bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Blood Markers and Functional Impairment in Peripheral Arterial Disease
Authors: McDermott Mary M. , Liu Kiang , Ferrucci Luigi , Tian Lu , Guralnik Jack M. , Green David , Tan Jin , Liao Yihua , Pearce William H. , Schneider Joseph R. , McCue Kimberly , Ridker Paul , Rifai Nader , Criqui Michael H.
Published: July 2008

OBJECTIVES: To determine whether higher levels of inflammatory blood markers, D‐dimer, and homocysteine were associated with greater impairment in lower extremity functioning in persons with peripheral arterial disease (PAD).

DESIGN: Cross‐sectional.

SETTING: Three Chicago‐area medical centers.

PARTICIPANTS: Four hundred twenty‐three persons with PAD (ankle–brachial index (ABI) <0.90).

MEASUREMENTS: Lower extremity performance was assessed using the 6‐minute walk and with usual‐ and fast‐paced 4‐m walking speed. Blood markers were D‐dimer, C‐reactive protein (CRP), interleukin‐6 (IL‐6), soluble vascular cellular adhesion molecule‐1 (sVCAM‐1), soluble intracellular adhesion molecule‐1 (sICAM‐1), and homocysteine. Calf muscle area was measured using computed tomography.

RESULTS: Adjusting for confounders, higher levels of D‐dimer (P<.001), IL‐6 (P<.001), sVCAM‐1 (P=.006), CRP (P=.01), homocysteine (P=.004), and sICAM‐1 (P=.046) were associated with poorer 6‐minute walk performance. Higher levels of D‐dimer (P<.001), IL‐6 (P=.003), sVCAM‐1 (P=.001), and homocysteine (P=.005) were associated with slower usual‐paced 4‐m walking speed. Higher levels of D‐dimer, sVCAM‐1, sICAM‐1, IL‐6, and homocysteine were associated with slower fast‐paced walking speed. Results were attenuated after additional adjustment for calf muscle area.

CONCLUSION: Higher levels of inflammation and D‐dimer were associated with poorer lower extremity performance in participants with PAD, independent of confounders including ABI.
Use of Postacute Care by Nursing Home Residents Hospitalized for Stroke or Hip Fracture: How Prevalent and to What End?
Authors: Hoverman Carrie , Shugarman Lisa R. , Saliba Debra , Buntin Melinda Beeuwkes
Published: July 2008

OBJECTIVES: To examine nursing home (NH) residents' use of Medicare‐paid skilled nursing facility (SNF) services and the outcomes of that care and to identify clinical and non‐clinical factors associated with that care.

DESIGN: Retrospective cohort.

SETTING: United States.

PARTICIPANTS: NH residents aged 65 and older with Medicare claims for a hospitalization for hip fracture or stroke during 2001 to 2003.

MEASUREMENTS: Resident diagnoses and use of SNF postacute care were measured using Medicare hospital claims. Market and provider characteristics were drawn from the Provider of Services file. Baseline characteristics, institutionalization, and mortality outcomes were drawn from the Minimum Data Set and Medicare Denominator File.

RESULTS: Of the NH population hospitalized for hip fracture (49,903) or stroke (23,084), 79.7% and 64.1%, respectively, used the SNF benefit. Residents not using the SNF benefit had poorer baseline health status; their mortality rates and rates of resuming long‐term care were similar to the rates of residents who used the SNF benefit.

CONCLUSION: NH residents used postacute SNF benefits at high rates yet had similar mortality and institutionalization outcomes as those without SNF care.
Maximizing Clinical Research Participation in Vulnerable Older Persons: Identification of Barriers and Motivators
Authors: Marcantonio Edward R. , Aneja Jasneet , Jones Richard N. , Alsop David C. , Fong Tamara G. , Crosby Gregory J. , Culley Deborah J. , Cupples L. Adrienne , Inouye Sharon K.
Published: July 2008

OBJECTIVES: To identify barriers and motivators to participation in long‐term clinical research by high‐risk elderly people and to develop procedures to maximize recruitment and retention.

DESIGN: Quantitative and qualitative survey.

SETTING: Academic primary care medicine and pre‐anesthesia testing clinics.

PARTICIPANTS: Fifty patients aged 70 and older, including 25 medical patients at high risk of hospitalization and 25 patients with planned major surgery.

MEASUREMENTS: Fifteen‐ to 20‐minute interviews involved open‐ and closed‐ended questions guided by an in‐depth script. Two planned study protocols were presented to each participant. Both involved serial neuropsychological assessments, blood testing, and magnetic resonance brain imaging (MRI); one added lumbar puncture (LP). Participants were asked whether they would be willing to participate in these protocols, rated barriers and incentives to participation, and were probed with open‐ended questions.

RESULTS: Of 50 participants (average age 78, 44% male, 40% nonwhite), 32 (64%) expressed willingness to participate in the LP‐containing protocol, with LP cited as the strongest disincentive. Thirty‐eight (76%) expressed willingness to participate in the protocol without LP, with phlebotomy and long interviews cited as the strongest disincentives. Altruism was a strong motivator for participation, whereas transportation was a major barrier. Study visits at home, flexible appointment times, assessments shorter than 75 minutes, and providing transportation and free parking were strategies developed to maximize study participation.

