Rapid CSS 2004 v5.23 serial key or number

Rapid CSS 2004 v5.23 serial key or number

Rapid CSS 2004 v5.23 serial key or number

Rapid CSS 2004 v5.23 serial key or number

of a document. The main content area consists of content that is directly related to or expands upon the central topic of a document, or the central functionality of an application.">Element/main

Support in all current engines.

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Categories:
Flow content.
Palpable content.
Contexts in which this element can be used:
Where flow content is expected, but only if it is a hierarchically correct element.
Content model:
Flow content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents the dominant contents of the document.

A document must not have more than one element that does not have the attribute specified.

A is one whose ancestor elements are limited to , , , without an accessible name, and autonomous custom elements. Each element must be a hierarchically correct element.

In this example, the author has used a presentation where each component of the page is rendered in a box. To wrap the main content of the page (as opposed to the header, the footer, the navigation bar, and a sidebar), the element is used.

In the following example, multiple elements are used and script is used to make navigation work without a server roundtrip and to set the attribute on those that are not current:

The element

Element/div

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HTMLDivElement

Support in all current engines.

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Categories:
Flow content.
Palpable content.
Contexts in which this element can be used:
Where flow content is expected.
As a child of a element.
Content model:
If the element is a child of a element: one or more elements followed by one or more elements, optionally intermixed with script-supporting elements.
If the element is not a child of a element: flow content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:

The element has no special meaning at all. It represents its children. It can be used with the , , and attributes to mark up semantics common to a group of consecutive elements. It can also be used in a element, wrapping groups of and elements.

Authors are strongly encouraged to view the element as an element of last resort, for when no other element is suitable. Use of more appropriate elements instead of the element leads to better accessibility for readers and easier maintainability for authors.

For example, a blog post would be marked up using , a chapter using , a page's navigation aids using , and a group of form controls using .

On the other hand, elements can be useful for stylistic purposes or to wrap multiple paragraphs within a section that are all to be annotated in a similar way. In the following example, we see elements used as a way to set the language of two paragraphs at once, instead of setting the language on the two paragraph elements separately:

Text-level semantics

The element

Element/a

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HTMLAnchorElement

Support in all current engines.

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Categories:
Flow content.
Phrasing content.
If the element has an attribute: Interactive content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Transparent, but there must be no interactive content descendant, element descendant, or descendant with the attribute specified.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
— Address of the hyperlink
— Browsing context for hyperlinknavigation
— Whether to download the resource instead of navigating to it, and its file name if so
— URLs to ping
— Relationship between the location in the document containing the hyperlink and the destination resource
— Language of the linked resource
— Hint for the type of the referenced resource
— Referrer policy for fetches initiated by the element
Accessibility considerations:
If the element has an attribute: for authors; for implementers.
Otherwise: for authors; for implementers.
DOM interface:

If the element has an attribute, then it represents a hyperlink (a hypertext anchor) labeled by its contents.

If the element has no attribute, then the element represents a placeholder for where a link might otherwise have been placed, if it had been relevant, consisting of just the element's contents.

The , , , , , , and attributes must be omitted if the attribute is not present.

If the attribute is specified on an element, then the attribute must also be specified.

If a site uses a consistent navigation toolbar on every page, then the link that would normally link to the page itself could be marked up using an element:

The , , , , and attributes affect what happens when users follow hyperlinks or download hyperlinks created using the element. The , , and attributes may be used to indicate to the user the likely nature of the target resource before the user follows the link.

The activation behavior of elements that create hyperlinks is to run the following steps:

  1. If the target of the event is an element with an attribute specified, then server-side image map processing must be performed, as follows:

    1. Let and be zero.
    2. If the event was a real pointing-device-triggered event on the element, then set to the distance in CSS pixels from the left edge of the image to the location of the click, and set to the distance in CSS pixels from the top edge of the image to the location of the click.
    3. If is negative, set to zero.
    4. If is negative, set to zero.
    5. Let be a U+F QUESTION MARK character, the value of expressed as a base-ten integer using ASCII digits, a U+C COMMA character (,), and the value of expressed as a base-ten integer using ASCII digits.
  2. Follow the hyperlink or download the hyperlink created by the element, as determined by the attribute and any expressed user preference, passing , if the steps above defined it.

.

Same as .

HTMLAnchorElement/rel

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The IDL attributes , , , , , and , must reflect the respective content attributes of the same name.

HTMLAnchorElement/relList

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cipsas.com table

The IDL attribute must reflect the content attribute.

The IDL attribute must reflect the content attribute, limited to only known values.

The attribute's getter must return this element's descendant text content.

The attribute's setter must string replace all with the given value within this element.

The element can be wrapped around entire paragraphs, lists, tables, and so forth, even entire sections, so long as there is no interactive content within (e.g., buttons or other links). This example shows how this can be used to make an entire advertising block into a link:

The following example shows how a bit of script can be used to effectively make an entire row in a job listing table a hyperlink:

The element

Element/em

Support in all current engines.

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Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents stress emphasis of its contents.

The level of stress that a particular piece of content has is given by its number of ancestor elements.

The placement of stress emphasis changes the meaning of the sentence. The element thus forms an integral part of the content. The precise way in which stress is used in this way depends on the language.

These examples show how changing the stress emphasis changes the meaning. First, a general statement of fact, with no stress:

By emphasizing the first word, the statement implies that the kind of animal under discussion is in question (maybe someone is asserting that dogs are cute):

Moving the stress to the verb, one highlights that the truth of the entire sentence is in question (maybe someone is saying cats are not cute):

By moving it to the adjective, the exact nature of the cats is reasserted (maybe someone suggested cats were mean animals):

Similarly, if someone asserted that cats were vegetables, someone correcting this might emphasize the last word:

By emphasizing the entire sentence, it becomes clear that the speaker is fighting hard to get the point across. This kind of stress emphasis also typically affects the punctuation, hence the exclamation mark here.

Anger mixed with emphasizing the cuteness could lead to markup such as:

The element isn't a generic "italics" element. Sometimes, text is intended to stand out from the rest of the paragraph, as if it was in a different mood or voice. For this, the element is more appropriate.

The element also isn't intended to convey importance; for that purpose, the element is more appropriate.

The element

Element/strong

Support in all current engines.

Firefox1+SafariYesChrome1+
OperaYesEdge79+
Edge (Legacy)12+Internet ExplorerYes
Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents strong importance, seriousness, or urgency for its contents.

Importance: the element can be used in a heading, caption, or paragraph to distinguish the part that really matters from other parts that might be more detailed, more jovial, or merely boilerplate. (This is distinct from marking up subheadings, for which the element is appropriate.)

For example, the first word of the previous paragraph is marked up with to distinguish it from the more detailed text in the rest of the paragraph.

Seriousness: the element can be used to mark up a warning or caution notice.

Urgency: the element can be used to denote contents that the user needs to see sooner than other parts of the document.

The relative level of importance of a piece of content is given by its number of ancestor elements; each element increases the importance of its contents.

Changing the importance of a piece of text with the element does not change the meaning of the sentence.

Here, the word "chapter" and the actual chapter number are mere boilerplate, and the actual name of the chapter is marked up with :

In the following example, the name of the diagram in the caption is marked up with , to distinguish it from boilerplate text (before) and the description (after):

In this example, the heading is really "Flowers, Bees, and Honey", but the author has added a light-hearted addition to the heading. The element is thus used to mark up the first part to distinguish it from the latter part.

Here is an example of a warning notice in a game, with the various parts marked up according to how important they are:

In this example, the element is used to denote the part of the text that the user is intended to read first.

The element

Element/small

Support in all current engines.

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Edge (Legacy)12+Internet ExplorerYes
Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents side comments such as small print.

Small print typically features disclaimers, caveats, legal restrictions, or copyrights. Small print is also sometimes used for attribution, or for satisfying licensing requirements.

The element does not "de-emphasize" or lower the importance of text emphasized by the element or marked as important with the element. To mark text as not emphasized or important, simply do not mark it up with the or elements respectively.

