Export Function Research Articles

Identification of the citrate exporter Cex1 of Yarrowia lipolytica.

Yarrowia lipolytica is a yeast with many talents, one of them being the production of citric acid. Although the citrate biosynthesis is well studied, little is known about the transport mechanism by which citrate is exported. To gain better insight into this mechanism, we set out to identify a transporter involved in citrate export of Y. lipolytica. A total of five proteins were selected for analysis based on their similarity to a known citrate exporter, but neither a citrate transport activity nor any other phenotypic function could be attributed to them. Differential gene expression analysis of two strains with a distinct citrate productivity revealed another three putative transporters, one of which is YALI0D20196p. Disrupting YALI0D20196g in Y. lipolytica abolished citrate production, while extrachromosomal expression enhanced citrate production 5.2-fold in a low producing wildtype. Furthermore, heterologous expression of YALI0D20196p in the non-citrate secreting yeast Saccharomyces cerevisiae facilitated citrate export. Likewise, expression of YALI0D20196p complemented the ability to secrete citrate in an export-deficient strain of Aspergillus niger, confirming a citrate export function of YALI0D20196p. This report on the identification of the first citrate exporter in Y. lipolytica, termed Cex1, represents a valuable starting point for further investigations of the complex transport processes in yeasts.

IκBα Nuclear Export Enables 4-1BB-Induced cRel Activation and IL-2 Production to Promote CD8 T Cell Immunity.

Optimal CD8 T cell immunity is orchestrated by signaling events initiated by TCR recognition of peptide Ag in concert with signals from molecules such as CD28 and 4-1BB. The molecular mechanisms underlying the temporal and spatial signaling dynamics in CD8 T cells remain incompletely understood. In this study, we show that stimulation of naive CD8 T cells with agonistic CD3 and CD28 Abs, mimicking TCR and costimulatory signals, coordinately induces 4-1BB and cRel to enable elevated cytosolic cRel:IκBα complex formation and subsequent 4-1BB-induced IκBα degradation, sustained cRel activation, heightened IL-2 production and T cell expansion. NfkbiaNES/NES CD8 T cells harboring a mutated IκBα nuclear export sequence abnormally accumulate inactive cRel:IκBα complexes in the nucleus following stimulation with agonistic anti-CD3 and anti-CD28 Abs, rendering them resistant to 4-1BB induced signaling and a disrupted chain of events necessary for efficient T cell expansion. Consequently, CD8 T cells in NfkbiaNES/NES mice poorly expand during viral infection, and this can be overcome by exogenous IL-2 administration. Consistent with cell-based data, adoptive transfer experiments demonstrated that the antiviral CD8 T cell defect in NfkbiaNES/NES mice was cell intrinsic. Thus, these results reveal that IκBα, via its unique nuclear export function, enables, rather than inhibits 4-1BB-induced cRel activation and IL-2 production to facilitate optimal CD8 T cell immunity.

The role of marine protected areas in sustaining fisheries: The case of the National Park of Banc d’Arguin, Mauritania

Mauritania is characterized by fast-growing fisheries that have developed over the past several decades from low levels of fishing to intense fishing and have led to severe decreases in biomass and severe signs of overexploitation. To ensure sustainable fisheries, a primary goal of science-based fisheries policy is to provide an adequate conservation status of marine habitats that are directly, or indirectly, fundamental for the lifecycle of fish populations of commercial interest. The National Park of Banc d’Arguin has been recognized for its nursery and fish biomass export functions. In this paper, we present the economic value of the fish provisioning service of marine coastal ecosystems of the protected area. We estimated the added value of artisanal fisheries, the spatial distribution of fishing activities, the contribution of the Park to the Mauritanian fisheries and the heritage value of artisanal fisheries.Overall, the average added value for artisanal fisheries is about 43 million MRU (1 million euros) over the period 2006–2017. It mainly benefits to the ship-owners, which generates inequalities and threatens the livelihoods of the Imraguen. The spatial distribution of fishing activities and associated revenues shows high variability throughout the years, the seasons and the geographic areas, and reveals the high adaptability of Imraguen fishers. Fishing grounds are mostly located close to the shore, associated with seagrass beds, confirming the service of fish provisioning rendered by this ecosystem. Furthermore, the high productivity of seagrass beds contributes to the spill-over of biomass. The contribution of the Park to fishing activities that occur within the Mauritanian Exclusive Economic Zone is estimated to 15%, representing an added value creation of 3.2 billion MRU (71 million euros). The heritage value of the fisheries is assessed, through fishers' willingness to accept to stop their fishing activities, at 17.5 million MRU (0.4 million euros). Thus, this paper highlights the necessity of incorporating an ecosystem-based approach along with fishers' knowledge and adaptability into future conservation plan of the National Park of Banc d’Arguin and fisheries management at the local, national and regional scale.

