Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity

The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97–116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti‐AChR antibody production and proliferation of AChR‐specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T‐helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1‐, Th2‐, and Th17‐cell subtypes. An EAMG‐preventive treatment regimen was established that consisted of (2‐(p‐(2‐carbonylethyl)phenylethylamino)‐5‐N‐ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T‐cell‐ and B‐cell‐mediated autoimmune diseases.
The Grünwald-Letnikov formula and its equivalent Horner's form accuracy comparison and evaluation for application to fractional order PID controllers

In this paper we discuss a problem of numerical calculation accuracy of the Fractional-order Backward Difference/Sum (FOBD/S) of some discrete functions applied in discrete control strategies, in real-time closed-loop systems. We compare Grünwald-Letnikov formula vs. its Horner's equivalent form, as well as their “simplified” forms, in our opinion, an interesting tool in minimization of the time and memory shortage problems often to meet in such systems.
Rethinking Heart Failure

An increasing body of clinical observations and experimental evidence suggests that cardiac dysfunction results from autonomic dysregulation of the contractile output of the heart. Excessive activation of the sympathetic nervous system and a decrease in parasympathetic tone are associated with increased mortality. Elevated levels of circulating catecholamines closely correlate with the severity and poor prognosis in heart failure. Sympathetic over-stimulation causes increased levels of catecholamines, which induce excessive aerobic metabolism leading to excessive cardiac oxygen consumption. Resulting impaired mitochondrial function causes acidosis, which results in reduction in blood flow by impairment of contractility. To the extent that the excessive aerobic metabolism resulting from adrenergic stimulation comes to a halt the energy deficit has to be compensated for by anaerobic metabolism. Glucose and glycogen become the essential nutrients. Beta-adrenergic blockade is used successfully to decrease hyperadrenergic drive. Neurohumoral antagonists block adrenergic over-stimulation but do not provide the heart with fuel for compensatory anaerobic metabolism. The endogenous hormone ouabain reduces catecholamine levels in healthy volunteers, promotes the secretion of insulin, induces release of acetylcholine from synaptosomes and potentiates the stimulation of glucose metabolism by insulin and acetylcholine. Ouabain stimulates glycogen synthesis and increases lactate utilisation by the myocardium. Decades of clinical experience with ouabain confirm the cardioprotective effects of this endogenous hormone. The so far neglected sympatholytic and vagotonic effects of ouabain on myocardial metabolism clearly make a clinical re-evaluation of this endogenous hormone necessary. Clinical studies with ouabain that correspond to current standards are warranted.
Metastasis in Patients with Breast Cancer Expression and Correlate with Lymph Node Antitumor Immune Responses through IDO Myeloid-Derived Suppressor Cells Suppress

Myeloid-derived suppressor cells (MDSCs) represent heterogeneous immunosuppressive cells in multiple cancer types and display potent immunosuppressive activity on T cells. We have shown the increased expression of IDO in breast cancer. Because IDO plays a pivotal role in immune tolerance via suppressing T cell function, the aim of this study was to investigate the expression of IDO in MDSCs in breast cancer and its role in MDSC-mediated inhibition of immune surveillance. The proportion of MDSCs with the phenotype of CD45 + CD13 + CD33 + CD14 2 CD15 2 signiﬁcantly increased in primary cancer tissues and patients’ peripheral blood. IDO expression was signiﬁcantly upregulated in MDSCs isolated from fresh breast cancer tissues (fresh MDSCs [fMDSCs]), which correlated with increased inﬁltration of Foxp3 + regulatory T cells in tumors and lymph node metastasis in patients. fMDSCs inhibited IL-2 and anti-CD3/CD28 mAb-induced T cell ampliﬁcation and Th1 polarization but stimulated apoptosis in T cells in an IDO-dependent manner. CD33 + progenitors isolated from healthy donors’ umbilical cord blood were cocultured with breast cancer cell line MDA-MB-231 cells to induce MDSCs. IDO expression was upregulated in induced MDSCs, which required phosphorylation of STAT3, but not STAT1. IDO was required for induced MDSCs’ immunosuppressive activity on T cells, which was blocked by IDO inhibitor 1-methyl- L -tryptophan or STAT3 antagonist JSI-124. Consistently, increased STAT3 phosphorylation level was found in fMDSCs. Together, our ﬁndings suggest (ARG1)–mediated local depletion of arginine and cysteine, inducible NO synthase (iNOS), and NADPH oxidase–dependent production of reactive oxygen species and reactive nitrogen species, and activation and expansion of Ag-speciﬁc regulatory T cells (Tregs) (15–17). Recent studies demonstrated a distinct correlation between IDO, a rate-limiting enzyme in the catabolism of tryptophan, and tumor-induced immunosuppression (18–20). IDO exerts its suppressive effects via reduction of local tryptophan and generation of cytotoxic metabolites at the tumor site and tumor-draining lymph nodes to block initiation of Ag-speciﬁc immune
Constructive visualization

