Miracle-dz/UniFAR-FTUs huggingface dataset:
The binding activity of Mel‐18 at the Il17a promoter is regulated by the integrated signals of the TCR and polarizing cytokines

We have previously shown that in differentiated T‐helper (Th)1 and Th2 cells, polycomb group (PcG) proteins are associated differentially with the promoters of the signature cytokine genes. The correlation of the binding activity of PcG proteins with gene expression is unusual, since they are well known as epigenetic regulators that maintain transcriptional silencing. Here we show that in Th17 cells, the more phenotypically flexible Th lineage, the PcG proteins Mel‐18 and less strikingly Ezh2 are associated differentially with the Il17a promoter. Using the RNAi approach, we found that Mel‐18 and Ezh2 positively regulate the expression of Il17a and Il17f. The inducible binding of Mel‐18 and Ezh2 at the Il17a promoter was dependent on signaling pathways downstream of the TCR. However, a continuous presence of TGF‐β, the cytokine that is necessary to maintain Il17a expression, was required to preserve the binding activity of Mel‐18, but not of Ezh2, following restimulation. The binding of Mel‐18 at the Il17a promoter was correlated with the recruitment of the lineage‐specifying transcription factor RORγt. Altogether, our results suggest that in Th17 cells the TCR and polarizing cytokines synergize to modulate the binding activity of Mel‐18 at the Il17a promoter, and consequently to facilitate Il17a expression.
Inference for environmental intervention studies using principal stratification

Previous research has found evidence of an association between indoor air pollution and asthma morbidity in children. Environmental intervention studies have been performed to examine the role of household environmental interventions in altering indoor air pollution concentrations and improving health. Previous environmental intervention studies have found only modest effects on health outcomes and it is unclear if the health benefits provided by environmental modification are comparable with those provided by medication. Traditionally, the statistical analysis of environmental intervention studies has involved performing two intention‐to‐treat analyses that separately estimate the effect of the environmental intervention on health and the effect of the environmental intervention on indoor air pollution concentrations. We propose a principal stratification approach to examine the extent to which an environmental intervention's effect on health outcomes coincides with its effect on indoor air pollution. We apply this approach to data from a randomized air cleaner intervention trial conducted in a population of asthmatic children living in Baltimore, Maryland, USA. We find that among children for whom the air cleaner reduced indoor particulate matter concentrations, the intervention resulted in a meaningful improvement of asthma symptoms with an effect generally larger than previous studies have shown. A key benefit of using principal stratification in environmental intervention studies is that it allows investigators to estimate causal effects of the intervention for sub‐groups defined by changes in the indoor air pollution concentration. Copyright © 2014 John Wiley & Sons, Ltd.
Omega‐3 fatty acid supplementation delays the progression of neuroblastoma in vivo

Epidemiological and preclinical studies have revealed that omega‐3 fatty acids have anticancer properties. We have previously shown that the omega‐3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15‐lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high‐risk neuroblastoma.
Regional Specializations of the PAZ Proteomes Derived from Mouse Hippocampus, Olfactory Bulb and Cerebellum

Neurotransmitter release as well as structural and functional dynamics at the presynaptic active zone (PAZ) comprising synaptic vesicles attached to the presynaptic plasma membrane are mediated and controlled by its proteinaceous components. Here we describe a novel experimental design to immunopurify the native PAZ-complex from individual mouse brain regions such as olfactory bulb, hippocampus, and cerebellum with high purity that is essential for comparing their proteome composition. Interestingly, quantitative immunodetection demonstrates significant differences in the abundance of prominent calcium-dependent PAZ constituents. Furthermore, we characterized the proteomes of the immunoisolated PAZ derived from the three brain regions by mass spectrometry. The proteomes of the release sites from the respective regions exhibited remarkable differences in the abundance of a large variety of PAZ constituents involved in various functional aspects of the release sites such as calcium homeostasis, synaptic plasticity and neurogenesis. On the one hand, our data support an identical core architecture of the PAZ for all brain regions and, on the other hand, demonstrate that the proteinaceous composition of their presynaptic active zones vary, suggesting that changes in abundance of individual proteins strengthen the ability of the release sites to adapt to specific functional requirements.
Fabrication of Silicon Microtips with Integrated Electrodes

