Past studies have shown that apoptosis mediated by TNF-related apoptosis-inducing ligand (TRAIL) is regulated by the expression of two death receptors [TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2] and two decoy receptors (TRAIL-R3 and TRAIL-R4) that inhibit apoptosis. In previous studies, we have shown that TRAIL but not other members of the tumor necrosis factor family induce apoptosis in approximately two-thirds of melanoma cell lines. Here, we examined whether the expression of TRAIL-R at the mRNA and protein level in a panel of 28 melanoma cell lines and melanocytes correlated with their sensitivity to TRAIL-induced apoptosis. We report that at least three factors appear to underlie the variability in TRAIL-induced apoptosis. (a) Four of nine cell lines that were insensitive to TRAIL-induced apoptosis failed to express death receptors, and in two instances, lines were devoid of all TRAIL-Rs. Southern analysis suggested this was due to loss of the genes for the death receptors. (b) Despite the presence of mRNA for the TRAIL-R, some of the lines failed to express TRAIL-R protein on their surface. This was evident for TRAIL-R1 and more so for the TRAIL decoy receptors TRAIL-R3 and -R4. Studies on permeabilized cells revealed that the receptors were located within the cytoplasm and redistribution from the cytoplasm may represent a posttranslational control mechanism. (c) Surface expression of TRAIL-R1 and -R2 (but not TRAIL-R3 and -R4) showed an overall correlation with TRAIL-induced apoptosis. However, certain melanoma cell lines and clones were relatively resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and moderate levels of TRAIL-R1 and -R2 expression. This may indicate the presence of inhibitors within the cells, but resistance to apoptosis could not be correlated with expression of the caspase inhibitor FLICE-inhibitory protein. mRNA for another TRAIL receptor, osteoprotegerin, was expressed in 22 of the melanoma lines but not on melanocytes. Its role in induction of apoptosis remains to be studied. These results appear to have important implications for future clinical studies on TRAIL.
Expression and function of the TRAIL apoptotic pathway was investigated in normal and malignant breast epithelial cells. Glutathione-S-transferase (GST)-TRAIL extracellular domain fusion proteins were produced to analyze TRAIL-induced apoptosis. Only GST-TRAIL constructs containing regions homologous to the Fas self-association and ligand binding domains could induce apoptosis. GST-TRAIL induced significant (>90%) apoptosis in just one of eight normal and one of eight malignant breast cell lines. All other lines were relatively resistant to TRAIL-induced apoptosis. Activating TRAIL receptors DR4 and DR5 were expressed in all normal and malignant breast cell lines. The inhibitory receptor TRID was highly expressed in one of four normal and two of seven malignant breast cell lines. DR4, DR5, or TRID expression did not correlate with sensitivity to TRAIL-induced apoptosis. Incubation of cell lines with doxorubicin or 5-fluorouracil significantly augmented TRAIL-induced apoptosis in most breast cell lines. By fractional inhibition analysis, the toxicity of the combination of TRAIL and doxorubicin or 5-fluorouracil was synergistic compared with either agent alone. In contrast, melphalan and paclitaxel augmented TRAIL-induced apoptosis in few cell lines, and methotrexate did not augment it in any cell line. Augmentation of TRAIL-induced apoptosis by doxorubicin or 5-fluorouracil was mediated through caspase activation. This was evidenced by the fact that chemotherapy agents that synergized with TRAIL (e.g., doxorubicin) themselves caused cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and their toxicity was blocked by the caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2 (ZVAD-fmk). The combination of TRAIL and doxorubicin caused significantly greater caspase-3 and PARP cleavage, and the combined toxicity also was inhibited by ZVAD-fmk. In contrast, chemotherapy agents that did not augment TRAIL-induced apoptosis (e.g., methotrexate) caused minimal caspase-3 and PARP cleavage by themselves, and their toxicity was not inhibited by ZVAD-fmk. These drugs also did not increase caspase-3 or PARP cleavage when combined with TRAIL. In summary, few breast cell lines are sensitive to TRAIL-induced apoptosis, and no difference in sensitivity is found between normal and malignant cell lines. Treatment with chemotherapy provides an approach to sensitize breast cancer cells to TRAIL-induced apoptosis.
