Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.

BACKGROUND The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deaminase-bearing cancer cells as an autologous tumor vaccine in a rat model that mimics liver metastasis from colon carcinoma. METHODS We introduced a plasmid vector containing the E. coli cytosine deaminase gene into a BDIX rat colon carcinoma cell line. Intrahepatic injection of the modified cells in syngeneic animals generates a single experimental liver "suicide tumor. " We then analyzed the effect of 5-fluorocytosine treatment in terms of regression of cytosine deaminase-expressing cells in vivo as well as protection against wild-type cancer cells. RESULTS Treatment with 5-fluorocytosine induced regression of cytosine deaminase-expressing (CD+) tumors, with seven of 11 treated animals being tumor free at the end of 30 days and a statistically significant difference in tumor volumes between treated and control animals (two-sided P<.0001). Intrahepatic injection of CD+ cells followed by 5-fluorocytosine treatment rendered the treated animals resistant to challenge with wild-type tumor cells, with no (zero of seven) treated animals developing wild-type tumors in contrast to all (four of four) control animals. Moreover, in animals with established wild-type liver tumors, injection of CD+ tumor cells followed by 5-fluorocytosine treatment produced a statistically significant increase in survival time (two-sided P<.0001). In vivo immunodepletion and immunohistologic analysis of experimental tumors indicate that natural killer cells are the major immune component involved in this antitumor effect. CONCLUSIONS AND IMPLICATIONS Taken together, these results suggest the potential use of suicide gene-modified tumor cells as therapeutic vaccines against liver metastasis from colon carcinoma.
Animal-Assisted Intervention for trauma: a systematic literature review

Animals have a long history of inclusion in psychiatric treatment. There has been a recent growth in the empirical study of this practice, known as Animal-Assisted Intervention (AAI). We conducted a systematic review of the empirical literature on AAI for trauma, including posttraumatic stress disorder (PTSD). Ten studies qualified for inclusion, including six peer-reviewed journal articles and four unpublished theses. Participants were predominantly survivors of child abuse, in addition to military veterans. The presentation of AAI was highly variable across the studies. The most common animal species were dogs and horses. The most prevalent outcomes were reduced depression, PTSD symptoms, and anxiety. There was a low level of methodological rigor in most studies, indicating the preliminary nature of this area of investigation. We conclude that AAI may provide promise as a complementary treatment option for trauma, but that further research is essential to establish feasibility, efficacy, and manualizable protocols.
Active-Set Newton Algorithm for Overcomplete Non-Negative Representations of Audio

This paper proposes a computationally efficient algorithm for estimating the non-negative weights of linear combinations of the atoms of large-scale audio dictionaries, so that the generalized Kullback-Leibler divergence between an audio observation and the model is minimized. This linear model has been found useful in many audio signal processing tasks, but the existing algorithms are computationally slow when a large number of atoms is used. The proposed algorithm is based on iteratively updating a set of active atoms, with the weights updated using the Newton method and the step size estimated such that the weights remain non-negative. Algorithm convergence evaluations on representing audio spectra that are mixtures of two speakers show that with all the tested dictionary sizes the proposed method reaches a much lower value of the divergence than can be obtained by conventional algorithms, and is up to 8 times faster. A source separation evaluation revealed that when using large dictionaries, the proposed method produces a better separation quality in less time.
ATP: a vasoactive signal in the pericyte‐containing microvasculature of the rat retina