The possibility of producing controlled mechanical movement or performing free movement in response to an external agent is the fundamental fact that supports the impressive evolution experimented by Micro Electro-Mechanical Systems (MEMS) [1,2,3] and by the enormous commercial importance that MEMS technology has reached in recent years in the sensors and actuators market [4,5]. However, besides the production and detection of movement, MEMS technology is strongly related to the capacity to fabricate microstructures with 3D geometry. Among these microstructures, silicon microtips are one of the more interesting due to their particular geometry and because they allow the development of low voltage electron field emitting devices. In this way, Si microtips exhibit applications in different fields, such as atomic force microscopy (AFM), electron beam lithography, microwave power amplifiers and in the so called Vacuum Microelectronics, specially for field emission displays (FED's) [6,7,8]. Different approaches have been reported for the fabrication of Si microtips but the simplest techniques are based in bulk micromaching of the Si substrate. For example, silicon tips with excellent geometry and size in the range of a few microns and smaller have been fabricated through wet anisotropic etching in alkaline solutions, mixed or not with dry isotropic corrosion steps, and followed by thermal oxidation sharpening [9,10]. Other processes utilize porous silicon as a sacrificial layer in isotropic wet etching, also in alkaline solutions and with similar results [11]. All these processes are simple but have the inconvenience that the polarization electrode must be positioned externally, through manually operated micromanipulators with resolution in the micron range. To overcome this problem, and taking advantage of the simplicity of silicon micromachinig in alkaline solutions, in this paper a method of fabricating silicon microtips with self-aligned integrated electrodes on (100) oriented Si wafers is proposed.
Yoga breathing through a particular nostril is associated with contralateral event-related potential changes

Background: In earlier studies uninostril yoga breathing was shown to influence the activity of the cerebral hemispheres differently, based on (i) auditory evoked potentials recorded from bilateral scalp sites, and (ii) performance in hemisphere-specific tasks. But change in P300 (event-related potential generated when subjects attend to and discriminate between stimuli) from bilateral scalp sites when subjects were practicing uni- and alternate-nostril breathing are yet to be explored. Aim: The present study was designed to determine whether or not immediately after uninostril or alternate nostril yoga breathing there would be a change in the ability to pay attention to a given stimulus. Materials and Methods: Twenty-nine healthy male volunteers, with ages between 20 and 45 years were randomly allocated to five sessions, viz., (i) right-, (ii) left-, (iii) alternate-nostril yoga breathing, (iv) breath awareness and (v) no intervention, each for 45 min on separate days. The P300 event related potential was recorded using an auditory oddball paradigm from sites on the left (C3) and right (C4), referenced to linked earlobes, before and after each session. Results: Post-hoc analysis with Bonferroni adjustment showed that the P300 peak latency was significantly lower at C3 compared to that at C4, following right nostril yoga breathing (P<0.05). Conclusion: These results suggest that right nostril yoga breathing facilitates the activity of contralateral (left) hemisphere, in the performance of the P300 task.
Dynamic Radius Species Conserving Genetic Algorithm for Test Generation for Structural Testing

Software testing is a critical and labor-intensive activity in software engineering. Much research has been done to help automate test case generation. This research proposes a new approach to structural test case generation. It uses a specialized genetic algorithm called Dynamic-radius Species-conserving Genetic Algorithm (DSGA) to find a structurally complete set of test cases for the Triangle Classification algorithm. DSGA is a Niche Genetic Algorithm (NGA) that uses a short-term memory structure to store optima. Each individual of the NGA represents the inputs for a test case. The fitness function encourages the algorithm to locate test cases that cover large areas of the structure of the program. A shared fitness encourages the NGA to locate other areas of the structure. DSGA is a novel approach to structurally complete test case generation.
Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses

Almost all eukaryotic proteins are subject to post-translational modifications during mitosis and cell cycle, and in particular, reversible phosphorylation being a key event. The recent use of high-throughput experimental analyses has revealed that more than 70% of all eukaryotic proteins are regulated by phosphorylation; however, the mechanism of dephosphorylation, counteracting phosphorylation, is relatively unknown. Recent discoveries have shown that many of the protein phosphatases are involved in the temporal and spatial control of mitotic events, such as mitotic entry, mitotic spindle assembly, chromosome architecture changes and cohesion, and mitotic exit. This implies that certain phosphatases are tightly regulated for timely dephosphorylation of key mitotic phosphoproteins and are essential for control of various mitotic processes. This review describes the physiological and pathological roles of mitotic phosphatases, as well as the versatile role of various protein phosphatases in several mitotic events.
The emerging role of protein kinase Cθ in cytoskeletal signaling

