Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism Underlying the Reversal of Drug Resistance in P-Glycoprotein-Expressing Leukemia Cells by Pinoresinol and the Study of a Derivative

P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy. With the aim of finding agents that circumvent the MDR phenotype mediated by P-gp, 15 compounds isolated from native and naturalized plants of Argentina were screened. Among these, the non-cytotoxic lignan (±) pinoresinol successfully restored sensitivity to doxorubicin from 7 μM in the P-gp overexpressed human myelogenous leukemia cells, Lucena 1. This resistance-reversing effect was confirmed by competitively increasing the intracellular doxorubicin accumulation and by significantly inhibiting the efflux of doxorubicin and, to a lesser extent, that of rhodamine 123. The activity obtained was similar to that observed with verapamil. No such results were observed in the sensitive parental K562 cell line. To gain deeper insight into the mode of action of pinoresinol, its effect on P-gp function and expression was examined. The docking simulations indicated that the lignan bound to P-gp at the apex of the V-shaped transmembrane cavity, involving transmembrane helices 4, 5, and 6, and partially overlapped the binding region of tariquidar, which was used as a positive control. These results would shed some light on the nature of its interaction with P-gp at molecular level and merit further mechanistic and kinetic studies. In addition, it showed a maximum 29% activation of ATP hydrolysis and antagonized verapamil-stimulated ATPase activity with an IC50 of 20.9 μM. On the other hand, pinoresinol decreased the presence of P-gp in the cell surface. Derivatives of pinoresinol with improved activity were identified by docking studies. The most promising one, the non-cytotoxic 1-acetoxypinoresinol, caused a reversion of doxorubicin resistance from 0.11 μM and thus higher activity than the lead compound. It also caused a significant increase in doxorubicin accumulation. Results were similar to those observed with verapamil. The results obtained positioned these compounds as potential candidates for effective agents to overcome P-gp-mediated MDR, leading to better outcomes for leukemia chemotherapy.
A priori estimates and precise regularity for parabolic systems with discontinuous data

We deal with linear parabolic (in the sense of Petrovskii) systems of order $2b$ with discontinuous principal coefficients. A priori estimates in Sobolev and Sobolev--Morrey spaces are proved for the strong solutions by means of potential analysis and boundedness of certain singular integral operators with kernels of mixed homogeneity. As a byproduct, precise characterization of the Morrey, $BMO$ and Holder regularity is given for the solutions and their derivatives up to order $2b-1. $
Enabling lock-free concurrent fine-grain access to massive distributed data: Application to supernovae detection

We consider the problem of efficiently managing massive data in a large-scale distributed environment. We consider data strings of size in the order of Terabytes, shared and accessed by concurrent clients. On each individual access, a segment of a string, of the order of Megabytes, is read or modified. Our goal is to provide the clients with efficient fine-grain access the data string as concurrently as possible, without locking the string itself. This issue is crucial in the context of applications in the field of astronomy, databases, data mining and multimedia. We illustrate these requirements with the case of an application for searching supernovae. Our solution relies on distributed, RAM-based data storage, while leveraging a DHT-based, parallel metadata management scheme. The proposed architecture and algorithms have been validated through a software prototype and evaluated in a cluster environment.
Endometrial carcinoma associated with breast carcinoma: Low incidence with tamoxifen use

Women treated with tamoxifen for breast cancer are at increased risk of endometrial cancer. This study examines the experience at Roswell Park Cancer Institute (RPCI) with women diagnosed with both endometrial carcinoma (EC) and breast carcinoma (BC) to determine the risk and stage of endometrial carcinoma among women treated with tamoxifen.
4D atlas of the mouse embryo for precise morphological staging

After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. Summary: This comprehensive developmental dataset, which combines optical projection tomography and image registration methods, provides a new and powerful staging system for mouse embryos.
An Effective 3D Ear Acquisition System

The human ear is a new feature in biometrics that has several merits over the more common face, fingerprint and iris biometrics. It can be easily captured from a distance without a fully cooperative subject. Also, the ear has a relatively stable structure that does not change much with the age and facial expressions. In this paper, we present a novel method of 3D ear acquisition system by using triangulation imaging principle, and the experiment results show that this design is efficient and can be used for ear recognition.
Japanese Word Reordering Integrated with Dependency Parsing

