| 1. |
- Aglago, Elom K., et al.
(författare)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 2. |
- Al-Zoubi, Noura, et al.
(författare)
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Influence of manganese on the bulk properties of Fe-Cr-Mn alloys : a first-principles study
- 2014
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Ingår i: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 89:12, s. 125702-
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the effect of manganese on lattice stability and magnetic moments of paramagnetic Fe-Cr-Mn steel alloys along the Bain path connecting the body-centered cubic (bcc) and face-centered cubic (fcc) structures. The calculations are carried out using the ab initio exact muffin-tin orbital method, in combination with the coherent potential approximation, and the paramagnetic phase is modeled by the disordered local magnetic moment scheme. For all Fe-Cr-Mn alloys considered here, the local magnetic moments on Fe atoms have the minimum values for the fcc structure and the maximum values for the bcc structure, whereas the local magnetic moments on Mn have almost the same value along the constant-volume Bain path. Our results show that Mn addition to paramagnetic Fe-Cr solid solution stabilizes the bcc structure. However, when considering the paramagnetic fcc phase relative to the ferromagnetic bcc ground state, then Mn turns out to be a clear fcc stabilizer, in line with observations.
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| 3. |
- Al-Zoubi, N., et al.
(författare)
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Phase stability and elastic properties of NbMoTaWMx (M = Al, V, Zr, Tc, Re and Ir) RHEAs: A first-principles assessment
- 2024
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Ingår i: Physica. B, Condensed matter. - : Elsevier B.V.. - 0921-4526 .- 1873-2135. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Using the exact muffin-tin orbital (EMTO) method in combination with the coherent potential approximation (CPA), we studied the influence of alloying elements Al, V, Zr, Tc, Re and Ir on the phase stability, lattice parameters, densities, and elastic properties of NbMoTaWMx (M = Al, V, Zr, Tc, Re, Ir; 0 ≤ x ≤ 1.0) refractory high entropy alloys. The predicted lattice parameter and elastic parameters agree with the available experimental and theoretical data. We calculated the atomic size difference (δ), the valence electron concentration (VEC) and the total energy of face-centered cubic (fcc), body-centered cubic (bcc) and hexagonal closed-pack (hcp) structures. We found that all studied NbMoTaWMx (M = Al, V, Zr, Tc, Re, Ir; 0 ≤ x ≤ 1.0) systems have the bcc structure. We showed that Al and Ir decrease the stability of the bcc structure and Zr significantly enlarges the lattice parameter of the host. Vanadium increases the ductility of NbMoTaW system. On the other hand, Al and Ir have strongly non-linear effect on the ductility, with clear minimum at x = 0.55. The present results provide consistent theoretical data and call for experimental investigation for these alloys.
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| 4. |
- Alcaide, Pilar, et al.
(författare)
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Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue
- 2007
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 204:2, s. 431-439
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor T-bet was identified in CD4(+) T cells, and it controls interferon gamma production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432-3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet(-/-) mice is reduced. This is reproduced in adhesion studies using bone marrow-derived MCs (BMMCs) from T-bet(-/-) mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule-1 (MAdCAM-1) and vascular cell adhesion molecule-1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet(-/-) mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet(-/-) mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.
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| 5. |
- Aleksandrov, Evgenii, et al.
(författare)
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Performance budgeting and institutional work as a ‘creative distraction' of accountability relations in a municipality
- 2019
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Konferensbidrag (refereegranskat)abstract
- Purpose – The paper explores how the implementation of performance budgeting unfolds public managers’ attention and responses to competing accountability demands over time. Design/methodology/approach – This is a longitudinal study of one Russian municipality’s implementation of PB under central government pressures during 2013–2017. Using triangulation of 25interviews, documentary analysis and field observations, we employed institutional logics to guide the study. Findings – The paper demonstrates the dynamic properties of PB construction under competing accountability demands via the “creative distraction” metaphor. PB was a “distraction” mechanism, which, on one hand, strengthened external accountability, while, on the other, distracting the municipality from internal municipal demands. Nevertheless, this “distraction” was also “creative,” as it produced proactive responses to competing accountability demands and creative effects over time. Specifically, PB also led to elements of creative PB negotiations between departments when managers started cooperating with redirecting the irrelevant constraints of performance information in budgeting into necessary manipulations for municipal survival. The demonstrated “creative distraction” is explained by the changing institutional logics of public managers supplemented by a set of individual factors. Originality/value – The paper responds to the recent calls to study PB practice under several accountability demands over time. In this regard, we show the value of public managers’ existing institutional logics as they shape PB’s capacity to balance competing accountability demands. As we revealed, this capacity can be limited, due to possible misalignment between managers’ attention toward “what to give an account for” during budget formation (input orientation driven by OPA logic) and “what is demanded” with the introduction of PB (output orientation driven by NPM logic). Yet, the elements of proactive managerial responses are still evident over time, explained by a set of individual factors within the presented case, namely: learning NPM logic, strengthened informal relationships and a common saturation point reflected by managers.
