Miracle-dz/UniFAR-FTUs huggingface dataset:
The Calpain/Calpastatin System Has Opposing Roles in Growth and Metastatic Dissemination of Melanoma

Conventional calpains are ubiquitous cysteine proteases whose activity is promoted by calcium signaling and specifically limited by calpastatin. Calpain expression has been shown to be increased in human malignant cells, but the contribution of the calpain/calpastatin system in tumorigenesis remains unclear. It may play an important role in tumor cells themselves (cell growth, migration, and a contrario cell death) and/or in tumor niche (tissue infiltration by immune cells, neo-angiogenesis). In this study, we have used a mouse model of melanoma as a tool to gain further understanding of the role of calpains in tumor progression. To determine the respective importance of each target, we overexpressed calpastatin in tumor and/or host in isolation. Our data demonstrate that calpain inhibition in both tumor and host blunts tumor growth, while paradoxically increasing metastatic dissemination to regional lymph nodes. Specifically, calpain inhibition in melanoma cells limits tumor growth in vitro and in vivo but increases dissemination by amplifying cell resistance to apoptosis and accelerating migration process. Meanwhile, calpain inhibition restricted to host cells blunts tumor infiltration by immune cells and angiogenesis required for antitumor immunity, allowing tumor cells to escape tumor niche and disseminate. The development of highly specific calpain inhibitors with potential medical applications in cancer should take into account the opposing roles of the calpain/calpastatin system in initial tumor growth and subsequent metastatic dissemination.
A quality preserving exact histogram specification

The state-of-the-art exact histogram specification algorithm by Coltuc and others is improved. We use the image generated by this method as our initial starting point and improve its visual quality by application of several histogram-invariant transformations on the image, making it more and more similar to the source image. Experimental results verify the superb performance of the proposed method.
Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma

Purpose Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development. Methods The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis. Results Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous. Conclusions OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.
Trends in Canadian Short‐Duration Extreme Rainfall: Including an Intensity–Duration–Frequency Perspective

Abstract Short-duration (5 minutes to 24 hours) rainfall extremes are important for a number of purposes, including engineering infrastructure design, because they represent the different meteorological scales of extreme rainfall events. Both single location and regional analyses of the changes in short-duration extreme rainfall amounts across Canada, as observed by tipping bucket rain gauges from 1965 to 2005, are presented. The single station analysis shows a general lack of a detectable trend signal, at the 5% significance level, because of the large variability and the relatively short period of record of the extreme short-duration rainfall amounts. The single station 30-minute to 24-hour durations show that, on average, 4% of the total number of stations have statistically significant increasing amounts of rainfall, whereas 1.6% of the cases have significantly decreasing amounts. However, regional spatial patterns are apparent in the single station trend results. Thus, for the same durations regional trends are presented by grouping the single station trend statistics across Canada. This regional trend analysis shows that at least two-thirds of the regions across Canada have increasing trends in extreme rainfall amounts, with up to 33% being significant (depending on location and duration). Both the southwest and the east (Newfoundland) coastal regions generally show significant increasing regional trends for 1- and 2-hour extreme rainfall durations. For the shortest durations of 5–15 minutes, the general overall regional trends in the extreme amounts are more variable, with increasing and decreasing trends occurring with similar frequency; however, there is no evidence of statistically significant decreasing regional trends in extreme rainfall amounts. The decreasing regional trends for the 5- to 15-minute duration amounts tend to be located in the St. Lawrence region of southern Quebec and in the Atlantic provinces. Additional analysis using criteria specified for traditional water management practice (e.g., Intensity-Duration-Frequency (IDF)) shows that fewer than 5.6% and 3.4% of the stations have significant increasing and decreasing trends, respectively, in extreme annual maximum single location observation amounts. This indicates that at most locations across Canada the traditional single station IDF assumption that historical extreme rainfall observations are stationary (in terms of the mean) over the period of record for an individual station is not violated. However, the trend information is still useful complementary information that can be considered for water management purposes, especially in terms of regional analysis.
Efficient detection and exploitation of infeasible paths for software timing analysis