CONCLUSION: Vulnerable elderly people expressed a high rate of willingness to participate in an 18‐month prospective study. Participants identified incentives and barriers that enabled investigators to develop procedures to maximize recruitment and retention.
Self‐Reported Napping and Duration and Quality of Sleep in the Lifestyle Interventions and Independence for Elders Pilot Study
Authors: Picarsic Jennifer L. , Glynn Nancy W. , Taylor Christopher A. , Katula Jeffrey A. , Goldman Suzanne E. , Studenski Stephanie A. , Newman Anne B.
Published: July 2008

OBJECTIVES: To determine the prevalence of self‐reported napping and its association with subjective nighttime sleep duration and quality, as measured according to sleep‐onset latency and sleep efficiency.

DESIGN: Cross‐sectional study.

SETTING: Lifestyle Interventions and Independence for Elders Pilot Study.

PARTICIPANTS: Community‐dwelling older adults (N=414) aged 70 to 89.

MEASUREMENTS: Self‐report questionnaire on napping and sleep derived from the Pittsburgh Sleep Quality Index (PSQI) scale.

RESULTS: Fifty‐four percent of participants reported napping, with mean nap duration of 55.0±41.2 minutes. Nappers were more likely to be male (37.3% vs 23.8%, P=.003) and African American (20.4% vs 14.4%, P=.06) and to have diabetes mellitus (28% vs 14.3%, P=.007) than non‐nappers. Nappers and non‐nappers had similar nighttime sleep duration and quality, but nappers spent approximately 10% of their 24‐hour sleep occupied in napping. In a multivariate model, the odds of napping were higher for subjects with diabetes mellitus (odds ratio (OR)=1.9, 95% confidence interval (CI)=1.2–3.0) and men (OR=1.9, 95% CI=1.2–3.0). In nappers, diabetes mellitus (β=12.3 minutes, P=.005), male sex (β=9.0 minutes, P=.04), higher body mass index (β=0.8 minutes, P=.02), and lower Mini‐Mental State Examination score (β=2.2 minutes, P=.03) were independently associated with longer nap duration.

CONCLUSION: Napping was a common practice in community‐dwelling older adults and did not detract from nighttime sleep duration or quality. Given its high prevalence and association with diabetes mellitus, napping behavior should be assessed as part of sleep behavior in future research and in clinical practice.
Behavioral, biochemical, and genetic analysis of iron metabolism in high‐intensity blood donors
Authors: Mast Alan E. , Foster Tisha M. , Pinder Holly L. , Beczkiewicz Craig A. , Bellissimo Daniel B. , Murphy Anthony T. , Kovacevic Steve , Wroblewski Victor J. , Witcher Derrick R.
Published: July 2008

BACKGROUND: Individuals donating whole blood 13 times in a 2‐year period without development of iron deficiency anemia (superdonors) are a self‐selected population that is deferred for low hematocrit (Hct) level less frequently than other donors.

STUDY DESIGN AND METHODS: Iron metabolism was assessed in 138 superdonors through a questionnaire and measurement of Hct, serum ferritin, serum hepcidin, and serum growth differentiation factor 15 (GDF15). Genetic testing for HFE and JAK‐2 mutations was also performed.

RESULTS AND CONCLUSIONS: Iron deficiency (ferritin level, <30 µg/L) is present in more than 60 percent of superdonors. Behaviors altering iron status included casual use of iron supplements in males, but not in females, and cigarette smoking that produced increased Hct associated with decreased ferritin. The striking biochemical characteristic of superdonors is greatly decreased serum hepcidin, consistent with their need to absorb maximal amounts of dietary iron to replace that lost from blood donation. GDF15 is normal in most superdonors, indicating that GDF15 overexpression arising from the expanded erythroid pool necessary to replace donated red cells is not the biochemical mechanism for the decreased serum hepcidin. Mutations in JAK‐2 were not found, indicating that undiagnosed polycythemia vera is not a common cause for successful repeated blood donation by superdonors. Mutations in HFE associated with hemochromatosis were present in superdonors at the same frequency as the normal population. However, superdonors heterozygous for the H63D mutation in HFE had significantly decreased hepcidin : ferritin ratios demonstrating for the first time that the heterozygous state for HFE mutations is associated with alterations in hepcidin expression.
An evaluation of the DiaMed assays for immunoglobulin A antibodies (anti‐IgA) and IgA deficiency
Authors: Brown Ross , Nelson Margaret , Aklilu Esther , Kabani Karieshma , Yang Shihong , Blayney Bernadette , Popp Hazel
Published: July 2008

BACKGROUND: Immunoglobulin A antibodies (anti‐IgA) are rare but can cause transfusion‐associated anaphylaxis. The detection of anti‐IgA has traditionally been performed using a labor‐intensive hemagglutination assay in a limited number of reference laboratories.

STUDY DESIGN AND METHODS: Two simple gel card assays are now available that can be used to screen for anti‐IgA and IgA deficiency. A total of 24 serum samples that had been previously assayed for anti‐IgA over a 3‐year period were used to assess the DiaMed anti‐IgA and IgA deficiency assays.

RESULTS: The DiaMed assays correctly identified patients (n = 6) who had significant IgA deficiency and anti‐IgA. All patients with an abnormal anti‐IgA titer by hemagglutination assay and who were also IgA‐deficient had anti‐IgA detected using the DiaMed screening test. One patient, previously shown to have an IgA level of less than 0.067 g per L, failed to be detected as IgA‐deficient in the DiaMed IgA deficiency test; however, anti‐IgA were not present. Samples with slightly increased anti‐IgA titers tended to have normal IgA levels.

