bluuebunny/crossref_metadata_2025 huggingface dataset:
Agonist‐Stimulated [35S]GTPγS Binding
Authors: Raddatz Rita , Alper Richard H.
Published: March 2007

This unit presents a convenient method for studying receptor function using a binding assay to assess the initial step in receptor‐mediated G protein activation in membranes prepared from rat brain. While the example procedure employs receptor agonists for serotonin1Areceptors in the hippocampus, the method can be employed to study the activity of any substance that activates a receptor coupled to a G protein, particularly Gi. Alternate protocols describe modifications that can be used to simplify and increase the accuracy of the basic protocol, as well the use of the basic protocol to study receptor antagonists.
RNA Secondary Structure Prediction
Authors: Mathews David H. , Turner Douglas H. , Zuker Michael
Published: March 2007

Details for predicting secondary structure of RNA sequences using free energy minimization are given. Protocols present the use of the RNAstructure computer program (for PCs) and the mfold server (for Unix platforms). The minimum free energy structure and a set of suboptimal structures with similar free energies are predicted. Prediction of high‐affinity oligonucleotide binding sites to a structured RNA target is also presented.
Synthesis of 2′‐ and 3′‐C‐Methylribonucleosides
Authors: Beigelman Leonid , Mikhailov Sergey N.
Published: March 2007

A simple, efficient method for the synthesis of 2′‐ and 3′‐C‐methylribonucleosides starting from a common precursor is described. This synthesis achieves conversion of 1,2:5,6‐di‐O‐isopropylidene‐3‐C‐methyl‐α‐D‐allofuranose into 1,2,3‐tri‐O‐acetyl‐5‐O‐benzoyl‐3‐C‐methyl‐α,β‐D‐ribofuranose followed by condensation with nucleic acid bases, with a final ammonolysis leading to 3′‐C‐methylribonucleosides. Alternatively, the same branched allofuranose converted to l,2,3‐tri‐O‐acetyl‐5‐O‐p‐methylbenzoyl‐2‐C‐methyl‐β‐D‐ribofuranose, after analogous Vorbruggen condensation and ammonolysis, provides 2′‐C‐methylribonucleosides.
Isolation of Renal Brush Borders
Authors: Morré D. James , Hammond Timothy
Published: March 2007

Methods are described to isolate intact brush borders and brush border membranes from renal cell homogenates. A rapid method yields sealed vesicles that reconstitute renal brush border transport. In one variation of this protocol, 10 to 20 mM CaCl2 or MgCl2 is added to aggregate non‐brush border structures for subsequent removal by centrifugation. For analytical studies, guidance is provided for subsequent purification steps including preparative free‐flow and aqueous two‐phase partition. Marker enzymes and morphological parameters are included for assessment of yield and fraction purity.
Biological Second and Third Harmonic Generation Microscopy
Authors: Friedl Peter , Wolf Katarina , Harms Gregory , von Andrian Ulrich H.
Published: March 2007

Multiphoton microscopy has become a standard method for noninvasive imaging of thick specimens with subcellular resolution. Higher harmonic generation microscopy (HHGM), based on nonlinear multiphoton excitation, is a contrast mechanism for the structural and molecular imaging of native samples in cell culture and in fixed and live tissues, for both, three‐dimensional and four‐dimensional reconstructions. HHGM comprises second and third harmonic generation (SHG, THG) of ordered molecules, can be obtained without exogenous labels, and provides detailed real‐time optical reconstruction of fibrillar collagen, myosin, microtubules, and membrane potential, as well as cell depolarization. This unit presents the principles of SHG and THG and the basic setup of a HHGM system, and summarizes current applications in cell biology. Multimodal multiphoton microscopy using HHGM together with two‐photon excited fluorescence will develop into a key approach to real‐time imaging of cell dynamics in the context of live tissues.
Analysis of Expression Data: An Overview
Authors: Grewal Anoop , Lambert Peter , Stockton Jordan
Published: March 2007

After providing a brief introduction to microarray chips and experimental details, this overview discusses analysis techniques. Data analysis from microarray experiments generally involves two parts: acquiring and normalizing the data, and interpreting it. This unit focuses mostly on the latter, as it is less technology‐specific.
X Window System Survival Guide
Authors: Stein Lincoln D.
Published: March 2007

