Everyone wants to avoid stress when they're starting a new venture in life. Whether it be on a smaller scale involving your personal family life, or on a larger scale that involves many other parties, like creating a business, is no matter. There's a lot you need to consider when it comes to these big decisions. Take business financing for example. Do you need a loan? If yes, what do you need to know or apply for before getting one? There's some questions you'll need to prepare yourself for, and here's a taste of them below.
Now this may seem your business and your business alone, but it's common practice for a bank to find out where their finances are needed. Knowing where their money is going is a bank's number one top priority. So you'll need to have a bona fide reason you need it, and probably a business plan to evidence you've set it out properly.
Don't just bring along your business plan however, a bank isn't going to invest in that alone.
Okay so this one seems obvious, but there's many ways to prove that you have plenty in the way of soft and hard assets to pay back the money and interest on top. It's the big question on all bank lenders' minds.
Do you have anything tucked away in your business that can act as collateral if necessary? Investopedia.com defines the what and why properly. If you have proof of assets with you, these will be checked and double checked and triple checked to make sure they actually exist. Your inventory details are incredibly important here, and are necessary to backup your payment claims, and for a bank to declare whether it's valuable enough or not.
Knowing if you're a possible liability or not affects a bank's judgement on lending you money. This is such an important question to anyone lending out money, let's face facts. Even for alternative lenders such as applying online with no face to face small talk, sites such as smallbusinessloans.co will have still an application process to go through. The internet is wonderful for many things but it still has its foundations in tried and tested business methods.
Make sure you take all your account details along with you to show where you're liable and where you thrive. Even if you do have debts, it doesn't mean you won't get a loan. You'll probably get a lot less than you were hoping for, but this is a chance to claim back all the money you've lost.
A lot of questions can be asked in loan meetings and initial reviews of your financing. The big three are the ones to prepare properly for and find out all accurate details you need to answer them. Getting a loan doesn't have to be intimidating when you know what to take, do, and say.


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Kimberly-Clark's Neenah Nonwovens facility closed earlier this year, though some employees have been hired at the company's Cold Spring plant in Fox Crossing.
BARRY ADAMS, STATE JOURNAL ARCHIVES
One year into state's deal with Kimberly-Clark, company works to expand Fox Valley plant
By Briana Reilly
Briana Reilly
One year after former Gov. Scott Walker struck a last-minute deal to keep a Fox Valley Kimberly-Clark plant open, officials with the company say they're "making great progress" on expanding a facility previously slated for closure.
In the midst of a $115 million investment at the company's Cold Spring plant that includes a new 135,000-square-foot warehouse, Kimberly-Clark has also hired 80 workers for the facility and is planning to bring more on in the future.
The $28 million deal, announced Dec. 13, 2018, came in the waning days of Walker's second term and shortly before the Republican signed a trio of Republican lame-duck bills into law. The agreement kept the Cold Spring facility in business, while the nearby Neenah Nonwovens plant still ultimately shut down.
Kimberly-Clark spokesman Ron Maturo wrote in an email the company appreciates its partnership with the state jobs agency, the Wisconsin Economic Development Corporation, and noted the current investment has targeted capital improvements at the Cold Spring plant and will continue for the next few years.
Meanwhile, WEDC Secretary and CEO Missy Hughes, who began in the role on Oct. 1 after being appointed by Gov. Tony Evers, said in an interview she toured the plant's manufacturing facility and warehouse last week Wednesday and found it to be "a very well-run facility."
Asked about the company's prospects for earning all the tax credits it's eligible for this year, she said she didn't "want to postulate on their success or not, although I will say that they were confident and shared their confidence with me" that they would meet the requirements for obtaining the credits.
"It is clear to me that they want to be a partner with Wisconsin, they're dedicated to being here in the state and they're really excited about the opportunities that they have coming forward in their market," she said. "They feel really competitive, they feel like they're continuing to grow. My impression is that they're on an all out sprint to meet the demands of the marketplace."
Under the five-year deal, the company is eligible to receive up to $8.5 million in tax credits, or 30% of the overall amount, in its first year alone spanning from Jan. 1, 2019, to Dec. 31, 2019.
To get the credits, Kimberly-Clark must retain 388 employees at the Cold Spring plant — with an annual payroll of more than $30 million — through 2023 and invest at least $200 million in the facility. In all, the company would also need to keep 2,418 individuals employed full-time statewide. Kimberly-Clark can also earn tax credits based on goods and services it purchases from Wisconsin companies.
Now, the company has around 2,700 workers across the state and 450 employees at the Fox Crossing plant that manufactures hygiene products that include Depend undergarments and Kotex pads, Maturo said. But officials are looking to hire a total of 120 workers at Cold Spring in all, Maturo added, though the target is flexible based on business needs.
Of the 80 that have been hired so far this year, Maturo didn't say how many came from the now shuttered Neenah Nonwovens plant. But he did say that "a number of new employees" had worked previously at other Kimberly-Clark locations.
The warehouse construction is expected to be completed by the end of next year, Maturo said, adding the building's exterior was recently finalized though work is underway on the interior.
The deal came about after Walker had called on the Legislature to pass legislation offering Kimberly-Clark $100 million in tax breaks similar to the ones the state is giving to the Foxconn technology company. The call followed the paper company's announcement that plants in Neenah and Fox Crossing were on a list of planned closures that would cut thousands of jobs worldwide and save the company hundreds of millions of dollars.
While the bill passed the Assembly, it languished in the Senate, leaving Walker looking for ways to strike a deal that didn't require legislative approval.
The agreement calls for Kimberly-Clark to submit reports, jobs numbers, wages paid and records surrounding capital investments made and more to WEDC in order to get tax credits each year. The reports, which cover an entire calendar year, are due by March 1 of each year. The state has yet to award any credits to Kimberly-Clark.
Going forward under the agreement, the company is eligible to receive up to $5.8 million in tax credits next year, or the deal's second year; $4.9 million in the third year of the deal and $4.4 million in each of the fourth and fifth years, with the final year running from Jan. 1, 2023 to Dec. 31, 2023.
Most of the credits come from capital investments, which make up $20 million of the $28 million deal. Any unearned capital investment credits could be carried forward for the company to earn in the later years of the deal.
Scott Walker strikes last-minute $28 million deal to keep Kimberly-Clark plant open
Kimberly-Clark will receive $25 million from the state of Wisconsin in exchange for keeping open a facility in the Fox Valley that employs 388 people. Gov. Scott Walker was able to strike the deal under a provision of state law that would not be available to his successor if Walker signs a set of lame-duck bills passed last week.
Kimberly-Clark talks continue as Scott Walker says he'll do 'everything in my power' to keep jobs in Wisconsin
Kimberly-Clark says it would invest $500 million in Wisconsin with incentive package, but bill still lacks votes
Briana Reilly covers state government and politics for the Cap Times. She joined the staff in 2019, after working at WisPolitics.com. Follow her on Twitter at @briana_reilly.
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redpajama_set_name: RedPajamaCommonCrawl


I have listed a new property at 5415 Thibault WYND NW in Edmonton.
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The Lowcountry Regatta is our largest regatta of the year and has achieved regional notoriety for its excellent racing, entertainment and socials, and welcoming southern hospitality. Multiple race courses accommodate the different classes, including dinghies and PHRF boats, and adults and juniors.
Participants frequently camp on the BYSC grounds and bring along the whole family to participate in the fun. Favorite highlights from years past include being met with ice cream and beer at the end of a tough day of racing, and the Saturday night dinner, an ever popular time for camaraderie, complete with live music. This highly competitive regatta is not to be missed!
Who: The regatta is open to one-design class sailboats.
Expected classes: VX1, EVO, SIOD; MC Scow; Lightning; Snipe; Y Flyer, JY 15; Laser: full-rig, radial, 4.7; 420; Sunfish; Optimists and Open Bics. Three boats shall constitute a class.
Pre-order sales are over but you can still purchase shirts at the regatta while supplies last.
Competitors will get one (1) shirt with regatta registration.


I'm so glad it was helpful! Thanks for stopping by.
This was so fun! I couldn't stop reading it! Such a great idea Tamara! I like how you put it all together on here after you finished on Twitter. Very clever. I will be on the look out for future tweeting interviews from you!
Christy Birmingham recently posted..What is Pink Shirt Day?
I like that she says "outlining IS brainstorming." I think that's true as you begin thinking about the character details, where the plot will go and so much more. Great Twitter chat here!
I thought that was an excellent point too!.I've always done a "flimsy" outline and character sketch. It is brainstorming and a bit of daydreaming at least for me. lol. Thanks for checking it out!


text:
Robert de Juliac (auch Robert de Juilly, Robertus Iuliacensis, Robertus de Iuli; † 29. Juli  1377) war ein französischer Adliger und von 1374 bis zu seinem Tod im Jahre 1377 der 31. Großmeister des Johanniterordens.

Er entstammte der Familie der Herren von Juilly in der Île-de-France, einer Nebenlinie des Adelsgeschlechtes Montmorency (siehe Stammliste der Montmorency).

Seit 1363 war er Großprior des Johanniterordens in Frankreich und wurde 1374 nach dem Tod des Raymond Berenger zu dessen Nachfolger als Großmeister gewählt.

