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As the increasing demand of the radio spectrum, the researchers pay more attention to the technology of cognitive radio networks to improve the use of the scarce spectrum resources. Recently, cooperative communications combining with cognitive radio have been proposed in many literatures to improve the channel capacity. The primary users with poor transmission environment transmit their packets with the assistance of the secondary users (SUs) by offering them spectrum resources. This paper first raises issues in existing works, such as non-optimal selection, selection collision, and transmission interruption. Aiming at these issues, we design a centralized system model and a cooperative relaying protocol for multiple primary user pairs to dynamically lease spectrum in exchange for the transmission assistance of SUs. Then we define 2 problems of the cooperative SU assignment to maximize total rate and maximize number of assigned SUs. We prove they are NP-hard and propose a local search algorithm for the objective of maximize total rate and a 1/2 approximation algorithm for another objective. Our simulation results show that our system and algorithms can effectively improve the performance of the wireless networks. [ABSTRACT FROM AUTHOR]

Cooperative communication has great potential to enhance the performance of wireless networks by exploiting relay nodes' spatial diversity. Relay assignment plays a vital role in making the most of this potential. However, most previous studies investigate relay assignment in a rather static manner which may lead to the under-utilisation of relay nodes, especially in the scenarios where source nodes' demands are time varying. Hence, in this study, the authors consider the relay assignment problem for cooperative networks using auction model with access flexibility, i.e. providing sufficient flexibility for source nodes to access relay nodes in time domain. They divide relay nodes' access time into multiple smaller access units and permit each source node to bid for a bundle of desired access units in the auction. This model is formulated as a combinational auction whose winner determination problem is NP hard. They thus present an auction mechanism with an elaborated greed strategy which not only achieves adorable properties such as truthfulness, individual rationality and computational efficiency, but also guarantees near-optimal social welfare. Finally, they conduct extensive evaluations to verify the performance of their mechanism. [ABSTRACT FROM AUTHOR]

Identity-based signature is an important technique for light-weight authentication. Recently, many efforts have been made to construct identity-based signatures over lattice assumptions since they would remain secure in future quantum age. In this paper we present a new identitybased signature scheme from lattice problems. This scheme is more efficient than other lattice-based identity-based signature schemes in terms of both computation and communication complexities. We prove its security in the random oracle model under short integer solution assumption that is as hard as approximating several worst-case lattice problems. We also extend the scheme to an identity-based message recovery signature scheme that has better performance. [ABSTRACT FROM AUTHOR]

Spectrum auction is an emerging economic scheme to stimulate both primary spectrum operators (POs) and secondary users (SUs) to be involved in spectrum sharing. Previous spectrum auction works mostly assume each PO can only have one type spectrum or each SU can only buy homogeneous spectrum bands from the same PO. However, in a ubiquitous network scenario, each PO possesses heterogeneous spectrum resources such as WiFi, 3G and each SU may request different types of spectrum bands from the same PO. Existing auction schemes cannot be used to effectively solve the problem. Therefore, the authors come out with a lightweight combinatorial double auction to tackle this challenge. Since spectrum combinatorial double auction problem is NP-hard, the authors develop a general greedy algorithm G-Greedy to solve the problem. Inspired by the recent group-buying discounts, they also invent an enhanced scheme E-Greedy to further optimise total utility. They theoretically prove the economy properties of the proposed schemes such as individual rationality, budget balance and truthfulness. Simulation results show that both of the two algorithms can yield higher utilities and are effective. [ABSTRACT FROM AUTHOR]

The key for cooperative collision avoidance (CCA) systems is the real-time and reliable delivery of safety-related messages among vehicles, which include periodical beacons and risk-triggered warning messages. In this paper, we first design a risk-aware dynamic medium-access control (R-MAC) protocol tailored for vehicular CCA applications. In this protocol, each frame is divided into two parts: TDMA segment for transferring beacons and CSMA segment for delivering warning messages. Then, we propose a stochastic model to predict the average total number of potential collisions in a platoon of vehicles, which determines the size of CSMA segment in the R-MAC protocol meticulously. Monte Carlo simulations validate that our model is reliable and practical. The performance of the R-MAC protocol is verified through theoretical analysis and extensive simulations under different traffic scenes. Simulation results show that R-MAC outperforms the traditional IEEE 802.11p protocol in terms of packets delivery rate and transmission delay, as well as the Jain's fairness index of the medium access between beacons and warning messages. [ABSTRACT FROM AUTHOR]