Accurate estimation of the worst-case execution time (WCET) of a program is important for real-time embedded software. Static WCET estimation involves program path analysis and architectural modeling. Path analysis is complex due to the inherent difficulty in detecting and exploiting infeasible paths in a program's control flow graph. In this paper, we propose an efficient method to exploit infeasible path information for WCET estimation without resorting to exhaustive path enumeration. We demonstrate the efficiency of our approach for some real-life control-intensive applications
An Essential Function for the ATR-Activation-Domain (AAD) of TopBP1 in Mouse Development and Cellular Senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development.
Modified Monotonic Simple Shear Tests on Silica Sand

Two major modifications were made to the Norwegian Geotechnical Institute (NGI) direct simple shear apparatus, and the wire reinforcement was replaced by cell pressure. A circumferential deformation device was developed and mounted around the cylindrical specimen. The soil specimen cross-section area change was corrected, based on the monitored values from radial deformation. The advantage under this configuration is that a truly K 0 condition could be maintained during shearing and the area correction can be applied in data reduction. The monotonic simple shear behavior of silica sand (loose and dense conditions) was investigated and stress states of pure shear and K 0 condition were applied to the specimen. Both stress path and the mobilized shear resistance under different consolidation pressures were also studied. K 0 values and confining stress levels were found to greatly influence both the peak and the residual shear stress mobilization. Based on the testing data, radial changes were relatively small within 10% shear strain, beyond which great radial change would happen. Although all specimens were sheared to their critical states, their stress paths stopped at different locations, thus yielded different critical state lines (CSL). The slope of CSL at K 0 = 0.5 condition was higher than that at pure shear condition.
An ensemble approach for feature selection of Cyber Attack Dataset

Feature selection is an indispensable preprocessing step when mining huge datasets that can significantly improve the overall system performance. Therefore in this paper we focus on a hybrid approach of feature selection. This method falls into two phases. The filter phase select the features with highest information gain and guides the initialization of search process for wrapper phase whose output the final feature subset. The final feature subsets are passed through the Knearest neighbor classifier for classification of attacks. The effectiveness of this algorithm is demonstrated on DARPA KDDCUP99 cyber attack dataset.
Depth Discontinuity-Based Cup Segmentation From Multiview Color Retinal Images

Accurate segmentation of the cup region from retinal images is needed to derive relevant measurements for glaucoma assessment. A novel, depth discontinuity (in the retinal surface)-based approach to estimate the cup boundary is proposed in this paper. The proposed approach shifts focus from the cup region used by existing approaches to cup boundary. The given set of images, acquired sequentially, are related via a relative motion model and the depth discontinuity at the cup boundary is determined from cues such as motion boundary and partial occlusion. The information encoded by these cues is used to approximate the cup boundary with a set of best-fitting circles. The final boundary is found by considering points on these circles at different sectors using a confidence measure. Four different kinds of data sets ranging from synthetic to real image pairs, covering different multiview scenarios, have been used to evaluate the proposed method. The proposed method was found to yield an error reduction of 16% for cup-to-disk vertical diameter ratio (CDR) and 13% for cup-to-disk area ratio (CAR) estimation, over an existing monocular image-based cup segmentation method. The error reduction increased to 33% in CDR and 18% in CAR with the addition of a third view (image) which indicates the potential of the proposed approach.
The mechanisms of human action: Introduction and background.