Seine Amtszeit war geprägt vom erfolglosen Versuch Papst Innozenz VI. den Orden zu reformieren, insbesondere griff dieser vielfach bei der Besetzung von Verwaltungsposten für die europäischen Ordensniederlassungen ein. Diese und andere Effekte führten zu Korruption und Undiszipliniertheit in den europäischen Niederlassungen, die die militärische Handlungsfähigkeit des Ordens auf Rhodos stark behinderten. So war der Orden weder in der Lage, 1374 König Peter I. von Zypern gegen Übergriffe der Genuesen beizustehen, noch 1375 König Leon VI. von Kleinarmenien vor der Eroberung seines Landes durch die Mamluken zu beschützen, und auch nicht 1376 die Katalanen in Theben und Athen gegen die Türken zu unterstützen.

Literatur
 Pierre d'Avity / Johann Ludwig Gottfried: Archontologiae Cosmicae. Buch III, Frankfurt am Main 1628, S. 38 (hier online)

Weblinks
 Robert de Juillac bei cilialacorte.com
 Robert de Juilly bei smom-za.org
 Die 79 Großmeister bei orderofmalta.org

Einzelnachweise

Familienmitglied des Adelsgeschlechts Montmorency
Großmeister des Malteserordens
Ritter (Mittelalter)
Person (Rhodos)
Franzose
Geboren im 14. Jahrhundert
Gestorben 1377
Mann

