/**
* Note: This file may contain artifacts of previous malicious infection.
* However, the dangerous code has been removed, and the file is now safe to use.
*/
/**
* @file
* Pathologic text filter for Drupal.
*
* This input filter attempts to make sure that link and image paths will
* always be correct, even when domain names change, content is moved from one
* server to another, the Clean URLs feature is toggled, etc.
*/
/**
* Implements hook_filter_info().
*/
function pathologic_filter_info() {
return array(
'pathologic' => array(
'title' => t('Correct URLs with Pathologic'),
'process callback' => '_pathologic_filter',
'settings callback' => '_pathologic_settings',
'default settings' => array(
'local_paths' => '',
'protocol_style' => 'full',
),
// Set weight to 50 so that it will hopefully appear at the bottom of
// filter lists by default. 50 is the maximum value of the weight menu
// for each row in the filter table (the menu is hidden by JavaScript to
// use table row dragging instead when JS is enabled).
'weight' => 50,
)
);
}
/**
* Settings callback for Pathologic.
*/
function _pathologic_settings($form, &$form_state, $filter, $format, $defaults, $filters) {
return array(
'reminder' => array(
'#type' => 'item',
'#title' => t('In most cases, Pathologic should be the last filter in the “Filter processing order” list.'),
'#weight' => -10,
),
'protocol_style' => array(
'#type' => 'radios',
'#title' => t('Processed URL format'),
'#default_value' => isset($filter->settings['protocol_style']) ? $filter->settings['protocol_style'] : $defaults['protocol_style'],
'#options' => array(
'full' => t('Full URL (http://example.com/foo/bar)'),
'proto-rel' => t('Protocol relative URL (//example.com/foo/bar)'),
'path' => t('Path relative to server root (/foo/bar)'),
),
'#description' => t('The Full URL option is best for stopping broken images and links in syndicated content (such as in RSS feeds), but will likely lead to problems if your site is accessible by both HTTP and HTTPS. Paths output with the Protocol relative URL option will avoid such problems, but feed readers and other software not using up-to-date standards may be confused by the paths. The Path relative to server root option will avoid problems with sites accessible by both HTTP and HTTPS with no compatibility concerns, but will absolutely not fix broken images and links in syndicated content.'),
'#weight' => 10,
),
'local_paths' => array(
'#type' => 'textarea',
'#title' => t('All base paths for this site'),
'#default_value' => isset($filter->settings['local_paths']) ? $filter->settings['local_paths'] : $defaults['local_paths'],
'#description' => t('If this site is or was available at more than one base path or URL, enter them here, separated by line breaks. For example, if this site is live at http://example.com/ but has a staging version at http://dev.example.org/staging/, you would enter both those URLs here. If confused, please read Pathologic’s documentation for more information about this option and what it affects.', array('!docs' => 'http://drupal.org/node/257026')),
'#weight' => 20,
),
);
}
/**
* Pathologic filter callback.
*
* Previous versions of this module worked (or, rather, failed) under the
* assumption that $langcode contained the language code of the node. Sadly,
* this isn't the case.
* @see http://drupal.org/node/1812264
* However, it turns out that the language of the current node isn't as
* important as the language of the node we're linking to, and even then only
* if language path prefixing (eg /ja/node/123) is in use. REMEMBER THIS IN THE
* FUTURE, ALBRIGHT.
*
* The below code uses the @ operator before parse_url() calls because in PHP
* 5.3.2 and earlier, parse_url() causes a warning of parsing fails. The @
* operator is usually a pretty strong indicator of code smell, but please don't
* judge me by it in this case; ordinarily, I despise its use, but I can't find
* a cleaner way to avoid this problem (using set_error_handler() could work,
* but I wouldn't call that "cleaner"). Fortunately, Drupal 8 will require at
* least PHP 5.3.5, so this mess doesn't have to spread into the D8 branch of
* Pathologic.
* @see https://drupal.org/node/2104849
*
* @todo Can we do the parsing of the local path settings somehow when the
* settings form is submitted instead of doing it here?