The element should not be used for extended spans of text, such as multiple paragraphs, lists, or sections of text. It is only intended for short runs of text. The text of a page listing terms of use, for instance, would not be a suitable candidate for the element: in such a case, the text is not a side comment, it is the main content of the page.

The element must not be used for subheadings; for that purpose, use the element.

In this example, the element is used to indicate that value-added tax is not included in a price of a hotel room:

In this second example, the element is used for a side comment in an article.

This is distinct from a sidebar, which might be multiple paragraphs long and is removed from the main flow of text. In the following example, we see a sidebar from the same article. This sidebar also has small print, indicating the source of the information in the sidebar.

In this last example, the element is marked as being important small print.

The element

Element/s

Support in all current engines.

Firefox1+SafariYesChromeYes
OperaYesEdgeYes
Edge (Legacy)12+Internet ExplorerYes
Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents contents that are no longer accurate or no longer relevant.

The element is not appropriate when indicating document edits; to mark a span of text as having been removed from a document, use the element.

In this example a recommended retail price has been marked as no longer relevant as the product in question has a new sale price.

The element

Element/cite

Support in all current engines.

Firefox1+SafariYesChromeYes
OperaYesEdgeYes
Edge (Legacy)12+Internet ExplorerYes
Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents the title of a work (e.g. a book, a paper, an essay, a poem, a score, a song, a script, a film, a TV show, a game, a sculpture, a painting, a theatre production, a play, an opera, a musical, an exhibition, a legal case report, a computer program, etc). This can be a work that is being quoted or referenced in detail (i.e. a citation), or it can just be a work that is mentioned in passing.

A person's name is not the title of a work — even if people call that person a piece of work — and the element must therefore not be used to mark up people's names. (In some cases, the element might be appropriate for names; e.g. in a gossip article where the names of famous people are keywords rendered with a different style to draw attention to them. In other cases, if an element is really needed, the element can be used.)

This next example shows a typical use of the element:

This is correct usage:

The following, however, is incorrect usage, as the element here is containing far more than the title of the work:

The element is obviously a key part of any citation in a bibliography, but it is only used to mark the title:

A citation is not a quote (for which the element is appropriate).

This is incorrect usage, because is not for quotes:

This is also incorrect usage, because a person is not a work:

The correct usage does not use a element:

As mentioned above, the element might be relevant for marking names as being keywords in certain kinds of documents:

The element

Element/q

Support in all current engines.

Firefox1+SafariYesChromeYes
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Edge (Legacy)12+Internet ExplorerYes
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Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
— Link to the source of the quotation or more information about the edit
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents some phrasing content quoted from another source.

Quotation punctuation (such as quotation marks) that is quoting the contents of the element must not appear immediately before, after, or inside elements; they will be inserted into the rendering by the user agent.

Content inside a element must be quoted from another source, whose address, if it has one, may be cited in the attribute. The source may be fictional, as when quoting characters in a novel or screenplay.

If the attribute is present, it must be a valid URL potentially surrounded by spaces. To obtain the corresponding citation link, the value of the attribute must be parsed relative to the element's node document. User agents may allow users to follow such citation links, but they are primarily intended for private use (e.g., by server-side scripts collecting statistics about a site's use of quotations), not for readers.

The element must not be used in place of quotation marks that do not represent quotes; for example, it is inappropriate to use the element for marking up sarcastic statements.

The use of elements to mark up quotations is entirely optional; using explicit quotation punctuation without elements is just as correct.

Here is a simple example of the use of the element:

Here is an example with both an explicit citation link in the element, and an explicit citation outside:

In the following example, the quotation itself contains a quotation:

In the following example, quotation marks are used instead of the element:

In the following example, there is no quote — the quotation marks are used to name a word. Use of the element in this case would be inappropriate.

The element

Element/dfn

Support in all current engines.

Firefox1+SafariYesChromeYes
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Firefox Android4+Safari iOSYesChrome AndroidYesWebView AndroidYesSamsung InternetYesOpera AndroidYes
Categories:
Flow content.
Phrasing content.
Palpable content.
Contexts in which this element can be used:
Where phrasing content is expected.
Content model:
Phrasing content, but there must be no element descendants.
Tag omission in text/html:
Neither tag is omissible.
Content attributes:
Global attributes
Also, the attribute has special semantics on this element: Full term or expansion of abbreviation.
Accessibility considerations:
For authors.
For implementers.
DOM interface:
Uses .

The element represents the defining instance of a term. The paragraph, description list group, or section that is the nearest ancestor of the element must also contain the definition(s) for the term given by the element.

: if the element has a attribute, then the exact value of that attribute is the term being defined. Otherwise, if it contains exactly one element child node and no child nodes, and that child element is an element with a attribute, then the exact value of that attribute is the term being defined. Otherwise, it is the descendant text content of the element that gives the term being defined.

If the attribute of the element is present, then it must contain only the term being defined.

The

Источник: [cipsas.com]
, Rapid CSS 2004 v5.23 serial key or number

In situ serial crystallography for rapid de novo membrane protein structure determination

Abstract

De novo membrane protein structure determination is often limited by the availability of large crystals and the difficulties in obtaining accurate diffraction data for experimental phasing. Here we present a method that combines in situ serial crystallography with de novo phasing for fast, efficient membrane protein structure determination. The method enables systematic diffraction screening and rapid data collection from hundreds of microcrystals in in meso crystallization wells without the need for direct crystal harvesting. The requisite data quality for experimental phasing is achieved by accumulating diffraction signals from isomorphous crystals identified post-data collection. The method works in all experimental phasing scenarios and is particularly attractive with fragile, weakly diffracting microcrystals. The automated serial data collection approach can be readily adopted at most microfocus macromolecular crystallography beamlines.

Introduction

Membrane proteins perform essential roles in signal and energy transduction, metabolism, and transport and contribute to the structural integrity of cells. They account for close to a third of all cellular proteins and are important drug targets. High-resolution three-dimensional structural information is key to understanding how membrane protein work at a molecular level and can be used to inform structure-based drug design and discovery1,2. The vast majority of membrane protein structure work has been performed using macromolecular crystallography. Recent advances in cryogenic electron microscopy (cryo-EM) and de novo prediction methods will undoubtedly contribute to providing much-needed new structures3,4. However, many membrane proteins are still too small to be imaged at high resolution by cryo-EM and de novo prediction methods, as yet, do not provide atomic-level resolution. Macromolecular crystallography is limited too in that membrane protein crystals of high diffraction quality are difficult to generate. The lipid cubic phase (LCP) or in meso method of crystallization has made important contributions in this regard, in part, because proteins crystallize from within and into a native membrane-like environment5. In recent years, the in meso method accounts for close to 40% of all new unique membrane protein crystal structures (Supplementary Fig. 1).

Another challenge associated with membrane protein structure determination is that most new and interesting targets have novel structures with which the most common phasing method, molecular replacement, is rarely useful. In such cases, de novo structure determination by experimental phasing is required6. Of the published unique membrane protein structures as of May (cipsas.com), were solved by crystallography, of which 46% used experimental phasing with single-wavelength anomalous diffraction (SAD) the most popular de novo experimental phasing method (Supplementary Fig. 1). Experimental phasing comes with its own challenges. It requires highly accurate diffraction data, which are difficult to acquire especially when using small, fragile crystals of the type commonly encountered with membrane proteins. Heavy atom experimental phasing of membrane proteins with serial crystallography approaches has been demonstrated using crystals harvested with micro-meshes or standard loops7,8,9. But harvesting of the large numbers of crystals required for serial data collection is very time-consuming and particularly challenging for crystals grown in meso. This background serves to highlight the requirement for efficient and robust de novo phasing methods for use with membrane protein microcrystals.