redpajama_set_name: RedPajamaWikipedia


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Researchers from the UPF, IMIM and UVIC have developed the website GUILDify to study the molecular environment of the proteins involved in diseases. The website is a promising tool to study the molecular mechanisms underlying a disease, to understand the relationships between two diseases and to propose potential drugs for their treatment.
The website GUILDify has been developed at the Structural Bioinformatics Group of GRIB (IMIM-UPF) led by Prof. Baldo Oliva with the objective to study the protein interactions involved in a disease. When accessing the website, the user finds an input box to introduce any disease name and the species of the interactome (human, mouse, rat...). After introducing the disease, GUILDify provides the user with a list of proteins whose corresponding genes are likely to be mutated when the disease occurs. The gene mutations are obtained from DisGeNET, a database of genes associated to human diseases. GUILDify uses these proteins as seeds for an algorithm that searches for the proteins in the interactome that are more connected to them. In the end, the user obtains the protein interactions that are more likely to cause the disease and a list of the biological functions affected.
Quim Aguirre, PhD student at the Structural Bioinformatics Group (SBI) of GRIB, behind this project, tells us all about it in an article on the El·lipse website.
]]> Mon, 17 Jun 2019 10:23:05 +0000 http://www.bioinformaticsbarcelona.eu/news//news/139/a-webserver-to-study-the-protein-networks-perturbed-in-diseases http://www.bioinformaticsbarcelona.eu/news/139 0 Computational method increases design efficiency of protein-based drugs
Researchers from the Institute of Biotechnology and Biomedicine (IBB), in collaboration with scientists from the University of Warsaw recently presented an important update to their AGGRESCAN 3D computational method, focused on facilitating and reducing the cost of developing new generation protein-based drugs, diminishing their propensity to form aggregates and keeping them stable and active for a longer period of time.
Protein aggregation is a common phenomenon found in a wide range of pathologies, from Parkinson's and Alzheimer's diseases to some cancers and type 2 diabetes. A growing molecular knowledge of this phenomenon has yielded the development of different algorithms capable of identifying and predicting the regions with a greater tendency to aggregate. Among the first was AGGRESCAN, developed by the same researchers of the IBB, which took into account the propensity of the linear sequence, but not the 3D structure acquired by globular proteins. Four years ago, this same team of researchers expressed the idea of conducting predictions on these protein structures by implementing the AGGRESCAN 3D (A3D) server. This server offered a higher precision than those based on linear sequencing to predict the aggregation properties of globular proteins. It also provided new features, such as the possibility of easily modelling pathogenic mutations, or a dynamic mode, which allowed modelling the flexibility of small proteins to find potentially hidden regions.
The latest update was presented as a web server freely accessible to the academic world, in addition to a desktop version compatible with Windows, MacOS and Linux. The new algorithm surpasses all previous limitations and substantially broadens computational costs to allow modelling the flexibility of molecules of biomedical interest. It also includes different tools such as an automatic generation of mutations to facilitate redesigns of proteins as antibodies to make them stable and at the same time more soluble, and an improved user interface with which to view the data directly on the website.
"With this update, the A3D becomes one of the most complete aggregation predictors. The fact that one same place offers you the chance to make protein aggregation predictions, model their flexibility, study options for a smart redesign and verify how different factors can affect them, represents a giant step forward with regard to other similar servers", affirms Salvador Ventura, researcher at the IBB and the Department of Biochemistry and Molecular Biology, as well as creator of the A3D. "Among other things, all of this will allow us to improve the production of protein-based drugs, reducing the costs of development, production, storage and distribution".
Protein aggregation, a key element in biomedicine and biotechnology
Protein aggregation has gone from being an ignored area of protein chemistry to becoming a key element within the biomedicine and biotechnology fields. "A bad protein folding and subsequent aggregation is behind a growing number of human disorders and one of the most important impediments to designing and manufacturing proteins for therapeutic applications. These therapies, which imply the use of monoclonal antibodies, growth factors and enzyme substitutions, have already demonstrated high precision of molecular targeting, and therefore the need to study them more in depth becomes even more transcendent", Salvador Ventura concludes.
Aleksander Kuriata, Valentín Iglesias, Jordi Pujols, Mateusz Kurcinski, Sebastian Kmiecik and Salvador Ventura. Aggrescan3D (A3D) 2.0: prediction and engineering of protein solubility Nucleic Acids Research, gkz321, doi.org/10.1093/nar/gkz321
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz321/5485072
Aleksander Kuriata, Valentín Iglesias, Salvador Ventura and Sebastian Kmiecik. Aggrescan3D standalone package for structure-based prediction of protein aggregation properties. Bioinformatics. 2019 pii: btz143. doi: 10.1093/bioinformatics/btz143.
https://academic.oup.com/bioinformatics/advance-article-abstract/doi/10.1093/bioinformatics/btz143/5368526?redirectedFrom=fulltext
To learn more about how AGGRESCAN3D works please visit the following website: http://biocomp.chem.uw.edu.pl/A3D2/
]]> Tue, 28 May 2019 07:43:23 +0000 http://www.bioinformaticsbarcelona.eu/news//news/137/computational-method-increases-design-efficiency-of-protein-based-drugs http://www.bioinformaticsbarcelona.eu/news/137 0 First stable simulations of DNA crystals
A research team has presented the first stable simulations of DNA crystals, according to a study published in the journal Chem -part of the publisher Cell- and led by Modesto Orozco, Professor from the Department of Biochemistry and Molecular Biomedicine of the Faculty of Biology of the UB, and head of a research group of the Institute for Research in Biomedicine (IRB Barcelona) and the platform Bioinformatics Barcelona (BIB).
The new study shows the most detailed description so far about the properties of crystal systems with DNA at an atomic scale. This scientific milestone enables explaining the importance of chemical additives which are experimentally used to reach suitable crystallization conditions to get stable crystals in the laboratories.
According to Pablo D. Dans, postdoctoral researcher at IRB Barcelona, "the first to benefit from the study is the community of computational physicists and the chemists and biophysicists, who now have a clear protocol and reference to get stable simulations of DNA crystals".
According to Professor Modesto Orozco, head of the Molecular Modelling and Bioinformatics laboratory of IRB Barcelona, "in the long run, the simulation of several crystals obtained in under different experimental conditions should allow us to predict the effect of a certain chemical additive, and guide crystallographers in their experiments, reducing the costs and the time to get the crystals".
]]> Thu, 30 May 2019 09:01:19 +0000 http://www.bioinformaticsbarcelona.eu/news//news/135/first-stable-simulations-of-dna-crystals http://www.bioinformaticsbarcelona.eu/news/135 0 Researchers discover the action mechanism of an antitumor drug to treat glioblastoma
Glioblastoma is a type of brain tumor with no cure, usually associated with mutations in the epidermal growth factor receptor (EGFR). The main EGFR mutation found in this tumor -known as EGFRvlll- is treated with the antibody mAb806, a drug developed by the Ludwig Institute for Cancer Research (United States) about twenty years ago, although its action mechanism was unknown. Now, a new study published in the journal Proceedings of the National Academy of Science (PNAS) reveals for the first time -the action mechanism of this antibody on the mutated EGFR receptor.
The results of the study, which open new pathways for the treatment of cancer, suggest the antibody mAb806 could be used in many tumours in which EGFR has mutated and not only in a specific mutation -like researchers believed so far. The study counts on the participation of experts from the University of Barcelona, the Institute for Research in Biomedicine (IRB Barcelona), Stockholm University (Sweden), and the University of California (United States), among other institutions.
Moreover, the scientific team proved that, even if EGFR has not mutated yet, it can be treated to make it sensitive to the protocol with the antibody mAb806. "These findings provide the rational basis to conduct anti-EGFR therapies combined with antibodies and kinase inhibitors, instead of blind testing them, as it has happened so far", notes Modesto Orozco, professor at the Department of Biochemistry and Molecular Biology at the Faculty of Chemistry of the UB, head of the Molecular Modelling and Bioinformatics Lab at IRB Barcelona and member of the Bioinformatics Barcelona platform (BIB).
]]> Thu, 23 May 2019 09:19:11 +0000 http://www.bioinformaticsbarcelona.eu/news//news/133/researchers-discover-the-action-mechanism-of-an-antitumor-drug-to-treat-glioblastoma http://www.bioinformaticsbarcelona.eu/news/133 0 Ready, set, go for crossing the barrier!
Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and executed, is thoroughly regulated like an assembly line with several things happening one after another.
Researchers at the Centre for Genomic Regulation (CRG) in collaboration with the Structural Bioinformatics group of GRIB (IMIM-UPF) led by Baldo Oliva and the Department of Molecular Epigenetics, Helmholtz Center Munich, Germany, have discovered a new step in this line, which controls the expression of some genes with an important role in cancer. "We observed that breast cancer cells need a particular modification to express a set of genes required for cellular proliferation and tumour progression," explains the CRG - Beatriu de Pinós postdoctoral researcher Priyanka Sharma, first author of the paper. "This modification allows the enzyme RNA polymerase II to overcome a pausing barrier and to continue to transcribe these genes," adds Sharma.
Cancer cells are willing to quickly proliferate so, genes involved in cell division and proliferation are really active and usually highly expressed. Such a precise and meticulous machinery involves many different molecules to properly function. In this case, when all the machinery to express proliferation genes is ready, it still has to wait for a particular modification to go. As in race when runners are asked to be ready, set and go. Here, the polymerase is also ready and set but still needs a final modification to cross the barrier for transcription and go.
Deciphering every single step and all actors involved in this process is an important achievement in terms of fundamental science. We are now able to better understand how an intricate mechanism of gene regulation actually works and this might be a new target for clinical researchers to study novel therapies for certain types of cancer," states Miguel Beato, CRG group leader and principal investigator in this work.
The work, which has been published in Molecular Cell, describes a novel modification of in the Carboxyl terminal domain of RNA Polymerase II, namely the de-imination of an arginine, by the enzyme PADI2, which allows the polymerase to transcribe genes relevant for cancer cell growth. "Most chemo-therapies are oriented at blocking the activity of enzymes, but we know that PADI2 participates in many different processes involving the nervous system, immune response and inflammation, among others. Thus, inhibiting PADI2 would have multiple side effects. Our results make it possible to target just the particular action of PADI2 on RNA polymerase needed for tumour progression without globally blocking the enzyme," explains Beato.
Reference article: Priyanka Sharma et al. "Arginine citrullination at the c-terminal domain controls RNA polymerase II transcription" Molecular Cell (2018) DOI: 10.1016/j.molcel.2018.10.01.
For further information and media requests, please, contact: Laia Cendrós, press officer, Centre for Genomic Regulation (CRG) - Tel. +34 93 316 0237. For press releases in spanish and catalan click here.
]]> Mon, 28 Jan 2019 13:00:20 +0000 http://www.bioinformaticsbarcelona.eu/news//news/125/ready-set-go-for-crossing-the-barrier http://www.bioinformaticsbarcelona.eu/news/125 0 First year of the european project eTRANSAFE: read the keynote from Prof. Ferran Sanz, Project Coordinator
The eTRANSAFE (Enhancing TRANslational SAFEty Assessment through Integrative Knowledge Management) project aims at enhancing the efficiency of translational safety assessment during the drug discovery and development process by means of the development of an integrative data infrastructure and innovative computational methods and tools. This infrastructure will be underpinned by legacy data sharing, the use of data standards, such as the SEND format for preclinical studies, and the implementation of a modular computational architecture.
eTRANSAFE started its journey in September 2017 and during the first year, we have set the foundations for the development of widely accepted guidelines on safe legacy data sharing, and we have been working in the extension of the preclinical database released in the previous IMI eTOX project, in terms of incorporation of individual animal data in SEND format together with structural and pharmacological information. In addition, identification of useful data available in the public domain, its integration with the data contributed from the EFPIA partners and the identification of potential challenges by means of prototypes and use cases have been the first steps to move forward the development of the eTRANSAFE Knowledge Hub.
In the past months, an internal group, which gathers representatives from all workpackages, has been intensively working on the development of a preliminary prototype solution that allows searching for compounds, annotation of those compounds with pre-clinical and clinical data and visualisation of that data. This has proven to be a useful exercise to provide the project a means to better explore how data will need to be integrated and accessed from the Final Knowledge Hub. This work will be further developed.
The Project is pleased of the progress achieved and will continue advancing towards the final objective of supporting and improving the drug discovery and development.
The eTRANSAFE consortium is a private and public partnership of 8 academic institutions, 6 SMEs and 12 pharmaceutical companies, and is coordinated by the Fundació Institut Mar d'Investigacions Mèdiques (IMIM) and led by the pharmaceutical company Novartis. Universitat Pompeu Fabra is partner of the Consortium.
Click here to read more about the eTRANSAFE project.
Click here to subscribe to the eTRANSAFE Newsletter to be up to date on the progress of the Project activities.
]]> Mon, 28 Jan 2019 13:00:03 +0000 http://www.bioinformaticsbarcelona.eu/news//news/123/first-year-of-the-european-project-etransafe-read-the-keynote-from-prof-ferran-sanz-project-coordinator http://www.bioinformaticsbarcelona.eu/news/123 0 The depths of the ocean and gut flora unravel the mystery of microbial genes
