The first spatial 2D quantum walk on a photonic chip with thousands of nodes is realized for future analog quantum computing.

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Summary Spongiform neurodegeneration is characterized by the appearance of vacuoles throughout the central nervous system. It has many potential causes, but the underlying cellular mechanisms are not well understood. Mice lacking the E3 ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1) develop age-dependent spongiform encephalopathy. We identified an interaction between a “PSAP” motif in MGRN1 and the ubiquitin E2 variant (UEV) domain of TSG101, a component of the endosomal sorting complex required for transport I (ESCRT-I), and demonstrate that MGRN1 multimonoubiquitinates TSG101. We examined the in vivo consequences of loss of MGRN1 on TSG101 expression and function in the mouse brain. The pattern of TSG101 ubiquitination differed in the brains of wild-type mice and Mgrn1 null mutant mice: at 1 month of age, null mutant mice had less ubiquitinated TSG101, while in adults, mutant mice had more ubiquitinated, insoluble TSG101 than wild-type mice. There was an associated increase in epidermal growth factor receptor (EGFR) levels in mutant brains. These results suggest that loss of MGRN1 promotes ubiquitination of TSG101 by other E3s and may prevent its disassociation from endosomal membranes or cause it to form insoluble aggregates. Our data implicate loss of normal TSG101 function in endo-lysosomal trafficking in the pathogenesis of spongiform neurodegeneration in Mgrn1 null mutant mice.

Quantum walks are powerful kernels in quantum computing protocols that possess strong capabilities in speeding up various simulation and optimisation tasks. One striking example is given by quantum walkers evolving on glued trees for their faster hitting performances than in the case of classical random walks. However, its experimental implementation is challenging as it involves highly complex arrangements of exponentially increasing number of nodes. Here we propose an alternative structure with a polynomially increasing number of nodes. We successfully map such graphs on quantum photonic chips using femtosecond laser direct writing techniques in a geometrically scalable fashion. We experimentally demonstrate quantum fast hitting by implementing two-dimensional quantum walks on these graphs with up to 160 nodes and a depth of 8 layers, achieving a linear relationship between the optimal hitting time and the network depth. Our results open up a scalable way towards quantum speed-up in complex problems classically intractable.Adapting well-known classical mathematical models in a way to include quantum mechanical laws has shown the emergence of new interesting behaviors. In some cases, the modified protocols have revealed an advantage with respect to the original ones in solving specific problems. This has clearly triggered the interest of the scientific community in the quest for a better understanding and exploitation of these new tools 1 . A striking example is given by quantum walks, the adaptation of the classical random walk to the world of quantum mechanics 2 . Quantum walks have already found applications in several scenarios, including spatial search problems 3,4 , the element distinctness problem 5 , testing matrix identities 6 , evaluating Boolean formulas 7 , judging graph isomorphism 8,9 , which all theoretically promise quantum speed-up and may inspire the breakthrough in real-life applications.One feature of quantum walks on complex graphs that is key in quantum algorithms is their ability to propagate from a node to a distant one in an efficient way. This is often denoted as fast hitting. In particular, fast hitting on a structure known as glued tree is extremely charming due to its exponential speed-up over its classical counterpart 10,11 . A glued tree is obtained by connecting the "final leaves" of two binary tree graphs 12 of the same depth, as shown in Fig.1(a). The process assumes a particle starting in the left-most vertex (called the Entry site), evolving through the graph, and finally hitting the right-most vertex (called the Exit site). It has been shown that, in a scenario where the central connections are randomly chosen, any algorithm exploiting a classical walker (i.e., a particle following the laws of classical mechanics) would require on average a time scaling exponentially with the graph depth to reach the Exit. On the other hand, a quantum walker will require a time that scales only linearly 11,13,14 . Due to the close relation between binary trees and decision trees in computer s...

Oxidative stress, ubiquitination defects and mitochondrial dysfunction are commonly associated with neurodegeneration. Mice lacking mahogunin ring finger-1 (MGRN1) or attractin (ATRN) develop age-dependent spongiform neurodegeneration through an unknown mechanism. It has been suggested that they act in a common pathway. As MGRN1 is an E3 ubiquitin ligase, proteomic analysis of Mgrn1 mutant and control brains was performed to explore the hypothesis that loss of MGRN1 causes neurodegeneration via accumulation of its substrates. Many mitochondrial proteins were reduced in Mgrn1 mutants. Subsequent assays confirmed significantly reduced mitochondrial complex IV expression and activity as well as increased oxidative stress in mutant brains. Mitochondrial dysfunction was obvious many months before onset of vacuolation, implicating this as a causative factor. Compatible with the hypothesis that ATRN and MGRN1 act in the same pathway, mitochondrial dysfunction and increased oxidative stress were also observed in the brains of Atrn mutants. Our results suggest that the study of Mgrn1 and Atrn mutant mice will provide insight into a causative molecular mechanism common to many neurodegenerative disorders.