bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Active Versus Usual Algorithmic Titration of Basal Insulin and Point-of-Care Versus Laboratory Measurement of HbA1c on Glycemic Control in Patients With Type 2 Diabetes
Authors: Kennedy Laurence , Herman William H. , Strange Poul , Harris Anthony ,   for the GOAL A1C Team
Published: April 2006

OBJECTIVE—The objective of this study was to assess the impact of active versus usual monitoring of algorithmic insulin titration and point-of-care (POC) versus laboratory HbA1c (A1C) measurement on glycemic control in primary care.

RESEARCH DESIGN AND METHODS—The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) study was a 24-week, randomized, parallel-group, four-arm, open-label study of 7,893 adults with type 2 diabetes uncontrolled by oral antidiabetic agents and requiring insulin. Patients were randomly assigned by investigators from 2,164 sites in the U.S. to insulin glargine with either 1) usual (no unsolicited contact between visits) insulin titration using a simple algorithm with laboratory A1C testing, 2) usual titration with POC A1C testing, 3) active (weekly monitored) titration with laboratory A1C testing, or 4) active titration with POC A1C testing. Outcome measures included a change in A1C and fasting self-monitoring of blood glucose (SMBG) levels, percentage of patients achieving A1C <7.0%, and hypoglycemia frequency.

RESULTS—Significant A1C and SMBG reductions were observed in all arms (P < 0.0001). Compared with usual insulin titration, active titration achieved greater A1C reduction (1.5 vs. 1.3%; P < 0.0001), SMBG reduction (88 vs. 79 mg/dl; P < 0.0001), and proportion of patients achieving A1C <7.0% (38 vs. 30%; P < 0.0001). Among patients receiving active titration, POC A1C testing was associated with an increase in the proportion achieving an A1C <7.0% (41% for POC vs. 36% for laboratory; P < 0.0001). Hypoglycemia rates were low (usual vs. active groups: 3.7 vs. 6.0 all confirmed episodes/patient-year [P < 0.001]; 0.09 vs. 0.14 severe episodes/patient-year [NS]).

CONCLUSIONS—In a predominantly primary care setting, addition of insulin glargine using a simple algorithm achieved significant improvements in glycemic control in patients with type 2 diabetes in all four study arms. Active titration resulted in significant incremental improvements in glycemic control, and, among patients receiving active titration, POC A1C testing resulted in a greater portion achieving A1C <7.0%.
Long-Term Effects of Ranirestat (AS-3201) on Peripheral Nerve Function in Patients With Diabetic Sensorimotor Polyneuropathy
Authors: Bril Vera , Buchanan Robert A. ,   the Ranirestat Study Group*
Published: April 2006

OBJECTIVES—We aimed to determine whether ranirestat, an aldose reductase inhibitor, maintains the improved nerve function observed in patients with diabetic sensorimotor polyneuropathy (DSP) after completing a 12-week nerve biopsy study.

RESEARCH DESIGN AND METHODS—Patients with mild to moderate DSP, as determined by the presence of sural nerve responses, were enrolled in a double-blind, placebo-controlled biopsy trial and randomized to placebo or 5 or 20 mg/day ranirestat for 12 weeks. Patients completing this biopsy study were offered a 48-week extension at the same ranirestat dose or at 5 mg/day ranirestat if they were originally treated with placebo. Electrophysiological tests, the Toronto Clinical Neuropathy Score, and vibration perception thresholds (VPTs) were performed at entry and at 12 (end of the biopsy study) and 60 (end of the 48-week extension) weeks.

RESULTS—Peroneal motor nerve conduction velocity (NCV) improved in the 20-mg/day group following 60 weeks of treatment. Sural and median sensory NCV improved after both 12 and 60 weeks of treatment with 20 mg/day. VPT improved after 60 weeks of treatment with 20 mg/day. Ranirestat was well tolerated with no difference in adverse events between the 5- and 20-mg/day groups.

CONCLUSIONS—Twenty milligrams ranirestat per day improves NCV and VPT following 60 weeks of administration. The improved sensory nerve function observed after 12 weeks of therapy was maintained at 60 weeks, and improved motor nerve function was observed at 60 weeks.
Population genetic structure of crimson snapper Lutjanus erythropterus in East Asia, revealed by analysis of the mitochondrial control region
Authors: Zhang Junbin , Cai Zeping , Huang Liangmin
Published: April 2006

