Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.
Regulated Cleavages at the West Nile Virus NS4A-2K-NS4B Junctions Play a Major Role in Rearranging Cytoplasmic Membranes and Golgi Trafficking of the NS4A Protein

ABSTRACT A common feature associated with the replication of most RNA viruses is the formation of a unique membrane environment encapsulating the viral replication complex. For their part, flaviviruses are no exception, whereupon infection causes a dramatic rearrangement and induction of unique membrane structures within the cytoplasm of infected cells. These virus-induced membranes, termed paracrystalline arrays, convoluted membranes, and vesicle packets, all appear to have specific functions during replication and are derived from different organelles within the host cell. The aim of this study was to identify which protein(s) specified by the Australian strain of West Nile virus, Kunjin virus (KUNV), are responsible for the dramatic membrane alterations observed during infection. Thus, we have shown using immunolabeling of ultrathin cryosections of transfected cells that expression of the KUNV polyprotein intermediates NS4A-4B and NS2B-3-4A, as well as that of individual NS4A proteins with and without the C-terminal transmembrane domain 2K, resulted in different degrees of rearrangement of cytoplasmic membranes. The formation of the membrane structures characteristic for virus infection required coexpression of an NS4A-NS4B cassette with the viral protease NS2B-3pro which was shown to be essential for the release of the individual NS4A and NS4B proteins. Individual expression of NS4A protein retaining the C-terminal transmembrane domain 2K resulted in the induction of membrane rearrangements most resembling virus-induced structures, while removal of the 2K domain led to a less profound membrane rearrangement but resulted in the redistribution of the NS4A protein to the Golgi apparatus. The results show that cleavage of the KUNV polyprotein NS4A-4B by the viral protease is the key initiation event in the induction of membrane rearrangement and that the NS4A protein intermediate containing the uncleaved C-terminal transmembrane domain plays an essential role in these membrane rearrangements.
Using learning analytics to evaluate a video-based lecture series

Abstract Background: The video-based lecture (VBL), an important component of the flipped classroom (FC) and massive open online course (MOOC) approaches to medical education, has primarily been evaluated through direct learner feedback. Evaluation may be enhanced through learner analytics (LA) – analysis of quantitative audience usage data generated by video-sharing platforms. Methods and results: We applied LA to an experimental series of ten VBLs on electroencephalography (EEG) interpretation, uploaded to YouTube in the model of a publicly accessible MOOC. Trends in view count; total percentage of video viewed and audience retention (AR) (percentage of viewers watching at a time point compared to the initial total) were examined. The pattern of average AR decline was characterized using regression analysis, revealing a uniform linear decline in viewership for each video, with no evidence of an optimal VBL length. Segments with transient increases in AR corresponded to those focused on core concepts, indicative of content requiring more detailed evaluation. We propose a model for applying LA at four levels: global, series, video, and feedback. Discussion and conclusions: LA may be a useful tool in evaluating a VBL series. Our proposed model combines analytics data and learner self-report for comprehensive evaluation.
Addressing cold-start problem in music recommendation with HMM-based Collaborative Profile Space analysis

In this paper, Collaborative Profile Space analysis, a novel approach based on HMM, is proposed to tackle the “new item” cold start problem in music recommendation task. By calculating the probability of generating a particular song from a set of trained HMMs, coordinates in the Collaborative Profile Space is defined, and used in the classifiers. With self-collected dataset and evaluation strategy, it is shown that the proposed method outperforms the traditional music classification approach in the application of recommendation.
Beneficial Metabolic Effects of Rapamycin Are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice

The “mechanistic target of rapamycin” (mTOR) is a central controller of growth, proliferation and/or motility of various cell-types ranging from adipocytes to immune cells, thereby linking metabolism and immunity. mTOR signaling is overactivated in obesity, promoting inflammation and insulin resistance. Therefore, great interest exists in the development of mTOR inhibitors as therapeutic drugs for obesity or diabetes. However, despite a plethora of studies characterizing the metabolic consequences of mTOR inhibition in rodent models, its impact on immune changes associated with the obese condition has never been questioned so far. To address this, we used a mouse model of high-fat diet (HFD)-fed mice with and without pharmacologic mTOR inhibition by rapamycin. Rapamycin was weekly administrated to HFD-fed C57BL/6 mice for 22 weeks. Metabolic effects were determined by glucose and insulin tolerance tests and by indirect calorimetry measures of energy expenditure. Inflammatory response and immune cell populations were characterized in blood, adipose tissue and liver. In parallel, the activities of both mTOR complexes (e. g. mTORC1 and mTORC2) were determined in adipose tissue, muscle and liver. We show that rapamycin-treated mice are leaner, have enhanced energy expenditure and are protected against insulin resistance. These beneficial metabolic effects of rapamycin were associated to significant changes of the inflammatory profiles of both adipose tissue and liver. Importantly, immune cells with regulatory functions such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were increased in adipose tissue. These rapamycin-triggered metabolic and immune effects resulted from mTORC1 inhibition whilst mTORC2 activity was intact. Taken together, our results reinforce the notion that controlling immune regulatory cells in metabolic tissues is crucial to maintain a proper metabolic status and, more generally, comfort the need to search for novel pharmacological inhibitors of the mTOR signaling pathway to prevent and/or treat metabolic diseases.
Reporting and Selection Bias in Case-Control Studies of Congenital Malformations

Retrospective studies of congenital malformations frequently rely on exposures reported by study subjects. Differential error in exposure reporting by cases and controls, which has alternatively been referred to as “recall bias” and “reporting bias,” may result in a biased effect measure. Some authors have attempted to avoid reporting bias by comparing exposures between two malformed groups, rather than between cases and nonmalformed controls. This approach, however may introduce its own bias, which we call selection bias. Both reporting bias and selection bias are shown to be algebraically equivalent to bias arising from exposure misclassification. The magnitudes of these biases are compared for a range of plausible parametric values. The case-control design is sensitive to both differential reporting and selection bias, and the choice of study design involves balancing these two sources of bias. (Epidemiology 1992;3:356–363)
Peripheral Notifications in Large Displays: Effects of Feature Combination and Task Interference

Visual notifications are integral to interactive computing systems. With large displays, however, much of the content is in the user's visual periphery, where human capacity to notice visual effects is diminished. One design strategy for enhancing noticeability is to combine visual features, such as motion and colour. Yet little is known about how feature combinations affect noticeability across the visual field, or about how peripheral noticeability changes when a user's primary task involves the same visual features as the notification. We addressed these questions by conducting two studies. Results of the first study showed that noticeability of feature combinations were approximately equal to the better of the individual features. Results of the second study suggest that there can be interference between the features of primary tasks and the visual features in the notifications. Our findings contribute to a better understanding of how visual features operate when used as peripheral notifications.
Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab

Graft-versus-host disease (GVHD) remains the downside of the graft-versus-leukemia effect following allogeneic stem cell transplantation. This investigation of 25 patients with myeloid malignancies treated with reduced intensity conditioning and with GVHD prophylaxis, has focused on cell populations and their correlation with outcome. Interesting imbalances of effector and regulatory CD4+ T cells were detected, which, if confirmed in larger cohorts, should provide insight into how the immunological storms accompanying allogeneic stem cell transplantation can be harnessed and weathered. Background A variety of immune pathways can lead to graft-versus-host disease. A better understanding of the type of immune response causing graft-versus-host disease in defined clinical hematopoietic stem cell transplant settings is required to inform development of methods for monitoring patients and providing them tailored care. Design and Methods Twenty-five patients were recruited presenting with myeloid malignancies and treated with a reduced intensity conditioning transplant regimen with graft-versus-host disease prophylaxis comprising in vivo lymphocyte depletion with alemtuzumab and cyclosporin. A prospective study was performed of lymphocyte subset reconstitution in peripheral blood in relation to the incidence of graft-versus-host disease. Results Acute graft-versus-host disease was associated with significantly higher numbers of natural killer cells and donor-derived effector CD4 T cells (CD45RO+ CD27−) early (day 30) after transplantation (p=0.04 and p=0.02, respectively). This association was evident before the emergence of clinical pathology in six out of seven patients. Although numbers of regulatory CD4 T cells (CD25high Foxp3+) were similar at day 30 in all patients, a significant deficit in those who developed acute graft-versus-host disease was apparent relative to effector CD4 T cells (median of 41 effectors per regulatory cell compared to 12 to 1 for patients without graft-versus-host disease) (p=0.03). By day 180, a functional regulatory CD4 T-cell population had expanded significantly in patients who developed chronic graft-versus-host disease, reversing the imbalance (median of 3 effectors per regulatory cell compared to 9.6 to 1 for patients without graft-versus-host disease) (p=0.018) suggesting no overt absence of immune regulation in the late onset form of the disease. Conclusions Imbalance of effector and regulatory CD4 T cells is a signature of graft-versus-host disease in this transplantation protocol.
Development of experimental radiation pneumonitis.