Effect of cultural intelligence and export experience on Export function: (Case study: export firms of Boushehr and Golestan provinces)

In the last two decades, information and communications technology (ICT) has influence seriously the quality and quantity of competition among the firms in access to the other countries markets. The fundamental question of every firm which is active in the international market and is faced with it, is that ((the firms, export functions is influenced by what factors? This research has been conducted to answer this question. Literature review indicates that cultural intelligence and export experience are the most prominent factors among many factors that may influence export function. Based on this theoretical finding, the research conceptual model was built and six hypotheses were tested in this study. This research was conducted to test the matching of experimental data with the conceptual model in the export firms of Boushehr and Golestan provinces. The research finding show that the study's two main hypotheses including the positive and significant effect of cultural intelligence on export function; and the relationship between the managers export experiences and hypotheses which indicate the positive and significant effect of the dimensions of cultural intelligence on the export performance, have been confirmed.

Dynamic Capture and Release of Endoplasmic Reticulum Exit Sites by Golgi Stacks in Arabidopsis.

SummaryProtein transport from the endoplasmic reticulum (ER) to Golgi stacks is mediated by the coat protein complex COPII, which is assembled at an ER subdomain called ER exit site (ERES). However, the dynamic relationship between ERESs and Golgi stacks is unknown. Here, we propose a dynamic capture-and-release model of ERESs by Golgi stacks in Arabidopsis thaliana. Using variable-angle epifluorescence microscopy with high-temporal-resolution imaging, COPII-component-bound ERESs were detected as punctate structures with sizes of 300–500 nm. Some punctate ERESs are distributed on ER tubules and sheet rims, whereas others gather around a Golgi stack in an ER-network cavity to form a beaded-ring structure. Free ERESs that wander into an ER cavity are captured by a Golgi stack in a cytoskeleton-independent manner. Then, they are released by the Golgi stack for recycling. The dynamic ERES cycling might contribute to efficient transfer of de novo synthesized cargo proteins from the ER to Golgi stacks.

An analysis of IT software and service exports from India

PurposeThe aims of the paper are to investigate IT software and service export function for India. First, cointegration tests have been used to investigate the long-run equilibrium relationship of the given variables. Second, long-run coefficients and associated error correction mechanism are estimated.Design/methodology/approachAnnual time series data on IT software and service exports, human capital, exchange rate, investment in IT, external demand and openness index have been used for the present study during the period 1980–2017. The data are collected from the National Association of Software and Service Companies (NASSCOM), Planning Commission of India, University Grants Commission (UGC) of India, real effective exchange rate (REER) database and World Bank development indicators. Auto regressive distributed lag (ARDL) model is used to analyze both short-run and long-run dynamic behaviour of economic variables with appropriate asymptotic inferences.FindingsResults of the analysis show the stable long-run equilibrium relationship among the given variables. It is found that external demand, exchange rate, human capital and openness index have a substantial long-run impact on the IT software and service exports. We also found that the coefficient of error correction term is negative and significant at 1% of the level of significance, which confirms the existence of stable long-run relationship which means adjustment will take place when there is a short-run deviation to its long-run equilibrium after a shock.Research limitations/implicationsThere may be other determinants of software and service exports apart from those considered by the present study. Due to the non-availability of data, the study considers only important determinants that determine the software and service exports in India. The IT exports are an emerging and dynamic field of economic activity and the rate of change is so rapid that the relevance of individual factors may change over time. The study period is also limited to available data.Practical implicationsThe paper has implications for achieving sustainability in IT software and service exports growth. It is recommended that policies directed at improving the performance of IT software and service exports should largely consider the long-run behaviour of these variables.Originality/valueThis paper focuses on originality in the analysis of the relationship among the given variables including IT software and service exports, human capital, exchange rate, investment in IT, external demand and openness index in India. All the work has been done in original by the authors, and the work used has been acknowledged properly.