CONCLUSION: The DiaMed gel card screening assays are appropriate screening tools for the investigation of transfusion‐related anaphylactic reactions and can be used in any routine blood bank laboratory.
Application of pulsed‐field gel electrophoresis to identify the source of bacterial contamination of peripheral blood progenitor cell products
Authors: Reich‐Slotky Ronit , Wu Fann , Della‐Latta Phyllis , Savage David G. , Schwartz Joseph
Published: July 2008

BACKGROUND: Positive microbial cultures of peripheral blood progenitor cell (PBPC) products, although estimated to be low, are serious events in the manufacture of hematopoietic progenitor cell (HPC) products that warrant a thorough investigation to determine the contamination source.

STUDY DESIGN AND METHODS: Two patients underwent autologous PBPC collection. The first patient was admitted before the collection and was febrile intermittently throughout hospitalization. The second patient spiked a low‐grade fever by the end of the procedure. The HPC products from each patient were cultured during processing and before infusion. Blood cultures were drawn during febrile episodes and before transplant. Bacterial identification and antimicrobial susceptibilities were performed on all positive cultures. All strains were typed using pulsed‐field gel electrophoresis (PFGE) to determine their relatedness.

RESULTS: The blood cultures from both patients and their corresponding HPC products grew Staphylococcus epidermidis. The PFGE pattern of the S. epidermidis recovered from each patient blood was indistinguishable from the one recovered from the corresponding HPC product. The gel pattern of the strains recovered from the first patient differed by four bands from the one recovered from the second. For each patient, the antibiotic susceptibility patterns of the blood cultures and the HPC products were identical. Infusion of the contaminated HPC had no adverse event, and the patients engrafted successfully.

CONCLUSION: By use of PFGE technology, the contamination source of PBPC products was identified. It is concluded that the contamination resulted from intermittent bacteremia in the donors and was not introduced during laboratory manufacturing.
Ecocultural Attributes: Evaluating Ecological Degradation in Terms of Ecological Goods and Services Versus Subsistence and Tribal Values
Authors: Burger Joanna , Gochfeld Michael , Pletnikoff Karen , Snigaroff Ronald , Snigaroff Daniel , Stamm Tim
Published: July 2008

It is becoming increasingly clear that scientists, managers, lawyers, public policymakers, and the public must decide how to value what is provided by, and is a consequence of, natural resources. While “Western” scientists have clear definitions for the goods and services that ecosystems provide, we contend that these categories do not encompass the full totality of the values provided by natural resources. Partly the confusion results from a limited view of natural resources derived from the need to monetize the value of ecosystems and their component parts. Partly it derives from the “Western” way of separating natural resources from cultural resources or values, and partly it derives from the false dichotomy of assuming that ecosystems are natural, and anything constructed by man is not natural. In this article, we explore the previous assumptions, and suggest that because cultural resources often derive from, and indeed require, intact and unspoiled natural ecosystems or settings, that these values are rightly part of natural resources. The distinction is not trivial because of the current emphasis on cleaning up chemically and radiologically contaminated sites, on restoration of damaged ecosystems, on natural resource damage assessments, and on long‐term stewardship goals. All of these processes depend upon defining natural resources appropriately. Several laws, regulations, and protocols depend upon natural resource trustees to protect natural resources on trust lands, which could lead to the circular definition that natural resources are those resources that the trustees feel they are responsible for. Where subsistence or tribal peoples are involved, the definition of natural resources should be broadened to include those ecocultural attributes that are dependent upon, and have incorporated, natural resources. For example, a traditional hunting and fishing ground is less valued by subsistence peoples if it is despoiled by contamination or physical ecosystem degradation; an Indian sacred ground is tarnished if the surrounding natural environment is degraded; a traditional homeland is less valued if the land itself is contaminated. Our argument is that intact natural resources are essential elements of many cultural resources, and this aspect requires and demands adequate consideration (and may therefore require compensation).
Electromagnetic Bandgap Structure Containing High‐K Dielectric Ceramics
Authors: Shen Zhiyuan , Wang Hong , Shi Jianzhang , Yao Xi
Published: July 2008

A square lattice two‐dimensional (2D) electromagnetic bandgap (EBG) structure containing high permittivity (high‐K) dielectric ceramics was investigated. A finite element method‐based band structure calculation technique was used. The calculation results for 2D EBG structures were presented. To verify the validity of the modeling results, an EBG structure prototype containing a series of high‐K dielectric ceramic pillars surrounded by polymethyl methacrylate polymer was fabricated by the dice‐and‐fill technique. The modeled EBG structure shows two transverse‐magnetic gaps spanning 11.06–17.29 and 21.5–24.7 Ghz, respectively. Using a transmission/reflection method, the transmission parameter of the prototype sample from 7 to 19 GHz was measured, and a gap width up to 44% has been demonstrated. The measured propagation characteristics agree well with the calculated results.
Crystal Structure and Proton Conductivity of BaZr0.9Sc0.1O3−δ
Authors: Ahmed Istaq , Karlsson Maths , Eriksson Sten‐Gunnar , Ahlberg Elisabet , Knee Christopher S. , Larsson Kristian , Azad Abul K. , Matic Aleksandar , Börjesson Lars
Published: July 2008

