation activities are increasingly using trails networks near urban areas. But differences in expectations, behaviors and values of trail users may create conflicts resulting in unsatisfactory experiences. The objective of this study was to test the efficacy of management practices that may reduce...

Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction and antitumor therapy.

Science.gov (United States)

Wang, Junjian; Wang, Haibin; Wang, Ling-Yu; Cai, Demin; Duan, Zhijian; Zhang, Yanhong; Chen, Peng; Zou, June X; Xu, Jianzhen; Chen, Xinbin; Kung, Hsing-Jien; Chen, Hong-Wu

2016-11-01

Recombinant TRAIL and agonistic antibodies to death receptors (DRs) have been in clinical trial but displayed limited anti-cancer efficacy. Lack of functional DR expression in tumors is a major limiting factor. We report here that chromatin regulator KDM4A/JMJD2A, not KDM4B, has a pivotal role in silencing tumor cell expression of both TRAIL and its receptor DR5. In TRAIL-sensitive and -resistant cancer cells of lung, breast and prostate, KDM4A small-molecule inhibitor compound-4 (C-4) or gene silencing strongly induces TRAIL and DR5 expression, and causes TRAIL-dependent apoptotic cell death. KDM4A inhibition also strongly sensitizes cells to TRAIL. C-4 alone potently inhibits tumor growth with marked induction of TRAIL and DR5 expression in the treated tumors and effectively sensitizes them to the newly developed TRAIL-inducer ONC201. Mechanistically, C-4 does not appear to act through the Akt-ERK-FOXO3a pathway. Instead, it switches histone modifying enzyme complexes at promoters of TRAIL and DR5 transcriptional activator CHOP gene by dissociating KDM4A and nuclear receptor corepressor (NCoR)-HDAC complex and inducing the recruitment of histone acetylase CBP. Thus, our results reveal KDM4A as a key epigenetic silencer of TRAIL and DR5 in tumors and establish inhibitors of KDM4A as a novel strategy for effectively sensitizing tumors to TRAIL pathway-based therapeutics.

Construction and expression of secreting type human TRAIL gene vector mediated by hypoxia/radiation double sensitive promoter

International Nuclear Information System (INIS)

Yang Yanming; Jia Xiaojing; Qu Yaqin; Li Yanbo

2009-01-01

Objective: To construct secreting type human TRAIL (shTRAIL) gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter, and observe the effect of hypoxia and radiation on shTRAIL. Methods: HRE upper and lower strands were gotten by chemical synthesis, double strands HRE was gotten by PCR; pMD19T-Egr1 was digested by Sac I and Hind III, then Egr1 was obtained, pshuttle-shTRAIL was digested by Kpn I and BamH I, then shTRAIL was obtained; HRE/Egr1 double sensitive promoter mediated shTRAIL expression vector pcDNA3.1-HRE/Egr1-shTRAIL was constructed by gene recombination technique, it was identified correctly by enzyme digestion, PCR and sequencing. A549 cells were divided into normal, hypoxia (0.1%), irradiation (6 Gy) and hypoxia + irradiation groups. Results: After enzyme digestion by BamH I and Sma I, the fragments which lengths were 1284 bp and 4 998 bp, 2 292 bp and 3 990 bp were obtained; the vector was amplified by PCR with Egr1 and shTRAIL primer, the products which lengthens were 469 bp and 820 bp were obtained; pcDNA3.1-HRE/Egr1-shTRAIL was sequenced, the result was same to designed, this demonstrated that the construction was right. The vectors were transfected into A549 cells of adenocarcinoma of lung, the expression levels of shTRAIL mRNA and protein were increased after treated with hypoxia and radiation, it had statistically significant differences compared with normal group (P<0.05), and when they were combinated, the effect was more obvious. Conclusion: Secreting type human TRAIL gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter is constructed successfully, and hypoxia and radiation could increase the expression of TRAIL, and they have synergetic effect. (authors)

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

International Nuclear Information System (INIS)

Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

2007-01-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

Association between exposure to HSV1 and cognitive functioning in a general population of adolescents. The TRAILS study.

Directory of Open Access Journals (Sweden)

Iris Jonker

Full Text Available Infections with different herpes viruses have been associated with cognitive functioning in psychiatric patients and healthy adults. The aim of this study was to find out whether antibodies to different herpes viruses are prospectively associated with cognitive functioning in a general adolescent population.This study was performed in TRAILS, a large prospective general population cohort (N = 1084, 54% female, mean age 16.2 years (SD 0.6. At age 16, immunoglobulin G antibodies against HSV1, HSV2, CMV and EBV were measured next to high sensitive C-Reactive Protein (hsCRP. Two years later, immediate memory and executive functioning were assessed using the 15 words task and the self ordered pointing task. Multiple linear regression analysis with bootstrapping was performed to study the association between viral infections and cognitive function, adjusting for gender, socioeconomic status, ethnicity, and cannabis use.Presence of HSV1 antibodies was associated with memory function ((B = -0.272, 95% CI = -0.556 to -0.016, p = 0.047, while the association with executive functioning did not reach statistical significance (B = 0.560, 95% CI is -0.053 to 1.184, p = 0.075. The level of HSV1 antibodies was associated with both memory function (B = -0.160, 95% CI = -0.280 to -0.039, p = 0.014 and executive functioning (B = 0.296, 95% CI = 0.011 to 0.578, p = 0.046. Other herpes viruses and hsCRP were not associated with cognitive functioning.Both presence and level of HSV1 antibodies are prospectively associated with reduced cognitive performance in a large cohort of adolescents.

Construction and identification of double-gene co-expression vector with radiation-inducible human TRAIL and endostatin

International Nuclear Information System (INIS)

Li Yanbo; Guo Caixia; Gong Pingsheng; Liu Yang; Liangshuo; Wang Hongfang; Wang Jianfeng; Gong Shouliang

2010-01-01

Objective: To construct a recombinant plasmid pshuttle-Egr1-shTRAIL-shES containing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin double genes. Methods: The secretary endostatin gene (shES) fragment was amplified from the pMD19T-endostatin vector by PCR. The shES gene was ligated to pMD19Tand sequenced. Finally, using the gene recombinant technique, the recombinant plasmid pshuttle-Egr1- shTRAIL-shES with radiation-inducible Egr1 promoter, secretary TRAIL and endostatin double-gene was constructed. Results: The sequence of the shES gene was in concordance with that anticipated indicating shES gene was acquired successfully.Moreover, the results acquired by PCR and restrictive digestion identification of the recombinant plasmid pshuttle-Egr1-shTRAIL-shES and all the vectors refered to its construction confirmed that pshuttle-Egr1-shTRAIL-shES was constructed correctly. Conclusion: The radiation-inducible double-gene co-expression vector pshuttle-Egr1-shTRAIL-shES is constructed successfully, which would set the experimental foundation for further study on the anti-tumor effect of TRAIL and endostatin double-gene-radiotherapy and its related mechanisms. (authors)

CD25 targeted therapy of chemotherapy resistant leukemic stem cells using DR5 specific TRAIL peptide

Directory of Open Access Journals (Sweden)

Jayaprakasam Madhumathi

2017-03-01

Full Text Available Chemotherapy resistant leukemic stem cells (LSCs are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81.25% in AML and 100% in CML, ALL and CLL. IL2-TRAIL peptide showed cytotoxicity in relapsed patient samples and was more effective than TRAIL or IL2-TRAIL proteins. Additionally, DR5 specific IL2-TRAIL peptide was effective in targeting and killing LSCs purified from cell lines [IC50: 952 nM in HL60, 714 nM in MOLT4] and relapsed patient blood samples with higher efficacy (85% than IL2-TRAIL protein (46%. Hence, CD25 and DR5 specific targeting by IL2-TRAIL peptide may be an effective strategy for targeting drug resistant leukemic cells and LSCs.

Comparison of trailside degradation across a gradient of trail use in the Sonoran Desert.

Science.gov (United States)

Rowe, Helen Ivy; Tluczek, Melanie; Broatch, Jennifer; Gruber, Dan; Jones, Steve; Langenfeld, Debbie; McNamara, Peggy; Weinstein, Leona

2018-02-01

As recreational visitation to the Sonoran Desert increases, the concern of scientists, managers and advocates who manage its natural resources deepens. Although many studies have been conducted on trampling of undisturbed vegetation and the effects of trails on adjacent plant and soil communities, little such research has been conducted in the arid southwest. We sampled nine 450-m trail segments with different visitation levels in Scottsdale's McDowell Sonoran Preserve over three years to understand the effects of visitation on soil erosion, trailside soil crusts and plant communities. Soil crust was reduced by 27-34% near medium and high use trails (an estimated peak rate of 13-70 visitors per hour) compared with control plots, but there was less than 1% reduction near low use trails (peak rate of two to four visitors per hour). We did not detect soil erosion in the center 80% of the trampled area of any of the trails. The number of perennial plant species dropped by less than one plant species on average, but perennial plant cover decreased by 7.5% in trailside plots compared with control plots 6 m off-trail. At the current levels of visitation, the primary management focus should be keeping people on the originally constructed trail tread surface to reduce impact to adjacent soil crusts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Marrero, Maria Teresa; Estevez, Sara; Negrin, Gledy; Quintana, Jose [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain); Lopez, Mariana; Perez, Francisco J.; Triana, Jorge [Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain); Leon, Francisco [Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain); Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)

2012-11-09

Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G{sub 2}-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x{sub L}. Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

Mutual Use of Trail-Following Chemical Cues by a Termite Host and Its Inquiline

Czech Academy of Sciences Publication Activity Database

Cristaldo, Paulo Fellipe; DeSouza, O.; Krasulová, Jana; Jirošová, Anna; Kutalová, Kateřina; Lima, E. R.; Šobotník, Jan; Sillam-Dusses, D.

2014-01-01

Roč. 9, č. 1 (2014), e85315/1-e85315/9 E-ISSN 1932-6203 Institutional support: RVO:61388963 Keywords : inquilinism * trail-following behaviour * termite association * Termitidae * chemical ecology Subject RIV: CC - Organic Chemistry Impact factor: 3.234, year: 2014 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085315

A Mathematics and Science Trail

Science.gov (United States)

Smith, Kathy Horak; Fuentes, Sarah Quebec

2012-01-01

In an attempt to engage primary-school students in a hands-on, real-world problem-solving context, a large urban district, a mathematics and science institute housed in a college of education, and a corporate sponsor in the southwest United States, joined forces to create a mathematics and science trail for fourth- and fifth-grade students. A…

Combination of systemic chemotherapy with local stem cell delivered S-TRAIL in resected brain tumors.

Science.gov (United States)

Redjal, Navid; Zhu, Yanni; Shah, Khalid

2015-01-01

Despite advances in standard therapies, the survival of glioblastoma multiforme (GBM) patients has not improved. Limitations to successful translation of new therapies include poor delivery of systemic therapies and use of simplified preclinical models which fail to reflect the clinical complexity of GBMs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and we have tested its efficacy by on-site delivery via engineered stem cells (SC) in mouse models of GBM that mimic the clinical scenario of tumor aggressiveness and resection. However, about half of tumor lines are resistant to TRAIL and overcoming TRAIL-resistance in GBM by combining therapeutic agents that are currently in clinical trials with SC-TRAIL and understanding the molecular dynamics of these combination therapies are critical to the broad use of TRAIL as a therapeutic agent in clinics. In this study, we screened clinically relevant chemotherapeutic agents for their ability to sensitize resistant GBM cell lines to TRAIL induced apoptosis. We show that low dose cisplatin increases surface receptor expression of death receptor 4/5 post G2 cycle arrest and sensitizes GBM cells to TRAIL induced apoptosis. In vivo, using an intracranial resection model of resistant primary human-derived GBM and real-time optical imaging, we show that a low dose of cisplatin in combination with synthetic extracellular matrix encapsulated SC-TRAIL significantly decreases tumor regrowth and increases survival in mice bearing GBM. This study has the potential to help expedite effective translation of local stem cell-based delivery of TRAIL into the clinical setting to target a broad spectrum of GBMs. © 2014 AlphaMed Press.

The Roles of ROS and Caspases in TRAIL-Induced Apoptosis and Necroptosis in Human Pancreatic Cancer Cells.

Directory of Open Access Journals (Sweden)

Min Zhang

Full Text Available Death signaling provided by tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL can induce death in cancer cells with little cytotoxicity to normal cells; this cell death has been thought to involve caspase-dependent apoptosis. Reactive oxygen species (ROS are also mediators that induce cell death, but their roles in TRAIL-induced apoptosis have not been elucidated fully. In the current study, we investigated ROS and caspases in human pancreatic cancer cells undergoing two different types of TRAIL-induced cell death, apoptosis and necroptosis. TRAIL treatment increased ROS in two TRAIL-sensitive pancreatic cancer cell lines, MiaPaCa-2 and BxPC-3, but ROS were involved in TRAIL-induced apoptosis only in MiaPaCa-2 cells. Unexpectedly, inhibition of ROS by either N-acetyl-L-cysteine (NAC, a peroxide inhibitor, or Tempol, a superoxide inhibitor, increased the annexin V-/propidium iodide (PI+ early necrotic population in TRAIL-treated cells. Additionally, both necrostatin-1, an inhibitor of receptor-interacting protein kinase 1 (RIP1, and siRNA-mediated knockdown of RIP3 decreased the annexin V-/PI+ early necrotic population after TRAIL treatment. Furthermore, an increase in early apoptosis was induced in TRAIL-treated cancer cells under inhibition of either caspase-2 or -9. Caspase-2 worked upstream of caspase-9, and no crosstalk was observed between ROS and caspase-2/-9 in TRAIL-treated cells. Together, these results indicate that ROS contribute to TRAIL-induced apoptosis in MiaPaCa-2 cells, and that ROS play an inhibitory role in TRAIL-induced necroptosis of MiaPaCa-2 and BxPC-3 cells, with caspase-2 and -9 playing regulatory roles in this process.

Comparing the impacts of hiking, skiing and horse riding on trail and vegetation in different types of forest.

Science.gov (United States)

Törn, A; Tolvanen, A; Norokorpi, Y; Tervo, R; Siikamäki, P

2009-03-01

Nature-based tourism in protected areas has increased and diversified dramatically during the last decades. Different recreational activities have a range of impacts on natural environments. This paper reports results from a comparison of the impacts of hiking, cross-country skiing and horse riding on trail characteristics and vegetation in northern Finland. Widths and depths of existing trails, and vegetation on trails and in the neighbouring forests were monitored in two research sites during 2001 and 2002. Trail characteristics and vegetation were clearly related to the recreational activity, research site and forest type. Horse trails were as deep as hiking trails, even though the annual number of users was 150-fold higher on the hiking trails. Simultaneously, cross-country skiing had the least effect on trails due to the protective snow cover during winter. Hiking trail plots had little or no vegetation cover, horse riding trail plots had lower vegetation cover than forest plots, while skiing had no impact on total vegetation cover. On the other hand, on horse riding trails there were more forbs and grasses, many of which did not grow naturally in the forest. These species that were limited to riding trails may change the structure of adjacent plant communities in the long run. Therefore, the type of activities undertaken and the sensitivity of habitats to these activities should be a major consideration in the planning and management of nature-based tourism. Establishment of artificial structures, such as stairs, duckboards and trail cover, or complete closure of the site, may be the only way to protect the most sensitive or deteriorated sites.

The pyrrolo-1,5-benzoxazepine, PBOX-15, enhances TRAIL-induced apoptosis by upregulation of DR5 and downregulation of core cell survival proteins in acute lymphoblastic leukaemia cells

Science.gov (United States)

NATHWANI, SEEMA-MARIA; GREENE, LISA M.; BUTINI, STEFANIA; CAMPIANI, GIUSEPPE; WILLIAMS, D. CLIVE; SAMALI, AFSHIN; SZEGEZDI, EVA; ZISTERER, DANIELA M.

2016-01-01

Apoptotic defects are frequently associated with poor outcome in pediatric acute lymphoblastic leukaemia (ALL) hence there is an ongoing demand for novel strategies that counteract apoptotic resistance. The death ligand TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) and its selective tumour receptor system has attracted exceptional clinical interest. However, many malignancies including ALL are resistant to TRAIL monotherapy. Tumour resistance can be overcome by drug combination therapy. TRAIL and its agonist antibodies are currently undergoing phase II clinical trials with established chemotherapeutics. Herein, we present promising therapeutic benefits in combining TRAIL with the selective anti-leukaemic agents, the pyrrolo-1,5-benzoxazepines (PBOXs) for the treatment of ALL. PBOX-15 synergistically enhanced apoptosis induced by TRAIL and a DR5-selective TRAIL variant in ALL-derived cells. PBOX-15 enhanced TRAIL-induced apoptosis by dual activation of extrinsic and intrinsic apoptotic pathways. The specific caspase-8 inhibitor, Z-IETD-FMK, identified the extrinsic pathway as the principal mode of apoptosis. We demonstrate that PBOX-15 can enhance TRAIL-induced apoptosis by upregulation of DR5, reduction of cellular mitochondrial potential, activation of the caspase cascade and downregulation of PI3K/Akt, c-FLIP, Mcl-1 and IAP survival pathways. Of note, the PI3K pathway inhibitor LY-294002 significantly enhanced the apoptotic potential of TRAIL and PBOX-15 validating the importance of Akt downregulation in the TRAIL/PBOX-15 synergistic combination. Considering the lack of cytotoxicity to normal cells and ability to downregulate several survival pathways, PBOX-15 may represent an effective agent for use in combination with TRAIL for the treatment of ALL. PMID:27176505

Interferon beta induces apoptosis in nasopharyngeal carcinoma cells via the TRAIL-signaling pathway.