We present a new approach to identify satellite trails (or other linear artifacts) in ACS/WFC imaging data using a modified Radon Transform. We demonstrate that this approach is sensitive to features with mean brightness significantly below the background noise level, and it is resistant to the influence of bright astronomical sources (e.g., stars, galaxies) in most cases. Comparing with a set of satellite trails identified by eye, we find a trail recovery rate of 85\% and a false detection rate (after removing diffraction spikes that are easily filtered) of 2.5\%. By performing an analysis using a much larger ACS/WFC data set where false trails are identified by their persistence across multiple images of the same field, we identify the Radon Transform parameter space and image properties where our algorithm is unreliable, and estimate a false detection rate of $\sim10\%$ elsewhere. We apply our method to ACS/WFC data taken between 2002 and 2022 to determine both the frequency of satellite trail contamination in science data and also the typical trail brightness as a function of time. We find the rate of satellite trail contamination has increased by approximately a factor of two
White-light observations from the WISPR instrument on NASA's Parker Solar Probe recently revealed the presence of a narrow, dense dust trail close to the orbit of asteroid 3200 Phaethon. Although Geminid-related, it aligns imperfectly with Phaethon's orbit and known Geminid meteoroid orbits. To address the nature of this dust trail, we performed a detailed comparison between the WISPR trail observations and several well-developed Geminid models. Simulating these models in the WISPR field of view visually demonstrates that the WISPR trail almost certainly represents the true ``density core'' of the Geminid stream. Trends in model trail width and offset from Phaethon's orbit, both as functions of true anomaly, agree with observations to varying extents. All the models, however, place their apparent core interior to the parent orbit due to Poynting-Robertson forces, contradictory to the WISPR trail which is exterior to Phaethon's orbit. Therefore, Phaethon's current orbit likely does not represent the orbit of the system parent, which most probably had a larger semi-major axis. These findings provide new initial conditions for future Geminid models, with WISPR identifying the Geminid
The increasing popularity of outdoor recreational activities (such as hiking and biking) has boosted the demand for a conversational AI system to provide informative and personalized suggestion on outdoor trails. Challenges arise in response to (1) how to provide accurate outdoor trail information via conversational AI; and (2) how to enable usable and efficient recommendation services. To address above, this paper discusses the preliminary and practical lessons learned from developing Judy, an outdoor trail recommendation chatbot based on the large language model (LLM) with retrieval augmented generation (RAG). To gain concrete system insights, we have performed case studies with the outdoor trails in Connecticut (CT), US. We have conducted web-based data collection, outdoor trail data management, and LLM model performance studies on the RAG-based recommendation. Our experimental results have demonstrated the accuracy, effectiveness, and usability of Judy in recommending outdoor trails based on the LLM with RAG.
We present the JWST discovery of a highly-extincted ($A_V\sim52$) candidate brown dwarf ($\sim0.018$M$_\odot$) in the outskirts of the Trapezium Cluster that appears to be coincident with the end of a $\sim 1700\,$au long, remarkably uniformly wide, dark trail that broadens only slightly at the end opposite the point source. We examine whether a dusty trail associated with a highly-extincted brown dwarf could plausibly be detected with JWST and explore possible origins. We show that a dusty trail associated with the brown dwarf could be observable if dust within it is larger than that in the ambient molecular cloud. For example, if the ambient cloud has a standard $\sim0.25$$μ$m maximum grain size and the trail contains micron-sized grains, then the trail will have a scattering opacity over an order of magnitude larger compared to the surroundings in NIRCam short-wavelength filters. We use a simple model to show that a change in maximum grain size can reproduce the high $A_V$ and the multi-filter NIRCam contrast seen between the trail and its surroundings. We propose and explore two possible mechanisms that could be responsible for the trail: i) a weak FUV radiation-driven wind fro