If visualization is to be democratized, we need to provide means for non-experts to create visualizations that allow them to engage directly with datasets. We present constructive visualization a new paradigm for the simple creation of flexible, dynamic visualizations. Constructive visualization is simple-in that the skills required to build and manipulate the visualizations are akin to kindergarten play; it is expressive in that one can build within the constraints of the chosen environment, and it also supports dynamics -- in that these constructed visualizations can be rebuilt and adjusted. We de- scribe the conceptual components and processes underlying constructive visualization, and present real-world examples to illustrate the utility of this approach. The constructive visualization approach builds on our inherent understanding and experience with physical building blocks, offering a model that enables non-experts to create entirely novel visualizations, and to engage with datasets in a manner that would not have otherwise been possible.
A Paintability Version of the Combinatorial Nullstellensatz, and List Colorings of k-partite k-uniform Hypergraphs

We study the list coloring number of $k$-uniform $k$-partite hypergraphs. Answering a question of Ramamurthi and West, we present a new upper bound which generalizes Alon and Tarsi's bound for bipartite graphs, the case $k=2$. Our results hold even for paintability (on" line list colorability). To prove this additional strengthening, we provide a new subject"=specific version of the Combinatorial Nullstellensatz .
Modular Data Clustering - Algorithm Design beyond MapReduce

In the context of Big Data, flexible and adjustable data analytics become more and more important, whereas an efficient, scalable and fault-tolerant execution is required as well. To fulfill the flexibility as well as the execution requirements, the specification of the analysis methods have to be in an appropriate and easy adjustable manner. The MapReduce approach has demonstrated that such flexible specification as well as scalable execution is possible and applicable. However, the MapReduce programming model is too generic and complicates the specification from a data analysis point of view. Therefore, we propose a novel programming approach using well-defined modular building blocks for a specific and highly utilized data analysis domain named data clustering in this paper. Our approach offers many advantages: (i) a unified and specific instruction set for data clustering which eases understanding and algorithm adaptation in an abstract way, and (ii) enables an efficient and scalable execution of all data clustering algorithms based on an efficient mapping of the unified instruction set to a specific target environment is possible.
A new worm exploiting IPv6 and IPv4-IPv6 dual-stack networks: experiment, modeling, simulation, and defense

It is commonly believed that the IPv6 protocol can provide good protection against network worms that try to find victims through random address scanning due to its huge address space. However, we discover that there is serious vulnerability in terms of worm propagation in IPv6 and IPv4-IPv6 dual-stack networks. It is shown in this article that a new worm can collect the IPv6 addresses of all running hosts in a local subnet very quickly, leading to accelerated worm propagation. Similar to modeling the self-replicating behaviors of biological viruses, a Species-Patch model and a discrete-time simulator are developed to study how the dual-stack worm spreads in networks with various topologies. It is shown that the worm could propagate in the IPv6 and IPv4-IPv6 dual-stack networks much faster than in the current IPv4 Internet. Several effective defense strategies focusing on network deployment are proposed.
Transient requirement for prolactin as a growth initiator following treatment of autonomous Nb2 node rat lymphoma cell cultures with butyrate.

A previous study described the development of cultures of Nb2 node rat lymphoma cells which specifically require a lactogenic hormone, e.g., prolactin (PRL), as a growth factor. In the present study, sublines of these cultures have been established, including clones, which do not depend on exogenous lactogens for growth; the cells do not appear to produce autocrine, PRL-like substances. Although these autonomous cells grew readily in the complete absence of lactogens, their growth rate was stimulated (up to approximately 30%) by PRL concentrations greater than or equal to 0.1 ng/ml. When cultures of the lactogen-dependent and of the cloned, autonomous lymphoma cells were incubated for 3 days with sodium n-butyrate (NaBT; 2 mM), cells were arrested in the G1 phase of the cell cycle, as shown by flow cytometric analysis. A substantial proportion of the G1-arrested cells was viable and readily resumed growth, within 1 day, when transferred to NaBT-free medium containing PRL (1-100 ng/ml). The resumption of growth of the cells from the lactogen-dependent cultures was critically dependent on PRL; in its absence cells lysed. Surprisingly, the rapid recovery of the cells from the lactogen-independent cultures also depended on the presence of PRL in the medium; in its absence growth did not resume for at least 2.3 days. The acquired need of the NaBT-treated, autonomous cells for PRL was only transient, since such cells reverted fully to the PRL-independent state within about 3 days of culturing in PRL-containing, NaBT-free medium. It is proposed, as a working hypothesis, that the autonomous lymphoma cells can be mitogenically activated by two different pathways, one requiring exogenous lactogens and another which is independent of lactogens; the latter pathway recovers much more slowly from the treatment with NaBT than the lactogen-dependent pathway. This model could explain the sensitivity of the autonomous lymphoma cells to PRL and their transient dependency on exogenous lactogens during their recovery from NaBT treatment. NaBT would appear to be a useful agent for studying the mechanism(s) by which the autonomous lymphoma cells circumvent the need for mitogenic lactogens.
Modeling and Identification of Amnioserosa Cell Mechanical Behavior by Using Mass-Spring Lattices