Solid‐state sintering has been used to prepare the perovskite BaZr0.9Sc0.1O3−δ. Analysis of X‐ray powder diffraction data shows that an increase of the unit cell parameter, a, was observed after deuteration. Rietveld analysis of room‐temperature neutron powder diffraction data confirmed cubic symmetry (space group Pm‐3m). Dynamic thermogravimetric analysis indicates that the hydration process occurs below 335°C and approximately 58% of the theoretical number of protonic defects can be filled. The presence of protons/deutrons is seen from the strong O–H/O–D stretch band in the infrared spectrum of the hydrated/deuterated samples. The proton conductivity of a prehydrated sample was investigated under dry and wet Ar atmospheres.
Effect of Reaction Parameters on the Hydrolysis of Tetramethyl Orthosilicate and Tetraethyl Orthosilicate and their Surface Morphology in an Ionic Liquid
Authors: Jacob David S , Gedanken Aharon
Published: July 2008

Silica with different morphologies is found to be an interesting class of material that receives significant attention nowadays. Here, we report a simple and efficient method for the room‐temperature synthesis of silica spheres (20–80 μm sizes) in room‐temperature ionic liquids (1‐butyl‐3‐methylimidazolium hexafluorophosphate). The effect of reaction parameters such as pH, temperature, time, and solvent on the hydrolysis products and their morphology is described in this research paper. The morphology of the hydrolysis products of tetramethoxy silane and tetraethoxy silane are studied with the help of scanning electron microscopy. These results demonstrate a practical method for synthesizing smooth and rough surface silica spheres by modifying the reaction conditions. The confinement of the ionic liquid in the silica is studied with the help of Raman spectroscopy and mass spectroscopy.
Mechanisms and Mechanics Governing the Indentation of Polycrystalline Alumina
Authors: Wei Zhensong , Deshpande Vikram S. , Evans Anthony G.
Published: July 2008

A constitutive model for the inelastic deformation of polycrystalline alumina that accounts for both microcrack growth and plastic slip is implemented into a commercial finite element code. To establish its applicability, the code is used to simulate the deformation that occurs upon spherical and conical indentation. Inelastic zones and indentation pressures are predicted over a range of grain size and compared with measurements. The model replicates the mechanism transition from plasticity control at small grain sizes to micro‐crack‐control at large grain sizes. It also predicts an extensive micro‐crack‐dominated inelastic zone at large grain size that reduces the indentation pressures.
Effects of Excess PbO and Zr/Ti Ratio on Microstructure and Electrical Properties of PZT Films
Authors: Park Chee‐Sung , Lee Sung‐Mi , Kim Hyoun‐Ee
Published: July 2008

Lead zirconate titanate films with different Zr/Ti ratios were fabricated on a platinized silicon substrate using radio frequency magnetron sputtering. Crack‐free films with a rhombohedral, morphotropic phase boundary and tetragonal compositions were deposited using single oxide targets containing various amounts of excess PbO. When the films showed a (111) preferred orientation, there were no cracks, regardless of the phase, and their microstructures were similar to one another. As the Zr/Ti ratio was changed, the amount of excess PbO necessary for the stoichiometry of the films also changed. When they had a stoichiometric composition, the films had a small grain size and similar microstructures. Moreover, their structural stability increased when the grains had an equiaxed morphology. The ferroelectric and piezoelectric properties of the films were characterized and correlated with their phase and microstructure.
Enhanced Visible‐Light Photocatalytic Disinfection of Bacterial Spores by Palladium‐Modified Nitrogen‐Doped Titanium Oxide
Authors: Wu Pinggui , Xie Rongcai , Shang Jian Ku
Published: July 2008

Palladium‐modified nitrogen‐doped titanium oxide (TiON/PdO) nanofibers were synthesized by a sol–gel process on activated carbon‐coated glass fiber (ACGF) template. The TiON/PdO fiber was tested for visible‐light‐activated photocatalysis usingBacillus subtilisendospore as a target. Our work shows that TiON/PdO nanofibers display an effective antimicrobial effect onBacillusspores. The palladium modification provides a strong enhancement over TiON in the photocatalytic disinfection. Microscopic characterization demonstrated that visible‐light photocatalysis on TiON/PdO fiber caused drastic damage on the spore coat and internal structure.
Measuring Pore Diameter Distribution of Gelcast Ceramic Foams from Two‐Dimensional Cross Sections
Authors: Williams Andrew M. , Garner Colin P. , Binner Jon G.P.
Published: July 2008

Increasing applications for gelcast ceramic foams is making the effective, accurate and cost effective measurement of pore diameter and distribution of significant value to a wide range of research fields. Current methods either do not directly measure pore diameter or they require high equipment and time costs. Measuring pore diameter directly from sample cross sections is both rapid and cost effective but, due to the random nature of the pore location during sectioning of the sample, it under predicts the pore diameter. The proposed method identified that the mean measured pore diameter was 79% (2 s.f.) of the actual pore diameter. Numerical methods for correcting the pore distribution as well as the average pore diameter are presented.
Preparation of Ultra‐Fine Silica Fibers Using Electrospun Poly(Vinyl Alcohol)/Silatrane Composite Fibers as Precursor
Authors: Krissanasaeranee Methira , Vongsetskul Thammasit , Rangkupan Ratthapol , Supaphol Pitt , Wongkasemjit Sujitra
Published: July 2008

