"Developers are leaking access tokens for Slack widely on GitHub, in public repositories, support tickets and public gists," a post from website security company Detectify published Thursday reads.
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If scientists could support the development of such MT systems for their fields, they could increasingly get usable gists of abstracts instantly, and find out which work might be worth full translation.
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Both "Commandment Keeper Church" and the Gists' sermons provide a context for "The Blood of Jesus" (1941), Williams's best-known film and by some accounts the most successful race movie ever made, screened for years in church basements and black-only theaters.
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The majority of GISTs present at ages 50–70 years. Across most of the age spectrum, the incidence of GIST is similar in men and women. Adult GISTs are rare before age 40. Pediatric GISTs are considered to be biologically distinct.
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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117).
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Unlike GISTs at other ages, pediatric GISTs are more common in girls and young women. They appear to lack oncogenic activating tyrosine kinase mutations in both KIT and PDGFRA. Pediatric GISTs are treated differently than adult GIST. Although the generally accepted definition of pediatric GIST is a tumor that is diagnosed at the age of 18 years or younger, "pediatric-type" GISTs can be seen in adults, which affects risk assessment, the role of lymph node resection, and choice of therapy.
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Lesser numbers of GISTs appear to be associated with neither c-kit nor PDGFR-α abnormalities. About 10-15% of gastrointestinal stromal tumors (GISTs) carry wild-type sequences in all hot spots of KIT and platelet-derived growth factor receptor alpha (PDGFRA) (wt-GISTs). These tumors are currently defined by having no mutations in exons 9, 11, 13, and 17 of the KIT gene and exons 12, 14, and 18 of the PDGFRA gene.
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In contrast-enhanced CT, small GISTs are seen as smooth, sharply defined intramural masses with homogeneous attenuation.
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For example, some previous diagnoses of stomach and small bowel leiomyosarcomas (malignant tumor of smooth muscle) would be reclassified as GISTs on the basis of immunohistochemical staining. All GIST tumors are now considered to have malignant potential, and no GIST tumor can be definitively classified as "benign". Hence, all GISTs are eligible for cancer staging in the AJCC (7th edition) / UICC.AJCC manual Nonetheless, different GISTs have different risk assessments of their tendency to recur or to metastasize, dependent on their site of origin, size, and number of mitotic figures.
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GISTs occur in 10-20 per one million people. The true incidence might be higher, as novel laboratory methods are much more sensitive in diagnosing GISTs. The estimated incidence of GIST in the United States is approximately 5000 cases annually. This makes GIST the most common form of sarcoma, which constitutes more than 70 types of cancer.
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Further, forked code can be pushed back to the original author in the form of a patch, so gists (pastes) can become more like mini-projects. Before February 18, 2018, unregistered users were able to upload text to the site. Since then, uploading gists has been deactivated for unregistered users with the aim to mitigate spamming.
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Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.
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Pastebins may allow commenting where readers can post feedback directly on the page. GitHub Gists are a type of pastebin with version control.
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Since GISTs arise from the bowel layer called muscularis propria (which is deeper to the mucosa and submucosa from a luminal perspective), small GIST imaging usually suggest a submucosal process or a mass within the bowel wall. In barium swallow studies, these GISTs most commonly present with smooth borders forming right or obtuse angles with the nearby bowel wall, as seen with any other intramural mass. The mucosal surface is usually intact except for areas of ulceration, which are generally present in 50% of GISTs. Ulcerations fill with barium causing a bull's eye or target lesion appearance.
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If an abnormality is seen, it will be an indirect sign due to the tumor mass effect on adjacent organs. On abdominal x-ray, stomach GISTs may appear as a radiopaque mass altering the shape of the gastric air shadow. Intestinal GISTs may displace loops of bowel and larger tumors may obstruct the bowel and films will show an obstructive pattern. If cavitations are present, plain radiographs will show collections of air within the tumor.
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Non-enhanced CT image of a small GIST in the posterior stomach wall (arrow). The lesion appears subserosal. Incidental finding. Plain radiographs are not very helpful in the evaluation of GISTs.
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Laparoscopic surgery, a minimally invasive abdominal surgery using telescopes and specialized instruments, has been shown to be effective for removal of these tumors without needing large incisions. The clinical issues of exact surgical indications for tumor size are controversial. The decision of appropriate laparoscopic surgery is affected by tumor size, location, and growth pattern. Radiotherapy has not historically been effective for GISTs and GISTs do not respond to most chemotherapy medications, with responses in less than 5%.
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Large tumors tend to exhibit malignant behavior but small GISTs may also demonstrate clinically aggressive behavior. gastric cardia. The lesion appears submucosal, is hypervascular and protrudes intraluminally. Upper GI bleeding led to endoscopy, finding an ulcerated mass.
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Antibodies to KIT are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for KIT, but negative for markers such as desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, KIT staining is typically cytoplasmic, with stronger accentuation along the cell membranes. KIT antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas.
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They rarely occur in other abdominal organs. GISTs are thought to arise from interstitial cells of Cajal (ICC), that are normally part of the autonomic nervous system of the intestine. They serve a pacemaker function in controlling motility.
