bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic Framework for Automated Analysis of Exposure to Road Collisions
Authors: Saunier Nicolas , Sayed Tarek
Published: January 2009

The advent of powerful sensing technologies, especially video sensors and computer vision techniques, has allowed for the collection of large quantities of detailed traffic data. These technologies allow further advancement toward completely automated systems for road safety analysis. This paper presents a comprehensive probabilistic framework for automated road safety analysis. Building on traffic conflict techniques and the concept of the safety hierarchy, it provides computational definitions of the probability of collision for road users involved in an interaction. It proposes new definitions for aggregated measures over time. This framework allows the interpretation of traffic from a safety perspective, by studying all interactions and their relationship to safety. New and more relevant exposure measures can be derived from this work, and traffic conflicts can be detected. A complete vision-based system is implemented to demonstrate the approach, providing experimental results on real-world video data.
Collision Models for Multilane Highway Segments to Examine Safety of Curbs
Authors: Baek Jongdae , Hummer Joseph E.
Published: January 2009

The objective of this study was to develop valid statistical collision models for multilane highway segments to examine the safety of curbs. For this, road geometric traffic and collision data for 2001 to 2003 were collected. The data included 2,274 collisions and 885 injury collisions that occurred on 191.85 mi of 199 directional segments in North Carolina. The authors applied a new modeling method of introducing variables into the model one by one in a multiplicative form. A nonlinear optimizing algorithm for estimating parameters using a negative binomial log likelihood function was adopted for the modeling. The functional form of the variable to be introduced was determined on the basis of the relationship between the recorded number of collisions and the number of collisions predicted by the current model without the variable. The integrate-differentiate method was applied to find candidate functional forms for each variable. Model selections were based on the −2 log likelihood and Bayesian information criterion statistics, and the cumulative residuals plot method to check the goodness of fit of the models was adopted. As a result of the modeling efforts, the annual average daily traffic, access point density, shoulder width, and shoulder type (including curb presence) variables were introduced to the final model for total collisions. The same variables except the shoulder type variable were introduced to the injury collision model. Overall, then, it appears that curbs mean fewer total collisions and no change in injury collisions as compared to no curbs on the sampled road segments.
Characteristics of Urban Arterial Crashes Relative to Proximity to Intersections and Injury Severity
Authors: Das Abhishek , Pande Anurag , Abdel-Aty Mohamed , Santos Joseph B.
Published: January 2009

Intersections of an urban arterial corridor may influence crashes that occur even beyond their physical area. This study examines the effect of the gradual change in the distance of intersection influence on crash characteristics that explain injury severity outcomes of arterial crashes. The approach adopted involves simultaneous estimation of two variables: an ordinal variable representing crash-injury severity and a binary variable representing crash location (intersection versus segment crashes). The dichotomy in crash location is based on the threshold distance of intersection influence. Five sets of bivariate simultaneous models were estimated by using five threshold distances of influence varying from 0 to 200 ft at 50-ft increments. A threshold of 0 ft essentially means that crashes only at the physical area of intersections are treated as intersection crashes. The other four thresholds define crashes 50, 100, 150, and 200 ft from the center of the intersections as intersection crashes. Simultaneous estimation allows accounting for common factors that affect both crash location and injury severity, but are explicitly included in neither model. Effects of these common unknown factors are reflected in the estimated correlation coefficient between the error terms for the two models. The correlation coefficients were found to be significant for influence distances of 150 and 200 ft and insignificant for influence distances 0 through 100 ft. The implications of these results are discussed. Results of the simultaneous estimation also reveal that crashes on the corridor are less severe during afternoon peak traffic conditions and on blacktop surfaces, while segments with a higher speed limit, a wider pavement surface, and a lower-than-median annual average daily traffic are likely to experience more severe crashes. At low-influence distance thresholds (≤50 ft), pavement surface condition (dry pavement) is significant in discriminating intersection crashes from segment crashes, while pavement surface type (blacktop surface) is significant at higher (≥150-ft) thresholds.
Vehicle Time Spent in Following
Authors: Zhang Chen , Ivan John N. , Ravishanker Nalini
Published: January 2009

This paper presents an investigation of a new exposure definition for same-direction collisions on two-lane rural roads. This new exposure definition, vehicle time spent in following other vehicles, is computed on the basis of the concept of percent time spent following as provided in Highway Capacity Manual (2000). In assessing the validity of this exposure measurement in crash prediction models, collisions are categorized by contributing factors. Two distinct categories emerge for same-direction collisions–(a) rear-end and (b) same-direction sideswipe and turning–from different distributions of contributing factors for observed collisions of each of these categories. Generalized linear models are used to estimate crash prediction models for each category separately and together, and different distribution assumptions used in the models are investigated to address overdispersion. According to the model results, the new exposure definition has a linear relationship with total same-direction collisions, especially rear-end collisions alone. The primary contributing factor reported for rear-end collisions is following too closely. Therefore, finding vehicle time spent following to be linearly related to these crashes suggests a key for identifying the appropriate exposure definition for any type of collision–to define the exposure so that it relates to opportunities for the corresponding contributing factor to come into play. This finding further suggests that, for development of prediction models, instead of categorizing collisions by the manner in which vehicles collide, it might be more effective to categorize them strictly by contributing factor.
Lower Frequency of Daily Teeth Brushing Is Related to High Prevalence of Cardiovascular Risk Factors
Authors: Fujita Misuzu , Ueno Koichi , Hata Akira
Published: January 2009