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| 6. |
- Aleksandrova, Elena V, et al.
(författare)
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Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally conserved adenine residue 2503 (A2503) of the 23S rRNA by the methyltransferase Cfr. Despite its clinical significance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. In this work, we developed a method to express a functionally-active Cfr-methyltransferase in the thermophilic bacterium Thermus thermophilus and report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-tRNAs. Our structures reveal that an allosteric rearrangement of nucleotide A2062 upon Cfr-methylation of A2503 is likely responsible for the inability of some PTC inhibitors to bind to the ribosome, providing additional insights into the Cfr resistance mechanism. Lastly, by determining the structures of the Cfr-methylated ribosome in complex with the antibiotics iboxamycin and tylosin, we provide the structural bases behind two distinct mechanisms of evading Cfr-mediated resistance.
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| 7. |
- Aleksandrova, Krasimira, et al.
(författare)
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A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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| 8. |
- Allen, Matthew S., et al.
(författare)
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Weakly nonlinear systems: Modeling and experimental methods
- 2020
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Ingår i: CISM International Centre for Mechanical Sciences, Courses and Lectures. - Cham : Springer International Publishing. - 2309-3706 .- 0254-1971. ; 594, s. 269-277
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The prior chapter presented rigorous theory and methods for nonlinear systems, which is necessary in general because many nonlinear systems exhibit strong modal coupling due to the nonlinearity; this is commonly the case for the geometrically nonlinear structures that were the focus of that chapter. However, one of the most common sources of nonlinearity in built-up structures is the joints, and in many cases, these introduce only a weak stiffness nonlinearity together with a significant damping nonlinearity. In this case, and in many others that are relevant to industry, one can obtain good estimates of the response of the structure using a weakly nonlinear model in which the linear modes of the structure are presumed to be preserved and coupling between modes is neglected. This chapter provides a brief introduction to these concepts.—Chapter Authors: Randall Mayes and Matt Allen.
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| 9. |
- Allen, Mark, et al.
(författare)
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THE TWO-PHASE FRACTIONAL OBSTACLE PROBLEM
- 2015
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Ingår i: SIAM Journal on Mathematical Analysis. - : Society for Industrial and Applied Mathematics. - 0036-1410 .- 1095-7154. ; 47:3, s. 1879-1905
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Tidskriftsartikel (refereegranskat)abstract
- We study minimizers of the functional integral(+)(B1) vertical bar del u vertical bar(2)x(n)(a) dx + 2 integral(')(B1)(lambda + u(+) + lambda-u(-)) dx' for a is an element of (- 1, 1). The problem arises in connection with heat flow with control on the boundary. It can also be seen as a nonlocal analogue of the, by now well studied, two-phase obstacle problem. Moreover, when u does not change signs this is equivalent to the fractional obstacle problem. Our main results are the optimal regularity of the minimizer and the separation of the two free boundaries Gamma(+) = partial derivative'{u(center dot, 0) > 0} and Gamma(-) = partial derivative' {u(center dot, 0) < 0} when a >= 0.
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| 10. |
- Arceo-Gomez, Eva O., et al.
(författare)
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Extreme temperatures and school performance of the poor: Evidence from Mexico
- 2024
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Ingår i: ECONOMICS LETTERS. - 0165-1765 .- 1873-7374. ; 238
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Tidskriftsartikel (refereegranskat)abstract
- As the risks associated with climate change intensify, understanding its impacts on human capital development is crucial. In this paper, we analyze the causal effects of temperature on the academic performance of students in Mexico, a middle-income country facing significant climate risks and socioeconomic challenges. Using panel data on over 5.5 million students, our results show that a 1 degrees C increase in annual average temperature leads to a 0.07 and 0.08 standard deviation decrease in Spanish and math test scores, respectively. Moreover, a one standard deviation (0.93 degrees C) increase in the long-term municipal temperature average is associated with 0.04 and 0.03 standard deviation declines in those scores. The effects are context-dependent - students in historically colder municipalities actually benefit from hotter temperatures, likely due to improved learning conditions in underinsulated schools and homes. However, the detrimental impacts appear consistent across urban, rural, and socioeconomically disadvantaged areas, underscoring the vulnerability of marginalized populations to the academic consequences of climate change. Overall, our findings highlight the urgency of addressing the educational dimensions of the global climate crisis through targeted interventions and adaptive policies, particularly in lowand middle-income countries.
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