1 unconsciously? How does an idea such as a mental image of a tree lead to the movements of a pen or paintbrush? Th ese are exciting times because such questions are beginning to be answered scientifi cally. It is our hope that this book will address most if not all questions regarding the nuts and bolts of human action, questions that have been surprisingly neglected in the history of experimental psychology (Nattkemper & Ziessler, 2004). Oversight of this important topic stemmed in part from the rigid, nonrepresentational stance of the behaviorist era and from psychology’s overall preference of the problem of knowledge representation, as in perception and memory, over that of action (Rosenbaum, 2005). A few minutes at a local café allow one to appreciate the wide array of actions that humans are capable of expressing— reading the newspaper, waiting for a friend, shaking hands, grabbing the waiter’s attention with a “cappuccino, please. ” Some actions at the café may be refl exive, automatic, voluntary, social, communicative, or refl ect that hidden resource called “will power. ” As ordinary as these actions are, they remain exceedingly diffi cult to understand from a scientifi c point of view. What are the neural and cognitive mechanisms by which actions are learned, mentally stored, and expressed? What is the diff erence between actions that are mediated consciously and those that are mediated Abstract
Novel Method To Identify Source-Associated Phylogenetic Clustering Shows that Listeria monocytogenes Includes Niche-Adapted Clonal Groups with Distinct Ecological Preferences

ABSTRACT While phylogenetic and cluster analyses are often used to define clonal groups within bacterial species, the identification of clonal groups that are associated with specific ecological niches or host species remains a challenge. We used Listeria monocytogenes, which causes invasive disease in humans and different animal species and which can be isolated from a number of environments including food, as a model organism to develop and implement a two-step statistical approach to the identification of phylogenetic clades that are significantly associated with different source populations, including humans, animals, and food. If the null hypothesis that the genetic distances for isolates within and between source populations are identical can be rejected (SourceCluster test), then particular clades in the phylogenetic tree with significant overrepresentation of sequences from a given source population are identified (TreeStats test). Analysis of sequence data for 120 L. monocytogenes isolates revealed evidence of clustering between isolates from the same source, based on the phylogenies inferred from actA and inlA (P = 0.02 and P = 0.07, respectively; SourceCluster test). Overall, the TreeStats test identified 10 clades with significant (P < 0.05) or marginally significant (P < 0.10) associations with defined sources, including human-, animal-, and food-associated clusters. Epidemiological and virulence phenotype data supported the fact that the source-associated clonal groups identified here are biologically valid. Overall, our data show that (i) the SourceCluster and TreeStats tests can identify biologically meaningful source-associated phylogenetic clusters and (ii) L. monocytogenes includes clonal groups that have adapted to infect specific host species or colonize nonhost environments.
A Physical Activities Healthcare System Based onWireless Sensing Technology

In this paper, a physical activities healthcare system (PATHS) combined ubiquitous computing and wireless sensing technology was proposed. This system includes a wearable wireless sensors unit (W2SU), a hand-held device and related analysis and wireless communication software. W2SU can record physical activities and ambulatory electrocardiogram. All data recorded by the unit can be transmitted to the hand-held device using Bluetooth in order that the software in hand-held device will monitor the entire exercises process and check the heart rate. Furthermore, the hand-held device can access Internet via Wi-Fi for telemedicine functions. The purposes of our system are to help subjects to develop individuated suitable physical activity plans and monitor the cardiac status continually. PATHS can also be used as an alert device to help person when abnormal rhythms is detected. The prototype system has been tested and it is found to fulfill the anticipated requirement. The proposed system provides an effective solution for construction of a large scale healthcare and telemedicine system.
Solute Transport Through an Integrated Heterogeneous Soil‐Groundwater System

The coupled transport process through an integrated soil-groundwater system is quantified for kinetically sorbing solute that originates from a time dependent source at the soil surface and is transported by steady random velocity. The derived expressions of ensemble mean solute breakthrough at some arbitrary control plane normal to the mean flow direction involve probability density functions (pdfs) of advective solute travel time through the unsaturated and the saturated zone of the transport domain. A nonstationary travel time pdf is derived for the saturated zone, to account for possible effects of flow nonuniformity due to recharge of water from the unsaturated zone. Nonuniform mean flow in the saturated zone decreases the relative influence of spatial variability within that zone on the ensemble mean solute breakthrough curve. Factors such as the longitudinal extent of the solute source and the unsaturated zone variability become more important for the spreading of the expected solute breakthrough as the degree of flow nonuniformity in the saturated zone increases. This implies that possible far-field simplifications based on the assumption that the transport process in an integrated soil-groundwater system is dominated by the transport conditions in the saturated zone may not be valid in cases with significant groundwater recharge from the unsaturated zone.
Correction to "Possible crippling of the core dynamo of Mars by Borealis impact"