In this study we tested the hypothesis that extracellular ATP regulates the function of the pericyte‐containing retinal microvessels. Pericytes, which are more numerous in the retina than in any other tissue, are abluminally located cells that may adjust capillary perfusion by contracting and relaxing. At present, knowledge of the vasoactive molecules that regulate pericyte function is limited. Here, we focused on the actions of extracellular ATP because this nucleotide is a putative glial‐to‐vascular signal, as well as being a substance released by activated platelets and injured cells. In microvessels freshly isolated from the adult rat retina, we monitored ionic currents via perforated‐patch pipettes, measured intracellular calcium levels with the use of fura‐2, and visualized microvascular contractions with the aid of time‐lapse photography. We found that ATP induced depolarizing changes in the ionic currents, increased calcium levels and caused pericytes to contract. P2X7 receptors and UTP‐activated receptors mediated these effects. Consistent with ATP serving as a vasoconstrictor for the pericyte‐containing microvasculature of the retina, the microvascular lumen narrowed when an adjacent pericyte contracted. In addition, the sustained activation of P2X7 receptors inhibited cell‐to‐cell electrotonic transmission within the microvascular networks. Thus, ATP not only affects the contractility of individual pericytes, but also appears to regulate the spatial and temporal dynamics of the vasomotor response.
Propriedades físicas, químicas e de barreira em filme formados por blenda de celulose bacteriana e fécula de batata

The association of bacterial cellulose with other polymers can be an effective method for increasing its characteristics and structure, providing new industrial applications. The purpose of this paper was to verify the influence from bacterial cellulose in the physical, chemical and barrier properties in films of bacterial cellulose blends and potato starch. The films were made according to a ternary mix planning, with bacterial cellulose, potato starch and glycerol as independent variables. Blends with higher concentrations of bacterial cellulose exhibited increase in thickness, weight, permeability rate of water steam and permeability to water steam and reduction of density, solubility, opacity, swelling index at pH 1.8 and 8.0 (1, 10, 30 and 60 minutes). The scanning electron microscopy showed films with cohesive matrix, but with irregular morphology, containing insoluble particles of bacterial cellulose. The pure bacterial cellulose film showed increased weight, opacity, permeability rate of water steam and at swelling at pH 1.8 at 1 minute and pH 8.0 at 1, 10, 30 and 60 minutes. The bacterial cellulose contributed to high capacity of retention, absorption and low water desorption, providing biofilms that acted as barrier for light and kept the humidity constant.
SINGULAR PERTURBATIONS AND TIME SCALES IN CONTROL THEORIES AND APPLICATIONS: AN OVERVIEW 2002-2012

This paper presents an overview of singular perturbations and time scales (SPaTS) in control theory and applications during the period 2002-2012. The previous overviews/surveys were provided for the period up to 1976 [241], 1976-1983 [377], and 1984-2001 [312]. Due to the limitations on the scope and space, this is in no way intended to be an exhaustive survey on the topic.
Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy

Polyploidy results from deregulated cell division and has been considered an undesirable event leading to increased mutation rate and cancer development. However, polyploidy may also render cancer cells more vulnerable to chemotherapy. Here, we identify a small-molecule inducer of polyploidy, R1530, which interferes with tubulin polymerization and mitotic checkpoint function in cancer cells, leading to abortive mitosis, endoreduplication and polyploidy. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found downregulated during R1530-induced exit from mitosis, a likely consequence of PLK4 inhibition. BubR1 knockdown in the presence of nocodazole induced an R1530-like phenotype, suggesting that BubR1 plays a key role in polyploidy induction by R1530 and could be exploited as a target for designing more specific polyploidy inducers.
Mapping English GP prescribing data: a tool for monitoring health-service inequalities

Objective The aim of this paper was to show that easily interpretable maps of local and national prescribing data, available from open sources, can be used to demonstrate meaningful variations in prescribing performance. Design The prescription dispensing data from the National Health Service (NHS) Information Centre for the medications metformin hydrochloride and methylphenidate were compared with reported incidence data for the conditions, diabetes and attention deficit hyperactivity disorder, respectively. The incidence data were obtained from the open source general practitioner (GP) Quality and Outcomes Framework. These data were mapped using the Ordnance Survey CodePoint Open data and the data tables stored in a PostGIS spatial database. Continuous maps of spending per person in England were then computed by using a smoothing algorithm and areas whose local spending is substantially (at least fourfold) and significantly (p<0.05) higher than the national average are then highlighted on the maps. Setting NHS data with analysis of primary care prescribing. Population England, UK. Results The spatial mapping demonstrates that several areas in England have substantially and significantly higher spending per person on metformin and methyphenidate. North Kent and the Wirral have substantially and significantly higher spending per child on methyphenidate. Conclusions It is possible, using open source data, to use statistical methods to distinguish chance fluctuations in prescribing from genuine differences in prescribing rates. The results can be interactively mapped at a fine spatial resolution down to individual GP practices in England. This process could be automated and reported in real time. This can inform decision-making and could enable earlier detection of emergent phenomena.
An abattoir study of genital pathology in cows : I. Ovary and oviduct

