Missing 90-year-old Rancho Bernardo man returns home safely Updated: 6:01 PM February 11, 2018 , SAN DIEGO (KUSI) — Police were searching Sunday for a man with Alzheimer’s disease who drove away from his Rancho Bernardo home, before returning in the evening.Terrence McCluer, 90, lefthis residence on Plaza del Curtidor at about 12:45 p.m., according to the San Diego Police Department.McCluer’s driver’s license has been suspended for more than a year due to his condition, police said. Posted: February 11, 2018 Categories: Local San Diego News FacebookTwitter
Journal information: Nature Materials Representative micrographs showing cross-sections of hMSCs 36 h after encapsulation into 3D matrices made from the shortest (P1) and the longest polymer (P6) and constant GRGDS density, visualized by bright-field microscopy. Credit: (c) Nature Materials (2015). DOI: 10.1038/nmat4483 The extracellular matrix (ECM) plays an important role in controlling what happens within a cell by way of physical properties like stiffness and topography. This type of interaction in which mechanical properties lead to a series of biochemical activity is known as mechanotransduction. One are of interest is how ECM stress-stiffness influences stem cell differentiation.In order to study the mechanism behind stiffness-induced cell differentiation, researchers have tried to mimic the ECM environment. Prior studies employed several different systems to do this, including ECM-protein-derived hydrogels, synthetic polymers, and elastomeric mircopost arrays. Each of these has its strengths and weakness in how well it replicates the ECM. Das, et al. have designed a new type of cell culture system to mimic a three-dimensional ECM. They developed a thermoresponsive hydrogel from oligo(ethylene)glycol polyisocyanopeptides (PICs) that they can use to study the effects of stress-stiffening on human mesenchymal stem cells (hMSCs) in a three-dimensional setting by changing the length of the ethylene glycol portion of the polymer.After making their synthetic polymers, they were functionalized with known stem cell adhesives. Analysis of the polymers showed that all of the polymers were soft and exhibited similar stiffness with critical stress measurements falling within a biologically relevant range. Additionally, critical stress was found to increase linearly as a function of polymer chain length. Das, et al. then used their hydrogel polymers to investigate how stress-stiffening affected hMSC differentiation. Cells were cultured in a 3D matrix of the hydrogel surrounding the hMSCs. Markers for differentiation appeared after 96 hours. The cultures were tested for markers for osteogenesis and adipogenesis. Das, et al. found that cells cultured in the gel with the lowest critical stress demonstrated adipogenesis, while cells cultured in higher critical stress progressively favored osteogenesis over adipogenesis. Additional studies using RGD-modified polymers in the presence of antibodies showed that ligand interactions played an important role in mediating how stress-stiffening informs differentiation.Das, et al. suspected that microtubule dynamics likely plays a role in stem cell fate based on the results of treating their cells with cytochalasin D, actin polymerization inhibitor, and Taxol, a microtubule stabilizing agent. They decided to investigate how exactly microtubule dynamics is at work in this system by looking at the role of DCAMKL1 and RUNX2 in stress-stiffening and hMSC cell fate. DCAMKL1 is a known microtubule-associated protein and represses RUNX2. RUNX2 is an early osteogenesis marker. They found that DCAMKL1 expression was lowest in the longest polymers, those with highest critical stress, and its expression increased in gels with lower critical stress. Additionally, RUNX2 expression was not observed in low critical stress polymers, but was in the higher ones. Analysis confirmed a switch-like relationship between DCAMKL1 and RUNX2 and correlates to hMSCs’ preference for osteogenesis in the presence of higher stress-stiffening. The authors report that this is the first time DCAMKL1, a microtubule-associated protein, has been shown to be involved in stress-stiffening-mediated mechanotransduction pathway and demonstrates how microtubule dynamics is involved in hMSC cell fate.This study provides a new three-dimensional hydrogel for investigating stress-stiffening, and using this new hydrogel, Das, et al. were able to identify a new mechanotransduction pathway that controls hMSC differentiation that is distinctly different from two-dimensional systems. (Phys.org)—Several properties of the extracellular matrix affect cellular interaction, including stem cell differentiation. Some of these are physical properties, such as topography and matrix stiffness. In an effort to investigate these physical properties, Rajat K. Das, Veronika Gocheva, Roel Hammink, Omar F. Zouani, and Alan E. Rowan from Radbound University in The Netherlands, and the company Histide in Switzerland designed a model 3D hydrogel polymer system that demonstrates how stress-stiffening in the extracellular matrix causes human mesenchymal stem cells to favor osteogenesis over adipogenesis. Using their new model system, they determined that the expression of DCAMKL1, a microtubule associated protein, is decreasing when stress-stiffness is higher, demonstrating a novel pathway in which microtubule dynamics affects cell fate. Their work appears in Nature Materials. Growing bone cells: New method allows for more control in the differentiation of stem cells into bone cells More information: Rajat K. Das et al. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels, Nature Materials (2015). DOI: 10.1038/nmat4483AbstractBulk matrix stiffness has emerged as a key mechanical cue in stem cell differentiation. Here, we show that the commitment and differentiation of human mesenchymal stem cells encapsulated in physiologically soft (~0.2–0.4 kPa), fully synthetic polyisocyanopeptide-based three-dimensional (3D) matrices that mimic the stiffness of adult stem cell niches and show biopolymer-like stress stiffening, can be readily switched from adipogenesis to osteogenesis by changing only the onset of stress stiffening. This mechanical behaviour can be tuned by simply altering the material’s polymer length whilst maintaining stiffness and ligand density. Our findings introduce stress stiffening as an important parameter that governs stem cell fate in a 3D microenvironment, and reveal a correlation between the onset of stiffening and the expression of the microtubule-associated protein DCAMKL1, thus implicating DCAMKL1 in a stress-stiffening-mediated, mechanotransduction pathway that involves microtubule dynamics in stem cell osteogenesis. © 2015 Phys.org Citation: New hydrogel gives clues to mechanism behind stress-stiffening-mediated mesenchymal stem cell fate (2015, December 17) retrieved 18 August 2019 from https://phys.org/news/2015-12-hydrogel-clues-mechanism-stress-stiffening-mediated-mesenchymal.html Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
December 1, 2014 Free Webinar | Sept. 9: The Entrepreneur’s Playbook for Going Global Growing a business sometimes requires thinking outside the box. Web design is a tricky subject.People have different opinions about what constitutes good web design and what doesn’t.Some people think your site needs to be super sleek with an up-to-date, modern design in order to get attention. Others believe that web design doesn’t really matter all that much and you just need a site that works and lets people do what they want, like Craigslist.Both answers are right depending on which industry or business you’re talking about. But, how do you figure out what’s right for you? And, how can you make sure you’re web designer knows what they’re talking about and won’t make mistakes?This post presents seven deadly web design sins you don’t want to make on your site. The good news is that they’re all simple principles every website should follow. So, whether you get a slick design or not, you still need to know about these design principles and how they apply to your site.Also, you can use these principles to make sure your web designer knows what they’re doing. Just because someone is a good designer doesn’t mean they know how to design for the web. And, just because someone designs websites doesn’t mean they know how to design a site that will convert. Pay close attention to the principles presented in this post, and use them if necessary to make sure your designer designs a site that’s optimized to get the results you need.Mistake #1: Fonts That Are Too SmallThe first mistake people make is creating a site with fonts that are too small.The reason for this is that, back in the day, most websites had small fonts. The standard was somewhere around 12 px, and nearly everyone followed that standard.But, over time, people started to realize that 12 px fonts are hard to read online. When a screen is 24 inches from someone’s face, small fonts make it difficult to read.People also started to realize that you have only a limited amount of time to get visitors’ attention and let them know they’re in the right place. One study even states that the average attention span in 2013 was 8 seconds, one second less than the average attention span of a goldfish. The same study also states that people read only 28% of the words on an average web page.A 2013 study found the average attention span of people is 8 seconds, one second less than that of a goldfish. Is that even possible? Flickr: photographer23, Creative Commons licenseIn order to get people’s attention right away, you need to do the following:Compose great headlines that grab readers’ attention.Write interesting content that will get them to read more than 28% of what you’ve writtenUse headline fonts that are big enough to demand attentionMake sure body fonts are large enough to read so readers don’t give up because they’re tired of squinting.For all the reasons mentioned above, font sizes have increased over the last few years to the point that many view 14 px as the very minimum font size, and many sites go even bigger with 18 px as a minimum, especially when a lot of reading is involved.Here are some examples of exceptional web design with great font sizes:KISSmetricsHeadline: 35 pxFooter: 15 pxVeroHeadline: 41 pxBody: 18 pxHelp Scout BlogIntro text: 26 pxBody: 19 pxThe point to keep in mind is that the purpose of writing copy is to get it read. When you pay a writer good money or painstakingly write website copy yourself, you want to make sure it gets read and doesn’t get hidden by a small font that makes the copy difficult to read.You also need to