Cytoskeletal rearrangements often occur as the result of transduction of signals from the extracellular environment. Efficient awakening of this powerful machinery requires multiple activation and deactivation steps, which usually involve phosphorylation or dephosphorylation of different signaling units by kinases and phosphatases, respectively. In this review, we discuss the signaling characteristics of one of the nPKC isoforms, PKCθ, focusing on PKCθ‐mediated signal transduction to cytoskeletal elements, which results in cellular rearrangements critical for cell type‐specific responses to stimuli. PKCθ is the major PKC isoform present in hematopoietic and skeletal muscle cells. PKCθ plays roles in T cell signaling through the IS, survival responses in adult T cells, and T cell FasL‐mediated apoptosis, all of which involve cytoskeletal rearrangements and relocation of this enzyme. PKCθ has been linked to the regulation of cell migration, lymphoid cell motility, and insulin signaling and resistance in skeletal muscle cells. Additional roles were suggested for PKCθ in mitosis and cell‐cycle regulation. Comprehensive understanding of cytoskeletal regulation and the cellular “modus operandi” of PKCθ holds promise for improving current therapeutic applications aimed at autoimmune diseases.
Mapping topics and topic bursts in PNAS

Scientific research is highly dynamic. New areas of science continually evolve; others gain or lose importance, merge, or split. Due to the steady increase in the number of scientific publications, it is hard to keep an overview of the structure and dynamic development of one's own field of science, much less all scientific domains. However, knowledge of “hot” topics, emergent research frontiers, or change of focus in certain areas is a critical component of resource allocation decisions in research laboratories, governmental institutions, and corporations. This paper demonstrates the utilization of Kleinberg's burst detection algorithm, co-word occurrence analysis, and graph layout techniques to generate maps that support the identification of major research topics and trends. The approach was applied to analyze and map the complete set of papers published in PNAS in the years 1982-2001. Six domain experts examined and commented on the resulting maps in an attempt to reconstruct the evolution of major research areas covered by PNAS.
An Unexpected Synergist Role of P-Glycoprotein and Breast Cancer Resistance Protein on the Central Nervous System Penetration of the Tyrosine Kinase Inhibitor Lapatinib (N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine; GW572016)

Lapatinib is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing human epidermal receptor 2 (ErbB2). This work investigated the role of P-glycoprotein (Pgp; the protein from the Mdr1a/b gene) and breast cancer resistance protein (Bcrp; the protein from the Bcrp1 gene) in modulating the central nervous system penetration of lapatinib at steady-state conditions in FVBn mice (wild-type), Mdr1a/b(–/–), Bcrp1(–/–), and Mdr1a/b(–/–)/Bcrp1(–/–) knockout mice. After an intravenous infusion of lapatinib for 24 h to a targeted steady-state plasma concentration of 700 ng/ml (0.3 mg/kg/h) or 7000 ng/ml (3 mg/kg/h), lapatinib brain-to-plasma ratios were approximately 3- to 4-fold higher in Mdr1a/b(–/–) knockout mice (ratio range from 0.09 to 0.16) compared with wild-type mice (ratio range from 0.03 to 0.04). There was no difference in the brain-to-plasma ratio in the Bcrp1(–/–) knockout mice (ratio range from 0.03 to 0.04) compared with wild-type mice. In contrast, Mdr1a/b(–/–)/Bcrp1(–/–) triple knockout mice had a 40-fold higher brain-to-plasma ratio (ratio range from 1.2 to 1.7), suggesting that Pgp and Bcrp work in concert to limit the brain-to-plasma ratio of lapatinib in mice. This finding has important potential consequences for the treatment of brain tumors in breast cancer patients treated with tyrosine kinase inhibitors as well as the basic understanding of ATP binding cassette transporters expressed in the blood-brain barrier on the central nervous system disposition of drugs.
Content aware multimedia communications

The demands for fast, economic and reliable dissemination of multimedia information are steadily growing within our society. While people and economy increasingly rely on communication technologies, engineers still struggle with their growing complexity. Complexity in multimedia communication originates from several sources. The most prominent is the unreliability of packet networks like the Internet. Recent advances in scheduling and error control mechanisms for streaming protocols have shown that the quality and robustness of multimedia delivery can be improved significantly when protocols are aware of the content they deliver. However, the proposed mechanisms require close cooperation between transport systems and application layers which increases the overall system complexity. Current approaches also require expensive metrics and focus on special encoding formats only. A general and efficient model is missing so far. This thesis presents efficient and format-independent solutions to support cross-layer coordination in system architectures. In particular, the first contribution of this work is a generic dependency model that enables transport layers to access content-specific properties of media streams, such as dependencies between data units and their importance. The second contribution is the design of a programming model for streaming communication and its implementation as a middleware architecture. The programming model hides the complexity of protocol stacks behind simple programming abstractions, but exposes cross-layer control and monitoring options to application programmers. For example, our interfaces allow programmers to choose appropriate failure semantics at design time while they can refine error protection and visibility of low-level errors at run-time. Based on some examples we show how our middleware simplifies the integration of stream-based communication into large-scale application architectures. An important result of this work is that despite cross-layer cooperation, neither application nor transport protocol designers experience an increase in complexity. Application programmers can even reuse existing streaming protocols which effectively increases system robustness.
A Visual Technique for Internet Anomaly Detection