This study sought to investigate relationships between frequency of daily teeth brushing and prevalences of diabetes mellitus, hypertension and dyslipidemia. Subjects were 54,551 residents of Chiba City, Japan (20,155 men and 34,396 women) who underwent routine health examinations in 2004. Diabetes mellitus was defined as a fasting plasma glucose level ≥126 mg/dl or a non-fasting plasma glucose level ≥200 mg/dl and/or receiving treatment for diabetes. Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg and/or receiving treatment for hypertension. Dyslipidemia was defined according to the two criteria: high triglyceride and/or low high density lipoprotein cholesterol (TG ≥ 150 mg and/or HDL-C < 40 mg/dl), and high total cholesterol (TC ≥ 220 mg/dl). According to Pearson’s chi-square tests and logistic regression analysis adjusted for age, BMI, smoking habit, alcohol consumption and daily walking time, lower frequency of teeth brushing is related to higher prevalences of diabetes mellitus, hypertension and high TG and/or low HDL-C, in both men and women. Total cholesterol status, however, showed no significant relationship. Maintaining good oral hygiene by regular teeth brushing may prevent type 2 diabetes, hypertension and dyslipidemia.
Activity Markers of the Anti-Breast Carcinoma Cell Growth Fractions of Vernonia amygdalina Extracts
Authors: Oyugi Daniel A. , Luo Xuan , Lee Ken S. , Hill Brandon , Izevbigie Ernest B.
Published: January 2009

Vernonia amygdalina (VA) is an edible plant of the Asteraceae family used in many herbal formulations prescribed by herbalists for many diseases. We have previously reported that aqueous VA extracts inhibit the growth of estrogen receptor-positive human breast cancerous cells in vitro. Activity markers of the VA extracts have not been previously identified or characterized. Hence, the objective of this study was to identify activity markers of the VA extracts associated with cell growth inhibition. Extraction of VA with multiple solvents of various polarity indexes yielded three fractions (A-1–2, B-1–3) that significantly inhibited cell growth ( P < 0.05) at 0.1 mg/ml concentration. At a higher concentration of 1 mg/ml, six fractions of hexane, chloroform, butanol, and ethyl acetate (A-1–3, B-1–4) inhibited DNA synthesis by 76%, 98%, 94%, 98%, 98%, and 96%, respectively. These fractions were UV-detected from 250–730 nm; and all showed three distinct peaks around 410, 431, and 664 nm. Furthermore, HPLC analysis of the fractions revealed similar retention times of 2.213, 2.167, and 2.151 min, respectively. Bioactivity assays showed that HPLC retention of approximately 2 min is required for cell growth-inhibitory activity of VA fractions. Interestingly, all active fractions exhibited HPLC peaks at approximately 2 min. Therefore, the UV and HPLC peaks may be used as predictive tools to determine VA extracts activities.
Association of Various Dimensions of Hot Flashes with Systemic Levels of Gonadal Steroids
Authors: Ratka Anna , Miller Vanessa , Brown Kimberly , Jenschke Monica , Simpkins James
Published: January 2009

Hot flashes, the cardinal sign of menopausal vasomotor symptoms, are experienced by millions of women. The experience of hot flashes is characterized by significant inter- and intra-individual variability among women. The goals of this study were to compare concentrations of gonadal hormones between menopausal women with hot flashes (HF) and those with no HF, and to characterize the association between steroid levels and multiple dimensions of hot flashes. Menopausal women, with HF and with no HF, participated in four study sessions, one every 2 months. The Menopausal Vasomotor Symptom (MVS) survey was used to collect subjective data on various dimensions of hot flashes. Concentrations of gonadal hormones were measure at each bi-monthly session. Steroid levels were correlated to duration, frequency, length of each episode, timing, intensity, and bothersomeness of hot flashes. Data from twenty ( n = 20) women with HF and fifteen ( n = 15) with no HF with similar demographic profiles were analyzed. The results from the present study showed that systemic levels of estrone and progesterone were significantly lower in women experiencing HF than in asymptomatic women. There was a significant association between levels of estradiol, estrone, progesterone, and androstenedione, but not testosterone, with duration, frequency, timing, intensity, and bothersomeness of HF. The findings from this preliminary study suggest that management of symptoms associated with vasomotor HF should be individualized and guided by two factors: (i) thorough assessment of subjectively reported multiple dimensions of hot flashes, and (ii) levels of circulating gonadal steroids representing an average from 2–4 measures. This approach may lead to more targeted, effective, and safe management of vasomotor symptoms in the rapidly growing population of menopausal women.
Monitoring the Channel Formation in Organic Field‐Effect Transistors via Photoinduced Charge Transfer
Authors: Singh Thokchom Birendra , Koeppe Robert , Sariciftci Niyazi Serdar , Morana Mauro , Brabec Christoph J.
Published: January 2009

Conducting channel formation in organic field‐effect transistors (OFETs) is considered to happen in the organic semiconductor layer very close to the interface with the gate dielectric. In the gradual channel approximation, the local density of accumulated charge carriers varies as a result of applied gate bias, with the majority of the charge carriers being localized in the first few semiconductor monolayers close to the dielectric interface. In this report, a new concept is employed which enables the accumulation of charge carriers in the channel by photoinduced charge transfer. An OFET employing C60 as a semiconductor and divinyltetramethyldisiloxane‐bis(benzocyclobutene) as the gate dielectric is modified by a very thin noncontinuous layer of zinc‐phthalocyanine (ZnPc) at the semiconductor/dielectric interface. With this device geometry, it is possible to excite the phthalocyanine selectively and photogenerate charges directly at the semiconductor/dielectric interface via photoinduced electron transfer from ZnPc onto C60. Thus the formation of a gate induced and a photoinduced channel in the same device can be correlated.
Multifunctional Nanobiomaterials for Neural Interfaces
Authors: Abidian Mohammad Reza , Martin David C.
Published: January 2009