Responding to this critical need, we introduce here a fully automated method for collecting, selecting, and merging data from hundreds to thousands of in meso-grown microcrystals. This approach boosts the collective phasing signal of many tiny crystals to a level where de novo phasing of highly challenging membrane protein targets becomes not only possible but also fast and high-throughput. We refer to it as the in meso in situ serial crystallography—experimental phasing (IMISX-EP) method. IMISX-EP has three components: (1) in meso crystallization (and in situ soaking where appropriate), (2) fast, automated grid scanning, and serial data collection in situ, and (3) real-time data processing and selection of data sets followed by structure solution (Fig. 1). IMISX-EP eliminates one of the major bottlenecks subsequent to in meso crystallization—direct crystal harvesting, and enables in situ diffraction data collection by combining in meso crystallization and in situ serial synchrotron crystallography10,11 at cryogenic temperatures. In addition, the method provides convenient and highly effective in situ soaking capabilities (Fig. 2). We demonstrate the utility of the method with four real-life integral membrane proteins using all major anomalous phasing methods, and show that IMISX-EP provides a fast, efficient, and a direct means for de novo structure determination of membrane protein as microcrystals.

Results

The first demonstration of IMISX-EP was carried out using the most popular experimental phasing method, SAD phasing, with the Se-Met labeled proteins, PepTSt and LspA. Instead of harvesting mesophase-containing individual or clusters of crystals from each well by the traditional loop-harvesting method, the entire IMISX well was removed from the plate, mounted on a pin and snap-cooled in liquid nitrogen (Methods, Supplementary Fig. 2). This enabled in situ X-ray diffraction data collection to be carried out subsequently on all crystals in the IMISX well. From two such wells, PepTSt crystals were measured, partial data sets were indexed and processed, and 89 were selected on the basis of diffraction intensity correlation coefficient (CCdataset) (Supplementary Fig. 3a, Table 1 and Table 2) for successful Se-SAD phasing with SHELXD/E12 (Fig. 3a, Table 2, Supplementary Figs. 4a, 5a). The second example of Se-SAD phasing proved to be a particularly challenging case study for serial crystallography because the target protein, LspA, was incompletely Se-Met labelled. The average Se-Met incorporation was estimated at 59% based on the refined Se anomalous scattering signal (Methods). In this instance, the high-throughput feature of the IMISX-EP method proved invaluable enabling diffraction data to be collected from LspA crystals in 32 IMISX wells (Table 1 and Table 2). The final data set derived from crystals (Supplementary Fig. 3b). The substructure was determined by SHELXD and an interpretable map was generated by CRANK213 (Fig. 3b, Table 2, Supplementary Figs. 4b, 5b).

When Se-Met labeling compromises expression and/or protein and crystal quality, traditional heavy atom derivatization is an alternative and proven approach for experimental phasing. The heavy atom can be introduced either by co-crystallizing it with the protein or by soaking it into the crystal. We demonstrated the IMISX-EP approach for both heavy atom derivatization methods with two membrane proteins, BacA and PgpB. Indeed, BacA is the first de novo structure solved by the IMISX-EP method14. BacA crystals were derivatized by in situ soaking with HgCl2 in IMISX wells directly (Fig. 2). These wells provide an ideal environment in which to optimize heavy atom concentration and soaking time. Further, labeling benefits from the sticky, viscous, and nanoporous nature of the mesophase in which the crystals are suspended during soaking and buffer exchange (Methods, Fig. 2). From the BacA crystals identified, two groups were created with which to evaluate two phasing methods (Supplementary Fig. 3c and 3d, Table 1 and Table 2). One contained , the other data sets. The first group was used successfully for SAD phasing with SHELXD and CRANK2 (Fig. 3c, Supplementary Figs. 4c, 5c). The smaller, second group was combined with a high-resolution native data set for phasing with single isomorphous replacement with anomalous scattering (SIRAS), and the structure was phased readily with SHELXD/E (Table 2, Supplementary Figs. 4d, 5d). This example illustrates convincingly how SIRAS with a relatively weak heavy atom data set can be combined with a higher resolution native data set for experimental phasing in serial crystallography.

IMISX-EP using heavy atom co-crystallization was demonstrated with BacA and PgpB. BacA, was labeled with HgCl2 in solution ahead of setting up trials in IMISX crystallization plates. Of the 66 crystals measured from two IMISX wells, 64 were indexed and integrated, and 55 were selected (Supplementary Fig. 3e, Table 1 and Table 2). Mercury sites were identified with SHELXD, and an interpretable map was obtained by employing 25 cycles of SHELXE density modification with autobuilding (Fig. 3d, Table 2, Supplementary Figs. 4e, 5e). PgpB was pre-incubated with Na2WO4 and subsequently crystallized in the cubic mesophase. The crystal used for data collection was relatively large and measured 10 × 50 ×  μm3. As the crystal had its flat face oriented approximately parallel to the windows of the well (Fig. 3e), it was possible to record ° of data using a rotation angle of ± 70° from this one crystal without compromising data quality at high-tilt angles (Supplementary Fig. 6). Because of the strong anomalous signal from tungsten and the high diffraction resolution, the structure was solved with the relatively low redundancy of and a completeness of 91% with SHELXD/E (Fig. 3e, Supplementary Figs. 4f, 5f). This example shows that the IMISX-EP approach can be used with large single crystals.

To demonstrate the full potential of IMISX-EP, the most-challenging experimental phasing method, native-SAD using the anomalous signal from light elements (Z ≤ 20) only, was attempted with unlabeled PepTSt crystals. The estimated Bijvoet ratio (ΔF/F) of sulfur (S)-PepTSt is ~ 1/ (1%) at 6 keV ( Å), which is approximately one-fourth that of Se-PepTSt at the Se absorption edge. Given the success of Se-SAD phasing using 89 Se-PepTSt crystals as described above, one expects that thousands of PepTSt microcrystals would be needed for native-SAD phasing. To expedite data collection on thousands of microcrystals, a high-throughput serial data collection protocol was implemented. It combined 50– Hz grid scanning of the entire 1–2 mm diameter LCP bolus with a micrometer-sized X-ray beam and automated data collection from each crystal identified on the basis of the grid scan (Methods, Supplementary Fig. 7). A total of 98,° of data were recorded from crystals in 59 IMISX wells using 27 h of beamtime. Of these, crystals were indexed and processed and the final data derived from crystals included 15,° of data (Supplementary Fig. 3f, g, Table 1 and Table 2). SHELXD located 13 of the 18 internal S sites in PepTSt and SHELXE produced an interpretable map (Fig. 3f, Table 2, Supplementary Figs. 4g, 5g).

Discussion

It is clear from the case studies presented that IMISX-EP is a powerful and generally applicable high-throughput method. It combines the advantages of conventional crystallography with those of serial crystallography7,8,9,10,11,15,16,17,18,19 and transforms traditional micro-crystallography20 to an in situ serial crystallography method that is considerably more efficient and that requires miniscule quantities of protein. Specifically, in the most-challenging native-SAD phasing example above, < 20 μg PepTSt was used. Not only does the method extend phasing to microcrystals while minimizing the detrimental effects of radiation damage, it also effectively reduces both random and systematic errors in diffraction data to such an extent that the weak anomalous signal from light elements can be extracted reliably. At first blush, serial crystallography may appear to differ dramatically from conventional crystallography. In fact, the two are similar in that both seek to accumulate sufficient diffraction signal; by exploiting the voluminous diffraction of a large single crystal in conventional crystallography and by combining the diffraction volume of many microcrystals in serial crystallography21,22. Therefore, IMISX-EP very effectively improves the success rate of the phasing experiment by simple signal accumulation using a highly efficient serial crystallography method. It represents a paradigm shift from the conventional, subjective selection of crystals based on appearance, ease of harvesting, available harvesting time, and storage space to an exhaustive measurement of all crystals to the limits of radiation damage from which accurate data can be gleaned based upon a carefully chosen subset of isomorphous crystals.

