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1.
Sobacchi C Frattini A Guerrini MM Abinun M Pangrazio A Susani L Bredius R Mancini G Cant A Bishop N Grabowski P Del Fattore A Messina C Errigo G Coxon FP Scott DI Teti A Rogers MJ Vezzoni P Villa A Helfrich MH 《Nature genetics》2007,39(8):960-962
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration. 相似文献
2.
Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
3.
The work of Thomas Kuhn has been very influential in Anglo-American philosophy of science and it is claimed that it has initiated the historical turn. Although this might be the case for English speaking countries, in France an historical approach has always been the rule. This article aims to investigate the similarities and differences between Kuhn and French philosophy of science or ‘French epistemology’. The first part will argue that he is influenced by French epistemologists, but by lesser known authors than often thought. The second part focuses on the reactions of French epistemologists on Kuhn’s work, which were often very critical. It is argued that behind some superficial similarities there are deep disagreements between Kuhn and French epistemology. This is finally shown by a brief comparison with the reaction of more recent French philosophers of science, who distance themselves from French epistemology and are more positive about Kuhn. Based on these diverse appreciations of Kuhn, a typology of the different positions within the philosophy of science is suggested. 相似文献
4.
Massimiliano Marcellino 《Journal of forecasting》2008,27(4):305-340
Predicting the future evolution of GDP growth and inflation is a central concern in economics. Forecasts are typically produced either from economic theory‐based models or from simple linear time series models. While a time series model can provide a reasonable benchmark to evaluate the value added of economic theory relative to the pure explanatory power of the past behavior of the variable, recent developments in time series analysis suggest that more sophisticated time series models could provide more serious benchmarks for economic models. In this paper we evaluate whether these complicated time series models can outperform standard linear models for forecasting GDP growth and inflation. We consider a large variety of models and evaluation criteria, using a bootstrap algorithm to evaluate the statistical significance of our results. Our main conclusion is that in general linear time series models can hardly be beaten if they are carefully specified. However, we also identify some important cases where the adoption of a more complicated benchmark can alter the conclusions of economic analyses about the driving forces of GDP growth and inflation. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
5.
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication 总被引:1,自引:0,他引:1
Di Micco R Fumagalli M Cicalese A Piccinin S Gasparini P Luise C Schurra C Garre' M Nuciforo PG Bensimon A Maestro R Pelicci PG d'Adda di Fagagna F 《Nature》2006,444(7119):638-642
Early tumorigenesis is associated with the engagement of the DNA-damage checkpoint response (DDR). Cell proliferation and transformation induced by oncogene activation are restrained by cellular senescence. It is unclear whether DDR activation and oncogene-induced senescence (OIS) are causally linked. Here we show that senescence, triggered by the expression of an activated oncogene (H-RasV12) in normal human cells, is a consequence of the activation of a robust DDR. Experimental inactivation of DDR abrogates OIS and promotes cell transformation. DDR and OIS are established after a hyper-replicative phase occurring immediately after oncogene expression. Senescent cells arrest with partly replicated DNA and with DNA replication origins having fired multiple times. In vivo DNA labelling and molecular DNA combing reveal that oncogene activation leads to augmented numbers of active replicons and to alterations in DNA replication fork progression. We also show that oncogene expression does not trigger a DDR in the absence of DNA replication. Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication. 相似文献
6.
Massimiliano Sassoli de Bianchi 《Foundations of Science》2013,18(2):213-243
Founding our analysis on the Geneva-Brussels approach to the foundations of physics, we provide a clarification and classification of the key concept of observation. An entity can be observed with or without a scope. In the second case, the observation is a purely non-invasive discovery process; in the first case, it is a purely invasive process, which can involve either creation or destruction aspects. An entity can also be observed with or without a full control over the observational process. In the latter case, the observation can be described by a symmetry breaking mechanism, through which a specific deterministic observational process is selected among a number of potential ones, as explained in Aerts’ hidden measurement approach. This is what is called a product test, or product observation, whose consequences are that outcomes can only be predicted in probabilistic terms, as it is the case in typical quantum measurements. We also show that observations can be about intrinsic (stable) properties of the observed entity, or about relational (ephemeral) properties between the observer and observed entities; also, they can be about intermediate properties, neither purely classical, nor purely quantum. Our analysis allows us to propose a general conceptual characterization of quantum measurements, as observational processes involving three aspects: (1) product observations, (2) pure creation aspects and (3) ephemeral relational properties. We also discuss the important concept of non-spatiality and emphasize some of the differences and similarities between quantum and classical/relativistic observations. 相似文献
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8.
Diederik Aerts Jonito Aerts Arguëlles Lester Beltran Suzette Geriente Massimiliano Sassoli de Bianchi Sandro Sozzo Tomas Veloz 《Foundations of Science》2018,23(2):337-365
In the first half of this two-part article (Aerts et al. in Found Sci. doi: 10.1007/s10699-017-9528-9, 2017b), we analyzed a cognitive psychology experiment where participants were asked to select pairs of directions that they considered to be the best example of Two Different Wind Directions, and showed that the data violate the CHSH version of Bell’s inequality, with same magnitude as in typical Bell-test experiments in physics. In this second part, we complete our analysis by presenting a symmetrized version of the experiment, still violating the CHSH inequality but now also obeying the marginal law, for which we provide a full quantum modeling in Hilbert space, using a singlet state and suitably chosen product measurements. We also address some of the criticisms that have been recently directed at experiments of this kind, according to which they would not highlight the presence of genuine forms of entanglement. We explain that these criticisms are based on a view of entanglement that is too restrictive, thus unable to capture all possible ways physical and conceptual entities can connect and form systems behaving as a whole. We also provide an example of a mechanical model showing that the violations of the marginal law and Bell inequalities are generally to be associated with different mechanisms. 相似文献
9.
Massimiliano Sassoli de Bianchi 《Foundations of Science》2017,22(3):627-653
In 1975, two experimental groups have independently observed the \(4\pi \)-symmetry of neutrons’ spin, when passing through a static magnetic field, using a three-blade interferometer made from a single perfect Si-crystal (analogous to the Mach Zehnder interferometer of light optics). In this article, we provide a complete analysis of the experiment, both from a theoretical and conceptual point of view. Firstly, we solve the Schrödinger equation in the weak potential approximation, to obtain the amplitude of the refracted and forward refracted beams, produced by the passage of neutrons through one of the three plates of the LLL interferometer. Secondly, we analyze their passage through a static magnetic field region. This allows us to find explicit expressions for the intensities of the four beams exiting the interferometer, two of which will be interfering and show a typical \(4\pi \)-symmetry, when the strength of the magnetic field is varied. In the last part of the article, we provide a conceptual analysis of the experiment, showing that a neutron’s phase change, when passing through the magnetic field, is due to a longitudinal Stern–Gerlach effect, and not to a Larmor precession. We also emphasize that these experiments do not prove the observability of the sign change of the wave function, when a neutron is \(2\pi \) rotated, but strongly indicate that the latter, like any other elementary “particle,” would be a genuinely non-spatial entity. 相似文献
10.
Coucke PJ Willaert A Wessels MW Callewaert B Zoppi N De Backer J Fox JE Mancini GM Kambouris M Gardella R Facchetti F Willems PJ Forsyth R Dietz HC Barlati S Colombi M Loeys B De Paepe A 《Nature genetics》2006,38(4):452-457
Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy. 相似文献