Miracle-dz/UniFAR-FTUs huggingface dataset:
Ammonium Trichloro(dioxoethylene-o,o′)tellurate (AS101) Sensitizes Tumors to Chemotherapy by Inhibiting the Tumor Interleukin 10 Autocrine Loop

Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o′)tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies.
Effects of nutrient optimization on intra-annual wood formation in Norway spruce.

In the Nordic countries, growth of Norway spruce (Picea abies (L.) Karst. ) is generally limited by low availability of nutrients, especially nitrogen. Optimizing forest management requires better insight on how growth responds to the environmental conditions and their manipulation. The aim of this study was to analyse the effects of nutrient optimization on timing and the rate of tracheid formation of Norway spruce and to follow the differentiation of newly formed tracheids. The study was performed during two growing seasons in a long-term nutrient optimization experiment in northern Sweden, where all essential macro- and micronutrients were supplied in irrigation water every second day from mid-June to mid-August. The control plots were without additional nutrients and water. Tracheid formation in the stem was monitored throughout the growing season by weekly sampling of microcores at breast height. The onset of xylogenesis occurred in early June, but in early summer there were no significant between-treatment differences in the onset and relative rate of tracheid formation. In both treatments, the onset of secondary cell wall formation occurred in mid-June. The maximum rate of tracheid formation occurred close to the summer solstice and 50% of the tracheids had been accumulated in early July. Optimized nutrition resulted in the formation of ∼50% more tracheids and delayed the cessation of tracheid formation, which extended the tracheid formation period by 20-50%, compared with control trees. The increased growth was mainly an effect of enhanced tracheid formation rate during the mid- and later-part of the growing season. In the second year, the increased growth rate also resulted in 11% wider tracheids. We conclude that the onset and rate of tracheid formation and differentiation during summer is primarily controlled by photoperiod, temperature and availability of nutrients, rather than supply of carbohydrates.
Journal of Graph Algorithms and Applications Mapsets: Visualizing Embedded and Clustered Graphs

In addition to objects and relationships between them, groups or clusters of objects are an essential part of many real-world datasets: party affiliation in political networks, types of living organisms in the tree of life, movie genres in the internet movie database. In recent visualiza-tion methods, such group information is conveyed by explicit regions that enclose related elements. However, when in addition to fixed cluster membership , the input elements also have fixed positions in space (e.g., geo-referenced data), it becomes difficult to produce readable visualizations. In such fixed-clustering and fixed-embedding settings, some methods produce fragmented regions, while other produce contiguous (connected) regions that may contain overlaps even if the input clusters are disjoint. Both fragmented regions and unnecessary overlaps have a detrimental effect on the interpretation of the drawing. With this in mind, we propose MapSets: a visualization technique that combines the advantages of both methods, producing maps with non-fragmented and non-overlapping regions. The proposed method relies on a theoretically sound geometric algorithm which guarantees contiguity and disjointness of the regions, and also optimizes the convexity of the regions. A fully functional implementation is available in an online system and is used in a comparison with related earlier methods.
Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain

Glucocorticoids have been used for 30 years to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery. Exposure to inappropriate levels of steroid, however, leads to altered maturation of the cardiovascular, metabolic and central nervous systems. The effects of betamethasone on neuronal development and function were determined in the fetal baboon brain by examination of cytoskeletal microtubule associated proteins (MAPs) and the presynaptic marker protein synaptophysin. At 0.73 gestation, commencing 28 weeks of gestation, pregnant baboons received four doses of saline (n= 8) or 87.5 µg (kg body weight)−1 betamethasone i.m. (n= 7) 12 h apart. This dose is equivalent to 12 mg betamethasone administered daily over two consecutive days to a 70 kg woman. Baboons underwent Caesarean section 12 h after the last injection. Paraffin sections of the fetal neocortex and the underlying white matter were labelled immunohistochemically against MAP1B, MAP2abc, MAP2ab and synaptophysin and stained histochemically with hematoxylin‐eosin and silver. Tissue staining was quantified morphometrically. Betamethasone exposure resulted in decreased immunoreactivity (IR) of MAP1B by 34.3 % and MAP2abc by 34.1 % (P < 0.05). Loss of MAP2 IR was due to loss of IR of the juvenile isoform MAP2c (P < 0.05). MAP1B and MAP2c are involved in neuritogenesis and neuronal plasticity. Synaptophysin IR was reduced by 51.8 % (P < 0.01). These changes might reflect functional neuronal disturbances because they were not accompanied by an alteration of the density of neurofibrils or neuronal necrosis. These results are in agreement with earlier findings of alterations of cytoskeletal proteins and presynaptic terminals in the fetal sheep brain after betamethasone infusion directly to the fetus and support a common effect of inappropriate fetal exposure to glucocorticoids on neuronal cytoskeleton and synapses in mammalian species.
Region-of-Interest video coding by fuzzy control for H.263+ standard