Science.gov (United States)

Makowska, Anna; Wahab, Lora; Braunschweig, Till; Kapetanakis, Nikiforos-Ioannis; Vokuhl, Christian; Denecke, Bernd; Shen, Lian; Busson, Pierre; Kontny, Udo

2018-03-06

The combination of neoadjuvant chemotherapy, radiochemotherapy, and maintenance therapy with interferon beta (IFNβ) has led to superior results in the treatment of children and adolescents with nasopharyngeal carcinoma (NPC). However, nothing is known about the mechanism of the antitumor activity of IFNβ in NPC. Here, we investigate the role of IFNβ on apoptosis in NPC cells. Six NPC cell lines, one patient-derived NPC xenograft (PDX) and one SV40-transformed nasoepithelial cell line were used. Induction of apoptosis by IFNβ was measured by flow cytometric analysis of subG1-DNA-content, Hoechst 33258 staining and activation of caspase-3. Dissection of death ligand signaling pathways included measuring surface expression of its components by flow cytometry, activation by death ligands and neutralization with specific antibodies and siRNA. IFNβ induced apoptosis at concentrations achievable in humans in five of six NPC cell lines and in PDX cells but not in nasoepithelial cells. Inhibition of caspases-3 and -8 abrogated this effect suggesting IFNβ promoted apoptosis through the extrinsic pathway. IFNβ induced surface expression of TRAIL and TRAIL-R2 and the addition of an anti-TRAIL-antibody or transfection with TRAIL-siRNA blocked IFNβ-induced apoptosis. No induction of TRAIL-expression was noted in the IFNβ-resistant cell line. In conclusion, IFNβ leads to apoptosis in NPC cells in an autocrine way via the induction of TRAIL expression and subsequent activation of the TRAIL-signaling pathway. The mechanism described could at least partly explain the clinical benefit of IFNβ in the treatment of NPC. Further studies in a mouse-xenograft model are warranted to substantiate this effect in vivo .

TRAIL causes deletions at the HPRT and TK1 loci of clonogenically competent cells

Energy Technology Data Exchange (ETDEWEB)

Miles, Mark A.; Shekhar, Tanmay M. [Department of Biochemistry and Genetics, La Trobe University, Bundoora, Victoria (Australia); La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia); Hall, Nathan E. [La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia); Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Melbourne, Victoria (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry and Genetics, La Trobe University, Bundoora, Victoria (Australia); La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria (Australia)

2016-05-15

Highlights: • Treatment with TRAIL or EMS provokes mutations in clonogenically viable TK6 cells. • TRAIL is 2–5-fold less mutagenic than an equivalently lethal concentration of EMS. • EMS mainly causes transition mutations at the HPRT and TK1 loci of TK6 cells. • Most loss-of-function HPRT or TK1 mutations caused by TRAIL treatment are deletions. - Abstract: When chemotherapy and radiotherapy are effective, they function by inducing DNA damage in cancerous cells, which respond by undergoing apoptosis. Some adverse effects can result from collateral destruction of non-cancerous cells, via the same mechanism. Therapy-related cancers, a particularly serious adverse effect of anti-cancer treatments, develop due to oncogenic mutations created in non-cancerous cells by the DNA damaging therapies used to eliminate the original cancer. Physiologically achievable concentrations of direct apoptosis inducing anti-cancer drugs that target Bcl-2 and IAP proteins possess negligible mutagenic activity, however death receptor agonists like TRAIL/Apo2L can provoke mutations in surviving cells, probably via caspase-mediated activation of the nuclease CAD. In this study we compared the types of mutations sustained in the HPRT and TK1 loci of clonogenically competent cells following treatment with TRAIL or the alkylating agent ethyl methanesulfonate (EMS). As expected, the loss-of-function mutations in the HPRT or TK1 loci triggered by exposure to EMS were almost all transitions. In contrast, only a minority of the mutations identified in TRAIL-treated clones lacking HPRT or TK1 activity were substitutions. Almost three quarters of the TRAIL-induced mutations were partial or complete deletions of the HPRT or TK1 genes, consistent with sub-lethal TRAIL treatment provoking double strand breaks, which may be mis-repaired by non-homologous end joining (NHEJ). Mis-repair of double-strand breaks following exposure to chemotherapy drugs has been implicated in the pathogenesis of

TRAIL causes deletions at the HPRT and TK1 loci of clonogenically competent cells

International Nuclear Information System (INIS)

Miles, Mark A.; Shekhar, Tanmay M.; Hall, Nathan E.; Hawkins, Christine J.

2016-01-01

Highlights: • Treatment with TRAIL or EMS provokes mutations in clonogenically viable TK6 cells. • TRAIL is 2–5-fold less mutagenic than an equivalently lethal concentration of EMS. • EMS mainly causes transition mutations at the HPRT and TK1 loci of TK6 cells. • Most loss-of-function HPRT or TK1 mutations caused by TRAIL treatment are deletions. - Abstract: When chemotherapy and radiotherapy are effective, they function by inducing DNA damage in cancerous cells, which respond by undergoing apoptosis. Some adverse effects can result from collateral destruction of non-cancerous cells, via the same mechanism. Therapy-related cancers, a particularly serious adverse effect of anti-cancer treatments, develop due to oncogenic mutations created in non-cancerous cells by the DNA damaging therapies used to eliminate the original cancer. Physiologically achievable concentrations of direct apoptosis inducing anti-cancer drugs that target Bcl-2 and IAP proteins possess negligible mutagenic activity, however death receptor agonists like TRAIL/Apo2L can provoke mutations in surviving cells, probably via caspase-mediated activation of the nuclease CAD. In this study we compared the types of mutations sustained in the HPRT and TK1 loci of clonogenically competent cells following treatment with TRAIL or the alkylating agent ethyl methanesulfonate (EMS). As expected, the loss-of-function mutations in the HPRT or TK1 loci triggered by exposure to EMS were almost all transitions. In contrast, only a minority of the mutations identified in TRAIL-treated clones lacking HPRT or TK1 activity were substitutions. Almost three quarters of the TRAIL-induced mutations were partial or complete deletions of the HPRT or TK1 genes, consistent with sub-lethal TRAIL treatment provoking double strand breaks, which may be mis-repaired by non-homologous end joining (NHEJ). Mis-repair of double-strand breaks following exposure to chemotherapy drugs has been implicated in the pathogenesis of

TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol

Directory of Open Access Journals (Sweden)

Zhiyu Zhang

2015-01-01

Full Text Available Among important components of American ginseng, protopanaxadiol (PPD showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.

TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol.

Science.gov (United States)

Zhang, Zhiyu; Li, Zejuan; Wu, Xiaohui; Zhang, Chun-Feng; Calway, Tyler; He, Tong-Chuan; Du, Wei; Chen, Jianjun; Wang, Chong-Zhi; Yuan, Chun-Su

2015-01-01

Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Physical properties of glasses exposed to Earth-facing and trailing-side environments on LDEF

Science.gov (United States)

Wiedlocher, David E.; Kinser, Donald L.; Weller, Robert A.; Weeks, Robert A.; Mendenhall, Marcus H.

1993-01-01

The exposure of 108 glass samples and 12 glass-ceramic samples to Earth-orbit environments permitted measurements which establish the effects of each environment. Examination of five glass types and one glass ceramic located on both the Earth-facing side and the trailing edge revealed no reduction in strength within experimental limits. Strength measurements subjected less than 5 percent of the sample surface area to stresses above 90 percent of the glass's failure strength. Seven micrometeorite or space debris impacts occurred on trailing edge samples. One of those impacts occurred in a location which was subjected to 50 percent of the applied stress at failure. Micrometeorite or space debris impacts were not observed on Earth-facing samples. The physical shape and structure of the impact sites were carefully examined using stereographic scanning electron microscopy. These impacts induce a stress concentration at the damaged region which influences mechanical strength. The flaw size produced by such damage was examined to determine the magnitude of strength degradation in micrometeorite or space-debris impacted glasses. Scanning electron microscopy revealed topographical details of impact sites which included central melt zones and glass fiber production. The overall crater structure is similar to much larger impacts of large meteorite on the Moon in that the melt crater is surrounded by shocked regions of material which fracture zones and spall areas. Residual stresses arising from shock compression and cooling of the fused zone cannot currently be included in fracture mechanics analyses based on simple flaw size examination.

A dynamic stall model for airfoils with deformable trailing edges

DEFF Research Database (Denmark)

Andersen, Peter Bjørn; Gaunaa, Mac; Bak, Christian

2009-01-01

, lead-lag, pitch, trailing-edge flapping. In the linear region, the model reduces to the inviscid model, which includes the aerodynamic effect of a thin airfoil with a deformable camberline in inviscid flow. Therefore, the proposed model can be considered a crossover between the work of Gaunaa......The present work contains an extension of the Beddoes-Leishman-type dynamic stall model. In this work, a deformable trailing-edge flap has been added to the dynamic stall model. The model predicts the unsteady aerodynamic forces and moments on an airfoil section undergoing arbitrary motion in heave...... for the attached flow region and Hansen et al. The model is compared qualitatively to wind tunnel measurements of a Riso/ B1-18 blade section equipped with deformable trailing-edge flap devices in the form of piezoelectric devices. Copyright © 2009 John Wiley & Sons, Ltd....

Trailing Edge Noise Model Validation and Application to Airfoil Optimization

DEFF Research Database (Denmark)

Bertagnolio, Franck; Aagaard Madsen, Helge; Bak, Christian

2010-01-01

The aim of this article is twofold. First, an existing trailing edge noise model is validated by comparing with airfoil surface pressure fluctuations and far field sound pressure levels measured in three different experiments. The agreement is satisfactory in one case but poor in two other cases...... across the boundary layer near the trailing edge and to a lesser extent by a smaller boundary layer displacement thickness. ©2010 American Society of Mechanical Engineers...

Effect of MeV Electron Radiation on Europa’s Surface Ice Analogs

Science.gov (United States)

Gudipati, Murthy; Henderson, Bryana; Bateman, Fred

2017-10-01

MeV electrons that impact Europa’s trailing hemisphere and cause both physical and chemical alteration of the surface and near-surface. The trailing hemisphere receives far lower fluxes above 25 MeV as compared with lower energy particles, but can cause significant chemical and physical modifications at these energies. With NASA's planned Europa Clipper mission and a Europa Lander Concept on the horizon, it is critical to understand and quantify the effect of Europa’s radiation environment on the surface and near surface.Electrons penetrate through ice by far the deepest at any given energy compared to protons and ions, making the role of electrons very important to understand. In addition, secondary radiation - Bremsstrahlung, in X-ray wavelengths - is generated during high-energy particle penetration through solids. Secondary X-rays are equally lethal to life and penetrate even deeper than electrons, making the cumulative effect of radiation on damaging organic matter on the near surface of Europa a complex process that could have effects several meters below Europa’s surface. Other physical properties such as coloration could be caused by radiation.In order to quantify this effect under realistic Europa trailing hemisphere conditions, we devised, built, tested, and obtained preliminary results using our ICE-HEART instrument prototype totally funded by JPL’s internal competition funding for Research and Technology Development. Our Ice Chamber for Europa High-Energy Electron And Radiation-Environment Testing (ICE-HEART) operates at ~100 K. We have also implemented a magnet that is used to remove primary electrons subsequent to passing through an ice column, in order to determine the flux of secondary X-radiation and its penetration through ice.Some of the first results from these studies will be presented and their relevance to understand physical and chemical properties of Europa’s trailing hemisphere surface.This work has been carried out at Jet

Trailing edge noise model applied to wind turbine airfoils

Energy Technology Data Exchange (ETDEWEB)

Bertagnolio, F.

2008-01-15

The aim of this work is firstly to provide a quick introduction to the theory of noise generation that are relevant to wind turbine technology with focus on trailing edge noise. Secondly, the socalled TNO trailing edge noise model developed by Parchen [1] is described in more details. The model is tested and validated by comparing with other results from the literature. Finally, this model is used in the optimization process of two reference airfoils in order to reduce their noise signature: the RISOE-B1-18 and the S809 airfoils. (au)

Dust dynamics in off-road vehicle trails: Measurements on 16 arid soil types, Nevada, USA.

Science.gov (United States)

Goossens, Dirk; Buck, Brenda

2009-08-01

Soil analyses and measurements with the Portable In Situ Wind Erosion Laboratory (PI-SWERL) were conducted on 16 soil types in an area heavily affected by off-road vehicle (ORV) driving. Measurements were performed in ORV trails as well as on undisturbed terrain to investigate how ORV driving affects the vulnerability of a soil to emit PM10 (particlestrail affects those properties of the topsoil that determine its capability to emit PM10. Also, recommendations are given for adequate management of ORV-designed areas. The type of surface (sand, silt, gravel, drainage) is a key factor with respect to dust emission in an ORV trail. Trails in sand, defined in this study as the grain size fraction 63-2000microm, show higher deflation thresholds (the critical wind condition at which wind erosion starts) than the surrounding undisturbed soil. Trails in silt (2-63microm) and in drainages, on the other hand, have lower deflation thresholds than undisturbed soil. The increase in PM10 emission resulting from the creation of a new ORV trail is much higher for surfaces with silt than for surfaces with sand. Also, the creation of a new trail in silt decreases the supply limitation in the top layer: the capacity of the reservoir of emission-available PM10 increases. For sand the situation is reversed: the supply limitation increases, and the capacity of the PM10 reservoir decreases. Finally, ORV trails are characterized by a progressive coarsening of the top layer with time, but the speed of coarsening is much lower in trails in silt than in trails in sand or in drainages. The results of this study suggest that, to minimize emissions of PM10, new ORV fields should preferably be designed on sandy terrain rather than in silt areas or in drainages.

Tinjauan Proses Perencanaan Heritage Trails Sebagai Produk Pariwisata dalam RIPPDA Kota Bandung

Directory of Open Access Journals (Sweden)

Teguh Amor Patria

2013-11-01

Full Text Available Despite the fact that Bandung boasts a large number of heritage buildings as tourism potentials which become one of priorities in Rencana Induk Pengembangan Pariwisata Daerah (RIPPDA Kota Bandung 2007-2016 (municipal tourism development plans, such plan is assumed as less detailed and comprehensive. It also emphasizes only on supply and spatial aspect. This paper reviewed the planning process of heritage trails as tourism product in the tourism development plan. A comparative study between actual and ideal condition was conducted and was presented in descriptive way. It consists of introduction, theoretical background relating to tourism product planning process and heritage tourism, research methodology, actual conditions of heritage trails development in Bandung, critical review of heritage trails in Bandung, and conclusion andrecommendation. Such findings reveal the actual condition of heritage trails development as a growing tourism product in Bandung today, which lacks details, depth, and comprehensiveness, data from the past, and review from supply side in order to plan for a better heritage tourism activity.

Why Individuals Hike the Appalachian Trail: A Qualitative Approach to Benefits

Science.gov (United States)

Goldenberg, Marni; Hill, Eddie; Freidt, Barbara

2008-01-01

The Appalachian Trail (AT) is a 2,175 mile-long National Scenic Trail extending from Maine to Georgia. Since its inception in the early 1920s, individuals, families, schools, and other organizations, just to name a few, have used the AT. Approximately 3 to 4 million visitors hike a portion of the AT each year (ATC, 2006). Throughout its 80-year…

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL

Directory of Open Access Journals (Sweden)

Karacay Bahri

2010-10-01

Full Text Available Abstract Background Lung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL and IKK inhibition (AdIKKβKA to overcome TRAIL resistance in lung cancer cells. Methods Fluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding. Results Neither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression. Conclusions Combination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer.

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL

International Nuclear Information System (INIS)

Aydin, Cigdem; Sanlioglu, Ahter D; Bisgin, Atil; Yoldas, Burcak; Dertsiz, Levent; Karacay, Bahri; Griffith, Thomas S; Sanlioglu, Salih

2010-01-01

Lung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL) and IKK inhibition (AdIKKβKA) to overcome TRAIL resistance in lung cancer cells. Fluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding. Neither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression. Combination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer

The interplay between scent trails and group-mass recruitment systems in ants

NARCIS (Netherlands)

Planque, R.; van den Berg, G.J.B.; Franks, N.R.