The population genetic structure of the crimson snapper Lutjanus erythropterus in East Asia was examined with a 427-bp hypervariable portion of the mtDNA control region. A total of 262 samples were collected and 75 haplotypes were obtained. Neutrality tests (Tajima's and Fu's) suggested that Lutjanus erythropterus in East Asia had experienced a bottleneck followed by population expansion since the late Pleistocene. Despite the low phylogeographic structures in mtDNA haplotypes, a hierarchical examination of populations in 11 localities from four geographical regions using analysis of molecular variance (AMOVA) indicated significant genetic differentiation among regions (ΦCT = 0.08564, p < 0.01). Limited gene flow between the eastern region (including a locality in the western Pacific Ocean and two localities in the East Sea) and three geographic regions of the South China Sea largely contributed to the genetic subdivision. However, comparisons among three geographic regions of the South China Sea showed little to no genetic difference. Populations of Lutjanus erythropterus in East Asia are inferred to be divided into two major groups: an eastern group, including populations of the western Pacific Ocean and the East Sea, and a South China Sea group, consisting of populations from northern Malaysia to South China. The results suggest that fishery management should reflect the genetic differentiation and diversity in East Asia.
Critical finite‐size scaling of energy and lifetime probability distributions of auroral emissions
Authors: Uritsky V. M. , Klimas A. J. , Vassiliadis D.
Published: April 2006

Based on statistical study of approximately 15,500 ultraviolet images of auroral emission regions provided by the UVI experiment on the POLAR spacecraft, we show that energy and duration probability distributions of particle precipitation events obey finite‐size scaling relations indicative of a self‐organized critical (SOC) dynamical state. The revealed relations are invariant with respect to significant changes in the spatial scale of the emission areas, and involve a set of mutually consistent critical exponents providing a quantitative basis for future theoretical studies of multiscale magnetospheric fluctuations. The reported statistical results highlight the importance of cross‐scale coupling in the development of nighttime geomagnetic disturbances and suggest that various manifestations of substorm activity associated with localized magnetic reconnections in the magnetotail (small to large scale substorms, pseudo‐breakups, BBFs and other types of short‐term localized excitations) can be coordinated on the global scale by universal dynamical principle represented by scale‐free avalanching in numerical SOC models.
Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL fromPseudomonas aeruginosa
Authors: Rutten Lucy , Geurtsen Jeroen , Lambert Wietske , Smolenaers Jeroen J. M. , Bonvin Alexandre M. , de Haan Alex , van der Ley Peter , Egmond Maarten R. , Gros Piet , Tommassen Jan
Published: April 2006

Pathogenic Gram-negative bacteria can modify the lipid A portion of their lipopolysaccharide in response to environmental stimuli. 3-O-deacylation of lipid A by the outer membrane enzyme PagL modulates signaling through Toll-like receptor 4, leading to a reduced host immune response. We found that PagL is widely disseminated among Gram-negative bacteria. Only four residues are conserved: a Ser, His, Phe, and Asn residue. Here, we describe the crystal structure of PagL fromPseudomonas aeruginosato 2.0-Å resolution. It consists of an eight-stranded β-barrel with the axis tilted by ≈30° with respect to the lipid bilayer. The structure reveals that PagL contains an active site with a Ser-His-Glu catalytic triad and an oxyanion hole that comprises the conserved Asn. The importance of active site residues was confirmed in mutagenesis studies. Although PagL is most likely active as a monomer, its active site architecture shows high resemblance to that of the dimeric 12-stranded outer membrane phospholipase A. Modeling of the substrate lipid X onto the active site reveals that the 3-O-acyl chain is accommodated in a hydrophobic groove perpendicular to the membrane plane. In addition, an aspartate makes a hydrogen bond with the hydroxyl group of the 3-O-acyl chain, probably providing specificity of PagL toward lipid A.
Computational and neurobiological mechanisms underlying cognitive flexibility
Authors: Badre David , Wagner Anthony D.
Published: April 2006

The ability to switch between multiple tasks is central to flexible behavior. Although switching between tasks is readily accomplished, a well established consequence of task switching (TS) is behavioral slowing. The source of this switch cost and the contribution of cognitive control to its resolution remain highly controversial. Here, we tested whether proactive interference arising from memory places fundamental constraints on flexible performance, and whether prefrontal control processes contribute to overcoming these constraints. Event-related functional MRI indexed neural responses during TS. The contributions of cognitive control and interference were made theoretically explicit in a computational model of task performance. Model estimates of two levels of proactive interference, “conceptual conflict” and “response conflict,” produced distinct preparation-related profiles. Left ventrolateral prefrontal cortical activation paralleled model estimates of conceptual conflict, dissociating from that in left inferior parietal cortex, which paralleled model estimates of response conflict. These computationally informed neural measures specify retrieved conceptual representations as a source of conflict during TS and suggest that left ventrolateral prefrontal cortex resolves this conflict to facilitate flexible performance.
Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans
Authors: Comeron Josep M.
Published: April 2006