Functions of Lysosomes in Mammalian Female Reproductive System

The lysosome is the most acidic membrane-bound intracellular organelle. Lysosomal acidity is primarily maintained by vacuolar H+-ATPase (V-ATPase) and counter ion channels. There are >60 hydrolytic enzymes in the lysosome for its fundamental digestive role. Lysosomes also play important roles in endocytosis, exocytosis, autophagy, and cell death. Studies that have implicated roles of lysosomes in the female reproductive system are reviewed here. In the ovary, lysosomes are implicated in the preparation of free cholesterol for steroidogenesis and degradation of regulators of steroidogenesis, regulation of follicular atresia, follicle rupture during ovulation, luteal cell survival, and luteal regression. In the oviduct, lysosomes are involved in endocytosis of both serum and oviductal luminal components. In the uterus during the menstrual/estrous cycle, lysosomes are associated with endometrial secretion, apoptosis, and menstruation. In the uterus during early pregnancy, lysosomes are involved in the temporal and directional changes of endocytosis, uterine epithelial acidification upon embryo implantation initiation, and embryo-maternal mutual communications via extracellular vesicles. In the placenta, lysosomes are implicated in nutrient transport and placental separation from the uterus for parturition. In the mammary gland, lysosomes are important for mammary gland development and involution. These findings suggest/demonstrate functions of lysosomes in multiple processes of female reproduction, from ovulation to ovarian steroidogenesis for pregnancy maintenance, and from essential in utero nurturing of developing embryos/fetuses via embryo/fetal-maternal communications, to optional postpartum nurturing of newborns via lactation. Future studies using genetically or modified animal models and pharmacological approaches will provide novel insights into the functions and mechanisms of lysosomes in the mammalian female reproductive system.

DDX39B interacts with the pattern recognition receptor pathway to inhibit NF-\u03baB and sensitize to alkylating chemotherapy

BackgroundNuclear factor-κB (NF-κB) plays a prominent role in promoting inflammation and resistance to DNA damaging therapy. We searched for proteins that modulate the NF-κB response as a prerequisite to identifying novel factors that affect sensitivity to DNA damaging chemotherapy.ResultsUsing streptavidin-agarose pull-down, we identified the DExD/H-box RNA helicase, DDX39B, as a factor that differentially interacts with κB DNA probes. Subsequently, using both RNA interference and CRISPR/Cas9 technology, we demonstrated that DDX39B inhibits NF-κB activity by a general mechanism involving inhibition of p65 phosphorylation. Mechanistically, DDX39B mediates this effect by interacting with the pattern recognition receptor (PRR), LGP2, a pathway that required the cellular response to cytoplasmic double-stranded RNA (dsRNA). From a functional standpoint, loss of DDX39B promoted resistance to alkylating chemotherapy in glioblastoma cells. Further examination of DDX39B demonstrated that its protein abundance was regulated by site-specific sumoylation that promoted its poly-ubiquitination and degradation. These post-translational modifications required the presence of the SUMO E3 ligase, PIASx-β. Finally, genome-wide analysis demonstrated that despite the link to the PRR system, DDX39B did not generally inhibit interferon-stimulated gene expression, but rather acted to attenuate expression of factors associated with the extracellular matrix, cellular migration, and angiogenesis.ConclusionsThese results identify DDX39B, a factor with known functions in mRNA splicing and nuclear export, as an RNA-binding protein that blocks a subset of the inflammatory response. While these findings identify a pathway by which DDX39B promotes sensitization to DNA damaging therapy, the data also reveal a mechanism by which this helicase may act to mitigate autoimmune disease.

FAKTOR YANG MEMPENGARUHI PERDAGANGAN ANTAR WILAYAH DI SUMATERA UTARA

This study aims to analyze the factors that affect trade between regions in the province of North Sumatra. Agrerat demand model was developed to regional economic model using simultaneous equations. 2 SLS method (two stage least squares) is used to estimate the function of inter-regional trade, interprovincial and expo rt fun ctions b etween province s impo rt fun ction. The estimation res ults indicate that the difference between the export price and the provincial transport costs have an influence on interprovincial trade balance, while the import price differences between provinces, other provinces income, revenue North Sumatra province, did not sign ificantly affect the balance of trade between provinces

*-DCC: A platform to collect, annotate, and explore a large variety of sequencing experiments.