2013-01-01

Large ant colonies invariably use effective scent trails to guide copious ant numbers to food sources. The success of mass recruitment hinges on the involvement of many colony members to lay powerful trails. However, many ant colonies start off as single queens. How do these same colonies forage

Sputtering from swift-ion trails in LiF: A hybrid PIC/MD simulation

Energy Technology Data Exchange (ETDEWEB)

Cherednikov, Yaroslav; Sun, Si Neng; Urbassek, Herbert M., E-mail: urbassek@rhrk.uni-kl.de

2013-11-15

We model the sputtering of a LiF crystal induced by swift-ion impact. The impinging ion creates a trail of doubly ionized F{sup +} ions, while simultaneously the corresponding electrons are set free. Ions move according to molecular dynamics, while excited electrons are treated by a particle-in-cell scheme. We treat the recombination time of electrons as a free parameter in our model. We find that the energy distribution of sputtered ions consists of 2 groups: a low-energy group centered at <1 eV, and a high-energy group at 7–8 eV. Fast ions (mainly Li{sup +}) are emitted early; these charge the surface negatively. Later, larger cluster ions and also neutral LiF molecules are emitted. Emission occurs at low angles to the surface normal. A jet along the normal direction can be observed, which is due to the electric field building up at the track surface. With increasing recombination time, processes are colder; sputtering decreases and the non-thermal jet structure becomes stronger.

Impacts of Different Hiking-trail Use Frequency on Soil Erosion: a Case of Mt. Mudeng National Park, Korea

Science.gov (United States)

Kim, J.; Kim, J. K.

2017-12-01

Mountain National Parks have been suffered serious soil erosion by hiking in Korea. To identify the impacts of different human's trampling intensities, a comparative study was conducted in Mt. Mudeungsan National Park where has been very intensive recreational activities. For this study, trail-conditions and soil properties were discovered on the 1.9km trail of high traffic (A) and 3.8km trail of low traffic (B) in the study area. Width was significantly wider on the A than B, but there was no significant difference in the values of other factors. With compaction and erosion of topsoil on the trail, penetration resistance and bulk density were significantly higher, but water content and the ratio of silt and clay were significantly lower than those of undisturbed areas around the trails. These were not statistically significant spatial difference from the use frequency of the trails. This result implies that the characteristics of surface soil on trails were not largely affected by use frequency, and the evolution of cross-section form of trails would be dominated by widening. This study will help in managing trail system and establishing conservation policy sustainably.

The role of TRAIL in fatigue induced by repeated stress from radiotherapy.

Science.gov (United States)

Feng, Li Rebekah; Suy, Simeng; Collins, Sean P; Saligan, Leorey N

2017-08-01

Fatigue is one of the most common and debilitating side effects of cancer and cancer treatment, and yet its etiology remains elusive. The goal of this study is to understand the role of chronic inflammation in fatigue following repeated stress from radiotherapy. Fatigue and non-fatigue categories were assessed using ≥ 3-point change in Functional Assessment of Cancer Therapy-Fatigue questionnaire (FACT-F) administered to participants at baseline/before radiotherapy and one year post-radiotherapy. Whole genome microarray and cytokine multiplex panel were used to examine fatigue-related transcriptome and serum cytokine changes, respectively. The study included 86 subjects (discovery phase n = 40, validation phase n = 46). The sample in the discovery phase included men with prostate cancer scheduled to receive external-beam radiotherapy. A panel of 48 cytokines were measured and the significantly changed cytokine found in the discovery phase was validated using sera from a separate cohort of men two years after completing radiotherapy for prostate cancer at a different institution. Effects of the significantly changed cytokine on cell viability was quantified using the MTT assay. During the discovery phase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL decoy receptor, TNFRSF10C (TRAIL-R3), were significantly upregulated in fatigued (≥3-point decrease from baseline to 1yr-post radiotherapy) subjects (n = 15). In the validation phase, TRAIL correlated with fatigue scores 2yrs post-radiotherapy. TRAIL caused selective cytotoxicity in neuronal cells, but not in microglial and muscle cells, in vitro. Late-onset inflammation directed by TRAIL may play a role in fatigue pathogenesis post-repeated stress from irradiation. Published by Elsevier Ltd.

Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

Directory of Open Access Journals (Sweden)

Vu T A Dang

Full Text Available Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01, as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05 in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05. In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05. These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

Science.gov (United States)

Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

2011-01-01

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

Continuous Fraud Detection in Enterprise Systems through Audit Trail Analysis

Directory of Open Access Journals (Sweden)

Peter J. Best

2009-03-01

Full Text Available Enterprise systems, real time recording and real time reporting pose new and significant challenges to the accounting and auditing professions. This includes developing methods and tools for continuous assurance and fraud detection. In this paper we propose a methodology for continuous fraud detection that exploits security audit logs, changes in master records and accounting audit trails in enterprise systems. The steps in this process are: (1 threat monitoring-surveillance of security audit logs for ‘red flags’, (2 automated extraction and analysis of data from audit trails, and (3 using forensic investigation techniques to determine whether a fraud has actually occurred. We demonstrate how mySAP, an enterprise system, can be used for audit trail analysis in detecting financial frauds; afterwards we use a case study of a suspected fraud to illustrate how to implement the methodology.

76 FR 54730 - Rubicon Trail Easement, Eldorado National Forest, Pacific Ranger District

Science.gov (United States)

2011-09-02

... waters of the state, and address human waste management on the Rubicon Trail. Proposed Action The... through these low spots thereby accelerating trail erosion and sedimentation. In July 2004, the El Dorado... fecal waste littered around the Spider Lake area. The amount of fecal waste was determined to pose a...

Optimization of the poro-serrated trailing edges for airfoil broadband noise reduction.

Science.gov (United States)

Chong, Tze Pei; Dubois, Elisa

2016-08-01

This paper reports an aeroacoustic investigation of a NACA0012 airfoil with a number of poro-serrated trailing edge devices that contain porous materials of various air flow resistances at the gaps between adjacent members of the serrated-sawtooth trailing edge. The main objective of this work is to determine whether multiple-mechanisms on the broadband noise reduction can co-exist on a poro-serrated trailing edge. When the sawtooth gaps are filled with porous material of low-flow resistivity, the vortex shedding tone at low-frequency could not be completely suppressed at high-velocity, but a reasonably good broadband noise reduction can be achieved at high-frequency. When the sawtooth gaps are filled with porous material of very high-flow resistivity, no vortex shedding tone is present, but the serration effect on the broadband noise reduction becomes less effective. An optimal choice of the flow resistivity for a poro-serrated configuration has been identified, where it can surpass the conventional serrated trailing edge of the same geometry by achieving a further 1.5 dB reduction in the broadband noise while completely suppressing the vortex shedding tone. A weakened turbulent boundary layer noise scattering at the poro-serrated trailing edge is reflected by the lower-turbulence intensity at the near wake centreline across the whole spanwise wavelength of the sawtooth.

Mental Health Problems during Puberty: Tanner Stage-Related Differences in Specific Symptoms. The TRAILS Study

Science.gov (United States)

Oldehinkel, Albertine J.; Verhulst, Frank C.; Ormel, Johan

2011-01-01

The aim of this study was to investigate associations between specific mental health problems and pubertal stage in (pre)adolescents participating in the Dutch prospective cohort study TRAILS (first assessment: N = 2230, age 11.09 [plus or minus] 0.56, 50.8% girls; second assessment: N = 2149, age 13.56 [plus or minus] 0.53, 51.0% girls). Mental…

The Relationship between Trail Running Withdrawals and Race Topography

Directory of Open Access Journals (Sweden)

Antonini Philippe Roberta

2017-12-01

Full Text Available Context: A growing amount of recent research in sport psychology has focused on trying to understand withdrawals from ultra-races. However, according to the Four E approach, the studies underestimated the embedded components of these experiences and particularly how they were linked to the specific environmental conditions in which the experiences occurred. Objective: This study aimed to characterize trail running withdrawals in relationship to race topography. Design: Qualitative design, involving self-confrontation interviews and use of a race map. Setting: Use of the race map for description of the race activity and self-confrontation interviews took place 1–3 days after the races. Participants: Ten runners who withdrew during an ultra-trail race. Data Collection and Analysis: Data on past activity traces and experiences were elicited from self-confrontation interviews. Data were coded and compared to identify common sequences and then each type of sequence was counted with regard to race topography. Results: Results showed that each sequence was related to runners’ particular possibilities for acting, feeling, and thinking, which were in turn embedded in the race topography. These sequences allowed the unfolding of the activity and increased its overall effectiveness in relation to the constraints of this specific sport. Conclusion: This study allowed us to highlight important information on how ultra-trail runners manage their races in relationship to the race environment and more specifically to its topography. The result will also help us to recommend potential adjustments to ultra-trail runners’ performance-oriented training and preparation.

A Functional Neuroimaging Analysis of the Trail Making Test-B: Implications for Clinical Application

Directory of Open Access Journals (Sweden)

Mark D. Allen

2011-01-01

Full Text Available Recent progress has been made using fMRI as a clinical assessment tool, often employing analogues of traditional “paper and pencil” tests. The Trail Making Test (TMT, popular for years as a neuropsychological exam, has been largely ignored in the realm of neuroimaging, most likely because its physical format and administration does not lend itself to straightforward adaptation as an fMRI paradigm. Likewise, there is relatively more ambiguity about the neural systems associated with this test than many other tests of comparable clinical use. In this study, we describe an fMRI version of Trail Making Test-B (TMTB that maintains the core functionality of the TMT while optimizing its use for both research and clinical settings. Subjects (N = 32 were administered the Functional Trail Making Test-B (f-TMTB. Brain region activations elicited by the f-TMTB were consistent with expectations given by prior TMT neurophysiological studies, including significant activations in the ventral and dorsal visual pathways and the medial pre-supplementary motor area. The f-TMTB was further evaluated for concurrent validity with the traditional TMTB using an additional sample of control subjects (N = 100. Together, these results support the f-TMTB as a viable neuroimaging adaptation of the TMT that is optimized to evoke maximally robust fMRI activation with minimal time and equipment requirements.

Sex-specific trail pheromone mediates complex mate finding behavior in Anoplophora glabripennis

Science.gov (United States)

Kelli Hoover; Melody Keena; Maya Nehme; Shifa Wang; Peter Meng; Aijun Zhang

2014-01-01

Anoplophora glabripennis (Motsch.) is a polyphagous member of the Cerambycidae, and is considered, worldwide, to be one of the most serious quarantine pests of deciduous trees. We isolated four chemicals from the trail of A. glabripennis virgin and mated females that were not present in trails of mature males. These compounds were...

Model Predictive Control of Trailing Edge Flaps on a wind turbine blade

DEFF Research Database (Denmark)

Castaignet, Damien; Poulsen, Niels Kjølstad; Buhl, Thomas

2011-01-01

Trailing Edge Flaps on wind turbine blades have been studied in order to achieve fatigue load reduction on the turbine components. We show in this paper how Model Predictive Control can be used to do frequency weighted control of the trailing edge flaps in order to reduce fatigue damage on the bl...

Asymptotic theory of two-dimensional trailing-edge flows

Science.gov (United States)

Melnik, R. E.; Chow, R.

1975-01-01

Problems of laminar and turbulent viscous interaction near trailing edges of streamlined bodies are considered. Asymptotic expansions of the Navier-Stokes equations in the limit of large Reynolds numbers are used to describe the local solution near the trailing edge of cusped or nearly cusped airfoils at small angles of attack in compressible flow. A complicated inverse iterative procedure, involving finite-difference solutions of the triple-deck equations coupled with asymptotic solutions of the boundary values, is used to accurately solve the viscous interaction problem. Results are given for the correction to the boundary-layer solution for drag of a finite flat plate at zero angle of attack and for the viscous correction to the lift of an airfoil at incidence. A rational asymptotic theory is developed for treating turbulent interactions near trailing edges and is shown to lead to a multilayer structure of turbulent boundary layers. The flow over most of the boundary layer is described by a Lighthill model of inviscid rotational flow. The main features of the model are discussed and a sample solution for the skin friction is obtained and compared with the data of Schubauer and Klebanoff for a turbulent flow in a moderately large adverse pressure gradient.

User Manual for SAHM package for VisTrails

Science.gov (United States)

Talbert, C.B.; Talbert, M.K.

2012-01-01

The Software for Assisted Habitat I\\•1odeling (SAHM) has been created to both expedite habitat modeling and help maintain a record of the various input data, pre-and post-processing steps and modeling options incorporated in the construction of a species distribution model. The four main advantages to using the combined VisTrail: SAHM package for species distribution modeling are: 1. formalization and tractable recording of the entire modeling process 2. easier collaboration through a common modeling framework 3. a user-friendly graphical interface to manage file input, model runs, and output 4. extensibility to incorporate future and additional modeling routines and tools. This user manual provides detailed information on each module within the SAHM package, their input, output, common connections, optional arguments, and default settings. This information can also be accessed for individual modules by right clicking on the documentation button for any module in VisTrail or by right clicking on any input or output for a module and selecting view documentation. This user manual is intended to accompany the user guide which provides detailed instructions on how to install the SAHM package within VisTrails and then presents information on the use of the package.

Primary control of a Mach scale swashplateless rotor using brushless DC motor actuated trailing edge flaps

Science.gov (United States)

Saxena, Anand

The focus of this research was to demonstrate a four blade rotor trim in forward flight using integrated trailing edge flaps instead of using a swashplate controls. A compact brushless DC motor was evaluated as an on-blade actuator, with the possibility of achieving large trailing edge flap amplitudes. A control strategy to actuate the trailing edge flap at desired frequency and amplitude was developed and large trailing edge flap amplitudes from the motor (instead of rotational motion) were obtained. Once the actuator was tested on the bench-top, a lightweight mechanism was designed to incorporate the motor in the blade and actuate the trailing edge flaps. A six feet diameter, four bladed composite rotor with motor-flap system integrated into the NACA 0012 airfoil section was fabricated. Systematic testing was carried out for a range of load conditions, first in the vacuum chamber followed by hover tests. Large trailing edge flap deflections were observed during the hover testing, and a peak to peak trailing edge flap amplitude of 18 degree was achieved at 2000 rotor RPM with hover tip Mach number of 0.628. A closed loop controller was designed to demonstrate trailing edge flap mean position and the peak to peak amplitude control. Further, a soft pitch link was designed and fabricated, to replace the stiff pitch link and thereby reduce the torsional stiffness of the blade to 2/rev. This soft pitch link allowed for blade root pitch motion in response to the trailing edge flap inputs. Blade pitch response due to both steady as well as sinusoidal flap deflections were demonstrated. Finally, tests were performed in Glenn L. Martin wind tunnel using a model rotor rig to assess the performance of motor-flap system in forward flight. A swashplateless trim using brushless DC motor actuated trailing edge flaps was achieved for a rotor operating at 1200 RPM and an advance ratio of 0.28. Also, preliminary exploration was carried out to test the scalability of the motor

Self-guided trails – a route to more responsible tourism?

OpenAIRE

MacLeod, Nicola

2016-01-01

In recent years, the tourism industry has faced criticism by turning its attention to the development of more responsible tourism. This is a form of tourism that is mindful of the diverse needs of host communities, local business and the visitor. This paper investigates the development of more responsible tourism from the perspective of a popular tourist product – the self-guided trail or route. The trail or route provides a themed and interpreted journey through the urban or rural landscape,...

Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Guo LG

2012-03-01

Full Text Available Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2 1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Shanghai, 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China; 4College of Pharmacy, University of Rhode Island, RI, USAAbstract: The intractability of non-small cell lung cancer (NSCLC to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4 or 5 (DR5. However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof

Cloning and Characterization of Genes that Inhibit TRAIL-Induced Apoptosis of Breast Cancer Cells

National Research Council Canada - National Science Library

Shu, Hong-Bing

2003-01-01

...). However, some cancer cells are resistant to TRAIL-induced apoptosis (3, 4, 6-13). The purpose of this proposed study is to clone and characterize such inhibitory genes of TRAIL-induced apoptosis...

The efficacy of combined educational and site management actions in reducing off-trail hiking in an urban-proximate protected area.

Science.gov (United States)

Hockett, Karen S; Marion, Jeffrey L; Leung, Yu-Fai

2017-12-01

Park and protected area managers are tasked with protecting natural environments, a particularly daunting challenge in heavily visited urban-proximate areas where flora and fauna are already stressed by external threats. In this study, an adaptive management approach was taken to reduce extensive off-trail hiking along a popular trail through an ecologically diverse and significant area in the Chesapeake and Ohio National Historical Park near Washington DC. Substantial amounts of off-trail hiking there had created an extensive 16.1 km network of informal (visitor-created) trails on a 39 ha island in the Potomac Gorge. A research design with additive treatments integrating educational and site management actions was applied and evaluated using self-reported behavior from an on-site visitor survey and unobtrusive observations of off-trail hiking behavior at two locations along the trail. Study treatments included: 1) trailhead educational signs developed using attribution theory and injunctive-proscriptive wording, 2) symbolic "no hiking" prompter signs attached to logs placed across all informal trails, 3) placement of concealing leaf litter and small branches along initial sections of informal trails, 4) restoration work on selected trails with low fencing, and 5) contact with a trail steward to personally communicate the trailhead sign information. The final, most comprehensive treatment reduced visitor-reported intentional off-trail hiking from 70.3% to 43.0%. Direct observations documented reduction in off-trail hiking from 25.9% to 2.0%. The educational message and site management actions both contributed to the decline in off-trail travel and the two evaluation methods enhanced our ability to describe the efficacy of the different treatments in reducing off-trail travel. Published by Elsevier Ltd.