Recent large-scale genomic and evolutionary studies have revealed the small but detectable signature of weak selection on synonymous mutations during mammalian evolution, likely acting at the level of translational efficacy (i.e., translational selection). To investigate whether weak selection, and translational selection in particular, plays any role in shaping the fate of synonymous mutations that are present today in human populations, we studied genetic variation at the polymorphic level and patterns of evolution in the human lineage after human–chimpanzee separation. We find evidence that neutral mechanisms are influencing the frequency of polymorphic mutations in humans. Our results suggest a recent increase in mutational tendencies toward AT, observed in all isochores, that is responsible for AT mutations segregating at lower frequencies than GC mutations. In all, however, changes in mutational tendencies and other neutral scenarios are not sufficient to explain a difference between synonymous and noncoding mutations or a difference between synonymous mutations potentially advantageous or deleterious under a translational selection model. Furthermore, several estimates of selection intensity on synonymous mutations all suggest a detectable influence of weak selection acting at the level of translational selection. Thus, random genetic drift, recent changes in mutational tendencies, and weak selection influence the fate of synonymous mutations that are present today as polymorphisms. All of these features, neutral and selective, should be taken into account in evolutionary analyses that often assume constancy of mutational tendencies and complete neutrality of synonymous mutations.
Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients
Authors: Herbeuval Jean-Philippe , Nilsson Jakob , Boasso Adriano , Hardy Andrew W. , Kruhlak Michael J. , Anderson Stephanie A. , Dolan Matthew J. , Dy Michel , Andersson Jan , Shearer Gene M.
Published: April 2006

Loss of CD4
+
T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-α produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4
+
T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN-α in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCs
in vivo
and
in vitro
. Expression of IFN-α was increased in lymphoid tonsillar tissue (LT) of patients with progressive (HIV
prog
) compared with nonprogressive (HIV
NP
) HIV-1 disease and to uninfected controls. LT from HIV
prog
exhibited higher TRAIL and DR5 mRNA levels than LT from HIV
NP
or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-α and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis.
Inhibition of Brassinosteroid Biosynthesis by Either a dwarf4 Mutation or a Brassinosteroid Biosynthesis Inhibitor Rescues Defects in Tropic Responses of Hypocotyls in the Arabidopsis Mutant nonphototropic hypocotyl 4
Authors: Nakamoto Daisuke , Ikeura Akimitsu , Asami Tadao , Yamamoto Kotaro T.
Published: April 2006

The nonphototropic hypocotyl 4 (nph4)/auxin response factor 7 (arf7) mutant of Arabidopsis (Arabidopsis thaliana) is insensitive to auxin and has defects in hypocotyl tropism, hook formation, differential leaf growth, and lateral root formation. To understand an auxin-signaling pathway through NPH4, we carried out screening of suppressor mutants of nph4-103 and obtained a dwarf suppressor mutant, suppressor of nph4 (snp2). snp2 had short hypocotyls in the dark condition and dark green and round leaves, short petioles, and more lateral shoots than the wild type in the light condition. The snp2 phenotypes were rescued by adding brassinolide to the growth medium in both light and dark conditions. Genetic mapping, sequence analysis, and a complementation test indicated that snp2 was a weak allele of DWARF4 (DWF4), which functions in brassinosteroid (BR) biosynthesis. snp2, which was renamed dwf4-101, exhibited photo- and gravitropisms of hypocotyls similar to those of the wild type with a slightly faster response in gravitropism. dwf4-101 almost completely suppressed defects in both tropisms of nph4-103 hypocotyls and completely suppressed hyponastic growth of nph4-103 leaves. Treatment with brassinazole, an inhibitor of BR biosynthesis, also partially rescued the tropic defects in nph4-103. Hypocotyls of nph4-103 were auxin insensitive, whereas hypocotyls of dwf4-101 were more sensitive than those of the wild type. dwf4-101 nph4-103 hypocotyls were as sensitive as those of dwf4-101. Auxin inducibility of massugu 2 (MSG2)/IAA19 gene expression was reduced in nph4-103. mRNA level of MSG2 was reduced in dwf4-101 and dwf4-101 nph4-103, but both mutants exhibited greater auxin inducibility of MSG2 than the wild type. Taken together, dwf4-101 was epistatic to nph4-103. These results strongly suggest that BR deficiency suppresses nph4-103 defects in tropic responses of hypocotyls and differential growth of leaves and that BR negatively regulates tropic responses.
Sequence-Level Analysis of the Diploidization Process in the TriplicatedFLOWERING LOCUS CRegion ofBrassica rapa
Authors: Yang Tae-Jin , Kim Jung Sun , Kwon Soo-Jin , Lim Ki-Byung , Choi Beom-Soon , Kim Jin-A , Jin Mina , Park Jee Young , Lim Myung-Ho , Kim Ho-Il , Lim Yong Pyo , Kang Jason Jongho , Hong Jin-Han , Kim Chang-Bae , Bhak Jong , Bancroft Ian , Park Beom-Seok
Published: April 2006

