| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Carninci, P, et al.
(författare)
-
The transcriptional landscape of the mammalian genome
- 2005
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
|
|
| 5. |
- Rolo, M. Da Rocha, et al.
(författare)
-
A custom readout electronics for the BESIII CGEM detector
- 2017
-
Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- For the upgrade of the inner tracker of the BESIII spectrometer, planned for 2018, a lightweight tracker based on an innovative Cylindrical Gas Electron Multiplier (CGEM) detector is now under development. The analogue readout of the CGEM enables the use of a charge centroid algorithm to improve the spatial resolution to better than 130 mu m while loosening the pitch strip to 650 mu m, which allows to reduce the total number of channels to about 10 000. The channels are readout by 160 dedicated integrated 64-channel front-end ASICs, providing a time and charge measurement and featuring a fully-digital output. The energy measurement is extracted either from the time-over-threshold (ToT) or the 10-bit digitisation of the peak amplitude of the signal. The time of the event is generated by quad-buffered low-power TDCs, allowing for rates in excess of 60 kHz per channel. The TDCs are based on analogue interpolation techniques and produce a time stamp (or two, if working in ToT mode) of the event with a time resolution better than 50 ps. The front-end noise, based on a CSA and a two-stage complex conjugated pole shapers, dominate the channel intrinsic time jitter, which is less than 5 ns r.m.s. The time information of the hit can be used to reconstruct the track path, operating the detector as a small TPC and hence improving the position resolution when the distribution of the cloud, due to large incident angle or magnetic field, is very broad. Event data is collected by an off-detector motherboard, where each GEM-ROC readout card handles 4 ASIC carrier FEBs (512 channels). Configuration upload and data readout between the off-detector electronics and the VME-based data collector cards are managed by bi-directional fibre optical links. This paper covers the design of a custom front-end electronics for the readout of the new inner tracker of the BESIII experiment, addressing the relevant design aspects of the detector electronics and the front-end ASIC for the CGEM readout, and reviewing the first silicon results of the chip prototype.
|
|
| 6. |
- Akbari, Parsa, et al.
(författare)
-
Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
- 2021
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
-
Tidskriftsartikel (refereegranskat)abstract
- Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
|
|
| 7. |
- Amoroso, A., et al.
(författare)
-
A cylindrical GEM detector with analog readout for the BESIII experiment
- 2016
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 824, s. 515-517
-
Tidskriftsartikel (refereegranskat)abstract
- A cylindrical GEM detector with analog readout is under development for the upgrade of the Inner Tracker of the BESIII experiment at IHEP (Beijing). The new detector will match the requirements for momentum resolution (sigma(pt) /p(t) similar to 0.5% at 1 GeV) and radial resolution (sigma(xy) similar to 120 mu m) of the existing drift chamber and will improve significantly the spatial resolution along the beam direction (sigma(z) similar to 150 mu m) with very small material budget (less than 1.5% of X-0). With respect to the state of the art the following innovations will be deployed: a lighter mechanical structure based on Rohacell, a new XV anode readout plane with jagged strip layout to reduce the parasitic capacitance, and the use of the analogue readout inside a high intensity magnetic field to have good spatial resolution without increasing the number of channels.
|
|
| 8. |
- Amoroso, A., et al.
(författare)
-
A cylindrical GEM Inner Tracker for the BESIII experiment
- 2016
-
Ingår i: Nuovo cimento della societa italiana de fisica. C, Geophysics and space physics. - 1124-1896 .- 1826-9885. ; 39:1
-
Tidskriftsartikel (refereegranskat)abstract
- We are developing a cylindrical GEM detector with analog readout to upgrade the Inner Tracker of the BESIII experiment at IHEP (Beijing). The new detector will match the requirements for momentum resolution (sigma(pt)/pt similar to 0.5% at 1GeV) and radial resolution (sigma(xy) similar to 100 mu m) of the existing drift chamber and will improve significantly the spatial resolution along the beam direction (sigma(z) similar to 150 mu m) with very small material budget (about 1% of X-0). A beam test has been performed at CERN in order to measure the performance of a BESIII GEM prototype in a magnetic field up to 1 tesla. An overview of the project and the preliminary results of the test will be presented in the talk. The project has been recognised as a Significant Research Project within the Executive Programme for Scientific and Technological Cooperation between Italy and PRC for the years 2013-2015, and more recently has been selected as one of the project funded by the European Commission within the call H2020-MSCA-RISE-2014.
|
|
| 9. |
- Bazzurro, V., et al.