BackgroundOver the past few years the variety of experimental designs and protocols for sequencing experiments increased greatly. To ensure the wide usability of the produced data beyond an individual project, rich and systematic annotation of the underlying experiments is crucial.FindingsWe first developed an annotation structure that captures the overall experimental design as well as the relevant details of the steps from the biological sample to the library preparation, the sequencing procedure, and the sequencing and processed files. Through various design features, such as controlled vocabularies and different field requirements, we ensured a high annotation quality, comparability, and ease of annotation. The structure can be easily adapted to a large variety of species. We then implemented the annotation strategy in a user-hosted web platform with data import, query, and export functionality.ConclusionsWe present here an annotation structure and user-hosted platform for sequencing experiment data, suitable for lab-internal documentation, collaborations, and large-scale annotation efforts.

Capturing Team Dynamics in the Wild: The Communication Analysis Tool

Capturing team processes, which are highly dynamic and quickly unfold over time, requires methods that go beyond standard self-report measures. However, quantitative observational methods are challenging when teams are observed in the wild, that is, in their full-situated context. Technologically advanced tools that enable high-resolution measurements in the wild are rare and, when they exist, expensive. The present research advances high-resolution measurement of team processes by introducing a technological application—the Communication Analysis Tool (CAT)—that captures fine-grained interactions in real workplace contexts. We introduce four core features of CAT: (a) customized coding measures, (b) session-based feedback on interrater reliability, (c) visualization and feedback options for displaying team dynamics, and (d) an export function to conduct advanced statistical analyses on effective team processes. We illustrate these core features using data from an organizational field project on multidisciplinary teams tasked with diagnosing patients with uncommon and highly complex medical conditions.

Exchange rate volatility in the eurozone

Abstract The current economic crisis has witnessed a strong deceleration in the growth of international trade. This has been even greater in the cases of the European Unionand the eurozone, where the rates of export growth have even reached negative figures. In this paper, the authors examine to which extent exchange rate volatility might account for the drop in the rate of growth of exports in the eurozone since the start of the crisis. To that end, they estimate export functions, augmented to include several measures of exchange rate volatility, for the four largest economies of the eurozone, i.e., France, Germany, Italy and Spain, for the period 1994:1–2014:4. In the empirical application, the authors make use of two alternative measures for exchange rate volatility, i.e., (i) the Standard deviation and (ii) the conditional variance from the GARCH methodology, of the change in the logarithm of the exchange rate, for both nominal and real exchange rates, and in the latter case computed using as deflators both Export prices and unit labour costs. The empirical results show no clear-cut evidence on the impact of exchange rate volatility on the exports of the countries analysed, suggesting that financial markets were developed enough so that exchange rate volatility does not hinder the evolution of exports.

Dbp5/DDX19 between Translational Readthrough and Nonsense Mediated Decay.

The DEAD-box protein Dbp5 (human DDX19) remodels RNA-protein complexes. Dbp5 functions in ribonucleoprotein export and translation termination. Termination occurs, when the ribosome has reached a stop codon through the Dbp5 mediated delivery of the eukaryotic termination factor eRF1. eRF1 contacts eRF3 upon dissociation of Dbp5, resulting in polypeptide chain release and subsequent ribosomal subunit splitting. Mutations in DBP5 lead to stop codon readthrough, because the eRF1 and eRF3 interaction is not controlled and occurs prematurely. This identifies Dbp5/DDX19 as a possible potent drug target for nonsense suppression therapy. Neurodegenerative diseases and cancer are caused in many cases by the loss of a gene product, because its mRNA contained a premature termination codon (PTC) and is thus eliminated through the nonsense mediated decay (NMD) pathway, which is described in the second half of this review. We discuss translation termination and NMD in the light of Dbp5/DDX19 and subsequently speculate on reducing Dbp5/DDX19 activity to allow readthrough of the PTC and production of a full-length protein to detract the RNA from NMD as a possible treatment for diseases.

