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Discovery of novel active-site-directed irreversible inhibitors of the tumour necrosis factor-alpha converting enzyme (TACE) as potential anticancer agents.
Overexpression of tumour necrosis factor (TNF)-alpha has been shown to correlate with the development of many cancers. The enzyme TACE (also known as ADAM17) is responsible for the release of soluble TNF-alpha from its precursor and so is an important target in cancer therapy. Here we describe the identification of a series of novel active-site-directed inhibitors of TACE with low nanomolar activity in cell-based assays that are selective for the TACE/TNF-alpha system over other ADAMs and susceptible to the covalent labelling of exposed cysteine residues in the active site. A heterocyclic structure is essential for optimal activity, and a new class of compounds, the 4-benzylthiazolidinone (4-BT) derivatives, was identified. These compounds show high potency in whole-cell assays (IC(50) range, 0.5-5 nM), with corresponding values of 0.1-0.5 nM in cell-free assays. Key structural features include the presence of either a short peripheral lipophilic group and an aromatic group on the C-5 position of the thiazolidine ring, or the presence of a short peripheral lipophilic group and a 5-benzyl (Bn) ester moiety on the C-4 position of the thiazolidine ring. These compounds show promising in vitro cytotoxicity in cancer cells, including those overexpressing TNF-alpha, as well as in vivo efficacy in a mouse xenograft model.Q:
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1932 World Table Tennis Championships – Men’s Doubles
The 1932 World Table Tennis Championships – Men’s Doubles was the seventh edition of the men’s doubles championship.
Chen Yung-tang and Hsiao Kuan-chi won the title after defeating Rikard Rangl and Gardy Gotthardt in the final by three sets to nil.
Results
See also
List of World Table Tennis Championships medalists
References
-Birmingham: a unique case for Pakistan
1. Pakistan was founded on the basis of religion and now it is being destroyed on the basis of religion. This is a reality that Pakistanis should face squarely.
2. As a nation, they have not yet understood the real meaning of the status ‘emperor’.
3. The preamble to the Constitution has not been amended to reflect the paradigm shift from a Muslim state to a secular society.
4. The Parliamentary system has not been reformed to reduce the majority-minority problem in the country.
5. The Press Council has not been implemented to ensure freedom of the press and access to information.
6. The Election Commission has not been democratised.
7. The ISI has not been democratised.
8. The judiciary has not been reformed.
9. The policy of neutralisation of the armed forces has not been implemented.
10. The armed forces have not been democratised.
11. The economy has not been privatised.
12. Although taxation has been reduced, the budget deficit has been kept high.
13. An elected federal government has not been established.
14. The judicial system has not been reformed.
15. The army’s role has not been reduced.
16. Media autonomy has been denied by the government.
17. The representative system has not been established.
18. The civil services have not been demilitarised.
19. The state has not been privat
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Sparse matrix vector multiplication [C]
I was reading about sparse matrices and in Cuda API sparse matrices are represented with struct. I was wondering whether the.* operator can be performed only in the sense of matrices, i.e., one operates on the matrix and returns only the nonzero elements of the result.
I would appreciate it if someone can throw some light.
A:
I assume you’re looking for the dot-product. Let’s look at the definition of the dot-product from The Python Algorithms Handbook:
x.dot(y): x.dot(y) = (x * y)
Looks like it could probably be done in C as:
int result;
for (int i = 0; i Human p21(WAF1/Cip1) protein, a candidate tumour suppressor gene product, is restricted to the G(1) and G(2) phases of the cell cycle.
We report the first evidence that p21(WAF1/Cip1) is a candidate suppressor gene product in vivo. This protein appears to be a part of a cell-cycle checkpoint as it is induced when cells are arrested at the G(1) or G(2) phase of the cell cycle by DNA-damaging agents. It is of interest that, in addition to being a key regulator of DNA-damage checkpoint functions, p21(WAF1/Cip1) also seems to be related to the fundamental growth control process since it is overexpressed in hyperplastic rat kidneys, where cell proliferation is increased. Finally, the highly restricted expression of p21(WAF
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