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Imatinib is used to treat chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. In 2006 the FDA expended approved use to include Dermatofibrosarcoma protuberans (DFSP), Myelodysplastic/myeloproliferative diseases (MDS/MPD), Aggressive systemic mastocytosis. (ASM).
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PAMT was first described by Takahashi et al. in 2007. Estimated frequency of PAMT is less than 1/150 compared to that of gastrointestinal stromal tumors (GISTs). The prevalence is similar in both genders and can develop at any age (7–75 years).
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The FDA first granted approval for advanced GIST patients in 2002. On 1 February 2012, imatinib was approved for use after the surgical removal of KIT-positive tumors to help prevent recurrence. The drug is also approved in unresectable KIT-positive GISTs.
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GISTs may present with trouble swallowing, gastrointestinal bleeding, or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor's outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made.
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GISTs are tumors of connective tissue, i.e. sarcomas; unlike most gastrointestinal tumors, they are nonepithelial. About 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity.
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Kallithea supports hosting repositories of Mercurial and Git version control systems. Repositories can be grouped and thus allow to define common properties like access control. Its web interface for projects allows to fork as well as management of pull requests. It can also be used to quickly exchange code snippets by means of a revision controlled pastebin ("gists").
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Calcification is an unusual feature of GIST but if present can be visible on plain films. Barium fluoroscopic examinations and CT are commonly used to evaluate the patient with abdominal complaints. Barium swallow images show abnormalities in 80% of GIST cases. However, some GISTs may be located entirely outside the lumen of the bowel and will not be appreciated with a barium swallow.
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Preferred imaging modalities in the evaluation of GISTs are CT and MRI, and, in selected situations, endoscopic ultrasound. CT advantages include its ability to demonstrate evidence of nearby organ invasion, ascites, and metastases. The ability of MRI to produce images in multiple planes is helpful in determining the bowel as the organ of origin (which is difficult when the tumor is very large), facilitating diagnosis.
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Image showing Gastrointestinal Stromal Tumor after surgical removal Localized, resectable adult GISTs, if anatomically and physiologically feasible, surgery is the primary treatment of choice. Surgery can be potentially curative, but watchful waiting may be considered in small tumors in carefully selected situations. Post-surgical adjuvant treatment may be recommended. Lymph node metastases are rare, and routine removal of lymph nodes is typically not necessary.
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Subsequent advances in molecular biology have led to the current terminology of gastrointestinal stromal tumors (GISTs).Boccon-Gibod L, Boman F, Boudjemaa S, Fabre M, Leverger G, Carney AJ. "Separate occurrence of extra-adrenal paraganglioma and gastrointestinal stromal tumor in monozygotic twins: probable familial Carney syndrome." Pediatr Dev Pathol. 2004;7(4):380-4. However, there is limited evidence to suggest that the gastrointestinal stromal tumors (GIST) in Carney triad lack CD117 (c-kit) mutations (i.e.
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Social cognitive theory is a learning theory based gists agree that the environment one grows up in contributes to behavior, the individual person (and therefore cognition) is just as important. People learn by observing others, with the environment, behavior, and cognition acting as primary factors that influence development in a reciprocal triadic relationship. Each behavior witnessed can change a person's way of thinking (cognition). Similarly, the environment one is raised in may influence later behaviors.
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However, three medications have been identified for clinical benefit in GIST: imatinib, sunitinib, and regorafenib. Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl inhibition, also inhibits both c-kit tyrosine kinase mutations and PDGFRA mutations other than D842V, is useful in treating GISTs in several situations. Imatinib has been used in selected neoadjuvant settings. In the adjuvant treatment setting, the majority of GIST tumors are cured by surgery, and do not need adjuvant therapy.
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KIT is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of KIT. In addition, the gene encoding KIT is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon. Mutations of KIT have also been implicated in leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumors (GISTs).
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Most GISTs are sporadic. Less than 5% occur as part of hereditary familial or idiopathic multitumor syndromes. These include, in descending order of frequency, neurofibromatosis Recklinghausen (NF-1), Carney's triad (gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma), germline gain-of-function mutations in c-Kit/PDGFRA, and the Carney-Stratakis syndrome. The Carney-Stratakis syndrome is a dyad of hereditary GIST and paraganglioma, that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase (SDH) subunits SDHD, SDHC and SDHB.
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A biopsy sample will be investigated under the microscope by a pathologist physician. The pathologist examines the histopathology to identify the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be confined to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen.
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When GIST is suspected-- as opposed to other causes for similar tumors--the pathologist can use immunohistochemistry (specific antibodies that stain the molecule CD117 [also known as c-kit] --see below). 95% of all GISTs are CD117-positive (other possible markers include CD34, DOG-1, desmin, and vimentin). Other cells that show CD117 positivity are mast cells. If the CD117 stain is negative and suspicion remains that the tumor is a GIST, the newer antibody DOG-1 (Discovered On GIST-1) can be used.