In this study, the experimental phasing examples used for purposes of demonstration ranged from simple and easy to perform to extremely challenging. The strength of the phasing signal, as estimated by the Bijvoet ratio, ranges from 1% in the case of native-SAD PepTSt to 7% for tungsten phasing of PgpB. The observable anomalous peak height, which determines the success of a SAD experiment, is proportional to the square root of the number of observed reflections23, which in turn is related directly to the diffraction resolution. Therefore, experimental phasing becomes considerably more difficult in going from working with the high-resolution data available for heavy atom-labeled W-PgpB to the mid-resolution data available for native S-PepTSt. This is clearly reflected in the total number of degrees of data used for successful phasing in six cases and is congruent with the results of comparable phasing studies in the literature, which include soluble proteins7,9,11,17 (Supplementary Fig. 8). The weaker the phasing signal, the more critical becomes the process of selecting out and combining isomorphous data sets. Different criteria and clustering methods have been tested and implemented recently24,25,26,27,28,29,30. For native-SAD PepTSt data that have a weak signal and a large number of data sets, an iterative procedure based on CCdataset proved most effective. It rejects non-isomorphous data sets, whilst retaining weak but isomorphous data sets, which contribute to providing the needed anomalous signal.

The IMISX method takes advantage of the intrinsic viscosity of the cubic mesophase in which crystals grow. Thus, the entire crystal-laden bolus is contained in a confined space within the IMISX well, which can be cryogenically cooled for safe storage and to extend crystal lifetime in the X-ray beam. Another advantage is the ease with which heavy atom and ligand-soaking experiments can be performed in true in situ fashion without ever touching the crystals, which remain suspended in the viscous mesophase. Wider use of this convenient soaking feature will greatly facilitate mechanistic studies and drug discovery with membrane protein targets.

IMISX-EP has wide ranging applicability. It can be used with all experimental phasing approaches for membrane protein structure determination extending from traditional heavy atom derivatization and Se-Met labeling to the more recent native-SAD6,21,31 and emerging methods that include iodo-detergent labeling32 and fast halide soaking9. IMISX-EP is compatible with different plate and sample holder types19,33,34,35 and can be performed at most modern synchrotron macromolecular crystallography beamlines. It is likely to prove important in the effective utilization of next generation synchrotron sources such as the Diffraction Limited Storage Ring36. Furthermore, it is anticipated that the entire IMISX well mounting, crystal-laden bolus centering, rastering, and serial data collection process will be carried out unattended once the initial data collection parameters are known. Taken together, IMISX-EP, and serial crystallography in general, will contribute to having membrane protein structures included in the protein structure knowledge base to a level that reflects the frequency with which they are found in the cell. Given the importance of membrane proteins as therapeutic targets, these methods, in turn, will greatly facilitate high-throughput structure-based drug design and discovery.

Methods

Protein purification

Four proteins were used in this study as follows: the peptide transporter, PepTSt, from Streptococcus thermophilus37, the lipoprotein signal peptidase II, LspA, from Pseudomonas aeruginosa (PAO1)38, the undecaprenyl-pyrophosphate phosphatase, BacA, from Escherichia coli (K)39, and the phosphatidic acid phosphatase, PgpB, from Bacillus subtilis40. Se-LspA, PgpB, BacA, and native S-PepTSt were produced recombinantly and purified from biomass following published protocols37,38,39,40. Se-PepTSt was produced by using E. coli C43 (DE3) (NEB) cells with the pWaldo-dtpT plasmid. Cells were grown in SelenoMet™ Medium (Molecular Dimensions) supplemented with 50 mg/L Se-Met (Sigma) and 50 mg/L kanamycin (Melford) following supplier’s instructions. Se-PepTSt was purified by following a published protocol37. All protein samples were stored at − 80 °C.

Crystallization

Crystals were grown from purified concentrated proteins by the LCP method41 in IMISX plates10. Complexes with globomycin (Sigma), cefadroxil (Sigma), and Ala-Phe (H-Ala-Phe-OH) (BACHEM) were used in the crystallization of Se-LspA, Se-PepTSt, and native S-PepTSt, respectively. Co-crystallization of Hg-derivatized BacA and W-derivatized PgpB was performed by pre-incubating protein solution at 4 °C with 2 mM HgCl2 (Hampton) for 10 min and  mM Na2WO4 (Hampton) for 30 min, respectively, before setting up crystallization trials. For Se-Met substituted LspA, Hg-derivatized BacA and W-derivatized PgpB, the mesophase was produced by homogenizing two volumes of protein solution at ~ 12 mg/mL with three volumes of monoolein ( monoacylglycerol, MAG) (NuCheck) in a LCP coupled syringe mixing device at 20 °C42. A similar protocol was used with PepTSt with the following modifications. The hosting lipid, MAG (Avanti), was used for native S-PepTSt and Se-PepTSt using equal volumes of lipid and protein solution to make the mesophase, and the concentration of the protein solution was 10 mg/mL. Crystallization trials were set up robotically at 20 °C using 50 nL protein-laden mesophase and – nL precipitant solution for Se-PepTSt, Se-LspA, Hg-derivatized BacA, and W-derivatized PgpB. In the case of native S-PepTSt, crystals were grown in syringes. For this purpose, 20 μL protein-laden LCP was injected into a  μL-syringe containing  μL precipitant solution43. Proteins were crystallized under the following conditions: Se-PepTSt (21–22 %(v/v) PEG- , – mM ammonium dihydrogen phosphate,  mM HEPES, pH , and 10 mM cefadroxil), Se-LspA (35–43 %(v/v) PEG,  mM MES, pH –, and 60– mM ammonium phosphate monobasic), Hg-derivatized BacA (40 %(v/v) PEG, – mM ammonium citrate dibasic and  mM sodium citrate pH ), W-derivatized PgpB (40 %(v/v) PEG,  mM HEPES pH 7 and  mM lithium citrate tribasic tetrahydrate) and native S-PepTSt (21–22 %(v/v) PEG, – mM ammonium dihydrogen phosphate,  mM HEPES, pH , and 10 mM Ala-Phe). Crystals of native-BacA for soaking experiments were grown in the same precipitant as was used for Hg-derivatized BacA crystal production. Se-PepTSt crystals grew as pyramids with an average size of 5 × 10 × 10 μm3. Se-LspA crystals grew as thin plates with an average size of 10 × 20 × 50 μm3. BacA crystals grew as thin plates with an average size of 5 × 10 × 20 μm3. Hg-BacA crystals grew as thin plates with an average size of 3 × 5 × 15 μm3. W-PgpB crystal grew as plates to a size of 10 × 50 ×  μm3. Native S-PepTSt crystals grew as pyramids with an average size of 10 × 10 × 10 μm3.

IMISX-soaking and sample preparation

All of the samples used for data collection were prepared using the IMISX method as described previously10,11 with two important modifications. First, a Y-shaped holder (Supplementary Fig. 2) was used to secure the flexible IMISX well stably in the cryo-stream for effective raster scanning and data collection (Supplementary Fig. 7). Second, soaking crystals with heavy atoms was performed directly in the IMISX well without touching the hosting mesophase or the crystals therein. For this purpose, the intact well containing the crystal-laden mesophase bolus was removed from the double-sandwich IMISX plate and was mounted on a Y-support. One corner of the well was snipped off with a scissor and precipitant solution was wicked away from around the mesophase bolus using a cotton bud or tissue paper. Heavy atom reagent, dissolved in the same precipitant solution, was pipetted into the well via the open corner and manipulated so as to make contact with and to fully bathe the mesophase bolus. After a period of incubation at 20 °C (Rumed incubator, model ), the IMISX well was snap-cooled immediately in liquid nitrogen (Fig. 1). Samples were placed in pucks and shipped in a Dewar to the Swiss Light Source for measurement. Screening for optimum heavy atom labeling conditions was performed directly in IMISX wells in a process that involved different soaking times, heavy atom concentrations and heavy atom types chosen based on BacA sequence analysis in conjunction with the HATODAS II server44. Soaking with 10 mM HgCl2 for 70 min provided sufficient labeling for successful experimental phasing.