*/
function _pathologic_filter($text, $filter, $format, $langcode, $cache, $cache_id) {
// Get the base URL and explode it into component parts. We add these parts
// to the exploded local paths settings later.
global $base_url;
$base_url_parts = @parse_url($base_url . '/');
// Since we have to do some gnarly processing even before we do the *really*
// gnarly processing, let's static save the settings - it'll speed things up
// if, for example, we're importing many nodes, and not slow things down too
// much if it's just a one-off. But since different input formats will have
// different settings, we build an array of settings, keyed by format ID.
$cached_settings = &drupal_static(__FUNCTION__, array());
if (!isset($cached_settings[$filter->format])) {
$filter->settings['local_paths_exploded'] = array();
if ($filter->settings['local_paths'] !== '') {
// Build an array of the exploded local paths for this format's settings.
// array_filter() below is filtering out items from the array which equal
// FALSE - so empty strings (which were causing problems.
// @see http://drupal.org/node/1727492
$local_paths = array_filter(array_map('trim', explode("\n", $filter->settings['local_paths'])));
foreach ($local_paths as $local) {
$parts = @parse_url($local);
// Okay, what the hellish "if" statement is doing below is checking to
// make sure we aren't about to add a path to our array of exploded
// local paths which matches the current "local" path. We consider it
// not a match, if…
// @todo: This is pretty horrible. Can this be simplified?
if (
(
// If this URI has a host, and…
isset($parts['host']) &&
(
// Either the host is different from the current host…
$parts['host'] !== $base_url_parts['host']
// Or, if the hosts are the same, but the paths are different…
// @see http://drupal.org/node/1875406
|| (
// Noobs (like me): "xor" means "true if one or the other are
// true, but not both."
(isset($parts['path']) xor isset($base_url_parts['path']))
|| (isset($parts['path']) && isset($base_url_parts['path']) && $parts['path'] !== $base_url_parts['path'])
)
)
) ||
// Or…
(
// The URI doesn't have a host…
!isset($parts['host'])
) &&
// And the path parts don't match (if either doesn't have a path
// part, they can't match)…
(
!isset($parts['path']) ||
!isset($base_url_parts['path']) ||
$parts['path'] !== $base_url_parts['path']
)
) {
// Add it to the list.
$filter->settings['local_paths_exploded'][] = $parts;
}
}
}
// Now add local paths based on "this" server URL.
$filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path']);
$filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path'], 'host' => $base_url_parts['host']);
// We'll also just store the host part separately for easy access.
$filter->settings['base_url_host'] = $base_url_parts['host'];
$cached_settings[$filter->format] = $filter->settings;
}
// Get the language code for the text we're about to process.
$cached_settings['langcode'] = $langcode;
// And also take note of which settings in the settings array should apply.
$cached_settings['current_settings'] = &$cached_settings[$filter->format];
// Now that we have all of our settings prepared, attempt to process all
// paths in href, src, action or longdesc HTML attributes. The pattern below
// is not perfect, but the callback will do more checking to make sure the
// paths it receives make sense to operate upon, and just return the original
// paths if not.
return preg_replace_callback('~ (href|src|action|longdesc)="([^"]+)~i', '_pathologic_replace', $text);
}
/**
* Process and replace paths. preg_replace_callback() callback.
*/
function _pathologic_replace($matches) {
// Get the base path.
global $base_path;
// Get the settings for the filter. Since we can't pass extra parameters
// through to a callback called by preg_replace_callback(), there's basically
// three ways to do this that I can determine: use eval() and friends; abuse
// globals; or abuse drupal_static(). The latter is the least offensive, I
// guess… Note that we don't do the & thing here so that we can modify
// $cached_settings later and not have the changes be "permanent."
$cached_settings = drupal_static('_pathologic_filter');
// If it appears the path is a scheme-less URL, prepend a scheme to it.
// parse_url() cannot properly parse scheme-less URLs. Don't worry; if it
// looks like Pathologic can't handle the URL, it will return the scheme-less
// original.
// @see https://drupal.org/node/1617944
// @see https://drupal.org/node/2030789
if (strpos($matches[2], '//') === 0) {
if (isset($_SERVER['https']) && strtolower($_SERVER['https']) === 'on') {
$matches[2] = 'https:' . $matches[2];
}
else {
$matches[2] = 'http:' . $matches[2];
}
}
// Now parse the URL after reverting HTML character encoding.