Although Japanese has relatively free word order, Japanese word order is not completely arbitrary and has some sort of preference. Since such preference is incompletely understood, even native Japanese writers often write Japanese sentences which are grammatically well-formed but not easy to read. This paper proposes a method for reordering words in a Japanese sentence so that the sentence becomes more readable. Our method can identify more suitable word order than conventional word reordering methods by concurrently performing dependency parsing and word reordering instead of sequentially performing the two processing steps. As the result of an experiment on word reordering using newspaper articles, we confirmed the effectiveness of our method.
Lymphocyte Apoptosis during Classical Swine Fever: Implication of Activation-Induced Cell Death

ABSTRACT Infection of pigs with classical swine fever virus (CSFV), a member of the Flaviviridae family, causes a severe leukopenia, particularly notable with the lymphocytes. The goal of this study was to analyze mechanisms behind this CSFV-induced lymphopenia. To this end, the kinetics of leukocyte depletion, the appearance of apoptotic cells, and virus infection of leukocytes after infection of pigs with the virulent CSFV strain Brescia were analyzed. Depletion of B and T lymphocytes was noted as early as 1 day postinfection (p.i.). Circulating viable lymphocytes with reduced mitochondrial transmembrane potential—a particular early marker for apoptosis—were also detectable as early as 1 day p.i. When isolated peripheral blood mononuclear cells were cultured for 6 h, significantly more sub-G1 cells with reduced DNA content were detected among the lymphocytes from CSFV-infected animals, again as early as 1 to 3 days p.i. The first time virus was first found in the plasma, as well as infection of leukocytes, was 3 days p.i. However, throughout the observation time of 1 week, <3% of the circulating leukocytes and no lymphocytes contained virus or viral antigen. Further analysis of the T lymphocytes from infected animals demonstrated an increase in CD49d, major histocompatibility complex class II, and Fas expression. An increased susceptibility to apoptosis in vitro was also observed, particularly after addition of concanavalin A as well as apoptosis-inducing anti-Fas antibody to the cultures. Taken together, these results imply that activation-induced programmed cell death was the mechanism behind lymphopenia during classical swine fever.
1 DIRECTION OF ARRIVAL ESTIMATION IN WIRELESS MOBILE COMMUNICATIONS USING MINIMUM VERIANCE DISTORSIONLESS RESPONSE

This paper presents a tool for the modelling, analysis, and simulation of direction-of-arrival (DOA) estimation in wireless mobile communication systems utilizing adaptive antenna arrays. The developed tool implements the Minimum Variance Distortionless Response (MVDR) algorithm. To demonstrate the versatility and accuracy of the developed tool, it is used to carry out a performance study of the MVDR algorithm by investigating the effect of various parameters related to the signal environment and sensor array.
Ubiquitination pathway as a target to develop abiotic stress tolerance in rice

Abiotic stresses may result in significant losses in rice grain productivity. Protein regulation by the ubiquitin/proteasome system has been studied as a target mechanism to optimize adaptation and survival strategies of plants to different environmental stresses. This article aimed at highlighting recent discoveries about the roles ubiquitination may play in the exposure of rice plants to different abiotic stresses, enabling the development of modified plants tolerant to stress. Responses provided by the ubiquitination process include the regulation of the stomatal opening, phytohormones levels, protein stabilization, cell membrane integrity, meristematic cell maintenance, as well as the regulation of reactive oxygen species and heavy metals levels. It is noticeable that ubiquitination is a potential means for developing abiotic stress tolerant plants, being an excellent alternative to rice (and other cultures) improvement programs.
Mucosal enzyme activity for butyrate oxidation; no defect in patients with ulcerative colitis.

