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1.
Unlikelihood that minimal phylogenies for a realistic biological study can be constructed in reasonable computational time 总被引:1,自引:0,他引:1
R. L. Graham 《Mathematical biosciences》1982,60(2):133-142
The problem of determining a phylogeny of maximum parsimony from a given set of protein sequences is defined. It is shown that this problem is what is called, in computer science, NP-complete. The implication of this result is that it is equivalent in difficulty to a host of other problems in combinatorial optimization which are notorious for their intractability. This implies that it is more fruitful to attempt to develop heuristic techniques (which do not guarantee maximum parsimony but which do run in reasonable computer time) than to try to develop exact algorithms for phylogeny construction 相似文献
2.
Minh C. Nguyen Guang Huan Tu Kathryn E. Koprivnikar Melissa Gonzalez-Edick Karin U. Jooss Thomas C. Harding 《Cancer immunology, immunotherapy : CII》2010,59(9):1313-1323
A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that
may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened
with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy.
Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis,
galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis
of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly
correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence
following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1
was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody
induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in
prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived
antibody responses. 相似文献
3.
Annette Graham 《Free radical research》1998,28(6):611-621
Compelling evidence suggests that low-density lipoprotein (LDL) is oxidized by cells within the arterial intima and that, once oxidized, it is profoundly atherogenic. The precise mechanism(s) by which cells promote the oxidation of LDL in vivo are not known; in vitro, however, oxidation of LDL can be enhanced by a number of differing mechanisms, including reaction with free and protein-bound metal ions, thiols, reactive oxygen species, lipoxygenase, myeloperoxidase and peroxynitrite. This review is concerned with the mechanisms by which cells enhance the oxidation of LDL in the presence of transition metals; in particular, the regulation, pro- and anti-oxidant consequences, and mechanism of action of cellular thiol production are examined, and contrasted with thiol-independent oxidation of LDL in the presence of transition metals. 相似文献
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6.
Neurofilament Protein Phosphorylation in Spinal Cord of Experimentally Diabetic Rats 总被引:1,自引:1,他引:0
This study was designed to determine if the known decrease in slow axonal transport of proteins in the sciatic nerve of experimentally diabetic rats is related to altered phosphorylation of neurofilament proteins (NFPs). Rats were rendered diabetic with 50 mg/kg of streptozotocin, i.p. At 3 and 6 weeks later, NFPs were prepared from spinal cord. The in vivo phosphorylation state of NFPs was examined by using phosphate-dependent (RT97) and -independent (RMd09) antibodies against high-molecular-mass NFPs on Western blots. Neurofilament-associated kinase activity was also measured in vitro by incubation of NFPs with [32P]ATP. Phosphorylation of all three NFPs (high, medium, and low molecular mass) occurred, as confirmed by gel electrophoresis and autoradiography. At 30 min of incubation, protein-bound radioactivity in NFPs from diabetic animals was reduced to 86.7 +/- 3.4 and 54.3 +/- 19.6% of that in nondiabetic animals at 3 and 6 weeks of diabetes, respectively (p less than 0.001 and p less than 0.05, respectively). NFPs were also incubated with acid phosphatase and rephosphorylated. Results showed that the increased in vivo phosphorylation contributed to the decreased in vitro phosphorylation. Extraction of protein kinases and addition back to the NFPs revealed, in addition, a reduced activity in the diabetic animals of the protein kinases measured in vitro. 相似文献
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8.
I. J. Pickering Graham N. George Verena Van Fleet-Stalder Thomas G. Chasteen Roger C. Prince 《Journal of biological inorganic chemistry》1999,4(6):791-794
Received: 2 April 1999 / Accepted: 17 September 1999 相似文献
9.
Kathryn L. Butler Vijayakrishnan Ambravaneswaran Nitin Agrawal Maryelizabeth Bilodeau Mehmet Toner Ronald G. Tompkins Shawn Fagan Daniel Irimia 《PloS one》2010,5(7)
Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72–120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions. 相似文献
10.