Strong evidence exists for polyploidy having occurred during the evolution of the tribe Brassiceae. We show evidence for the dynamic and ongoing diploidization process by comparative analysis of the sequences of four paralogous Brassica rapa BAC clones and the homologous 124-kb segment of Arabidopsis thaliana chromosome 5. We estimated the times since divergence of the paralogous and homologous lineages. The three paralogous subgenomes of B. rapa triplicated 13 to 17 million years ago (MYA), very soon after the Arabidopsis and Brassica divergence occurred at 17 to 18 MYA. In addition, a pair of BACs represents a more recent segmental duplication, which occurred ∼0.8 MYA, and provides an exception to the general expectation of three paralogous segments within the B. rapa genome. The Brassica genome segments show extensive interspersed gene loss relative to the inferred structure of the ancestral genome, whereas the Arabidopsis genome segment appears little changed. Representatives of all 32 genes in the Arabidopsis genome segment are represented in Brassica, but the hexaploid complement of 96 has been reduced to 54 in the three subgenomes, with compression of the genomic region lengths they occupy to between 52 and 110 kb. The gene content of the recently duplicated B. rapa genome segments is identical, but intergenic sequences differ.
Contribution of whole blood to the control of plasma asymmetrical dimethylarginine
Authors: Billecke Scott S. , Kitzmiller Laura A. , Northrup Joseph J. , Whitesall Steven E. , Kimoto Masumi , Hinz Alia V. , D'Alecy Louis G.
Published: April 2006

The endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is elevated in many patients and may contribute to the initiation and progression of their disease. While some mechanistic pathways have been identified, tissue-specific contributions to ADMA control remain unclear. We sought to determine if whole blood (WB) could participate in ADMA control ex vivo. Anesthetized male Sprague-Dawley rats underwent exsanguinations, and WB preparations were incubated at 37°C for 5 h. ADMA and symmetrical dimethylarginine were analyzed by high-pressure liquid chromatography. Incubation of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA that was blocked by 4124W, a synthetic inhibitor of dimethylarginine dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA. Hydrolysis of ADMA was diminished by addition of physiologically relevant concentrations of zinc (i.e., 20 μM). Conversely, when rat WB or WB supernatant was incubated at 37°C, it liberated quantities of free ADMA (1–2 μM) that in vivo would likely have pathological consequences. Addition of arginine methyltransferase inhibitors to these incubations did not reduce ADMA release, indicating no dominant role for active protein methylation during these incubations. This ADMA liberation was significantly reduced by addition of protease inhibitors, indicating a dependence on peptide bond hydrolysis. Total ADMA (protein incorporated plus free) was determined by acid hydrolysis and found to be 43.18 ± 4.79 μM in WB with ∼95% of this in RBCs. These ex vivo data demonstrate the potential of blood to control the NO-NOS system by modulating free ADMA.
Transient permeabilization of cell membranes by ultrasound-exposed microbubbles is related to formation of hydrogen peroxide
Authors: Juffermans L. J. M. , Dijkmans P. A. , Musters R. J. P. , Visser C. A. , Kamp O.
Published: April 2006

In the present study, we addressed the interactions among ultrasound, microbubbles, and living cells as well as consequent arising bioeffects. We specifically investigated whether hydrogen peroxide (H2O2) is involved in transient permeabilization of cell membranes in vitro after ultrasound exposure at low diagnostic power, in the presence of stable oscillating microbubbles, by measuring the generation of H2O2 and Ca2+ influx. Ultrasound, in the absence or presence of SonoVue microbubbles, was applied to H9c2 cells at 1.8 MHz with a mechanical index (MI) of 0.1 or 0.5 during 10 s. This was repeated every minute, for a total of five times. The production of H2O2 was measured intracellularly with CM-H2DCFDA. Cell membrane permeability was assessed by measuring real-time changes in intracellular Ca2+ concentration with fluo-4 using live-cell fluorescence microscopy. Ultrasound, in the presence of microbubbles, caused a significant increase in intracellular H2O2 at MI 0.1 of 50% and MI 0.5 of 110% compared with control ( P < 0.001). Furthermore, we found increases in intracellular Ca2+ levels at both MI 0.1 and MI 0.5 in the presence of microbubbles, which was not detected in the absence of extracellular Ca2+. In addition, in the presence of catalase, Ca2+ influx immediately following ultrasound exposure was completely blocked at MI 0.1 ( P < 0.01) and reduced by 50% at MI 0.5 ( P < 0.001). Finally, cell viability was not significantly affected, not even 24 h later. These results implicate a role for H2O2 in transient permeabilization of cell membranes induced by ultrasound-exposed microbubbles.
Modelling of dynamic recrystallisation kinetics in austenitic stainless and hypereutectoid steels
Authors: Stewart G. R. , Elwazri A. M. , Yue S. , Jonas J. J.
Published: April 2006

Two important parameters for dynamic recrystallisation can be derived from changes in the strain hardening rate: the critical strain for initiation of dynamic recrystallisation and the point of maximum softening. In the present work, these values are determined from stress–strain data obtained by compression testing over the range of 900–1100°C. The resulting strains are used to derive a kinetic model of dynamic recrystallisation for two materials: 304 austenitic stainless steel and a hypereutectoid plain carbon steel. The values of the mechanical parameters used to define the proposed model are confirmed with the aid of metallographic analysis of the recrystallised microstructures.
Preparation of nanoporous silica–zirconia layers by in situ sol–gel method
Authors: Eriksson M. , Klein L. C. , Lidén E. , Lindqvist K.
Published: April 2006

