Fundamental Structural Constraint of Random Scale-Free Networks

We study the structural constraint of random scale-free networks that determines possible combinations of the degree exponent $\gamma$ and the upper cutoff $k_c$ in the thermodynamic limit. We employ the framework of graphicality transitions proposed by [Del Genio and co-workers, Phys. Rev. Lett. {\bf 107}, 178701 (2011)], while making it more rigorous and applicable to general values of kc. Using the graphicality criterion, we show that the upper cutoff must be lower than $k_c N^{1/\gamma}$ for $\gamma < 2$, whereas any upper cutoff is allowed for $\gamma > 2$. This result is also numerically verified by both the random and deterministic sampling of degree sequences.Comment: 5 pages, 4 figures (7 eps files), 2 tables; published versio

Lock-free Concurrent Data Structures

Concurrent data structures are the data sharing side of parallel programming. Data structures give the means to the program to store data, but also provide operations to the program to access and manipulate these data. These operations are implemented through algorithms that have to be efficient. In the sequential setting, data structures are crucially important for the performance of the respective computation. In the parallel programming setting, their importance becomes more crucial because of the increased use of data and resource sharing for utilizing parallelism. The first and main goal of this chapter is to provide a sufficient background and intuition to help the interested reader to navigate in the complex research area of lock-free data structures. The second goal is to offer the programmer familiarity to the subject that will allow her to use truly concurrent methods.Comment: To appear in "Programming Multi-core and Many-core Computing Systems", eds. S. Pllana and F. Xhafa, Wiley Series on Parallel and Distributed Computin

Deep Neural Networks Rival the Representation of Primate IT Cortex for Core Visual Object Recognition

The primate visual system achieves remarkable visual object recognition performance even in brief presentations and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition). This remarkable performance is mediated by the representation formed in inferior temporal (IT) cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs). It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations such as the amount of noise, the number of neural recording sites, and the number trials, and computational limitations such as the complexity of the decoding classifier and the number of classifier training examples. In this work we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of "kernel analysis" that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.Comment: 35 pages, 12 figures, extends and expands upon arXiv:1301.353

Cell-type specific potent Wnt signaling blockade by bispecific antibody.

Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting

Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

Hierarchical Modular Optimization of Convolutional Networks Achieves Representations Similar to Macaque IT and Human Ventral Stream

Humans recognize visually-presented objects rapidly and accurately. To understand this ability, we seek to construct models of the ventral stream, the series of cortical areas thought to subserve object recognition. One tool to assess the quality of a model of the ventral stream is the Representational Dissimilarity Matrix (RDM), which uses a set of visual stimuli and measures the distances produced in either the brain (i.e. fMRI voxel responses, neural firing rates) or in models (fea-ures). Previous work has shown that all known models of the ventral stream fail to capture the RDM pattern observed in either IT cortex, the highest ventral area, or in the human ventral stream. In this work, we construct models of the ventral stream using a novel optimization procedure for category-level object recognition problems, and produce RDMs resembling both macaque IT and human ventral stream. The model, while novel in the optimization procedure, further develops a long-standing functional hypothesis that the ventral visual stream is a hierarchically arranged series of processing stages optimized for visual object recognition