Automated serial data collection

X-ray diffraction experiments were carried out on protein crystallography beamlines X06SA-PXI and X10SA-PXII at the Swiss Light Source, Villigen, Switzerland. Data were collected at  K using cryo-cooled IMISX wells in a cryo-stream, as described11. Measurements were made in steps of –° at a speed of  s/step with either an EIGER 16 M or a PILATUS 6M-F detector operated in continuous/shutterless data collection mode45. Beam size was adjusted according to crystal dimensions to optimize signal/noise for data collection and typically measured 10 × 10 μm2 or 20 × 20 μm2. With the Swiss Light Source data acquisition software (DA+)46 an automated serial data collection protocol (CY+) was developed enabling grid scan rates of 50– Hz47. This made it possible to raster scan an entire 2 × 2 mm2 mesophase bolus with X-rays at micrometer resolution in about 8 min. The resulting finely sampled grid map accurately located all crystals in the bolus and provided a ranking of diffraction quality in heat map form. Immediately after completing the grid scan, the automated data collection protocol CY+ was launched for serial data collection on crystals above a defined diffraction quality threshold over a specified rotation range (typically 10–20°) and a defined beam attenuation. Following this protocol, a few hundred crystals were measured in an hour (Supplementary Fig. 7). Radiation damage per crystal was maintained below 5 MGy for all proteins except Se-PepTSt where a dose of 17 MGy per crystal was used.

Data processing, selection, and merging

In serial crystallography, real-time data analysis is indispensable. This was implemented in the current IMISX-EP workflow by combining parallel data processing using XDS with data set selection and merging based on correlation coefficient and diffraction signal strength (Supplementary Fig. 3). Data collection wedges of 10–° per crystal were indexed and processed using XDS48,49, as described11. For data set selection, all data sets were initially sorted in ascending order based on the averaged Rmeas values calculated from the three lowest resolution shells of each data set. Next, the sorted data sets were scaled and merged with XSCALE to obtain a preliminary scaled and merged data set. Then, the correlation coefficients (CCdataset) based on intensities in resolution shells were calculated between the preliminary merged data and each individual data set. The selection of data sets was carried out on the basis of the CCdataset values of each data set in a chosen resolution shell and the data sets below a certain CCdataset were rejected. This CCdataset selection process is usually carried out in an iterative manner based on a case-by-case basis. With Se-LspA, an additional selection based on the asymptotic < I/σ > ratio (ISa)50, as determined by XSCALE, was used to remove outlier data sets before CCdataset selection. Final data sets were scaled and merged with XSCALE. Data collection and processing statistics are provided in Table 1.

Structure determination and refinement

The SAD method was employed for experimental phasing using anomalous diffraction data sets from crystals of Se-PepTSt, Se/S-LspA, W-PgpB, Hg-BacA (soaking), Hg-BacA (co-crystallization), and native S-PepTSt. The SIRAS method was also used for Hg-BacA (soaking). Heavy atom location, structure phasing, and density modification were performed using the HKL2MAP51 interface of SHELXC/D/E12 for all structures and produced interpretable electron density maps for Se-PepTSt, Hg-BacA (soaking, SIRAS), Hg-BacA (co-crystallization), W-PgpB, and native S-PepTSt. Additional phase improvement and iterative auto-model building were carried out with CRANK213 for Se/S-LspA and Hg-BacA (soaking, SAD). From the experimentally phased maps, BUCCANEER52 and PHENIX AutoBuild53 were used for initial model building and models were completed manually using COOT54. cipsas.com55

Источник: [cipsas.com]
Rapid CSS 2004 v5.23 serial key or number

Chromium (web browser)

Free and open-source cross-platform web browser
Chromium 78 running in GNOME Shell on Ubuntu, displaying the Settings page, and with the opened menu
Original author(s)Google
Developer(s)Google, Microsoft, Igalia, Yandex[1]
Initial releaseSeptember&#;2, ; 12&#;years ago&#;()
Repository
Written inC, C++, JavaScript[2][3]
EnginesBlink, V8
Operating system
PlatformIA, x, ARM
TypeWeb browser
License
Websitecipsas.com

Chromium is a free and open-source software project from Google. The source code can be compiled into a web browser.

Google uses the code to make its Chrome browser, which has more features than Chromium. Many other browsers are also based on Chromium code, most notably Microsoft Edge and Opera. In addition, some parties (although not Google) build the code as-is and release browsers with the Chromium name.

Chromium's user interface is minimalist. Google sought to make the browser "feel lightweight (cognitively and physically) and fast."[10]

New Chromium versions are released daily, however there is no "stable" Chromium version unlike other web browsers.[11]

Licensing[edit]

Chromium is an entirely free and open-source software project. The Google-authored portion is released under the 3-clause BSD license.[12] Other parts are subject to a variety of licenses, including MIT, LGPL, Ms-PL, and an MPL/GPL/LGPLtri-license.[13]

Differences from Google Chrome[edit]

Chromium provides the vast majority of source code for Google Chrome, including the user interface, the Blinkrendering engine, and the V8JavaScript engine. Thus Google chose the "Chromium" name as an analogy of chromium metal forged into chrome plating.[14]

Features[edit]

Chrome has features that are not present in a default Chromium build. However, some are enabled or manually added to a Chromium build, for Linux distributions.[15]

Branding and licensing[edit]

While Chrome has the same user interface functionality as Chromium, it changes the color scheme to the Google-branded one. Unlike Chromium, Chrome is not open-source, so its binaries are licensed as freeware under the Google Chrome Terms of Service.[16]

History[edit]

An early alpha build of Chromium for Linux, which clarifies its separation from Google Chrome

Version numbers[edit]

Releases are identified by a four-part version number, e.g. (Chromium 47 initial release 23 August ).[17] The components are cipsas.com[18]

cipsas.com reflects scheduling policy
cipsas.com identifies content progression

A cipsas.com branch point schedule is published.[18] Branch points occur roughly every six to seven weeks.[19] The published dates are a last branch date of each Chromium (Major) release and are tied to the Google Chrome development cycle. They lag the initial Chromium release by about 40 days and precede the next by about 2. Details are described in Chrome Release cycles.

[edit]

Google Chrome was introduced in September , and along with its release, the Chromium source code was also made available, allowing builds to be constructed from it. The initial code release included builds for Windows and macOS, and a build for Linux, at a very early stage of development and lacking complete functionality. Chromium was released in December and with it Chrome was removed from beta status for Windows only.[20][21]

Upon its first release in September Chromium was criticized for storing saved passwords in a manner so that any casual user of a computer can easily read them from the GUI. Chromium users have filed many bug reports and feature requests asking for a master password option to access stored passwords, but Chromium developers have consistently insisted that this provides no real security against knowledgeable hackers. Users have argued that it would protect against co-workers or family members borrowing a computer and seeing the stored passwords in clear text. In December , Chromium developer P. Kasting stated: "A master password was issue That issue is closed. We will not implement a master password. Not now, not ever. Arguing for it won't make it happen. 'A bunch of people would like it' won't make it happen. Our design decisions are not democratic. You cannot always have what you want."[22][23]

[edit]

In January the first development versions of Chromium were made available, featuring a bookmark manager and support for non-standard CSS features, including gradients, reflections and masks.[24]

In May the first alpha Linux version of Chromium was made available. In reviewing that alpha version Ryan Paul said that it was "still missing features and [has] lots of rendering bugs, but it is clearly moving in the right direction." The first developer releases for Chrome on the Linux and macOS platforms were made available in June , although they were in a very early stage and lacked Adobe Flash, privacy settings, the ability to set the default search provider and even printing at that point. In July Chromium incorporated native theming for Linux, using the GTK+ toolkit to allow it fit into the GNOME desktop environment.[25][26][27][28]

Chromium was released on 28 May as version [29][30] Chrome followed in September and introduced a much faster JavaScript engine, a system for user-selectable themes, improvements to the Omnibox and a redesigned new tab display page.[31]

Chromium was the first Chromium version and appeared on 22 September [29][32] with Chrome publicly released in December Both brought support for extensions, plus synchronization of bookmarks along with Chrome beta versions for macOS and Linux. The all-platform market penetration of Chrome/Chromium combined was at % by the end of April [33][34][35][36]

