| 1. |
- Aad, G., et al.
(author)
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- 2011
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swepub:Mat__t (peer-reviewed)
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| 2. |
- Aad, G., et al.
(author)
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- 2011
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swepub:Mat__t
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| 3. |
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| 4. |
- Aad, G., et al.
(author)
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- 2010
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swepub:Mat__t
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| 5. |
- Aad, G., et al.
(author)
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- 2010
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swepub:Mat__t
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| 6. |
- Aad, G., et al.
(author)
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- 2010
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swepub:Mat__t
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| 7. |
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| 8. |
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| 9. |
- Aad, G., et al.
(author)
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- 2010
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swepub:Mat__t
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| 10. |
- Aad, G., et al.
(author)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Journal article (peer-reviewed)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 11. |
- Aad, G., et al.
(author)
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The ATLAS Simulation Infrastructure
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Journal article (peer-reviewed)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 12. |
- Aad, G., et al.
(author)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Journal article (peer-reviewed)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 13. |
- Aad, G., et al.
(author)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Journal article (peer-reviewed)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 14. |
- Aad, G., et al.
(author)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Journal article (peer-reviewed)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 15. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Bernal, Ximena E., et al.
(author)
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Empowering Latina scientists
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Journal article (other academic/artistic)
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| 23. |
- Danesh, John, et al.
(author)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Research review (peer-reviewed)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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| 24. |
- Lønborg, C., et al.
(author)
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A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
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In: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
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Journal article (peer-reviewed)abstract
- Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters.
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| 25. |
- Güsten, R., et al.
(author)
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APEX - The Atacama Pathfinder Experiment
- 2006
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6267 I
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Conference paper (peer-reviewed)abstract
- APEX, the Atacama Pathfinder Experiment, has been successfully commissioned and is in operation now. This novel submillimeter telescope is located at 5107 m altitude on Llano de Chajnantor in the Chilean High Andes, on what is considered one of the world's outstanding sites for submillimeter astronomy. The primary reflector with 12 m diameter has been carefully adjusted by means of holography. Its surface smoothness of 17-18 μm makes APEX suitable for observations up to 200 μm, through all atmospheric submm windows accessible from the ground.
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| 26. |
- Juran, S., et al.
(author)
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The Development and Inclusion of Questions on Surgery in the 2018 Zambia Demographic and Health Survey
- 2021
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In: Global Health-Science and Practice. - : Johns Hopkins School Bloomberg School of Public Health, Center for Communication Programs. - 2169-575X. ; 9:4, s. 905-914
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Journal article (peer-reviewed)abstract
- Background: While primary data on the unmet need for surgery in low- and middle-income countries is lacking, household surveys could provide an entry point to collect such data. We describe the first development and inclusion of questions on surgery in a nationally representative Demographic and Health Survey (DHS) in Zambia. Method: Questions regarding surgical conditions were developed through an iterative consultative process and integrated into the rollout of the DHS survey in Zambia in 2018 and administered to a nationwide sample survey of eligible women aged 15-49 years and men aged 15-59 years. Results: In total, 7 questions covering 4 themes of service delivery, diagnosed burden of surgical disease, access to care, and quality of care were added. The questions were administered across 12,831 households (13,683 women aged 15-49 years and 12,132 men aged 15-59 years). Results showed that approximately 5% of women and 2% of men had undergone an operation in the past 5 years. Among women, cesarean delivery was the most common surgery; circumcision was the most common procedure among men. In the past 5 years, an estimated 0.61% of the population had been told by a health care worker that they might need surgery, and of this group, 35% had undergone the relevant procedure. Conclusion: For the first time, questions on surgery have been included in a nationwide DHS. We have shown that it is feasible to integrate these questions into a large-scale survey to provide insight into surgical needs at a national level. Based on the DHS design and implementation mechanisms, a country interested in including a set of questions like the one included in Zambia, could replicate this data collection in other settings, which provides an opportunity for systematic collection of comparable surgical data, a vital role in surgical health care system strengthening.
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| 27. |
- Ortiz, L., et al.