(författare)
-
Involvement of GABA(A) receptors containing alpha(6) subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two-photon uncaging
- 2022
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:5, s. 4505-4513
-
Tidskriftsartikel (refereegranskat)abstract
- The antisecretory factor (AF) is an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions in vivo. It has been detected in many mammalian tissues and plasma, but its mechanisms of action are largely unknown. To study the pharmacological action of the AF on different GABA(A) receptor populations in cerebellar granule cells, we took advantage of the two-photon uncaging method as this technique allows to stimulate the cell locally in well-identified plasma membrane parts. We compared the electrophysiological response evoked by releasing a caged GABA compound on the soma, the axon initial segment and neurites before and after administering AF-16, a 16 amino acids long peptide obtained from the amino-terminal end of the AF protein. After the treatment with AF-16, we observed peak current increases of varying magnitude depending on the neuronal region. Thus, studying the effects of furosemide and AF-16 on the electrophysiological behaviour of cerebellar granules, we suggest that GABA(A) receptors, containing the alpha(6) subunit, may be specifically involved in the increase of the peak current by AF, and different receptor subtype distribution may be responsible for differences in this increase on the cell.
|
|
| 10. |
- Mandelli, GE, et al.
(författare)
-
Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer
- 2020
-
Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. Results: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T cells and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model. Conclusions: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.
|
|
| 11. |
- Verweij, Niek, et al.
(författare)
-
Germline Mutations in CIDEB and Protection against Liver Disease
- 2022
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 387:4, s. 332-344
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, -1.24 U per liter; 95% confidence interval [CI], -1.66 to -0.83; P=4.8×10-9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P=9.9×10-7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, -0.98; 95% CI, -1.54 to -0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS Rare germline mutations in CIDEB conferred substantial protection from liver disease.
|
|
| 12. |
- Amoroso, A., et al.
(författare)
-
The CGEM-IT readout chain
- 2021
-
Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 16:8
-
Tidskriftsartikel (refereegranskat)abstract
- An innovative Cylindrical Gas Electron Multiplier (CGEM) detector is under construction for the upgrade of the inner tracker of the BESIII experiment. A novel system has been worked out for the readout of the CGEM detector, including a new ASIC, dubbed TIGER -Torino Integrated GEM Electronics for Readout, designed for the amplification and digitization of the CGEM output signals. The data output by TIGER are collected and processed by a first FPGA-based module, GEM Read Out Card, in charge of configuration and control of the front-end ASICs. A second FPGA-based module, named GEM Data Concentrator, builds the trigger selected event packets containing the data and stores them via the main BESIII data acquisition system. The design of the electronics chain, including the power and signal distribution, will be presented together with its performance.
|
|
| 13. |
- Ardighieri, L, et al.
(författare)
-
Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
- 2021
-
Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
|
|
| 14. |
- Bazzurro, V., et al.
(författare)
-
Antisecretory Factor Modulates GABAA Receptor Activity in Neurons
- 2018
-
Ingår i: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 64:2, s. 312-320
-
Tidskriftsartikel (refereegranskat)abstract
- The antisecretory factor is an endogenous protein found in all mammalian tissues investigated so far. It acts by counteracting intestinal hypersecretion and various forms of inflammation, but the detailed mechanism of antisecretory factor (AF) action is unknown. We tested neuronal GABAA receptors by means of AF-16, a potent AF peptide derived from amino acids 36–51 from the NH2 part of AF. Cultured rat cerebellar granule cells were used, and the effects on the GABA-mediated chloride currents were determined by whole-cell patch clamp. Both the neurotransmitter GABA and AF-16 were added by perfusion of the experimental system. A 3-min AF-16 preincubation was more efficacious than 30s in significantly elevating the rapidly desensitizing GABA-activated chloride current. No effect was found on the tonic, slowly desensitizing current. The GABA-activated current increase by AF-16 demonstrated a low k of 41pM with a maximal increase of 37% persisting for some minutes after AF washout, independent from GABA concentration. This indicates an effect on the maximal stimulation (E%Max) excluding an altered affinity between GABA and its receptor. An immunocytochemical fluorescence approach with anti γ2 subunit antibodies demonstrated an increased expression of GABAA receptors. Thus, both the electrophysiological and the immunofluorescence approach indicate an increased appearance of GABAA receptors on the neuronal membrane. The rationale of the experiments was to test the effect of AF on a defined neuronal population of GABAA receptors. The implications of the results on the impact of AF on the enteric nervous system or on brain function are discussed. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
|
|
| 15. |
- Gatta, R, et al.