Gentoo Linux has had Chromium in the official repository since September [37]FreeBSD has had Chromium available since late and a port has been available from the FreeBSD ports system since late [38][39]OpenBSD has had Chromium available for i and amd64 platforms since late [40] Although OpenBSD supports many browsers,[41] recent releases only officially highlight Chromium and Firefox.[42]

[edit]

Original Chromium logo used from the project's inception until Chromium 11

Chromium was released on 26 January with as the initial version.[29][43] Google Chrome followed on 25 May and provided stable (non-beta) releases for all platforms. At that time the web magazine, OMG! Ubuntu!, reported that Chrome/Chromium usage was at % for Linux browsers, compared to % for Firefox and % for Opera.[34][44][45][46]

Lubuntu used Chromium as the default browser since its first release, Lubuntu in April , until Lubuntu in October when it moved to Firefox instead.[47]Ubuntu started offering Chromium through the Ubuntu Software Center starting with Ubuntu LTS as part of the "universe" repository. The initial version available in April was , with brand-new versions delivered as updates.[48]Puppy Linux has had Chromium available starting with Chromium on Lucid Puppy , based on the Ubuntu application repository.[49]Maemo, Nokia's former mobile operating system, offered a proof-of-concept version of Chromium with an unmodified user interface which was released on 11 April [50]

Chromium was introduced in May with the first release version In July Chromium 6 daily builds introduced new features focusing on user interface minimalism, including a unified single page and tools menu, no home button by default (although user configurable), no "go button", a combined "reload/stop" button, bookmark bar deactivated by default, an integrated PDF reader, WebM and VP8 support for use with HTML5 video, and a smarter URL bar.[29][51][52] Chrome 6 was released in both a stable and beta version on 2 September as version The switch to brought security fixes, a slightly updated user interface, improvements to form autofilling, synchronizing of both extensions and autofill data, along with increased speed and stability.[53]

Acid3 test results on Chromium 7

Chromium was released on 17 August , with as the first version made available. This version boosted HTML5 performance to double the speed of Chromium 6. It also added hardware acceleration, which speeds up the browser in complex graphics situations by a factor of times, integration of instant search, UI Tabs to move all the remaining user interface windows into the browser tabs, including the "options" menu, and has 3% faster JavaScript performance.[29][54][55][56]

7 October marked the release of Chromium , seven and a half weeks after that of Chromium 7. The initial release in this series was version The development of Chromium focused on improved integration into Chrome OS and improved cloud features. These include background web applications, host remoting (allowing users centrally to control features and settings on other computers) and cloud printing.[29][56] On 12 January versions of Chrome and Chromium prior to version were identified by US-CERT as "contain[ing] multiple memory corruption vulnerabilities. These vulnerabilities include a stack corruption vulnerability in the PDF renderer component, two memory corruption vulnerabilities in the Vorbis decoder and a video frame size error resulting in a bad memory access&#; By convincing a user to view a specially crafted HTML document, PDF file, or video file, an attacker can cause the application to crash or possibly execute arbitrary code." This vulnerability was publicized after Chrome version was released fixing these problems, to alert users to upgrade versions as soon as possible.[57]

Chromium was released on 23 October , just 16 days after Chromium , with as the initial version. The new version introduced an infobar refresh feature with the aim of preventing website spoofing attacks. Reviewer Wolfgang Gruener noted that the first builds of Chrome 9 have now doubled in size between Chrome 3 and Chrome 9 to a compressed download of MB, calling it "notably more bloated". Gruener also criticized the seemingly arbitrary numbering breaks between major versions, saying, "even by more progressive standards, the version numbering may be a bit excessive. By the end of this year, Google will have gone through seven or eight different browser versions. Some may doubt the benefit of that strategy."[29][58] Chromium 9 introduced two new test features in November intended to load web pages more quickly, "pre-rendering" and "false start", plus sandboxing for Adobe Flash. Stable releases of Chrome and Chromium were version and included features such as Instant Search which allows the URL bar to act through Google Instant when Google is the default search. Other features included GPU/hardware acceleration, default 3D graphics though WebGL and access to the Chrome Web Store on the New Tab page.[59][60][61]

Chromium was released on 3 December , with as the initial version. It introduced 18 new features, including "Instant Type" searching and "GPU accelerated compositing". Development of "Webpage pre-rendering" was reduced to an inactive feature while a selectable "snap start" was introduced.[29][62]

[edit]

Logo introduced with Chromium 11

Chromium was released on 28 January , with as the initial version. Development work in this version centered on cleaning up the settings menu, including the Sync menu and eliminating all checkboxes. Reviewer Wolfgang Gruener said "The Settings menu isn't quite as messy anymore and looks much more like what you would expect from a professionally designed software." Language and spell checking support was expanded to languages. Chromium 11 used WebKit and V8 which resulted in improved speed in JavaScript and other benchmark tests. In early testing Chromium 11 was faster than Firefox 4 in V8 and Kraken benchmarks, but was 12% slower than Internet Explorer 9 in Sunspider tests.[29][61]

In February , Google's Jeff Chang announced to Chromium developers that Google was considering further large-scale interface changes. Under consideration were eliminating the "Omnibox" URL bar and combining the two-line layout which has tabs on one line and navigation buttons, a menu and URL bar on a second line into one single line, thus freeing up more screen space for content. (Such a layout was later adopted by Internet Explorer 9.) Chang acknowledged that this would result in URLs not always being visible to the user, that navigation controls and menus may lose their context and that the resulting single line could be quite crowded. Other proposed changes include being able to log into multiple accounts in different windows and improved URL suggestions from the user's history.[63] By the middle of , after some experimentation, the developers decided that eliminating the URL bar was too risky and shelved the idea.[64] Chromium 11 also introduced a new simplified 2D logo that replaced the 3D logo used from the project since its inception.[65]

Mageia first offered Chromium 11 in Mageia v1 during [66][67]

Chromium was released on 11 March , with as the first version. Initial changes in the first versions of Chromium 12 included updates of test features, incorporating an fps counter for hardware acceleration benchmarks, a P2P API that may indicate future platform data exchange features, an enhanced URL bar and small changes to the tabs. Chromium 12 incorporated WebKit and V8 JavaScript engine version It is anticipated that a URL bar web app launcher would be added during the development cycle. Early in the Chromium 12 cycle the history quick provider was introduced. This feature automatically searches the browser history for websites visited in the past 72 hours looking for matching page titles and URLs. It also searches through URLs that have been typed at least twice and URLs that have been visited at least four times ever.[29][68]

In March Google announced directions for the project for the year, including a plan for seven new major versions, planning to end the year with Chrome 17 out. Development priorities focus on reducing the browser's size, integrating web applications and plug-ins, cloud capabilities and touch interface. The size is a concern to developers, who have noted that Chrome 1 was MB in Windows download size, compared to Chrome 10 for Windows at MB, as a result they have created a "bloat taskforce". Larger download sizes are a problem for a number of reasons, as Chrome Developer Ian Fette explained: "1. We do distribution deals with Chrome, where we bundle Chrome with other products. These get difficult when our binary grows. 2. We see increased download failures/ install dropoffs as the binary grows, especially in countries with poor bandwidth like India. India also happens to be a very good market for Chrome (we have good market share there and growing), so that's also very problematic."[69][70]

With the release of Chromium on 19 April the interface incorporated many changes, the most significant since Chromium 6 was released. A multi-profile button was introduced allowing users to log into multiple Google and other accounts in the same browser instance. The new tab page was also redesigned and separated into four horizontally scrollable screens, providing access to most visited pages, Google apps, plus two identified pages. The page reload button was also redesigned along with minor changes to the URL bar. The first stable version of Chrome and Chromium 12 released was which brought malware detection and support for hardware-accelerated 3D CSS transforms.[71][72]