SUMMARY In the present study, the aim was to investigate the pathologic conditions of ovary and oviduct of cows slaughtered at abattoir in Konya, Turkey. For this purpose, the reproductive tracts of 1113 cows from different breeds were examined and some pathological changes were detected in 67 cases (6.02 %). The incidence of the pathological changes in and around ovary were found as 5.21 per cent. These lesions were classified as follows ; follicular cyst (1.88 %), cystic corpora lutea (2.51 %), parovarian cyst (0.72 %), cystic bursa ovarica (0.18 %), periovaritis and adhesions (0.27 %), granulosa cell tumor (0.27 %) and hemangioma (0.09 %). In 9 cases (0.81 %) pathological changes were found in oviduct, and these lesions were hydrosalpinx (0.36 %), mesosalpingitis - adhesions (0.09 %) and salpingitis (0.45 %).
Spatially Regularized Compressed Sensing for High Angular Resolution Diffusion Imaging

Despite the relative recency of its inception, the theory of compressive sampling (aka compressed sensing) (CS) has already revolutionized multiple areas of applied sciences, a particularly important instance of which is medical imaging. Specifically, the theory has provided a different perspective on the important problem of optimal sampling in magnetic resonance imaging (MRI), with an ever-increasing body of works reporting stable and accurate reconstruction of MRI scans from the number of spectral measurements which would have been deemed unacceptably small as recently as five years ago. In this paper, the theory of CS is employed to palliate the problem of long acquisition times, which is known to be a major impediment to the clinical application of high angular resolution diffusion imaging (HARDI). Specifically, we demonstrate that a substantial reduction in data acquisition times is possible through minimization of the number of diffusion encoding gradients required for reliable reconstruction of HARDI scans. The success of such a minimization is primarily due to the availability of spherical ridgelet transformation, which excels in sparsifying HARDI signals. What makes the resulting reconstruction procedure even more accurate is a combination of the sparsity constraints in the diffusion domain with additional constraints imposed on the estimated diffusion field in the spatial domain. Accordingly, the present paper describes an original way to combine the diffusion- and spatial-domain constraints to achieve a maximal reduction in the number of diffusion measurements, while sacrificing little in terms of reconstruction accuracy. Finally, details are provided on an efficient numerical scheme which can be used to solve the aforementioned reconstruction problem by means of standard and readily available estimation tools. The paper is concluded with experimental results which support the practical value of the proposed reconstruction methodology.
Deterioration of left ventricular function following atrio-ventricular node ablation and right ventricular apical pacing in patients with permanent atrial fibrillation.

AIMS Transcatheter radiofrequency ablation of the atrio-ventricular (AV) node followed by ventricular pacing has been shown to improve symptoms and quality of life of patients with atrial fibrillation (AF). It is assumed that function improves, but this has been less well demonstrated. The aim of this study was to assess the long-term effect of AV node ablation and ventricular pacing on left ventricular ejection fraction (LVEF) in patients with permanent AF. METHODS AND RESULTS All 12 patients studied had permanent AF for at least 12 months (mean age 70 years, range 41 to 78). LVEF was determined 6 days and 3 months after AV node ablation by radionuclide ventriculography, at a paced rate of 80 beats . min (-1). Cardiac dimensions were measured by means of transthoracic echocardiography. No major changes in pharmacological therapy were made during 3 months follow-up period. LVEF showed a significant deterioration after 3 months follow-up period for the group (47.5 +/- 14.4%; 6 days after ablation vs 43.2 +/- 13.7%; 3 months after ablation, P < 0.05). There were no significant differences in left ventricular cavity dimensions directly after AV node ablation and 3 months later (LVEDD 51.2 +/- 10.7 mm vs 52.6 +/- 8.6 mm, P = NS: LVESD: 36.1 +/- 14.2 mm vs 36.6 +/- 9.7 mm, P = NS). Left atrial size did not show reduction 3 months after AV node ablation (50.8 +/- 13.6 mm vs 51.0 +/- 14.1 mm, P = NS). CONCLUSION The restoration of a regular ventricular rhythm following AV node ablation for patients in permanent AF does not result in improvement in left ventricular function.
An In Silico Modeling Approach to Understanding the Dynamics of Sarcoidosis

