/**
* 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);
}
Remyelination in multiple sclerosis | MRC Centre for Regenerative Medicine
In the brain and spinal cord, nerves are covered by an insulating sheath of membrane called a myelin sheath. This allows fast transmission of electrical impulses and protects and maintains the nerve. In multiple sclerosis (MS), patches of demyelination occur, where these myelin sheaths are damaged and stripped off the nerve. This causes neurological symptoms such as paralysis, sensory changes and blindness. Replacement of these myelin sheaths (remyelination) can happen in MS, which can restore nerve function. This is generally inefficient, and often a scar forms instead, causing a long-term problem for the patient. Remyelination is carried out by oligodendrocyte precursor cells which are attracted to the damaged area, make contact with nerves, mature and form myelin sheaths to replace those that are damaged. A failure of remyelination can occur with a problem at any one of these steps. If we can understand the mechanisms of each step, we may be able to manipulate them to improve the efficiency of remyelination.
Understand why remyelination fails in Multiple Sclerosis, and
Improve the efficiency of remyelination in MS.
Approach
To study this we use in vitro and ex vivo cultures of rodents and use human ES derived cells, human post mortem tissue and in vivo rodent and zebrafish models. We seek to understand better the remyelination process (often using imaging), and find targets to be able to manipulate it, using both candidate and screening approaches. We manipulate levels of molecules of interest with recombinant proteins, lentiviral transduction and using transgenic animals. We are particularly interested in molecules that control recruitment of oligodendrocyte precursor cells into demyelinated lesions, and are currently investigating small molecule inhibitors of chemorepulsive factors for OPCs.
Recent publication
Our group recently published on the therapeutic potential of drugs to reverse endothelial dysfunction in the treatment of Small Vessel Disease, a major cause of dementia and stroke. To obtain free access to this publication, follow the links below.
Rajani et al (2018). Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats. Science Translational Medicine 04 Jul 2018: Vol. 10, Issue 448, eaam9507. DOI: 10.1126/scitranslmed.aam9507 Abstract | Reprint | Full text
This video describes the work (Ranjani et al, 2018) and its implications.
Related activities
Clinical work: I am also an honorary consultant neurologist, and I carry out general neurology and MS clinics in the Royal Infirmary of Edinburgh.
MRC UK Regenerative Medicine Platform - Exploring the Stem Cell Niche Hub - Co-applicant, with Hub receiving £5.6 million. Starts Nov 2013 for 5 years.
Scottish Senior Fellowship – May 2013-2017 £330k CSO - Targeting OPC migration towards remyelination therapies in multiple sclerosis May 2013. 12 months. £95k.
Wellcome Trust Intermediate Fellowship - Semaphorins in the control of remyelination in multiple sclerosis– May 2008-May2013 - £824,795.
Co-applicant for CSO grant with Prof. Steve Anderton - Probing regulatory T cells in multiple sclerosis brain Jan 2011-July 2012 - £165k.
Wellcome Trust Institutional Strategic Support Fund (WT-ISSF)- Highly multiplexed single-cell RNA sequencing with Dr Keisuke Kaji and Dr Sally Lowell – June-sept 2012 - £20k
Wellcome Trust Institutional Strategic Support Fund (WT-ISSF) - Label-free imaging of compact myelin;enabling high-throughput screens for novel remyelination therapies – with Prof. Alistair Elfick, Dr Rabah Mouras, School of Engineering, and Prof. Charles ffrench-Constant July -Nov 2012 - £50k
Alzheimer’s Research UK Pilot Grant, Three-dimensional modelling of endothelial cell dysfunction in cerebral small vessel disease. 2016-2017 £50k
GSK - CNS slice cultures as a tool for remyelination research – starts April 2015 for 2 years. £350k
Sanofi-Genzyme - Identification of selective and potent inhibitors of the Semaphorin 3A Receptor Neuropilin-1 interaction on oligodendrocyte precursor cells to promote remyelination in Multiple Sclerosis – march 2015 for 2 years.
MS society innovative grant - Optogenetic cell ablation in a focal CNS demyelination model in slice cultures – starts January 2015 for 1 year. £40k
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