Understanding the functions of genes in bacteria that form part of the human microbiome-the collection of microbes found inside our bodies-is important because these genes might explain mechanisms of bacterial infection or cohabitation in the host, antibiotic resistance, or the many effects-positive and negative-that the microbiome has on human health.
Surprisingly, the functions of a huge number of microbial genes are still unknown. This knowledge gap can be thought of as "genomic dark matter" in microbes, and neither computational biology nor current lab techniques have been able address this gap.
This challenge has now been tackled through an international collaboration between the Institute for Research in Biomedicine (IRB Barcelona) and two other interdisciplinary research centres, namely the IJS in Ljubljana (Slovenia) and RBI in Zagreb (Croatia). The findings have been published recently in Microbiome, the international journal of reference in microbiome research. The study was led by Fran Supek, computational biologist and leader of the Genome Data Science lab at IRB Barcelona, and first-authored by Vedrana Vidulin, a computer scientist affiliated to the centres in Slovenia and Croatia.
Intelligent prediction method
The researchers have developed a new computational method able to examine thousands of metagenomes simultaneously and identify the evolutionary signal that can predict the function of many microbial genes. This method, which analyses "big data" from human microbiomes (e.g. from the intestine or skin) and other metagenomes (e.g. from the soil or ocean) is based on a special kind of machine learning algorithm: it can create "decision trees" to predict hundreds of different functions at once, finding links between genes and at the same time predicting what they do in the microbial cell.
"This makes the algorithm very good at not getting confused by the noise in the metagenomic data, meaning that it is accurate and can confidently propose a biological role for a large number of genes with unknown functions. Intriguingly, it also proposes many additional functions for genes that already have some known role," says Supek.
The most important finding to emerge from this research is that the analysis of human microbiomes and other metagenomic data, such as those of the soil and ocean, allows researchers to assign hundreds of gene functions that have evaded current computational genomics approaches until now. "In other words, metagenomes allow scientists to see what ordinary genomes don't," explains the Croatian researcher, who was recently awarded a grant from the European Research Council (ERC).
Diversity is key
The scientists have found that different types of environments can predict different types of gene functions. For example, metagenomes from the ocean can be used to predict the genes used by bacteria for photosynthesis. But as the researchers point out, this could not have been discovered from the bacteria in the human gut. In contrast, the gut microbiome has been very useful for predicting key genes involved in the mechanisms underlying the development of disease and in the metabolism of alcohol and the biosynthesis of certain amino acids-predictions that would have been more difficult to make using microbiomes from the environment.
The authors conclude that, through machine learning, a large and diverse set of environments allows us to learn about many different gene functions in microbes. "Computational methods like this one are shedding light on the "dark matter" within microbial genomes -- the enormous number of genes in bacteria and in archaea whose functions are a mystery," says Supek.
The thousands of computational predictions generated will need to be validated in experiments. Once validated, they may lead to the discovery of new genes that explain how bacteria shape the ecosystems around us and indeed the ecosystem within us-the human microbiome.
This study has been funded through the European FP7 'Future and Emerging Technologies' Programme and an ERC Starting Grant.
Reference article:
The evolutionary signal in metagenome phyletic profiles predicts many gene functions
Vedrana Vidulin, Tomislav Šmuc, Sašo Džeroski and Fran Supek
Microbiome (2018) 6:129 Doi: https://doi.org/10.1186/s40168-018-0506-4
VIDEO MEET OUR SCIENTISTS. Fran Supek: "Solving the riddle of DNA"
]]> Wed, 18 Jul 2018 08:26:59 +0000 http://www.bioinformaticsbarcelona.eu/news//news/121/the-depths-of-the-ocean-and-gut-flora-unravel-the-mystery-of-microbial-genes http://www.bioinformaticsbarcelona.eu/news/121 0 A new computational method for exploring the reuse of drugs
Researchers led by Emre Guney of the research programme on Biomedical Informatics (GRIB), a joint programme of Pompeu Fabra University (UPF) and the Hospital del Mar Medical Research Institute (IMIM), have developed a new computational method to reuse drugs that target biological pathways common to more than one disease.
Drug reuse, an efficient strategy
A significant percentage of marketed drugs are not effective in patients due to the complexity of the biological processes involved in diseases and genetic differences between people. Despite recent technological advances, the discovery of new effective treatments takes a long time and continues to be expensive. For this reason, the reuse of medicines, i.e., the use of existing drugs for other diseases, is a very interesting alternative to reduce the costs of drug development.
In order to explore this reuse, the researchers have developed a new computational method called Proximal pathway Enrichment Analysis (PxEA), which assesses whether the proteins on which the drug acts are involved only in one specific disease or share common pathways for different diseases.
"PxEA reveals that most drugs currently used for autoimmune disorders such as arthritis, psoriasis, ulcerative colitis and multiple sclerosis do not target specifically the proteins that cause the disease", says Emre Guney, a researcher with the GRIB's Integrated Biomedical Informatics group and the Structural Bioinformatics group led by Laura I. Furlong and Baldo Oliva, respectively. "The targets of these drugs are often common immune response proteins and belong to the inflammation-related pathways that are involved in several autoimmune diseases", he continues.
Application of the method for comorbidity
Joaquim Aguirre-Plans, first author of the study, explains "we also show that PxEA can be applied to reuse drugs that can target shared mechanisms involved in comorbid diseases (occurring simultaneously in one patient)".
Type 2 diabetes and Alzheimer's disease are highly prevalent in an increasingly ageing society. Due to the interplay of various biological processes shared between these two diseases, they are commonly observed in the same patient, and recent efforts aim to reuse antidiabetic agents to prevent insulin resistance in Alzheimer's disease.
"As far as we know, PxEA is the first systematic method that can identify drugs targeting common pathological processes involved in two diseases, such as type 2 diabetes and Alzheimer's disease", says Emre Guney.
The study also involved researchers of the Research Centre for Molecular Medicine of the Austrian Academy of Sciences and the University of Maastricht in the Netherlands.
Aguirre-Plans J, Piñero J, Menche J, Sanz F, Furlong LI, Schmidt HHHW, Oliva B, Guney E. Proximal Pathway Enrichment Analysis for Targeting Comorbid Diseases via Network Endopharmacology. Pharmaceuticals. June, 2018. DOI: https://doi.org/10.3390/ph11030061
]]> Thu, 12 Jul 2018 08:19:47 +0000 http://www.bioinformaticsbarcelona.eu/news//news/119/a-new-computational-method-for-exploring-the-reuse-of-drugs http://www.bioinformaticsbarcelona.eu/news/119 0 Inauguration of the interuniversity Doctoral Program in Bioinformatics
The inauguration of the interuniversity doctoral program took place in the auditorium of the Faculties of Sciences and Biosciences of the Universitat Autònoma de Barcelona (UAB) on June 20, 2018.
The new interuniversity doctoral program in Bioinformatics has been promoted by the Bioinformatics Barcelona Association (BIB), and involves six universities: UAB, UPC, UdG, UdL, UOC and UVic-UCC.
The opening speech was given by the Vice-Rector for Research and Transference of UAB, Armand Sánchez, the President of the BIB association, Ana Ripoll, and the coordinator of the program, Xavier Daura, and had the presence of institutional representatives of the participating universities: Victoria Nogués, Academic Secretary of the Doctoral School, UAB; Francesc Sepulcre, Director of the Doctoral School, UPC; Robert Martí, Delegate of the Rector for International Masters, UdG; Gemma Bellí, Academic Secretary of the Doctoral School, UdL; Agatha Lapedriza, Director of the Master in Bioinformatics, UOC-UB; Josep Prieto, Director of Computer Science, Multimedia and Telecomunications, UOC and Antoni Tort, Director of the Doctoral School, UVic-UCC.
The event included the conference "Personalized Medicine as a Bioinformatic Challenge", given by Alfonso Valencia, ICREA Research Professor, Director of Life Sciences at BSC-CNS and Head of the Spanish node of the European Infrastructure for Life-Science Information, ELIXIR. Alfonso Valencia reviewed the challenges faced by bioinformatics in the developing field of precision medicine and the current state of the research in this field, and presented the strategic positioning of the BSC-CNS in this area.
The Doctorate in Bioinformatics aims to train the outstanding researchers of tomorrow in a highly strategic field. The research lines included in the program are Omics and Molecular Bioinformatics, Biomolecular Modelling and Simulation, Systems and Synthetic Biology, Data Science in Bioinformatics, and Biostatistics and Mathematical Modelling in Bioinformatics.
]]> Wed, 27 Jun 2018 08:44:16 +0000 http://www.bioinformaticsbarcelona.eu/news//news/117/inauguration-of-the-interuniversity-doctoral-program-in-bioinformatics http://www.bioinformaticsbarcelona.eu/news/117 0 A new therapy proves effective against brain metastasis
A study published in Nature Medicine by a team led by researchers at the Spanish National Cancer Research Centre (CNIO), with the participation of Mind the Byte, shows that the administration of silibinin in patients with brain metastasis reduces lesions without causing any adverse effects. This preliminary trial provides proof of concept that this compound could be a new effective and safe alternative to treat brain metastasis.
"We have demonstrated, taking into account all the considerations relevant to a compassionate use trial such as ours, that we can successfully treat brain metastasis", highlights Valiente, from CNIO. "This treatment could also be valid for any type of brain metastasis, regardless of the primary tumour that generated it", he added.
One of the biggest challenges in oncology is brain metastasis. It is estimated that between 10% and 40% of primary tumours generate metastasis in the brain, a situation that worsens patient prognosis considerably. Few advances have been made in terms of treatment; currently, brain metastasis is still being treated with surgery and/or radiotherapy. In recent years, some alternatives have appeared in terms of targeted therapies or immunotherapy, but the percentage of patients who might benefit from these therapies is just 20% in the best-case scenario.
The tumour microenvironment as a critical factor in metastasis
The role of the cellular context (microenvironment) in which a tumour develops is becoming increasingly important, not only with a view to understanding how cancer cells grow but also so we can know how to attack them. In the brain, an inhospitable environment for any element that is foreign to it, the role of the microenvironment is as relevant as it is unknown.
Scientists have been studying this aspect for years, focusing in particular on two elements. On the one hand, on a population of cells known as astrocytes, which respond to damage by entering into a reactive state and which are associated with metastasis. And on the other, on the STAT3 gene, which has already been proved to be involved with brain metastasis. As shown in this research, the activation of STAT3 is significant in a subpopulation of reactive astrocytes that are key to establishing a pro-metastatic environment.
When this gene is eliminated from the reactive astrocytes, the viability of brain metastasis is compromised. With this information on the table, Valiente's research group used a novel drug screening strategy developed by them called METPlatform. This tool is capable of analysing the relationship between hundreds of compounds and the metastatic cells found in the target organ simultaneously; in this case in the brain.
"This strategy allows us to assess experimental drugs as well as those that are already in use for other types of pathologies that might or might not be linked to cancer. We believe that by using METPlatform we can be more efficient in developing new therapeutic options, since we can study the metastatic cell growing in the organ being colonised", explained Valiente.
One of the compounds tested in this preparation was silibinin, whose anti-tumour potential had previously been established by Joaquim Bosch, Head of the Lung Cancer Unit at Catalonia's Cancer Institute (ICO) in Girona, and co-author of this study. "In 2016, we reported positive brain responses in two patients with no other treatment options who received silibinin, but we did not know how it worked. Thanks to this research, led by Valiente's group, we now understand how it acts at the level of the brain", said Bosch.
A new therapeutic concept with encouraging results
Following the good results obtained by blocking STAT3 with silibinin in mice, the authors established a cohort of 18 patients with lung cancer and brain metastasis for whom compassionate use to this drug was granted in combination with standard treatment. 75% of the patients reacted positively at the level of brain metastasis. Three patients (20%) displayed a total response, and 10 (55%) a partial response. Average survival rate was 15.5 months, whereas in the control group (composed of patients treated for this disease in the same institution during 2015-2016) it was four months.
"Our treatment mainly targets the brain environment that has been altered by metastasis. This is a new therapeutic concept", said Valiente. "We are also attacking an alteration that is only seen when there is brain metastasis, and which is necessary for its viability", he added.
Scientists led by Melchor Sanchez-Martinez, Scientific Director at Mind the Byte, were responsible for the structural studies of STAT3 protein and its binding to silibinin. Combining homology modelling, in silico mutagenesis, docking studies and molecular dynamics, they computationally explored how the interaction occurs and how this is affected by the different STAT3 mutations. This information supports in vivo results and will help further improve the design of new inhibitors.
Original article: Priego N; Zhu L; Monteiro C; Mulders M; Wasilewski D; Bindeman W; Doglio L; Martínez L; Martínez-Saez E; Ramón y Cajal S; Megías D; Hernández-Encinas E; Blanco-Aparicio C; Martínez L; Zarzuela E; Muñoz J, Fustero-Torres C, Pineiero E; Hernández-Laín A; Bertero L; Poli V; Sanchez-Martinez M; Menendez JA; Soffietti R; Bosch-Barrera J, Valiente M. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nature Medicine 2018 [ePub ahead of Print]. https://doi.org/10.1038/s41591-018-0044-4.
Text adapted from CNIO's press release (link).
Image: The picture shows metastatic cells in the brain (in green. GFP) surrounded by reactive astrocytes (in white. GFAP) some of which activate STAT3 pathway (red nuclei- pSTAT3). pSTAT3+ reactive astrocytes help cancer cells to develop and grow in the brain by modulating local immunity. CNIO.
]]> Fri, 22 Jun 2018 09:19:47 +0000 http://www.bioinformaticsbarcelona.eu/news//news/115/a-new-therapy-proves-effective-against-brain-metastasis http://www.bioinformaticsbarcelona.eu/news/115 0