(author)
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Measuring the fracture toughness of single WC grains of cemented carbides by means of microcantilever bending and micropillar splitting
- 2021
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In: International journal of refractory metals & hard materials. - : Elsevier. - 0263-4368. ; 98
-
Journal article (peer-reviewed)abstract
- The main goal of this work is to obtain a reliable value of the fracture toughness of single grains of tungsten carbide (WC). It is attempted by testing microcantilever and micropillar samples shaped out, by means of focused ion beam milling, of individual WC particles embedded within a WC-Co cemented carbide grade. Experimental testing included the use of a nanoindenter for inducing microcantilever bending and micropillar splitting, as well as sampling WC grains with basal and prismatic orientations. Experimental results are compared with those previously assessed through implementation of the indentation microfracture technique. Bending of notched microcantilevers yielded more consistent results than those measured out of micropillar splitting tests. In this regard, the average value of fracture toughness for single WC grains, within the two-phase interpenetrated network existing in cemented carbides, is found to be 5.6 ± 0.8 MPa·m1/2. Such a relatively high value – coherent with local plastic features evidenced in nanoindentation imprints - is in satisfactory agreement with results indirectly estimated from other macromechanical tests.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Al-Shammari, I., et al.
(author)
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Implementation of an international standardized set of outcome indicators in pregnancy and childbirth in Kenya: Utilizing mobile technology to collect patient-reported outcomes
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10
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Journal article (peer-reviewed)abstract
- Background Limited data exist on health outcomes during pregnancy and childbirth in low- and middleincome countries. This is a pilot of an innovative data collection tool using mobile technology to collect patient-reported outcome measures (PROMs) selected from the International Consortium of Health Outcomes Measurement (ICHOM) Pregnancy and Childbirth Standard Set in Nairobi, Kenya. Methods Pregnant women in the third trimester were recruited at three primary care facilities in Nairobi and followed prospectively throughout delivery and until six weeks postpartum. PROMs were collected via mobile surveys at three antenatal and two postnatal time points. Outcomes included incontinence, dyspareunia, mental health, breastfeeding and satisfaction with care. Hospitals reported morbidity and mortality. Descriptive statistics on maternal and child outcomes, survey completion and follow-up rates were calculated. Results In six months, 204 women were recruited: 50% of women returned for a second ante-natal care visit, 50% delivered at referral hospitals and 51% completed the postnatal visit. The completion rates for the five PROM surveys were highest at the first antenatal care visit (92%) and lowest in the postnatal care visit (38%). Data on depression, dyspareunia, fecal and urinary incontinence were successfully collected during the antenatal and postnatal period. At six weeks postpartum, 86% of women breastfeed exclusively. Most women that completed the survey were very satisfied with antenatal care (66%), delivery care (51%), and post-natal care (60%). Conclusion We have demonstrated that it is feasible to use mobile technology to follow women throughout pregnancy, track their attendance to pre-natal and post-natal care visits and obtain data on PROM. This study demonstrates the potential of mobile technology to collect PROM in a low-resource setting. The data provide insight into the quality of maternal care services provided and will be used to identify and address gaps in access and provision of high quality care to pregnant women. © 2019 Al-Shammari et al.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Franssen, D, et al.
(author)
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AMP-activated protein kinase (AMPK) signaling in GnRH neurons links energy status and reproduction.
- 2021
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In: Metabolism: clinical and experimental. - 1532-8600. ; 115
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Journal article (peer-reviewed)abstract
- Reproduction is tightly coupled to body energy and metabolic status. GnRH neurons, master elements and final output pathway for the brain control of reproduction, directly or indirectly receive and integrate multiple metabolic cues to regulate reproductive function. Yet, the molecular underpinnings of such phenomenon remain largely unfolded. AMP-activated protein kinase (AMPK), the fundamental cellular sensor that becomes activated in conditions of energy deficit, has been recently shown to participate in the control of Kiss1 neurons, essential gatekeepers of the reproductive axis, by driving an inhibitory valence in situations of energy scarcity at puberty. However, the contribution of AMPK signaling specifically in GnRH neurons to the metabolic control of reproduction remains unknown.Double immunohistochemistry (IHC) was applied to evaluate expression of active (phosphorylated) AMPK in GnRH neurons and a novel mouse line, named GAMKO, with conditional ablation of the AMPK α1 subunit in GnRH neurons, was generated. GAMKO mice of both sexes were subjected to reproductive characterization, with attention to puberty and gonadotropic responses to kisspeptin and metabolic stress.A vast majority (>95%) of GnRH neurons co-expressed pAMPK. Female (but not male) GAMKO mice displayed earlier puberty onset and exaggerated LH (as surrogate marker of GnRH) responses to kisspeptin-10 at the prepubertal age. In adulthood, GAMKO females retained increased LH responsiveness to kisspeptin and showed partial resilience to the inhibitory effects of conditions of negative energy balance on the gonadotropic axis. The modulatory role of AMPK in GnRH neurons required preserved ovarian function, since the differences in LH pulsatility detected between GAMKO and control mice subjected to fasting were abolished in ovariectomized animals.Altogether, our data document a sex-biased, physiological role of AMPK signaling in GnRH neurons, as molecular conduit of the inhibitory actions of conditions of energy deficit on the female reproductive axis.