remember that not all fonts are the same size. A 16 px Arial font can be smaller than a 16 px version of another font. This is something you need to be aware of when choosing a font size, so you don’t arbitrarily pick 19 px because another site did, only to find out your 19 px version isn’t as big.Keep in mind that footer fonts can be on the smaller side and so can subtext, but if you’ve written something you want people to read, consider using a 16 px font at a minimum. And, in case you don’t want to take my word for it, Smashing Magazine preaches the same thing in this article: 16 Pixels for Body Copy. Anything Less Is a Costly Mistake.Pro Tip: In order to get a feel for the size font you’d like to use, based on websites you like, download the WhatFont extension for Google Chrome. It’s a Chrome plugin that makes it really easy to click on fonts in order to find out what font type and size a website is using.Mistake #2: Moving SlidersI still don’t understand why so many websites use moving sliders.Are they effective? Do they convert? Are they the best way to present your information to customers?In most cases, they are not.Peep Laja wrote an article for ConversionXL titled Don’t Use Automatic Image Carousels or Sliders, Ignore the Fad. In the article he quotes Chris Goward of WiderFunnel and Tim Ash of SiteTuners as saying the following:We have tested rotating offers many times and have found it to be a poor way of presenting home page content.-Chris GowardAnd…Rotating banners are absolutely evil and should be removed immediately.-Tim AshLaja also mentions two studies where rotating sliders were proven to be ineffective:The first was by usability guru Jakob Nielsen. He asked a visitor if Siemens had any special offers for washing machines on their site. In fact, they did have an offer in 98-point font that said customers could get cash back on a new appliance. Unfortunately, the user didn’t see the offer because it was cloaked in a moving slider and ended up being completely missed.This points to a theory among conversion experts that sliders cause banner blindness similar to ads in a sidebar. People are used to lame ads in a sidebar, so they have a tendency to ignore them. This principle seems to apply to rotating sliders as well.The second study was from the University of Notre Dame. They found that only around 1% of visitors clicked on the slider, with 84% of the clicks on the item in the first position.What’s the point of having a website slider if only 1% of people click on the item that is taking up your most valuable homepage real estate, especially when 84% of those clicks are on the first item anyway? Why annoy people with something moving that’s difficult to keep track of? Why not give them a single option to choose from since the majority click the first item anyway?So, why do so many people use sliders since they appear to be so ineffective?The best theory I can come up with is that it seems like a cool and high-tech feature, and it’s easy for web developers to implement. Based on those two factors, business owners say, “Hey, I want one of those fancy moving slider things,” and web designers comply because they look “cool” and aren’t that hard to do.But website owners need to consider whether they’ll be effective and whether they’re the best way to convey information on their site, something Peep Laja, Chris Goward, Tim Ash, and many other smart internet marketing folks no longer believe is the case.To solve this problem, start by asking yourself what is the best way to present your information instead of picking a site you like and copying their design, including the cool-looking slider they use on the homepage.I used this approach with a friend of mine a few years ago for a website he was building for his tutoring company – Genesis Tutoring.He and his business partner approached me and said, “Hey we want to build a website…and we want to have a slider on the homepage that has this information,” and then he showed me a flyer they hand out at schools to advertise their service. The flyer was beautiful, presented the information incredibly well, and, surprise, surprise, didn’t include a slider (those pesky sliders just don’t seem to translate well into the world of printed flyers).So, I suggested, “Why don’t you just duplicate your brochure that’s already working on your homepage and then put a contact button along with your phone number and email underneath.” We tried that, and here’s how it turned out…The site ended up looking great, avoided the dreaded default slider, and converts well. What’s not to like?When it comes to building your own site, follow these instructions to get the same results:Remember not to blindly add a slider just because everyone else is doing it (even if your designer recommends one).Consider what is the best way to present your information on your homepage instead of just blindly copying what your competitors are doing.Choose a single important offer to list in the A-Space on your homepage and go with that. There will always be other things you want to promote, but you can do that farther down on the page or with a button at the top of the page. Pick one offer, make it prominent, and then get out of the way and let your website go to work.And to really hammer down the last point: think about the #1 goal you want your website to