Background Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis. Methodology/Results Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNFα, IFNγ) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and “sarcoidosis-like” (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships. Conclusions/Significance Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials.
Gradient Boosting With Piece-Wise Linear Regression Trees

Gradient Boosted Decision Trees (GBDT) is a very successful ensemble learning algorithm widely used across a variety of applications. Recently, several variants of GBDT training algorithms and implementations have been designed and heavily optimized in some very popular open sourced toolkits including XGBoost, LightGBM and CatBoost. In this paper, we show that both the accuracy and efficiency of GBDT can be further enhanced by using more complex base learners. Specifically, we extend gradient boosting to use piecewise linear regression trees (PL Trees), instead of piecewise constant regression trees, as base learners. We show that PL Trees can accelerate convergence of GBDT and improve the accuracy. We also propose some optimization tricks to substantially reduce the training time of PL Trees, with little sacrifice of accuracy. Moreover, we propose several implementation techniques to speedup our algorithm on modern computer architectures with powerful Single Instruction Multiple Data (SIMD) parallelism. The experimental results show that GBDT with PL Trees can provide very competitive testing accuracy with comparable or less training time.
Retinoic acid fails to reverse emphysema in adult mouse models

Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-α transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-α transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.
Business Ecosystem as the New Approach to Complex Adaptive Business Environments

This paper discusses the concept of business ecosystem. Business ecosystem is a relatively new concept in the field of business research, and there is still a lot of work to be done to establish it. First the subject is approached by examining a biological ecosystem, especially how biological ecosystems are defined, how they evolve and how they are classified and structured. Second, different analogies of biological ecosystem are reviewed, including industrial ecosystem, economy as an ecosystem, digital business ecosystem and social ecosystem. Third, business ecosystem concept is outlined by discussing views of main contributors and then bringing authors’ own definition out. Fourth, the emerging research field of complexity in social sciences is brought out due to authors’ attitude to consider ecosystems and business ecosystems as complex, adaptive systems. The focal complexity aspects appearing in business ecosystems are presented; they are self-organization, emergence, co-evolution and adaptation. By connecting business ecosystem concept to complexity research, it is possible to bring new insights to changing business environments.
Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers

Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier. Here, we show the role in this process of TAG-1, a glycosyl-phosphatidyl-inositol–anchored cell adhesion molecule. In the absence of TAG-1, axonal Caspr2 did not accumulate at juxtaparanodes, and the normal enrichment of shaker-type K+ channels in these regions was severely disrupted, in the central and peripheral nervous systems. In contrast, the localization of protein 4.1B, an axoplasmic partner of Caspr2, was only moderately altered. TAG-1, which is expressed in both neurons and glia, was able to associate in cis with Caspr2 and in trans with itself. Thus, a tripartite intercellular protein complex, comprised of these two proteins, appears critical for axo–glial contacts at juxtaparanodes. This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo–glial interactions.
Accurate Prediction of Crosstalk for RC Interconnects

This work proposes an accurate crosstalk noise estimation method in the presence of multiple RC lines for use in design automation tools. The method correctly models the loading effects of non switching aggressors and aggressor tree branches using resistive shielding effect and realistic exponential input waveform. Noise peak and width expressions derived show very good results in comparison to HSPICE results. Results show that average error for noise peak is 4.1% and for the width is 6.8% while allowing for very fast analysis.