Silica–zirconia membranes were prepared using a sol–gel process, never before used on this system. Thin layers of gel were grown on the outside of porous alumina support tubes using the permeation of water through pores of the tube to control the rate of hydrolysis with a reactive silica–zirconia alkoxide solution. A recipe was developed and optimum coating conditions were found to be the ratios of tetraethylorthosilicate (TEOS) to Zr propoxide to 1-propanol molar ratios (1:0·5:17), with a coating time of 300 s. The method allowed the formation of a membrane in a single step compared with repeated coating and firing. The coatings could be prepared adherent and without cracks when properly prepared.
Development of radiation resistant materials for advanced nuclear power plant
Authors: Little E. A.
Published: April 2006

A unique feature of the environment of nuclear power reactors is the presence of high energy neutron radiation, which can lead to degradation processes in the materials of critical components. An understanding of the operative elevated temperature radiation damage mechanisms enables these effects to be minimised by appropriate alloy selection together with compositional optimisation. An overview of these aspects relevant to advanced fission and fusion reactor systems is presented. Several key examples are highlighted and include radiation embrittlement of low alloy pressure vessel steels for pressurised water reactors, coating designs for fuel in high temperature pebble bed reactors, and selection and design of low activation materials for proposed tokomak fusion reactor devices. In addition, void swelling, non-equilibrium solute segregation and radiation induced precipitation processes in alloys at high displacement doses and relevant to several reactor systems are covered. Likely trends in future nuclear power plant design and associated materials requirements are discussed.
Principles of survey development for telemedicine applications
Authors: Demiris George
Published: April 2006

Surveys can be used in the evaluation of telemedicine applications but they must be properly designed, consistent and accurate. The purpose of the survey and the resources available will determine the extent of testing that a survey instrument should undergo prior to its use. The validity of an instrument is the correspondence between what is being measured and what was intended to be measured. The reliability of an instrument describes the 'consistency' or 'repeatability' of the measurements made with it. Survey instruments should be designed and tested following basic principles of survey development. The actual survey administration also requires consideration, for example data collection and processing, as well as the interpretation of the findings. Surveys are of two different types. Either they are self-administered, or they are administered by interview. In the latter case, they may be administered by telephone or in a face-to-face meeting. It is important to design a survey instrument based on a detailed definition of what it intends to measure and to test it before administering it to the larger sample.
Telemedicine as a means of delivering cognitive-behavioural therapy to rural and remote mental health clients
Authors: Griffiths Lucille , Blignault Ilse , Yellowlees Peter
Published: April 2006

We explored the feasibility and acceptability of delivering cognitive-behavioural therapy (CBT) via videoconference to clients with depression and/or anxiety living in rural north Queensland. The study involved 15 mental health clients and their five case managers. First, each case manager was instructed in the use of telemedicine for clinical consultation, and given training in CBT. This was done via videoconference. Then the clients were introduced to telemedicine. Following six to eight intensive weekly sessions of CBT, there was improvement in certain clinical outcome measures (i.e. the Mental Health Inventory and the Health of the Nation Outcome Scale). There was a significant improvement ( P<0.05 using a t-test) in the client Mental Health Inventory scores before (mean = 109) and after treatment (mean = 148). However, in the absence of a control condition, it was not possible to conclude that the treatment had a specific effect on the disorders studied. Both clients and case managers found telemedicine consultations acceptable. Clients' ratings ranged from 3 to 4.5, while case mangers' ratings ranged from 3 to 5 ('average' to 'much better than average').
Global health care – bridging the gap
Authors: Lugn Nancy E
Published: April 2006

The World Health Assembly has acknowledged that telehealth could play an important role in providing access to health care for populations at risk worldwide. The Cambodia Teleconsultation Programme or Village Leap Programme connects those in need of health care, with those willing to share their medical expertise. Telemedicine clinics are run every other week at one of two villages in northern Cambodia. The nurse is responsible for gathering medical information and transmitting it by email to physicians in the USA, and to the Sihanouk Hospital of Hope in Phnom Phen. Poorer countries do not and are not likely to have national telemedicine programmes in the near future. But as the experience in Cambodia shows, grass-root telemedicine programmes can make a difference. The need is great and we can no longer wait for governments to lead. Thoughtfully implemented telemedicine programmes providing medical education, health care and screening may change the health of the world.
Production of Electricity from Proteins Using a Microbial Fuel Cell
Authors: Heilmann Jenna , Logan Bruce E.
Published: April 2006