Neural electrodes are designed to interface with the nervous system and provide control signals for neural prostheses. However, robust and reliable chronic recording and stimulation remains a challenge for neural electrodes. Here, a novel method for the fabrication of soft, low impedance, high charge density, and controlled releasing nanobiomaterials that can be used for the surface modification of neural microelectrodes to stabilize the electrode/tissue interface is reported. The fabrication process includes electrospinning of anti‐inflammatory drug‐incorporated biodegradable nanofibers, encapsulation of these nanofibers by an alginate hydrogel layer, followed by electrochemical polymerization of conducting polymers around the electrospun drug‐loaded nanofibers to form nanotubes and within the alginate hydrogel scaffold to form cloud‐like nanostructures. The three‐dimensional conducting polymer nanostructures significantly decrease the electrode impedance and increase the charge capacity density. Dexamethasone release profiles show that the alginate hydrogel coating slows down the release of the drug, significantly reducing the burst effect. These multifunctional materials are expected to be of interest for a variety of electrode/tissue interfaces in biomedical devices.
Genetic linkage findings for DSM‐IV nicotine withdrawal in two populations
Authors: Pergadia Michele L. , Agrawal Arpana , Loukola Anu , Montgomery Grant W. , Broms Ulla , Saccone Scott F. , Wang Jen C. , Todorov Alexandre A. , Heikkilä Kauko , Statham Dixie J. , Henders Anjali K. , Campbell Megan J. , Rice John P. , Todd Richard D. , Heath Andrew C. , Goate Alison M. , Peltonen Leena , Kaprio Jaakko , Martin Nicholas G. , Madden Pamela A.F.
Published: January 2009

Nicotine withdrawal (NW) is both an important contributor to difficulty quitting cigarettes and because of mood‐related withdrawal symptoms a problem of particular relevance to psychiatry. Twin‐studies suggest that genetic factors influence NW (heritability = 45%). Only one previous linkage study has published findings on NW [Swan et al. (2006); Am J Med Genet Part B 141B:354–360; LOD = 2.7; Chr. 6 at 159 cM]. As part of an international consortium, genome‐wide scans (using over 360 autosomal microsatellite markers) and telephone diagnostic interviews were conducted on 289 Australian (AUS) and 161 Finnish (FIN, combined (COMB) N = 450 families) families ascertained from twin registries through index‐cases with a lifetime history of cigarette smoking. The statistical approach used an affected‐sib‐pair design (at least two adult full siblings reported a history of DSM‐IV NW) and conducted the linkage analyses using MERLIN. Linkage signals with LOD scores >1.5 were found on two chromosomes: 6 (FIN: LOD = 1.93 at 75 cM) and 11 at two different locations (FIN: LOD = 3.55 at 17 cM, and AUS: LOD = 1.68 with a COMB: LOD = 2.30 at 123 cM). The multipoint LOD score of 3.55 on chromosome 11p15 in FIN met genomewide significance (P = 0.013 with 1,000 simulations). At least four strong candidate genes lie within or near this peak on chromosome 11: DRD4, TPH, TH, and CHRNA10. Other studies have reported that chromosome 11 may harbor genes associated with various aspects of smoking behavior. This study adds to that literature by highlighting evidence for NW. © 2009 Wiley‐Liss, Inc.
Totalsynthese des antiviralen Peptidantibiotikums Feglymycin
Authors: Dettner Frank , Hänchen Anne , Schols Dominique , Toti Luigi , Nußer Antje , Süssmuth Roderich D.
Published: January 2009

Hochkonvergent verlief die stereoselektive Totalsynthese von Feglymycin (1) und dessen Enantiomer durch Kupplung sich in der Struktur wiederholender Peptidfragmente. Nur schwach basische Reaktionsbedingungen während des gesamten Syntheseverlaufs unterdrückten eine Epimerisierung empfindlicher Arylglycine. 1 zeigt nicht nur eine bemerkenswerte Anti‐HIV‐Aktivität, sondern, entgegen früheren Ergebnissen, auch eine beachtliche antibakterielle Aktivität gegen Staphylococcus aureus.

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A Bistable Poly[2]catenane Forms Nanosuperstructures
Authors: Olson Mark A. , Braunschweig Adam B. , Fang Lei , Ikeda Taichi , Klajn Rafal , Trabolsi Ali , Wesson Paul J. , Benítez Diego , Mirkin Chad A. , Grzybowski Bartosz A. , Stoddart J. Fraser
Published: January 2009

Ein bistabiles seitenkettentragendes Poly[2]catenan wurde synthetisiert, das hierarchische hohle Überstrukturen mit nanoskaligen Abmessungen in Lösung bildet und elektromechanisch schaltbar ist (siehe Bild). Die Gleichgewichtsthermodynamik im Grundzustand und die Schaltkinetiken wurden untersucht, und die Ergebnisse dienen als Basis für die Entwicklung von molekular‐elektronischen Bauelementen und nanoelektromechanischen Systemen.