Histologic changes were studied in the lungs of rats irradiated with 3000 r to the thorax witn shielding of the remainder of the body. In some animals the same total dose was given as 5 weekly doses of 600 r or in 2 doses spaced 50 daya apart. Development of radiation pneumonitis in rats was characterized by an early inflammatory reaction with progressive organization of fibrin-rich edema fluid in alveolar septa. Later stages showed thickened aiveolar septa containing large numbers of heavy reticulum fibers. Fractionation of radiation, either by multiple weekly doses or 2 large doses at a 7-week interval, did not appreclably alter the development of radiation pneumonitis. This suggests that previous exposure does not make the lung more radiosensitive but that the parenchymal changes are a function primarily of the total radiation dosage. Observations in the lung conformed with results in longevity studies showing that there is relatively rapid recovery from radiosensitivity induced by previous exposure. Rats exposed to massive thoracic radiation developed acute necrotizing esophagitis, resulting in extensive mortality. In contrast to the changes in man foliowing thoracic radiation, the development of a hyaline membrane was not conspicuous in rats. Thus it is doubtful that organization ofmore » a hyaiine membrane plays a significant part in the fibrous thickening of alveolar septa in the animals. (H.H.D.)« less
Methodology for extracting thermoelectric module parameters

The fundamental temperature-dependent parameters of a thermoelectric module (TEM), such as Seebeck coefficient, electrical resistance, thermal conductance, and figure-of-merit are necessary, among other factors, for conception of models for this type of devices. This paper presents a new methodology to experimentally determine these parameters from observable variables obtained from temperature, voltage, and electric current measurements made on a working TE device. Calculated parameters are plotted against the module's average temperature. Results are verified by inserting the average-value parameters into an electrothermal SPICE model of a TEM and comparing simulation and measured results for a given test configuration.
Mondrian Forests: Efficient Online Random Forests

Ensembles of randomized decision trees, usually referred to as random forests, are widely used for classification and regression tasks in machine learning and statistics. Random forests achieve competitive predictive performance and are computationally efficient to train and test, making them excellent candidates for real-world prediction tasks. The most popular random forest variants (such as Breiman's random forest and extremely randomized trees) operate on batches of training data. Online methods are now in greater demand. Existing online random forests, however, require more training data than their batch counterpart to achieve comparable predictive performance. In this work, we use Mondrian processes (Roy and Teh, 2009) to construct ensembles of random decision trees we call Mondrian forests. Mondrian forests can be grown in an incremental/online fashion and remarkably, the distribution of online Mondrian forests is the same as that of batch Mondrian forests. Mondrian forests achieve competitive predictive performance comparable with existing online random forests and periodically retrained batch random forests, while being more than an order of magnitude faster, thus representing a better computation vs accuracy tradeoff.
An Effective Gray-Box Identification Procedure for Multicore Thermal Modeling

Aggressive thermal management is a critical feature for high-end computing platforms, as worst-case thermal budgeting is becoming unaffordable. Reactive thermal management, which sets temperature thresholds to trigger thermal capping actions, is too “near-sighted,” and it may lead to severe performance degradation and thermal overshoots. More aggressive proactive thermal managements minimize performance penalty with smooth optimal control. These techniques require knowledge of thermal models, which have to be accurate and simple to make the controls effective, while keeping their complexity limited. In practice, these models are not provided by manufacturers, and in most cases, they strongly depend on the deployment environment. Hence, procedures to automatically derive thermal models in the field are needed. In this paper, we propose a gray-box procedure to learn a compact and physically consistent model for multicore chips. We leverage the physical consistency of the proposed model to tame the model complexity and to face large quantization noise in measurements. We exploit Output Error structures along with Levenberg-Marquardt and Least Squares optimization algorithms. We tackle the problem in a real-life contest: we developed a complete infrastructure for model building and thermal data collection in the Linux environment, and we tested it on an Intel Nehalem-based server CPU.
Identify amino acid candidates critical for function of rat imidase by cross-reference voting in imidase superfamily