Electricity generation was examined from proteins and a protein‐rich wastewater using a single chamber microbial fuel cell (MFC). The maximum power densities achieved were 354 ± 10 mW/m2 using bovine serum albumin (BSA) and 269 ± 14 mW/m2 using peptone (1100 mg/L BSA and 300 mg/L peptone). The recovery of organic matter as electricity, defined as the Coulombic efficiency (CE), was comparable to that obtained with other substrates with CE = 20.6% for BSA and CE = 6.0% for peptone. A meat packing wastewater (MPW), diluted to 1420 mg/L chemical oxygen demand, produced 80 ± 1 mW/m2, and power was increased by 33% by adding salt (300 mg/L sodium chloride) to increase solution conductivity. A wastewater inoculum generated 33% less power than the MPW inoculum. The MFC was an effective method of wastewater treatment, demonstrated by >86% of biochemical oxygen demand and total organic carbon removal from wastewater.
Growth Kinetics and Competition Between Methanosarcina and Methanosaeta in Mesophilic Anaerobic Digestion
Authors: Conklin Anne , Stensel H. David , Ferguson John
Published: April 2006

Methanosarcina species with a high maximum specific growth rate (μmax) and high half‐saturation coefficient (K S) and Methanosaeta species with a low μmax and low K S are the only known aceticlastic methanogens. Because of Methanosaeta's low K S, the low acetate concentrations in conventional, mesophilic anaerobic digestion yield Methanosaeta dominance. However, Methanosarcina absorbs increases in acetate more efficiently and thus promotes more stable digestion. This paper tests the hypothesis that decreasing digester feeding frequencies can increase Methanosarcina predominance. Two acetate‐fed reactors were established at a 17‐day solids retention time. One reactor was fed hourly, and one was fed once daily. Microscopic and molecular methods were used to verify that the hourly fed reactor enriched for Methanosaeta, while the daily fed reactor enriched for Methanosarcina. Growth and substrate‐use kinetics were measured for each reactor. A digester overload condition was simulated, and the Methanosarcina‐enriched reactor was found to perform better than the Methanosaeta‐enriched reactor. These findings indicate that Methanosarcina dominance can be achieved with infrequent feedings, leading to more stable digestion.
Subsidiarity as a Structural Principle of International Human Rights Law
Authors: Carozza Paolo G.
Published: April 2006

There is an inherent tension in international human rights law between affirming a universal substantive vision of human dignity and respecting the diversity and freedom of human cultures. Although understanding and securing human rights in international law requires us to grapple with that conflict, classic notions of state sovereignty cannot adequately address the issue. The principle of subsidiarity, instead, gives us a conceptual tool to mediate the polarity of pluralism and the common good in a globalized world and helps us make sense of international human rights law. I argue that we should regard subsidiarity as a structural principle of international human rights law.
Human Rights in 2002: The Annual Sessions of the UN Commission on Human Rights and the Economic and Social Council
Authors: Dennis Michael J.
Published: April 2006

The fifty-eighth session of the United Nations Commission on Human Rights opened with the United States in an observer seat for the first time ever. The Commission ultimately adopted ninety-two resolutions and eighteen decisions, thirty-nine of which were adopted by roll-call vote. Subsequently, at its July 2002 session, the Economic and Social Council (ECOSOC, the parent body of the Commission) approved nearly all of the Commission's decisions by similar votes. The United States was also reelected to the Commission for its fiftyninth session during a separate ECOSOC meeting.

The debate during the Commission's deliberations was more chaotic and fractious than in prior years, reflecting the membership of an increased number of repressive governments that sought to block international scrutiny of their human rights practices.
Enhancing the Legitimacy and Accountability of Prosecutorial Discretion at the International Criminal Court
Authors: Danner Allison Marston
Published: April 2006

The rapid ratification of the Rome Statute of the International Criminal Court (ICC) and the orderly election of its judges and prosecutor belie the radical nature of the new institution. The Court has jurisdiction over genocide, aggression, crimes against humanity, and war crimes—crimes of the utmost seriousness often committed by governments themselves, or with their tacit approval. The ICC has the formal authority to adjudge the actions of high state officials as criminal and to send them to jail, no matter how lofty the accused’s position or undisputed the legality of those acts under domestic law. While the International Criminal Tribunals for the Former Yugoslavia (ICTY) and Rwanda (ICTR) also possess this authority, those institutions operate directly under the control of the United Nations Security Council and within narrow territorial limits. The ICC, by contrast, is largely independent of the Council and vests the power to investigate and prosecute the politically sensitive crimes within its broad territorial sweep in a single individual, its independent prosecutor.
International Law as Part of Our Law
Authors: Koh Harold Hongju
Published: April 2006

What did the United States Supreme Court mean when it famously said, “International law is part of our law, and must be ascertained and administered by the courts of justice of appropriate jurisdiction, as often as questions of right depending upon it are duly presented for their determination”? Perhaps the Court was suggesting that, in an interdependent world, United States courts should not decide cases without paying “a decent respect to the opinions of mankind,” in the memorable words of the Declaration of Independence. The framers and early Justices understood that the global legitimacy of a fledgling nation crucially depended upon the compatibility of its domestic law with the rules of the international system within which it sought acceptance. Their recognition seems both prudent and sensible. Even today, for any nation consciously to ignore global standards not only would ensure constant frictions with the rest of the world, but also would diminish that nation's ability to invoke those international rules that served its own national purposes.
The Right of the Accused to Self-Representation Before International Criminal Tribunals
Authors: Jørgensen Nina H. B.
Published: April 2006