The efficacy of combined educational and site management actions in reducing off-trail hiking in an urban-proximate protected area

Science.gov (United States)

Hockett, Karen; Marion, Jeff; Leung, Yu-Fai

2017-01-01

Park and protected area managers are tasked with protecting natural environments, a particularly daunting challenge in heavily visited urban-proximate areas where flora and fauna are already stressed by external threats. In this study, an adaptive management approach was taken to reduce extensive off-trail hiking along a popular trail through an ecologically diverse and significant area in the Chesapeake and Ohio National Historical Park near Washington DC. Substantial amounts of off-trail hiking there had created an extensive 16.1 km network of informal (visitor-created) trails on a 39 ha island in the Potomac Gorge. A research design with additive treatments integrating educational and site management actions was applied and evaluated using self-reported behavior from an on-site visitor survey and unobtrusive observations of off-trail hiking behavior at two locations along the trail. Study treatments included: 1) trailhead educational signs developed using attribution theory and injunctive-proscriptive wording, 2) symbolic “no hiking” prompter signs attached to logs placed across all informal trails, 3) placement of concealing leaf litter and small branches along initial sections of informal trails, 4) restoration work on selected trails with low fencing, and 5) contact with a trail steward to personally communicate the trailhead sign information. The final, most comprehensive treatment reduced visitor-reported intentional off-trail hiking from 70.3% to 43.0%. Direct observations documented reduction in off-trail hiking from 25.9% to 2.0%. The educational message and site management actions both contributed to the decline in off-trail travel and the two evaluation methods enhanced our ability to describe the efficacy of the different treatments in reducing off-trail travel.

Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

International Nuclear Information System (INIS)

Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

2011-01-01

Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

Directory of Open Access Journals (Sweden)

Taylor David J

2011-11-01

Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL.

Science.gov (United States)

Bae, S I; Cheriyath, V; Jacobs, B S; Reu, F J; Borden, E C

2008-01-17

Human melanoma cell lines, SK-MEL-3 and SK-MEL-28, despite induction of the proapoptotic cytokine, Apo2L/TRAIL, did not undergo apoptosis in response to interferons (IFN-alpha2b or IFN-beta). Postulating that genes important for apoptosis induction by IFNs might be silenced by methylation, the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZAdC) was assessed. DR4 (TRAIL-R1) was identified as one of the genes reactivated by 5-AZAdC with a >3-fold increase in 8 of 10 melanoma cell lines. Pretreatment with 5-AZAdC sensitized SK-MEL-3 and SK-MEL-28 cells to apoptosis induced by IFN-alpha2b and IFN-beta; methylation-specific PCR and bisulfite sequencing confirmed demethylation of 5'CpG islands of DR4 and flow cytometry showed an increase in DR4 protein on the cell surface. In cells with reactivated DR4, neutralizing mAB to TRAIL reduced apoptosis in response to IFN-beta or Apo2L/TRAIL. To further confirm the role of DR4, it was expressed by retroviral vector in SK-MEL-3 and SK-MEL-28 cells with reversal of resistance to IFN-beta and Apo2L/TRAIL. Thus, reexpressing DR4 by 5-AZAdC or retroviral transfection in melanoma cell in which promoter methylation had suppressed its expression, potentiated apoptosis by IFN-alpha2b, IFN-beta and Apo2L/TRAIL. Reactivation of silenced proapoptotic genes by inhibitors of DNA methylation may enhance clinical response to IFNs or Apo2L/TRAIL.

The Paracrine Induction of TRAIL by Genotoxic Agents

National Research Council Canada - National Science Library

Spalding, Aaron

2002-01-01

TNF related apoptosis inducing ligand, TRAIL, is a recently cloned cytokine that has been shown to induce apoptosis in a synergistic fashion with chemotherapeutic agents on several cancer cell lines...

Identification of Flap Motion Parameters for Vibration Reduction in Helicopter Rotors with Multiple Active Trailing Edge Flaps

Directory of Open Access Journals (Sweden)

Uğbreve;ur Dalli

2011-01-01

Full Text Available An active control method utilizing the multiple trailing edge flap configuration for rotorcraft vibration suppression and blade loads control is presented. A comprehensive model for rotor blade with active trailing edge flaps is used to calculate the vibration characteristics, natural frequencies and mode shapes of any complex composite helicopter rotor blade. A computer program is developed to calculate the system response, rotor blade root forces and moments under aerodynamic forcing conditions. Rotor blade system response is calculated using the proposed solution method and the developed program depending on any structural and aerodynamic properties of rotor blades, structural properties of trailing edge flaps and properties of trailing edge flap actuator inputs. Rotor blade loads are determined first on a nominal rotor blade without multiple active trailing edge flaps and then the effects of the active flap motions on the existing rotor blade loads are investigated. Multiple active trailing edge flaps are controlled by using open loop controllers to identify the effects of the actuator signal output properties such as frequency, amplitude and phase on the system response. Effects of using multiple trailing edge flaps on controlling rotor blade vibrations are investigated and some design criteria are determined for the design of trailing edge flap controller that will provide actuator signal outputs to minimize the rotor blade root loads. It is calculated that using the developed active trailing edge rotor blade model, helicopter rotor blade vibrations can be reduced up to 36% of the nominal rotor blade vibrations.

Novel HTS strategy identifies TRAIL-sensitizing compounds acting specifically through the caspase-8 apoptotic axis.

Directory of Open Access Journals (Sweden)

Darren Finlay

Full Text Available Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7 compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be "weeded out" in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries.

Trailing vortices from low speed flyers

Science.gov (United States)

Waldman, Rye; Kudo, Jun; Breuer, Kenneth

2009-11-01

The structure and strength of the vortex wake behind a airplane or animal flying with a fixed or flapping wing contains valuable information about the aerodynamic load history. However, the amount of vorticity measured in the trailing vortex is not always in agreement with the known lift generated, and the behavior of these vortices at relatively low Reynolds numbers is also not well-understood. We present the results from a series of wind tunnel PIV experiments conducted behind a low-aspect ratio rectangular wing at a chord-Reynolds numbers of 30,000. In addition to wake PIV measurements measured in the cross-stream (Trefftz) plane, we measure the lift and drag directly using a six-axis force-torque transducer. We discuss how vortex size, shape, strength and position vary in time and downstream location, as well as the challenges associated with the use of PIV wake measurements to accurate determine aerodynamic forces.

Linear perturbation growth at the trailing edge of a rarefaction wave

International Nuclear Information System (INIS)

Wouchuk, J.G.; Carretero, R.

2003-01-01

An analytic model for the perturbation growth inside a rarefaction wave is presented. The objective of the work is to calculate the growth of the perturbations at the trailing edge of a simple expanding wave in planar geometry. Previous numerical and analytical works have shown that the ripples at the rarefaction tail exhibit linear growth asymptotically in time [Yang et al., Phys. Fluids 6, 1856 (1994), A. Velikovich and L. Phillips, ibid. 8, 1107 (1996)]. However, closed expressions for the asymptotic value of the perturbed velocity of the trailing edge have not been reported before, except for very weak rarefactions. Explicit analytic solutions for the perturbations growing at the rarefaction trailing edge as a function of time and also for the asymptotic perturbed velocity are given, for fluids with γ<3. The limits of weak and strong rarefactions are considered and the corresponding scaling laws are given. A semi-qualitative discussion of the late time linear growth at the trailing edge ripple is presented and it is seen that the lateral mass flow induced by the sound wave fluctuations is solely responsible for that behavior. Only the rarefactions generated after the interaction of a shock wave with a contact discontinuity are considered

Effect of density on traffic and velocity on trunk trails of Formica pratensis.

Science.gov (United States)

Hönicke, C; Bliss, P; Moritz, R F A

2015-04-01

The allocation of large numbers of workers facilitates the swift intake of locally available resources which is essential for ant colony survival. To organise the traffic between nest and food source, the black-meadow ant Formica pratensis establishes permanent trunk trails, which are maintained by the ants. To unravel the ant organisation and potential traffic rules on these trails, we analysed velocity and lane segregation under various densities by experimentally changing feeding regimes. Even under the highest ant densities achieved, we never observed any traffic jams. On the contrary, velocity increased after supplementary feeding despite an enhanced density. Furthermore, inbound ants returning to the nest had a higher velocity than those leaving the colony. Whilst at low and medium density the ants used the centre of the trail, they used the full width of the trail at high density. Outbound ants also showed some degree of lane segregation which contributes to traffic organisation.

Angular and polarization trails from effective interactions of Majorana neutrinos at the LHeC

Science.gov (United States)

Duarte, Lucía; Zapata, Gabriel; Sampayo, Oscar A.

2018-05-01

We study the possibility of the LHeC facility to disentangle different new physics contributions to the production of heavy sterile Majorana neutrinos in the lepton number violating channel e-p→ lj+ + 3 jets (l_j≡e ,μ ). This is done investigating the angular and polarization trails of effective operators with distinct Dirac-Lorentz structure contributing to the Majorana neutrino production, which parameterize new physics from a higher energy scale. We study an asymmetry in the angular distribution of the final anti-lepton and the initial electron polarization effect on the number of signal events produced by the vectorial and scalar effective interactions, finding both analyses could well separate their contributions.

Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

National Research Council Canada - National Science Library

Behbakht, Kian

2008-01-01

.... TRAIL therapies are particularly exciting because TRAIL reverses chemoresistance to standard chemotherapy as well as having a direct growth inhibitory effect on ovarian cancer cells, while sparing normal...

Interferon-α and cyclooxygenase-2 inhibitor cooperatively mediates TRAIL-induced apoptosis in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Zuo, Chaohui, E-mail: zuochaohui@vip.sina.com [Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Hunan Province Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan Province (China); Department of Pathology, Immunology and Laboratory Medicine and Shands Cancer Center, University of Florida, Gainesville, FL (United States); Qiu, Xiaoxin [Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Hunan Province Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan Province (China); Cancer Research Institute, University of South China, Hengyang, Hunan Province (China); Liu, Nianli; Yang, Darong [Cancer Research Institute, University of South China, Hengyang, Hunan Province (China); Xia, Man [Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Hunan Province Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan Province (China); Department of Pathology, Immunology and Laboratory Medicine and Shands Cancer Center, University of Florida, Gainesville, FL (United States); Liu, Jingshi [Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Hunan Province Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan Province (China); Wang, Xiaohong [Cancer Research Institute, University of South China, Hengyang, Hunan Province (China); and others

2015-05-01

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Interferon-alpha (IFN-α) has recently been recognized to harbor therapeutic potential in the prevention and treatment of HCC, but it remains controversial as to whether IFN-α exerts direct cytotoxicity against HCC. Cyclooxygenase-2 (COX-2) is overexpressed in HCC and is considered to play a role in hepatocarcinogenesis. Therefore, we aimed to elucidate the combined effect of a COX-2 inhibitor, celecoxib, and IFN-α on in vitro growth suppression of HCC using the hepatoma cell line HLCZ01 and the in vivo nude mouse xenotransplantation model using HLCZ01 cells. Treatment with celecoxib and IFN-α synergistically inhibited cell proliferation in a dose- and time-dependent manner. Apoptosis was identified by 4',6-diamidino-2-phenylindole dihydrochloride and fluorescent staining. IFN-α upregulated the expression of TRAIL, while celecoxib increased the expression of TRAIL receptors. The combined regimen with celecoxib and IFN-α reduced the growth of xenotransplanted HCCs in nude mice. The regulation of IFN-α- and COX-2 inhibitor-induced cell death is impaired in a subset of TRAIL-resistant cells. The molecular mechanisms of HCC cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. Interferon-α and the COX-2 inhibitor celecoxib synergistically increased TRAIL-induced apoptosis in hepatocellular carcinoma. These data suggest that IFN-α and celecoxib may offer a novel role with important implications in designing new therapeutics for TRAIL-resistant tumors. - Highlights: ●The cytotoxic effect of TRAIL on a developed HCC HLCZ01 cells infected with HBV. ●IFN-α and celecoxib induced apoptosis in HLCZ01 cells infected with HBV. ●The combined regime reduced the growth of xenotransplanted HCCs in nude mice model.

Mesospheric temperature estimation from meteor decay times of weak and strong meteor trails

Science.gov (United States)

Kim, Jeong-Han; Kim, Yong Ha; Jee, Geonhwa; Lee, Changsup

2012-11-01

Neutral temperatures near the mesopause region were estimated from the decay times of the meteor echoes observed by a VHF meteor radar during a period covering 2007 to 2009 at King Sejong Station (62.22°S, 58.78°W), Antarctica. While some previous studies have used all meteor echoes to determine the slope from a height profile of log inverse decay times for temperature estimation, we have divided meteor echoes into weak and strong groups of underdense meteor trails, depending on the strength of estimated relative electron line densities within meteor trails. We found that the slopes from the strong group are inappropriate for temperature estimation because the decay times of strong meteors are considerably scattered, whereas the slopes from the weak group clearly define the variation of decay times with height. We thus utilize the slopes only from the weak group in the altitude region between 86 km and 96 km to estimate mesospheric temperatures. The meteor estimated temperatures show a typical seasonal variation near the mesopause region and the monthly mean temperatures are in good agreement with SABER temperatures within a mean difference of 4.8 K throughout the year. The meteor temperatures, representing typically the region around the altitude of 91 km, are lower on average by 2.1 K than simultaneously measured SATI OH(6-2) rotational temperatures during winter (March-October).

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

International Nuclear Information System (INIS)

Dai, Yao; Liu, Meilan; Tang, Wenhua; Li, Yongming; Lian, Jiqin; Lawrence, Theodore S; Xu, Liang

2009-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells. The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay. SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression. These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling

Recreational trails as a source of negative impacts on the persistence of keystone species and facilitation.

Science.gov (United States)

Ballantyne, Mark; Pickering, Catherine Marina

2015-08-15

Hiking trails, which are among the most common forms of infrastructure created for nature-based tourism, can alter key ecological processes. Trails can damage plants that facilitate the establishment and growth of other species leading to changes in community and functional composition. This can be a particular concern in harsh alpine ecosystems where plant communities are often dominated by one or two keystone species that provide shelter to a suite of beneficiary species. We analysed how a hiking trail affects interspecific facilitation by a dominant trampling-sensitive nurse shrub in the highest National Park in Australia. First we assessed the effects of the trail on the abundance, size and density of the nurse shrub at different distances from the trail. We then compared species richness and composition between areas in, and out, of the nurse shrub's canopy at different distances from the trail. To better understand why some species may benefit from facilitation and any effects of the trail on the quality of facilitation we compared functional composition between quadrats using community trait weighted means calculated by combining plant composition with species functional traits (canopy height, leaf area, % dry weight of leaves and specific leaf area). The abundance, size and density of nurse shrubs was lower on the trail edges than further away, particularly on the leeward edge, where there was more bare ground and less shrub cover. There were differences in species richness, cover, composition and functional composition in and outside the nurse shrub canopy. The shrubs appeared to facilitate species with more competitive, but less stress tolerant traits (e.g. taller plants with leaves that were larger, had high specific leaf area and low dry matter content). However, despite reductions in nurse shrubs near the trail, where they do exist, they appear to provide the same 'quality' of facilitation as nurse shrubs further away. However, longer-term effects may

Tumor trailing strategy for intensity-modulated radiation therapy of moving targets

International Nuclear Information System (INIS)

Trofimov, Alexei; Vrancic, Christian; Chan, Timothy C. Y.; Sharp, Gregory C.; Bortfeld, Thomas

2008-01-01

Internal organ motion during the course of radiation therapy of cancer affects the distribution of the delivered dose and, generally, reduces its conformality to the targeted volume. Previously proposed approaches aimed at mitigating the effect of internal motion in intensity-modulated radiation therapy (IMRT) included expansion of the target margins, motion-correlated delivery (e.g., respiratory gating, tumor tracking), and adaptive treatment plan optimization employing a probabilistic description of motion. We describe and test the tumor trailing strategy, which utilizes the synergy of motion-adaptive treatment planning and delivery methods. We regard the (rigid) target motion as a superposition of a relatively fast cyclic component (e.g., respiratory) and slow aperiodic trends (e.g., the drift of exhalation baseline). In the trailing approach, these two components of motion are decoupled and dealt with separately. Real-time motion monitoring is employed to identify the 'slow' shifts, which are then corrected by applying setup adjustments. The delivery does not track the target position exactly, but trails the systematic trend due to the delay between the time a shift occurs, is reliably detected, and, subsequently, corrected. The ''fast'' cyclic motion is accounted for with a robust motion-adaptive treatment planning, which allows for variability in motion parameters (e.g., mean and extrema of the tidal volume, variable period of respiration, and expiratory duration). Motion-surrogate data from gated IMRT treatments were used to provide probability distribution data for motion-adaptive planning and to test algorithms that identified systematic trends in the character of motion. Sample IMRT fields were delivered on a clinical linear accelerator to a programmable moving phantom. Dose measurements were performed with a commercial two-dimensional ion-chamber array. The results indicate that by reducing intrafractional motion variability, the trailing strategy

Geology along Mosca Pass Trail, Great Sand Dunes National Park and Preserve, Colorado

Science.gov (United States)

Lindsey, David A.; Klein, Terry L.; Valdez, Andrew; Webster, Robert J.

