1,721,277 research outputs found
Solving l0-penalized problems with simple constraints via the Frank–Wolfe reduced dimension method
No full textMalattie professionali e prevenzione.
No full textLe malattie professionali e la loro prevenzione dall'Unità d'Italia fino ai giorni nostri
Path loss prediction in urban environment using learning machines and dimensionality reduction techniques
No full textPath loss prediction, Learning machines, Dimensionality reduction techniques,
New results on the equivalence between zero-one programming and continuous concave programming
No full textA fast active set block coordinate descent algorithm for l1-regularized least squares
Full text linkThe problem of nding sparse solutions to underdetermined systems of linear equa-
tions arises in several applications (e.g., signal and image processing, compressive sensing, statistical
inference). A standard tool for dealing with sparse recovery is the L-1
regularized least squares approach that has been recently attracting the attention of many researchers. In this paper, we describe
an active set estimate (i.e., an estimate of the indices of the zero variables in the optimal solution)
for the considered problem that tries to quickly identify as many active variables as possible at a
given point, while guaranteeing that some approximate optimality conditions are satis ed. A rele-
vant feature of the estimate is that it gives a signi cant reduction of the objective function when
setting to zero all those variables estimated to be active. This enables us to easily embed it into a
given globally converging algorithmic framework. In particular, we include our estimate into a block
coordinate descent algorithm for
`
1
-regularized least squares, analyze the convergence properties of
this new active set method, and prove that its basic version converges with a linear rate. Finally, we
report some numerical results showing the e ectiveness of the approac
Misure di contrasto della povertà e condizionalità. Una sintesi realista delle evidenze
No full textElucidating the BRCA2-RAD51 interaction through an integrated structural biophysics approach
No full textDifferent kinds of lesions can occur to DNA, and among them, one of the most dangerous is the double strand break (DSB). DSBs can result in mutations, chromosome translocation or deletion. For this kind of lesions, depending on cell cycle phase as well as DNA-end resection, cells have developed specific repair pathways. Among these the error-free homologous recombination (HR) plays a crucial role. HR takes place during S/G2 phases, since the sister chromatids can be used as homologous templates. In this process, hRAD51 and BRCA2 are key players. hRAD51 is a recombinase of 339 amino-acids highly conserved through evolution that displays an intrinsic tendency to form oligomeric structures. BRCA2 is a very large protein of 3418 amino-acids, essential for the recruitment and accumulation of hRAD51 in the nucleus repairing-foci. BRCA2 interacts with hRAD51 through eight, so-called, BRC repeats, composed of 35-40 amino acids. Mutations within this region have been linked to an increased risk of ovarian cancer development. Several reports highlighted that missense mutations within one BRC repeat can hamper BRCA2 activity. Considering the close homology between the BRC repeats, it is striking how these mutations cannot be counterbalanced by the other non-mutated repeats preserving the function and the interactions of BRCA2 with hRAD51. To date the only interaction that has been structurally elucidated, is the one taking place amid the fourth BRC repeat and hRAD51. Nevertheless, due to the structural complexity and dynamics of RAD51, the mechanistic details of each step of RAD51 recruitment and DNA repair remain elusive.
To shed light on the mechanism of hRAD51 defibrillation driven by BRC4, in presence or absence of co-factors, negative staining transmission electron microscopy experiments were combined with size exclusion chromatography data revealing that BRC4 erodes hRAD51 fibrils from their termini and does not attack the fibril at random positions. Nevertheless, the propensity to oligomerization of the WT protein hampered further biophysical studies. A novel stabilized fully human monomeric hRAD51 allowed us to investigate its interaction with BRC4 through orthogonal biophysical methods. SAXS experiments were also carried out on the hRAD51-BRC4 complex to provide novel structural insights on their behavior in complex. Atomistic modelling of generated Alphafold2 models revealed that both proteins display flexible N-terminal domains. These results, along with previous evidence on hRAD51 WT fibrils, suggest that BRC4 binding triggers a conformational rearrangement on the hRAD51 N-terminal domain from a more ordered to an intrinsically disordered state
Frank–Wolfe and friends: a journey into projection-free first-order optimization methods
Full text linkInvented some 65 years ago in a seminal paper by Marguerite Straus-Frank and Philip Wolfe, the Frank-Wolfe method recently enjoys a remarkable revival, fuelled by the need of fast and reliable first-order optimization methods in Data Science and other relevant application areas. This review tries to explain the success of this approach by illustrating versatility and applicability in a wide range of contexts, combined with an account on recent progress in variants, both improving on the speed and efficiency of this surprisingly simple principle of first-order optimization
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