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Q: Symbols '$£¥ €' missing from font after ios system upgrade from 9 - 10 This is a strange one.
Font in question: GrotesqueMT-Regular.ttf
I have an array called currencyPickerData and I use this information to populate my HMSegmentedControl.
    let currencyPickerData = ["$", "€", "¥", "£","FREE"]

with iOS 9 this is what it looked like.
iOS9 font is there!
with iOS 10 the "$", "€", "¥", "£" symbols are missing, I can still use the HMSegmentedControl but 4 out of the 5 segments are just empty.
iOS10 font is missing!
I have not upgraded to swift 3 worried about all the bugs it will cause. Do you think I should? Any help appreciated.

A: I just needed to update the HMSegmentedControl framework! its working again Thanks!

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Banbury's iconic piece of working history is hoping to pave the way in boat repair and dock management training by formulating a new recognised apprenticeship scheme.
The ambitious plan would be yet another string to the bow of the dry dock and would be a UK first if approved.
Proprietor of Tooley's, Matthew Armitage, knows first-hand the frustration that studying non-boat specific courses with just a smattering of transferable skills can create.
Matt said: "For myself I'm a basic garage mechanic. As well as other things I have NVQs in vehicle mechanics, things like spark ignition and compression in both petrol and diesel.
During his 15-year tenure at the dry dock Matt has taken would-be coach painters under his wing and had to resort to some creative thinking in order to provide them with a pen and ink qualification.
In the new year Tooley's is hoping to employ an apprentice to learn all aspects of working in a boatyard including management, painting, basic boat repair and mechanics but wants the student to leave with an industry standard modern apprenticeship qualification.
With over 200 years of boat repair at the site and with the wealth of knowledge stored within the minds of the current employees, Tooley's provides the natural foundation on which a Modern Apprenticeship can be built.
Matt has already been in contact with a leading manufacturer of boat engines and Banbury and Bicester College in order to supplement his vision and create a qualification.
Matt said: "What it would be is being involved in setting the standard. So it would have to involve a college and it would involve other people in the industry.
If approved the qualification would revolutionise the narrow boat industry that still operates in the tried and tested methodology of learning on the job and gaining experience.


Reasi: Department of Floriculture, Parks and Gardens Wednesday organised a district level event on commercial floriculture at SMVD Spritual Growth Centre, Katra under centrally sponsored scheme MIDH in which more than 400 farmers participated.
Deputy Commissioner, Dr Sagar Dattatray Doifode, was the chief guest on the occasion while SDM Katra, Ashok Kumar was the guest of honour. Director Floriculture Babila Rakwal was also present.
Speaking on the occasion, DC stressed on the need to generate business opportunities for locals keeping in view huge inflow of tourists to the district. He appreciated the efforts of Floriculture and other departments directly associated with the development of farmers.
Dr Banarasi Lal, Head of KVK Reasi, Scientists Suza Qureshi and Dr Sanjay Kaushal and AFO Pawan Kumar delivered informative lectures and educated the farmers about latest technologies of flower cultivation, value addition to flower products and organic farming.
During the event, various promotional stalls were also put up for awareness of farmers and general public in which agriculture implements, organic seeds, organic fertilisers etc were put on display. The stalls were put up by Krishi Vigyan Kendra, SBI Rural Self Employment Institute, Fisheries Department, Agriculture Department, Horticulture Department and others.
The event was also attended by Deputy Director and Nodal Officer, CSS Floriculture Jammu, SK Sultan; Deputy Director Floriculture (P&S), Priti Aggarwal, Landscape Officer Sunil Singh and AFOs.


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The Problem with Religious Faith: "It's Indistinguishable From a Con."
A comment here from Stephen argues that "At the beginning of every mythology, every cult, every religion in history, is a con-artist who figured out how to sell a racket so that he could get rich while doing "god's work.'" [Full Text below] I think this can be shown with regard to L. Ron Hubbard and the rise of Scientology, as well with Joseph Smith and the rise of Mormonism. In my book WIBA, I argued that the empty tomb story probably started with the Gospel of Mark, who was a liar for Jesus. Don't think so? Think again. In fact, liars for Jesus abound.
No, it's not god who wants you to step out in faith, and it's not god who is pleased when you do. It's somebody else.
It's con artists who want you to step out in faith. It is always con artists who want you to suspend your "god-given" ability to think critically, refrain from noticing that various claims might or might not make any sense, or assess the likelihood of various statements to be true or not. These con artists might be sincere, simply because they're not the one in-the-know up in the penthouse suite of the church palace. But at the beginning of every mythology, every cult, every religion in history, is a con artist who figured out how to sell a racket so that he could get rich while doing "god's work."
And that's the problem with religious faith. It's indistinguishable from a con. That is not an accident! If there really were a god of integrity who had your best interests in mind, he would provide better evidence for his existence and power than that provided by every con artist in history. He wouldn't couch his "truth" in the world so that it blended in with the background clutter of every liar in history.
There was a time when I "believed" that there was a reality to religion. But I ceased to "believe" because of the lack of effects, effects which were promised, but failed to materialize. This has never been the case for gravity. Gravity has always pulled me down, and never once has it let me down. God on the other hand, has let me down. If god were as reliable as gravity, I'd still be religious. LINK.