2012-01-01

Mosca Pass Trail takes the hiker on a journey into the Earth's crust. Here you can see the results of tremendous tectonic forces that bend and tear rocks apart and raise mountain ranges. The trail begins near the Sangre de Cristo fault, which separates the Sangre de Cristo Range from the San Luis Valley. The valley is part of the Rio Grande rift, a series of fault basins extending from southern New Mexico to central Colorado, wherein the Earth's crust has been pulled apart during the last 30 million years. Thousands of feet of sediment, brought by streams mostly from the Sangre de Cristo Range, fill the San Luis Valley beneath the Great Sand Dunes. The trail ends at Mosca Pass overlooking Huerfano Park. The park is part of the larger Raton Basin, formed by compression of the Earth's crust during the Laramide orogeny, which occurred 70–40 million years ago. Massive highlands, the remnants of which are preserved in the Sangre de Cristo Range, were uplifted and pushed over the western side of the Raton Basin. Streams eroded the highland as it rose and filled the Raton Basin with sediment. After the sediment was compacted and cemented to form sedimentary rock, the Huerfano River and other streams began to excavate the basin. Over an unknown but long timespan that probably lasted millions of years, relatively soft sedimentary rocks were removed by the river to form the valley we call "Huerfano Park." Between the ends of the trail, the hiker walks through an erosional "window," or opening, into red sedimentary rocks overridden by gneiss, a metamorphic rock, during the Laramide orogeny. This window gives the hiker a glimpse into the Laramide highland of 70–40 million years ago that preceded the present-day Sangre de Cristo Range. The window is the focus of this trail guide. At the east end of the trail, near Mosca Pass, another trail follows the ridgeline south to Carbonate Mountain. Immediately after reaching the first summit above tree line, this trail crosses a

DNR Division of Parks and Trails District Boundaries

Data.gov (United States)

Minnesota Department of Natural Resources — This data shows the DNR Division of Parks and Trails District Boundaries as of May 2010. The boundaries were created by the Division Leadership Team. Boundaries are...

A cellular automata model for ant trails

Indian Academy of Sciences (India)

In this study, the unidirectional ant traffic flow with U-turn in an ant trail was inves- tigated using ... the literature, it was considered in the model that (i) ant colony consists of two kinds of ants, good- ... ponents without a central controller [8].

Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx

International Nuclear Information System (INIS)

Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck; Choi, Yung-Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree; Kim, Gi-Young

2012-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.

Synergistic effects of rmhTRAIL and 17-AAG on the proliferation and apoptosis of multiple myeloma cells.

Science.gov (United States)

Wang, Jing; Li, Yun; Sun, Wei; Liu, Jing; Chen, Wenming

2018-03-22

This study aimed to investigate synergistic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 -allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and apoptosis of multiple myeloma (MM) cells. MTT assays evaluated inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and treatment durations on the proliferation of RPMI8226 and U266 cells. The half maximal inhibitory concentration was calculated using OriginPro7.5. Synergistic effects of rmhTRAIL and 17-AAG on apoptosis of MM cells were detected using flow cytometry at 24 and 48 h post-treatment. To evaluate synergistic effects of rmhTRAIL and 17-AAG, the Q-value was calculated using King's formula. rmhTRAIL exhibited significant inhibitory effects on the proliferation of RPMI8226 cells in a dose- and time-dependent manner (>50%), whereas U266 cells were not sensitive to rmhTRAIL (80%). Significant synergistic effects of rmhTRAIL and 17-AAG on the proliferation of RPMI8226 cells were revealed (Q-value > 1.15), whereas synergistic effects were not evident on the proliferation of U266 cells (Q-value effects on apoptosis of RPMI8226 and U266 cells (Q-value > 1.15). The combined application of rmhTRAIL and 17-AAG revealed favorable synergistic effects in the treatment of MM.

Assessment and selection of geomorphosites and trails in the Miage Glacier area (Western Italian alps).

Science.gov (United States)

Bollati, Irene; Smiraglia, Claudio; Pelfini, Manuela

2013-04-01

Glacial environments are considered geomorphosites because they exhibit all of the features that characterise sites of geomorphological interest. The Miage Glacier, in particular, is the most important debris-covered glacier of the Italian Alps, and it has been extensively studied since the 18th century because of its scientific features. In this area, the geomorphological and geological attributes are evaluated at 11 sites that have been individuated along the three main touristic trails, which allow an exploration of the surroundings of the glacial tongue and its two main lobes. Using a methodology previously tested in a fluvial environment, single sites and trails are quantitatively assessed to determine the most suitable trail for educational purposes. Hazards that could potentially affect the trails are considered in terms of both risk education and final selection of the most suitable trails for the various possible user groups. The richness of scientific data in this area should increase its importance as a geomorphosite by increasing the educational value of the Miage Glacier and the Veny Valley.

Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts

International Nuclear Information System (INIS)

El-Zawahry, Ahmed; McKillop, John; Voelkel-Johnson, Christina

2005-01-01

Prostate cancer is a significant health problem among American men. Treatment strategies for androgen-independent cancer are currently not available. Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, including androgen-independent PC3 prostate carcinoma cells. In vitro, TRAIL-mediated apoptosis of prostate cancer cell lines can be enhanced by doxorubicin and correlates with the downregulation of the anti-apoptotic protein c-FLIP. This study evaluated the effects of doxorubicin on c-FLIP expression and tumor growth in combination with Apo2L/TRAIL in a xenograft model. In vitro cytotoxic effects of TRAIL were measured using a MTS-based viability assay. For in vivo studies, PC3 prostate carcinoma cells were grown subcutaneously in athymic nude mice and tumor growth was measured following treatment with doxorubicin and/or Apo2L/TRAIL. c-FLIP expression was determined by western blot analysis. Apoptosis in xenografts was detected using TUNEL. Statistical analysis was performed using the student t-test. In vitro experiments show that PC3 cells are partially susceptible to Apo2L/TRAIL and that susceptibility is enhanced by doxorubicin. In mice, doxorubicin did not significantly affect the growth of PC3 xenografts but reduced c-FLIP expression in tumors. Expression of c-FLIP in mouse heart was decreased only at the high doxorubicin concentration (8 mg/kg). Combination of doxorubicin with Apo2L/TRAIL resulted in more apoptotic cell death and tumor growth inhibition than Apo2L/TRAIL alone. Combination of doxorubicin and Apo2L/TRAIL is more effective in growth inhibition of PC3 xenografts in vivo than either agent alone and could present a novel treatment strategy against hormone-refractory prostate cancer. The intracellular mechanism by which doxorubicin enhances the effect of Apo2L/TRAIL on PC3 xenografts may be by reducing expression of c-FLIP

The association between herpes virus infections and functional somatic symptoms in a general population of adolescents. The TRAILS study.

Directory of Open Access Journals (Sweden)

Iris Jonker

Full Text Available FSS have been suggested to follow activation of the immune system, triggered by herpes virus infections. The aim of this study was to find out whether herpes virus infections were associated with the experience of FSS in adolescents, and whether this association was mediated by hsCRP, as a general marker of immune activation.This study was performed in TRAILS, a large prospective population cohort of 2230 adolescents (mean age: 16.1 years, SD = .66, 53.4% girls. FSS were assessed using the somatic complaints subscale of the Youth Self-Report. FSS were analyzed as total scores and divided in two group clusters based on previous studies in this cohort. Levels of hsCRP and antibody levels to the herpes viruses HSV1, HSV2, CMV, EBV and HHV6 were assessed in blood samples at age 16. Also a value for pathogen burden was created adding the number of viruses the adolescents were seropositive for. Multiple regression analysis with bootstrapping was used to analyze the association between viral antibodies and pathogen burden, hsCRP and FSS scores.Antibody levels and pathogen burden were not associated with FSS total scores or FSS scores in both symptom groups. hsCRP was associated with the total FSS score (B = .02, 95% CI: .004 to .028, p = .01 and FSS score in the symptom group of headache and gastrointestinal complaints (B = .02, 95% CI: .001 to .039, p = .04.Our study showed no association between herpes virus infections and FSS in general or specific FSS symptom clusters. A role for inflammatory processes in FSS development was supported by the significant association we found between hsCRP levels and FSS, especially in the symptom group of headache and gastrointestinal complaints.

The association between herpes virus infections and functional somatic symptoms in a general population of adolescents. The TRAILS study.

Science.gov (United States)

Jonker, Iris; Schoevers, Robert; Klein, Hans; Rosmalen, Judith

2017-01-01

FSS have been suggested to follow activation of the immune system, triggered by herpes virus infections. The aim of this study was to find out whether herpes virus infections were associated with the experience of FSS in adolescents, and whether this association was mediated by hsCRP, as a general marker of immune activation. This study was performed in TRAILS, a large prospective population cohort of 2230 adolescents (mean age: 16.1 years, SD = .66, 53.4% girls). FSS were assessed using the somatic complaints subscale of the Youth Self-Report. FSS were analyzed as total scores and divided in two group clusters based on previous studies in this cohort. Levels of hsCRP and antibody levels to the herpes viruses HSV1, HSV2, CMV, EBV and HHV6 were assessed in blood samples at age 16. Also a value for pathogen burden was created adding the number of viruses the adolescents were seropositive for. Multiple regression analysis with bootstrapping was used to analyze the association between viral antibodies and pathogen burden, hsCRP and FSS scores. Antibody levels and pathogen burden were not associated with FSS total scores or FSS scores in both symptom groups. hsCRP was associated with the total FSS score (B = .02, 95% CI: .004 to .028, p = .01) and FSS score in the symptom group of headache and gastrointestinal complaints (B = .02, 95% CI: .001 to .039, p = .04). Our study showed no association between herpes virus infections and FSS in general or specific FSS symptom clusters. A role for inflammatory processes in FSS development was supported by the significant association we found between hsCRP levels and FSS, especially in the symptom group of headache and gastrointestinal complaints.

Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells

Directory of Open Access Journals (Sweden)

Xiaoyan Zhang

2013-05-01

Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

Film cooling adiabatic effectiveness measurements of pressure side trailing edge cooling configurations

Directory of Open Access Journals (Sweden)

R. Becchi

2015-12-01

Full Text Available Nowadays total inlet temperature of gas turbine is far above the permissible metal temperature; as a consequence, advanced cooling techniques must be applied to protect from thermal stresses, oxidation and corrosion the components located in the high pressure stages, such as the blade trailing edge. A suitable design of the cooling system for the trailing edge has to cope with geometric constraints and aerodynamic demands; state-of-the-art of cooling concepts often use film cooling on blade pressure side: the air taken from last compressor stages is ejected through discrete holes or slots to provide a cold layer between hot mainstream and the blade surface. With the goal of ensuring a satisfactory lifetime of blades, the design of efficient trailing edge film cooling schemes and, moreover, the possibility to check carefully their behavior, are hence necessary to guarantee an appropriate metal temperature distribution. For this purpose an experimental survey was carried out to investigate the film covering performance of different pressure side trailing edge cooling systems for turbine blades. The experimental test section consists of a scaled-up trailing edge model installed in an open loop suction type test rig. Measurements of adiabatic effectiveness distributions were carried out on three trailing edge cooling system configurations. The baseline geometry is composed by inclined slots separated by elongated pedestals; the second geometry shares the same cutback configuration, with an additional row of circular film cooling holes located upstream; the third model is equipped with three rows of in-line film cooling holes. Experiments have been performed at nearly ambient conditions imposing several blowing ratio values and using carbon dioxide as coolant in order to reproduce a density ratio close to the engine conditions (DR=1.52. To extend the validity of the survey a comparison between adiabatic effectiveness measurements and a prediction by

TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data.

Science.gov (United States)

Gamie, Zakareya; Kapriniotis, Konstantinos; Papanikolaou, Dimitra; Haagensen, Emma; Da Conceicao Ribeiro, Ricardo; Dalgarno, Kenneth; Krippner-Heidenreich, Anja; Gerrand, Craig; Tsiridis, Eleftherios; Rankin, Kenneth Samora

2017-11-28

Bone sarcomas are rare, highly malignant mesenchymal tumours that affect teenagers and young adults, as well as older patients. Despite intensive, multimodal therapy, patients with bone sarcomas have poor 5-year survival, close to 50%, with lack of improvement over recent decades. TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumour necrosis factor (TNF) ligand superfamily (TNFLSF), has been found to induce apoptosis in cancer cells while sparing nontransformed cells, and may therefore offer a promising new approach to treatment. We cover the existing preclinical and clinical evidence about the use of TRAIL and other death receptor agonists in bone sarcoma treatment. In vitro studies indicate that TRAIL and other death receptor agonists are generally potent against bone sarcoma cell lines. Ewing's sarcoma cell lines present the highest sensitivity, whereas osteosarcoma and chondrosarcoma cell lines are considered less sensitive. In vivo studies also demonstrate satisfactory results, especially in Ewing's sarcoma xenograft models. However, the few clinical trials in the literature show only low or moderate efficacy of TRAIL in treating bone sarcoma. Potential strategies to overcome the in vivo resistance reported include co-administration with other drugs and the potential to deliver TRAIL on the surface of primed mesenchymal or immune cells and the use of targeted single chain antibodies such as scFv-scTRAIL. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of p73 and TRAIL in odontogenic cysts and tumors.

Science.gov (United States)

Mascitti, Marco; Santarelli, Andrea; Zizzi, Antonio; Procaccini, Maurizio; Lo Muzio, Lorenzo; Rubini, Corrado

2016-01-01

Odontogenic tumors are a group of lesions arising from the odontogenic apparatus. Although the mechanism of oncogenesis and tumor progression in these lesions remains unknown, certain proteins, such as those involved in apoptosis, seem to be involved in the differentiation and proliferation of odontogenic epithelial cells. The aim of this study was to analyze the expression of p73 and TNF-related apoptosis-inducing ligand (TRAIL) in odontogenic tumors and cysts, and to clarify changes in the expression of these proteins. Immunohistochemical analysis was performed on 21 ameloblastomas, 15 keratocystic odontogenic tumors and 15 dentigerous cysts. We carried out quantitative assessment of p73 and TRAIL expression by determining the percentages of positive cells on a continuous scale. Five cases of orthokeratinized odontogenic cyst were also examined. The percentages of cells immunohistochemically positive for p73 were 52.6 ± 25.4% in ameloblastomas, 76.0 ± 13.1% in keratocystic odontogenic tumors, and 26.7 ± 30.7% in odontogenic cysts, whereas the corresponding figures for TRAIL were 57.6 ± 16.1%, 8.9 ± 10.0%, and 1.5 ± 0.5%, respectively. Imbalance of the apoptosis pathway, with dysregulation of p73 and TRAIL, seems to play a role in the oncogenesis of odontogenic tumors.(J Oral Sci 58, 459-464, 2016).

The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence.

Science.gov (United States)

Forde, Hannah; Harper, Emma; Davenport, Colin; Rochfort, Keith D; Wallace, Robert; Murphy, Ronan P; Smith, Diarmuid; Cummins, Philip M

2016-04-01

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that belongs to the tumour necrosis factor (TNF) cytokine superfamily. TRAIL is expressed by numerous cell types including vascular cells, immune cells and adipocytes. Although originally thought to induce apoptosis in malignant or transformed cells only, it is now known that TRAIL can bind up to 5 distinct receptors to activate complex signalling pathways, and is capable of exerting pleiotropic effects in non-transformed cells. In this respect, a number of clinical and animal studies point to the potential vasoprotective influence of TRAIL, with TRAIL deficiency being linked to accelerated atherosclerosis and vascular calcification. Moreover, exogenous TRAIL administration has been shown to exhibit anti-atherosclerotic activity in-vivo. In-vitro studies on TRAIL in this context have yielded conflicting results however, with evidence of both pro-atherogenic and vasoprotective effects ascribed to TRAIL. Notwithstanding these various studies, mechanistic information on the precise nature of TRAIL-mediated injury/protection within the vasculature, as well as the identity of the downstream molecular/cellular targets of TRAIL, is still quite limited. In this review, we will summarize our current knowledge of TRAIL regulation, signalling mechanisms, and its apparent involvement in CVD pathogenesis as a prelude to examining the existing evidence for TRAIL-mediated vasoprotection. To this end, extensive in vitro, in vivo, and clinical studies will be reviewed and critical findings highlighted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

Science.gov (United States)

Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

2012-01-01

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium.

Science.gov (United States)

Dalle Nogare, Damian; Somers, Katherine; Rao, Swetha; Matsuda, Miho; Reichman-Fried, Michal; Raz, Erez; Chitnis, Ajay B

2014-08-01

Collective migration of cells in the zebrafish posterior lateral line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when chemokine signaling is blocked in the PLLp. However, movement of the trailing fragment toward the leading cells, which was also thought to be chemokine dependent, persists. This suggested that a chemokine-independent mechanism, not accounted for in our models, is responsible for this behavior. Further investigation of trailing cell behavior shows that their movement toward leading cells depends on FGF signaling and it can be re-oriented by exogenous FGF sources. Together, our observations reveal the simple yet elegant manner in which leading and trailing cells coordinate migration; while leading cells steer PLLp migration by following chemokine cues, cells further back play follow-the-leader as they migrate toward FGFs produced by leading cells. © 2014. Published by The Company of Biologists Ltd.

Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation.

Science.gov (United States)

Henrich, C J; Brooks, A D; Erickson, K L; Thomas, C L; Bokesch, H R; Tewary, P; Thompson, C R; Pompei, R J; Gustafson, K R; McMahon, J B; Sayers, T J

2015-02-26

Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.

Understanding Trail Runners' Activity on Online Community Forums: An Inductive Analysis of Discussion Topics.

Science.gov (United States)

Rochat, Nadège; Hauw, Denis; Gür, Gaëlle; Seifert, Ludovic

2018-03-01

Recreational trail runners often participate in online community forums where they can freely read posted messages, join discussions and/or introduce new discussion topics. This tool can enhance learning as runners connect with other trail runners and reflect on how they can better organize their own practice. Studying forum activity would provide greater insight into the relationship between field practice and dedicated forums. The aim of this study was therefore to detect the topics discussed online by trail runners in order to understand how they collectively look for solutions that help them adapt to issues that emerge during actual practice. The discussion topics (n = 171) on the forum hosted by the Raidlight brand were examined using inductive content analysis, which distinguished two general dimensions. The first dimension was training and had four first-order themes (i.e., "specific trail running sessions", "complementary trail running sessions". "training plans" and "specific questions about races") grouped into two second-order themes (i.e., "training session contents" and "structure and schedule"). The second dimension was health and had seven first-order themes (i.e., "tendinitis", "muscle issues", "foot issues", "sprains and fractures", "pain", "physiology" and "substances and practitioners") grouped into two second-order themes (i.e., "pain and injury" and "prevention"). The results indicate that the issues that trail runners discuss on forums are significant and that the successions of questions and solutions are a fruitful means for building, enriching and adjusting their activity as they cope with constraints. As a practical consequence, suggestions for improving such online platforms are made.

Modeling the transient aerodynamic effects during the motion of a flexible trailing edge

International Nuclear Information System (INIS)

Wolff, T; Seume, J R

2016-01-01

Wind turbine blades have been becoming longer and more slender during the last few decades. The longer lever arm results in higher stresses at the blade root. Hence, the unsteady loads induced by turbulence, gust, or wind shear increase. One promising way to control these loads is to use flexible trailing edges near the blade tip. The unsteady effects which appear during the motion of a flexible trailing edge must be considered for the load calculation during the design process because of their high influence on aeroelastic effects and hence on the fatigue loads. This is not yet possible in most of the wind turbine simulation environments. Consequently, an empirical model is developed in the present study which accounts for unsteady effects during the motion of the trailing edge. The model is based on Fourier analyses of results generated with Reynolds-Averaged Navier-Stokes (RANS) simulations of a typical thin airfoil with a deformable trailing edge. The validation showed that the model fits Computational Fluid Dynamics (CFD) results simulated with a random time series of the deflection angle. (paper)

Rehabilitation of a secondary network of forest traffic infrastructure (skid roads - skid trails

Directory of Open Access Journals (Sweden)

Bajrić Muhamed

2015-01-01

Full Text Available Forest transport infrastructure is the key segment of rational forest resource management. One of its constituent and inseparable segments are skid roads and skid trails whose network density significantly exceeds the primary network, i.e. truck roads. Skid road -skid trail network density in high economic forests of FB&H is most often between 40 and 100 m/ha. Simplified way of construction, non-existence of road construction, objects for surface water drainage as well as significant longitudinal inclination (up to 50% in which they are constructed, makes them subject to erosion processes. The lack of rehabilitation measures on skid roads - skid trails causes significant damages in post-exploitation period, and very often to the extent that the ones in the following exploitation round are unusable for skidding. Utilization of skid roads - skid trails damaged by erosion processes for forest operations often represents a significant expense. This paper considers rehabilitation measures efficient from the point of remedying erosion processes, and at the same time, acceptable from the point of financial expenditure for forest operations.

A dynamic stall model for airfoils with deformable trailing edges

DEFF Research Database (Denmark)

Andersen, Peter Bjørn; Gaunaa, Mac; Bak, Dan Christian

2007-01-01

on an airfoil section undergoing arbitrary motion in heave, lead-lag, pitch, Trailing Edge (TE) flapping. In the linear region, the model reduces to the inviscid model of Gaunaa [4], which includes the aerodynamic effect of a thin airfoil with a deformable camberline in inviscid flow. Therefore, the proposed......The present work contains an extension of the Beddoes-Leishman (B-L) type dynamic stall model, as described by Hansen et al. [7]. In this work a Deformable Trailing Edge Geometry (DTEG) has been added to the dynamic stall model. The model predicts the unsteady aerodynamic forces and moments...

Influence of hiking trails on montane birds

Science.gov (United States)

William V. Deluca; David I. King

2014-01-01

Montane forests contribute significantly to regional biodiversity. Long-term monitoring data, often located along hiking trails, suggests that several indicator species of this ecosystem have declined in recent decades. Declining montane bird populations have been attributed to anthropogenic stressors such as climate change and atmospheric deposition. Several studies...

Pneumatic artificial muscles for trailing edge flap actuation: a feasibility study

Science.gov (United States)

Woods, Benjamin K. S.; Kothera, Curt S.; Sirohi, Jayant; Wereley, Norman M.

2011-10-01

In this study a novel aircraft trailing edge flap actuation system was developed and tested. Pneumatic artificial muscles (PAMs) were used as the driving elements of this system to demonstrate their feasibility and utility as an alternative aerospace actuation technology. A prototype flap/actuator system was integrated into a model wing section and tested on the bench-top under simulated airloads for flight at 100 m s-1 (M = 0.3) and in an open-jet wind tunnel at free stream velocities ranging up to 45 m s-1 (M = 0.13). Testing was performed for actuator pressures ranging from 0.069 to 0.62 MPa (10-90 psi) and actuation frequencies from 0.1 to 31 Hz. Results show that the PAM-driven trailing edge flap system can generate substantial and sustainable dynamic deflections, thereby proving the feasibility of using pneumatic artificial muscle actuators in a trailing edge flap system. Key issues limiting system performance are identified, that should be resolved in future research.

Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex.

Science.gov (United States)

Zhang, Rui; Xu, Jian; Zhao, Jian; Bai, Jinghui

2017-07-11

MicroRNAs have been proved to participate in multiple biological processes in cancers. For developing resistance to cytotoxic drug, cancer cells, especially the cancer stem cells, usually change their microRNA expression profile to survive in hostile environments. In the present study, we found that expression of microRNA-27a was increased in colorectal cancer stem cells. High level of microRNA-27a was indicated to induce the resistance to TNF-related apoptosis-inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer stem cells to TRAIL-induced cell death. Mechanically, the gene of Apaf-1, which is associated with the mitochondrial apoptosis, was demonstrated to be the target of microRNA-27a in colorectal cancer stem cells. Knockdown of microRNA-27a increased the expression level of Apaf-1, thus enhancing the formation of Apaf-1-caspase-9 complex and subsequently promoting the TRAIL-induced apoptosis in colorectal cancer stem cells. These findings suggested that knockdown of microRNA-27a in colorectal cancer stem cells by the specific antioligonucleotides was potential to reverse the chemoresistance to TRAIL. It may represent a novel therapeutic strategy for treating the colorectal cancer more effectively.

Fast Trailed Vorticity Modeling for Wind Turbine Aerodynamics and its Influence on Aeroelastic Stability

DEFF Research Database (Denmark)

Pirrung, Georg

In this work, an aerodynamic model for the use in aeroelastic wind turbine codes is presented. It consists of a simplified lifting line model covering the induction due to the trailed vorticity in the near wake, a 2D shed vorticity model and a far wake model using the well known blade element...... to earlier implementations, the model has been improved in several ways: Among other things, the need for model-specific user input has been removed, the effect of downwind convection of the trailed vorticity is modeled, the near wake induction is iterated to stabilize the computations and the numerical......-of-plane vibrations agrees much better with high fidelity models. Further, the trailed vorticity effects on the aerodynamic work are found to be of the same order of magnitude as the shed vorticity effects. The trailed vorticity effects are, however, mainly important close to the tip in the investigated cases, which...

Rats track odour trails accurately using a multi-layered strategy with near-optimal sampling.

Science.gov (United States)

Khan, Adil Ghani; Sarangi, Manaswini; Bhalla, Upinder Singh

2012-02-28

Tracking odour trails is a crucial behaviour for many animals, often leading to food, mates or away from danger. It is an excellent example of active sampling, where the animal itself controls how to sense the environment. Here we show that rats can track odour trails accurately with near-optimal sampling. We trained rats to follow odour trails drawn on paper spooled through a treadmill. By recording local field potentials (LFPs) from the olfactory bulb, and sniffing rates, we find that sniffing but not LFPs differ between tracking and non-tracking conditions. Rats can track odours within ~1 cm, and this accuracy is degraded when one nostril is closed. Moreover, they show path prediction on encountering a fork, wide 'casting' sweeps on encountering a gap and detection of reappearance of the trail in 1-2 sniffs. We suggest that rats use a multi-layered strategy, and achieve efficient sampling and high accuracy in this complex task.

Collective accelerator for electron colliders

Energy Technology Data Exchange (ETDEWEB)

Briggs, R.J.

1985-05-13

A recent concept for collective acceleration and focusing of a high energy electron bunch is discussed, in the context of its possible applicability to large linear colliders in the TeV range. The scheme can be considered to be a member of the general class of two-beam accelerators, where a high current, low voltage beam produces the acceleration fields for a trailing high energy bunch.

Collective accelerator for electron colliders

International Nuclear Information System (INIS)

Briggs, R.J.

1985-01-01

A recent concept for collective acceleration and focusing of a high energy electron bunch is discussed, in the context of its possible applicability to large linear colliders in the TeV range. The scheme can be considered to be a member of the general class of two-beam accelerators, where a high current, low voltage beam produces the acceleration fields for a trailing high energy bunch

Factors influencing the imposition of a charge on the entrance to the interpretive trails in the large protected areas

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Josef Navrátil

2013-01-01

Full Text Available The aim of this paper is to assess the relation between the character of the interpretive trail and the imposition of a charge on the entrance. This was done using the discrete choice experiment that involves eight attributes, seven of which are with three levels: the overall character of the trail, the way that the route signs are used in the terrain, the ways of providing information, the length of the trail, the way of the routing, the focus of the trail, and the price of the entrance. There is also one with two levels that involves the existence of the places for rest. The fractional factorial design was used (the orthogonal main effects plan and the Multinomial Logit Model was used in analyzing the data. The 2,830 choices were done by random sampled visitors from eight tourist locations in the Tourist Regions of the Šumava Mts. and South Bohemia during the summer season 2012. The impact of the character of the trail was especially detected in the model. Except for that, the equipment of the trail and its length have had the fundamental impact on the choice of the trail as well. Those longer and worse equipped trails have a significantly lower degree of utility for the respondents. What is quite surprising is that the respondents refused the ecotourism elements of the interpretive trails, such as the possibility of going through the trail on horseback or the accompaniment of an expert who would provide some comments, as it is common to do this at historical attractions within those sightseeing paths.

The Murine Natural Cytotoxic Receptor NKp46/NCR1 Controls TRAIL Protein Expression in NK Cells and ILC1s

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Sam Sheppard

2018-03-01

Full Text Available Summary: TRAIL is an apoptosis-inducing ligand constitutively expressed on liver-resident type 1 innate lymphoid cells (ILC1s and a subset of natural killer (NK cells, where it contributes to NK cell anti-tumor, anti-viral, and immunoregulatory functions. However, the intrinsic pathways involved in TRAIL expression in ILCs remain unclear. Here, we demonstrate that the murine natural cytotoxic receptor mNKp46/NCR1, expressed on ILC1s and NK cells, controls TRAIL protein expression. Using NKp46-deficient mice, we show that ILC1s lack constitutive expression of TRAIL protein and that NK cells activated in vitro and in vivo fail to upregulate cell surface TRAIL in the absence of NKp46. We show that NKp46 regulates TRAIL expression in a dose-dependent manner and that the reintroduction of NKp46 in mature NK cells deficient for NKp46 is sufficient to restore TRAIL surface expression. These studies uncover a link between NKp46 and TRAIL expression in ILCs with potential implications in pathologies involving NKp46-expressing cells. : Sheppard et al. find that mice deficient in the activating receptor NCR1/NKp46 (Ncr1−/− fail to express the apoptosis-inducing ligand TRAIL at the surface of group 1 innate lymphoid cells (ILC1s. Keywords: NK cell, natural killer cell, NKp46, ILC1, TRAIL, IL-15, IL-2

Response of Runoff and Sediment on Skid Trails of Varying Gradient and Traffic Intensity over a Two-Year Period

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Meghdad Jourgholami

2017-12-01

Full Text Available Compacted soil has lower water infiltration and hydraulic conductivity, which contributes to increased runoff and erosion on slopes. The aim of the present study was to assess runoff and sediment on three skidding trail longitudinal gradients (15%, 25%, and 35% and different levels of machine traffic (low, medium, and high, over a two-year period following the impact in the Hyrcanian forest, Iran. The results show that trail gradient and traffic intensity have a significant effect on soil bulk density and total porosity on the skid trails. The average runoff amount varied significantly among trail gradients and ranged from 1.59 mm on the 15% trail gradient and 2.76 mm on the 25% trail gradient, to 4.76 mm on the 35% trail gradient in the low traffic intensity. Average sediment also increased significantly with increasing trail gradient. Average sediment was 0.01 kg m−2, 0.03 kg m−2, and 0.05 kg m−2 on the low traffic intensity in the first year for the 15%, 25%, and 35% trail gradients, respectively. The largest runoff and sediment occurred in the first year and stressed the need for applying forestry Best Management Practices such as the use of brush mats during harvesting operations, as well as the installation of water diversion structures or seeding immediately after initial soil compaction and disturbance, in order to protect the bare soil from heavy rainfall.

Woody invasions of urban trails and the changing face of urban forests in the great plains, USA

Science.gov (United States)

Nemec, K.T.; Allen, Craig R.; Alai, A.; Clements, G.; Kessler, A.C.; Kinsell, T.; Major, A.; Stephen, B.J.

2011-01-01

Corridors such as roads and trails can facilitate invasions by non-native plant species. The open, disturbed habitat associated with corridors provides favorable growing conditions for many non-native plant species. Bike trails are a corridor system common to many urban areas that have not been studied for their potential role in plant invasions. We sampled five linear segments of urban forest along bike trails in Lincoln, Nebraska to assess the invasion of woody non-native species relative to corridors and to assess the composition of these urban forests. The most abundant plant species were generally native species, but five non-native species were also present: white mulberry (Morus alba), common buckthorn (Rhamnus cathartica), tree-of-heaven (Ailanthus altissima), honeysuckle (Lonicera spp.) and elm (Ulmus spp.). The distribution of two of the woody species sampled, common buckthorn and honeysuckle, significantly decreased with increasing distance from a source patch of vegetation (P = 0.031 and 0.030). These linear habitats are being invaded by non-native tree and shrub species, which may change the structure of these urban forest corridors. If non-native woody plant species become abundant in the future, they may homogenize the plant community and reduce native biodiversity in these areas. ?? 2011 American Midland Naturalist.

HIF-2α dictates the susceptibility of pancreatic cancer cells to TRAIL by regulating survivin expression

Science.gov (United States)

Harashima, Nanae; Takenaga, Keizo; Akimoto, Miho; Harada, Mamoru

2017-01-01

Cancer cells develop resistance to therapy by adapting to hypoxic microenvironments, and hypoxia-inducible factors (HIFs) play crucial roles in this process. We investigated the roles of HIF-1α and HIF-2α in cancer cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) using human pancreatic cancer cell lines. siRNA-mediated knockdown of HIF-2α, but not HIF-1α, increased susceptibility of two pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL in vitro under normoxic and hypoxic conditions. The enhanced sensitivity to TRAIL was also observed in vivo. This in vitro increased TRAIL sensitivity was observed in other three pancreatic cancer cell lines. An array assay of apoptosis-related proteins showed that knockdown of HIF-2α decreased survivin expression. Additionally, survivin promoter activity was decreased in HIF-2α knockdown Panc-1 cells and HIF-2α bound to the hypoxia-responsive element in the survivin promoter region. Conversely, forced expression of the survivin gene in HIF-2α shRNA-expressing Panc-1 cells increased resistance to TRAIL. In a xenograft mouse model, the survivin suppressant YM155 sensitized Panc-1 cells to TRAIL. Collectively, our results indicate that HIF-2α dictates the susceptibility of human pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL by regulating survivin expression transcriptionally, and that survivin could be a promising target to augment the therapeutic efficacy of death receptor-targeting anti-cancer therapy. PMID:28476028

Camønoen: A pilgrim trail conceived along a communitarian business model

DEFF Research Database (Denmark)

Meged, Jane Widtfeldt; Gyimóthy, Szilvia

2017-01-01

This paper presents an alternative experiment of building an operative communitarian business model to leverage tourism in Southern Denmark. Coastal communities in Denmark have experienced a steady socioeconomic decline, which has further been aggravated by a stagnating tourism and agricultural...... sector. Within this context, coastal regions are attempting to harness the potentials of the emerging collaborative economy by experimenting with communitarian business models. Such is the case of a digitally facilitated pilgrim trail in Denmark, the Camøno, which was conceived in 2016 to mobilize sparse...... and loosely connected local resources to create value for tourists and citizens. The trail sustains over 200 small local actors and attracted over 75.000 visitors after less than a year of operation. Our paper explores the rapid success and consolidation of the Camøno trail by analyzing the performativity...