This paper proposes an Region-of-Interest(ROI) video coding algorithm based on H.263+. The ability to give higher priority to ROI is the emerging functionality for video coding nowadays. In most videoconferencing and videophony, most existing compression schemes treat the entire image uniformly. However, the background is much less critical than the foreground, i.e., human face, moving objects, etc., for communication. A region-based video codec based on the H.263+ with the optional mode of modified quantization is set up. A new algorithm based on TMN8 utilizes a fuzzy logic control method to give adaptively weighted factors to each macroblock(MB) and allocate different bits to each MB according to the complexity and the variance variation in the rate-and-distortion model. From experimental results, the proposed method can significantly improve the quality at ROI and multiple ROI functionality also has been implemented. Our method is suitable for real time videoconferencing.
A Simple Method to Determine Mixed Exhaled CO2 Using a Standard Circle Breathing Circuit

INTRODUCTION:Mixed exhaled CO2 and CO2 excretion (VCO2) are not routinely monitored during anesthesia because they are difficult to measure using standard equipment. We conducted two experiments to test the hypothesis that the ventilator bellows contains mixed exhaled CO2. METHODS:In the laboratory experiment, a lung model was assembled with a CO2 source. The gasses were sampled from the bellows and VCO2 was calculated. These values were compared to VCO2 measured by the NICO monitor (Novametrix Medical Systems), a commercially available mainstream capnometer. In the clinical experiment, gasses were sampled from the ventilator bellows in nine subjects under general anesthesia. VCO2 was calculated and compared to values obtained from the NICO monitor. RESULTS:VCO2 measured from the bellows connected to the lung model resulted in an overall precision of 26 mL/min, bias of −24 mL/min, and average error of −12.0% compared to set CO2 flow. In the clinical trial, calculated VCO2 sampled from the bellows compared to measured VCO2 from the NICO monitor had a bias of −0.15 mL/min, and precision of 33.16 mL/min. CONCLUSION:VCO2 calculated from the bellows was not as accurate as NICO VCO2 in the laboratory; however, it can be done using standard anesthesia equipment. Furthermore, in nine anesthetized subjects, the bellows method of VCO2 determination had an overall percent error of 1.34% from NICO VCO2. Given this small percent error between the bellows method and the NICO monitor, we believe that the bellows method of VCO2 determination is suitable for clinical practice.
Geometrically Compensating Effect of End-to-End Latency in Moving-Target Selection Games

Effects of unintended latency on gamer performance have been reported. End-to-end latency can be corrected by post-input manipulation of activation times, but this gives the player unnatural gameplay experience. For moving-target selection games such as Flappy Bird, the paper presents a predictive model of latency on error rate and a novel compensation method for the latency effects by adjusting the game's geometry design -- e.g., by modifying the size of the selection region. Without manipulation of the game clock, this can keep the user's error rate constant even if the end-to-end latency of the system changes. The approach extends the current model of moving-target selection with two additional assumptions about the effects of latency: (1) latency reduces players' cue-viewing time and (2) pushes the mean of the input distribution backward. The model and method proposed have been validated through precise experiments.
CERENA: ChEmical REaction Network Analyzer—A Toolbox for the Simulation and Analysis of Stochastic Chemical Kinetics