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Possible cause of MS? How a gene variant can combine with environmental factors to cause MS
By Steve Cimino
The distinct way immune cells respond to viruses like Epstein-Barr in people with the HLA-DR15 gene variant plays a significant role in the development of multiple sclerosis (MS), according to new research into what causes the autoimmune disease. "Fitness to cope with dangerous pathogens in the context of certain HLA molecules comes at the price of misguided immune responses," Jian Wang, PhD, a postdoctoral researcher in the neurology clinic at the University Hospital Zürich, and colleagues wrote in Cell.
To determine how exactly HLA-DR15 contributes to the genesis of MS, the researchers launched an interdisciplinary international study on the HLA gene complex.
"The association of MS with the HLA-DR15 haplotype was actually known since the early 1970s," said study coauthor Roland Martin, MD, of the department of neurology at the University Hospital Zürich, in an interview. "It was, to my knowledge, the first discovered association of an HLA molecule with a human autoimmune disease. But until recently, it was not known functionally how it translates into disease susceptibility and disease onset."
It was also known that carriers of HLA-DR15 who come down with the Epstein-Barr virus (EBV) along with infectious mononucleosis have a 15-fold greater risk of MS, but the underlying mechanisms were not fully understood.
Dr. Roland Martin
"Late EBV infection means a greater risk of MS, but it's still very difficult to say if EBV is an absolute requirement or if people with MS then also activate this virus," Dr. Martin said. "It's fair to say that MS without EBV doesn't exist. But 25% of the healthy population is DR15 positive, and in MS it's approximately 50%. Many people are DR15 positive and they don't get MS."
"We wanted to figure out, on a functional level, how HLA molecules contribute to MS," he added.
We wanted to figure out, on a functional level, how HLA molecules contribute to MS.
Determining altered behaviors
Patients with MS who were age 18 years or older from a single outpatient neurology clinic were recruited for the study between July 2018 and February 2019. Receiving treatments through participation in a clinical trial (which thereby eases financial burden) was among the exclusion criteria.
Participants who were included in the analysis (n = 243) filled out a paper survey that took about 15 minutes to complete. Among the assessment tools was the modified Comprehensive Score for Financial Toxicity Patient-Reported Outcome (COST) instrument, which was previously validated to assess cancer patients.
The survey also assessed HRQOL and alterations in lifestyle to compensate for financial lack, such as decreased spending on food, clothing, or leisure; withdrawal from savings accounts; and increased use of credit cards. Care-altering coping behaviors also were assessed and defined as foregoing imaging tests and nonadherence to medications because of the costs. For patients who received their MS diagnosis more than 3 months before study entrance, information on disease severity and disease type (i.e., relapsing remitting, primary or secondary progressive) was obtained. Patients were also asked about demographics, health insurance, financial self-efficacy as measured by the Financial Self-Efficacy Scale, and health literacy.
As HLA-DR15 molecules often can be found on the surface of white blood cells, where they present various protein fragments to T cells, the study began by investigating which fragments are presented. In the thymus, where immune cells are trained, they found that the HLA-DR15 molecules also presented fragments of themselves.
As those trained T cells then migrate into the blood, they come into contact with viruses or bacteria that they are tuned to recognize – at a cost.
"When the cells are activated by, for example, EBV infections, they become memory cells and more sensitive to antigenic stimulus," Dr. Martin said. "Then, if the autoantigen that is involved in the MS itself and expressed in the brain also becomes available, the cells are more strongly activated, we assume that they can then go to the brain and cause damage."
Beyond EBV, the researchers also confirmed a distinct reaction to the intestinal bacterium Akkermansia muciniphila, which is observed at relatively higher numbers in the gut of MS patients.
Top image credit: nobeastsofierce/Shutterstock
Image credit: CNRI / Science Source
Why these two environmental factors? Dr. Martin believes that the carriers of this common gene have adapted to new surroundings, which leaves them unexpectedly prone to MS.
"The way I envision it," he said, "is that, in certain geographic areas of the world, where people have migrated over the last several thousand years, they are encountering certain pathogens. In Africa, it's more parasites and certain distinct infections. In Europe and North America, we are confronted with viruses and also bacterial infections. The HLA background that we have has adapted to that, endowing people in those areas to cope with those infections efficiently."
"The downside of being able to recognize certain infectious agents very well," he added, "is that similarities between antigens from the virus or from the bacterium with certain self-antigens can lead to autoimmune diseases like MS."
In terms of research next steps, Dr. Martin expressed optimism that their findings could lead to novel treatment approaches that go beyond MS.
"In many autoimmune diseases, there is a very strong HLA association," he said. "Rheumatoid arthritis, diabetes, celiac disease, psoriasis. All of these have an association with different HLA molecules. What we've described here, in principle, could play a role in other autoimmune diseases as well.
The downside of being able to recognize certain infectious agents very well is that similarities between antigens from the virus or from the bacterium with certain self-antigens can lead to autoimmune diseases like MS.
"What's already been shown, in diabetes and also in an MS model, is that if you take small molecules that block the HLA binding pocket, you can block T-cell activity against antigens of the pancreas in models of diabetes or MS. And treat the disease, so to speak," Dr. Martin said.
He also emphasized that, in the long run, their work would hopefully contribute to a better understanding of MS's origins.
"Our study primarily shows how we educate an immune system, if we are DR15 positive, in a way that sets you up for developing this brain- and spinal cord–specific autoimmune disease," he said. "But what is at the very beginning? What starts the MS process? This is still not known."
The study was supported by a European Research Council grant and the Clinical Research Priority Program MS at the University of Zürich. Three of the authors reported being cofounders and co-owners of Cellerys, a company that is developing cell therapies for MS. Dr. Martin reported receiving grants and lecture fees from various pharmaceutical companies.
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Even as a kid, Jen Kennedy (Finance '92) had an eye for real estate. She was introduced to it by her dad, a lawyer who dabbled in real estate. When she didn't tag along with him, she'd study listings in the newspaper.
Now that she's broker-owner of Edmonton's Kennedy Real Estate, Kennedy still has a keen eye for pricing, but she's matched it with a talent for staging, the decorating and accentuating that makes a listed property pop when potential buyers come through the door. With the market clearly in their favour, that's more important than ever.
In the last quarter of 2018, Edmonton saw a 5% year-over-year drop in overall sales, while supply continued to rise. Housing inventory is at its highest in more than a decade in Calgary as well. In the near-term, there's little sign that things will change.
So what makes a particular home stick in the mind of a buyer? Here are Kennedy's tips on staging your home to sell fast and sell well.
Not every part of the house needs to be dressed for success. Kennedy is selective in her efforts, letting them be guided by key questions.
"Where do you hang out? What are things that you're going to miss the most about your home?" Likely, those will also appeal to the next resident. "Highlight those areas," says Kennedy.
For too many months each year in Edmonton, Kennedy sells homes in the dark. This creates an obvious challenge, but also an opportunity that persists into after-dusk showings during warmer months.
"Lighting is everything absolutely. It starts with that."
Turn off harsh overhead illumination and turn on accent and ambient lights, even over a kitchen counter or in the bathroom. When thinking about the entire space, do so as if you were staging a party where you wanted your guests to feel comfortable, not blinded.
Back at her office, Kennedy keeps a room of items for staging: bath towels and accessories, table settings, accent pillows, blankets, framed pictures, mirrors, silk plants and much more. She doesn't use everything at once, adhering to the old adage that less is more.
The common goal is cozy.
Every space will require different treatment. But the common goal is cozy, like a bedroom with a bed that's properly made and lit softly by lamps on either side. That's the kind of thing that makes a house shopper think: "Yeah, I could retire here at the end of the day," says Kennedy.
Art is used sparingly in new showhomes, Kennedy points out, with the emphasis placed on windows instead. She approaches older homes she sells the same way. Any art left on the walls should have broad appeal. Otherwise, pack it up.
Keeping a house clean for showings goes without saying. Almost. Kennedy says that many sellers tend to overlook areas that need it most – those where the eye tends to be drawn even though they're not points of interest. Look for fingerprints and dirt on door handles, for example, and on frames nearby.
A space won't shine if it's buried in junk.
A space also won't shine if it's buried in junk. After having moved several times when her four boys were less than five years old, Kennedy has "bin" there, done that, and knows what she's talking about. When the kids are done playing, chuck the toys in a box and shove it behind the couch. Keep toothbrushes and toiletries in a container to stow in the bathroom cupboard.


WELLCOM's networking groups is a member benefit for the 2019 calendar year! We are excited to bring Iowa WELLCOM members together in this way, simply to connect over a cup of coffee or breakfast!
WELLCOM members are doing so many great things with their workplace wellness initiatives, and we know it can be extremely beneficial for members to talk with one another, discuss common struggles, and learn from each other's successes. The WELLCOM networking groups in Iowa will provide a fun opportunity to do exactly that!
Connects member companies to discuss wellness hot topics in a small, friendly setting!
To see networking opportunities in Nebraska, click here!