Neutrophil trails guide influenza-specific CD8+ T cells in the airways

Science.gov (United States)

Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J.; Kim, Minsoo

2016-01-01

During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells is unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8+ T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditional knock-out mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8+ T cell recruitment and effector functions. Collectively, these results suggest neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8+ T cell migration and localization in influenza-infected tissues. PMID:26339033

A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

International Nuclear Information System (INIS)

Stagni, Venturina; Santini, Simonetta; Barilà, Daniela

2012-01-01

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed

Understanding Trail Runners’ Activity on Online Community Forums: An Inductive Analysis of Discussion Topics

Directory of Open Access Journals (Sweden)

Rochat Nadège

2018-03-01

Full Text Available Recreational trail runners often participate in online community forums where they can freely read posted messages, join discussions and/or introduce new discussion topics. This tool can enhance learning as runners connect with other trail runners and reflect on how they can better organize their own practice. Studying forum activity would provide greater insight into the relationship between field practice and dedicated forums. The aim of this study was therefore to detect the topics discussed online by trail runners in order to understand how they collectively look for solutions that help them adapt to issues that emerge during actual practice. The discussion topics (n = 171 on the forum hosted by the Raidlight brand were examined using inductive content analysis, which distinguished two general dimensions. The first dimension was training and had four first-order themes (i.e., “specific trail running sessions”, “complementary trail running sessions”. “training plans” and “specific questions about races” grouped into two second-order themes (i.e., “training session contents” and “structure and schedule”. The second dimension was health and had seven first-order themes (i.e., “tendinitis”, “muscle issues”, “foot issues”, “sprains and fractures”, “pain”, “physiology” and “substances and practitioners” grouped into two second-order themes (i.e., “pain and injury” and “prevention”. The results indicate that the issues that trail runners discuss on forums are significant and that the successions of questions and solutions are a fruitful means for building, enriching and adjusting their activity as they cope with constraints. As a practical consequence, suggestions for improving such online platforms are made.

Uni-directional trail sharing by two species of ants a Monte Carlo study

International Nuclear Information System (INIS)

Kunduraci, T; Kayacan, O

2015-01-01

We study insect traffic, specifically ant traffic on a uni-directional trail which is shared by two species of ants, one of which is ‘good’ at smelling and the other ‘poor’. The two distinct species of ants are placed mixed on the same trail and individuals of both are permitted to make a U-turn when they encounter another ant in front of them. The theoretical scheme for the ant traffic is based on an asymmetric simple exclusion model. The ant traffic on the uni-directional trail is studied as a function of the number of ‘good-smelling’ ants and the evaporation probability of pheromones by keeping the number of ‘poor-smelling ants’ constant during Monte Carlo simulations. (paper)

Systemically administered AAV9-sTRAIL combats invasive glioblastoma in a patient-derived orthotopic xenograft model

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Matheus HW Crommentuijn

2016-01-01

Full Text Available Adeno-associated virus (AAV vectors expressing tumoricidal genes injected directly into brain tumors have shown some promise, however, invasive tumor cells are relatively unaffected. Systemic injection of AAV9 vectors provides widespread delivery to the brain and potentially the tumor/microenvironment. Here we assessed AAV9 for potential glioblastoma therapy using two different promoters driving the expression of the secreted anti-cancer agent sTRAIL as a transgene model; the ubiquitously active chicken β-actin (CBA promoter and the neuron-specific enolase (NSE promoter to restrict expression in brain. Intravenous injection of AAV9 vectors encoding a bioluminescent reporter showed similar distribution patterns, although the NSE promoter yielded 100-fold lower expression in the abdomen (liver, with the brain-to-liver expression ratio remaining the same. The main cell types targeted by the CBA promoter were astrocytes, neurons and endothelial cells, while expression by NSE promoter mostly occurred in neurons. Intravenous administration of either AAV9-CBA-sTRAIL or AAV9-NSE-sTRAIL vectors to mice bearing intracranial patient-derived glioblastoma xenografts led to a slower tumor growth and significantly increased survival, with the CBA promoter having higher efficacy. To our knowledge, this is the first report showing the potential of systemic injection of AAV9 vector encoding a therapeutic gene for the treatment of brain tumors.

Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

International Nuclear Information System (INIS)

Geelen, Caroline MM van; Pennarun, Bodvael; Le, Phuong TK; Vries, Elisabeth GE de; Jong, Steven de

2011-01-01

rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948

Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

Directory of Open Access Journals (Sweden)

de Vries Elisabeth GE

2011-01-01

Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

Road Expansion and Its Influence on Trail Sustainability in Bhutan

Directory of Open Access Journals (Sweden)

Taiichi Ito

2011-12-01

Full Text Available Bhutan was an inhabited wilderness until 1961, when road construction started after the closure of the Tibetan border. Since then, the road network has expanded from the Indian boarder, often tracing traditional trails. This has accelerated commerce as well as movement of people from India, benefitting both the Bhutanese and foreign tourists. At the same time, dependence on imported automobiles and fossil fuel has risen, and roadless areas have begun to shrink. This brought an inevitable loss of traditional environmental knowledge, such as the care of mules for packing, and reduction in physical and mental health among the Bhutanese. People who lost jobs as horsemen moved into towns to find jobs. Road extension is also a double-edged sword for visitors. It has resulted in shrinking trekking areas and loss of traditional culture, both of which have been sacrificed for easy access. Protected areas often function as fortifications against mechanical civilization. However, protected-area status or its zoning does not guarantee that an area will remain roadless where there is considerable resident population. An analysis in Jigme Dorji National Park showed the gradual retreat of trailheads and increasing dependence on automobiles among residents and trekkers. B. MacKaye, a regional planner in the Eastern United States, proposed using trails as a tool to control such mechanical civilization. His philosophy of regional planning suggests two measures; one is consolidated trailheads as dams, and the other is confinement of roads by levees, consisting of new trails and wilderness belts. According to case studies, the author proposed six options for coexistence of trails with roads.

Using cognitive status to predict crash risk: blazing new trails?

Science.gov (United States)

Staplin, Loren; Gish, Kenneth W; Sifrit, Kathy J

2014-02-01

A computer-based version of an established neuropsychological paper-and-pencil assessment tool, the Trail-Making Test, was applied with approximately 700 drivers aged 70 years and older in offices of the Maryland Motor Vehicle Administration. This was a volunteer sample that received a small compensation for study participation, with an assurance that their license status would not be affected by the results. Analyses revealed that the study sample was representative of Maryland older drivers with respect to age and indices of prior driving safety. The relationship between drivers' scores on the Trail-Making Test and prospective crash experience was analyzed using a new outcome measure that explicitly takes into account error responses as well as correct responses, the error-compensated completion time. For the only reliable predictor of crash risk, Trail-Making Test Part B, this measure demonstrated a modest gain in specificity and was a more significant predictor of future safety risk than the simple time-to-completion measure. Improved specificity and the potential for autonomous test administration are particular advantages of this measure for use with large populations, in settings such as health care or driver licensing. © 2013.

VisTrails SAHM: visualization and workflow management for species habitat modeling

Science.gov (United States)

Morisette, Jeffrey T.; Jarnevich, Catherine S.; Holcombe, Tracy R.; Talbert, Colin B.; Ignizio, Drew A.; Talbert, Marian; Silva, Claudio; Koop, David; Swanson, Alan; Young, Nicholas E.

2013-01-01

The Software for Assisted Habitat Modeling (SAHM) has been created to both expedite habitat modeling and help maintain a record of the various input data, pre- and post-processing steps and modeling options incorporated in the construction of a species distribution model through the established workflow management and visualization VisTrails software. This paper provides an overview of the VisTrails:SAHM software including a link to the open source code, a table detailing the current SAHM modules, and a simple example modeling an invasive weed species in Rocky Mountain National Park, USA.

Numerical Investigation of Flow Control Feasibility with a Trailing Edge Flap

DEFF Research Database (Denmark)

Zhu, Wei Jun; Shen, Wen Zhong; Sørensen, Jens Nørkær

2014-01-01

the control system, a standard PID controller is implemented in a finite volume based incompressible flow solver. An immersed boundary method is applied to treat the problem of simulating a deformable airfoil trailing edge. The flow field is solved using a 2D Reynolds averaged Navier-Stokes finite volume...... solver. In order to more accurately simulate wall bounded flows around the immersed boundary, a modified boundary condition is introduced in the k- ω turbulence model. As an example, turbulent flow over a NACA 64418 airfoil with a deformable trailing edge is investigated. Results from numerical...

Validations and improvements of airfoil trailing-edge noise prediction models using detailed experimental data

DEFF Research Database (Denmark)

Kamruzzaman, M.; Lutz, Th.; Würz, W.

2012-01-01

This paper describes an extensive assessment and a step by step validation of different turbulent boundary-layer trailing-edge noise prediction schemes developed within the European Union funded wind energy project UpWind. To validate prediction models, measurements of turbulent boundary-layer pr...... with measurements in the frequency region higher than 1 kHz, whereas they over-predict the sound pressure level in the low-frequency region. Copyright © 2011 John Wiley & Sons, Ltd.......-layer properties such as two-point turbulent velocity correlations, the spectra of the associated wall pressure fluctuations and the emitted trailing-edge far-field noise were performed in the laminar wind tunnel of the Institute of Aerodynamics and Gas Dynamics, University of Stuttgart. The measurements were...... carried out for a NACA 643-418 airfoil, at Re  =  2.5 ×106, angle of attack of −6° to 6°. Numerical results of different prediction schemes are extensively validated and discussed elaborately. The investigations on the TNO-Blake noise prediction model show that the numerical wall pressure fluctuation...

HSP27 phosphorylation modulates TRAIL-induced activation of Src-Akt/ERK signaling through interaction with β-arrestin2.

Science.gov (United States)

Qi, Shimei; Xin, Yinqiang; Qi, Zhilin; Xu, Yimiao; Diao, Ying; Lan, Lei; Luo, Lan; Yin, Zhimin

2014-03-01

Heat shock protein 27 (HSP27) regulates critical cellular functions such as development, differentiation, cell growth and apoptosis. A variety of stimuli induce the phosphorylation of HSP27, which affects its cellular functions. However, most previous studies focused on the role of HSP27 protein itself in apoptosis, the particular role of its phosphorylation state in signaling transduction remains largely unclear. In the present study, we reported that HSP27 phosphorylation modulated TRAIL-triggered pro-survival signaling transduction. In HeLa cells, suppression of HSP27 phosphorylation by specific inhibitor KRIBB3 or MAPKAPK2 (MK2) knockdown and by overexpression of non-phosphorylatable HSP27(3A) mutant demonstrated that hindered HSP27 phosphorylation enhanced the TRAIL-induced apoptosis. In addition, reduced HSP27 phosphorylation by KRIBB3 treatment or MK2 knockdown attenuated the TRAIL-induced activation of Akt and ERK survival signaling through suppressing the phosphorylation of Src. By overexpression of HSP27(15A) or HSP27(78/82A) phosphorylation mutant, we further showed that phosphorylation of HSP27 at serine 78/82 residues was essential to TRAIL-triggered Src-Akt/ERK signaling transduction. Co-immunoprecipitation and confocal microscopy showed that HSP27 interacted with Src and scaffolding protein β-arrestin2 in response of TRAIL stimulation and suppression of HSP27 phosphorylation apparently disrupted the TRAIL-induced interaction of HSP27 and Src or interaction of HSP27 and β-arrestin2. We further demonstrated that β-arrestin2 mediated HSP27 action on TRAIL-induced Src activation, which was achieved by recruiting signaling complex of HSP27/β-arrestin2/Src in response to TRAIL. Taken together, our study revealed that HSP27 phosphorylation modulates TRAIL-triggered activation of Src-Akt/ERK pro-survival signaling via interacting with β-arrestin2 in HeLa cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo.

Science.gov (United States)

Cartland, Siân P; Genner, Scott W; Zahoor, Amna; Kavurma, Mary M

2016-12-02

Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A) and fibroblast growth-factor-2 (FGF-2) either separately (10 ng/mL) or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1) cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.

Electron acceleration by a self-diverging intense laser pulse

International Nuclear Information System (INIS)

Singh, K.P.; Gupta, D.N.; Tripathi, V.K.; Gupta, V.L.

2004-01-01

Electron acceleration by a laser pulse having a Gaussian radial and temporal profile of intensity has been studied. The interaction region is vacuum followed by a gas. The starting point of the gas region has been chosen around the point at which the peak of the pulse interacts with the electron. The tunnel ionization of the gas causes a defocusing of the laser pulse and the electron experiences the action of a ponderomotive deceleration at the trailing part of the pulse with a lower intensity rather than an acceleration at the rising part of the laser pulse with a high intensity, and thus gains net energy. The initial density of the neutral gas atoms should be high enough to properly defocus the pulse; otherwise the electron experiences some deceleration during the trailing part of the pulse and the net energy gain is reduced. The rate of tunnel ionization increases with the increase in the laser intensity and the initial density of neutral gas atoms, and with the decreases in the laser spot size, which causes more defocusing of the laser pulse. The required initial density of neutral gas atoms decreases with the increase in the laser intensity and also with the decrease in the laser spot size

Radar observations of meteor trails, and their interpretation using Fresnel holography: a new tool in meteor science

Directory of Open Access Journals (Sweden)

W. G. Elford

2004-01-01

Full Text Available A Fresnel transform technique has been developed at Adelaide to analyse radar meteor echoes detected in the transverse mode. The genesis for this technique was the study of the structure of the scattering ionization immediately behind the head of the trail, in order to deduce the degree of fragmentation of the ablating meteoroid. The technique has been remarkably successful in not only giving insight into the fragmentation of meteoroids, but also revealing other significant features of the trails including diffusion, lateral motion of the trail during formation due to wind drift, and phase of the scattered signal in the vicinity of the head of the trail. A serendipitous outcome of the analysis is the measurement of the speed and deceleration of the meteoroid producing the trail to a precision far exceeding that available from any other method applied to transverse scatter data. Examples of the outcomes of the technique applied to meteor echoes obtained with a 54MHz narrow beam radar are presented.

LES tests on airfoil trailing edge serration

International Nuclear Information System (INIS)

Zhu, Wei Jun; Shen, Wen Zhong

2016-01-01

In the present study, a large number of acoustic simulations are carried out for a low noise airfoil with different Trailing Edge Serrations (TES). The Ffowcs Williams-Hawkings (FWH) acoustic analogy is used for noise prediction at trailing edge. The acoustic solver is running on the platform of our in-house incompressible flow solver EllipSys3D. The flow solution is first obtained from the Large Eddy Simulation (LES), the acoustic part is then carried out based on the instantaneous hydrodynamic pressure and velocity field. To obtain the time history data of sound pressure, the flow quantities are integrated around the airfoil surface through the FWH approach. For all the simulations, the chord based Reynolds number is around 1.5x10 6 . In the test matrix, the effects from angle of attack, the TE flap angle, the length/width of the TES are investigated. Even though the airfoil under investigation is already optimized for low noise emission, most numerical simulations and wind tunnel experiments show that the noise level is further decreased by adding the TES device. (paper)

Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

Directory of Open Access Journals (Sweden)

Gao S

2015-12-01

Full Text Available Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf-modified polyamidoamine dendrimer (PAMAM was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL-encoding plasmid open reading frame (pORF-hTRAIL, Trail, was condensed by Tf-modified PAMAM to form nanoparticles (NPs. PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days, temozolomide (24.5 days, PAMAM-PEG-Tf/pEGFP (19 days, or saline (17 days. The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the

On the nature and shape of tubulin trails: implications on microtubule self-organization.