Ultra‐fine composite fibers made from poly(vinyl alcohol) (PVA)/silatrane, an inexpensive and moisture‐stable silicon‐containing compound, were prepared by a combined sol–gel processing and electrospinning technique with average diameters ranging between 119 and 405 nm. These fibers were subsequently converted to ultrafine silica fibers by calcination treatment, with the aim of producing a silica structure with a high surface area‐to‐mass ratio. Upon calcination at 500°C, the PVA/silica composite fibers were converted into amorphous silica fibers, while calcination of the composite fibers at temperatures ≥700°C resulted in the formation of cristobalite fibers. The average diameter of these silica fibers ranged between 162 and 213 nm.
Branded Into Submission: Brand Attributes and Hierarchization Behavior in Same‐Sex and Mixed‐Sex Dyads
Authors: Fennis Bob M.
Published: July 2008

In 2 experiments, the role of brand attributes in the process of nonconscious hierarchization in dyadic interactions was examined. Experiment 1 showed that in same‐sex dyads, brands that are associated with an agent and that are rated high on the brand personality dimension of competence (Aaker, 1997) induced patterns of nonverbal submissive behavior on the part of the interaction partner. This effect was more pronounced for individuals with a low intrinsic tendency for dominant behavior. Experiment 2 extended these findings to mixed‐sex dyads and brands that varied in overall status. Moreover, participant gender moderated the effects, such that the impact of brand status on hierarchization behavior and on agent likability was more pronounced for women than for men.
When Do Employees Identify? An Analysis of Cross‐Sectional and Longitudinal Predictors of Training Group and Organizational Identification1
Authors: Eisenbeiss Kerstin K. , Otten Sabine
Published: July 2008

Organizational research has shown the impact of organizational identification on employees' attitudes and behavior, and its relevance for economic success (Haslam, 2004). Furthermore, the necessity to differentiate levels of identification within organizations has been emphasized (van Knippenberg & van Schie, 2000). Little is known, however, about predictors of different identification levels within organizations and their influence on the development of identification. In a longitudinal study with training groups of flight attendants, we investigated how foci of identification (training group, organization) were differentially predicted by cross‐sectional and longitudinal variables. Interpersonal attraction related to training group identification, whereas professional motivation related to organizational identification. Furthermore, expected job circumstances and professional motivation were longitudinal predictors for training group identification and organizational identification, respectively.
Atrophy of type II fibres in myasthenia gravis muscle in thymectomized patients: steroid‐induced change with prognostic impact
Authors: Zamecnik Josef , Vesely Dan , Jakubicka Branislav , Cibula Adrian , Pitha Jiri , Schutzner Jan , Mazanec Radim
Published: July 2008

Selective atrophy of type II muscle fibres has been long recognized as an enigmatic but consistent feature of myasthenia gravis (MG) muscle; however, the pathophysiology and the mechanism of that change have remained obscure. In the present study, the results of histomorphometric analysis performed on muscle biopsies from 207 thymectomized seropositive MG patients were correlated with clinical features of MG to demonstrate possible pathophysiological associations and potential prognostic impact. The atrophy of type II fibres was verified in 35 cases (16.9%), being more pronounced in fibres of IIB subtype. It was neither significantly associated with the duration and severity of MG nor with the age of the patients. On the other hand, we demonstrated that the atrophy associated with long‐term treatment with corticosteroids, and correlated with increasing doses. Thus, we suppose that the atrophy of type II muscle fibres in seropositive MG is steroid induced rather than MG‐associated event. Although the MG patients with atrophy of type II fibres did not differ from the remaining MG cases in terms of improvement in the disease during the follow‐up period, our analysis provides clear evidence that they presented a significantly slower tendency to reach an asymptomatic state after thymectomy. Therefore, the steroid‐induced atrophy of type II fibres in MG muscle might be considered to be an unfavourable prognostic factor.
Fibroblast growth factor 2‐induced angiogenesis in zebrafish: the zebrafish yolk membrane (ZFYM) angiogenesis assay
Authors: Nicoli Stefania , De Sena Giulia , Presta Marco
Published: July 2008

Angiogenesis plays a key role in tumour growth and metastasis. The teleost zebrafish (Danio rerio) represents a promising alternative model in cancer research. Here, we describe a zebrafish yolk membrane (ZFYM) angiogenesis assays based on the injection of 1–30 ng of human recombinant FGF2 (rFGF2) in the perivitelline space of zebrafish embryos in the proximity of developing subintestinal vein vessels (SIVs) at 48 hrs after fertilization. The rFGF2 induces a rapid and dose‐dependent angiogenic response from the SIV basket, characterized by the ectopic growth of newly formed, alkaline phosphatase‐positive blood vessels. These vessels are formed by proliferating cells that incorporate bromodeoxyuridine and express the endothelial cell markers vegfr2/kdr and fli1. Microangiography shows that rFGF2‐induced vessels are patent and connected to the systemic circulation of the embryo. In keeping with these observations, fli1:EGFP+ cells isolated from transgenic tg(fli1:EGFP)y1 zebrafish embryos express the tyrosine kinase (TK) FGF receptor‐1 (FGFR1) and activate extracellular signal‐regulated kinase signalling when stimulated in vitro by rFGF2. The low molecular weight TK‐FGFR1 inhibitor SU5402 and the high molecular weight FGF2 antagonist long‐pentraxin 3 inhibit the angiogenic activity of rFGF2 when added to fish water or when co‐injected with the growth factor, respectively. Moreover, similar to rFGF2, injection of the zebrafish form of vascular endothelial growth factor‐A (VEGF‐A) induces a significant angiogenic response in the ZFYM assay that is suppressed by the VEGF receptor‐2/KDR TK inhibitor SU5416. The ZFYM assay represents a novel tool for testing the activity of low and high molecular weight inhibitors targeting a defined angiogenic growth factor in zebrafish. The assay may offer significant advantages when compared to other animal models.
AAK1 Regulates Numb Function at an Early Step in Clathrin‐Mediated Endocytosis
Authors: Sorensen Erika B. , Conner Sean D.
Published: July 2008