// @see http://drupal.org/node/1672932
$original_url = htmlspecialchars_decode($matches[2]);
// …and parse the URL
$parts = @parse_url($original_url);
// Do some more early tests to see if we should just give up now.
if (
// If parse_url() failed, give up.
$parts === FALSE
|| (
// If there's a scheme part and it doesn't look useful, bail out.
isset($parts['scheme'])
// We allow for the storage of permitted schemes in a variable, though we
// don't actually give the user any way to edit it at this point. This
// allows developers to set this array if they have unusual needs where
// they don't want Pathologic to trip over a URL with an unusual scheme.
// @see http://drupal.org/node/1834308
// "files" and "internal" are for Path Filter compatibility.
&& !in_array($parts['scheme'], variable_get('pathologic_scheme_whitelist', array('http', 'https', 'files', 'internal')))
)
// Bail out if it looks like there's only a fragment part.
|| (isset($parts['fragment']) && count($parts) === 1)
) {
// Give up by "replacing" the original with the same.
return $matches[0];
}
if (isset($parts['path'])) {
// Undo possible URL encoding in the path.
// @see http://drupal.org/node/1672932
$parts['path'] = rawurldecode($parts['path']);
}
else {
$parts['path'] = '';
}
// Check to see if we're dealing with a file.
// @todo Should we still try to do path correction on these files too?
if (isset($parts['scheme']) && $parts['scheme'] === 'files') {
// Path Filter "files:" support. What we're basically going to do here is
// rebuild $parts from the full URL of the file.
$new_parts = @parse_url(file_create_url(file_default_scheme() . '://' . $parts['path']));
// If there were query parts from the original parsing, copy them over.
if (!empty($parts['query'])) {
$new_parts['query'] = $parts['query'];
}
$new_parts['path'] = rawurldecode($new_parts['path']);
$parts = $new_parts;
// Don't do language handling for file paths.
$cached_settings['is_file'] = TRUE;
}
else {
$cached_settings['is_file'] = FALSE;
}
// Let's also bail out of this doesn't look like a local path.
$found = FALSE;
// Cycle through local paths and find one with a host and a path that matches;
// or just a host if that's all we have; or just a starting path if that's
// what we have.
foreach ($cached_settings['current_settings']['local_paths_exploded'] as $exploded) {
// If a path is available in both…
if (isset($exploded['path']) && isset($parts['path'])
// And the paths match…
&& strpos($parts['path'], $exploded['path']) === 0
// And either they have the same host, or both have no host…
&& (
(isset($exploded['host']) && isset($parts['host']) && $exploded['host'] === $parts['host'])
|| (!isset($exploded['host']) && !isset($parts['host']))
)
) {
// Remove the shared path from the path. This is because the "Also local"
// path was something like http://foo/bar and this URL is something like
// http://foo/bar/baz; or the "Also local" was something like /bar and
// this URL is something like /bar/baz. And we only care about the /baz
// part.
$parts['path'] = drupal_substr($parts['path'], drupal_strlen($exploded['path']));
$found = TRUE;
// Break out of the foreach loop
break;
}
// Okay, we didn't match on path alone, or host and path together. Can we
// match on just host? Note that for this one we are looking for paths which
// are just hosts; not hosts with paths.
elseif ((isset($parts['host']) && !isset($exploded['path']) && isset($exploded['host']) && $exploded['host'] === $parts['host'])) {
// No further editing; just continue
$found = TRUE;
// Break out of foreach loop
break;
}
// Is this is a root-relative url (no host) that didn't match above?
// Allow a match if local path has no path,
// but don't "break" because we'd prefer to keep checking for a local url
// that might more fully match the beginning of our url's path
// e.g.: if our url is /foo/bar we'll mark this as a match for
// http://example.com but want to keep searching and would prefer a match
// to http://example.com/foo if that's configured as a local path
elseif (!isset($parts['host']) && (!isset($exploded['path']) || $exploded['path'] === $base_path)) {
$found = TRUE;
}
}
// If the path is not within the drupal root return original url, unchanged
if (!$found) {
return $matches[0];
}
// Okay, format the URL.
// If there's still a slash lingering at the start of the path, chop it off.