Logging in to a Unix system from a console typically initiates a graphical desktop environment that is similar to the Microsoft Windows and Apple Macintosh desktops. Logging in remotely to a Unix system, however, typically limits the user to a small text‐only window, which is unable to launch graphical applications. This appendix describes the two main options for overcoming this obstacle: a Virtual Network Computer (VNC) and the X Window System.
Adhesion of nanosized nickel catalysts in the nanocatalysis/UF system
Authors: Zhong Zhaoxiang , Xing Weihong , Jin Wanqin , Xu Nanping
Published: March 2007

A system combining nanocatalytic reaction with crossflow ultrafiltration (UF) was used to prepare p‐aminophenol from p‐nitrophenol. In this system, nanosized nickel catalysts in suspension were employed during reaction, and then separated from slurry by an UF membrane filter. The adhesion of nickel particles to contact surfaces caused a rapid decline in the hydrogenation rate and UF flux. In order to understand the effect of materials properties, and operating parameters on adhesion of catalysts, the nickel adhesion was investigated by measuring the mass of nickel remaining on solid surfaces after contact. Surface materials with different roughness and hydrophilicity have been tested, such as poly(tetrafluoroethylene) (PTFE), stainless steel (AISI 304) and glass. The results show that rougher surfaces have more adhesion than smooth ones. Hydrophilic glass has less adhesion than hydrophobic PTFE, while intermediately hydrophilic stainless steel has the most adhesion due to its surface magnetic effect. During ultrafiltration, adhesion decreases with increasing crossflow velocity and increases with increasing suspension concentration. With the addition of microsized alumina particles in suspension, the adhesion of nanosized nickel can be inhibited effectively. © 2007 American Institute of Chemical Engineers AIChE J, 2007.
Martsolf syndrome in Japanese siblings
Authors: Ehara Hiroaki , Utsunomiya Yasushi , Ieshima Atsushi , Maegaki Yoshihiro , Nishimura Gen , Takeshita Kenzo , Ohno Kousaku
Published: March 2007

We describe a Japanese brother and sister with Martsolf syndrome. They had short stature, severe mental retardation, cataract, hypogonadism, craniofacial dysmorphism, and bone and joint symptoms including scoliosis, lax finger joints, and talipes valgus. Previously undescribed findings included proximal femoral epiphyseal dysplasia reminiscent of Legg–Calve–Perthes disease in both patients, and Klippel–Feil malformation and osteopathia striata in one patient. Brain MRI showed mild frontal and temporal lobe atrophy, and mild ventricular enlargement. Severe GH deficiency was demonstrated after insulin tolerance and glucagon/propranolol tolerance tests. No responses to serum LH and FSH after a gonadotropin‐releasing hormone (GnRH) test suggested secondary hypogonadism, that is, hypogonadotropic hypogonadism, due to hypothalamus‐pituitary axis insufficiency in both patients. © 2007 Wiley‐Liss, Inc.
Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes
Authors: Marziliano Nicola , Mannarino Savina , Nespoli Luisa , Diegoli Marta , Pasotti Michele , Malattia Clara , Grasso Maurizia , Pilotto Andrea , Porcu Emanuele , Raisaro Arturo , Raineri Claudia , Dore Roberto , Maggio Pietro Paolo , Brega Agnese , Arbustini Eloisa
Published: March 2007

Barth syndrome is an X‐linked recessive disorder caused by the tafazzin (TAZ) gene mutations and includes dilated cardiomyopathy (DCM) with left ventricular non‐compaction, neutropenia, skeletal myopathy, abnormal mitochondria and 3‐methylglutaconic aciduria. Dilated cardiomyopathy with left ventricular non‐compaction transmitted as an autosomal dominant condition has also been associated with LIM domain‐binding 3 (LDB3) gene defects. We describe a family in which the 12‐year‐old proband had left ventricular non‐compaction and DCM. His mother had five miscarriages, two other sons who died in infancy, and a healthy son and daughter. The proband showed left ventricular non‐compaction–DCM, skeletal myopathy, recurrent oral aphthous ulcers and cyclic neutropenia. The DCM progressively improved with age; medical therapy was discontinued at 5 years of age. At present, left ventricular function is normal and arrhythmias are absent. Magnetic resonance imaging documented left ventricular non‐compaction. However, oral aphthous ulcers and cyclic neutropenia have recurred. In the proband we identified two novel mutations, one of maternal origin in the TAZ gene (p.[Glu202ValfsX15]) and one of paternal origin in the LDB3 gene (p.[Thr350Ile]). The mother, brother and father are healthy; although the latter two show prominent left ventricle trabeculation without dysfunction. Expression studies of TAZ and LDB3 genes were conducted in family members and controls. In the proband, brother and father, LDB3 expression was similar to control cases. TAZ and LDB3 expression progressively declined with age in control both blood and myocardial samples. However, an endomyocardial biopsy performed in the proband at 6 months of age, showed significantly lower TAZ and LDB3 expression than in age‐matched myocardial controls. We believe that the clinical, genetic and expression data support the hypothesis that tafazzins are essential during fetal and early post‐natal life. © 2007 Wiley‐Liss, Inc.
Compound heterozygosity of SHOX‐encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD)
Authors: Campos‐Barros Ángel , Benito‐Sanz Sara , Ross Judith L. , Zinn Andrew R. , Heath Karen E.
Published: March 2007