Numb is an endocytic protein that is proposed to influence clathrin‐coated pit assembly, although its mode of action and the mechanisms that regulate its activity are unknown. In this study, we show that Numb binds to and is phosphorylated by adaptor‐associated kinase 1 (AAK1), a key endocytic kinase. We find that AAK1 redistributes Numb to perinuclear endosomes when overexpressed, while kinase depletion causes Numb to accumulate at the plasma membrane. Overexpression of a Numb point mutant (T102A) that lacks the AAK1 phosphorylation site potently disrupts transferrin and low‐density lipoprotein internalization but does not impact EGF uptake. Consistent with Numb redistribution results, we find that T102A Numb no longer localizes to perinuclear endosomes. Instead, it is enriched at the plasma membrane where it shows elevated levels of colocalization with coated pit markers. Collectively, these observations demonstrate that Numb endocytic activity is regulated by AAK1 and that phosphorylation may be a critical step in promoting coated pit maturation.
ORIGINAL ARTICLE: How Should Data on Murine Spontaneous Abortion Rates be Expressed and Analyzed?
Authors: Clark David A. , Petitbarat Marie , Chaouat Gerard
Published: July 2008

Problem  Spontaneous abortions in the CBA × DBA/2 model are normally reported as number of resorptions/total number of implantations (R/T), pooling data from individual mice. The significance of differences between groups has been determined using non‐parametric statistics (e.g. chi‐square or Fisher’s Exact test) based on a priori predictions. Recently, it has been argued that medians with box plots should replace the accepted standard, but this deprives readers of data needed to verify P‐values, and leads to inferences incompatible with biological and statistical reality.

Method of study  Raw data on 173 individual CBA × DBA/2 matings were analyzed by median and mean, along with R/T data from 18 independent experiments containing 5–10 mice per group. Raw data from 19 CBA × BALB/c matings were similarly analyzed.

Results  Individual CBA × DBA/2 mouse resorption rates showed a non‐Gaussian distribution, but the mean and median differed by <0.5%. Resorption data from 6 and 12 independent pools of mice were normally distributed. Only the mean enabled a between‐group P‐value calculation. CBA × BALB/c matings gave a median of 0 and mean of 5.1%; the data were not normally distributed, but that was because of a bimodal distribution. One group of mice had 0 abortions, and the second a mean of 13.9% abortions, and the data from the latter group were normally distributed.

Conclusion  Although it is possible to compare individual mice, and even individual implantation sites, in resorption (abortion) studies, as the relevant question is the significance of differences between treatment groups of mice, and reproducibility, the established classical method of reporting R/T should continue to be provided. In CBA × BALB/c matings, where abortion rates are low, using the median is misleading and may obscure the existence of two distinct populations.
Partial dissociation of molecular and behavioral measures of song habituation in adult zebra finches
Authors: Dong S. , Clayton D. F.
Published: July 2008

Initial playback of recorded birdsong triggers a number of responses in zebra finches, including overt listening behavior and ERK pathway‐dependent activation ofzenkgene transcription in the auditory lobule of the forebrain. Repetition of one song stimulus leads to persistent habituation of these responses, as measured by subsequent presentations 1 day later. In this study, we examined the causal relationships between behavioral and molecular (ERK/zenk) habituation. In a within‐subject comparison, we found a strong correlation with the level of prior training for both responses (duration of behavioral listening and magnitude ofzenkexpression), but little correlation between these responses for birds within the same treatment group. We then tested the hypothesis that ERK/zenkactivation during training is necessary for the development of habituation measured 1 day later. Cannula‐directed infusion of a pharmacological inhibitor of ERK activation (U0126) immediately before training blocked the development of habituation of thezenkgene response. However, measurement of the effect on behavioral habituation was confounded because birds that were infused with a non‐active drug analogue (U0124) showed a decreased response 1 day later, even to novel songs. We conclude that the behavioral response to song stimulation is strongly influenced by factors other than song familiarity, whereas thezenkresponse in the forebrain may be a more accurate indicator of actual experience hearing a particular song.
Porous Titanium Granules Used as Osteoconductive Material for Sinus Floor Augmentation: A Clinical Pilot Study
Authors: Bystedt Hans , Rasmusson Lars
Published: July 2008

Background: Resorption of grafting material may lead to unpredictable long‐term results when rehabilitating the resorbed posterior maxilla. Nonresorbable, osteoconductive bone substitutes may therefore be an advantage over autogenous bone grafts.

Purpose: The aim of the present pilot study was to test titanium granules as bone substitute in patients planned for augmentation of the sinus floor prior to or in conjunction with placement of dental implants.