Science.gov (United States)

Glade, Nicolas

2012-06-01

Microtubules, major elements of the cell skeleton are, most of the time, well organized in vivo, but they can also show self-organizing behaviors in time and/or space in purified solutions in vitro. Theoretical studies and models based on the concepts of collective dynamics in complex systems, reaction-diffusion processes and emergent phenomena were proposed to explain some of these behaviors. In the particular case of microtubule spatial self-organization, it has been advanced that microtubules could behave like ants, self-organizing by 'talking to each other' by way of hypothetic (because never observed) concentrated chemical trails of tubulin that are expected to be released by their disassembling ends. Deterministic models based on this idea yielded indeed like-looking spatio-temporal self-organizing behaviors. Nevertheless the question remains of whether microscopic tubulin trails produced by individual or bundles of several microtubules are intense enough to allow microtubule self-organization at a macroscopic level. In the present work, by simulating the diffusion of tubulin in microtubule solutions at the microscopic scale, we measure the shape and intensity of tubulin trails and discuss about the assumption of microtubule self-organization due to the production of chemical trails by disassembling microtubules. We show that the tubulin trails produced by individual microtubules or small microtubule arrays are very weak and not elongated even at very high reactive rates. Although the variations of concentration due to such trails are not significant compared to natural fluctuations of the concentration of tubuline in the chemical environment, the study shows that heterogeneities of biochemical composition can form due to microtubule disassembly. They could become significant when produced by numerous microtubule ends located in the same place. Their possible formation could play a role in certain conditions of reaction. In particular, it gives a mesoscopic

Detection of X-ray fluorescence of light elements by electron counting in a low-pressure gaseous electron multiplier

International Nuclear Information System (INIS)

Pansky, A.; Breskin, A.; Chechik, R.; Malamud, G.

1992-12-01

Ionization electrons deposited by soft X-rays in a low pressure (10 Torr) gas medium are efficiently counted by a multistage electron multiplier, providing an accurate measurement of the X-ray photon energy. Energy resolution of 56-28% FWHM were measured for X-rays of 110-676 eV, recording electrical induced charges or visible photons emitted during the avalanche process. It is demonstrated that a combined analysis of the number of electron trail length of an event, provides a powerful and competitive way of resolving ultra soft X-rays. We present the experimental technique, discuss the advantages and limitations of the Primary Electron Counter, and suggest ways to improve its performances. (authors)

Web-Based Museum Trails on PDAs for University-Level Design Students: Design and Evaluation

Science.gov (United States)

Reynolds, R.; Walker, K.; Speight, C.

2010-01-01

This paper describes the development and evaluation of web-based museum trails for university-level design students to access on handheld devices in the Victoria and Albert Museum (V&A) in London. The trails offered students a range of ways of exploring the museum environment and collections, some encouraging students to interpret objects and…

Human embryonic and induced pluripotent stem cells express TRAIL receptors and can be sensitized to TRAIL-Iiduced apoptosis

Czech Academy of Sciences Publication Activity Database

Vinarsky, V.; Krivanek, J.; Rankel, Liina; Nahácka, Zuzana; Barta, T.; Jaros, J.; Anděra, Ladislav; Hampl, A.

2013-01-01

Roč. 22, č. 22 (2013), s. 2964-2974 ISSN 1547-3287 R&D Projects: GA ČR GAP301/10/1971 Grant - others:GA MŠk(CZ) ED1.100/02/0123 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : TRAIL * apoptosis * pluripotent stem cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.202, year: 2013

Targeting pro-apoptotic trail receptors sensitizes HeLa cervical cancer cells to irradiation-induced apoptosis

NARCIS (Netherlands)

Maduro, John H.; de Vries, Elisabeth G. E.; Meersma, Gert-Jan; Hougardy, Brigitte M. T.; van der Zee, Ate G. J.; De Jong, Steven

2008-01-01

Purpose: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. Methods and Materials: Recombinant human TRAIL

Pneumatic artificial muscles for trailing edge flap actuation: a feasibility study

International Nuclear Information System (INIS)

Woods, Benjamin K S; Wereley, Norman M; Kothera, Curt S; Sirohi, Jayant

2011-01-01

In this study a novel aircraft trailing edge flap actuation system was developed and tested. Pneumatic artificial muscles (PAMs) were used as the driving elements of this system to demonstrate their feasibility and utility as an alternative aerospace actuation technology. A prototype flap/actuator system was integrated into a model wing section and tested on the bench-top under simulated airloads for flight at 100 m s −1 (M = 0.3) and in an open-jet wind tunnel at free stream velocities ranging up to 45 m s −1 (M = 0.13). Testing was performed for actuator pressures ranging from 0.069 to 0.62 MPa (10–90 psi) and actuation frequencies from 0.1 to 31 Hz. Results show that the PAM-driven trailing edge flap system can generate substantial and sustainable dynamic deflections, thereby proving the feasibility of using pneumatic artificial muscle actuators in a trailing edge flap system. Key issues limiting system performance are identified, that should be resolved in future research

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

Science.gov (United States)

Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

2016-01-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

Directory of Open Access Journals (Sweden)

Yuan Feng

Full Text Available Tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5 induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

Science.gov (United States)

Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

2012-05-01

Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

A cellular automata model for ant trails

Indian Academy of Sciences (India)

In this study, the unidirectional ant traffic flow with U-turn in an ant trail was investigated using one-dimensional cellular automata model. It is known that ants communicate with each other by dropping a chemical, called pheromone, on the substrate. Apart from the studies in the literature, it was considered in the model that ...

4D planning over the full course of fractionation: assessment of the benefit of tumor trailing

Science.gov (United States)

McQuaid, D.; Bortfeld, T.

2011-11-01

Tumor trailing techniques have been proposed as a method of reducing the problem of intrafraction motion in radiotherapy. However the dosimetric assessment of trailing strategies is complicated by the requirement to study dose deposition over a full fraction delivery. Common 4D planning strategies allowing assessment of dosimetric motion effects study a single cycle acquired with 4DCT. In this paper, a methodology to assess dose deposited over an entire treatment course is advanced and used to assess the potential benefit of tumor trailing strategies for lung cancer patients. Two digital phantoms mimicking patient anatomy were each programmed to follow the tumor respiratory trajectory observed from 33 lung cancer patients. The two phantoms were designed to represent the cases of a small (volume = 13.6 cm3) and large (volume = 181.7 cm3) lung lesion. Motion margins required to obtain CTV coverage by 95% of the prescription dose to 90% of the available cases were computed for a standard treatment strategy and a trailing treatment strategy. The trailing strategy facilitated a margin reduction of over 30% relative to the conventional delivery. When the dose was computed across the entire delivery for the 33 cases, the trailing strategy was found to significantly reduce the underdosage to the outlier cases and the reduced trailing margin facilitated a 15% (small lesion) and 4% (large lesion) reduction for the mean lung dose and 7% (small lesion) and 10% (large lesion) for the mean esophagus dose. Finally, for comparison an ideal continuous tracking strategy was assessed and found to further reduce the mean lung and esophagus dose. However, this improvement comes at the price of increased delivery complexity and increased reliance on tumor localization accuracy.

4D planning over the full course of fractionation: assessment of the benefit of tumor trailing

International Nuclear Information System (INIS)

McQuaid, D; Bortfeld, T

2011-01-01

Tumor trailing techniques have been proposed as a method of reducing the problem of intrafraction motion in radiotherapy. However the dosimetric assessment of trailing strategies is complicated by the requirement to study dose deposition over a full fraction delivery. Common 4D planning strategies allowing assessment of dosimetric motion effects study a single cycle acquired with 4DCT. In this paper, a methodology to assess dose deposited over an entire treatment course is advanced and used to assess the potential benefit of tumor trailing strategies for lung cancer patients. Two digital phantoms mimicking patient anatomy were each programmed to follow the tumor respiratory trajectory observed from 33 lung cancer patients. The two phantoms were designed to represent the cases of a small (volume = 13.6 cm 3 ) and large (volume = 181.7 cm 3 ) lung lesion. Motion margins required to obtain CTV coverage by 95% of the prescription dose to 90% of the available cases were computed for a standard treatment strategy and a trailing treatment strategy. The trailing strategy facilitated a margin reduction of over 30% relative to the conventional delivery. When the dose was computed across the entire delivery for the 33 cases, the trailing strategy was found to significantly reduce the underdosage to the outlier cases and the reduced trailing margin facilitated a 15% (small lesion) and 4% (large lesion) reduction for the mean lung dose and 7% (small lesion) and 10% (large lesion) for the mean esophagus dose. Finally, for comparison an ideal continuous tracking strategy was assessed and found to further reduce the mean lung and esophagus dose. However, this improvement comes at the price of increased delivery complexity and increased reliance on tumor localization accuracy.

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Siân P. Cartland

2016-12-01

Full Text Available Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A and fibroblast growth-factor-2 (FGF-2 either separately (10 ng/mL or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1 cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.

Noise model for serrated trailing edges compared to wind tunnel measurements

DEFF Research Database (Denmark)

Fischer, Andreas; Bertagnolio, Franck; Shen, Wen Zhong

2016-01-01

A new CFD RANS based method to predict the far field sound pressure emitted from an aerofoil with serrated trailing edge has been developed. The model was validated by comparison to measurements conducted in the Virginia Tech Stability Wind Tunnel. The model predicted 3 dB lower sound pressure...... levels, but the tendencies for the different configurations were predicted correctly. Therefore the model can be used to optimise the serration geometry. A disadvantage of the new model is that the computational costs are significantly higher than for the Amiet model for a straight trailing edge. However...

DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8.

Science.gov (United States)

Kurita, Satoshi; Higuchi, Hajime; Saito, Yoshimasa; Nakamoto, Nobuhiro; Takaishi, Hiromasa; Tada, Shinichiro; Saito, Hidetsugu; Gores, Gregory J; Hibi, Toshifumi

2010-06-01

DNA methylation plays a critical role in chromatin remodeling and gene expression. DNA methyltransferases (DNMTs) are hypothesized to mediate cellular DNA methylation status and gene expression during mammalian development and in malignant diseases. In this study, we examined the role of DNA methyltransferase 1 (DNMT1) and DNMT3b in cell proliferation and survival of hepatocellular carcinoma (HCC) cells. Gene silencing of both DNMT1 and DNMT3b by targeted siRNA knockdown reduces cell proliferation and sensitizes the cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death. The proapoptotic protein caspase-8 demonstrated promoter hypermethylation in HCC cells and was up-regulated by knockdown of DNMT1 and DNMT3b both at mRNA and protein levels. In addition, death receptor TRAIL-R2/DR5 (TRAIL receptor 2/death receptor 5) did not exhibit promoter hypermethylation in HCC cells but was also up-regulated by knockdown of DNMT1 and DNMT3b both at mRNA and protein levels. Consistent with this observation, the combined transfection of DNMT1-siRNA plus DNMT3b-siRNA enhanced formation of the TRAIL-death-inducing signaling complex formation in HCC cells. In conclusion, our data suggest that DNA methylation of specific genomic regions maintained by DNMT1 and DNMT3b plays a critical role in survival of HCC cells, and a simultaneous knockdown of both DNMT1 and DNMT3b may be a novel anticancer strategy for the treatment of HCC.

pupil initiatives in urban nature trail development: pmb moss

African Journals Online (AJOL)

.ritzburg is provided. Negotiations and procedures initiated by standard 9 pupils in stimulating authorities and the public to recog~ nise the need for urban trail development and metropolitan open space. (MOSS) are outlined. long-tenn ...

Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells.

Science.gov (United States)

Griffith, Thomas S; Brincks, Erik L; Gurung, Prajwal; Kucaba, Tamara A; Ferguson, Thomas A

2011-01-15

Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8(+) regulatory T cells. This study examined the mechanism by which these CD8(+) regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4(+) T cells and led to increased TRAIL expression by splenic CD8(+) T cells. Unlike wild-type mice, Trail(-/-) or Dr5(-/-) mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8(+) T cells from Trail(-/-) mice that were first injected via the AC with Ag were unable to transfer tolerance to naive recipient wild-type mice, but CD8(+) T cells from AC-injected wild-type or Dr5(-/-) mice could transfer tolerance. Importantly, the transferred wild-type (Trail(+/+)) CD8(+) T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail(-/-) CD8(+) T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that "helpless" CD8(+) regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye.

Electronic health records: what does your signature signify?

Directory of Open Access Journals (Sweden)

Victoroff MD Michael S

2012-08-01

Full Text Available Abstract Electronic health records serve multiple purposes, including clinical communication, legal documentation, financial transaction capture, research and analytics. Electronic signatures attached to entries in EHRs have different logical and legal meanings for different users. Some of these are vestiges from historic paper formats that require reconsideration. Traditionally accepted functions of signatures, such as identity verification, attestation, consent, authorization and non-repudiation can become ambiguous in the context of computer-assisted workflow processes that incorporate functions like logins, auto-fill and audit trails. This article exposes the incompatibility of expectations among typical users of electronically signed information.

The predatory mite Neoseiulus womersleyi (Acari: Phytoseiidae) follows extracts of trails left by the two-spotted spider mite Tetranychus urticae (Acari: Tetranychidae).

Science.gov (United States)

Shinmen, Tsubasa; Yano, Shuichi; Osakabe, Mh

2010-10-01

As it walks, the two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) spins a trail of silk threads, that is followed by the predatory mite, Neoseiulus womersleyi Schicha (Acari: Phytoseiidae). Starved adult female N. womersleyi followed T. urticae trails laid down by five T. urticae females but did not follow a trail of one T. urticae female, suggesting that the amount of spun threads and their chemical components should correlate positively with the number of T. urticae individuals. To examine whether chemical components of T. urticae trails are responsible for the predatory mite's trail following, we collected separate T. urticae threads from the exuviae and eggs, and then washed the threads with methanol to separate chemical components from physical attributes of the threads. Female N. womersleyi did not follow T. urticae trails that had been washed with methanol but contained physical residues, but they did follow the direction to which the methanol extracts of the T. urticae trails was applied. These results suggest that the predatory mite follows chemical, not physical, attributes of T. urticae trails.

Interpreter's Guide to Blackbird Marsh Nature Trail.

Science.gov (United States)

Environmental Studies Center, Pensacola, FL.

This booklet was prepared to help the user interpret the natural history of Blackbird Marsh Nature Trail in Escambia County, Florida, and serves as a guide to the animal and plant life. The publication is part of a series of illustrated guides designed for use by teachers and students of all levels in conjunction with field trips to the 1200-acre…

Effect of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) combined with ionizing radiation on proliferation and apoptosis of breast cancer MCF-7 cell lines

International Nuclear Information System (INIS)

Zhang Yusong; Fu Jinxiang; Zhou Jianying; Zhou Liying; Guo Xiaokui; Zhuang Zhixiang

2007-01-01

Objective: To investigate the effect of Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) on breast cancer MCF-7 cell lines and the possibility of TRAIL combined with radiotherapy. Methods: 1 x 10 4 /ml MCF-7 cell suspension were added to each well of 96-well plates, MCF cell were treated with radiotherapy(RT), TRAIL at different concentration or RT combined with TRAIL. MTT working solution was added and calculated the inhibitory rates of MCF-7 cells. MCF-7 cell suspension was added to 6-well plates then treated with TRAIL(1 μg/ml), 8 Gy RT or TRAIL combined with 8 Gy RT. The rates of apoptosis were detected by flow cytometry after incubated 48 h. RT-PCR methods were employed to analyze the expression of apoptosis related gene in different treatment group. Results: MCF-7 cell lines were resistant to TRAIL, but the inhibitory rate was upregulated when MCF-7 cell was treated with TRAIL combined with RT, which had a significant difference compared with RT or TRAIL alone. The expression of Bcl-2 and Bcl-Xl gene were down-regulated when MCF-7 cell lines was treated with 8 Gy RT combined with TRAIL. Conclusions: In vitro, MCF-7 cell lines are resistant to TRAIL, but TRAIL combined with radiotherapy increased the cytotoxic effect. TRAIL has a promising prospect in clinical use. (authors)

Trail making test performance in youth varies as a function of anatomical coupling between the prefrontal cortex and distributed cortical regions

Directory of Open Access Journals (Sweden)

Nancy Raitano Lee

2014-07-01

Full Text Available While researchers have gained a richer understanding of the neural correlates of executive function in adulthood, much less is known about how these abilities are represented in the developing brain and what structural brain networks underlie them. Thus, the current study examined how individual differences in executive function, as measured by the Trail Making Test (TMT, relate to structural covariance in the pediatric brain. The sample included 146 unrelated, typically developing youth (80 females, ages 9-14 years, who completed a structural MRI scan of the brain and the Halstead-Reitan TMT (intermediate form. TMT scores used to index executive function included those that evaluated set-shifting ability: Trails B time (number-letter sequencing and the difference in time between Trails B and A (number sequencing only. Anatomical coupling was measured by examining correlations between mean cortical thickness (MCT across the entire cortical ribbon and individual vertex thickness measured at ~81,000 vertices. To examine how TMT scores related to anatomical coupling strength, linear regression was utilized and the interaction between age-normed TMT scores and both age and sex-normed MCT was used to predict vertex thickness. Results revealed that stronger Trails B scores were associated with greater anatomical coupling between a large swath of prefrontal cortex and the rest of cortex. For the difference between Trails B and A, a network of regions in the frontal, temporal and parietal lobes was found to be more tightly coupled with the rest of cortex in stronger performers. This study is the first to highlight the importance of structural covariance in the prediction of individual differences in executive function skills in youth. Thus, it adds to the growing literature on the neural correlates of childhood executive functions and identifies neuroanatomic coupling as a biological substrate that may contribute to executive function and dysfunction in

Trail making test performance in youth varies as a function of anatomical coupling between the prefrontal cortex and distributed cortical regions

Science.gov (United States)

Lee, Nancy Raitano; Wallace, Gregory L.; Raznahan, Armin; Clasen, Liv S.; Giedd, Jay N.