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CF Activation at Rhodium Boryl Complexes: Formation of 2‐Fluoroalkyl‐1,3,2‐Dioxaborolanes by Catalytic Functionalization of Hexafluoropropene
Authors: Braun Thomas , Ahijado Salomon Marcel , Altenhöner Kai , Teltewskoi Michael , Hinze Silke
Published: January 2009

Fluorierte Bausteine durch C‐F‐Bindungsspaltung: Die Synthese neuartiger Dioxaborolane durch katalytische C‐F‐Aktivierung wird vorgestellt (siehe Schema). Die Reaktionen verlaufen bei Raumtemperatur, wobei als katalytische Zwischenstufen vermutlich Rhodiumhydrid‐ und Borylspezies auftreten.

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Total Synthesis of the Antiviral Peptide Antibiotic Feglymycin
Authors: Dettner Frank , Hänchen Anne , Schols Dominique , Toti Luigi , Nußer Antje , Süssmuth Roderich D.
Published: January 2009

An adaptable approach: The first highly convergent stereoselective synthesis of feglymycin (see structure) and its enantiomer is based on the coupling of repeating peptide fragments. The use of weakly basic conditions throughout the synthesis suppressed the epimerization of sensitive aryl glycine units. Feglymycin has strong anti‐HIV activity as well as potent (previously identified as weak) antibacterial activity against Staphylococcus aureus.

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Semisynthesis of a Homogeneous Glycoprotein Enzyme: Ribonuclease C: Part 2
Authors: Piontek Christian , Varón Silva Daniel , Heinlein Christian , Pöhner Claudia , Mezzato Stefano , Ring Petra , Martin Andreas , Schmid Franz Xaver , Unverzagt Carlo
Published: January 2009

Active RNase glycoprotein from three pieces: The glycoprotein enzyme ribonuclease C, which contains a complex saccharide N‐glycan, was synthesized by sequential native chemical ligation. An optimized ligation and isolation protocol allowed the efficient assembly and refolding of the 124 amino acid enzyme.

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Trapping of a Thiolate→Dibromine Charge‐Transfer Adduct by a Macrocyclic Dinickel Complex and Its Conversion into an Arenesulfenyl Bromide Derivative
Authors: Steinfeld Gunther , Lozan Vasile , Krüger Hans‐Jörg , Kersting Berthold
Published: January 2009

Stuck on sulfur: The first transition‐metal complexes with SBr units are surprisingly stable. Solid 3 is stable for at least six months and under vacuum solid 2 does not lose Br2. The formation of the first structurally characterized transition‐metal arenesulfenyl bromide complex 3 occurs with a change of the spin ground state from S=2 to S=0.

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Reaction of a Metallamacrocycle Leading to a Mercury(II)⋅⋅⋅Palladium(II)⋅⋅⋅Mercury(II) Interaction
Authors: Sharma Sagar , Baligar Rajesh S. , Singh Harkesh B. , Butcher Ray J.
Published: January 2009

All wrapped up: The reaction of a 22‐membered macrocycle derived from bis(o‐formylphenyl)mercury and 1,2‐phenylenediamine with palladium(II) results in cleavage of the macrocycle and concomitant formation of a trimetallic complex (see picture; phenyl rings truncated for clarity). The nature of the HgII⋅⋅⋅PdII⋅⋅⋅HgIIinteraction was investigated by theoretical studies.

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Evidence for a Stereoelectronic Effect in Human Oxygen Sensing
Authors: Loenarz Christoph , Mecinović Jasmin , Chowdhury Rasheduzzaman , McNeill Luke A. , Flashman Emily , Schofield Christopher J.
Published: January 2009

How PHDs achieve specificity: trans‐4‐prolyl hydroxylation of the transcription factor HIF occurs with stereochemical retention. Substrate‐analogue studies show how the von Hippel Lindau tumor suppressor protein (pVHL) and the oxygen‐sensing hydroxylases (PHDs) achieve specificity for hydroxyprolyl/prolyl residues for the C4‐exo/endo prolyl conformations, respectively.

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STM Insight into Hydrogen‐Bonded Bicomponent 1 D Supramolecular Polymers with Controlled Geometries at the Liquid–Solid Interface
Authors: Ciesielski Artur , Schaeffer Gaël , Petitjean Anne , Lehn Jean‐Marie , Samorì Paolo
Published: January 2009

Bicomponent supramolecular polymers, consisting of two alternating molecules bridged through six H‐bonds, are observed by STM at the solid–liquid interface. Control of the geometry of the 1D architecture was obtained by using two different connecting molecules with different conformational rigidity, affording either linear (see picture, left) or zigzag (right) motifs.

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Addition of Hydrogen or Ammonia to a Low‐Valent Group 13 Metal Species at 25 °C and 1 Atmosphere
Authors: Zhu Zhongliang , Wang Xinping , Peng Yang , Lei Hao , Fettinger James C. , Rivard Eric , Power Philip P.
Published: January 2009

Mild‐mannered: The low‐valent aryl gallium(I) species :GaAr′ (Ar′=2,6‐(2,6‐iPr2C6H3)2C6H3) undergoes addition to H2 or NH3 at room temperature and one atmosphere of pressure to afford 1 or 2 (see scheme), which were characterized by X‐ray crystallography and NMR and IR spectroscopy.

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Facilitated bone mineral density testing versus hospital‐based case management to improve osteoporosis treatment for hip fracture patients: Additional results from a randomized trial
Authors: Morrish Donald W. , Beaupre Lauren A. , Bell Neil R. , Cinats John G. , Hanley David A. , Harley Charles H. , Juby Angela G. , Lier Douglas A. , Maksymowych Walter P. , Majumdar Sumit R.
Published: January 2009

Objective

We previously demonstrated that a case manager intervention improved osteoporosis (OP) treatment within 6 months of hip fracture compared with usual care. The second phase of the randomized trial compared a less intensive intervention, facilitated bone mineral density (BMD) testing, with usual care and the case manager intervention.