Materials and Methods: Sixteen patients with uni‐ or bilateral edentulism and need for augmentation of the sinus floor were included in the study. Residual bone height was 2 to 5 mm. Grafting and installation of the dental implants (18 fixtures) was carried out in the same session if primary stability of the implants could be achieved (12 patients). A staged protocol with implant placement 3 to 7 months after the augmentation procedure was used when primary implant stability was impossible to achieve (four patients). In all, 23 TiOblast™ (Astra Tech AB, Mölndal, Sweden) implants were installed.

Results: The patients have been followed 12 to 36 months after prosthetic loading. Three implants were found mobile and were removed (13.0%). Two of these were in patients where grafting and implant installation were carried out in separate procedures. The implants were found mobile at abutment connection and were removed. One patient in the single‐stage group had a postoperative sinus infection, which was successfully treated with antibiotics. However, one out of two implants in this patient was found mobile and was removed after 1 year in function.

Conclusions: In the present study, titanium granules seem to function as augmentation material in the sinus floor. It is, however, not clear if the material can be safely used for two‐stage procedures. Further investigations with longer healing time before implant installation are required. Also, the possible risk of granule displacement during preparation of the fixture site should be further investigated. Additionally, biopsies from patients are requested to confirm any bone ingrowth between the granules.
Morbidity after Chin Bone Harvesting – A Retrospective Long‐Term Follow‐Up Study
Authors: Weibull Lucy , Widmark Göran , Ivanoff Carl‐Johan , Borg Eva , Rasmusson Lars
Published: July 2008

Background: Resorption of the alveolar bone after tooth extraction may result in insufficient bone volume for implant placement. Augmentation of the resorbed site using autogenous bone grafts harvested from the maxillofacial region, for example, the chin, is a common method; however, it also involves donor site morbidity. Chin graft morbidity involves impaired sensibility in the frontal teeth, the gingival, and skin postoperatively.

Materials and Methods: A group of 60 patients with partial edentulism in the maxilla and insufficient bone volume for implant therapy were augmented with bone grafts from the mandibular symphysis. The grafting procedure was performed between 1991 and 2001 with a follow‐up period of 1 year after surgery. Postoperative sensibility of the lip, teeth, and gingiva was registered. Forty‐six patients (18 women and 28 men) also participated in a long‐term follow‐up study. The mean age was 49 years (range 23–81 years) and the mean follow‐up time was 7.5 years (range 4–14 years). The donor site was evaluated in four parts: a standardized clinical examination, radiographic examination and measurements, a mail‐in questionnaire, and a survey of the medical records regarding complications and graft size. In the donor site, both hard tissue (mandibular symphysis and teeth) and soft tissue (ie, lower lip, infralabial area, and chin) were evaluated. A questionnaire was also answered by 38 of 46 patients.

Results: In the long‐term follow‐up, impaired tactility and sensitivity of the soft tissues were registered in 7.6%. Adjacent teeth (incisors, canines, first and second premolar) (n = 418), showed increased lamina dura in seven cases (1.7%) and four teeth had apical pathology (1.0%). The donor site (n = 45) showed good remineralization in 42 patients (93.3%), and 28 patients (62.2%) had a noticeable concavity radiologically. The questionnaires from 38 patients (answer frequency 82.3%) rated high satisfaction with the grafting and implant treatment.

Conclusions: This study indicates that long‐term follow‐up of the chin graft donor site shows some postoperative morbidity. The most frequent disturbance was impaired sensibility in the soft tissues of the chin. The lower lip and teeth showed fewer disturbances. The rate of subjective symptoms was higher than the clinical findings but did, in general, not affect the patient in daily life. At radiographic examination, bone healing after chin graft harvesting did not regenerate to the preoperative level. The donor site showed good remineralization but left a radiologic concavity in the majority of cases.
Keats's ‘Dull Rhymes’ and the Making of the Ode Stanza
Authors: Mulrooney Jonathan
Published: July 2008

This article focuses on how John Keats's experimentation with the sonnet genre led to the development of his famous ode stanza. Several sonnets written in 1818 and 1819, most notably ‘If by dull rhymes our english must be chain'd’, illustrate Keats's dissatisfaction with traditional forms and his desire for a stanza that could present a more meditative speaker. Providing a brief survey of critical approaches to Keats's odes, the author stresses that the vital connection between ode stanza and the sonnet needs renewed discussion. With close readings of the interplay between syntax and form in the stanzas of Ode on Melancholy, Ode to a Nightingale, and To Autumn, the article attempts in a preliminary way to explore how the odes highlight their speaker's revision of tradition, presenting a lyric voice conscious of its own position in literary history.
British Garden Literature: Historiography and Idiomatic Change
Authors: Crawford Rachel
Published: July 2008

British garden literature, limited in this essay to horticulture, has been published since the advent of printing. The writing of garden history, however, is usually identified with Stephen Switzer's first, historical chapter in his Nobleman, Gentleman, and Gardener's Recreation (1715); yet garden histories are a convention of the earliest printed literature on gardens. Because early modern garden literature incorporates different historiographic conventions than modern, this aspect of it has been neglected by critics. In an additional complication, two great idiomatic changes punctuate the timeline of garden histories: the first begins in the decades before the Interregnum, a transformation from a Catholic idiom to one that is Protestant; the second in the latter half of the eighteenth century, from an idiom that was religious, mythical, and legendary to one that is aesthetic. Only in recent decades, with the pressure to reinsert history into literatures generally, have the embedded histories in early modern garden literature once again become legible.
The Transnational Epic in America
Authors: Morley Catherine
Published: July 2008