Natural environments pose significant challenges for autonomous robot navigation, particularly due to their unstructured and ever-changing nature. Hiking trails, with their dynamic conditions influenced by weather, vegetation, and human traffic, represent one such challenge. This work introduces a novel approach to autonomous hiking trail navigation that balances trail adherence with the flexibility to adapt to off-trail routes when necessary. The solution is a Traversability Analysis module that integrates semantic data from camera images with geometric information from LiDAR to create a comprehensive understanding of the surrounding terrain. A planner uses this traversability map to navigate safely, adhering to trails while allowing off-trail movement when necessary to avoid on-trail hazards or for safe off-trail shortcuts. The method is evaluated through simulation to determine the balance between semantic and geometric information in traversability estimation. These simulations tested various weights to assess their impact on navigation performance across different trail scenarios. Weights were then validated through field tests at the West Virginia University Core Arboretum, d
Astrometric measurements are significantly challenged by the relative motion between the point source and the telescope, primarily due to the difficulty in accurately determining the position of the point source at the mid-exposure moment. Especially when the trail is irregular in shape or results from nonuniform relative motion, determining the centroid of such a trail becomes significantly more challenging. To address this issue, a new centroiding algorithm for point-source trails has been developed. This algorithm employs a piecewise linear model to approximate the irregular trajectory of a point source. An estimated intensity distribution of the trail is constructed by integrating the point-spread function with the approximated trajectory. The cost function is defined as the difference between the estimated and observed trail intensity distributions, with an added smoothness constraint term. Optimizing this cost function yields a refined trajectory fit. A coarse-to-fine iterative approach is used to progressively converge on the true trajectory of the point source, ultimately determining both the trail's centroid and the trajectory of the point source. The efficacy of the algor
While most dwarf galaxies are strongly dark matter dominated, two remarkable objects in the NGC 1052 field, DF2 and DF4, appear to lack dark matter. DF2 and DF4 were recently found to be part of a trail of low luminosity galaxies that follow a linear relation between their position and radial velocity. If the other galaxies on this trail formed together with DF2 and DF4, e.g., from gas that was separated from dark matter through a 'bullet dwarf' collision, they may lack dark matter as well. Here we constrain the mass of DF9, the galaxy on the trail that most closely resembles DF2 and DF4. Using Keck/KCWI we find that DF9's stellar velocity dispersion is $6.5^{+3.9}_{-4.3}$ km s$^{-1}$. This is consistent with the $8.3^{+0.9}_{-1.4}$ km s$^{-1}$ dispersion that is expected from DF9's $1.4\times 10^8$ M$_\odot$ stellar mass alone, and we conclude that - like DF2 and DF4 - dark matter is not required to explain the kinematics of DF9. The dispersion is far below the $24\pm3$ km s$^{-1}$ expected if DF9 had a $1.4\times 10^{10}$ M$_\odot$ dark matter halo falling on the stellar mass-halo mass relation. As demonstrated in Appendix B, these results are not sensitive to the assumed distanc
The Lighthouse pulsar (PSR J1101$-$6101) sports a bright X-ray trail and filament. The synchrotron emission from both structures is expected to be polarized, with electric vector position angle (EVPA) perpendicular to the magnetic field direction and polarization degree (PD) indicating the local degree of magnetic turbulence. We present a 1 megasecond Imaging X-ray Polarimetry Explorer (IXPE) observation of the Lighthouse complex. At the 99% confidence level, we detect the filament polarization with PD $55 \pm 18\%$ and EVPA indicating a magnetic field parallel to the filament axis. The large PD implies a turbulent magnetic field weaker than the background field, in conflict with some existing models. We also detect polarization from the pulsar and trail. The trail's X-ray polarization is nearly orthogonal to the radio polarization, suggesting spatial separation between the X-ray- and radio-emitting leptons. The pulsar polarization is well-fit by the rotating vector model.
In this paper, the properties of minimal trails in a directed acyclic graph that is restricted not to contain an active cycle are studied. We are motivated by an application of the results in the copula-based Bayesian Network model developed recently. We propose a partial order on the set of trails activated by a certain subset of nodes, and show that every minimal trail, according to such an order, has a simple structure.