Methods

We initially randomized 220 hip fracture patients to either an OP case manager intervention or usual care. After completing the original trial at 6 months postfracture, usual care patients were reallocated to facilitated BMD testing; BMD tests were arranged and results sent to primary care physicians. Main outcomes (bisphosphonate treatment, BMD tests, receipt of appropriate care) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care.

Results

Compared with usual care, facilitated BMD testing increased testing from 29% to 68% (P < 0.001), bisphosphonate use from 22% to 38% (P < 0.001), and receipt of appropriate care from 26% to 45% (P < 0.001). The more intensive (70 versus 30 minutes) and expensive ($56 versus $24 Canadian per patient) OP case manager intervention led to significantly higher bisphosphonate use (54% versus 38%; P = 0.03), receipt of appropriate care (71% versus 45%; P < 0.001), and more BMD testing (80% versus 68%; P = 0.06) than usual care followed by facilitated BMD testing.

Conclusion

Compared with usual care, 2 different inexpensive interventions resulted in significant increases in appropriate management of OP after hip fracture. The magnitude of improvements achieved was directly related to the intensity of the interventions.
Work loss and work entry among persons with systemic lupus erythematosus: Comparisons with a national matched sample
Authors: Yelin Edward , Tonner Chris , Trupin Laura , Panopalis Pantelis , Yazdany Jinoos , Julian Laura , Katz Patricia , Criswell Lindsey A.
Published: January 2009

Objective

To prospectively track work loss among those employed and work entry among those not employed in a cohort of persons with systemic lupus erythematosus (SLE), assess risk factors for these outcomes, and compare rates of the outcomes with a matched national sample.

Methods

The present study analyzed 4 years of data from the Lupus Outcomes Study (LOS), augmented by information on the local labor market from the Census Bureau and the Bureau of Labor Statistics. We used the Kaplan‐Meier method to assess time from study initiation until work loss or work entry, and Cox proportional hazards regression to estimate factors affecting these outcomes. Finally, we compared rates of work loss and work entry in the LOS with rates in the Survey of Income and Program Participation (SIPP).

Results

At study initiation, 394 LOS participants (51%) were employed, of whom 92 (23.4%) experienced work loss. In multivariate analysis, older age, lower cognitive and physical functioning, and higher reports of depressive symptoms predicted work loss. In comparison with the SIPP sample, rates of work loss did not differ. Of the 376 LOS participants not employed, 76 (20.2%) experienced work entry. In multivariate analysis, less disease activity, fewer lung manifestations, better physical functioning, and shorter time since last employment predicted work entry. In comparison with the SIPP, rates of work entry were only lower between ages 35 and 55 years.

Conclusion

Until age 55 years, low rates of employment among persons with SLE may be due to lower rates of work entry rather than higher rates of work loss. Beyond age 55 years, both high rates of work loss and low rates of work entry contribute to low rates of employment.
The NOD2 defect in Blau syndrome does not result in excess interleukin‐1 activity
Authors: Martin Tammy M. , Zhang Zili , Kurz Paul , Rosé Carlos D. , Chen Hong , Lu Huiying , Planck Stephen R. , Davey Michael P. , Rosenbaum James T.
Published: January 2009

Objective

Blau syndrome is a rare, autosomal‐dominant, autoinflammatory disorder characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics studies have shown that the disease is caused by single nonsynonymous substitutions in NOD‐2, a member of the NOD‐like receptor or NACHT–leucine‐rich repeat (NLR) family of intracellular proteins. Several NLRs function in the innate immune system as sensors of pathogen components and participate in immune‐mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene related to NOD‐2, NLRP3, are responsible for excess caspase 1–dependent interleukin‐1β (IL‐1β) in cryopyrinopathies such as Muckle‐Wells syndrome. Furthermore, functional studies demonstrate that caspase 1–mediated release of IL‐1β also involves NOD‐2. The aim of this study was to test the hypothesis that IL‐1β may mediate the inflammation seen in patients with Blau syndrome.

Methods

IL‐1β release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation.

Results

We observed no evidence for increased IL‐1β production in cells obtained from subjects with Blau syndrome compared with healthy control subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant human IL‐1 receptor antagonist (anakinra) was ineffective treatment.

Conclusion

Taken together, these data suggest that in contrast to related IL‐1β–dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL‐1β or other IL‐1 activity.
Therapeutic effect of exosomes from indoleamine 2,3‐dioxygenase–positive dendritic cells in collagen‐induced arthritis and delayed‐type hypersensitivity disease models
Authors: Bianco Nicole R. , Kim Seon Hee , Ruffner Melanie A. , Robbins Paul D.
Published: January 2009

Objective

We have demonstrated previously that dendritic cells (DCs) modified with immunosuppressive cytokines, and exosomes derived from DCs can suppress the onset of murine collagen‐induced arthritis (CIA) and reduce the severity of established arthritis. Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan‐degrading enzyme that is important for immune regulation and tolerance maintenance. DCs expressing functional IDO can inhibit T cells by depleting them of essential tryptophan and/or by producing toxic metabolites, as well as by generating Treg cells. This study was undertaken to examine the immunosuppressive effects of bone marrow (BM)–derived DCs genetically modified to express IDO, and of exosomes derived from IDO‐positive DCs.

Methods

BM‐derived DCs were adenovirally transduced with IDO or CTLA‐4Ig (an inducer of IDO), and the resulting DCs and exosomes were tested for their immunosuppressive ability in the CIA and delayed‐type hypersensitivity (DTH) murine models.

