Fine-Grained Derandomization: From Problem-Centric to Resource-Centric Complexity

We show that popular hardness conjectures about problems from the field of fine-grained complexity theory imply structural results for resource-based complexity classes. Namely, we show that if either k-Orthogonal Vectors or k-CLIQUE requires n^{epsilon k} time, for some constant epsilon>1/2, to count (note that these conjectures are significantly weaker than the usual ones made on these problems) on randomized machines for all but finitely many input lengths, then we have the following derandomizations: - BPP can be decided in polynomial time using only n^alpha random bits on average over any efficient input distribution, for any constant alpha>0 - BPP can be decided in polynomial time with no randomness on average over the uniform distribution This answers an open question of Ball et al. (STOC \u2717) in the positive of whether derandomization can be achieved from conjectures from fine-grained complexity theory. More strongly, these derandomizations improve over all previous ones achieved from worst-case uniform assumptions by succeeding on all but finitely many input lengths. Previously, derandomizations from worst-case uniform assumptions were only know to succeed on infinitely many input lengths. It is specifically the structure and moderate hardness of the k-Orthogonal Vectors and k-CLIQUE problems that makes removing this restriction possible. Via this uniform derandomization, we connect the problem-centric and resource-centric views of complexity theory by showing that exact hardness assumptions about specific problems like k-CLIQUE imply quantitative and qualitative relationships between randomized and deterministic time. This can be either viewed as a barrier to proving some of the main conjectures of fine-grained complexity theory lest we achieve a major breakthrough in unconditional derandomization or, optimistically, as route to attain such derandomizations by working on very concrete and weak conjectures about specific problems

Tighter Connections between Derandomization and Circuit Lower Bounds

We tighten the connections between circuit lower bounds and derandomization for each of the following three types of derandomization: - general derandomization of promiseBPP (connected to Boolean circuits), - derandomization of Polynomial Identity Testing (PIT) over fixed finite fields (connected to arithmetic circuit lower bounds over the same field), and - derandomization of PIT over the integers (connected to arithmetic circuit lower bounds over the integers). We show how to make these connections uniform equivalences, although at the expense of using somewhat less common versions of complexity classes and for a less studied notion of inclusion. Our main results are as follows: 1. We give the first proof that a non-trivial (nondeterministic subexponential-time) algorithm for PIT over a fixed finite field yields arithmetic circuit lower bounds. 2. We get a similar result for the case of PIT over the integers, strengthening a result of Jansen and Santhanam [JS12] (by removing the need for advice). 3. We derive a Boolean circuit lower bound for NEXP intersect coNEXP from the assumption of sufficiently strong non-deterministic derandomization of promiseBPP (without advice), as well as from the assumed existence of an NP-computable non-empty property of Boolean functions useful for proving superpolynomial circuit lower bounds (in the sense of natural proofs of [RR97]); this strengthens the related results of [IKW02]. 4. Finally, we turn all of these implications into equivalences for appropriately defined promise classes and for a notion of robust inclusion/separation (inspired by [FS11]) that lies between the classical "almost everywhere" and "infinitely often" notions

Agnostic Learning from Tolerant Natural Proofs

We generalize the "learning algorithms from natural properties" framework of [CIKK16] to get agnostic learning algorithms from natural properties with extra features. We show that if a natural property (in the sense of Razborov and Rudich [RR97]) is useful also against functions that are close to the class of "easy" functions, rather than just against "easy" functions, then it can be used to get an agnostic learning algorithm over the uniform distribution with membership queries. * For AC0[q], any prime q (constant-depth circuits of polynomial size, with AND, OR, NOT, and MODq gates of unbounded fanin), which happens to have a natural property with the requisite extra feature by [Raz87, Smo87, RR97], we obtain the first agnostic learning algorithm for AC0[q], for every prime q. Our algorithm runs in randomized quasi-polynomial time, uses membership queries, and outputs a circuit for a given Boolean function f that agrees with f on all but at most polylog(n)*opt fraction of inputs, where opt is the relative distance between f and the closest function h in the class AC0[q]. * For the ideal case, a natural proof of strongly exponential correlation circuit lower bounds against a circuit class C containing AC0[2] (i.e., circuits of size exp(Omega(n)) cannot compute some n-variate function even with exp(-Omega(n)) advantage over random guessing) would yield a polynomial-time query agnostic learning algorithm for C with the approximation error O(opt)