Garfield Realty » Croatia is Europe's Best Kept Secret!
Spring and summer are the very best times to visit Croatia, when the crystal clear, aquamarine waters of the Adriatic are most inviting. Whether you're seeking a respite from reality or a traveler's paradise, below are some tips for enjoying your stay.
You can catch Split's coastal Mediterranean beauty on display in Game of Thrones. Split is Croatia's second largest city and a beautiful mix of the old and new. Buzzing with energy but also relaxed in its coastal pace, this is a hotspot for culture, history, and breathtaking scenery.
You can't miss Diocletian's Palace, a Unesco World Heritage site, and one of the world's best-preserved monuments of the Roman era, which comprises about half the old town of Split. Built around the 4th century in 295 AD as a retirement villa for the Roman Emperor's family and their 700 servants and guards, this ancient fortress is incredibly well preserved and now contains a multitude of shops, cafes, restaurants, and apartments along its narrow streets. There is no entrance fee for the palace itself, and it is open all hours of the day and night; most shops are open Monday to Friday 9am-1pm and 5-8pm, Saturdays 9am-1pm, and sometimes on Sundays.
Some sites inside the palace require a ticket, such as the underground tour, Cathedral of Saint Domnius (where you can attend a Sunday Mass), Split's Bell Tower (with 360 degree panoramic views of the city), and Temple of Jupiter. After a tour you can wander and explore the maze of side streets and boutiques or dance to live music in the center of the Peristyle (the palace's courtyard). Just outside the northern wall of the palace is an enormous statue of Gregory of Nin, a Croatian bishop hailed as a hero. When Christianity was fading in popularity on the island in 926 AD, he defied the Vatican and held services in Croatian rather than Latin. This encouraged the uneducated and poorer populace to embrace Christianity; today, nearly 90% of Croatians are Catholic. Go ahead and rub the statue's shiny big toe for good luck.
The Riva is the main public hub of the city, where locals congregate and events take place. This wide, tree-lined esplanade is buzzing with energy in the late afternoon and throughout the evening. You'll often hear the serenading sounds of locals singing klapa, traditional a capalla Adriatic tunes with soulful harmonies, sung in small groups.
Partake in a Split Culinary Tour. An expert will meet you at the Peskarija fish market and Pazar green market in the center of Split to help you choose the best fresh fish and produce of the day. These charming open-air markets are open Monday through Saturday from 8am-2pm and Sundays 8am-11am. From there, you will head nearby to the Diocletian Wine House, where the chef will prepare a delicious multi-course meal for you from the food you've hand-selected.
Tucked within the stone walls of Diocletian's Palace is the exceptional and affordable Makarun Konoba and Bar. The ambiance is relaxed and romantic but family-friendly, the food is incredibly fresh and beautifully prepared, and the service is fantastic. If you are looking to try a classic Croatian specialty, head to the family-run Konoba Fetivi, known for serving the best black cuttlefish risotto on the island. Be sure to also save room for their apple strudel, made from an old family recipe.
Within a scenic hour-long drive from Split is a day-tripper's paradise, Krka National Park. Fully immerse yourself in nature by hiking along the many miles of walking paths overlooking 12 stunning waterfalls, and jump into the water whenever the mood strikes. You can even swim in front of the largest waterfall in Krka, Skradinski Buk. This park is much easier for families to navigate than the larger Plitvice Lakes. If you prefer to take a bus from Split, head to Skradin (the town Bill Gates visits every summer), stroll 5 minutes down the road to the visitor's center to buy your entry ticket, and board the boat headed down the Ria River through Krka Valley directly into the park.
Roughly 2-1/2 hours from Split by car, Plitvice Lakes is a wondrous and expansive series of 16 interconnected lakes with ample hiking and gorgeous vistas. You can book a day tour or arrange an extended stay. Be aware that it will be quite crowded in the summertime and difficult to explore with small children due to narrow tracks and trails. You are not allowed to swim at Plitvice, but you can enjoy the sights and capture breathtaking pictures of its stunning natural beauty.
To journey from Split to Vis, take a breezy 2-1/2 hour ferry ride. Head to the top deck of the Jadrolinija with a good book to soak up some sun and enjoy the views along the way. When you arrive in the port of Vis, purchase a cheap pair of water shoes to protect your feet on the white stone beaches from sea urchins nestled inside the rocks.
With a population of around 2,000 residents, Vis is known as the gastronomic capital of the Adriatic. Visiting Vis is like stepping back in time, where you are forced to recalibrate to a more mellow, relaxed pace. Until Croatia gained its independence in 1991, the entire island was forbidden to tourists; it was annexed as a closed military base completely isolated from the outside world. When the Yugoslavian army abandoned Vis virtually overnight in 1992, regular life and tourism slowly returned to this gorgeous, sleepy, and under-developed island. Beyond the pristine white stone beaches and waterfront vistas this island is known for the simple daily delight of observing butterflies dance around wild lavender bushes.
We highly recommend putting local driver Toni Vitaljic on speed dial. He can take you anywhere you need to go, and will arrive on time, every time: vitaljictoni@yahoo.com/ tel +385-98-777-314. Toni grew up in Komiza and lives in Vis, where he seems to know everyone on the island. He became our defacto tour guide.
A trip to Stiniva Beach is a must. This small and pristine white stone beach was named one of the top beaches in Europe. It has been speculated that it was once a cave that collapsed forming this secluded cove. With proper shoes, you can hike a rugged path down from Plisko Polje, or hire a boat to take you from Srebnra Beach to Stiniva (Toni can connect you to a speedboat driver). Tavern Peruka offers refreshments and snacks on the beach. Stiniva tends to be more populated than other area beaches, but is definitely worth the trip.
Srebrna Beach was a short hike from our retreat center, Estate Under the Paintbrush, and might have been my favorite of all the beaches we visited. Because we were virtually the only ones there on a daily basis, it felt like our own private paradise. You can sit and meditate on the flat rocks nearby at Bili Bok (be aware this is a pro-nudist spot), soak up the sun, and jump into the purest waters to cool off. Another favorite is Teplus Beach. After a swim at Teplus, take a short walk from the shore to Restoran Dalmatino for a plate of grilled sardines, Dalmatinska garnitura (a common local side dish of swiss chard with potatoes), and delicious French fries.
Head to the Blue Cave in Bisevo, a lovely, albeit touristy destination. Arrive between 11am-12noon, directly when the sun hits its peak and creates the natural phenomenon at the mouth of the Blue Grotto, Modra Spilja. Afterwards, take a boat to the sandy shores of Porat Beach. Enjoy a fresh seafood lunch at Restoran Kod Jaske directly on the beach, followed by a natural hike around Bisevo and a relaxing day by the water.
Vis is known for it's dry white Vugava and red Plavac Mali wines, produced from Dalmatian grapes grown on the island's fertile soil. Antonio Lipanovic is a former cricket player and current crusader of Vis's wine and local winemakers. His winery is housed in a cave at the hub of a network of military tunnels that were forged by Tito's army after 1945. If you can't get an appointment to taste wine onsite, it's worth looking out for the Liponavic label at many local restaurants.
Climb or take a drive up Mount Hum and head to the highest point in Vis for breathtaking panoramic views over the town. While you're there, step inside the charming Chapel of Saint Duh – it's simple, but worth a peek. Tito and his supporters famously took refuge along the southern slopes of Mount Hum during WWII. Though no longer signposted, Tito's Cave can be identified by the large parking bay under a stone wall to the right of the road as you're heading up. Another path from the summit of Mount Hum leads to the former rocket base.
Stop to smell the lavender and enjoy a simple glass of wine at the charming Aeorodrom Gostionica Wine House. Call Konoba Golub in advance to order a traditional Croatian meal of Ispod Peke, a stew containing fish, lamb or octopus that is slow-cooked for hours over hot coals in a peka, a long-handled pan with a domed lid. We enjoyed scorpion fish that our waiter caught with his bare hands during a deep dive that morning. The views from the outdoor terrace overlooking Vis are a treat, and you can sip various flavors of homemade grappa from the back room as an aperitif after your meal.
If the mood for pizza strikes, head to Karijola. With the freshest of ingredients served on a terrace overlooking the sea, the traditional pizza experience is naturally elevated. Stop by the wine shop near Caffe Bar Bejbi to book a dinner reservation at Roki's for a top-notch meal served on an operating vineyard nestled between cricket grounds and olive groves. Roki also serves its own tasty Plvac and Vugava wines.
Roughly a 20-minute drive from Vis, Komiza is a beautiful coastal village and a popular destination among Croats. This small town offers a quaint bohemian atmosphere with seaside shops and restaurants.
Enjoy a leisurely lunch along the water at any number of restaurants – you truly can't go wrong. All the food is freshly prepared and most restaurants offer shaded waterfront views. If you are craving lobster, Konoba Jastozera is a premier destination. Bako is another local favorite offering a beautiful seaside setting and relaxed ambiance with flavorful food. The restaurant's founder dove for decades in the surrounding waters and discovered some ancient Greek and Roman artifacts, which you can see on display. Do not miss a stop at Slasticarnica Cukar for dessert.
The US dollar will take you far in Croatia. The current exchange rate is roughly 6 Croatian Kuna per USD. Croatia is often listed as one of the top 20 safest countries in the world (for reference, the US is currently ranked 84th). Doors are left unlocked in Vis, and we felt safe wherever we went at any time of day. People throughout Croatia are neighborly, welcoming, and respectful. English is spoken wherever you go, but they do appreciate if you learn some common words and phrases in Croatian. Be prepared to shake off your New York edge and embrace the 'pomalo' Dalmatian lifestyle, where a leisurely pace and enjoying life in the moment will become your top priority.
We want to thank our fellow real estate agent, yoga teacher, and dear friend, Miya Signor, for introducing us to Croatia and creating an amazing annual yoga retreat. For anyone looking for an expansive and immersive adventure, book any of Miya's future retreats and check out her weekly classes at Area Yoga in Brooklyn.
Until next time, sigurna putovanja (safe travels)!


But to the nation's surprise, after making his statement the chancellor downed his trowel, took off his helmet and hi-vis jacket, and was driven away in a Rolls Royce.
Builder Tim Twanks said "I was really pissed off. He turned up this morning and we thought 'finally, he's going to do something useful', but he just laid one brick, spoke to the cameras for ten minutes, and fucked off.
Television-watcher, Wendy Nailinthehead, said "I can't remember anything Mr Osborne said, because he used sentences with difficult words, like 'deficit'. I was pleased, however, to see he was doing an honest day's labour building one of those new houses he keeps promising the country.
The contractor, Homes For Everyone, announced this afternoon it has had to lay off 30% of its staff to pay Mr Osborne for the brick he laid.
Posted on November 26, 2015 at 12:40 pm in Economy, Journalism, Politics, Satire, Society, UK	| RSS feed You can	trackback	from your own site.


