Toward a framework for data quality in cloud-based health information system

This Cloud computing is a promising platform for health information systems in order to reduce costs and improve accessibility. Cloud computing represents a shift away from computing being purchased as a product to be a service delivered over the Internet to customers. Cloud computing paradigm is becoming one of the popular IT infrastructures for facilitating Electronic Health Record (EHR) integration and sharing. EHR is defined as a repository of patient data in digital form. This record is stored and exchanged securely and accessible by different levels of authorized users. Its key purpose is to support the continuity of care, and allow the exchange and integration of medical information for a patient. However, this would not be achieved without ensuring the quality of data populated in the healthcare clouds as the data quality can have a great impact on the overall effectiveness of any system. The assurance of the quality of data used in healthcare systems is a pressing need to help the continuity and quality of care. Identification of data quality dimensions in healthcare clouds is a challenging issue as data quality of cloud-based health information systems arise some issues such as the appropriateness of use, and provenance. Some research proposed frameworks of the data quality dimensions without taking into consideration the nature of cloud-based healthcare systems. In this paper, we proposed an initial framework that fits the data quality attributes. This framework reflects the main elements of the cloud-based healthcare systems and the functionality of EHR

Motion of the Zinc Ions in Catalysis by a Dizinc Metallo-β-Lactamase

We report rapid-freeze-quench X-ray absorption spectroscopy of a dizinc metallo-β-lactamase (MβL) reaction intermediate. The Zn(II) ions in the dinuclear active site of the S. maltophilia Class B3 MβL move away from each other, by ∼0.3 Å after 10 ms of reaction with nitrocefin, from 3.4 to 3.7 Å. Together with our previous characterization of the resting enzyme and its nitrocefin product complex, where the Zn(II) ion separation relaxes to 3.6 Å, these data indicate a scissoring motion of the active site that accompanies the ring-opening step. The average Zn(II) coordination number of 4.5 in the resting enzyme appears to be maintained throughout the reaction with nitrocefin. This is the first direct structural information available on early stage dizinc metallo-β-lactamase catalysis

Short-term memory for words with a perceptual-motor interpolated activity,

It was maintained that the Brown-Peterson short-term memory (STM) task bears important similarities to procedures used in the study of division of attention, since during STM retention intervals there is competition between the tendencies to rehearse the memory item and to execute the filler activity. It follows that when both retention and filler-task performance are scored, either or both should be sensitive to variables known to affect the division of attention, such as task-complexity and practice. In two experiments recall for 5-word stimuli was tested after 24-sec intervals filled with a self-paced keypressing task as the interpolated activity. Evidence for the presence of rehearsal was the finding that keypressing scores were lower on memory trials than on control trials where no words were recalled. Furthermore, retention scores were found to be a complex joint function of the S-R compatibility, coherence (repetitiveness), and prior practice on the keypressing activity. The conclusions were that rehearsal is objectively demonstrable in STM, that its extent may be controlled by variation of the filler task, and that the relationships revealed by such variation are consistent with the experimental literature on divided attention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33280/1/0000672.pd

A Five-coordinate Metal Center in Co(II)-substituted VanX

In an effort to structurally probe the metal binding site in VanX, electronic absorption, EPR, and extended x-ray absorption fine structure (EXAFS) spectroscopic studies were conducted on Co(II)-substituted VanX. Electronic spectroscopy revealed the presence of Co(II) ligand field transitions that had molar absorptivities of ∼100 m–1 cm–1, which suggests that Co(II) is five-coordinate in Co(II)-substituted VanX. Low temperature EPR spectra of Co(II)-substituted VanX were simulated using spin Hamiltonian parameters of M = |±½〉, E/D = 0.14, greal(x,y) = 2.37, and grealS(z) = 2.03. These parameters lead to the prediction that Co(II) in the enzyme is five-coordinate and that there may be at least one solvent-derived ligand. Single scattering fits of EXAFS data indicate that the metal ions in both native Zn(II)-containing and Co(II)-substituted VanX have the same coordination number and that the metal ions are coordinated by 5 nitrogen/oxygen ligands at ∼ 2.0 Å. These data demonstrate that Co(II) (and Zn(II) from EXAFS studies) is five-coordinate in VanX in contrast to previous crystallographic studies (Bussiere, D. E., Pratt, S. D., Katz, L., Severin, J. M., Holzman, T., and Park, C. H. (1998) Mol. Cell 2, 75–84). These spectroscopic studies also demonstrate that the metal ion in Co(II)-substituted VanX when complexed with a phosphinate analog of substrate d-Ala-d-Ala is also five-coordinate