We present the clinical and molecular characteristics of a multi‐generation family in which the proband presented with clinical features of Langer mesomelic dysplasia (LMD) whilst different family members had a diagnosis of Léri–Weill dyschondrosteosis (LWD) and/or pseudoachondroplasia (PSACH). In the LMD proband two different deletions were identified in the pseudoautosomal 1 region (PAR1) of the X and Y chromosomes: a SHOX‐encompassing deletion inherited from his father and a downstream PAR1 deletion, which did not include SHOX, inherited from his mother. The individuals with PSACH features presented the previously described G719D mutation in the C‐terminal globular domain of the cartilage oligomeric matrix protein gene (COMP). The LMD proband described here represents the first LMD case due to compound heterozygosity for deletions of the two different PAR1 regions, SHOX‐encompassing and downstream from SHOX, that have been shown to be implicated in the pathogenesis of LWD and LMD. © 2007 Wiley‐Liss, Inc.
Synthesis and properties of flame‐retardant epoxy resins based on DOPO and one of its analog DPPO
Authors: Schäfer Alexander , Seibold Sebastian , Lohstroh Wiebke , Walter Olaf , Döring Manfred
Published: March 2007

Two phosphorus‐containing heterocyclic flame retardants ‐9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) and 2,8‐dimethyl‐phenoxaphosphin‐10‐oxide (DPPO) ‐ and their derivatives were characterized and incorporated in the backbone of epoxy novolac to obtain flame‐retardant epoxy resins. The structures and spectroscopic data including high‐resolution mass spectroscopy of these flame retardants were determined. Flame‐retardant epoxy resins with a phosphorus content of up to 2% based on heterocyclic DOPO and DPPO were cured with 4,4′‐diaminodiphenylmethane (DDM), and their features were examined by UL 94, LOI, and DSC. In this manner, high‐performance polymers with glass transition temperatures around 190°C and the UL 94 rating V0 were obtained. These polymers were compared with epoxy resins incorporating diphenyl phosphite and diphenyl phosphate, which are nonheterocyclic and do not pass the UL 94 test up to 2% phosphorus. DPPO has a similar flame retardancy like the commercially available DOPO. Furthermore, to explain the difference in the efficiency of the tested flame retardants, key experiments for the determination of the active species during the flame‐retarding process were performed and the PO radical was identified. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.
Concepts important to patients with psoriatic arthritis are not adequately covered by standard measures of functioning
Authors: Stamm Tanja A. , Nell Valerie , Mathis Mona , Coenen Michaela , Aletaha Daniel , Cieza Alarcos , Stucki Gerold , Taylor William , Smolen Josef S. , Machold Klaus P.
Published: March 2007

Objective

To explore whether the concepts important to patients with psoriatic arthritis (PsA) are covered by self‐report instruments assessing functioning.

Methods

We conducted a qualitative focus group study with PsA patients about their problems in daily functioning. Focus groups were tape recorded and transcribed verbatim. The transcribed texts were divided into meaning units, and concepts contained in these meaning units were extracted. Self‐report instruments assessing functioning in PsA were identified in a structured literature search. Using the International Classification of Functioning, Disability and Health (ICF) as a common frame of reference, we determined whether each concept identified in the focus groups was covered by each of the instruments.

Results

Thirty‐one patients participated in 6 focus groups. The following 9 instruments were included in the present analysis: Arthritis Impact Measurement Scale Short Form; Bath Ankylosing Spondylitis Disease Activity Index; Disabilities of the Arm, Shoulder, and Hand Questionnaire; Dermatology Quality of Life Index; Dougados Functional Index; Health Assessment Questionnaire (HAQ); HAQ‐S (HAQ adapted for spondylarthropathies); PsA‐specific Quality of Life Instrument; and Short Form 36 Health Survey. Of the 54 concepts identified in 590 meaning units in the transcribed data, 19 concepts (35%) were not covered by any of the instruments. Of these, 11 concepts that were linked to the ICF component environmental factors were not covered by any of the instruments, whereas all concepts linked to the ICF component activities and participation were covered by at least 1 of the instruments (but no single instrument covered all concepts).