Results

Both DCs and exosomes derived from DCs overexpressing IDO had an antiinflammatory effect in CIA and DTH murine models. The suppressive effects were partially dependent on B7 costimulatory molecules. In addition, gene transfer of CTLA‐4Ig to DCs resulted in induction of IDO in the DCs and in exosomes able to reduce inflammation in an IDO‐dependent manner.

Conclusion

These results demonstrate that both IDO‐expressing DCs and DC‐derived exosomes are immunosuppressive and antiinflammatory, and are able to reverse established arthritis. Therefore, exosomes from IDO‐positive DCs may represent a novel therapy for rheumatoid arthritis.
Physical activity and incident clinical knee osteoarthritis in older adults
Authors: Verweij Lisanne M. , van Schoor Natasja M. , Deeg Dorly J. H. , Dekker Joost , Visser Marjolein
Published: January 2009

Objective

To study the relationship between 4 components of physical activity and the 12‐year incidence of clinical knee osteoarthritis (OA) among older adults.

Methods

Longitudinal data from 1,678 men and women, ages 55–85 years, were collected in the Longitudinal Aging Study Amsterdam. Incident clinical knee OA was defined by an algorithm using self‐report and general practitioner data. Physical activity was assessed by a validated questionnaire from which 4 physical activity component scores were created: muscle strength, intensity, mechanical strain, and turning actions. Cox proportional hazards models were conducted to examine the relationship between these scores and incident knee OA and reported as hazard ratios (HRs) with 95% confidence intervals (95% CIs).

Results

During 12 years of followup, 463 respondents (28%) developed clinical knee OA. A high mechanical strain score (HR 1.43, 95% CI 1.15–1.77) and a low muscle strength score (HR 1.30, 95% CI 1.01–1.68) were associated with an increased risk of knee OA after adjustment for age, sex, region of living, education, lifetime physical work demands, lifetime general physical activity, body mass index, current total physical activity level, and depression. No association was observed in the intensity and turning actions components. The results were similar for men and women, and for obese and nonobese respondents.

Conclusion

Older adults who perform low muscle strength activities or activities causing high mechanical strain had an increased risk of clinical knee OA. These results suggest that specific components of physical activity may influence the development of knee OA.
Exercise prescription for chronic back or neck pain: Who prescribes it? who gets it? What is prescribed?
Authors: Freburger Janet K. , Carey Timothy S. , Holmes George M. , Wallace Andrea S. , Castel Liana D. , Darter Jane D. , Jackman Anne M.
Published: January 2009

Objective

To describe exercise prescription in routine clinical practice for individuals with chronic back or neck pain because, although current practice guidelines promote exercise for chronic back and neck pain, little is known about exercise prescription in routine care.

Methods

We conducted a computer‐assisted telephone survey of a representative sample of individuals (n = 684) with chronic back or neck pain who saw a physician, chiropractor, and/or physical therapist (PT) in the past 12 months. Individuals were asked about whether they were prescribed exercise, the amount of supervision received, and the type, duration, and frequency of the prescribed exercise. Descriptive and multivariable regression analyses were conducted.

Results

Of the 684 subjects, 48% were prescribed exercise. Of those prescribed exercise, 46% received the prescription from a PT, 29% from a physician, 21% from a chiropractor, and 4% from other. In multivariable analyses, seeing a PT or a chiropractor were the strongest predictors of exercise prescription. The likelihood of exercise prescription was increased in women, those with higher education, and those receiving worker's compensation. PTs were more likely to provide supervision and prescribe strengthening exercises compared with physicians and chiropractors, and were more likely to prescribe stretching exercises compared with physicians.

Conclusion

Our findings suggest that exercise is being underutilized as a treatment for chronic back and neck pain and, to some extent, that the amount of supervision and types of exercises prescribed do not follow current practice guidelines. Exercise prescription provided by PTs appears to be most in line with current guidelines.
β2‐glycoprotein i is a cofactor for tissue plasminogen activator–mediated plasminogen activation
Authors: Bu Chunya , Gao Lei , Xie Weidong , Zhang Jainwei , He Yuhong , Cai Guoping , McCrae Keith R.
Published: January 2009

Objective

Regulation of the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA) is critical in the control of fibrin deposition. While several plasminogen activators have been described, soluble plasma cofactors that stimulate fibrinolysis have not been characterized. The purpose of this study was to investigate the effects of β2‐glycoprotein I (β2GPI), an abundant plasma glycoprotein, on tPA‐mediated plasminogen activation.

Methods

The effect of β2GPI on tPA‐mediated activation of plasminogen was assessed using amidolytic assays, a fibrin gel, and plasma clots. Binding of β2GPI to tPA and plasminogen was determined in parallel. The effects of IgG fractions and anti‐β2GPI antibodies from patients with antiphospholipid syndrome (APS) on tPA‐mediated plasminogen activation were also measured.

Results

Beta2‐glycoprotein I stimulated tPA‐dependent plasminogen activation in the fluid phase and within a fibrin gel. The β2GPI region responsible for stimulating tPA activity was shown to be at least partly contained within β2GPI domain V. In addition, β2GPI bound tPA with high affinity (Kd ∼20 nM), stimulated tPA amidolytic activity, and caused an overall 20‐fold increase in the catalytic efficiency (Kcat/Km) of tPA‐mediated conversion of Glu‐plasminogen to plasmin. Moreover, depletion of β2GPI from plasma led to diminished rates of clot lysis, with restoration of normal lysis rates following β2GPI repletion. Stimulation of tPA‐mediated plasminogen activity by β2GPI was inhibited by monoclonal anti‐β2GPI antibodies as well as by anti‐β2GPI antibodies from patients with APS.

