| 1. |
- Abazov, V. M., et al.
(author)
-
The upgraded DO detector
- 2006
-
In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
-
Journal article (peer-reviewed)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
|
|
| 2. |
- Boswell, M. T., et al.
(author)
-
Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
-
In: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
-
Journal article (peer-reviewed)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
|
|
| 3. |
- Boswell, Michael T., et al.
(author)
-
TRIM22 genotype is not associated with markers of disease progression in children with HIV-1 infection
- 2021
-
In: AIDS (London, England). - 1473-5571. ; 35:15, s. 2445-2450
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Untreated perinatal HIV-1 infection is often associated with rapid disease progression in children with HIV (CWH), characterized by high viral loads and early mortality. TRIM22 is a host restriction factor, which directly inhibits HIV-1 transcription, and its genotype variation is associated with disease progression in adults. We tested the hypothesis that TRIM22 genotype is associated with disease progression in CWH. DESIGN: ART-naive CWH, aged 6-16 years, were recruited from primary care clinics in Harare, Zimbabwe. We performed a candidate gene association study of TRIM22 genotype and haplotypes with markers of disease progression and indicators of advanced disease. METHODS: TRIM22 exons three and four were sequenced by Sanger sequencing and single nucleotide polymorphisms were associated with markers of disease progression (CD4+ T-cell count and HIV viral load) and clinical indicators of advanced HIV disease (presence of stunting and chronic diarrhoea). Associations were tested using multivariate linear and logistic regression models. RESULTS: A total of 241 children, median age 11.4 years, 50% female, were included. Stunting was present in 16% of participants. Five SNPs were analyzed including rs7935564, rs2291842, rs78484876, rs1063303 and rs61735273. The median CD4+ count was 342 (IQR: 195-533) cells/μl and median HIV-1 viral load 34 199 (IQR: 8211-90 662) IU/ml. TRIM22 genotype and haplotypes were not associated with CD4+ T-cell count, HIV-1 viral load, stunting or chronic diarrhoea. CONCLUSION: TRIM22 genotype was not associated with markers of HIV disease progression markers or advanced disease in CWH.
|
|
| 4. |
- Chen, Hongxia, et al.
(author)
-
PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
- 2024
-
In: Molecular Cancer Research. - 1541-7786. ; 22:1, s. 94-103
-
Journal article (peer-reviewed)abstract
- Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