Teams of mobile [aerial, ground, or aquatic] robots have applications in resource delivery, patrolling, information-gathering, agriculture, forest fire fighting, chemical plume source localization and mapping, and search-and-rescue. Robot teams traversing hazardous environments -- with e.g. rough terrain or seas, strong winds, or adversaries capable of attacking or capturing robots -- should plan and coordinate their trails in consideration of risks of disablement, destruction, or capture. Specifically, the robots should take the safest trails, coordinate their trails to cooperatively achieve the team-level objective with robustness to robot failures, and balance the reward from visiting locations against risks of robot losses. Herein, we consider bi-objective trail-planning for a mobile team of robots orienteering in a hazardous environment. The hazardous environment is abstracted as a directed graph whose arcs, when traversed by a robot, present known probabilities of survival. Each node of the graph offers a reward to the team if visited by a robot (which e.g. delivers a good to or images the node). We wish to search for the Pareto-optimal robot-team trail plans that maximize tw
We present TRAIL: an algorithm that uses a novel consensus procedure to tolerate failed or malicious shards within a blockchain-based cryptocurrency. Our algorithm takes a new approach of selecting validator shards for each transaction from those that previously held the assets being transferred. This approach ensures the algorithm's robustness and efficiency. TRAIL is presented using PBFT for internal shard transaction processing and a modified version of PBFT for external cross-shard validation. We describe TRAIL, prove it correct, analyze its message complexity, and evaluate its performance. We propose various TRAIL optimizations: we describe how it can be adapted to other Byzantine-tolerant consensus algorithms, how a complete system may be built on the basis of it, and how TRAIL can be applied to existing and future sharded blockchains.
Asteroid detections in astronomical images may appear as trails due to a combination of their apparent rate of motion and exposure duration. Nearby asteroids in particular typically have high apparent rates of motion and acceleration. Their recovery, especially on their discovery apparition, depends upon obtaining good astrometry from the trailed detections. We present an analytic function describing a trailed detection under the assumption of a Gaussian point spread function (PSF) and constant rate of motion. We have fit the function to both synthetic and real trailed asteroid detections from the Pan-STARRS1 survey telescope to obtain accurate astrometry and photometry. For short trails our trailing function yields the same astrometric and photometry accuracy as a functionally simpler 2-d Gaussian but the latter underestimates the length of the trail - a parameter that can be important for measuring the object's rate of motion and assessing its cometary activity. For trails longer than about 10 pixels (> 3xPSF) our trail fitting provides 3-times better astrometric accuracy and up to 2 magnitudes improvement in the photometry. The trail fitting algorithm can be implemented at th
The X-ray source CXOU J163802.6-471358is thought to be a pulsar wind nebula (PWN), as it shows an extended, $\approx 40$ arcsec trail from a compact source. Here we present GMRT observations of this source at 330 and 1390 MHz, which reveal a remarkable linear radio trail $\approx 90$ arcsec in extent. Although the radio trail points back to the supernova remnant (SNR) G338.1+0.4, $\approx 50$ arcmin from ,CXOU J163802.6-471358 associating it with this remnant would require a very large velocity for the pulsar. There are no known galactic SNRs close to the PWN and radio trail. No pulsar has yet been identified in CXOU J163802.6-471358, but if one could be found, this would allow more quantitative studies of the PWN and radio trail to be made.
The increasing adoption of agentic workflows across diverse domains brings a critical need to scalably and systematically evaluate the complex traces these systems generate. Current evaluation methods depend on manual, domain-specific human analysis of lengthy workflow traces - an approach that does not scale with the growing complexity and volume of agentic outputs. Error analysis in these settings is further complicated by the interplay of external tool outputs and language model reasoning, making it more challenging than traditional software debugging. In this work, we (1) articulate the need for robust and dynamic evaluation methods for agentic workflow traces, (2) introduce a formal taxonomy of error types encountered in agentic systems, and (3) present a set of 148 large human-annotated traces (TRAIL) constructed using this taxonomy and grounded in established agentic benchmarks. To ensure ecological validity, we curate traces from both single and multi-agent systems, focusing on real-world applications such as software engineering and open-world information retrieval. Our evaluations reveal that modern long context LLMs perform poorly at trace debugging, with the best Gemini