Deontay Wilder - Bio, Boxing Record, Net Worth, Who Is The Wife Or Girlfriend?
The WBC champion and one of the most feared boxers, Deontay Wilder believes himself to be the No. 1 heavyweight in the world. Once a high school football and basketball star, the 6-foot-7 Alabama champ was forced to change his priorities during his first year of college after he became the father to a special needs child as a teenager.
Forced to drop out of college and work hard in order to support his daughter, Wilder's focus in life became clear and he was motivated to thrive against all odds. Be inspired to success with facts about the incredible achiever who began boxing at the age of 20, turned pro in 2008, and is now the world's second best current heavyweight champion.
The African-American heavyweight was born Deontay Leshun Wilder on 22nd October 1985. He attended Central High School in his hometown of Tuscaloosa, Alabama where he was a football and basketball star. He later proceeded to Shelton State Community College.
But at age 19, Wilder had to quit school following the arrival of his daughter Naieya who was born with a debilitating birth defect, spina bifida. Left without a choice than to properly provide for his family, Wilder transitioned from a college student to an employee as he began working several menial jobs, including one as a beer truck driver and waiting tables. Though his college dream was over, Wilder chose to work hard and make a good living. More so, he didn't give up on his athletic career but soon picked up boxing to add to his various sources of income. More than anything else, Naieya's existence was Wilder's motivation and the reason he thrived against all odds to now become a World Boxing Council heavyweight champion.
The towering heavyweight debuted his boxing career at age 23, in November 2008 in a victorious match against Ethan Cox. Deontay continued with his winning streaks and after about 21 fights in less than 3 years, he became an Olympian.
Following his bronze medal win as an amateur boxer at the 2008 Olympic games in Beijing, Wilder earned himself a new nickname – The Bronze Bomber. Wilder won his first professional boxing title in December 2012 in a bout against Kelvin Price, a champion who until that day was undefeated on the ring.
So far, Wilder Deontay who averages a knockout every 22 minutes and 25 seconds, boasts of 40 phenomenal fight wins, out of which 39 matches were won by knockout and one (his 2015 WBC victory) by a unanimous decision. He is a two-time (2016 and 2017) Premier Boxing Champion and currently holds the World Boxing Council (WBC) Heavyweight title.
In January 2015 and at age 29, the Alabama champ became the first American in nine years to win a title when he defeated WBC champion Bermane Stiverne in Las Vegas. Since then, Wilder has been defending the World Heavyweight title. An incredible achiever, Deontay is also the 17th longest reigning world heavyweight champion ever. With the burning desire to become the world's undisputed heavyweight champion, Wilder's star continues to rise.
Following his numerous winning streaks on the ring, the Bronze Bomber has a bank balance that is quite befitting of his status as a world champ. So far, Deontay has done well for himself as he is reported to pocket an annual revenue of about $2m-$5.5 million.
The biggest fight purse earning of his career was the match against Cuban boxer Luis Ortiz wherein he added a hefty $2.1m (£1.5m) to his bank balance. More so, a combination of Wilder's two fights against Luis Ortiz and Bermane Stiverne earned him $2.5 million (£1.9m). Currently, Deontay Wilder's net worth is believed to be $16 million (£12.2m), a value which is set to greatly increase with future fights against bigger opponents.
See Also: Manny Pacquiao Boxing Record, Net Worth, Wife, Age, Height, Is He Gay?
In 2009, the Tuscaloosa, Alabama native married the love of his life, Jessica Scales and together, they have three children – Ava, Dereon, and D.J. (Deontay Wilder Jr). According to reports, Wilder had his first daughter Naieya with his ex-girlfriend Helen as a teenager. While Deontay's kids have been his major motivation and reason for living, it is his first child Naeiya who crafted the vision for his world.
However, Wilder and Scales have since parted ways and he is currently dating Telli Swift Shuntel, an American nurse, model, and TV-personality. As a nurse, Swift was an employee at the Beverly Hills Plastic Surgeons' recovery unit.
The pair who have been dating for more than three years have a child together, although details about the child are not available to the public. Their relationship was once featured on WAGS Atlanta. Beyond being a supportive partner, Swift also supports the Spina Bifida Association which promotes awareness about Deontay's daughter condition.


The most common box style we manufacture. The regular slotted container is the most popular shipping box in the world. It has 4 flaps on the top and bottom, where the outer (length) flaps meet at the center of the box.


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Updated on May 3, 2016
Why Community Health Is Crashing by 11% Today
By Todd Campbell Fool.com
IMAGE SOURCE: COMMUNITY HEALTH SYSTEMS, INC.
What:After Community Health Systems reportedearnings per share far shy of industry watcher's forecasts, its stockdropped by 11.6% at 11:00 a.m. ET today.
So what: The major hospital operator reported ex-items EPS of $0.27 that was well below the consensus estimate projection of $0.74. Adjusted EBITDA in the quarter was $633 million, down from $715 million a year ago and represented an 11.5% decline.
On an operating basis, Community Health's total admissions dipped 2.6% year over year. On a same-store basis, admissions fell 2% on an unadjusted basis but ticked up 1.3% on an adjusted basis. Same-store net operating revenue improved 2.2% in the quarter versus a year ago and reported revenue inched 1.9% higher to $5.75 billion.
The results were muddied by line items related to its prior acquisition of HMA and its spinoff of Quorum Health Corporation, a compilation of 38 hospitals in 16 states.
Now what: After the Quorum Health spinoff, Community Health still runs 160 hospitals in 22 states and management expects that those hospitals will generate net operating revenue of at least $17.8 billion this year. The company is also guiding for full-year EPS of at least $2.50 and adjusted same-store admissions growth of 0.5% or higher.
Clearly, this is a transformative year for the company. The benefits of integrating HMA's hospitals and right-sizing its hospital portfolio may take some time to be realized. Investors might also want to consider that the company plans to use the $1.2 billion raised via the Quorum deal to pay down debt. Additional divestitures are also planned that could reduce debt even further. After its divestitures are complete, it should be left with a portfolio that includes its highest-margin hospitals. That could position it to capitalize on future admissions growth related to an American population that is increasingly larger and living longer. In the meantime, however, investors will need to deal with some messy quarters and that could make this the most risky hospital stock in the industry.
The article Why Community Health Is Crashing by 11% Today originally appeared on Fool.com.
Todd Campbell has no position in any stocks mentioned.Todd owns E.B. Capital Markets, LLC. E.B. Capital's clients may have positions in the companies mentioned. Like this article? Follow him onTwitter where he goes by the handle@ebcapitalto see more articles like this.The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.


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Something To Salute: A Mortgage Program For Military Members
How VyStar Credit Union turned member input into tangible features for its Military Heroes Mortgage.
Surveys helped VyStar Credit Union determine important features it should offer in a new mortgage program designed specifically for service members.
The program provides down payment help and requires no mortgage insurance, plus, certified military lending specialists serve as originators and processors.
VyStar Credit Union($11.4B, Jacksonville, FL) has already made the new year a happy one for its borrowers who have taken advantage of the cooperatives new Military Heroes Mortgage.
VyStar announced the launch of its new lending product a week before Veterans Day in November, and it has already closed the first few loans. The loans might be a minor portion of Vystar's real estate mortgage portfolio which has grown 6.95% in the past year to $3.99 billion as of Sept. 30but they will make a major difference in the lives of borrowers.
"We understand the unique challenges our troops face when purchasing a home, and the Military Heroes Mortgage is designed to make the process more efficient and more affordable", says Jennifer Kouchis, VyStar's senior vice president of real estate lending. "Since our founding at Naval Air Station JAX in 1952, supporting our military members and their families has been at the core of what we do."
Jennifer Kouchis, SVP of Real Estate Lending, VyStar Credit Union
VyStar's Military Heroes Mortgage includes the following features:
No down payment or mortgage insurance required.
Up to $5,000 toward closing costs or a 0.25% rate discount.
Up to a $10,000 grant to be used toward a down payment or closing costs.
Discounts up to $7,500 available from top national and local retailers.
Charitable activities.
Loan originators who are certified military housing specialists.
"Our legacy is rooted with our military and civil service families, so we built this product with them in mind", Kouchis says. "This sets us apart because we are able to deliver the tools and knowledge necessary to provide prompt and competitive service to our military members, especially in a fast-paced market."
It took VyStar approximately one year to develop the program. Notably, the credit union relied heavily on member input, surveying military families and those with military affiliations to find out what they wanted and craft the best benefits. For example, those surveyed indicated they wanted more low and no down payment options. So, VyStar offers 100% financing, a grant component, and a choice between lower closing costs or a lower rate.
4 Tips To Launch A Successful Mortgage Product
Jennifer Kouchis, senior vice president of real estate lending, offers advice based on her experience with VyStar Credit Union's new Military Heroes Mortgage.
Focus on a gap that is not being served, and take time for due diligence.
Create for purpose, not profit.
Proprietary programs come with risk. Mitigate risk with performance testing, specific underwriting guidelines, thorough procedures, and experienced team members.
Carefully consider every factor about the execution and launch.
Survey responses also indicated borrowers want easier communication and more transparency about the mortgage process. The result? VyStar's Military Heroes Mortgage provides a package of infographics, welcome letters, and support through every contact method, including direct dial. It even has specialized greetings by ranks.
The surveys also prompted the credit union to offer specific training to certify teams originators and processors as military housing specialists who understand military and family challenges.
VyStar will keep the new mortgages in-house as portfolio loans and markets the program through multiple channels, including direct mail, social, email, print, and digital.
"The response has been incredibly positive", Kouchis says.
The real estate executive has one parting piece of advice for other cooperatives that want to create a similar program for a specific segment within their membership.
"Get support from every level", she says. "Your organization needs to understand the vision to get behind it and see it through."
Florida Lending Mortgages


>> Have You Taken A Step To Going Green With Your Energy Provider?
We Are Full of Energy At Eceau And Have A New Provider Too!
Last month we moved to much smarter and larger offices so we can accommodate our new recruits! It feels good to have more space, provide a better working environment and we even have a breakout room!
Always at the forefront of our minds at Eceau, we want to be as environmentally friendly as possible in our workplace. We have been looking into our business energy supplier options and found a great solution that provides us with 100% renewable energy.
Octopus Energy were winners of Uswitch, Supplier of the Year in 2018 and this helped us make the decision to switch our business energy supplier. They have clear and simple pricing and bills that really make sense. It's a win, win for us all. We were interested to read that Which? reviewed 31 energy suppliers and surveyed almost 9,000 customers on customer service, value for money and accuracy of bills, and could only recommend one supplier: Octopus Energy. We were sold on the idea.
Switching over to Octopus Energy is so simple, can be done online within a few minutes online so give it a go.