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Protein—fragment complex structures derived by NMR Molecular Replacement

RSC Med. Chem., 2020, Accepted Manuscript
DOI: 10.1039/D0MD00068J, Research Article
Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Felix Torres, Dhiman Ghosh, Dean Strotz, Celestine Chi, Ben Davis, Julien Orts
Recently we have established an NMR Molecular Replacement method, which is capable of solving the structure of the interaction site of protein-ligand complexes in a fully automated manner. While the...
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Inpatient PCI Volume and Transcatheter Aortic Valve Replacement or Mitral Valve Repair Outcomes

This cross-sectional study investigates whether hospital inpatient percutaneous coronary intervention volume is associated with rates of 30-day risk-adjusted mortality and hospital readmission after transcatheter aortic valve replacement and transcatheter mitral valve repair.




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CSS image replacement. One more time.

An accessible image replacement method using pseudo-elements and generated-content. This method works with images and/or CSS off, with semi-transparent images, doesn’t hide text from screen-readers or search engines, and provides fallback for IE 6 and IE 7.

Known support: Firefox 1.5+, Safari 3+, Chrome 3+, Opera 9+, IE 8+

What’s wrong with current methods?

The two most widely used image replacement techniques are the Gilder/Levin Method and the Phark Method. Both have different flaws.

The Gilder/Levin Method requires the addition of presentational HTML (an empty span) and doesn’t work with transparent images as the default text shows through. The Phark Method uses a negative text-indent to hide the text and so it is not visible when CSS is on and images are off.

Resurrecting the NIR method

Using pseudo-elements and generated-content as an image replacement technique isn’t a new idea. It was proposed and demonstrated by Paul Nash back in 2006. This is the Nash Image Replacement method.

<h1 class="nir">[content]</h1>
.nir {
   height: 100px; /* height of replacement image */
   padding: 0;
   margin: 0;
   overflow: hidden;
}

.nir:before {
   content: url(image.gif);
   display: block;
}

The height value is equal to that of the replacement image. Setting overflow:hidden ensures that the original content is not visible on screen when the image is loaded. The replacement image is inserted as generated content in the :before pseudo-element which is set to behave like a block element in order to push the element’s original content down.

What about IE 6 and IE 7?

Neither browser supports :before; if you need to support them you’ll have to rely on the Phark method. This can be done using conditional comments or safe IE6/7 hacks to serve alternative styles to legacy versions of IE .

<!--[if lte IE 7]>
<style>
.nir {
   height: 100px;
   padding: 0;
   margin: 0;
   overflow: hidden;
   text-indent: -9000px;
   background: url(image.gif) no-repeat 0 0;
}
</style>
<![endif]-->

Using the NIR method allows you to keep your HTML semantic and deliver improved accessibility to users of modern browsers. The Phark Method can then be served to IE 6 and IE 7.

Improving the NIR method

The first problem with NIR is that if images are disabled all browsers leave whitespace above the element’s content. Opera 10.5 even displays the text string “image”! If the height of the element is small enough this whitespace causes the element’s content to overflow and be partially or completely hidden when images are disabled.

Another consideration is what happens if an image doesn’t exist or fails to load. Safari and Chrome will display a “missing image” icon that cannot be removed. Once again, this can cause the element’s content to overflow and become partially or completely hidden to users.

A more robust version of the NIR method is the following modification:

.nir {
   height: 100px; /* height of replacement image */
   width: 400px; /* width of replacement image */
   padding: 0;
   margin: 0;
   overflow: hidden;
}

.nir:before {
   content: url(image.gif);
   display: inline-block;
   font-size: 0;
   line-height: 0;
}

Setting font-size and line-height to 0 avoids the whitespace problems in all browsers. Setting the element’s width equal to that of the replacement image and getting the pseudo-element to act as an inline-block helps minimise the problems in webkit browsers should an image fail to load.

Ideally browsers would avoid displaying anything in a pseudo-element when its generated-content image fails to load. If that were the case, the original NIR method would be all that is needed.

What about using sprites?

One of the most common uses of image replacement is for navigation. This often involves using a large sprite with :hover and :active states as a background image. It turns out that using sprites is not a problem for modern browsers. When using the modified-NIR method the sprite is included as a generated-content image that is positioned using negative margins.

This is an example that rebuilds the right-hand category navigation from Web Designer Wall using a sprite and the modified-NIR method.

<ul id="nav">
  <li id="nav-item-1"><a href="#non">Tutorials</a></li>
  <li id="nav-item-2"><a href="#non">Trends</a></li>
  <li id="nav-item-3"><a href="#non">General</a></li>
</ul>
/* modified-NIR */

#nav a {
  display: block;
  width: 225px;
  height: 46px;
  overflow: hidden;
}

#nav a:before {
   content:url(sprite.png);
   display:-moz-inline-box; /* for Firefox 1.5 & 2 */
   display:inline-block;
   font-size:0;
   line-height:0;
}

/* repositioning the sprite */

#nav-item-1 a:hover:before,
#nav-item-1 a:focus:before,
#nav-item-1 a:active:before {margin:-46px 0 0;}

#nav-item-2 a:before        {margin:-92px 0 0;}
#nav-item-2 a:hover:before,
#nav-item-2 a:focus:before,
#nav-item-2 a:active:before {margin:-138px 0 0;}

#nav-item-3 a:before        {margin:-184px 0 0;}
#nav-item-3 a:hover:before,
#nav-item-3 a:focus:before,
#nav-item-3 a:active:before {margin:-230px 0 0;}

/* :hover hack for IE8 if no a:hover styles declared */
#nav a:hover {cursor:pointer;}

For some reason IE8 refuses to reposition the image when the mouse is over the link unless a style is declared for a:hover. In most cases you will have declared a:hover styles for the basic links on your webpage, and this is enough. But it is worth being aware of this IE8 behaviour.