Gene expression, signal transduction and many other cellular processes are subject to stochastic fluctuations. The analysis of these stochastic chemical kinetics is important for understanding cell-to-cell variability and its functional implications, but it is also challenging. A multitude of exact and approximate descriptions of stochastic chemical kinetics have been developed, however, tools to automatically generate the descriptions and compare their accuracy and computational efficiency are missing. In this manuscript we introduced CERENA, a toolbox for the analysis of stochastic chemical kinetics using Approximations of the Chemical Master Equation solution statistics. CERENA implements stochastic simulation algorithms and the finite state projection for microscopic descriptions of processes, the system size expansion and moment equations for meso- and macroscopic descriptions, as well as the novel conditional moment equations for a hybrid description. This unique collection of descriptions in a single toolbox facilitates the selection of appropriate modeling approaches. Unlike other software packages, the implementation of CERENA is completely general and allows, e.g., for time-dependent propensities and non-mass action kinetics. By providing SBML import, symbolic model generation and simulation using MEX-files, CERENA is user-friendly and computationally efficient. The availability of forward and adjoint sensitivity analyses allows for further studies such as parameter estimation and uncertainty analysis. The MATLAB code implementing CERENA is freely available from http://cerenadevelopers.github. io/CERENA/.
The safety of Bruton’s tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia

ABSTRACT Introduction: The approval of ibrutinib has revolutionized the therapeutic landscape of chronic lymphocytic leukemia (CLL). Currently ibrutinib is indicated for patients that are both treatment naïve as well as those with relapsed CLL. Ibrutinib is generally well-tolerated with durable responses that improve over time in most patients. Important toxicities include atrial fibrillation and bleeding. Areas cover: This review covers the pharmacokinetics, pharmacodynamics, safety and efficacy of ibrutinib in the treatment of CLL. We also compare ibrutinib with other kinase inhibitors and chemoimmunotherapy regimens using data from clinical trials. A literature search utilized the PubMed database. Expert opinion: Despite the efficacy and tolerability of ibrutinib, important questions remain, which include selection of patients receiving ibrutinib in the first and subsequent lines of treatment, optimal dosing, sequential use of ibrutinib versus other kinase inhibitors and combination therapy. Prospective studies should incorporate minimal residual disease (MRD) status as a clinical endpoint to determine whether patients can be taken off kinase inhibitors.
Physiological unmasking of new glutamatergic pathways in the dentate gyrus of hippocampal slices from kainate-induced epileptic rats.

In humans with temporal lobe epilepsy and kainate-treated rats, the mossy fibers of the dentate granule cells send collateral axons into the inner molecular layer. Prior investigations on kainate-treated rats demonstrated that abnormal hilar-evoked events can occasionally be observed in slices with mossy fiber sprouting when gamma-aminobutyric acid-A (GABAA)-mediated inhibition is blocked with bicuculline. However, these abnormalities were observed infrequently, and it was unknown whether these rats were epileptic. Wuarin and Dudek reported that in slices from kainate-induced epileptic rats (3-13 mo after treatment), hilar stimulation evoked abnormal events in most slices with mossy fiber sprouting exposed simultaneously to bicuculline and elevated extracellular potassium concentration [K+]o. Using the same rats, extracellular recordings were obtained from granule cells in hippocampal slices to determine whether 1) hilar stimulation could evoke abnormal events in slices with sprouting in normal artificial cerebrospinal fluid (ACSF), 2) adding only bicuculline could unmask hilar-evoked abnormalities and glutamate-receptor antagonists could block these events, and 3) increasing only [K+]o could unmask these abnormalities. In normal ACSF, hilar stimulation evoked abnormal field potentials in 27% of slices with sprouting versus controls without sprouting (i.e., saline-treated or only 2-4 days after kainate treatment). In bicuculline (10 microM) alone, hilar stimulation triggered prolonged field potentials in 84% of slices with sprouting, but not in slices from the two control groups. Addition of the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5), either blocked the bursts or reduced their probability of occurrence. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), always eliminated the epileptiform bursts. In kainate-treated rats with sprouting, but not in saline-treated controls, abnormal hilar-evoked responses were also revealed in 6-9 mM [K+]o. Additionally, 63% of slices with sprouting generated spontaneous bursts lasting 1-40 s in ACSF containing 9 mm [K+]o; similar bursts were not observed in controls. These results indicate that 1) mossy fiber sprouting is associated with new glutamatergic pathways, and although NMDA receptors are important for propagation through these circuits, AMPA receptor activation is crucial, 2) modest elevations of [K+]o, in a range that would have relatively little effect on granule cells, can unmask these new excitatory circuits and generate epileptiform bursts, and 3) this new circuitry underlies an increased electrographic seizure susceptibility when inhibition is depressed or membrane excitability is increased.
Evidence for abnormal platelet glycoprotein expression in diabetes mellitus

