| 1. |
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- Antel, C., et al.
(author)
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Feebly-interacting particles : FIPs 2022 Workshop Report
- 2023
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In: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 83:12
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Research review (peer-reviewed)abstract
- Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.
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| 5. |
- Rossi, R., et al.
(author)
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The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome
- 2021
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 51:2, s. 545-551
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Journal article (peer-reviewed)abstract
- Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H-1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.
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| 6. |
- Mereuta, O. M., et al.
(author)
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Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke
- 2021
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In: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 30:12
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Journal article (peer-reviewed)abstract
- Objectives: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. Materials and methods: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. Results: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. Conclusions: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.
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| 7. |
- Arboleda-Velasquez, Joseph F, et al.
(author)
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Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
- 2019
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In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 25:11, s. 1680-1683
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Journal article (peer-reviewed)abstract
- We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
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| 8. |
- Rossi, R., et al.
(author)
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Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization
- 2021
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In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 6:3, s. 254-261
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Journal article (peer-reviewed)abstract
- Introduction: We assessed the correlation between thrombus size before and after mechanical thrombectomy, measured as length by Computed Tomography Angiography/Non-Contrast Computed Tomography (CTA/NCCT) and Extracted Clot Area, ECA, respectively. We also assessed the influence of thrombus size on the number of passes required for clot removal and final recanalization outcome. Materials and methods: Acute ischaemic stroke (AIS) thrombi retrieved by mechanical thrombectomy from 500 patients and data of clot length by CTA/NCCT were collected from three hospitals in Europe. ECA was obtained by measuring the area of the extracted clot. Non-parametric tests were used for data analysis. Results: A strong positive correlation was found between clot length on CTA/NCCT and ECA (rho = 0.619,N = 500, P < 0.0001*). Vessel size influences clot length on CTA/NCCT (H2 = 98.6, P < 0.0001*) and ECA (H2 = 105.6,P < 0.0001*), but the significant correlation between CTA/NCCT length and ECA was evident in all vessels. Poorer revascularisation outcome was associated with more passes (H5 = 73.1, P < 0.0001*). More passes were required to remove longer clots (CTA/NCCT; H4 = 31.4, P < 0.0001*; ECA; H4 = 50.2, P < 0.0001*). There was no significant main association between recanalization outcome and length on CTA/NCCT or ECA, but medium sized clots (ECA 20-40 mm(2)) were associated with least passes and highest revascularisation outcome (N = 500, X-2 = 16.2, P < 0.0001*). Conclusion: Clot length on CTA/NCCT strongly correlates with ECA. Occlusion location influences clot size. More passes are associated with poorer revascularisation outcome and bigger clots. The relationship between size and revascularisation outcome is more complex. Clots of medium ECA take less passes to remove and are associated with better recanalization outcome than both smaller and larger clots.
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| 9. |
- Zabriskie, Matthew S., et al.
(author)
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BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
- 2014
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
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Journal article (peer-reviewed)abstract
- Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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| 13. |
- Kos, K., et al.
(author)
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DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue : DPP-IV inhibition in human adipose tissue
- 2009
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In: Diabetes Obes Metab. - 1463-1326. ; 11:4, s. 285-92
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Journal article (peer-reviewed)abstract
- CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27 micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.
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| 14. |
- O'Hare, C. A. J., et al.
(author)
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Axion helioscopes as solar magnetometers
- 2020
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In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 102:4
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Journal article (peer-reviewed)abstract
- Axion helioscopes search for solar axions and axionlike particles via inverse Primakoff conversion in strong laboratory magnets pointed at the Sun. Anticipating the detection of solar axions, we determine the potential for the planned next-generation helioscope, the International Axion Observatory (IAXO), to measure or constrain the solar magnetic field. To do this we consider a previously neglected component of the solar axion flux at sub-keV energies arising from the conversion of longitudinal plasmons. This flux is sensitively dependent to the magnetic field profile of the Sun, with lower energies corresponding to axions converting into photons at larger solar radii. If the detector technology eventually installed in IAXO has an energy resolution better than 200 eV, then solar axions could become an even more powerful messenger than neutrinos of the magnetic field in the core of the Sun. For energy resolutions better than 10 eV, IAXO could access the inner 70% of the Sun and begin to constrain the field at the tachocline: the boundary between the radiative and convective zones. The longitudinal plasmon flux from a toroidal magnetic field also has an additional 2% geometric modulation effect which could be used to measure the angular dependence of the magnetic field.
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| 15. |
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| 16. |
- Bodda, C., et al.
(author)
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HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
- 2020
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:7
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Journal article (peer-reviewed)abstract
- Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain. © 2020 Bodda et al.