Cooperative communication is shown to be a promising technology to significantly increase the capacity of wireless networks. Due to the competition among multiple source-destination pairs for the same relay node set in the relay assignment problem, each pair may cheat others to achieve a more individual revenue. However, the cheating behavior may decrease the overall performance of the network greatly. Thus, there is a challenge for designing a truthful protocol that maximizes a pair's payoff only when this pair reveals its true individual information. In this paper, we propose a relay assignment protocol (RA-VCG) for cooperative communication to maximize the total social value (i.e., the total true value of all pairs) while guaranteeing truthfulness in an auction-theoretic sense by charging each pair an extra payment. Specially, RA-VCG implements a variation of the well-known VCG mechanism for the truthful relay assignment problem in the network with selfish source-destination pairs. Then, we prove the validity of this protocol and also show several surprising properties (such as no positive transfer and individual rationality) associated with this protocol. The simulation results show that the total social value achieved when each node takes untruthfully is about 23.3% less than that achieved when nodes behave truthfully. [ABSTRACT FROM AUTHOR]

With the development of information technology, we envision that the key of improving coal mine safety is how to get realtime positions of miners. In this paper, we propose a prototype system for real-time coal miner localization and tracking based on self-organized sensor networks. The system is composed of hardware and software platform. We develop a set of localization hardware devices with the Safety Certificate of Approval for Mining Products include miner node, wired fixed access station, and base with optical port. On the software side, we develop a layered software architecture of node application, server management, and information dissemination and broadcasting. We also develop three key localization technologies: an underground localization algorithm using received signal strength indication- (RSSI-) verifying algorithm to reduce the influence of the severe environment in a coal mine; a robust fault-tolerant localization mechanism to improve the inherent defect of instability of RSSI localization; an accurate localization algorithm based on Monte Carlo localization (MCL) to adapt to the underground tunnel structure. In addition, we conduct an experimental evaluation based on a real prototype implementation using MICA2 motes. The results show that our system is more accurate and more adaptive in general than traditional localization algorithms. [ABSTRACT FROM AUTHOR]

We propose an efficient teleportation scheme for an unknown state to either one of two receivers via GHZ-like states. We also discuss the fidelity of the quantum state when the control party is uncooperative. [ABSTRACT FROM AUTHOR]

Oxidation of SCN-, Br-, and Cl- (X-) by horseradish peroxidase (HRP) and other plant and fungal peroxidases results in the addition of HOX to the heme vinyl group. This reaction is not observed with lactoperoxidase (LPO), in which the heme is covalently bound to the protein via two ester bonds between carboxylic side chains and heme methyl groups. To test the hypothesis that the heme of LPO and other mammalian peroxidases is protected from vinyl group modification by the hemeprotein covalent bonds, we prepared the F41E mutant of HRP in which the heme is attached to the protein via a covalent bond between Glu41 and the heme 3-methyl. We also examined the E375D mutant of LPO in which only one of the two normal covalent heme links is retained. The prosthetic heme groups of F41E HRP and E375D LPO are essentially not modified by the HOBr produced by these enzymes. The double E375D/D225E mutant of LPO that can form no covalent bonds is inactive and could not be examined. These results unambiguously demonstrate that a single heme-protein link is sufficient to protect the heme from vinyl group modification even in a protein (HRP) that is normally highly susceptible to this reaction. The results directly establish that one function of the covalent heme-protein bonds in mammalian peroxidases is to protect their prosthetic group from their highly reactive metabolic products. [ABSTRACT FROM AUTHOR]