The Internet can be made more secure and efficient with effective anomaly detection. In this paper, we describe a visual method for anomaly detection using archived Border Gateway Protocol (BGP) data. A special encoding of IP addresses built into an interactive visual interface design allows a user to quickly detect Origin AS changes by browsing through 2D visual representation of selected aspects of the BGP data. We demonstrate that each visually spotted anomaly agrees with actual anomaly on record. It is clear that this visual approach can play a major role in an anomaly detection system.
High Untreated Phytic-Acid In The Diet, May Lead To Mineral Deficiencies, Specifically, During Pregnancy

—Wheat bread, rice and unfermented soy, are the main part of the many industrialized country’s people diet. Due to improper preparation and fermentation, Phytic-acid, The compound which bounds with calcium, magnesium and zinc and reduce the absorption of these important minerals, is one important cause of mineral deficiencies in men and women. Improper sourdough fermentation and not enough time to fermentation process, will not reduce the amounts of phytic-acid in bread and legumes. The certain mineral deficiency during pregnancy is one of the main health issues that is important to be considered by physicians. Magnesium, iron, zinc and calcium are three of the main mineral for the healthy mother and child which could be depleted by consuming high-phytate diets.
Arabidopsis Roots and Shoots Show Distinct Temporal Adaptation Patterns toward Nitrogen Starvation1[W]

Nitrogen (N) is an essential macronutrient for plants. N levels in soil vary widely, and plants have developed strategies to cope with N deficiency. However, the regulation of these adaptive responses and the coordinating signals that underlie them are still poorly understood. The aim of this study was to characterize N starvation in adult Arabidopsis (Arabidopsis thaliana) plants in a spatiotemporal manner by an integrative, multilevel global approach analyzing growth, metabolites, enzyme activities, and transcript levels. We determined that the remobilization of N and carbon compounds to the growing roots occurred long before the internal N stores became depleted. A global metabolite analysis by gas chromatography-mass spectrometry revealed organ-specific differences in the metabolic adaptation to complete N starvation, for example, for several tricarboxylic acid cycle intermediates, but also for carbohydrates, secondary products, and phosphate. The activities of central N metabolism enzymes and the capacity for nitrate uptake adapted to N starvation by favoring N remobilization and by increasing the high-affinity nitrate uptake capacity after long-term starvation. Changes in the transcriptome confirmed earlier studies and added a new dimension by revealing specific spatiotemporal patterns and several unknown N starvation-regulated genes, including new predicted small RNA genes. No global correlation between metabolites, enzyme activities, and transcripts was evident. However, this multilevel spatiotemporal global study revealed numerous new patterns of adaptation mechanisms to N starvation. In the context of a sustainable agriculture, this work will give new insight for the production of crops with increased N use efficiency.
Investigation of three-dimensional theory on sound transmission through compressed poroelastic sandwich cylindrical shell in various boundary configurations

The present work applies three-dimensional elasticity theory as well as extended full method based on Biot’s theory to inspect the effect of compressing porous material on sound transmission loss of the multilayered cylindrical shell subjected to porous core and air-gap insulation in the presence of external flow considering various boundary configurations. According to this fact, first, three-dimensional elasticity theory is employed for the double-walled laminated composite parts of the structure which leads to governing equations with no extra assumptions as well as considering extended full method for poroelastic section which models the structure in three directions with no need to identify the frequency domain (unlike the simplified method). Consequently, the obtained equations are solved applying state space method based on approximate laminate model beside transfer matrix approach. Likewise, the procedure is followed to obtain sound transmission loss in appropriate boundary condition. Second, the influence of compressing porous core on acoustic transmission of the current structure is cleared. Furthermore, this paper includes some configurations which compare the obtained results with those available in literature to indicate the accuracy, reliability and simplicity of the present method particularly in comparison with the simplified method. Finally, some configurations are appeared in numerical result section to show the effects of the various parameters on sound transmission loss.