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The essence of semantic memory is that its contents are not tied to any particular instance of experience, as in episodic memory. Instead, what is stored in semantic memory is the "gist" of experience, an abstract structure that applies to a wide variety of experiential objects and delineates categorical and functional relationships between such objects. Thus, a complete theory of semantic memory must account not only for the representational structure of such "gists", but also for how they can be extracted from experience. Numerous models of semantic memory have been proposed; they are summarized below.
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In the case of Gleevec (Imatinib), which targets the BCR-ABL fusion gene in chronic myeloid leukemia, resistance often develops through a mutation that changes the shape of the binding site of the drug. Sequential application of drugs can lead to the sequential evolution of resistance mutations to each drug in turn. Gleevec is not as selective as was originally thought. It turns out that it targets other tyrosine kinase genes and can be used to control gastrointestinal stromal tumors (GISTs) that are driven by mutations in c-KIT.
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Tyrosine kinase inhibitors (such as sunitinib, pazopanib, and dasatinib) have shown some effect against several cancer types, most notably Imatinib-mesylate in gastrointestinal stromal tumors (GISTs). Tyrosine kinase (a subclass of protein kinases) is an enzyme that transfers a phosphate group from an ATP molecule to a protein in a cell. It functions as an “on” or “off” switch for many cellular functions, including signaling within the cell, and cell division. Tyrosine kinases can contain mutations that cause them to become constitutively active, or stuck in the “on” position, resulting in unregulated cell division (a hallmark of cancer).
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The selection criteria underpinning the decision for possible use of imatinib in these settings include a risk assessment based on pathological factors such as tumor size, mitotic rate, and location can be used to predict the risk of recurrence in GIST patients. Tumors <2 cm with a mitotic rate of <5/50 HPF have been shown to have lower risk of recurrence than larger or more aggressive tumors. Following surgical resection of GISTs, adjuvant treatment with imatinib reduces the risk of disease recurrence in higher risk groups. In selected higher risk adjuvant situations, imatinib is recommended for 3 years.
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In contrast enhanced CT images, large GISTs appear as heterogeneous masses due to areas of living tumor cells surrounding bleeding, necrosis or cysts, which is radiographically seen as a peripheral enhancement pattern with a low attenuation center. In MRI studies, the degree of necrosis and bleeding affects the signal intensity pattern. Areas of bleeding within the tumor will vary its signal intensity depending on how long ago the bleeding occurred. The solid portions of the tumor are typically low signal intensity on T1-weighted images, are high signal intensity on T2-weighted images and enhance after administration of gadolinium.
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Additionally, in the absence of specific therapy, the diagnostic categorization had only a limited influence on prognosis and therapy. The understanding of GIST biology changed significantly with identification of the molecular basis of GIST, particularly c-KIT. Historically, literature reviews prior to the molecular definition of GIST, and for a short time thereafter, asserted that 70-80% of GISTs were benign. The identification of a molecular basis for GIST led to the exclusion of many tumors that had been considered as GIST previously, and also the incorporation of a much larger number of tumors that had been labeled as other types of sarcomas and undifferentiated carcinomas.
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During his postdoctoral training in the Jacks Laboratory, Tuveson learned how to engineer mouse models to study human cancer. During this time, he also studied gastrointestinal stromal tumors (GISTs), and worked with Dr. George Demetri to develop imatinib as a treatment for GIST. When he started his own laboratory at the University of Pennsylvania, Tuveson developed some of the first genetically engineered mouse models to aid in the study of pancreatic cancer. Using these mice, Tuveson has made several important discoveries in the biology of pancreatic cancer, including the work that contributed to the idea that the stromal cells of pancreatic tumors act as a barrier for therapies.
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The misattribution error often leads to conclusions of an inefficient memory system, however some researchers believe that the error is a cost associated with the benefits of a functioning and adequate memory system. The misattribution error reflects an adaptive memory system in which information that does not require people to remember all the specific details is lost. Specific details would only be preserved in situations where the specific details need to be remembered, such as memories of a highly emotional experience. The use of semantic gists may be a fundamental mechanism of memory, allowing people to categorize information and generalize across situations, a function associated with higher intelligence.
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The efficacy of imatinib (trade name Gleevec), a KIT inhibitor, is determined by the mutation status of KIT: When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemias), the receptor is not inhibited by imatinib. In those cases other inhibitors such as dasatinib and nilotinib can be used. Researchers investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting computational analysis.
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Although the BCR region also expresses serine/threonine kinases, the tyrosine kinase function is very relevant for drug therapy. As the N-terminal Y177 and CC domains from BCR encode the constitutive activation of the ABL1 kinase, these regions are targeted in therapies to downregulate BCR-ABL1 kinase activity. Tyrosine kinase inhibitors specific to such domains as CC, Y177, and Rho (such as imatinib and sunitinib) are important drugs against a variety of cancers including CML, renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GISTs). The fused BCR-ABL1 protein interacts with the interleukin-3 receptor beta(c) subunit and is moderated by an activation loop within its SH1 domain, which is turned “on” when bound to ATP and triggers downstream pathways.
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