The addition of display:-moz-inline-box; is required to reposition the sprite in versions of Firefox prior to Firefox 3.0. They are very rare browsers but I’ve included it in case that level of legacy support is needed.

If you want image replacement in IE 6 and IE 7 the following additional styles can be served to those browsers using conditional comments.

/* Phark IR method */

#nav a {
   text-indent: -9000px;
   background: url(sprite.png) no-repeat;
}

/* repositioning the sprite */

#nav-item-1 a:hover,
#nav-item-1 a:active { background-position: 0 -46px; }

#nav-item-2 a        { background-position: 0 -92px; }
#nav-item-2 a:hover,
#nav-item-2 a:hover  { background-position: 0 -138px; }

#nav-item-3 a        { background-position: 0 -184px; }
#nav-item-3 a:hover,
#nav-item-3 a:active { background-position: 0 -230px; }

/* hack for IE6 */
#nav a:hover { margin: 0; }

The changes are fairly simple. But IE 6 applies the margins declared for a:hover:before to a:hover and so they need to be reset in the styles served to IE 6.

See the modified-NIR (using sprites) demo.




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Another CSS image replacement technique

A new image replacement technique was recently added to the HTML5 Boilerplate project. This post explains how it works and how it compares to alternative image replacement techniques.

[15 December 2012] This technique is no longer used in HTML5 Boilerplate. It’s been replaced by another, more reliable approach.

Here’s the CSS behind the recent update to the image replacement helper class in HTML5 Boilerplate. It has also made its way into the Compass framework.

.ir {
  font: 0/0 a;
  text-shadow: none;
  color: transparent;
}

What does each declaration do?

  • font:0/0 a – a shorthand property that zeros out the font size and line-height. The a value acts as a very short font-family (an idea taken from the BEM implementation of this method). The CSS validator complains that using 0/0 in the shorthand font property is not valid, but every browser accepts it and this appears to be an error in the validator. Using font:0px/0 a passes validation but it displayed as font:0/0 a in the code that the validator flags as valid.
  • text-shadow:none – makes sure that any inherited text shadow is removed for the text. This prevents the chance of any text shadow colors showing over the background.
  • color:transparent – needed for browsers than don’t completely crush the text to the point of being invisible. Safari 4 (extremely rare) is an example of such a browser. There may also be mobile browsers than require this declaration. IE6/7/8 don’t recognise this value for color, but fortunately IE7/8 don’t show any trace of the text. IE6 shows a faint trace.

In the HTML5 Boilerplate image replacement helper, we’ve also removed any border and background-color that may be on the element. This makes it easier to use the helper class on elements like button or with links that may included background or border properties as part of a design decision.

Benefits over text-indent methods

The new technique avoids various problems with any text-indent method, including the one proposed by Scott Kellum to avoid iPad 1 performance problems related to large negative text indents.

  • Works in IE6/7 on inline-block elements. Techniques based on text indentation are basically “broken”, as shown by this test case: http://jsfiddle.net/necolas/QZvYa/show/
  • Doesn’t result in any offscreen box being created. The text-indent methods result in a box being drawn (sometimes offscreen) for any text that have been negatively or positively indented. It can sometimes cause performance problems but the font-based method sidesteps those concerns.
  • No need to specify a text-alignment and hide the overflow since the text is crushed to take up no space.
  • No need to hide br or make all fallback HTML display:inline to get around the constraints of using a text indentation. This method is not affected by those problems.
  • Fewer styles are needed as a result of these improvements.

Drawbacks

No image replacement hack is perfect.

  • Leaves a very small trace of the text in IE6.
  • This approach means that you cannot use em units for margins on elements that make use of this image replacement code. This is because the font size is set to 0.
  • Windows-Eyes has a bug that prevents the reading of text hidden using this method. There are no problems with all other screenreaders that have been tested. Thanks to @jkiss for providing these detailed results and to @wilto for confirming this technique works for JAWS 12 in IE 6/7/8 and Firefox 4/5/6.
  • Like so many IR methods, it doesn’t work when CSS is loaded but images are not.
  • Text may not be hidden if a visitor is using a user style sheet which has explicitly set important font-size declarations for the element type on which you have applied the IR class.

It’s worth noting that the NIR image replacement technique avoids these drawbacks, but lacks support in IE6/7.

Closing comments

I’ve been using this technique without significant problems for nearly a year, ever since Jonathan Neal and I used it in a clearfix experiment. The BEM framework also makes use of it for their icon components. The core idea was even proposed back in 2003 but the browser quirks of the day may have prevented wider use.

If you come across any problems with this technique, please report them at the HTML5 Boilerplate GitHub issue tracker and include a test case when appropriate.

Translations






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