It is a useful strategy to understand structure-function relationship of proteins by aligning and analyzing their sequences. Database search techniques that can extract the functional or structural information from amino acid sequence are urgently needed. Imidase superfamily provides an interesting case for developing such method. Imidase super family contains a variety of related proteins that differ in functions and sequence identities. We developed a Cross-Reference Voting algorithm with complexity O(nm2), where n is the number of total sequences and m is the maximum lenght of the sequence, to identify amino acid candidates that are critical for function of rat imidase. After analyzing more than 80 members of imidase superfamily, several amino acid residues of rat imidase are selected and examined. His67, His69, Lys159, His192, His248 and Asp326 of rat imidase are found corresponding to critical residues of hydantoinase studied by site-directed mutagenesis and structure information of hydantoinase. His67, His69, Asp100, His217, His248, His420 and His459 of rat imidase are found corresponding to critical residues of dihydroorotase and allantoinase in separate studies. These results indicated that our algorithm could successfully extract functionally related amino acid candidates in imidase superfamily.
Granulocytic sarcoma: 32 cases and review of the literature

Thirty-two cases of granulocytic sarcoma (GS) are reported in this paper. Age range was from 16 – 70 years. GS was accompanied by AML in 13 cases, ALL (My+) in one case, CML in 11 cases and MDS in two cases. GS was diagnosed simultaneously with leukemia in five cases and preceded the leukemia in eight. Lymph node and soft tissue were the most commonly detected localizations. Seven cases had first been diagnosed as NHL. Histopathologically blastic, immature and mature variants were found in 11, nine and 11 cases respectively and overall survival was shortest in the blastic type. Myeloperoxidase and lysozyme were found to be positive in 30 and 24 cases respectively. Therapy was radiation in five cases and surgery in three. Systemic chemotherapy was given to the cases. The clinical outcome of the patients after the diagnosis of GS was poor. GS is a unique entity; prognosis is poor but it is important to detect the signaling pathways associated with migration of myeloid cells to the extra-medullary tissues. The critical factors for detecting this interesting tumor are to be aware of this disease, cooperation between clinician and pathologist and the application of special stains to detect the myeloid origin.
The Density Profile of Equilibrium and Nonequilibrium Dark Matter Halos

We study the diversity of the density profiles of dark matter halos based on a large set of high-resolution cosmological simulations of 2563 particles. The cosmological models include four scale-free models and three representative cold dark matter models. The simulations have good force resolution. In each cosmological model, there are about 400 massive halos that have more than 104 particles within the virial radius. Our unbiased selection of all massive halos enables us to quantify how well the bulk of dark matter halos can be described by the Navarro, Frenk, & White (NFW) profile, which was established for equilibrium halos. We find that about 70% of the halos can be fitted by the NFW profile with a fitting residual dvimax < 0.3 in Ω0 = 1 universes. This percentage is higher in the low-density cosmological models of Ω0 = 0.3. The rest of the halos exhibit larger deviations from the NFW profile for more significant internal substructures. There is a considerable amount of variation in the density profile even among the halos that can be fitted by the NFW profile (i.e., dvimax < 0.30). The distribution of the profile parameter, the concentration c, can be described well by a lognormal function with the mean value slightly smaller (15%) than the NFW result and the dispersion, σc, in ln c, of about 0.25. More virialized halos with dvimax < 0.15 have a mean value in better agreement with the NFW result, and their dispersion, σc, is also slightly smaller (about 0.2). Our results can alleviate some of the conflicts found recently between the theoretical NFW profile and observational results. Implications for theoretical and observational studies of galaxy formation are discussed.