$parts['path'] = ltrim($parts['path'],'/');
// Examine the query part of the URL. Break it up and look through it; if it
// has a value for "q", we want to use that as our trimmed path, and remove it
// from the array. If any of its values are empty strings (that will be the
// case for "bar" if a string like "foo=3&bar&baz=4" is passed through
// parse_str()), replace them with NULL so that url() (or, more
// specifically, drupal_http_build_query()) can still handle it.
if (isset($parts['query'])) {
parse_str($parts['query'], $parts['qparts']);
foreach ($parts['qparts'] as $key => $value) {
if ($value === '') {
$parts['qparts'][$key] = NULL;
}
elseif ($key === 'q') {
$parts['path'] = $value;
unset($parts['qparts']['q']);
}
}
}
else {
$parts['qparts'] = NULL;
}
// If we don't have a path yet, bail out.
if (!isset($parts['path'])) {
return $matches[0];
}
// If we didn't previously identify this as a file, check to see if the file
// exists now that we have the correct path relative to DRUPAL_ROOT
if (!$cached_settings['is_file']) {
$cached_settings['is_file'] = !empty($parts['path']) && is_file(DRUPAL_ROOT . '/'. $parts['path']);
}
// Okay, deal with language stuff.
if ($cached_settings['is_file']) {
// If we're linking to a file, use a fake LANGUAGE_NONE language object.
// Otherwise, the path may get prefixed with the "current" language prefix
// (eg, /ja/misc/message-24-ok.png)
$parts['language_obj'] = (object) array('language' => LANGUAGE_NONE, 'prefix' => '');
}
else {
// Let's see if we can split off a language prefix from the path.
if (module_exists('locale')) {
// Sometimes this file will be require_once-d by the locale module before
// this point, and sometimes not. We require_once it ourselves to be sure.
require_once DRUPAL_ROOT . '/includes/language.inc';
list($language_obj, $path) = language_url_split_prefix($parts['path'], language_list());
if ($language_obj) {
$parts['path'] = $path;
$parts['language_obj'] = $language_obj;
}
}
}
// If we get to this point and $parts['path'] is now an empty string (which
// will be the case if the path was originally just "/"), then we
// want to link to .
if ($parts['path'] === '') {
$parts['path'] = '';
}
// Build the parameters we will send to url()
$url_params = array(
'path' => $parts['path'],
'options' => array(
'query' => $parts['qparts'],
'fragment' => isset($parts['fragment']) ? $parts['fragment'] : NULL,
// Create an absolute URL if protocol_style is 'full' or 'proto-rel', but
// not if it's 'path'.
'absolute' => $cached_settings['current_settings']['protocol_style'] !== 'path',
// If we seem to have found a language for the path, pass it along to
// url(). Otherwise, ignore the 'language' parameter.
'language' => isset($parts['language_obj']) ? $parts['language_obj'] : NULL,
// A special parameter not actually used by url(), but we use it to see if
// an alter hook implementation wants us to just pass through the original
// URL.
'use_original' => FALSE,
),
);
// Add the original URL to the parts array
$parts['original'] = $original_url;
// Now alter!
// @see http://drupal.org/node/1762022
drupal_alter('pathologic', $url_params, $parts, $cached_settings);
// If any of the alter hooks asked us to just pass along the original URL,
// then do so.
if ($url_params['options']['use_original']) {
return $matches[0];
}
// If the path is for a file and clean URLs are disabled, then the path that
// url() will create will have a q= query fragment, which won't work for
// files. To avoid that, we use this trick to temporarily turn clean URLs on.
// This is horrible, but it seems to be the sanest way to do this.
// @see http://drupal.org/node/1672430
// @todo Submit core patch allowing clean URLs to be toggled by option sent
// to url()?
if (!empty($cached_settings['is_file'])) {
$cached_settings['orig_clean_url'] = !empty($GLOBALS['conf']['clean_url']);
if (!$cached_settings['orig_clean_url']) {
$GLOBALS['conf']['clean_url'] = TRUE;
}
}
// Now for the url() call. Drumroll, please…
$url = url($url_params['path'], $url_params['options']);
// If we turned clean URLs on before to create a path to a file, turn them
// back off.
if ($cached_settings['is_file'] && !$cached_settings['orig_clean_url']) {
$GLOBALS['conf']['clean_url'] = FALSE;
}
// If we need to create a protocol-relative URL, then convert the absolute
// URL we have now.
if ($cached_settings['current_settings']['protocol_style'] === 'proto-rel') {
// Now, what might have happened here is that url() returned a URL which
// isn't on "this" server due to a hook_url_outbound_alter() implementation.