Identification, expression profiling and localization of thoc in common carp ovary: Influence of thoc3-siRNA transient silencing

THO complex is a multisubunit family with a function in transcription and mRNA export. In the present study, transcripts of THO complex (thoc) were identified in developing ovary of common carp and their role during ovarian development and growth has been characterized for the first time in a teleost using expression profiling and transient siRNA silencing. Thoc expression revealed a spatiotemporal pattern in the gonads with high levels at 120 days post-hatch, with moderately high levels thereafter. In situ hybridization and immunohistochemical localization revealed the presence of thoc3 in follicular layer of stage-III/IV oocytes. High levels of thoc3, thoc5, and thoc7 genes in the follicular layer suggest a possible role in ovarian growth. Reduced levels of serum estradiol-17β and 17α, 20β-dihydroxypregn-4-en-3-one after thoc3 transient silencing indicated differential action on steroidogenic enzyme, transcription factor, and growth factor genes. Furthermore, transient silencing of thoc3, in vivo and in vitro, downregulated ad4bp/sf1, amh, cyp19a1a, foxl2, hsd3b, hsd11b1, hsd20b, hsd17b1, rspo1, and vtg. Incidentally, gdf9 and igf1 were upregulated, while no change was seen in esr1/2, nanos, and vasa. These observations imply that thoc3 seems to regulate ovarian function including steroidogenesis, either directly or indirectly.

Myosins in the Nucleus.

Although originally characterized as a cytoplasmic protein, myosin of various classes also performs key functions in the nucleus. We review the data concerning the nuclear localization, mechanism of entry, and functional interactions of myosin I, II, V, VI, X, XVI, and XVIII. To date, the first-characterized "nuclear myosin I" (or, in the prevailing nomenclature, myosin IC isoform B) remains the best-studied nuclear myosin, although results are rapidly accumulating that illuminate the roles of other myosin classes, and an outline of a unified picture of myosin functions in the nucleus is beginning to emerge. Reflecting the state of knowledge in this field, the review concentrates on the mechanisms mediating and regulating import of myosin IC into the nucleus and its role, alongside myosin V and VI, in transcription. Myosin functions in chromatin dynamics, epigenetic mechanisms, intranuclear motility, and nuclear export of RNA and protein are also addressed. Partners and regulators of myosin, such as nuclear actin, kinases, and phosphatases are briefly covered. Problem areas are identified and testable hypotheses areoffered with an aim of focusing the research efforts on overcoming the gaps on the way toward a systems-level understanding of processes involving nuclear myosins and their place in cell physiology as a whole.

방위산업 수출함수 추정을 통한 방위산업 진흥방안 연구

방위산업 수출함수 추정을 통한 방위산업 진흥방안 연구

Sec16 function in ER export and autophagy is independent of its phosphorylation in Saccharomyces cerevisiae.

Coat protein complex II (COPII) protein assembles at the endoplasmic reticulum exit site (ERES) to form vesicle carrier for transport from the ER to the Golgi apparatus. Sec16 has a critical role in COPII assembly to form ERES. Sec16∆565N mutant, which lacks the N-terminal 565 amino acids, is defective in ERES formation and ER export. Several phosphoproteomic studies have identified 108 phosphorylated Ser/Thr/Tyr residues in Sec16 of Saccharomyces cerevisiae, of which 30 residues are located in the truncated part of Sec16∆565N. The exact role of the phosphorylation in Sec16 function remains to be determined. Therefore, we analyzed nonphosphorylatable Sec16 mutants, in which all identified phosphorylation sites are substituted with Ala. These mutants show ERES and ER export comparable to those of wild-type Sec16, although the nonphosphorylatable mutant binds the COPII subunit Sec23 more efficiently than the wild-type protein. Because nutrient starvation–induced autophagy depends on Sec16, Sec16∆565N impairs autophagy, whereas the nonphosphorylatable mutants do not affect autophagy. We conclude that Sec16 phosphorylation is not essential for its function.

