125 research outputs found
A semi-coherent generalization of the 5-vector method to search for continuous gravitational waves
The emission of continuous gravitational waves (CWs), with duration much
longer than the typical data taking runs, is expected from several sources,
notably spinning neutron stars, asymmetric with respect to their rotation axis
and more exotic sources, like ultra-light scalar boson clouds formed around
Kerr black holes and sub-solar mass primordial binary black holes. Unless the
signal time evolution is well predicted and its relevant parameters accurately
known, the search for CWs is typically based on semi-coherent methods, where
the full data set is divided in shorter chunks of given duration, which are
properly processed, and then incoherently combined. In this paper we present a
semi-coherent method, in which the so-called \textit{5-vector} statistics is
computed for the various data segments and then summed after the removal of the
Earth Doppler modulation and signal intrinsic spin-down. The method can work
with segment duration of several days, thanks to a double stage procedure in
which an initial rough correction of the Doppler and spin-down is followed by a
refined step in which the residual variations are removed. This method can be
efficiently applied for directed searches, where the source position is known
to a good level of accuracy, and in the candidate follow-up stage of
wide-parameter space searches.Comment: 16 pages, 12 figure
Validación del Ãndice compuesto DAPSA (Disease Activity for Psoriatic Arthritis) en una cohorte de pacientes con artritis psoriásica en Argentina y determinación de sus valores de corte
Objetivos: Validar el Ãndice DAPSA en pacientes con Artritis Psoriásica (APs) en Argentina, comparar su rendimiento con Ãndices compuestos y con la ultrasonografÃa (US) y establecer valores de corte
Patrones de tratamiento con agentes biológicos. Eficacia y sobrevida a largo plazo en pacientes con artritis reumatoidea
En nuestro paÃs existen pocos datos acerca de los patrones de tratamiento y la sobrevida de las Drogas Modificadoras de la Artritis Reumatoidea biológicas (DMARb) en pacientes con Artritis Reumatoidea (AR). El objetivo de nuestro estudio fue estimar la sobrevida del 1° y 2° agente biológico, determinar sus causas de suspensión y evaluar factores que influyan en la sobrevida de estos agentes
Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study
Binding between Crossveinless-2 and Chordin Von Willebrand Factor Type C Domains Promotes BMP Signaling by Blocking Chordin Activity
BACKGROUND: Crossveinless-2 (CV2) is an extracellular BMP modulator protein of the Chordin family, which can either enhance or inhibit BMP activity. CV2 binds to BMP2 via subdomain 1 of the first of its five N-terminal von Willebrand factor type C domains (VWC1). Previous studies showed that this BMP binding is required for the anti-, but not for the pro-BMP effect of CV2. More recently, it was shown that CV2 can also bind to the BMP inhibitor Chordin. However, it remained unclear which domains mediate this binding, and whether it accounts for an anti- or pro-BMP effect. PRINCIPAL FINDINGS: Here we report that a composite interface of CV2 consisting of subdomain 2 of VWC1 and of VWC2-4, which are dispensable for BMP binding, binds to the VWC2 domain of Chordin. Functional data obtained in zebrafish embryos indicate that this binding of Chordin is required for CV2's pro-BMP effect, which actually is an anti-Chordin effect and, at least to a large extent, independent of Tolloid-mediated Chordin degradation. We further demonstrate that CV2 mutant versions that per se are incapable of BMP binding can attenuate the Chordin/BMP interaction. CONCLUSIONS: We have physically dissected the anti- and pro-BMP effects of CV2. Its anti-BMP effect is obtained by binding to BMP via subdomain1 of the VWC1 domain, a binding that occurs in competition with Chordin. In contrast, its pro-BMP effect is achieved by direct binding to Chordin via subdomain 2 of VWC1 and VWC2-4. This binding seems to induce conformational changes within the Chordin protein that weaken Chordin's affinity to BMP. We propose that in ternary Chordin-CV2-BMP complexes, both BMP and Chordin are directly associated with CV2, whereas Chordin is pushed away from BMP, ensuring that BMPs can be more easily delivered to their receptors
Requirement of argininosuccinate lyase for systemic nitric oxide production
Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases
The BMP Antagonist Follistatin-Like 1 Is Required for Skeletal and Lung Organogenesis
Follistatin-like 1 (Fstl1) is a secreted protein of the BMP inhibitor class. During development, expression of Fstl1 is already found in cleavage stage embryos and becomes gradually restricted to mesenchymal elements of most organs during subsequent development. Knock down experiments in chicken and zebrafish demonstrated a role as a BMP antagonist in early development. To investigate the role of Fstl1 during mouse development, a conditional Fstl1 KO allele as well as a Fstl1-GFP reporter mouse were created. KO mice die at birth from respiratory distress and show multiple defects in lung development. Also, skeletal development is affected. Endochondral bone development, limb patterning as well as patterning of the axial skeleton are perturbed in the absence of Fstl1. Taken together, these observations show that Fstl1 is a crucial regulator in BMP signalling during mouse development
Tumour genomic and microenvironmental heterogeneity as integrated predictors for prostate cancer recurrence: a retrospective study
Clinical prognostic groupings for localised prostate cancers are imprecise, with 30–50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors
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