// We don't want to convert the URL in that case. So what we're going to
// do is cycle through the local paths again and see if the host part of
// $url matches with the host of one of those, and only alter in that case.
$url_parts = @parse_url($url);
if (!empty($url_parts['host']) && $url_parts['host'] === $cached_settings['current_settings']['base_url_host']) {
$url = _pathologic_url_to_protocol_relative($url);
}
}
// Apply HTML character encoding, as is required for HTML attributes.
// @see http://drupal.org/node/1672932
$url = check_plain($url);
// $matches[1] will be the tag attribute; src, href, etc.
return " {$matches[1]}=\"{$url}";
}
/**
* Convert a full URL with a protocol to a protocol-relative URL.
*
* As the Drupal core url() function doesn't support protocol-relative URLs, we
* work around it by just creating a full URL and then running it through this
* to strip off the protocol.
*
* Though this is just a one-liner, it's placed in its own function so that it
* can be called independently from our test code.
*/
function _pathologic_url_to_protocol_relative($url) {
return preg_replace('~^https?://~', '//', $url);
}
Adult tissue cell plasticity, reprogramming, fate change and regeneration | MRC Centre for Regenerative Medicine
Adult tissue cell plasticity, reprogramming, fate change and regeneration
Our group studies a pioneering approach from a natural bacterial infection process with cellular reprogramming capacity to address the basic biology of stem cells and cell fate changes in adult tissues. Our recent discovery that human bacterial pathogens like Mycobacterium leprae hijacks the notable plasticity of its adult host tissue niche Schwann cells and reprograms them to stem cell-like cells opens up new premise of investigations not only for developing safer strategies for cell fate change in vivo for tissue regeneration but also for targeting key host-encoded functions of cell reprogramming for combating bacterial infections, particularly the emerging global threat by drug/antibiotic-resistant bacteria.
Our laboratory brings an innovative approach from a natural infection process to address basic biology of progenitor/stem cells and to develop new strategies for reprogramming adult tissue cells to safer progenitor/stem cells or different lineage committed cells in vivo. We study how certain intracellular bacteria, like Mycobacterium leprae as a model, hijack the adult tissue cell plasticity for their advantage. Many years of our studies on cell biology of Mycobacterium leprae infection of peripheral glial cells Schwann cells (highlighted in: Cell, 1997; 2000; Science, 1998; 2002; PNAS, 1999, 2005; Nature Medicine, 2006), led to the discovery that this bacterium has a striking capacity to reprogram adult Schwann cells to stem cell-like cells (Cell, 2013). Our current studies are focused on how these natural bacterial secrets and ingenuity of cell fate change can be exploited to regenerate injured or diseased tissues. We are also studying how these reprogrammed progenitor/stem cells can be combined with endogenous innate immune cells with natural regenerative properties to promote repair processes in demyelinating neurodegenerative, neuromuscular and liver diseases in varying model systems.
Development of translational applications of our discovery requires that we define the mechanisms and regulations of bacterial-induced host cell reprogramming processes at transcriptional, epigenetic and metabolic levels. With such mechanistic as tools our long-term goals will focus on how the property of adult tissue plasticity can be exploited to generate stem cell-like cells or different lineage committed cells in vivo that could eventually be developed into safer therapeutics in regenerative medicine. To execute our goals we use a multidisciplinary approach with a unique combination of infection biology, stem cell biology, neurobiology and synthetic biology with most up-to-date technologies in cell biology, synthetic genomics, next-generation sequencing and imaging.
We are also applying our new approach of fusion of infection biology and stem cell biology themes to develop new strategies of host-encoded functions of cell reprogramming to combat bacterial infectious diseases. In particular, since drug/antibiotic resistant bacteria are emerging as a global health threat, developing therapeutics that target host-encoded functions required for infections could be potentially effective common approach for combating drug-resistant bacteria. Such interventions would have broad-spectrum efficacy and are less likely to pressure on microbes to emerge drug resistance, a major global concern and challenge.