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| 36. |
- Garcia, P, et al.
(author)
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Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer
- 2020
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:4
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Journal article (peer-reviewed)abstract
- Gallbladder cancer is an aggressive disease with late diagnosis and no efficacious treatment. The Hippo-Yes-associated protein 1 (YAP1) signaling pathway has emerged as a target for the development of new therapeutic interventions in cancers. However, the role of the Hippo-targeted therapy has not been addressed in advanced gallbladder cancer (GBC). This study aimed to evaluate the expression of the major Hippo pathway components mammalian Ste20-like protein kinase 1 (MST1), YAP1 and transcriptional coactivator with PDZ-binding motif (TAZ) and examined the effects of Verteporfin (VP), a small molecular inhibitor of YAP1-TEA domain transcription factor (TEAD) protein interaction, in metastatic GBC cell lines and patient-derived organoids (PDOs). Immunohistochemical analysis revealed that advanced GBC patients had high nuclear expression of YAP1. High nuclear expression of YAP1 was associated with poor survival in GBC patients with subserosal invasion (pT2). Additionally, advanced GBC cases showed reduced expression of MST1 compared to chronic cholecystitis. Both VP treatment and YAP1 siRNA inhibited the migration ability in GBC cell lines. Interestingly, gemcitabine resistant PDOs with high nuclear expression of YAP1 were sensitive to VP treatment. Taken together, our results suggest that key components of the Hippo-YAP1 signaling pathway are dysregulated in advanced gallbladder cancer and reveal that the inhibition YAP1 may be a candidate for targeted therapy.
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| 37. |
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| 38. |
- Gordon, S., et al.
(author)
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Mechanical integrity of PVD TiAlN-coated PcBN : Influence of substrate bias voltage and microstructural assemblage
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In: Ceramics International. - 0272-8842.
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Journal article (peer-reviewed)abstract
- Polycrystalline cubic boron nitrides (PcBN) have been increasingly used together with PVD coatings, mainly for hard turning operations. Within this context, effectiveness of coated PcBN as cutting tool is usually addressed by evaluation of its machining performance. Meanwhile, studies aiming to assess and understand the correlation between microstructural features and mechanical behaviour of the coating-substrate system are rather limited. Aiming to overcome such lack of information, in this study the influence of substrate bias voltage (−35 V as compared to −60 V) and microstructural assemblage (as a function of cBN content and binder chemical nature) on the mechanical integrity of TiAlN-coated PcBN systems is investigated. In doing so, contact damage response and coating adhesion strength of different coated-PcBNs are evaluated by means of indentation testing using distinct loading conditions (static and sliding) and tip geometries (spherical and conical). Such testing program is complemented by detailed FESEM inspection of the involved failure micromechanisms, as well as microstructural and micromechanical characterization of the deposited films. Results indicate that resistance against crack nucleation and propagation of coated PcBN, induced by either spherical or conical indentation, is enhanced by using harder (high content of cBN particles) and tougher (metallic binder) substrates (H-PcBN). Regarding bias voltage, systems with coatings deposited using a higher value (−60 V as compared to −35 V) show improved adhesive strength, this being particularly true for combinations involving low cBN content and ceramic binder substrate (L-PcBN). Similar beneficial effect was found, but exclusively in coated L-PcBN systems, regarding resistance to radial cracking emergence and to material removal through cohesive-failure chipping induced in Rockwell C tests. Although these findings are linked to the higher compressive residual stresses exhibited by coatings deposited under −60 V bias voltage, the latter does not translate in significant changes in microstructural and intrinsic mechanical properties of the TiAlN coating itself.
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| 39. |
- Jia, TY, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
- 2021
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:8, s. 3884-3895
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Journal article (peer-reviewed)abstract
- DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
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| 40. |
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| 41. |
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| 42. |
- Roa, J., et al.
(author)
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Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function. Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.
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| 43. |
- Sainz, Isabel, et al.