[1] In the paper “Possible crippling of the core dynamo of Mars by Borealis impact” by Jafar Arkani‐Hamed (Journal of Geophysical Research, 115, E12021, doi:10.1029/ 2010JE003602, 2010) the impact heating of Mars by the Borealis impact, which likely created the northern lowland basin, was calculated. Using the crater scaling laws [Holsapple, 1993; Melosh, 1989] the basin diameter was related to the size of the impactor. Following the impact, a nearly uniform shock pressurewas generated inside an isobaric region in the mantle, outside which the shock pressure decreased exponentially with distance from the isobaric center following the average model of Pierazzo et al. [1997]. After crossing the core‐mantle boundary, the shock wave travelled in the core where the shock pressure again decayed with distance travelled from the isobaric center according to Pierazzo et al.’s average model but with the physical parameters of the core. The corresponding impact temperature increase is obtained using the Foundering model of Watters et al. [2009]. [2] The impact‐heated core stratified within a few tens of years and the possible pre‐existing core dynamo decayed with the characteristic time of 10–15 kyr [Arkani‐Hamed and Olson, 2010]. Shortly after the stratification, convection started in a thin layer in the outer core, the thickness of which increased in time as convection penetrated to deeper parts of the core until the entire core convected on a global scale. It took ∼60 Myr for the core to develop global convection and power a new core dynamo. [3] Here I describe a correction required in the calculation of the shock pressure distribution in the core. This correction is important because it increases the crippling time of the Martian core dynamo by a factor of larger than 4. The source of the required correction is the transmission coefficient of the shock wave across the core‐mantle boundary (CMB), the ratio of the shock pressure at the top of the core to that at the base of the mantle. The transmission coefficient was determined on the basis of seismic ray theory [Aki and Richards, 2002, section 5.2]. It resulted in a sudden drop of shock pressure as passing from the mantle to the core, in contrast to the sudden jump of the pressure according to recent Hydrocode models [Ivanov et al., 2010; Bierhaus et al., 2011].
Randomized algorithms for robustness analysis: a distributed approach

Randomized algorithms are a useful tool for analyzing the performance of complex uncertain systems. Their implementation requires the generation of a large number N of random samples representing the uncertainty scenarios, and the corresponding evaluation of system performance. When N is very large and/or performance evaluation is costly or time consuming, it can be necessary to distribute the computational burden of such algorithms among many cooperating computing units. This paper studies distributed versions of randomized algorithms for expected value and probability estimation over a network of computing nodes with possibly time-varying communication links. Explicit a-priori bounds are provided for the sample and communication complexity of these algorithms in terms of number of local samples, number of computing nodes and communication iterations.
Real-time estimation of the parameters of long-range dependence

An on-line version of the Abry-Veitch (see IEEE GLOBECOM'98, Sydney, Australia,p.3716-21, 1998) wavelet-based estimator of the Hurst parameter is presented. It has very low memory and computational requirements and scales naturally to arbitrarily high data rates, enabling its use in real-time applications such as admission control, and avoiding the need to store huge data sets for off-line analysis. The performance of the estimator as a function of the length of data processed is demonstrated using simulated data. An implementation for 10-Mb/s Ethernet based on standard hardware supporting sampling rates of 1 data point per millisecond is described, and results of its operation presented, as is an implementation for 155-Mb/s asynchronous transfer mode networks. Finally we illustrate the power of on-line measurements by collecting measurements over a period of five months, and using them to look for diurnal trends in scaling properties of the data.