Selected publications
Masaki T, McGlinchey A, Cholewa-Waclaw J, Qu J, Tomlinson SR, Rambukkana A. 2014. Innate Immune Response Precedes Mycobacterium leprae-Induced Reprogramming of Adult Schwann Cells. Cell Reprogram. 16(1):9-17. doi:10.1089/cell.2013.0064. Epub 2013 Nov 26.
Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. 2013. Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection. Cell 152(1):51-67.
Tapinos N, Ohnishi M, Rambukkana A. 2006. ErbB2 receptor tyrosine kinase mediates early demyelination induced by leprosy bacilli. Nature Medicine 12:961-966.
Tapinos N, Rambukkana A. 2005. Insights into regulation of human Schwann cell proliferation by ERK-1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli. Proc. Natl. Acad. Sci. USA 102:9188-9193. See perspective in Science STKE. Nov 8:309, pe52.
Rambukkana A*, Zanazzi G, Tapinos N, Salzer JL. 2002. Contact-dependent demyelination by Mycobacterium leprae in the absence of immune responses. Science 296:927-931. *corresponding author
Ng V, Zanazzi G, Salzer JL, Timpl R, Talts JF, Brennan P, Rambukkana A. 2000. Role of the cell wall Phenolic Glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae. Cell 103:511-524.
Biography Prof Rambukkana
Prof Rambukkana relocated to the MRC Centre for Regenerative Medicine in 2010 from The Rockefeller University New York where he was a faculty member since 2000; his laboratory was funded mainly by NIH (NINDS and NIAID) grants. He obtained his PhD from the University of Amsterdam, The Netherlands, and continued his first postdoctoral training in the Academic Medical Center, University of Amsterdam. He then moved to Rockefeller University for his second postdoctoral training before obtaining his faculty position there. Prof Rambukkana is also a member of Edinburgh Infectious Diseases (EID) and Centre for Neuroregeneration (CNR).
Past lab members and their current faculty / scientific positions
2001: Yoshihiro Shimoj, Chief Scientist, Bacterial and Parasitic Diseases Research Division, and visiting professor of Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Lab publications: PNAS, 1999; PLosOne 2011);
2003: Vincent Ng, Assistant professor of Biology, Northern Virginia Community College, Virginia, USA (Lab publications, PNAS 1999; Cell, 2000);
2006: Makato Ohinishi, Head, Department of Bacteriology, National Institute of Health, Tokyo, Japan (lab publication: Nature Medicine, 2006);
2007: Nikos Tapinos, Assistant professor, Weis Center for Research, Geisinger Clinic, Danville, PA, USA (lab publications: Science, 2002; PNAS, 2005; J. Immunol. 2006; Nature Medicine, 2006);
2008: Ryan Raaum, Asst. Professor, Lehman College & The Graduate Center, The City University of New York, USA (Lab publication: Cell 2013);
2010: Jinrong Qu, Research Scientist, Memorial Sloan Kettering Cancer Center, New York, USA (Lab publications: Cell 2013; F1000Research 2013; Cell Reprogam 2014);
2012: Justyna Cholewa-Waclaw, Research Associate, Adrian Bird’s Laboratory, Center for Cell Biology University of Edinburgh, UK (Lab publications: Cell 2013; Cell Reprogam 2014);
2012: Toshihiro Masaki, Professor, Teikyo University, Tokyo, Japan (Lab publications: Cell 2013; F1000Research 2013; Cell Reprogam 2014; Book Chapter 2014).
Lab in the news
The discovery that a human bacterial pathogen naturally reprograms adult tissue cells to stem cells and implications of this finding in regenerative medicine and combatting infectious diseases made headlines in major news portal around the world and in all top ranking journals including its selection to Best of Cell 2013 collection from Cell Press.
Recommendations Faculty1000, ranked the publication on top of the top ten in the year-end ranking in 2013 with 21 stars under the exceptional category. Also published on the University of Edinburgh News website as well as on the Edinburgh Infectious Diseases website, here and here.
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