Background: Newborn screening for deficiency in the lysosomal enzymes that cause Fabry, Gaucher, Krabbe, Niemann-Pick A/B, and Pompe diseases is warranted because treatment for these syndromes is now available or anticipated in the near feature. We describe a multiplex screening method for all five lysosomal enzymes that uses newborn-screening cards containing dried blood spots as the enzyme source. Methods: We used a cassette of substrates and internal standards to directly quantify the enzymatic activities, and tandem mass spectrometry for enzymatic product detection. Rehydrated dried blood spots were incubated with the enzyme substrates. We used liquid-liquid extraction followed by solid-phase extraction with silica gel to remove buffer components. Acarbose served as inhibitor of an interfering acid ␣-glucosidase present in neutrophils, which allowed the lysosomal enzyme implicated in Pompe disease to be selectively analyzed. Results: We analyzed dried blood spots from 5 patients with Gaucher, 5 with Niemann-Pick A/B, 11 with Pompe, 5 with Fabry, and 12 with Krabbe disease, and in all cases the enzyme activities were below the minimum activities measured in a collection of heterozygous carriers and healthy noncarrier individuals. The enzyme activities measured in 5-9 heterozygous carriers were approximately one-half those measured with 15-32 healthy individuals, but there was partial overlap of each condition between the data sets for carriers and healthy individuals. Conclusion: For all five diseases, the affected individuals were detected. The assay can be readily automated,

Salacinol (4) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheses of salacinol (4), the enantiomer of salacinol (5), and a diastereomer (7) are described. The synthetic strategy relies on the selective nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D- or L-arabinitol at C-1 of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The work serves to resolve the ambiguity about the exact structure of salacinol and establishes conclusively the structure of the natural product.

In the treatment of Type II (noninsulin-dependent) diabetes, management of blood glucose levels is critical. One strategy is to delay digestion of ingested carbohydrates, thereby lowering postprandial blood glucose concentration [1]. This can be achieved by inhibiting the activity of pancreatic a-amylase, which mediates the hydrolysis of complex starches to oligosaccharides, and ⁄ or membrane-bound intestinal a-glucosidases, which hydrolyze these oligosaccharides to glucose in the small intestine [1]. Carbohydrate analogues, such as acarbose (1) and miglitol (2) (Fig. 1 Inhibitors targeting pancreatic a-amylase and intestinal a-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an a-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective a-glucosidase inhibitors modeled after salacinol, a naturally occurring a-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity.Abbreviations HPA, human pancreatic a-amylase; MGA, maltase glucoamylase; MGAnt, maltase glucoamylase N-terminal catalytic domain; pNP, paranitrophenyl; SIM, sucrase isomaltase.

Quantum gates in experiment are inherently prone to errors that need to be characterized before they can be corrected. Full characterization via quantum process tomography is impractical and often unnecessary. For most practical purposes, it is enough to estimate more general quantities such as the average fidelity. Here we use a unitary 2-design and twirling protocol for efficiently estimating the average fidelity of Clifford gates, to certify a 7-qubit entangling gate in a nuclear magnetic resonance quantum processor. Compared with more than 10 8 experiments required by full process tomography, we conducted 1656 experiments to satisfy a statistical confidence level of 99%. The average fidelity of this Clifford gate in experiment is 55.1%, and rises to 87.5% if the infidelity due to decoherence is removed. The entire protocol of certifying Clifford gates is efficient and scalable, and can easily be extended to any general quantum information processor with minor modifications. . Introduction. Benchmarking protocols for characterizing the level of coherent control are fundamental in evaluating potential quantum information processing (QIP) devices. They provide an objective comparison of quantum control capabilities between diverse QIP devices, and also indicate the prospects of a given platform with respect to fault-tolerant quantum computation [1]. The traditional approach of using quantum process tomography (QPT) [2,3] is useful for completely characterizing a quantum channel, and has been applied to at most 3-qubit systems in experiment [4][5][6][7][8][9][10][11]. However, QPT requires number of measurements that scale exponentially with number of qubits n (≈ 2 4n ), making it impractical even in relatively small systems. Moreover,for many practical purposes, such as benchmarking, the full description of a particular quantum channel is not necessary and more accessible properties of the gates are sufficient. To benchmark a gate it is enough to estimate the distance between the implemented channel and the ideal gate. Several methods such as randomized benchmarking [12][13][14], twirling [15][16][17], and Monte Carlo estimations [18,19] have been proposed to evaluate a particular quantum channel in an efficient manner, each with its own restrictions and drawbacks. Here, in order to benchmark our coherent controls on a 7-qubit nuclear magnetic resonance (NMR) system, we adopted the twirling protocol [17] to estimate the average fidelity of an important Clifford gate in QIP. The gate of interest generates maximal coherence from single coherence with the aid of lo-

No abstract