do. Focus on that and can all the other calls-to-actions.Again, in case you don’t want to take my word on this, here are some articles you can read that support this point:Rotating Banners? Just Say No!Rotating Offers – The Scourge of Homepage DesignMistake #3: Low Contrast FontsAnother huge mistake people make is using low contrast fonts.Low contrast means a lighter font on a light background or a darker font on a dark background. I’m not sure if this is something that looks ok in print design, but it’s never a good idea on the web.You always want to make sure your website content is as easy to read as possible. The Smashing Magazine article referenced above told us that the amount of light that gets through our eyes at age 40 is only half the amount of light that gets through our eyes at age 20. This drops to 20% by age 60. On top of that, nearly 9% of Americans are visually impaired.With these stats in mind, do you really want to make it harder for visitors to read your content, especially after you’ve paid so much and worked so hard to get them to your site in the first place?Low contrast for fonts is always a bad idea.You can solve this by always using high contrast fonts. If the background is dark, the font should be light, and if the background is light, the font should be dark.Actually, I’ll take this even one step further. Rarely are there times when you need to use any font colors besides black or white. Sometimes designers choose a lighter gray font on a white background or a light blue font on a dark blue background.Why? Is that really easier to read, or are you just trying to add “visual appeal”? Books use black fonts on a white background for a reason – it’s easy to read. Websites would do well to follow this example.Here are some samples of great font contrast:Help Scout BlogEvernoteThis is an example of good contrast on an image, which is not easy to do.Harry’sThe lesson to remember is that fonts should always have a high contrast with the background behind them. If you find the text difficult to read and feel like there should be more contrast, don’t hesitate to call your designer and let them know. Your website isn’t a design showcase. It’s a place to make sales and increase conversions.Bonus Tip: Not only is high contrast important, but you also want to use reverse type sparingly. (Reverse type is white text on a black (or color) background instead of black text on a white background.)In fact, David Ogilvy, one of the greatest ad men of all time, said ads should never be set in reverse type. Colin Wheildon, editor of the largest Australian motoring publication, set out to test this theory. His findings were astounding.According to the study, below is a list of the comprehension level for different colors and backgrounds:Black text on white: 70% good, 19% fair, 11% poorWhite text on black: 0% good, 12% fair, 88% poorWhite text on purple: 2% good, 16% fair, 82% poorWhite text on royal blue: 0% good, 4% fair, 96% poorIsn’t that incredible? The results from black text on a white background compared with white text on a color background are nearly the exact opposite!The takeaways are:Always remember to use high contrast fonts, but also…Use reverse type sparingly.Sometimes reverse type looks good, but it can have a drastic impact on readability and retention. As such, you should use it only for parts of your site that don’t require as much reading and aren’t as important. Overall, you’d be smart to think twice before using reverse type.This reverse type looks “cool” on HubSpot’s homepage, but it may not be the best for readability and comprehension, especially in the most important space on the entire site.Mistake #4: Poor Line Height for TextLine height for text is something that often gets overlooked. A lot of web designers and developers choose a font, pick a size, arbitrarily select a line height, and then call it a day.But line height has a surprisingly significant impact on a site’s overall design and appeal. Choosing the wrong line height can leave fonts looking crowded. It can ruin your entire design.The good news is that talented web designers have a good eye for this and will automatically select a good height for you. The bad news is that the average web developer doesn’t have an eye for this design and will often pick the wrong line height.Chris Pearson of DIYThemes felt so strongly about this that he built a line height calculator configured to something known as the golden ratio. Here’s Google’s definition of the golden ratio:A more simple definition is that the golden ratio is a proportion that’s believed to be aesthetically pleasing. Without boring you with more detail, Chris Pearson used this ratio to build a calculator that combines font size and content width to come up with the ideal line height. The good news is that the calculator makes this super easy to do. You simply plug in your font size and content width, and the calculator will tell you what your line height should be.You may not have realized it, but there’s a reason some designs and font combinations are more pleasing than others. Great designers know how to achieve the golden ratio on their own, but Chris Pearson’s calculator makes it easy for everyone else to do the same.Mistake #5: Line Length That’s Too LongAnother mistake you can make is creating lines of text that are too