This beginning graduate textbook describes both recent achievements and classical results of computational complexity theory. Requiring essentially no background apart from mathematical maturity, the book can be used as a reference for self-study for anyone interested in complexity, including physicists, mathematicians, and other scientists, as well as a textbook for a variety of courses and seminars. More than 300 exercises are included with a selected hint set. The book starts with a broad introduction to the field and progresses to advanced results. Contents include: definition of Turing machines and basic time and space complexity classes, probabilistic algorithms, interactive proofs, cryptography, quantum computation, lower bounds for concrete computational models (decision trees, communication complexity, constant depth, algebraic and monotone circuits, proof complexity), average-case complexity and hardness amplification, derandomization and pseudorandom constructions, and the PCP theorem.

Abstract. Informally, an obfuscator O is an (efficient, probabilistic) "compiler" that takes as input a program (or circuit) P and produces a new program O(P ) that has the same functionality as P yet is "unintelligible" in some sense. Obfuscators, if they exist, would have a wide variety of cryptographic and complexity-theoretic applications, ranging from software protection to homomorphic encryption to complexity-theoretic analogues of Rice's theorem. Most of these applications are based on an interpretation of the "unintelligibility" condition in obfuscation as meaning that O(P ) is a "virtual black box," in the sense that anything one can efficiently compute given O(P ), one could also efficiently compute given oracle access to P . In this work, we initiate a theoretical investigation of obfuscation. Our main result is that, even under very weak formalizations of the above intuition, obfuscation is impossible. We prove this by constructing a family of functions F that are inherently unobfuscatable in the following sense: there is a property π : F → {0, 1} such that (a) given any program that computes a function f ∈ F, the value π(f ) can be efficiently computed, yet (b) given oracle access to a (randomly selected) function f ∈ F, no efficient algorithm can compute π(f ) much better than random guessing. We extend our impossibility result in a number of ways, including even obfuscators that (a) are not necessarily computable in polynomial time, (b) only approximately preserve the functionality, and (c) only need to work for very restricted models of computation (TC 0). We also rule out several potential applications of obfuscators, by constructing "unobfuscatable" signature schemes, encryption schemes, and pseudorandom function families.

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The simulation paradigm is central to cryptography. A simulator is an algorithm that tries to simulate the interaction of the adversary with an honest party, without knowing the private input of this honest party. Almost all known simulators use the adversary's algorithm as a black-box. We present the first constructions of nonblack-box simulators. Using these new non-black-box techniques we obtain several results that were previously proven to be impossible to obtain using black-box simulators. Specifically, assuming the existence of collision resistent hash functions, we construct a new zeroknowledge argument system for NP that satisfies the following properties: 1. This system has a constant number of rounds with negligible soundness error. 2. It remains zero knowledge even when composed concurrently n times, where n is the security parameter. Simultaneously obtaining 1 and 2 has been recently proven to be impossible to achieve using black-box simulators. 3. It is an Arthur-Merlin (public coins) protocol. Simultaneously obtaining 1 and 3 was known to be impossible to achieve with a black-box simulator. 4. It has a simulator that runs in strict polynomial time, rather than in expected polynomial time. All previously known constant-round, negligibleerror zero-knowledge arguments utilized expected polynomial-time simulators.

SUMMARY Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.