An extensible software platform for interdisciplinary cardiovascular imaging research

Background and objectiveCardiovascular imaging is an exponentially growing field with aspects ranging from image acquisition and analysis to disease characterization, and evaluation of therapy approaches.The transfer of innovative new technological and algorithmic solutions into clinical practice is still slow. In addition to the verification of solutions, their integration in the clinical processing workflow must be enabled for the assessment of clinical impact and risks. The goal of our software platform for cardiac image processing – CAIPI – is to support researchers from different specialties such as imaging physics, computer science, and medicine by a common extensible platform to address typical challenges and hurdles in interdisciplinary cardiovascular imaging research. It provides an integrated solution for method comparison, integrated analysis, and validation in the clinical context. The interface concept enables a combination with existing frameworks that address specific aspects of the pipeline, such as modeling (e.g., OpenCMISS, CARP) or image reconstruction (Gadgetron). MethodsIn our platform, we developed a concept for import, integration, and management of cardiac image data. The integration approach considers the spatiotemporal properties of the beating heart through a specific data model. The solution is based on MeVisLab and provides functionalities for data retrieval and storage. Two types of plugins can be added. While ToolPlugins usually provide processing algorithms such as image correction and segmentation, AnalysisPlugins enable interactive data exploration and reporting. GUI integration concepts are presented for both plugin types. We developed domain-specific reporting and visualization tools (e.g., AHA segment model) to enable validation studies by clinical experts. The platform offers plugins for calculating and reporting quantitative parameters such as cardiac function, which can be used to, e.g., evaluate the effect of processing algorithms on clinical parameters. Export functionalities include quantitative measurements to Excel, image data to PACS, and STL models to modeling and simulation tools. ResultsTo demonstrate the applicability of this concept both for method development and clinical application, we present use cases representing different problems along the innovation chain in cardiac MR imaging.Validation of an image reconstruction method (MRI T1 mapping)Validation of an image correction method for real-time 2D-PC MRIComparison of quantification methods for blood flow analysisTraining and integration of machine learning solutions with expert annotationsClinical studies with new imaging techniques (flow measurements in the carotid arteries and peripheral veins as well as cerebral spinal fluid). ConclusionThe presented platform can be used in interdisciplinary teams, in which engineers or data scientists perform the method validation, followed by clinical research studies in patient collectives. The demonstrated use cases show how it enables the transfer of innovations through validation in the cardiovascular application context.

Exportación hortofrutícola de México hacia los Estados Unidos de América

Objetivos: analizar el comportamiento de la exportación hortofrutícola de México hacia los EUA y, elaborar la función de exportación hortofrutícola de la república mexicana; el periodo de estudio fue de 1993-2013. Metodología: se caracterizó la situación comercial hortofrutícola existente entre México y los Estados de América y se utilizó el método de máxima verosimilitud. Resultados: los resultados mostraron un superávit comercial hortofrutícola de México a lo largo del periodo analizado; en el modelo se encontró que la elasticidad precio real por tonelada de exportación fue de 2.41 %, la elasticidad ingreso fue de 1.41 % y el del tipo de cambio real de 1.02 %. La variable que tuvo mayor impacto sobre la exportación hortofrutícola fue la variable precio; un incremento del precio internacional provoca el crecimiento de la exportación hortofrutícola. Limitaciones: para explicar el comportamiento de la exportación hortofrutícola, faltaron incluir variables como son la distancia y los factores medioambientales. Conclusiones: se espera que la balanza comercial hortofrutícola superavitaria de México se mantenga en el mediano plazo. En el corto plazo, para influir en el incremento de la exportación hortofrutícola, el instrumento de política comercial más efectivo que puede utilizar el gobierno mexicano es: el del tipo de cambio. México puede diversificar mercados de exportación si aprovecha los diferentes acuerdos comerciales que posee hoy en día.

Dynalogo: an interactive sequence logo with dynamic thresholding of matched quantitative proteomic data.

Current web-based sequence logo analyses for studying domain-peptide interactions are often conducted only on high affinity binders due to conservative data thresholding. We have developed Dynalogo, a combination of threshold varying tool and sequence logo generator written in the R statistical programming language, which allows on-the-fly visualization of binding specificity over a wide range of affinity interactions. Hence researchers can easily explore their dataset without the constraint of an arbitrary threshold. After importing quantitative data files, there are various data filtering and visualizing features available. Using a threshold control, users can easily track the dynamic change of enrichment and depletion of amino acid characters in the sequence logo panel. The built-in export function allows downloading filtered data and graphical outputs for further analyses. Dynalogo is optimized for analysis of modular domain-peptide binding experiments but the platform offers a broader application including quantitative proteomics. Dynalogo application, user manual and sample data files are available at https://dynalogo.cam.uchc.edu. The source code is available at https://github.com/lafontaine-uchc/dynalogo. Supplementary data are available at Bioinformatics online.