BACKGROUND: Butyrate is an important energy source for the colon and its metabolism has been reported to be defective in ulcerative colitis. One mechanism for defective butyrate metabolism in patients with ulcerative colitis could be an enzyme deficiency in the beta-oxidation pathway of butyrate. AIMS: This study was undertaken to measure the activity of each enzyme involved in the beta-oxidation pathway of butyrate in colonic epithelium. PATIENTS: Patients with ulcerative colitis (n = 33), Crohn's colitis (n = 10), and control subjects with colorectal cancer or diverticular disease (n = 73) were studied. METHODS: Analysis was carried out using fluorometric and spectrophotometric techniques on homogenised epithelial biopsy specimens. RESULTS: Significantly increased butyryl CoA dehydrogenase activity was found in mucosa from patients with ulcerative colitis (33.2 (28.3, 38.1) mumol/g wet weight/min:mean (95% CI)) compared with activity in mucosa from control patients (24.3 (20.9, 27.7) mumol/g wet weight/min:mean (95% CI)) p < 0.02. No significant increase in activity of the enzymes butyryl-CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in patients with ulcerative colitis. In contrast the mucosal thiolase activity was significantly lower in those patients with quiescent colitis (3.21 (2.61, 3.81) mumol/g wet weight/min:mean (95% CI)) when compared with control mucosa (5.69 (5.09, 6.29) mumol/g wet weight/min:mean (95% CI)) p < 0.001. However, mucosal thiolase activity increases with the age of the donor patient and differences in the age range of the patient groups probably account for this finding. CONCLUSIONS: This study shows no substantial deficiency of enzyme activity in the beta-oxidation pathway of butyrate in the mucosa of patients with ulcerative colitis in histological remission.
The “Globularization Hypothesis” of the Language-ready Brain as a Developmental Frame for Prosodic Bootstrapping Theories of Language Acquisition

In recent research (Boeckx and Benítez-Burraco, 2014a,b) have advanced the hypothesis that our species-specific language-ready brain should be understood as the outcome of developmental changes that occurred in our species after the split from Neanderthals-Denisovans, which resulted in a more globular braincase configuration in comparison to our closest relatives, who had elongated endocasts. According to these authors, the development of a globular brain is an essential ingredient for the language faculty and in particular, it is the centrality occupied by the thalamus in a globular brain that allows its modulatory or regulatory role, essential for syntactico-semantic computations. Their hypothesis is that the syntactico-semantic capacities arise in humans as a consequence of a process of globularization, which significantly takes place postnatally (cf. Neubauer et al., 2010). In this paper, I show that Boeckx and Benítez-Burraco's hypothesis makes an interesting developmental prediction regarding the path of language acquisition: it teases apart the onset of phonological acquisition and the onset of syntactic acquisition (the latter starting significantly later, after globularization). I argue that this hypothesis provides a developmental rationale for the prosodic bootstrapping hypothesis of language acquisition (cf. i.a. Gleitman and Wanner, 1982; Mehler et al., 1988, et seq.; Gervain and Werker, 2013), which claim that prosodic cues are employed for syntactic parsing. The literature converges in the observation that a large amount of such prosodic cues (in particular, rhythmic cues) are already acquired before the completion of the globularization phase, which paves the way for the premises of the prosodic bootstrapping hypothesis, allowing babies to have a rich knowledge of the prosody of their target language before they can start parsing the primary linguistic data syntactically.
Context-Based Analytics - Establishing Explicit Links between Runtime Traces and Source Code

Diagnosing problems in large-scale, distributed applications runningin cloud environments requires investigating different sources ofinformation to reason about application state at any given time. Typical sources of information available to developers and operatorsinclude log statements and other runtime information collectedby monitors, such as application and system metrics. Just as importantly, developers rely on information related to changes to the source code andconfiguration files (program code) when troubleshooting. This information is generally scattered, and it is up to the troubleshooterto inspect multiple implicitly-connected fragments thereof. Currently, different tools need to be used in conjunction, e.g., logaggregation tools, source-code management tools, and runtime-metricdashboards, each requiring different data sources and workflows. Notsurprisingly, diagnosing problems is a difficult proposition. In this paper, we propose Context-Based Analytics, an approach that makes the links between runtime informationand program-code fragments explicit by constructing a graph based on anapplication-context model. Implicit connections between informationfragments are explicitly represented as edges in the graph. We designeda framework for expressing application-context models and implemented a prototype. Further, we instantiated our prototype framework with an application-contextmodel for two real cloud applications, one from IBM and another from a major telecommunications provider. We applied context-based analytics to diagnose twoissues taken from the issue tracker of the IBM application and foundthat our approach reduced the effort of diagnosing these issues. In particular, context-based analytics decreased the number of required analysis steps by 48% and the number ofneeded inspected traces by 40% on average as compared to a standard diagnosis approach.
Statistical mechanics of a single particle in a multiscale random potential: Parisi landscapes in finite-dimensional Euclidean spaces

