Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions.

In this work, we propose an adder for the 2D NTC architecture, designed to match the architectural constraints of many quantum computing technologies. The chosen architecture allows the layout of logical qubits in two dimensions and the concurrent execution of one-and two-qubit gates with nearest-neighbor interaction only. The proposed adder works in three phases. In the first phase, the first column generates the summation output and the other columns do the carry-lookahead operations. In the second phase, these intermediate values are propagated from column to column, preparing for computation of the final carry for each register position. In the last phase, each column, except the first one, generates the summation output using this column-level carry. The depth and the number of qubits of the proposed adder are Θ( √ n) and O(n), respectively. The proposed adder executes faster than the adders designed for the 1D NTC architecture when the length of the input registers n is larger than 58.Keywords: quantum arithmetic algorithms, quantum circuit, depth lower bound, adder, 2D NTC quantum computer architecture Communicated by: to be filled by the Editorial IntroductionQuantum computers have been proposed to exploit the exotic properties of quantum mechanics for information processing. Among many potential uses, two quantum algorithms have received the bulk of the attention. One is Shor's large number factoring algorithm [1], and the other is Grover's unstructured database search algorithm [2], though there has also been much progress recently on other algorithms [3,4,5]. Quantum algorithms are often shown to a A two-page short abstract was presented at AQIS 2010. This version includes all details of design and analysis of the proposed adder. b Corresponding Author, bschoi3@gmail.com c rdv@sfc.wide.ad.jp 1 2 An Θ( √ n)-depth Quantum Adder on a 2D NTC Quantum Computer Architecture be more efficient than classical ones by analyzing the number of queries to an oracle. However, for a more exact performance analysis, we need to analyze the quantum algorithms in terms of the detailed quantum circuits necessary to implement them. Among many circuits, as in classical computation, a core set of subroutines whose behavior will strongly impact the performance of the overall algorithm is arithmetic, hence we focus on the adder in this work.Numerous quantum addition circuits have been proposed using abstract models of the computer itself. The basic elementary quantum arithmetic operations including addition

We consider decomposition for a controlled-Rn gate with a standard set of universal gates. For this problem, a method exists that uses a single ancillary qubit to reduce the number of gates. In this work, we extend this method to three ends. First, we find a method that can decompose into fewer gates than the best known results in decomposition of controlled-Rn. We also confirm that the proposed method reduces the total number of gates of the quantum Fourier transform. Second, we propose another efficient decomposition that can be mapped to a nearest-neighbor architecture with only local CNOT gates. Finally, we find a method that can minimize the depth to 5 gate steps in a nearest-neighbor architecture with only local CNOT gates.

By the weight of a Boolean function f , denoted by wt(f ), we mean the number of inputs for which f outputs 1. Given a promise that an n-variable Boolean function (available in the form of a black box and the output is available in constant time once the input is supplied) is of weight either wN or (1 − w)N (0 < w < 1, N = 2 n ), we present a detailed study of quantum algorithms to find out which one actually it is. To solve this problem we apply the Grover's operator.First we consider the restricted problem. Given a promise that an n-variable Boolean function is of weight either ⌊N sinπ 2 ⌉ (⌊q⌉ means the nearest integer corresponding to the real value q), we show that one can suitably apply Grover's operator for k-many iterations to decide which case this is with a probability almost unity for large n and k in O(poly(n)). On the other hand, the best known probabilistic classical algorithm has a success probability close to 0.5 (from above) after k many steps when k is large. We further show that the best known probabilistic classical algorithm can achieve a success probability almost unity only after k s many iterations where s > 2. This indicates a quadratic speed up (and also agrees to the quadratic speed up by the use of Grover's algorithm in database search) on time complexity in the quantum domain with respect to the best known result in the classical domain.Second, we modify the basic randomized algorithm into a sure success algorithm, which can distinguish Boolean functions of weights wN or (1 − w)N for any w, (0 < w < 1). To do that we have exploited a sure success Grover search algorithm, which modifies the very last operation. For the weight decision problem, we show that the very last two operations should be changed to distinguish any weight with certainty and found the phase conditions for the last two operations.As quantum counting methods exist, which can count the number of solutions, here we compare our method with that. Since the quantum counting method needs to exploit period information, which requires many Grover operations, we have found that our method is faster than the quantum counting method.

In this work, we propose the dual-code quantum computation model-a fault-tolerant quantum computation scheme which alternates between two different quantum error-correction codes. Since the chosen two codes have different sets of transversal gates, we can implement a universal set of gates transversally, thereby reducing the overall cost. We use code teleportation to convert between quantum states in different codes. The overall cost is decreased if code teleportation requires fewer resources than the fault-tolerant implementation of the non-transversal gate in a specific code. To analyze the cost reduction, we investigate two cases with different base codes, namely the Steane and Bacon-Shor codes. For the Steane code, neither the proposed dual-code model nor another variation of it achieves any cost reduction since the conventional approach is simple. For the Bacon-Shor code, the three proposed variations of the dual-code model reduce the overall cost. However, as the encoding level increases, the cost reduction decreases and becomes negative. Therefore, the proposed dual-code model is advantageous only when the encoding level is low and the cost of the non-transversal gate is relatively high.