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| 17. |
- Caputo, Andrea, et al.
(author)
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Dark photon limits : A handbook
- 2021
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In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 104:9
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Journal article (peer-reviewed)abstract
- The dark photon is a massive hypothetical particle that interacts with the Standard Model by kinetically mixing with the visible photon. For small values of the mixing parameter, dark photons can evade cosmological bounds to be a viable dark matter candidate. Due to the similarities with the electromagnetic signals generated by axions, several bounds on dark photon signals are simply reinterpretations of historical bounds set by axion haloscopes. However, the dark photon has a property that the axion does not: an intrinsic polarization. Due to the rotation of the Earth, accurately accounting for this polarization is nontrivial, highly experiment dependent, and depends upon assumptions about the dark photon's production mechanism. We show that if one does account for the dark photon polarization, and the rotation of the Earth, an experiment's discovery reach can be enhanced by over an order of magnitude. We detail the strategies that would need to be taken to properly optimize a dark photon search. These include judiciously choosing the location and orientation of the experiment, as well as strategically timing any repeated measurements. Experiments located at 135 degrees or 155 degrees latitude, making three observations at different times of the sidereal day, can achieve a sensitivity that is fully optimized and insensitive to the dark photon's polarization state, and hence its production mechanism. We also point out that several well-known searches for axions employ techniques for testing signals that preclude their ability to set exclusion limits on dark photons, and hence should not be reinterpreted as such.
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| 18. |
- Liffen, Tom, et al.
(author)
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Profiling, the below ground biomass of an emergent macrophyte using an adapted ingrowth core method
- 2013
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In: Aquatic Botany. - : Elsevier BV. - 0304-3770 .- 1879-1522. ; 110, s. 97-102
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Journal article (peer-reviewed)abstract
- In the context of our work exploring the role of Sparganium erectum as a physical ecosystem engineer, we aimed to test our hypothesis that the root and rhizome biomass of this species would be largely confined to the uppermost sediment layers, thereby having the effect of reinforcing newly deposited material and facilitating the growth of in-channel macrophyte stands and sediment accumulations. Detailed measurements of the below ground structures of linear emergent macrophytes, in terms of their biomass and architecture, are complicated by difficulties associated with sampling in the highly saturated sediments that these morphotypes typically occupy. In this paper, we describe the development of an adapted ingrowth core method, which allows the extrusion of an undisturbed root-soil matrix from highly saturated environments. The approach combines an ingrowth core, which is commonly used to measure fine-root production in forest topsoil, with an outer casing that facilitates the retention of a sample rep.. resentative of field conditions, and a laboratory protocol that enables extrusion and measurement of biomass at different depth increments. The new approach enabled detailed depth profiling of S. erectum, and confirmed our hypothesis by demonstrating that root and rhizome biomass was predominantly located in the 10 cm of sediment closest to the sediment-water interface throughout our study.
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| 19. |
- Palmieri, C, et al.
(author)
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The expression of oestrogen receptor (ER)-beta and its variants, but not ERalpha, in adult human mammary fibroblasts
- 2004
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In: Journal of molecular endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 33:1, s. 35-50
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Journal article (peer-reviewed)abstract
- Whilst oestrogen receptor (ER)-alpha and ERbeta have been shown to be important in the development of the mammary gland, the cell-specific expression pattern of these two receptors within the human breast is not clear. Although it is well established that in the developing rodent mammary gland stromal ERalpha mediates the secretion of growth factors which stimulate the proliferation of the ductal epithelium, the expression of ERalpha in human adult breast stromal fibroblasts is controversial, and the expression of ERbeta has not been properly defined. In the present study, we have evaluated the expression of ERalpha and ERbeta by immunohistochemistry in normal tissue samples, and in purified human breast fibroblasts by Western blotting, RT-PCR analysis and ligand-binding sucrose gradient assay. Our data clearly demonstrated that ERbeta variants, including ERbeta1, ERbeta2, ERbeta5, ERbetadelta and ERbetains, but not ERalpha, are expressed in human adult mammary fibroblasts. These results are supported by the findings that an ERbeta-selective ligand, BAG, but not the ERalpha high-affinity ligand oestradiol, can induce fibroblast growth factor-7 release and activate transcription from an oestrogen-responsive element promoter in these adult human mammary fibroblasts. Together, these observations revealed that, in the adult breast and in breast cancer, the proliferative signals derived from the stroma of adult mammary glands in response to oestrogen are not mediated by ERalpha and provide new insights into the nature of stromal-epithelial interactions in the adult mammary gland. In addition, the expression of these ERbeta variants in cells where there is no ERalpha suggested that these ERbeta splice forms may have functions other than that of modulating ERalpha activity.
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| 20. |
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