This article explores the roots of the epic fiction of John Updike and Philip Roth. The author makes the case that each writer has been profoundly influenced not only by great American forebears such as Emerson and Melville, but by a European tradition that stretches back to Homer, Virgil and the classical epic, and also by the example of James Joyce, whose great workUlyssesrecast the epic for the modernist age. Looking closely at such works as Updike's Rabbit novels and Roth'sAmerican PastoralandThe Human Stain, and drawing on recent theories of transatlantic cultural exchange, the author shows how each writer has been inspired by both American and European forerunners to produce epic works that subtly deconstruct the founding myths of American national identity.
New Directions in British Art History of the Eighteenth Century
Authors: Fordham Douglas
Published: July 2008

This essay examines new developments in the history of eighteenth‐century British art since the publication of David Solkin'sPainting for Money: The Visual Arts and the Public Sphere in Eighteenth‐Century Englandin 1993. While Solkin's account of an urban professional class recasting a civic humanist ideology in its own polite and commercial image continues to hold tremendous sway in the field, this state of the field article identifies three major trends that have tempered and challenged that account. Recent scholarship dealing with gender, space, and empire has subtly reoriented the field towards a more inclusive notion of artistic agency and reception, a more synchronic and spatial approach, and an increasingly global perspective.
Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?
Authors: McDevitt Christopher A. , Crowley Emily , Hobbs Gemma , Starr Kate J. , Kerr Ian D. , Callaghan Richard
Published: July 2008

ABCG2 confers resistance to cancer cells by mediating the ATP‐dependent outward efflux of chemotherapeutic compounds. Recent studies have indicated that the protein contains a number of interconnected drug binding sites. The present investigation examines the coupling of drug binding to ATP hydrolysis. Initial drug binding to the protein requires a high‐affinity interaction with the drug binding site, followed by transition and reorientation to the low‐affinity state to enable dissociation at the extracellular face. [3H]Daunomycin binding to the ABCG2R482G isoform was examined in the nucleotide‐bound and post‐hydrolytic conformations. Binding of [3H]daunomycin was displaced by ATP analogues, indicating transition to a low‐affinity conformation prior to hydrolysis. The low‐affinity state was observed to be retained immediately post‐hydrolysis. Therefore, the dissociation of phosphate and/or ADP is likely to be responsible for resetting of the transporter. The data indicate that, like ABCB1 and ABCC1, the ‘power stroke’ for translocation in ABCG2R482G is the binding of nucleotide.
Human GLTP and mutant forms of ACD11 suppress cell death in the Arabidopsis acd11 mutant
Authors: Petersen Nikolaj H. T. , McKinney Lea V. , Pike Helen , Hofius Daniel , Zakaria Asif , Brodersen Peter , Petersen Morten , Brown Rhoderick E. , Mundy John
Published: July 2008

The Arabidopsis acd11 mutant exhibits runaway, programmed cell death due to the loss of a putative sphingosine transfer protein (ACD11) with homology to mammalian GLTP. We demonstrate that transgenic expression in Arabidopsis thaliana of human GLTP partially suppressed the phenotype of the acd11 null mutant, resulting in delayed programmed cell death development and plant survival. Surprisingly, a GLTP mutant form impaired in glycolipid transfer activity also complemented the acd11 mutants. To understand the relationship between functional complementarity and transfer activity, we generated site‐specific mutants in ACD11 based on homologous GLTP residues required for glycolipid transfer. We show that these ACD11 mutant forms are impaired in their in vitro transfer activity of sphingolipids. However, transgenic expression of these mutant forms fully complemented acd11 mutant cell death, and transgenic plants showed normal induction of hypersensitive cell death upon infection with avirulent strains of Pseudomonas syringae. The significance of these findings with respect to the function(s) of ACD11 in sphingolipid transport and cell death regulation is discussed.
Characterization of membrane‐bound prolyl endopeptidase from brain
Authors: Tenorio‐Laranga Jofre , Venäläinen Jarkko I. , Männistö Pekka T. , García‐Horsman J. A.
Published: July 2008

Prolyl oligopeptidase (POP) is a serine protease that cleaves small peptides at the carboxyl side of an internal proline residue. Substance P, arginine–vasopressin, thyroliberin and gonadoliberin are proposed physiological substrates of this protease. POP has been implicated in a variety of brain processes, including learning, memory, and mood regulation, as well as in pathologies such as neurodegeneration, hypertension, and psychiatric disorders. Although POP has been considered to be a soluble cytoplasmic peptidase, significant levels of activity have been detected in membranes and in extracellular fluids such as serum, cerebrospinal fluid, seminal fluid, and urine, suggesting the existence of noncytoplasmic forms. Furthermore, a closely associated membrane prolyl endopeptidase (PE) activity has been previously detected in synaptosomes and shown to be different from the cytoplasmic POP activity. Here we isolated, purified and characterized this membrane‐bound PE, herein referred to as mPOP. Although, when attached to membranes, mPOP presents certain features that distinguish it from the classical POP, our results indicate that this protein has the same amino acid sequence as POP except for the possible addition of a hydrophobic membrane anchor. The kinetic properties of detergent‐soluble mPOP are fully comparable to those of POP; however, when attached to the membranes in its natural conformation, mPOP is significantly less active and, moreover, it migrates anomalously in SDS/PAGE. Our results are the first to show that membrane‐bound and cytoplasmic POP are encoded by variants of the same gene.