Various mechanical models of live amnioserosa cells during Drosophila melanogaster’s dorsal closure are proposed. Such models account for specific biomechanical oscillating behaviors and depend on a different set of parameters. The identification of the parameters for each of the proposed models is accomplished according to a least-squares approach in such a way to best fit the cellular dynamics extracted from live images. For the purpose of comparison, the resulting models after identification are validated to allow for the selection of the most appropriate description of such a cell dynamics. The proposed methodology is general and it may be applied to other planar biological processes.
Comparative Analysis of Timing Yield Improvement under Process Variations of Flip-Flops Circuits

In synchronous systems, any violation of the timing constraints of the flip-flops can cause the overall system to malfunction. Moreover, the process variations create a large variability in the flip-flop delay in scaled technologies impacting the timing yield. Overtime, many gate sizing algorithms have been introduced to improve the timing yield. This paper presents an analysis of timing yield improvement of four commonly used flip-flops under process variations. These flip-flops are designed using STMicroelectronics 65-nm CMOS technology. The analyzed flip-flops are compared for power and power-delay product (PDP) overheads to achieve this timing yield improvement. The analysis shows that the sense amplifier based flip flop (SA-FF) has a power overhead and PDP overhead of 1.7X and 2.8X, respectively, much higher than that of the transmission-gate master-slave flip flop(TG-MSFF) . The TG-MSFF exhibits the lowest relative power and PDP overheads of 30.87% and 9% ,respectively.
Lower bounds on the bounded coefficient complexity of bilinear maps

We prove lower bounds of order n log n for both the problem to multiply polynomials of degree n, and to divide polynomials with remainder, in the model of bounded coefficient arithmetic circuits over the complex numbers. These lower bounds are optimal up to order of magnitude. The proof uses a recent idea of R. Raz [Proc. 34th STOC 2002] proposed for matrix multiplication. It reduces the linear problem to multiply a random circulant matrix with a vector to the bilinear problem of cyclic convolution. We treat the arising linear problem by extending J. Morgenstern's bound [J. ACM 20, pp. 305-306, 1973] in a unitarily invariant way. This establishes a new lower bound on the bounded coefficient complexity of linear forms in terms of the singular values of the corresponding matrix.
On Upscaling of Soil Microbial Processes and Biogeochemical Fluxes From Aggregates to Landscapes

Soil microbial communities respond to spatial and temporal variations in environmental conditions (e.g., saturation and ambient temperatures) as reflected in the dynamics of microbially produced greenhouse gas (GHG) fluxes (primarily CO2, N2O, and CH4) emitted from soil surfaces. Despite considerable progress in resolving key soil microbial processes, their quantification remains largely empirical with limited predictability. We report a mechanistic and analytical modeling framework for integrating local environmental effects on GHG‐producing microbial processes primarily in soil aggregates (or other hot spots) and the upscaling of these to regional GHG fluxes. The mechanistic model enables systematic evaluation of how soil structural features (e.g., aggregation and layers), spatial variability, and dynamic ambient conditions (e.g., temperature and hydration) affect soil microbial functioning. The upscaling of microbial processes from aggregates of different sizes to soil profiles and landscapes implements mechanistically derived microbial response functions with spatial information on soil type, land cover, and resource distribution. The modeling framework was evaluated using reported field data for seasonal N2O emissions from subarctic regions resulting in reasonable agreement. The proposed analytical framework offers a practical compromise balancing a simplified representation of dynamic microbial processes that respond to local conditions with an upscalable representation of soil GHG fluxes over landscapes under changing environmental conditions.
Customized work based learning support system for less academically prepared adults in online environment