The mammalian peroxidases eosinophil peroxidase, lactoperoxidase (LPO), and myeloperoxidase oxidize thiocyanate to the antimicrobial agents hypothiocyanous acid (HOSCN) and (SCN)2 and are part of a defense system that protects the host from infections. Horseradish peroxidase (HRP), a plant enzyme, also oxidizes thiocyanate. We report here that the prosthetic heme vinyl groups of HAP react with the catalytically generated HOSCN and (SCN)2 to form at least nine vinyl-modified heme adducts. Mass spectrometry combined with analysis of the equivalent reactions of HRP reconstituted with 2- or 4-cyclopropylheme, or mesoheme-d4, shows that all of the prosthetic heme modifications result from addition of oxidized thiocyanate to the heme vinyl groups. No δ-meso-substitution of the heme was observed, in contrast to what is observed with radical agents. Model studies show that incubation of either HRP with preformed HOSCN or a solution of heme with preformed (SCN)2 gives rise to the same products obtained in the HRP-catalyzed reaction. Model studies also demonstrate that the SCN· radical, if formed, should add to a meso-carbon. These findings implicate an electrophilic addition mechanism. In contrast, oxidation by LPO of thiocyanate, the normal substrate of this enzyme, does not result in heme modification. In view of the demonstrated intrinsic reactivity of the heme group, LPO must actively suppress heme modification. As the key difference between LPO (and other mammalian peroxidases) and HRP is the presence of two covalent ester links between the heme and the protein, we propose that these links contribute to steric protection of the adjacent heme vinyl groups. [ABSTRACT FROM AUTHOR]

Background: The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether--lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIVinfected pregnant women. Methods: A prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz. Results: Nine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration--time curve0-8hr (35%, P = 0.057) and lumefantrine area under the concentration--time curve0-∞ (34%, P = 0.063) with efavirenz therapy. Conclusions: Pregnant HIV-infected women receiving efavirenzbased antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women. [ABSTRACT FROM AUTHOR]

Recently, local differential privacy (LDP), as a strong and practical notion, has been applied to deal with privacy issues in data collection. However, existing LDP-based strategies mainly focus on utility optimization at a single privacy level while ignoring various privacy preferences of data providers and multilevel privacy demands for statistics. In this paper, we for the first time propose a framework to optimize the utility of histogram estimation with these two privacy requirements. To clarify the goal of privacy protection, we personalize the traditional definition of LDP. We design two independent approaches to minimize the utility loss: Advanced Combination, which composes multilevel results for utility optimization, and Data Recycle with Personalized Privacy, which enlarges the sample size for an estimation. We demonstrate their effectiveness on privacy and utility, respectively. Moreover, we embed these approaches within a Recycle and Combination Framework and prove that the framework stably achieves the optimal utility by quantifying its error bounds. On real-world datasets, our approaches are experimentally validated and remarkably outperform baseline methods. [ABSTRACT FROM AUTHOR]

Objectives: The selection and dose of antibiotic therapy for biofilm-related infections are based on traditional pharmacokinetic studies using planktonic bacteria. The objective of this study was to characterize the time course and spatial activity of human exposure levels of meropenem and tobramycin against Pseudomonas aeruginosa biofilms grown in an in vitro flow-chamber model.Methods: Pharmacokinetic profiles of meropenem and tobramycin used in human therapy were administered to GFP-labelled P. aeruginosa PAO1 grown in flow chambers for 24 or 72 h. Images were acquired using confocal laser scanning microscopy throughout antibiotic treatment. Bacterial biomass was measured using COMSTAT and pharmacokinetic/pharmacodynamic models were fitted using NONMEM7.Results: Meropenem treatment resulted in more rapid and sustained killing of both the 24 and 72 h PAO1 biofilm compared with tobramycin. Biofilm regrowth after antibiotic treatment occurred fastest with tobramycin. Meropenem preferentially killed subpopulations within the mushroom cap of the biofilms, regardless of biofilm maturity. The spatial killing by tobramycin varied with biofilm maturity. A tobramycin-treated 24 h biofilm resulted in live and dead cells detaching from the biofilm, while treatment of a 72 h biofilm preferentially killed subpopulations on the periphery of the mushroom stalk. Regrowth occurred primarily on the mushroom caps. Combination meropenem and tobramycin therapy resulted in rapid and efficient killing of biofilm cells, with a spatial pattern similar to meropenem alone.Conclusions: Simulated human concentrations of meropenem and tobramycin in young and mature PAO1 biofilms exhibited differences in temporal and spatial patterns of killing and antibiotic tolerance development. [ABSTRACT FROM AUTHOR]

Background. The optimal treatment of malaria in human immunodeficiency virus (HIV)-infected children requires consideration of critical drug-drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. Methods. We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. Results. One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. Conclusions. The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted. [ABSTRACT FROM AUTHOR]