In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54100 times 1·27±1 vs. 39100 times 1·3±1 GPIIB/IIIA: 77500 times 1·3±1 vs. 62700 times 1·3±1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0·52 ± 0·07; r (diabetic) = 0·46 ± 0·1). Additionally, von Willebrand factor‐related antigen (vWF: AG) was increased to 129% × 1·3 ± 1 in diabetics vs. 111% × 1·4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0·38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone‐marrow megakaryocyto‐ thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.
Plastic Accumulation in the Mediterranean Sea

Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2), as well as its frequency of occurrence (100% of the sites sampled), are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources. The accumulation of floating plastic in the Mediterranean Sea (between 1,000 and 3,000 tons) is likely related to the high human pressure together with the hydrodynamics of this semi-enclosed basin, with outflow mainly occurring through a deep water layer. Given the biological richness and concentration of economic activities in the Mediterranean Sea, the affects of plastic pollution on marine and human life are expected to be particularly frequent in this plastic accumulation region.
Psychometric assessment of scales measuring HIV public stigma, drug-use public stigma and fear of HIV infection among young adolescents and their parents

The objective of this study was to design and assess measurement instruments that accurately measure the levels of stigma among individuals with a primarily collectivist culture. A cross-sectional study was conducted among middle school students and their parents or guardians in a rural area of China. Exploratory and confirmatory factor analyses were used to examine and determine the latent factors of the sub-scales of stigma respectively, among students and their parents. Factor analyses identified three sub-scales: HIV public stigma (seven items), drug-use public stigma (nine items), and fear of HIV infection (seven items). There were no items with cross-loading onto multiple factors, supporting the distinctness of the constructs that these scales were meant to measure. Goodness of fit indices indicated that a three-factor solution fit, the data at an acceptable level in the student sample (χ2 /degree ratio=1.98, comparative fit index [CFI]=0.92, root mean square error of approximation [RMSEA]=0.055, standardized root mean square residual [SRMR]=0.057) and in the parent sample (χ2/degree ratio=1.95, CFI=0.91, RMSEA=0.06, SRMR=0.059). Reliability of the three scales was excellent (Cronbach's alpha: 0.78–0.92 for students; 0.80–0.94 for parents or guardians) and stable across split samples and for the data as a whole. The scales are brief and suitable for use in developing countries where the collectivist culture prevails.
A Cold Shock-Induced Cyanobacterial RNA Helicase

ABSTRACT The ability to modify RNA secondary structure is crucial for numerous cellular processes. We have characterized two RNA helicase genes, crhB and crhC, which are differentially expressed in the cyanobacterium Anabaena sp. strain PCC 7120. crhC transcription is limited specifically to cold shock conditions while crhB is expressed under a variety of conditions, including enhanced expression in the cold. This implies that both RNA helicases are involved in the cold acclimation process in cyanobacteria; however, they presumably perform different roles in this adaptation. Although both CrhB and CrhC belong to the DEAD box subfamily of RNA helicases, CrhC encodes a novel RNA helicase, as the highly conserved SAT motif is modified to FAT. This alteration may affect CrhC function and its association with specific RNA targets and/or accessory proteins, interactions required for cold acclimation. Primer extension and analysis of the 5′ untranslated region of crhC revealed the transcriptional start site, as well as a number of putative cold shock-responsive elements. The potential role(s) performed by RNA helicases in the acclimation of cyanobacteria to cold shock is discussed.
A Belief System's Organization Based on a Computational Model of the Dynamic Context: First Approximation

In this article we present a model of organization of a belief system based on a set of binary recursive functions that characterize the dynamic context that modifies the beliefs. The initial beliefs are modeled by a set of two-bit words that grow, update, and generate other beliefs as the different experiences of the dynamic context appear. Reason is presented as an emergent effect of the experience on the beliefs. The system presents a layered structure that allows a functional organization of the belief system. Our approach seems suitable to model different ways of thinking and to apply to different realistic scenarios such as ideologies.
ISPAD Clinical Practice Consensus Guidelines 2018: Nutritional management in children and adolescents with diabetes

Nutritional management is one of the cornerstones of diabetes care and education. Different countries and regions have widely varying cultures and socio- economic status that influence and dominate dietary habits. Although there is strong evidence for nutritional requirements in young people the scientific evidence base for many aspects of diabetes dietary management is still emerging and it is important to individualize nutrition interventions and meal plans. This article is protected by copyright. All rights reserved.