long.So, what’s the optimum line length?The Baymard Institute published an article that says 50 to 60 characters per line is best, with up to 75 characters being acceptable.The reason line length is so important is because long lines of text are intimidating to read online. If the line length is too long, some people will not begin reading because it doesn’t look like a very good reading experience.On the other hand, if line length is too short, readers have to start and stop lines frequently, which becomes annoying.This problem is compounded by the popularity of responsive design. If you don’t set a maximum width for content section, you have no way of knowing how long the line length will be for your blog or any other piece of text since screen sizes vary so much.At the time the referenced article was written, The Baymard Institute dealt with this problem by setting a maximum width for their text of 516 pixels which leaves an average of 65 characters per line at a font size of 18 px. This creates a great reading experience, as you can see in the image below.Once again, this is a design detail that not all designers are going to pay attention to, but now that you know long lines of text are intimidating to read, you can direct your designer and developer to make sure you deliver an optimal experience for readers.Mistake #6: No Accent Color for Calls to ActionThe next web design sin is not using an accent color. Here’s what I mean:Smart internet marketers know that you need a good accent color to draw attention to key calls to action. If you’re asking someone to “Buy Now” or “Start a Free Trial,” you want to make sure you use a button color that will draw people’s attention so they’ll click and take the action you want them to take.This seems simple enough, but I’ve seen multiple occasions where designers didn’t reserve an accent color for the most important calls to action. Instead, they chose a color that’s already used on the site for something else. That’s not a good idea.Here are some rules of thumb to follow for accent colors:It needs to be bright enough to draw attention to whatever you’re attempting to draw attention to.It needs to be complementary with the other colors on your website so that it doesn’t clash.It needs to stand out from whatever background it’s on. This means that a blue button on a blue background probably isn’t a good idea.It needs to be reserved for key calls to action so it doesn’t blend in by getting overused on the site.In the example below, you’ll notice that the CTA button is bright orange. This helps it stand out from the white background. Also, orange is not used anywhere else in the design (except for a splash in the logo which is small enough that it doesn’t compete for attention). You can check out the full page here if you’d like.Mistake #7: Common Design Principle ViolationsThe final deadly mistake is not following common design principles, which is something that Steve Krug talks about in his book Don’t Make Me Think.The point he makes is that website visitors are used to being able to find certain features in certain places. For example, they’re used to finding logos and taglines in the top left of a page, and menus in the top right. They’re also used to being able to find an About page and a Contact page if they want to learn more about the organization or get in touch.This means it’s a good idea to include those features on your site and that you should think twice before breaking common design principles. This may be something you think is obvious, but it’s not always.Some website owners, for example, decide to be super creative and come up with a different way to display the menu. Instead of being at the top where it’s normally found, it’s included in the branches of a tree that’s built into the background design (or some other creative way to include a menu other than the standard way).Sometimes these crazy new approaches work, but often they don’t. In most cases, it is much better to follow common design principles (so you don’t confuse visitors) than it is to come up with a crazy new layout that may be creative but not intuitive.ConclusionHopefully, you’ve learned a lot by reading about these seven deadly web design sins. Most of them seem to be common sense, but they all get broken more frequently than you would think.Remember, if you’re going to do any design changes at all, make sure you test your changes to see how they affect your bottom line! (hint: use KISSmetrics for this.)Now that you’re aware of these principles, pay attention to the websites you come across and see how many follow these rules. I’m confident you’ll start to realize how important these rules are, which will reinforce why they are important to follow.Over to you: Did I miss any deadly web design sins you frequently see committed online? Leave a comment to add to this list.About the Author: Joe Putnam (@josephputnam) is a Growth Manager for iSpionage, a PPC competitive intelligence tool that makes it easier for smart advertisers (and agencies) to set up profitable campaigns faster. Sign up today for a free iSpy competitor alert to get automatic updates about new PPC keywords, ad copy, and SEO terms for the website of your choice. Register Now » This story originally appeared on KISSmetrics 15+ min read
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