As the size of smartphone touchscreens has become larger and larger in recent years, operability with a single hand is getting worse, especially for female users. We envision that user experience can be significantly improved if smartphones are able to recognize the current operating hand, detect the hand-changing process and then adjust the user interfaces subsequently. In this paper, we proposed, implemented and evaluated two novel systems. The first one leverages the user-generated touchscreen traces to recognize the current operating hand, and the second one utilizes the accelerometer and gyroscope data of all kinds of activities in the user’s daily life to detect the hand-changing process. These two systems are based on two supervised classifiers constructed from a series of refined touchscreen trace, accelerometer and gyroscope features. As opposed to existing solutions that all require users to select the current operating hand or confirm the hand-changing process manually, our systems follow much more convenient and practical methods and allow users to change the operating hand frequently without any harm to the user experience. We conduct extensive experiments on Samsung Galaxy S4 smartphones, and the evaluation results demonstrate that our proposed systems can recognize the current operating hand and detect the hand-changing process with 94.1% and 93.9% precision and 94.1% and 93.7% True Positive Rates (TPR) respectively, when deciding with a single touchscreen trace or accelerometer-gyroscope data segment, and the False Positive Rates (FPR) are as low as 2.6% and 0.7% accordingly. These two systems can either work completely independently and achieve pretty high accuracies or work jointly to further improve the recognition accuracy. [ABSTRACT FROM AUTHOR]

Background: Anti-malarial chemoprevention with dihydroartemisinin-piperaquine (DHA/PQ) is a promising tool for malaria control, but its efficacy in children may be limited by inadequate drug exposure. Methods: Children were enrolled in a non directly-observed trial of DHA/PQ chemoprevention in a high transmission setting in Uganda. Children were randomized at 6 months of age to no chemoprevention (n = 89) or monthly DHA/PQ (n = 87) and followed through 24 months of age, with pharmacokinetic sampling performed at variable times following monthly dosing of DHA/PQ. A previously published pharmacokinetic model was used to estimate piperaquine (PQ) exposure in each child, and associations between PQ exposure and the protective efficacy (PE) of DHA/PQ were explored. Results: The incidence of malaria was 6.83 and 3.09 episodes per person year at risk in the no chemoprevention and DHA/PQ arms, respectively (PE 54 %, 95 % CI 39-66 %, P < 0.001). Among children randomized to DHA/PQ, 493 pharmacokinetic samples were collected. Despite nearly 100 % reported adherence to study drug administration at home, there was wide variability in PQ exposure, and children were stratified into three groups based on average PQ exposure during the intervention that was determined by model generated percentiles (low, n = 40; medium, n = 37, and high, n = 10). Gender and socioeconomic factors were not significantly associated with PQ exposure. In multivariate models, the PE of DHA/PQ was 31 % in the low PQ exposure group (95 % CI 6-49 %, P = 0.02), 67 % in the medium PQ exposure group (95 % CI 54-76 %, P < 0.001), and 97 % in the high PQ exposure group (95 % CI 89-99 %, P < 0.001). Conclusions: The protective efficacy of DHA/PQ chemoprevention in young children was strongly associated with higher drug exposure; in children with the highest PQ exposure, monthly DHA/PQ chemoprevention was nearly 100 % protective against malaria. Strategies to ensure good adherence to monthly dosing and optimize drug exposure are critical to maximize the efficacy of this promising malaria control strategy. [ABSTRACT FROM AUTHOR]