Conclusion

The impact of environmental factors, attitudes towards individuals with health problems, and loss of leisure time may represent important aspects addressing participation that are currently not covered in the instruments assessing functioning in PsA.
A brief pain management program compared with physical therapy for low back pain: Results from an economic analysis alongside a randomized clinical trial
Authors: Whitehurst D. G. T. , Lewis M. , Yao G. L. , Bryan S. , Raftery J. P. , Mullis R. , Hay E. M.
Published: March 2007

Objective

Guidelines for the management of acute low back pain in primary care recommend early intervention to address psychosocial risk factors associated with long‐term disability. We assessed the cost utility and cost effectiveness of a brief pain management program (BPM) targeting psychosocial factors compared with physical therapy (PT) for primary care patients with low back pain of <12 weeks' duration.

Methods

A total of 402 patients were randomly assigned to BPM or PT. We adopted a health care perspective, examining the direct health care costs of low back pain. Outcome measures were quality‐adjusted life years (QALYs) and 12‐month change scores on the Roland and Morris disability questionnaire. Resource use data related to back pain were collected at 12‐month followup. Cost effectiveness was expressed as incremental ratios, with uncertainty assessed using cost‐effectiveness planes and acceptability curves.

Results

There were no statistically significant differences in mean health care costs or outcomes between treatments. PT had marginally greater effectiveness at 12 months, albeit with greater health care costs (BPM £142, PT £195). The incremental cost‐per‐QALY ratio was £2,362. If the UK National Health Service were willing to pay £10,000 per additional QALY, there is only a 17% chance that BPM provides the best value for money.

Conclusion

PT is a cost‐effective primary care management strategy for low back pain. However, the absence of a clinically superior treatment program raises the possibility that BPM could provide an additional primary care approach, administered in fewer sessions, allowing patient and doctor preferences to be considered.
Effect of anatomic realignment on muscle function during gait in patients with medial compartment knee osteoarthritis
Authors: Ramsey Dan K. , Snyder‐Mackler Lynn , Lewek Michael , Newcomb William , Rudolph Katherine S.
Published: March 2007

Objective

Individuals with medial compartment knee osteoarthritis (OA) and genu varum use different movement and muscle activation patterns to increase joint stability during gait. The purpose of this study was to ascertain whether opening‐wedge high‐tibial osteotomy (OW‐HTO) corrected pathomechancial abnormalities associated with the progression of knee OA.

Methods

Fifteen patients diagnosed with medial knee OA and genu varum who were scheduled for OW‐HTO were tested prior to and 1 year following OW‐HTO. Fifteen age‐ and sex‐matched controls were also tested. Frontal plane laxity was measured from stress radiographs. All participants underwent quadriceps strength testing with a burst superimposition technique and gait analysis with surface electromyography to calculate knee joint kinematics and kinetics and muscle co‐contraction during the stance phase of gait. Participants rated their knee function and instability using a self‐report questionnaire.

Results

Static alignment improved following the surgery. Medial laxity (P= 0.003) and instability (P= 0.002) significantly improved, and statistical reductions in the adduction moment resulted in lower levels of vastus medialis‐medial gastrocnemius muscle co‐contractions (P= 0.089). Despite improvements in global rating of knee function (P= 0.001), the OA group's ratings remained significantly lower than those of the healthy controls (P= 0.001). Quadriceps strength deficits and knee flexion impairments persisted.

Conclusion

Persistent quadriceps weakness and impaired knee kinematics after realignment suggest that the movement strategy may perpetuate joint destruction and impede the long‐term success of realignment. Rehabilitation should focus on quadriceps strength and improving joint mobility to improve the long‐term function of individuals with medial knee OA.
Work‐related repetitive strain injury and leisure‐time physical activity
Authors: Ratzlaff C. R. , Gillies J. H. , Koehoorn M. W.
Published: March 2007

Objective

To investigate the relationship between leisure‐time physical activity and work‐related repetitive strain injury (RSI), adjusted for sociodemographic characteristics and work‐related physical and stress factors.