We construct an N-dimensional Gaussian landscape with multiscale, translation invariant, logarithmic correlations and investigate the statistical mechanics of a single particle in this environment. In the limit of high dimension N → ∞ the free energy of the system and overlap function are calculated exactly using the replica trick and Parisi's hierarchical ansatz. In the thermodynamic limit, we recover the most general version of the Derrida's generalized random energy model (GREM). The low-temperature behaviour depends essentially on the spectrum of length scales involved in the construction of the landscape. If the latter consists of K discrete values, the system is characterized by a K-step replica symmetry breaking solution. We argue that our construction is in fact valid in any finite spatial dimensions N ⩾ 1. We discuss the implications of our results for the singularity spectrum describing multifractality of the associated Boltzmann–Gibbs measure. Finally we discuss several generalizations and open problems, such as the dynamics in such a landscape and the construction of a generalized multifractal random walk.
Saccades in presymptomatic and early stages of Huntington disease

Objective: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). Methods: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington’s Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. Results: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. Conclusions: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.
Meclizine and placebo in treating vertigo of vestibular origin. Relative efficacy in a double-blind study.

In a double-blind crossover study, meclizine hydrochloride was shown to be significantly more effective than placebo in treating patients with positional and continuous vertigo of vestibular origin. Meclizine reduced the severity and frequency of attacks, as well as signs and symptoms associated with the vertigo. These included nausea, positional and positioning nystagmus, and postural instability. There was no difference in the response of patients with disease of the peripheral or central vestibular system.
CENTERA: A Centralized Trust-Based Efficient Routing Protocol with Authentication for Wireless Sensor Networks †

In this paper, we present CENTERA, a CENtralized Trust-based Efficient Routing protocol with an appropriate authentication scheme for wireless sensor networks (WSN). CENTERA utilizes the more powerful base station (BS) to gather minimal neighbor trust information from nodes and calculate the best routes after isolating different types of “bad” nodes. By periodically accumulating these simple local observations and approximating the nodes' battery lives, the BS draws a global view of the network, calculates three quality metrics—maliciousness, cooperation, and compatibility—and evaluates the Data Trust and Forwarding Trust values of each node. Based on these metrics, the BS isolates “bad”, “misbehaving” or malicious nodes for a certain period, and put some nodes on probation. CENTERA increases the node's bad/probation level with repeated “bad” behavior, and decreases it otherwise. Then it uses a very efficient method to distribute the routing information to “good” nodes. Based on its target environment, and if required, CENTERA uses an authentication scheme suitable for severely constrained nodes, ranging from the symmetric RC5 for safe environments under close administration, to pairing-based cryptography (PBC) for hostile environments with a strong attacker model. We simulate CENTERA using TOSSIM and verify its correctness and show some energy calculations.
Weekly Calendar Planning Activity for University Students: Comparison of Individuals With and Without ADHD by Gender

Objective: To introduce a revised version of the Weekly Calendar Planning Activity (WCPA) adapted for university students (Weekly Calendar Performance Activity for students [WCPA-S]) and compare the performance of this activity between students with and without ADHD and across gender groups. Method: Participants included a total of 157 students, ages 20 to 30, enrolled in universities/colleges and divided into two groups: students with ADHD (male = 23, female = 38) and without ADHD (male = 33, female = 63). A two-way ANOVA was used for data analyses. The WCPA-S was administered to each student individually. Results: Significant differences were found between students with and without ADHD and across genders in performance, duration of performance, and in the number of strategies used. Conclusion: The WCPA-S proved to be an effective performance-based diagnostic tool for the utilization of executive functions in the daily life of university students. This instrument can be used to predict success in higher education and to support learning among university students with ADHD.
Evaluation of Experiences from Applying the PREDIQT Method in an Industrial Case Study

We have developed a method called PREDIQT for model-based prediction of impacts of architectural design changes on system quality. A recent case study indicated feasibility of the PREDIQT method when applied on a real-life industrial system. This paper reports on the experiences from applying the PREDIQT method in a second and more recent case study -- on an industrial ICT system from another domain and with a number of different system characteristics, compared with the previous case study. The analysis is performed in a fully realistic setting. The system analyzed is a critical and complex expert system used for management and support of numerous working processes. The system is subject to frequent changes of varying type and extent. The objective of the case study has been to perform an additional and more structured evaluation of the PREDIQT method and assess its performance with respect to a set of success criteria. The evaluation argues for feasibility and usefulness of the PREDIQT-based analysis. Moreover, the study has provided useful insights into the weaknesses of the method and suggested directions for future research and improvements.