(author)
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Quantum phase transitions in an effective Hamiltonian : fast and slow systems
- 2008
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In: JOURNAL OF PHYSICS A-MATHEMATICAL AND THEORETICAL. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 41:35, s. 355301-
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Journal article (peer-reviewed)abstract
- An effective Hamiltonian describing interaction between generic fast and slow systems is obtained in the strong interaction limit. The result is applied for studying the effect of quantum phase transition as a bifurcation of the ground state of the slow subsystem. Examples such as atom-field and atom-atom interactions are analyzed in detail.
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| 44. |
- Velasco, I., et al.
(author)
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Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis
- 2019
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In: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 98:September, s. 84-94
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Journal article (peer-reviewed)abstract
- Background: Kisspeptins, encoded by Kiss1, have emerged as essential regulators of puberty and reproduction by primarily acting on GnRH neurons, via their canonical receptor, Gpr54. Mounting, as yet fragmentary, evidence strongly suggests that kisspeptin signaling may also participate in the control of key aspects of body energy and metabolic homeostasis. However, characterization of such metabolic dimension of kisspeptins remains uncomplete, without an unambiguous discrimination between the primary metabolic actions of kisspeptins vs. those derived from their ability to stimulate the secretion of gonadal hormones, which have distinct metabolic actions on their own. In this work, we aimed to tease apart primary vs. secondary effects of kisspeptins in the control of key aspects of metabolic homeostasis using genetic models of impaired kisspeptin signaling and/or gonadal hormone status. Methods: Body weight (BW) gain and composition, food intake and key metabolic parameters, including glucose tolerance, were comparatively analyzed, in lean and obesogenic conditions, in mice lacking kisspeptin signaling due to global inactivation of Gpr54 (displaying profound hypogonadism; Gpr54−/−) vs. Gpr54 null mice with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg), where kisspeptin signaling elsewhere than in GnRH neurons is ablated but gonadal function is preserved. Results: In male mice, global elimination of kisspeptin signaling resulted in decreased BW, feeding suppression and increased adiposity, without overt changes in glucose tolerance, whereas Gpr54−/− female mice displayed enhanced BW gain at adulthood, increased adiposity and perturbed glucose tolerance, despite reduced food intake. Gpr54−/−Tg rescued mice showed altered postnatal BW gain in males and mildly perturbed glucose tolerance in females, with intermediate phenotypes between control and global KO animals. Yet, body composition and leptin levels were similar to controls in gonadal-rescued mice. Exposure to obesogenic insults, such as high fat diet (HFD), resulted in exaggerated BW gain and adiposity in global Gpr54−/− mice of both sexes, and worsening of glucose tolerance, especially in females. Yet, while rescued Gpr54−/−Tg males displayed intermediate BW gain and feeding profiles and impaired glucose tolerance, rescued Gpr54−/−Tg females behaved as controls, except for a modest deterioration of glucose tolerance after ovariectomy. Conclusion: Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. Summary of translational relevance: Kisspeptins, master regulators of reproduction, may also participate in the control of key aspects of body energy and metabolic homeostasis; yet, the nature of such metabolic actions remains debatable, due in part to the fact that kisspeptins modulate gonadal hormones, which have metabolic actions on their own. By comparing the metabolic profiles of two mouse models with genetic inactivation of kisspeptin signaling but different gonadal status (hypogonadal vs. preserved gonadal function), we provide herein a systematic dissection of gonadal-dependent vs. -independent metabolic actions of kisspeptins. Our data support a global role of kisspeptin signaling in the control of body weight and metabolic homeostasis, with a dominant contribution of gonadal hormone-dependent actions. However, our results document also discernible primary effects of kisspeptin signaling in the regulation of body weight gain, feeding and responses to obesogenic insults, which occur in a sexually-dimorphic manner. These data pave the way for future analyses addressing the eventual contribution of altered kisspeptin signaling in the development of metabolic alterations especially in conditions linked to reproductive dysfunction. © 2019 Elsevier Inc.
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| 45. |
- Yang, Jie, et al.
