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공개·회원 9명
John Jackson
John Jackson

FULL Alias Surface 2015 Activation


Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene.[5] LAG3, which was discovered in 1990[6] and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000,[7] is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.[8]




FULL Alias Surface 2015 Activation


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In May 2004 the St. Jude Children's Research Hospital team showed, through LAG3 knockout mice, that LAG-3 negatively regulates T cell expansion and controls the size of the memory T cell pool.[17] This was in spite of earlier in vitro work that seemed to suggest that LAG-3 was necessary for T cell expansion.[16] Work at Johns Hopkins University published in October 2004 identified LAG3's key role in regulatory T cells.[18] The St. Jude Children's Research Hospital team reported in December 2004 that LAG-3 is cleaved within the D4 transmembrane domain into two fragments that remain membrane-associated: a 54-kDa fragment that contains all the extracellular domains and oligomerizes with full-length LAG-3 (70 kDa) on the cell surface via the D1 domain, and a 16-kDa peptide that contains the transmembrane and cytoplasmic domains and is subsequently released as soluble LAG-3.[46]


In 2010 scientists at Swiss Federal Institute of Technology in Zurich showed that LAG3 was an exhaustion marker for CD8+ T cells specific for Lymphocytic choriomeningitis virus, but alone did not significantly contribute to T-cell exhaustion.[56] A team at Roswell Park Comprehensive Cancer Center showed that CD8+ Tumor-infiltrating lymphocytes that were specific for NY-ESO-1 were negatively regulated by LAG-3 and PD-1 in ovarian cancer.[57] The St. Jude Children's Research Hospital group reported that most LAG3 was housed intracellularly in multiple domains before rapid translocation to the cell surface potentially facilitated by the microtubule organizing center and recycling endosomes during T-cell activation.[58] Scientists at the Istituto Nazionale dei Tumori in Milan, collaborating with the Triebel group, showed that LAG3 defines a potent regulatory T cell subset that shows up more frequently in cancer patients and is expanded at tumor sites.[59] Geneticists working at the National Cancer Institute reported that SNPs in the LAG3 gene were associated with higher risk of multiple myeloma.[60]


(D) Experimental ppERK dose response of naïve OT-1 T cells activated for 3 min with peptide-pulsed RMA-S cells, plotted as the percentage of responding cells. The Hill coefficient measured for this dose response is 1.9 0.1 (n = 3). The threshold for activation (midpoint) is 24 4 SIINFEKL-Kb on each RMA-S APC. Because the T cell's surface area is three times less than that of an RMA-S cell, as few as eight SIINFEKL-Kb ligands may be sufficient to trigger a full ppERK response if a full surface sweep of the RMA-S membrane by the T cell is not accomplished before signaling takes place.


(E) Dose response for ERK phosphorylation among naïve OT-1 T cells, after 3 min of activation by RMA-S APC pulsed with SIINFEKL peptide variants. The peptide SIINFEKL is a known agonist for OT-1 T cells, whereas EIINFEKL and SIIRFEKL are non-agonists. The percentage of responding cells is plotted as a function of the number of peptide-Kb ligands presented on the surface of each RMA-S APC.


Question: I added an index hint in my query, but the hint is being ignored. What is the correct syntax for an index hint and how do I force the index hint to be used in my query?Answer: Oracle index hint syntax is tricky because of the index hint syntax is incorrect it is treated as a comment and not implemented. Here is an example of the correct syntax for an index hint:select /*+ index(customer cust_primary_key_idx) */ * from customer;Also note that of you alias the table, you must use the alias in the index hint:select /*+ index(c cust_primary_key_idx) */ * from customer c;Also, be vary of issuing hints that conflict with an index hint. In this index hint example, the full hint is not consistent with an index hint:select /*+ full(c) index(c cust_primary_key_idx) */ * from customer c; 350c69d7ab


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