We observed 34 comets using the 24 micron camera on the Spitzer Space Telescope. Each image contains the nucleus and covers at least 10^6 km of each comet's orbit. Debris trails due to mm-sized or larger particles were found along the orbits of 27 comets; 4 comets had small-particle dust tails and a viewing geometry that made debris trails impossible to distinguish; and only 3 had no debris trail despite favorable observing conditions. There are now 30 Jupiter-family comets with known debris trails, of which 22 are reported in this paper for the first time. The detection rate is >80%, indicating that debris trails are a generic feature of short-period comets. By comparison to orbital calculations for particles of a range of sizes ejected over 2 yr prior to observation, we find that particles comprising 4 debris trails are typically mm-sized while the remainder of the debris trails require particles larger than this. The lower-limit masses of the debris trails are typically 10^11 g, and the median mass loss rate is 2 kg/s. The mass-loss rate in trail particles is comparable to that inferred from OH production rates and larger than that inferred from visible-light scattering in co
We investigate the problem of packing and covering odd $(u,v)$-trails in a graph. A $(u,v)$-trail is a $(u,v)$-walk that is allowed to have repeated vertices but no repeated edges. We call a trail odd if the number of edges in the trail is odd. Let $ν(u,v)$ denote the maximum number of edge-disjoint odd $(u,v)$-trails, and $τ(u,v)$ denote the minimum size of an edge-set that intersects every odd $(u,v)$-trail. We prove that $τ(u,v)\leq 2ν(u,v)+1$. Our result is tight---there are examples showing that $τ(u,v)=2ν(u,v)+1$---and substantially improves upon the bound of $8$ obtained in [Churchley et al 2016] for $τ(u,v)/ν(u,v)$. Our proof also yields a polynomial-time algorithm for finding a cover and a collection of trails satisfying the above bounds. Our proof is simple and has two main ingredients. We show that (loosely speaking) the problem can be reduced to the problem of packing and covering odd $(uv,uv)$-trails losing a factor of 2 (either in the number of trails found, or the size of the cover). Complementing this, we show that the odd-$(uv,uv)$-trail packing and covering problems can be tackled by exploiting a powerful min-max result of [Chudnovsky et al 2006] for packing verte
This paper proposes a methodology for documenting data mining (DM) projects, Rastro-DM (Trail Data Mining), with a focus not on the model that is generated, but on the processes behind its construction, in order to leave a trail (Rastro in Portuguese) of planned actions, training completed, results obtained, and lessons learned. The proposed practices are complementary to structuring methodologies of DM, such as CRISP-DM, which establish a methodological and paradigmatic framework for the DM process. The application of best practices and their benefits is illustrated in a project called 'Cladop' that was created for the classification of PDF documents associated with the investigative process of damages to the Brazilian Federal Public Treasury. Building the Rastro-DM kit in the context of a project is a small step that can lead to an institutional leap to be achieved by sharing and using the trail across the enterprise.
The observation that TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF cytokine family, induces apoptosis in a number of different tumor cell types led us to compare the tumoricidal effects of TRAIL to those of other TNF family molecules on human melanoma cells. We found that a high proportion of the melanoma cell lines tested were killed by TRAIL, whereas all the melanoma lines were resistant to the other TNF family cytokines tested. TRAIL-induced death was characterized by caspase activation and cellular protein cleavage within minutes of TRAIL addition, and death could be completely inhibited by the caspase inhibitors Ile-Glu-Thr-Asp (IETD) and Val-Ala-Asp (VAD), indicating the presence of a TRAIL receptor signaling pathway similar to that identified for Fas and TNF receptors. Specific TRAIL receptor expression was determined by RT-PCR, and the presence of mRNA encoding the "protective" TRAIL receptors did not correspond to resistance or sensitivity to TRAIL-induced apoptosis. Addition of protein synthesis inhibitors to TRAIL-resistant melanomas rendered them sensitive to TRAIL, indicating that the presence or the absence of intracellular apoptosis inhibitors may mediate resistance or sensitivity to TRAIL-mediated apoptosis. Expression of one such inhibitor, FLICE-inhibitory protein (FLIP), was highest in the TRAIL-resistant melanomas, while being low or undetectable in the TRAIL-sensitive melanomas. Furthermore, addition of actinomycin D to TRAIL-resistant melanomas resulted in decreased intracellular concentrations of FLIP, which correlated with their acquisition of TRAIL sensitivity. Collectively, our results indicate that TRAIL-induced apoptosis occurs through a caspase signaling cascade and that resistance is controlled by intracellular regulators of apoptosis.