Hardness Amplification for Non-Commutative Arithmetic Circuits

We show that proving mildly super-linear lower bounds on non-commutative arithmetic circuits implies exponential lower bounds on non-commutative circuits. That is, non-commutative circuit complexity is a threshold phenomenon: an apparently weak lower bound actually suffices to show the strongest lower bounds we could desire. This is part of a recent line of inquiry into why arithmetic circuit complexity, despite being a heavily restricted version of Boolean complexity, still cannot prove super-linear lower bounds on general devices. One can view our work as positive news (it suffices to prove weak lower bounds to get strong ones) or negative news (it is as hard to prove weak lower bounds as it is to prove strong ones). We leave it to the reader to determine their own level of optimism

Imatinib mesylate therapy in chronic myeloid leukemia patients in stable complete cytogenetic response after interferon-alpha results in any high complete molecular response.

To determine the impact on minimal residual disease by switching to imatinib chronic phase chronic myeloid leukaemia (CP-CML) patients responsive to interferon-alpha (IFNα), in stable complete cytogenetic response (CCR) but with persistent PCR positivity. Twenty-six Philadelphia positive (Ph+) CML patients in stable CCR after IFNα but persistently positive at PCR analysis during this treatment, were given imatinib mesylate at standard dose. At enrolment into the study, median IFN treatment and CCR duration were 88 months (range 15–202) and 73 months (range 10–148), respectively. Imatinib treatment resulted in a progressive and consistent decline of the residual disease as measured by quantitative PCR (RQ-PCR) in all but one of the 26 patients; at the end of follow-up, after a median of 32 months (range 21–49) of treatment, a major molecular response (BCR/ABL levels <0.1) was reached in 20 patients (77%), and BCR/ABL transcripts were undetectable in 13 (50%). The achievement of molecular response was significantly correlated with post-IFN baseline transcript level (mean 1.194 for patients achieving complete molecular response versus 18.97 for those who did not; p < 0.001), but not with other clinical/biological disease characteristics. These results indicate that patients induced into CCR by IFN treatment represent a subset with very favourable prognosis, which can significantly improve molecular response with imatinib and further support investigative treatment schedules combining these two drugs

Learning Algorithms from Natural Proofs

Based on Hastad\u27s (1986) circuit lower bounds, Linial, Mansour, and Nisan (1993) gave a quasipolytime learning algorithm for AC^0 (constant-depth circuits with AND, OR, and NOT gates), in the PAC model over the uniform distribution. It was an open question to get a learning algorithm (of any kind) for the class of AC^0[p] circuits (constant-depth, with AND, OR, NOT, and MOD_p gates for a prime p). Our main result is a quasipolytime learning algorithm for AC^0[p] in the PAC model over the uniform distribution with membership queries. This algorithm is an application of a general connection we show to hold between natural proofs (in the sense of Razborov and Rudich (1997)) and learning algorithms. We argue that a natural proof of a circuit lower bound against any (sufficiently powerful) circuit class yields a learning algorithm for the same circuit class. As the lower bounds against AC^0[p] by Razborov (1987) and Smolensky (1987) are natural, we obtain our learning algorithm for AC^0[p]

MAL/VIP17, a New Player in the Regulation of NKCC2 in the Kidney

In this work, we demonstrate that MAL/VIP17 increases the cell surface retention of NKCC2 at the apical membrane of thick ascending limb cells by attenuating its internalization. This coincides with an increase in cotransporter phosphorylation. Thus, MAL/VIP17 could play an important role in the regulated absorption of Na+ and Cl− in the kidney