Conformational Dynamics of metallo-β-lactamase CcrA during Catalysis Investigated by Using DEER Spectroscopy

Previous crystallographic and mutagenesis studies have implicated the role of a position-conserved hairpin loop in the metallo-β-lactamases in substrate binding and catalysis. In an effort to probe the motion of that loop during catalysis, rapid-freeze-quench double electron–electron resonance (RFQ-DEER) spectroscopy was used to interrogate metallo-β-lactamase CcrA, which had a spin label at position 49 on the loop and spin labels (at positions 82, 126, or 233) 20–35 Å away from residue 49, during catalysis. At 10 ms after mixing, the DEER spectra show distance increases of 7, 10, and 13 Å between the spin label at position 49 and the spin labels at positions 82, 126, and 233, respectively. In contrast to previous hypotheses, these data suggest that the loop moves nearly 10 Å away from the metal center during catalysis and that the loop does not clamp down on the substrate during catalysis. This study demonstrates that loop motion during catalysis can be interrogated on the millisecond time scale

An Interactive Program for the Analysis of Data from Two-Level Factorial Experiments via Probability Plotting

An interactive computer program that expedites the analysis for unreplicated two-level factorial and fractional factorial experimental designs advocated by Daniel (1976) and Box, Hunter, and Hunter (1978) is presented. The program calculates estimated effects via the Yates algorithm, identifies statistically detectable effects via normal plots and half normal plots, fits candidate models via the reverse Yates algorithm, and enables evaluation of candidate models through residual plots. The program can handle the analysis of standard 2p-q fractional factorial experiments where p - q √ 7 and can be modified to allow p - q \u3e 7

Differential Binding of Co(II) and Zn(II) to Metallo-β-Lactamase Bla2 from \u3cem\u3eBacillus anthracis\u3c/em\u3e

In an effort to probe the structure, mechanism, and biochemical properties of metallo-β-lactamase Bla2 from Bacillus anthracis, the enzyme was overexpressed, purified, and characterized. Metal analyses demonstrated that recombinant Bla2 tightly binds 1 equiv of Zn(II). Steady-state kinetic studies showed that mono-Zn(II) Bla2 (1Zn-Bla2) is active, while di-Zn(II) Bla2 (ZnZn-Bla2) was unstable. Catalytically, 1Zn-Bla2 behaves like the related enzymes CcrA and L1. In contrast, di-Co(II) Bla2 (CoCo-Bla2) is substantially more active than the mono-Co(II) analogue. Rapid kinetics and UV−vis, 1H NMR, EPR, and EXAFS spectroscopic studies show that Co(II) binding to Bla2 is distributed, while EXAFS shows that Zn(II) binding is sequential. To our knowledge, this is the first documented example of a Zn enzyme that binds Co(II) and Zn(II) via distinct mechanisms, underscoring the need to demonstrate transferability when extrapolating results on Co(II)-substituted proteins to the native Zn(II)-containing forms

Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e

ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer

Probing substrate binding to Metallo-β-Lactamase L1 from Stenotrophomonas maltophilia by using site-directed mutagenesis

BACKGROUND: The metallo-β-lactamases are Zn(II)-containing enzymes that hydrolyze the β-lactam bond in penicillins, cephalosporins, and carbapenems and are involved in bacterial antibiotic resistance. There are at least 20 distinct organisms that produce a metallo-β-lactamase, and these enzymes have been extensively studied using X-ray crystallographic, computational, kinetic, and inhibition studies; however, much is still unknown about how substrates bind and the catalytic mechanism. In an effort to probe substrate binding to metallo-β-lactamase L1 from Stenotrophomonas maltophilia, nine site-directed mutants of L1 were prepared and characterized using metal analyses, CD spectroscopy, and pre-steady state and steady state kinetics. RESULTS: Site-directed mutations were generated of amino acids previously predicted to be important in substrate binding. Steady-state kinetic studies using the mutant enzymes and 9 different substrates demonstrated varying K(m) and k(cat) values for the different enzymes and substrates and that no direct correlation between K(m) and the effect of the mutation on substrate binding could be drawn. Stopped-flow fluorescence studies using nitrocefin as the substrate showed that only the S224D and Y228A mutants exhibited weaker nitrocefin binding. CONCLUSIONS: The data presented herein indicate that Ser224, Ile164, Phe158, Tyr228, and Asn233 are not essential for tight binding of substrate to metallo-β-lactamase L1. The results in this work also show that K(m) values are not reliable for showing substrate binding, and there is no correlation between substrate binding and the amount of reaction intermediate formed during the reaction. This work represents the first experimental testing of one of the computational models of the metallo-β-lactamases