(författare)
-
What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper
- 2020
-
Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:18
-
Tidskriftsartikel (refereegranskat)abstract
- In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?
|
|
| 16. |
|
|
| 17. |
- Micheli, A, et al.
(författare)
-
Cancer prevalence in European registry areas
- 2002
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 13:6, s. 840-865
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Information on cancer prevalence is of major importance for health planning and resource allocation. However, systematic information on cancer prevalence is largely unavailable. MATERIALS AND METHODS: Thirty-eight population-based cancer registries from 17 European countries, participating in EUROPREVAL, provided data on almost 3 million cancer patients diagnosed from 1970 to 1992. Standardised data collection and validation procedures were used and the whole data set was analysed using proven methodology. The prevalence of stomach, colon, rectum, lung, breast, cervix uteri, corpus uteri and prostate cancer, as well as of melanoma of skin, Hodgkin's disease, leukaemia and all malignant neoplasms combined, were estimated for the end of 1992. RESULTS: There were large differences between countries in the prevalence of all cancers combined; estimates ranged from 1170 per 100000 in the Polish cancer registration areas to 3050 per 100000 in southern Sweden. For most cancers, the Swedish, Swiss, German and Italian areas had high prevalence, and the Polish, Estonian, Slovakian and Slovenian areas had low prevalence. Of the total prevalent cases, 61% were women and 57% were 65 years of age or older. Cases diagnosed within 2 years of the reference date formed 22% of all prevalent cases. Breast cancer accounted for 34% of all prevalent cancers in females and colorectal cancer for 15% in males. Prevalence tended to be high where cancer incidence was high, but the prevalence was highest in countries where survival was also high. Prevalence was low where general mortality was high (correlation between general mortality and the prevalence of all cancers = -0.64) and high where gross domestic product was high (correlation = +0.79). Thus, the richer areas of Europe had higher prevalence, suggesting that prevalence will increase with economic development. CONCLUSIONS: EUROPREVAL is the largest project on prevalence conducted to date. It has provided complete and accurate estimates of cancer prevalence in Europe, constituting essential information for cancer management. The expected increases in prevalence with economic development will require more resources; allocation to primary prevention should therefore be prioritised.
|
|
| 18. |
|
|
| 19. |
- Tagliaferri, Luca, et al.
(författare)
-
ENT COBRA ONTOLOGY : the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy)
- 2018
-
Ingår i: Journal of Contemporary Brachytherapy. - : Termedia Publishing. - 1689-832X .- 2081-2841. ; 10:3, s. 260-266
-
Forskningsöversikt (refereegranskat)abstract
- Purpose: Clinical data collecting is expensive in terms of time and human resources. Data can be collected in different ways; therefore, performing multicentric research based on previously stored data is often difficult. The primary objective of the ENT COBRA (COnsortium for BRachytherapy data Analysis) ontology is to define a specific terminological system to standardized data collection for head and neck (H&N) cancer patients treated with interventional radiotherapy.Material and methods: ENT-COBRA is a consortium for standardized data collection for H&N patients treated with interventional radiotherapy. It is linked to H&N and Skin GEC-ESTRO Working Group and includes 11 centers from 6 countries. Its ontology was firstly defined by a multicentric working group, then evaluated by the consortium followed by a multi-professional technical commission involving a mathematician, an engineer, a physician with experience in data storage, a programmer, and a software expert.Results: Two hundred and forty variables were defined on 13 input forms. There are 3 levels, each offering a specific type of analysis: 1. Registry level (epidemiology analysis); 2. Procedures level (standard oncology analysis); 3. Research level (radiomics analysis). The ontology was approved by the consortium and technical commission; an ad-hoc software architecture ("broker") remaps the data present in already existing storage systems of the various centers according to the shared terminology system. The first data sharing was successfully performed using COBRA software and the ENT COBRA Ontology, automatically collecting data directly from 3 different hospital databases (Lubeck, Navarra, and Rome) in November 2017.Conclusions: The COBRA Ontology is a good response to the multi-dimensional criticalities of data collection, retrieval, and usability. It allows to create a software for large multicentric databases with implementation of specific remapping functions wherever necessary. This approach is well-received by all involved parties, primarily because it does not change a single center's storing technologies, procedures, and habits.
|
|