Background: To mitigate increased risk of premature cardiovascular disease in antiretroviral therapy (ART) suppressed adults living with HIV (PWH), low-dose methotrexate (LDMTX) was evaluated in a multicenter randomized placebo controlled clinical trial of 176 PWH taking various ART regimens (ACTG A5314). Given shared methotrexate (MTX) and tenofovir (TFV) pharmacokinetic (PK) pathways, a substudy was conducted to investigate whether LDMTX alters TFV exposure. Methods: Adults virally suppressed on ART for >24 weeks were randomized to LDMTX or placebo. The first 66 participants taking a tenofovir disoproxil fumarate-containing regimen underwent intensive PK sampling over 24 hours after the second dose of LDMTX 10 mg or placebo. TFV and MTX levels were quantified using validated mass spectrometry methods. TFV PK between LDMTX and placebo groups were compared and MTX PK was characterized. Results: Forty-eight participants completed this substudy (n = 20 on LDMTX and 28 on placebo). Baseline characteristics were balanced except for protease inhibitor (PI)-use (25% in LDMTX and 43% in placebo groups). For TFV, AUC6 (primary endpoint), and AUC24,imputed, Cmax, and Cmin (secondary endpoints) were on average 22%, and 24%, 27%, and 31% less in the LDMTX versus placebo groups, with reductions in secondary endpoints reaching statistical significance. Additional analyses suggested a greater reduction in the absence of PI although not significant. Conclusion: Lower TFV AUC24,imputed and Cmax indicates that LDMTX reduces TFV exposure in PWH. However, this change was modest, not warranting a change in TFV dosing at this time. Further studies of TFV PK with LDMTX, especially without PI co-administration, are warranted. [ABSTRACT FROM AUTHOR]

Background: A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug-drug interaction pharmacokinetic (PK) study found that pregnant human immunodeficiency virus (HIV)-infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population.Methods: Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period.Results: PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), <1% of women achieved defined protective PQ coverage. Weekly (960 mg PQ) or low-dose daily (320 or 160 mg PQ) regimens achieved protective PQ coverage for 34% and >96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase.Conclusions: For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing.Clinical Trials Registration: NCT02282293. [ABSTRACT FROM AUTHOR]

Background: In a recent trial of intermittent preventive treatment in pregnancy (IPTp) in Uganda, dihydroartemisinin-piperaquine (DP) was superior to sulfadoxine-pyrimethamine (SP) in preventing maternal and placental malaria.Methods: We compared genotypes using sequencing, fluorescent microsphere, and quantitative polymerase chain reaction assays at loci associated with drug resistance in Plasmodium falciparum isolated from subjects receiving DP or SP.Results: Considering aminoquinoline resistance, DP was associated with increased prevalences of mutations at pfmdr1 N86Y, pfmdr1 Y184F, and pfcrt K76T compared to SP (64.6% vs 27.4%, P < .001; 93.9% vs 59.2%, P < .001; and 87.7% vs 75.4%, P = .03, respectively). Increasing plasma piperaquine concentration at the time of parasitemia was associated with increasing pfmdr1 86Y prevalence; no infections with the N86 genotype occurred with piperaquine >2.75 ng/mL. pfkelch13 propeller domain polymorphisms previously associated with artemisinin resistance were not identified. Recently identified markers of piperaquine resistance were uncommon and not associated with DP. Considering antifolate resistance, SP was associated with increased prevalence of a 5-mutation haplotype (pfdhfr 51I, 59R, and 108N; pfdhps 437G and 581G) compared to DP (90.8% vs 60.0%, P = .001).Conclusions: IPTp selected for genotypes associated with decreased sensitivity to treatment regimens, but genotypes associated with clinically relevant DP resistance in Asia have not emerged in Uganda. [ABSTRACT FROM AUTHOR]

In this paper, we address the problem of cache replacement for transcoding proxy caching. Transcoding proxy is a proxy that has the functionality of transcoding a multimedia object into an appropriate format or resolution for each client. We first propose an effective cache replacement algorithm for transcoding proxy. In general, when a new object is to be cached, cache replacement algorithms evict some of the cached objects with the least profit to accommodate the new object. Our algorithm takes into account of the inter-relationships among different versions of the same multimedia object, and selects the versions to replace according to their aggregate profit which usually differs from simple summation of their individual profits as assumed in the existing algorithms. It also considers cache consistency, which is not considered in the existing algorithms. We then present a complexity analysis to show the efficiency of our algorithm. Finally, we give extensive simulation results to compare the performance of our algorithm with some existing algorithms. The results show that our algorithm outperforms others in terms of various performance metrics. [ABSTRACT FROM AUTHOR]

Human heme oxygenase-1 (hHO-1) catalyzes the O2dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the α-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXα. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the γ-meso- rather than at the normal, unsubstituted α-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the potphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXα and oxidizes 15phenylheme at the α-meso position to give 10-phenylbiliverdin IXα. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-Å crystal structures of the hHO-1 complexes with 1and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylhemehHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the α-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity. [ABSTRACT FROM AUTHOR]