(author)
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Grinding-induced metallurgical alterations in the binder phase of WC-Co cemented carbides
- 2017
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In: Materials Characterization. - : ELSEVIER SCIENCE INC. - 1044-5803 .- 1873-4189. ; 134, s. 302-310
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Journal article (peer-reviewed)abstract
- The metallic binder phase dictates the toughening behavior of WC-Co cemented carbides (hardmetals), even though it occupies a relative small fraction of the composite. Studies on deformation and phase transformation of the binder constituent are scarce. Grinding represents a key manufacturing step in machining of hardmetal tools, and is well-recognized to induce surface integrity alterations. In this work, metallurgical alterations of the binder phase in ground WC-Co cemented carbides have been assessed by a combination of electron back scattered diffraction and transmission electron microscopy techniques. The Co-base binder experiences a martensitic phase transformation from fcc to hcp crystal structure, predominantly in the first 5 mu m below the surface. The hcp fraction decreases gradually along a depth of 10 mu m. Surface Co displays severe plastic deformation under the highest strain, resulting in formation of nanocrystalline grains in the first micrometer below the surface. Microstructural refinement within the binder phase is observed even at greater depth. Stacking faults were detected in most of the refined grains. The metallurgical alterations of the binder phase modify the local stress distribution during grinding, which affects the discerned subsurface microcracking. The resulting residual stress profile is the sum of multiple subsurface changes, such as phase transformation, severe plastic deformation and grain refinement, where it is discerned that the depth profile of the transformed hcp-Co fraction coincides with the grinding-induced residual stress profile.
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| 46. |
- Yang, Jie, et al.
(author)
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Implementation of advanced characterisation techniques for assessment of grinding effects on the surface integrity of WC-Co cemented carbides
- 2018
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In: Powder Metallurgy. - : Taylor & Francis. - 0032-5899 .- 1743-2901. ; 61:2, s. 100-105
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Journal article (peer-reviewed)abstract
- Grinding is a key step on the manufacturing process of WC-Co cemented carbides (hardmetals). In this work, an investigation of grinding effects on the surface integrity of hardmetals is conducted. It is done by combining diverse advanced characterisation techniques: X-ray diffraction, field emission-scanning electron microscopy, electron back scatter diffraction, focused ion beam - 3D tomography and transmission electron microscopy. The study is carried out in a fine-grained WC-Co grade. Besides ground state, polished surface finish condition is assessed for comparison purposes. It is evidenced that grinding induces significant alterations: 3D tomography illustrates microcracking exists down to 2.5 mu m depth with a highly anisotropic distribution at the subsurface, large compressive residual stresses extending until subsurface levels of about 12 mu m, and phase transformation of binder from the original fcc phase into the hcp one, as well as severe plastic deformation observed within the binder at the surface level.
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| 47. |
- Yang, J., et al.
(author)
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Substrate surface finish effects on scratch resistance and failure mechanisms of TiN-coated hardmetals
- 2015
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In: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 265, s. 174-184
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Journal article (peer-reviewed)abstract
- In this study, the influence of substrate surface finish on scratch resistance and associated failure mechanisms is investigated in the case of a TiN-coated hardmetal. Three different surface finish conditions are studied: as-sintered (AS), ground (G), and mirror-like polished (P). For G conditioned samples, scratch tests are conducted both parallel and perpendicular to the direction of the grinding grooves. It is found that coated AS, G and P samples exhibit similar critical load for initial substrate exposure and the same brittle adhesive failure mode. However, the damage scenarios are different, i.e. the substrate exposure is discrete and localized to the scratch tracks for G samples while a more pronounced and continuous exposure is seen for AS and P ones. Aiming to understand the role played by the grinding-induced compressive residual stresses, the study is extended to coated systems where ground substrates are thermal annealed (for relieving stresses) before being ion etched and coated. It yielded lower critical loads and changes in the mechanisms for the scratch-related failure; the latter depending on the relative orientation between scratching and grinding directions. (C) 2015 Elsevier B.V. All rights reserved.
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| 48. |
- Yang, Jie, et al.
(author)
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Thermally induced surface integrity changes of ground WC-Co hardmetals
- 2016
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In: 3RD CIRP CONFERENCE ON SURFACE INTEGRITY. - : Elsevier. ; , s. 91-94
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Conference paper (peer-reviewed)abstract
- Ground hardmetals are exposed to high temperatures during both processing (e.g. coating deposition) and use (e.g. as a cutting tool). However, studies on thermally induced changes of surface integrity are limited. Here we address this by means of FIB/FESEM and EBSD investigation, with special focus on the binder phase characterization. Our findings indicate that thermal treatment causes two main surface modifications. First, an unexpected microporosity appears in the binder within the subsurface layer when ground surfaces are heated. Second, the metallic phase underneath the ground surface experiences metallurgical changes, in terms of grain and crystallographic phase structures. The mechanisms responsible for these modifications of the binder are discussed in terms of grinding-induced and thermally-reversed phase transformation as well as recrystallization phenomena. We also note that no additional heat treatment related changes such as microcracking and carbide fragmentation in the subsurface layer, are discerned. (C) 2016 The Authors. Published by Elsevier B.V.
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