Conventional wisdom holds that a lawyer who represents himself has a fool for a client. Perhaps surprisingly, several of the highest profile accused persons before the International Criminal Tribunal for the Former Yugoslavia (ICTY) have received some form of legal training. Less surprisingly, it is precisely those accused who are asserting a right to self-representation. Slobodan Miloševic, for example, has a degree in law and by the end of his trial will have earned himself several years of advocacy experience. Vojislav Šešelj, a professor of law at Belgrade University, was somewhat affronted by the judge's suggestion that he should request legal assistance and exclaimed in open court, “I have never met a better lawyer dian I am in my whole life.” Are these accused fools to want to represent themselves? What about an accused with no legal experience at all who asserts this right in the face of charges of genocide and crimes against humanity? As one accused remarked when clarifying to the court that he did not wish to represent himself, “No. It would be insane if I did that ….”
The ICJ’s Advisory Jurisdiction and the Crumbling Wall Between the Political and the Judicial
Authors: Pomerance Michla
Published: April 2006

It is hardly surprising that the controversial advisor)’ opinion of the International Court of Justice in the case concerning the Israeli security fence raised serious concerns in many quarters, on multiple grounds. Most prominently, as some of the judges and numerous commentators have noted, the restriction of the right of self-defense under Article 51 of the United Nations Charter to attacks by “states” is unwarranted on the basis of the text. It is also, of course, illogical in an era when the worldwide terrorist threats stem primarily from nonstate actors. Additionally, in the current case, while the Court assimilated “Palestine” to a state for the purpose of granting it certain rights (including procedural rights before the Court), the ICJ made no corresponding acknowledgment of Palestine’s obligation to refrain from engaging in an armed attack. This, as Judge Rosalyn Higgins recognized, was “formalism of an unevenhanded sort.”
Effect of Combined Antisense Oligonucleotides Against High-Glucose–and Diabetes-Induced Overexpression of Extracellular Matrix Components and Increased Vascular Permeability
Authors: Oshitari Toshiyuki , Polewski Peter , Chadda Manish , Li An-Fei , Sato Tsuyoshi , Roy Sayon
Published: April 2006

The effect of combined antisense oligonucleotides (AS-oligos) against overexpression of extracellular matrix (ECM) components, fibronectin, laminin, and collagen IV and on cell monolayer permeability was examined in rat microvascular endothelial cells (RMECs) grown in high glucose medium and on retinal vascular permeability in diabetic rats. RMECs grown in high glucose for 10 days and transfected with combined AS-oligos showed a significantly reduced fibronectin, laminin, and collagen IV protein level. In parallel studies, high-glucose–induced excess monolayer permeability was also reduced in RMECs transfected with the combined AS-oligos. Similarly, diabetic rats intravitreally injected with the combined AS-oligos and examined after 2 months of diabetes showed significant reduction in retinal fibronectin, laminin, and collagen IV expression. In addition, vascular permeability, as determined from extravasation of fluorescein isothiocyanate–BSA in the surrounding areas of the retinal capillaries, was partially reduced in the combined AS-oligos–treated diabetic retinas. Our results indicate that the combined AS-oligos strategy is effective in simultaneously reducing fibronectin, collagen IV, and laminin overexpression and reducing vascular leakage in the retinal capillaries of diabetic rat retinas. The findings suggest that abnormal synthesis of ECM components may contribute to vascular leakage in the diabetic retina.
Natural Killer T-Cells Participate in Rejection of Islet Allografts in the Liver of Mice
Authors: Toyofuku Atsushi , Yasunami Yohichi , Nabeyama Kentaroh , Nakano Masahiko , Satoh Masayuki , Matsuoka Nobuhide , Ono Junko , Nakayama Toshinori , Taniguchi Masaru , Tanaka Masao , Ikeda Seiyo
Published: April 2006

A role of natural killer T (NKT) cells in transplant rejection remains unknown. Here, we determined whether NKT cells participate in rejection of islet allografts, using NKT cell–deficient mice. Survival of islet allografts in streptozotocin-induced diabetic CD1d−/− mice or Vα14 NKT cell−/− mice was significantly prolonged without immunosuppression when grafted into the liver, but not beneath the kidney capsule, compared with wild-type mice. Acceptance of intrahepatic islet allografts was achieved in CD1d−/− mice by a subtherapeutic dose of rapamycin, which was abrogated in conjunction with the transfer of hepatic mononuclear cells from wild-type, but not from CD1d−/−, mice at islet transplantation. The second islet grafts from a donor-specific, but not from a third-party, strain in CD1d−/− mice bearing functional islet allografts were accepted without immunosuppression at 120 days after the initial transplantation. These findings demonstrate that NKT cells play a significant role in rejection of islet allografts in the liver of mice, but that NKT cells are not essential for induction of donor-specific unresponsiveness in this model. The current study indicates that NKT cells might be considered as a target for intervention to prevent islet allograft rejection when the liver is the site of transplantation.
Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand
Authors: Vaidyula Vijender R. , Rao A. Koneti , Mozzoli Maria , Homko Carol , Cheung Peter , Boden Guenther
Published: April 2006

Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.
Increased Lipid Availability Impairs Insulin-Stimulated ATP Synthesis in Human Skeletal Muscle
Authors: Brehm Attila , Krssak Martin , Schmid Albrecht I. , Nowotny Peter , Waldhäusl Werner , Roden Michael
Published: April 2006

Insulin resistance correlates with intramyocellular lipid content (IMCL) and plasma free fatty acids (FFAs) and was recently linked to mitochondrial dysfunction. We examined the underlying relationships by measuring skeletal muscle ATP synthase flux, glucose transport/phosphorylation, and IMCL in response to different plasma insulin and plasma FFA concentrations. Healthy men were studied twice during hyperinsulinemic-euglycemic clamps with (LIP) or without (CON) lipid infusion (plasma FFA: CON ∼36 vs. LIP ∼1,034 μmol/l, P < 0.001). ATP synthase flux, glucose-6-phosphate (G6P), and IMCL were determined before and during the clamp in calf muscle using 31P and 1H magnetic resonance spectroscopy. Plasma lipid elevation resulted in ∼46% reduced whole-body glucose metabolism (180–360 min; P < 0.0001 vs. CON) and a 70% lower rise of G6P (P < 0.05 vs. CON) without significant changes in IMCL (LIP 117 ± 12% vs. CON 93 ± 3% of basal, P = 0.073). During the clamp, ATP synthase flux increased by ∼60% under control conditions (P = 0.02 vs. baseline) and was 24% lower during lipid infusion (LIP 11.0 ± 0.9 vs. CON 14.6 ± 1.2 μmol · g muscle−1 · min−1, P < 0.05). Physiologically increased plasma FFA concentrations reduce insulin-stimulated muscle ATP synthase flux in parallel with induction of insulin resistance.
A Single Factor Underlies the Metabolic Syndrome
Authors: Pladevall Manel , Singal Bonita , Williams L. Keoki , Brotons Carlos , Guyer Heidi , Sadurni Josep , Falces Carles , Serrano-Rios Manuel , Gabriel Rafael , Shaw Jonathan E. , Zimmet Paul Z. , Haffner Steven
Published: April 2006

OBJECTIVE—Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor.

RESEARCH DESIGN AND METHODS—Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models.

RESULTS—The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome.

CONCLUSIONS—These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.
Association Between Complementary and Alternative Medicine Use, Preventive Care Practices, and Use of Conventional Medical Services Among Adults With Diabetes
Authors: Garrow Donald , Egede Leonard E.
Published: April 2006

OBJECTIVE—To assess the association between complementary and alternative medicine (CAM) use, preventive care practices, and use of conventional medical services among adults with diabetes.

RESEARCH DESIGN AND METHODS—We analyzed data on 2,474 adults with diabetes. We created an overall CAM-use category based on use of any of the following: diets, herbs, chiropractic care, yoga, relaxation, acupuncture, ayuverda, biofeedback, chelation, energy healing, Reiki therapy, hypnosis, massage, naturopathy, and homeopathy. We used multiple logistic regression to assess the effect of CAM use on preventive care practices (receipt of influenza and pneumonia vaccines) and use of conventional medical services (number of primary care and emergency department visits). STATA was used for statistical analysis to account for the complex survey design.

RESULTS—A total of 48% of adults with diabetes used some form of CAM. CAM use was independently associated with receipt of pneumonia vaccination (odds ratio 1.56 [95% CI 1.26–1.94]) but not significantly associated with receipt of influenza vaccination (1.17 [0.92–1.48]). CAM use was independently associated with visiting the emergency department (1.34 [1.06–1.70]), having six or more primary care visits (1.44 [1.14–1.83]), and having eight or more primary care visits (1.66 [1.22–2.25]).

CONCLUSIONS—In contrast to the findings of previous studies, CAM use appears to be associated with increased likelihood of receipt of preventive care services and increased emergency department and primary care visits. CAM use may not be a barrier to use of conventional medical services in adults with diabetes.
Measurement of HCN in the middle atmosphere by EOS MLS
Authors: Pumphrey H. C. , Jimenez Carlos J. , Waters J. W.
Published: April 2006

The EOS MLS instrument on NASA's Aura satellite has made the first continuous global measurements of HCN in the middle atmosphere. The measurements are in broad agreement with most earlier measurements, showing HCN to be a long‐lived tracer with sources in the troposphere and sinks in the middle atmosphere. There is no evidence in the data for a proposed mesospheric source of HCN.