Conclusion

These findings suggest that β2GPI may be an endogenous regulator of fibrinolysis. Impairment of β2GPI‐stimulated fibrinolysis by anti‐β2GPI antibodies may contribute to the development of thrombosis in patients with APS.
Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing
Authors: Videman Tapio , Saarela Janna , Kaprio Jaakko , Näkki Annu , Levälahti Esko , Gill Kevin , Peltonen Leena , Battié Michele C.
Published: January 2009

Objective

To examine the allelic diversity of structural, inflammatory, and matrix‐modifying gene candidates and their association with disc degeneration.

Methods

Subjects were 588 men ages 35–70 years. We investigated associations of single‐nucleotide polymorphisms in AGC1 and in 12 collagen, 8 interleukin, and 4 matrix metalloproteinase genes with quantitative magnetic resonance imaging measurements of disc desiccation and disc bulging and height narrowing scores, after controlling for age and suspected risk factors. Analyses were performed using QTDT software.Pvalues were derived from 1,000 permutations, and empiricalPvalues for global significance also were applied.

Results

Twelve of the 99 variants in 25 selected candidate genes provided evidence of association (P< 0.05) with disc signal intensity in the upper and/or lower lumbar regions. Allelic variants of AGC1 (rs1042631;P= 0.001), COL1A1 (rs2075555;P= 0.005), COL9A1 (rs696990;P= 0.00008), and COL11A2 (rs2076311;P= 0.018) genes provided the most significant evidence of association with disc signal intensity. The same variants of AGC1 (P= 0.010) and COL9A1 (P= 0.014), as well as variants in the COL11A1 gene (rs1463035 [P= 0.004]; rs1337185 [P= 0.015]) were also associated with disc bulging, as was AGC1 with disc height narrowing (rs1516797;P= 0.005). In addition, 4 allelic variants in the immunologic candidate genes (rs2071375 in IL1A [P= 0.027]; rs1420100 in IL18RAP [P= 0.005]) were associated with disc signal intensity.

Conclusion

Genetic variants account for interindividual differences in disc matrix synthesis and degradation. The accuracy of the quantitative disc signal intensity measurements we used likely enhanced our ability to observe these associations. Our findings shed light on possible mechanisms of degeneration and support the view that disc degeneration is a polygenetic condition.
Self‐report and physical performance measures of physical function in hip osteoarthritis: Relationship to isometric quadriceps torque development
Authors: Pua Yong‐Hao , Wrigley Tim V. , Collins Marnie , Cowan Sallie M. , Bennell Kim L.
Published: January 2009

Objective

Quadriceps strength (knee extensor torque) is an important correlate of physical function in individuals with hip osteoarthritis (OA). However, it remains unclear whether the ability to rapidly generate quadriceps torque in the early phase of muscle contraction (maximal rate of torque development [MRTD]) is also associated with physical function. The purpose of this study was to quantify the independent impact of quadriceps strength and quadriceps MRTD on self‐report and physical performance measures of physical function in community‐dwelling adults with hip OA.

Methods

Ninety‐two adults with radiographically confirmed symptomatic hip OA (mean age 62 years) participated. Unilateral isometric quadriceps strength and MRTD were measured using a dynamometer. Self‐report measure of physical function was assessed by the Short Form 36 (SF‐36) questionnaire, and physical performance was assessed by the timed stair and step tests.

Results

In the hierarchical regression models, high maximal quadriceps strength and high quadriceps MRTD uniquely covaried with high SF‐36 physical function scores after accounting for demographic, anthropometric, and pain measures. For the timed stair test, all else being equal, in 2 participants with low but identical levels of quadriceps strength, the one with a higher MRTD had better stair‐climbing function. For the step test, quadriceps MRTD was not associated with step test performance over and above that of quadriceps strength.

Conclusion

In individuals with hip OA, maximal quadriceps strength and quadriceps MRTD positively impact self‐report and physical performance measures of physical function. These findings are of importance in developing intervention strategies, but they call for further study.
Different amplifying mechanisms of interleukin‐17 and interferon‐γ in Fcγ receptor–mediated cartilage destruction in murine immune complex–mediated arthritis
Authors: Grevers Lilyanne C. , van Lent Peter L. E. M. , Koenders Marije I. , Walgreen Birgitte , Sloetjes Annet W. , Nimmerjahn Falk , Sjef Verbeek J. , van den Berg Wim B.
Published: January 2009

Objective

Previously, we reported that interferon‐γ (IFNγ) aggravates cartilage destruction in immune complex (IC)–mediated arthritis via up‐regulation of activating Fcγ receptors (FcγR). Recently, we found that interleukin‐17 (IL‐17) also aggravates cartilage destruction in arthritis models in which ICs are involved, but the underlying mechanism remains unknown. This study was undertaken to determine the role of IL‐17 in FcγR‐mediated cartilage destruction in IC‐mediated arthritis and to compare its effect with that of IFNγ.

Methods

IC‐mediated arthritis was passively induced in γ‐chain−/− mice, which lack functional activating FcγR, and in wild‐type controls. AdIL‐17 or a control vector was injected into the knee joints 1 day prior to induction of IC‐mediated arthritis. Knee joints were isolated for histologic analysis, and synovium samples were obtained for reverse transcriptase–polymerase chain reaction (RT‐PCR). Macrophage (RAW 264.7) cell lines and polymorphonuclear cell (PMN; 32Dcl3) lines were stimulated with IFNγ or IL‐17 for analysis of FcγR expression using RT‐PCR and fluorescence‐activated cell sorting.