Chromium was released on 26 April , with as the initial version.[29] Early versions of Chromium 13 included a menu button to enable users to switch between multiple Google profiles, multi-selection of tabs and an improved omnibox engine. This version also included several minor GUI changes, including a slightly lightened menu bar.[73] By early May the results of Google's attempts to reduce the file size of Chromium were already being noted. Much of the early work in this area concentrated on shrinking the size of WebKit, by removing Wireless Markup Language (WML), the Image Resizer, datagrids and the Android build system. The largest Chromium nightly build was MB on 15 April , but this was reduced to MB by 20 April [74] Later builds of Chromium and Chrome in mid-May introduced the optional "compact navigation view", aimed at mobile device users. This view combined the tabs, URL bar and menu bar into one bar, by making the URL bar hide when not in use, thus saving 30 pixels of vertical space.[75][76]

Chromium was released on 2 June , with as the initial version. This initial version included testing support for preloading instant searches, permitting the user to preload the default search engine used in instant search and GPU acceleration on all pages. Default changes include a 2D-accelerated canvas and the task manager incorporated a frames-per-second counter. There was also support for the Page Visibility API. By the time development of Chromium 14 had been completed and Chrome 14 stable released this version also incorporated Mac OS X Lion scrollbar compatibility and "presentation mode". It also had support for the new Web Audio API and Google Native Client (NaCl) which permits native code supplied by third parties as platform-neutral binaries to be securely executed within the browser itself.[29][77][78]

Chromium was released on 28 July , with as the initial version. Work in this version included integrating the profiles and synchronization features, including moving synchronization into the main menu and introducing a profile manager. Synchronization data will be encrypted by default. Chromium 15 also expands webpage pre-rendering. Dan Bailey of Conceivably Tech stated about this version and the development of it, "it is obvious that Google is plugging along and is fine-tuning its browser&#;… Chrome isn't surrendering its perception of the most advanced browser today anytime soon." As development wound up in early September Chromium 15 also gained a "self-crashing" feature that crashes the browser if a close command is not completed in 25 seconds, smooth scrolling when using the space bar, automatic pre- and auto-logins to Google's own web pages, task bar logos to show different profiles, greatly enhanced synchronization customization, including optional search engine synchronization and improvements to the pre-rendering process.[29][79][80]

Chromium was released on 10 September , with as the initial version.[29] Early in the development of version 16 an experimental Offscreen Tabs Module was incorporated which allows simultaneous user interaction with multiple web pages. This version for macOS included a move to Google's Skia 2D graphics library in place of Apple's core graphics as previously used. This aligned Chromium for macOS with the Windows and Linux versions.[81][82]

Chromium was released on 19 October , with the initial release version [29] This version introduced HTTP pipelining as a test feature to increase web page load speed, starting with build Development on Chromium 17 near the end of November included the Gamepad API, specifically intended to allow game inputs from joysticks and other gaming-oriented pointing devices. Other work included being able to move profile icons directly to the desktop in Windows.[83][84]

Chromium was released on 7 December , with the initial release version [29] Nightly builds of Chromium 18 showed that this cycle included work on menu organization. In January the builds reworked the Options menu to eliminate the Basics, Personal Stuff and Under the Hood pages and unite them into one menu named options. The new menu simplifies selections and hides privacy and proxy settings and security certificate management. Additional features included omnibox suggestion visualization.[85]

[edit]

Chromium was released on 2 February , with the initial release version [29] Support for Android was added. Chromium 19 development led to the release of Chrome on 15 May , which incorporated many bug fixes along with a tab synchronization feature that allowed users to have the same tabs open on Chrome on different devices through "signing into Chrome".[86][87][88]

Chromium was released on 29 March , with the initial release version This development cycle resulted in the release of Google Chrome on 26 June , which was predominately a bug-fix update with few new features.[29][89][90]

Chromium was released on 11 May , with the initial release version This development cycle resulted in Google Chrome for macOS and Linux and Chrome for Windows and Chrome Frame, released on 31 July Chrome 21 incorporated a new API to enable high-quality video and audio communication, complete support for Apple's retina display and a large number of bug fixes. The release included the getUserMedia JavaScript API, which permits web applications access the user's webcam and microphone after asking permission to do so.[29][91][92]

Chromium was released on 21 June , with the initial release version This development cycle resulted in the release of Google Chrome on 25 September It incorporated Mouse Lock API availability for JavaScript, Windows 8 and HiDPI/Retina improvements, and many security and bug fixes.[29][93]

Chromium was released on 9 August , with the initial release version [29] This development cycle resulted in the release of Chrome on 6 November , which incorporated easier website permissions, plus GPU accelerated video decoding for Windows.[94]

Chromium was released on 20 September , with the initial release version [29][95] This development cycle resulted in the release of Chrome on 10 January , which incorporated support for MathML which allows mathematical equations to be displayed, HTML5 datalists for date and time and a large number of security and bug fixes.[96] This release marked a total of a 26% increase in page loading speed achieved in the releases over the previous 12 months.[97]

Chromium was released on 1 November , with the initial release version This development cycle resulted in the release of Chrome for Windows and Linux and for macOS on 21 February This release introduced extension improvements, improved support for HTML5 time and date inputs, JavaScript Web Speech API support and improved WebGL error handling, plus many bug fixes.[29][98]

Chromium was released on 20 December , with the initial release version [29] This development cycle resulted in the release of Chrome on 26 March This release incorporated a new "Ask Google for suggestions", spell checking feature improvements, which includes grammar and homonym checking, desktop shortcuts for multiple users on Windows, and asynchronous DNS resolver improvements for Mac OS-X and Linux.[99]

[edit]

The first new release for , Chromium , first appeared on 14 February , as This development cycle resulted in the release of Chrome on 21 May This version incorporated a page-loading speed-improvement of an average of 5%, the cipsas.comleSystem API, improved prediction-ranking and Omnibox predictions, and improved spelling-correction.[29][]

Chromium was released on 28 March , with the initial release version This development cycle resulted in the release of Google Chrome for Linux only on 17 June On Linux this version requires Ubuntu , Debian 7, openSUSE or Fedora Linux 17 and later releases to run.[29][]

Chromium was released on 9 May , with the initial release version [29] This development cycle resulted in the release of Chrome on 20 August [] This version incorporated improved Omnibox suggestions, the ability to reset user profiles, new applications and extension APIs and improvements in stability and performance.[] The Blinkbrowser engine (a fork of the WebKit engine[][]) was introduced on 4 April in Chromium []

Chromium was released on 27 June , with the initial release version [29] This development cycle resulted in the release of Chrome on 1 October This incorporated improved image searching, new applications and extension APIs, performance and stability enhancements and 50 bug fixes.[]

Chromium was released on 13 August , with the initial release version [29] This development cycle resulted in the release of Chrome on 12 November This version of Chrome introduced only bug fixes with no new features.[]

Chromium was considered as the default browser for Ubuntu , which was released on 17 October , but Firefox remained the default browser due to problems keeping the Chromium packages up-to-date.[]

Chromium was released on 25 September , with the initial release version [29] This development cycle resulted in the release of Chrome for Windows and Chrome Frame and for Mac and Linux on 14 January This release incorporated tab indicators for sound, webcam and casting, visual changes to the version for Windows 8 in Metro mode, automatically blocking of files detected as malware, several new apps and extension APIs, and improved stability and performance.[]

Chromium was released on 6 November , with the initial release version [29] This development cycle resulted in the release of Chrome on 20 February , which was predominately a bug-fix release.[]

The developers released Chromium on 18 December , with the initial release version [29] This cycle resulted in the release of Chrome on 8 April This version included the ability to import supervised users onto new computers, additional new apps/extension APIs and a different appearance for Chrome in Windows 8 Metro mode.[]

[edit]

Chromium was released on 20 February , with the initial release version [29] This development cycle resulted in the release of Chrome on 20 May Chrome 35 incorporated improved developer control over touch input, new JavaScript features, an unprefixed Shadow DOM, some new apps and extension APIs, plus stability and performance enhancements.[]

Chromium was released on 31 March , with the initial release version [29] This development cycle resulted in the release of Chrome on 16 July The release included improvements to notifications, a new incognito and guest NTP design, a new crash recovery bubble, an application launcher for Linux, improvements to stability and performance and 26 security fixes.[]