In these dynamic times, when everything changes fast, being unprepared is not an excuse. Work-based learning is used as a tool to achieve the goal of converting tacit knowledge into explicit by maximizing learning opportunities and internalizing knowledge by practical experience in the workplace. Information and communication technology plays an important role in the knowledge management process, helping academically prepared adults learn and solve lots of different problems more effectively. In this regard, it is very important to figure out the principal directions for implementing work-based learning strategies in the learning process. The work with knowledge implies creation of content: generation of a new knowledge in order to stimulate the development of innovative processes. The goal of the paper is to get a new perspective on and understanding of the future of work-based learning involving the use of new technological opportunities. The research idea is to describe the principles of a system focusing on an online support system for adults, the influence of different conditions and the unique patterns of development in each individual. In order to find the most efficient application of ICT resources and knowledge management technologies with an aim to save time and use work-based learning to its utmost potential, it is necessary to study different theories, which will help us understand how information systems have to be created and structured to reach the set goals. The result of the research is the analysis of the information system as an online learning platform, improved quality of knowledge flow, and recommendations for developing work-based learning with regard to the encouragement of efficient knowledge management.
A method to derive smoke emission rates from MODIS fire radiative energy measurements

Present methods of emissions estimation from satellite data often use fire pixel counts, even though fire strengths and smoke emission rates can differ by some orders of magnitude between pixels. Moderate Resolution Imaging Spectroradiometer (MODIS) measurements of fire radiative energy (FRE) release rates R/sub fre/ range from less than 10 to more than 1700 MW per pixel at 1-km resolution. To account for the effect of such a wide range of fire strengths/sizes on smoke emission rates, we have developed direct linear relationships between the MODIS-measured R/sub fre/ and smoke aerosol emission rates R/sub sa/ (in kilograms per second), derived by analyzing MODIS measurements of aerosol spatial distribution around the fires with National Center for Environmental Prediction/National Center for Atmospheric Research wind fields. We applied the technique to several regions around the world and derived a FRE-based smoke emission coefficient, C/sub e/ (in kilograms per megajoule), which can be simply multiplied by R/sub fre/ to calculate R/sub sa/. This new coefficient C/sub e/ is an excellent remote sensing parameter expressing the emission strength of different ecosystems and regions. Analysis of all 2002 MODIS data from Terra and Aqua satellites yielded C/sub e/ values of 0.02-0.06 kg/MJ for boreal regions, 0.04-0.08 kg/MJ for both tropical forests and savanna regions, and 0.08-0.1 kg/MJ for Western Russian regions. These results are probably overestimated by about 50% because of uncertainties in some of the data, parameters, and assumptions involved in the computations. This 50% overestimation is comparable to uncertainties in traditional emission factors. However, our satellite method shows great promise for accuracy improvement, as better knowledge is gained about the sources of the uncertainties.
International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits.

Nicotinic acetylcholine receptors (nACh receptors2) in jawed vertebrates are prototypical members of the multisubunit, neurotransmitter-gated superfamily of ion channels (ionotropic neurotransmitter receptors; see Section IV for selected seminal papers, reviews, and collections). nACh receptors
Flop transitions in M theory cosmology

We study flop-transitions for M-theory on Calabi-Yau three-folds and their applications to cosmology in the context of the effective five-dimensional supergravity theory. In particular, the additional hypermultiplet which becomes massless at the transition is included in the effective action. We find the potential for this hypermultiplet which includes quadratic and quartic terms as well as additional dependence on the Kahler moduli. By constructing explicit cosmological solutions, it is demonstrated that a flop-transition can indeed by achieved dynamically, as long as the hypermultiplet is set to zero. Once excitations of the hypermultiplet are taken into account we find that the transition is generically not completed but the system is stabilised close to the transition region. Regions of moduli space close to flop-transitions can, therefore, be viewed as preferred by the cosmological evolution.
PMAL: Enabling lightweight adaptation of legacy file systems on persistent memory systems

The advent of Persistent Memory (PM), which is anticipated to have byte-addressable access latency in par with DRAM and yet nonvolatile, has stepped up interest in using PM as storage. Hence, PM storage targeted file systems are being developed under the premise that legacy file systems are suboptimal on memory bus attached PM-based storage. However, many years of time and effort are ingrained in legacy file systems that are now time-tested and mature. Simply scrapping them altogether may be unwarranted. In this paper, we look into how we can leverage the maturity ingrained in legacy file systems to the fullest, while, at the same time, reaping the high performance offered by PM. To this end, we first go through a thorough analysis of legacy Ext4 file systems, and compare it with NOVA, PMFS, and Ext4 with DAX extension, which are new PM file systems available in Linux. Based on these analyses, we then propose the Persistent Memory Adaptation Layer (PMAL) module that is lightweight (roughly 180 LoC) and can easily be integrated into legacy file systems to take advantage of PM storage. Using Ext4, we show that the performance of PMAL integrated Ext4 is in par with PM file systems for the Filebench and key-value store benchmarks.