Results

IL‐17 overexpression prior to induction of IC‐mediated arthritis significantly aggravated cartilage destruction and inflammation, characterized by a massive influx of PMNs, which adhered to the cartilage surface. Although IL‐17 overexpression increased FcγR messenger RNA levels in the synovium, in vitro stimulation of macrophages and PMNs revealed that, in contrast to IFNγ, IL‐17 did not directly regulate FcγR expression. Despite similar inflammation in AdIL‐17–enhanced IC‐mediated arthritis in γ‐chain−/− mice and wild‐type controls, severe cartilage destruction and PMN adherence were completely absent in γ‐chain−/− mice.

Conclusion

Our findings indicate that IL‐17–mediated aggravation of cartilage destruction in IC‐mediated arthritis is FcγR dependent. However, in contrast to IFNγ, which directly up‐regulates FcγR expression on macrophages and PMNs, IL‐17 enhances cartilage destruction by increasing the local amount of FcγR‐bearing neutrophils.
Revision of the Absolute Configuration at C(23) of Lanostanoids and Isolation of Secondary Metabolites from Formosan Soft Coral Nephthea erecta
Authors: Cheng Shi‐Yie , Wen Zhi‐Hong , Wang Shang‐Kewi , Chiang Michael Y. , El‐Gamal Ali A. H. , Dai Chang‐Feng , Duh Chang‐Yih
Published: January 2009

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Three new oxygenated ergostanoids, 1–3, one known ergostanoid, 4, one new trinoreudesmadienone, 5, one new calamenene type sesquiterpene, 6, and one known aristolane‐type sesquiterpene, (−)‐aristolone (7), have been isolated from the AcOEt extract of the soft coral Nephthea erecta. The structures of these compounds were determined by extensive spectroscopic and X‐ray crystallographic analysis, as well as Mosher's method. We revised the absolute configuration at C(23) in the side chain of some lanostanoids as a result of the Mosher's products of 1 (i.e., 1a and 1b). The cytotoxicities against selected cancer cells and the anti‐inflammatory effects of these tested metabolites 1–7 were determined in vitro.
Composition of the Cloacal Gland Secretion of Tuatara, Sphenodon punctatus
Authors: Flachsbarth Birte , Fritzsche Matthias , Weldon Paul J. , Schulz Stefan
Published: January 2009

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The lipophilic content of the cloacal gland secretion of the tuatara (Sphenodon punctatus) was investigated. GC/EI‐MS Analysis of CH2Cl2 extracts of the secretions revealed triacylglycerols as major glandular constituents. Twelve major medium‐chain fatty acids were found to be conjugated to glycerol in different combinations, resulting in complex mixtures. These acids were identified by transesterification and subsequent derivatization of natural samples, and their structures were verified by synthesis. The natural glycerides contain predominantly three of the following acids: octanoic (A), (E)‐ and (Z)‐oct‐4‐enoic (B and C, resp.), (4E,6Z)‐octa‐4,6‐dienoic (tuataric acid; D), (R)‐2,6‐dimethylheptanoic (E), (R)‐2,6‐dimethylhept‐5‐enoic (F), (Z)‐dec‐4‐enoic (G), (4Z,7Z)‐deca‐4,7‐dienoic (H), (R)‐3,7‐dimethyloct‐6‐enoic (I), (R)‐4,8‐dimethylnon‐7‐enoic (J), (2R,6S)‐2,6,10‐trimethylundec‐9‐enoic (K), and (2R,5E)‐2,6,10‐trimethylundeca‐5,9‐dienoic acids (L). Several additional acids, occurring in trace amounts only, were tentatively identified by MS. The elucidation of the absolute configuration of the acids was performed by GC on chiral phases. Individual tuatara show specific mixtures of glycerides with up to 100 components. The individual mixtures may permit individual recognition because the bouquets seem to be stable over years.
Two‐Way Molecular Switches with Large Nonlinear Optical Contrast
Authors: Mançois Fabien , Pozzo Jean‐Luc , Pan Jianfeng , Adamietz Frédéric , Rodriguez Vincent , Ducasse Laurent , Castet Frédéric , Plaquet Aurélie , Champagne Benoît
Published: January 2009

Molecular switches: Highly efficient acido‐ and photoswitchable frequency doublers (see scheme) based on the indolinooxazolidine core are studied by means of hyper‐Rayleigh experiments and quantum‐chemical calculations.

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To optimize the nonlinear optical (NLO) contrast, a series of indolinooxazolidine derivatives with electron‐withdrawing substituents in the para position on the indolinic residue have been synthesized. Their linear and nonlinear optical properties have been characterized by UV‐visible absorption and hyper‐Rayleigh scattering measurements, as well as by ab initio calculations. The two‐way photo‐ or pH‐triggered switching mechanism has been demonstrated by comparing the absorption spectra of the zwitterionic and protonated open forms (POF). Hyper‐Rayleigh measurements have revealed that the second‐order NLO contrast between the closed indolinooxazolidine and the open π‐conjugated colored forms remain very large upon substitution. Theory and measurements show that for the POFs the amplitude of the first hyperpolarizability follows the Hammett parameters of the withdrawing groups. However, because the measurements are performed in resonance, to recover this behavior, elaborate procedures including homogeneous and inhomogeneous broadenings, as well as single‐mode vibronic structures are necessary to extrapolate to the static limit.