Chromium was released on 11 May , with the initial release version [29] This development cycle resulted in the release of Chrome on 26 August Chrome 37 included Windows DirectWrite support to improve font rendering, new apps/extension APIs, improvements to stability and performance, and 50 security fixes.[]

Chromium was released on 22 June , with the initial release version [29] This development cycle resulted in the release of Chrome on 7 October Chrome 38 included just bug fixes and improvements to stability and performance.[]

Chromium was released on 17 August , with the initial release version [29] This development cycle resulted in the release of Chrome on 18 November Chrome 39 included bit support for Mac computers, some new application and extension APIs as well as stability and performance enhancements.[]

Chromium was released on 28 September , with the initial release version The development cycle resulted in the release of Chrome on 21 January This version was predominately a bug-fix release with 62 security issues addressed.[17][]

Chromium was released on 9 November , with the initial release version [17] This development cycle resulted in the release of Chrome on 3 March This version was predominately a "stability and performance" and bug-fix release with 51 security issues addressed.[]

[edit]

Chromium was released on 12 January , with the initial release version [17] This development cycle resulted in the release of Chrome on 14 April This release included new application and API support and improvements to stability and performance. In deference to its version number Google also claimed that it contained, "the answer to life, the universe and everything".[]

Chromium was released on 22 February , with the initial release version [17] This development cycle resulted in the release of Chrome on 19 May It was primarily a security-fix update.[] Chromium 43 was reported by Debian developers as automatically downloading the binary blobChrome Hotword Shared Module extension, a library for Google's OK Google voice recognition feature. Security researchers have indicated that this code carries a risk of invasion of privacy. This was fixed in Chromium with newer versions no longer automatically downloading the Chrome Hotword Shared Module, but the Debian community remained suspicious of the browser and Google.[][][][]

Chromium was released on 7 April , with the initial release version [17] This development cycle resulted in the release of Chrome on 21 July This version included some new apps and extension APIs, some changes to improve stability and performance and 43 security fixes.[]

The remainder of the Chromium releases for the year were just bug and security fix updates, with no other significant changes.[17][][][][][]

[edit]

Chromium , released on 18 January , added support for Brotli compression via the Accept-encoding header.[] Chrome 54, released on 12 October and based upon Chromium 54, introduced support for HTML Custom Elements.[][]

The remainder of the Chromium releases for were only bug and security fix updates, with no other significant changes.

[edit]

Chromium , released on 4 March , added support for the Animated Portable Network Graphics (APNG) file format.[17][][]

The remainder of the Chromium releases for were only bug and security fix updates, with no other significant changes.

[edit]

Chromium , first released on 20 January , introduced audio muting for all autoplaying video content by default.[17][]

Chromium , first released on 19 July and the stable version on 4 September , introduced a new material theme as part of year project anniversary.[][]

Chromium 71, was first released on 1 September and resulted in Chrome 71, released on 4 December This version incorporated new measures aimed at abusive advertising, including misleading advertising and advertising for cell phones that aims to bill users.[17][]

Snapshots[edit]

Chromium snapshots are built automatically several times a day by BuildbotBuildworkers and made available as binary code releases.[] Once a snapshot has been built, it is placed in a directory in the chromium-browser-snapshots root directory[] and it is automatically tested.[] If the snapshot passes the automated testing, it is placed in a directory in the chromium-browser-continuous root directory.[]

Chromium builds can be downloaded for most Linux distributions and BSD operating systems from their respective software repositories. Chromium builds for Windows and Mac can be downloaded directly. Unlike Chrome releases, Chromium releases do not automatically update.[]

Browsers based on Chromium[edit]

In addition to Google Chrome, many other notable web browsers have been based on the Chromium code.

Active[edit]

  • Amazon Silk
  • Avast Secure Browser developed by Avast
  • Beaker, a peer-to-peer web browser
  • Blisk is a browser available for Windows 7 and later, OS X and later that aims to provide an array of useful tools for Web development.
  • Brave is an open-source web browser that aims to block website trackers and remove intrusive internet advertisements.
  • CodeWeaversCrossOver Chromium is an unofficial bundle of a Wine derivative and Chromium Developer Build 21 for Linux and macOS, first released on 15 September by CodeWeavers as part of their CrossOver project.[][]
  • Comodo Dragon is a rebranded version of Chromium for bit Windows , 8, Windows 7 and Vista[] produced by the Comodo Group. According to the developer, it provides improved security and privacy features.[]
  • Cốc Cốc is a freeware web browser focused on the Vietnamese market, developed by Vietnamese company Cốc Cốc, based on Chromium open-source code for Windows.[] According to data published by StatCounter in July , Cốc Cốc has passed Opera to become one of the top 5 most popular browsers in Vietnam[] within 2 months after its official release.[]
  • Epic Browser is a privacy-centric web browser developed by Hidden Reflex of India and based on Chromium source code.[]
  • Falkon a Qt-based GUI, based on the Chromium core.[]
  • Microsoft Edge is Chromium-based as of January 15, [][]
  • Naver Whale is a South Korean freewareweb browser developed by Naver Corporation, which is also available in English. It became available on Android on April 13,
  • Opera began to base its web browser on Chromium with version []
  • Qihoo Secure Browser is a popular web browser in China.[]
  • SalamWeb is a web browser based on Chromium for Muslims allowing to view positive websites/information only (called Halal).
  • Samsung Internet shipped its first Chromium-based browser in a Galaxy S4 model released in []
  • Sleipnir is a Chromium derivative browser for Windows and macOS. One of its main features is linking to Web apps (Facebook, Twitter, Dropbox, etc.) and smartphone apps (Google Map, etc.). It also boasts what it calls "beautiful text," and has unique graphical tabs, among other features.[]
  • Slimjet: A Chromium-based web browser released by FlashPeak that features built-in webpage translation, PDF viewing capability and a PPAPI flash plugin, features usually missing from Chromium-based browsers currently not supported.
  • SRWare Iron is a freeware release of Chromium for Windows, macOS and Linux, offering both installable and portable versions. Iron disables certain configurable Chromium features that could share information with third parties and additional tracking features that Google adds to its Chrome browser.[]
  • Torch is a browser based on Chromium for Windows. It specializes in media downloading and has built-in media features, including a torrent engine, video grabber and sharing button.[]
  • Vivaldi is a browser for Windows, macOS and Linux developed by Vivaldi Technologies.[][] Chromium-based Vivaldi aims to revive the rich features of the Presto-era Opera with its own proprietary modifications.
  • Yandex browser is a browser created by the Russian software company Yandex for macOS, Windows and Linux.[] The browser integrates Yandex services, which include a search engine, a machine translation service and cloud storage.

Discontinued[edit]

  • Flock – a browser that specialized in providing social networking and had Web facilities built into its user interface. It was based on Chromium starting with version Flock was discontinued in April [][]
  • Redcore – a browser developed by Chinese company Redcore Times (Beijing) Technology Ltd.. and marketed as a domestic product that was developed in-house, but was revealed to be based on Chromium[]
  • Rockmelt – a Chromium-based browser for Windows, macOS, Android and iOS under a commercial proprietary licence. It integrated features from Facebook and Twitter, but was discontinued in April and fully retired at 10am PT on July 31, [][] On August 2, , Rockmelt was acquired by Yahoo! Rockmelt's extensions and its website was shut down after August 31, Yahoo! plans to integrate Rockmelt's technology into other products.[]

Toolkit[edit]

Chromium as a toolkit is also commonly used, but without Google's acceptance[citation needed] a stable ABI or API upstream, every project using it as a toolkit[citation needed], maintains a fork of Chromium with an API wrapper. Many of the browsers listed previously are based on these forks rather than the upstream project directly.[citation needed] All actively maintained forks however rebase frequently onto the main branch avoiding them forking off to being completely separate projects over time.[citation needed]

Active toolkit forks include:

See also[edit]

References[edit]

Источник: [cipsas.com]
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