Methods

The data source was the 2003 Canadian Community Health Survey, a national cross‐sectional survey of 134,072 respondents. The analysis was limited to a sample of the survey population reporting full‐time work during the past 12 months (n = 58,622). The outcome of interest was work‐related RSI of the upper body. Multiple logistic regression was used to examine the relationship between the outcome and leisure‐time physical activity level, adjusted for sociodemographic, health, and occupational characteristics. The potential effect of leisure‐time physical activity with a high upper‐body load was investigated in a secondary analysis.

Results

The prevalence of upper‐body work‐related RSI was 5.9% in the Canadian population in 2003. An active lifestyle during leisure time was associated with a lower prevalence of work‐related upper‐body RSI (odds ratio 0.84, 99% confidence interval 0.75–0.95), after adjustment for work physical demands and other covariates. Female sex, obesity, smoking, age, work‐related stress, and work physical demands were associated with RSI. In the secondary analysis, we did not find that participating in leisure‐time activities with a high upper‐body load was a risk factor for RSI.

Conclusion

Our study results indicate that being physically active during leisure time is associated with a decreased risk of upper‐body occupational RSI, adding another potential health benefit to participation in leisure‐time physical activity.
Daily health status registration (patient diary) in patients with rheumatoid arthritis: A comparison between personal digital assistant and paper‐pencil format
Authors: Heiberg Turid , Kvien Tore K. , Dale Øystein , Mowinckel Petter , Aanerud Gerd J. , Songe‐Møller Ann B. , Uhlig Till , Hagen Kåre B.
Published: March 2007

Objective

The patient perspective workshops at the Outcome Measures in Rheumatology Clinical Trials have included daily measures of health status (patient diary) and use of electronic tools for data collection in the research agenda. The objective of this study was to compare daily and weekly registrations of self‐reported health status measures between personal digital assistant (PDA) and paper‐pencil (PP) format regarding scores, variation, and feasibility.

Methods

Thirty‐eight patients with stable rheumatoid arthritis recorded their health status during 84 days in a repeated crossover design, using PDA or PP format during four 21‐day periods. Visual analog scales (VAS) for pain, fatigue, and global disease and the Rheumatoid Arthritis Disease Activity Index were scored daily; the Short Form 36 and Modified Health Assessment Questionnaire were scored weekly.

Results

The average scores and measures of variation of the 4 daily health status measures over 21 days did not differ significantly between PDA and PP formats in either of the 2 crossover periods. The values for the average range between the maximum and minimum values for daily measures were similar between the 2 formats, but showed considerable variation (e.g., range for pain VAS was 19–28 mm over each 21‐day period). The time to complete the instruments was similar between the 2 formats. Missing daily data entries were generally low for both periods and somewhat higher for PDA. The majority of patients (82.9%) preferred using PDA.

Conclusion

Daily assessments with PDA may be efficiently used for frequent data collection because this format performs similarly to the traditional PP format.
Risk of congestive heart failure with nonsteroidal antiinflammatory drugs and selective Cyclooxygenase 2 inhibitors: A class effect?
Authors: Hudson Marie , Rahme Elham , Richard Hugues , Pilote Louise
Published: March 2007

Objective

Nonsteroidal antiinflammatory drugs (NSAIDs) as a class have been shown to increase the risk of congestive heart failure (CHF) compared with celecoxib. The magnitude of the risk for individual NSAIDs is not known.

Methods

Using administrative databases, we performed a nested case–control study in a population‐based cohort of patients ages ≥66 years admitted for CHF between January 1998 and March 2003. Cases were patients readmitted for CHF after cohort entry (index date). Four controls were matched to each case on date of cohort entry and time between cohort entry and index date. Exposure was the current use of an NSAID or a coxib in the 7 days prior to CHF readmission. Using conditional logistic regression, we calculated the odds of readmission for CHF in patients exposed to naproxen, diclofenac, ibuprofen, indomethacin, or rofecoxib compared with celecoxib, after adjusting for possible confounding variables.

Results

We identified 8,512 cases and 34,048 controls. The baseline characteristics between the groups were similar in general. The odds of being readmitted for CHF were higher in patients currently exposed to indomethacin (odds ratio [OR] 2.04, 95% confidence interval [95% CI] 1.16–3.58) or rofecoxib (OR 1.58, 95% CI 1.19–2.11) compared with celecoxib. There was no difference between naproxen, diclofenac, and ibuprofen compared with celecoxib, although the numbers of exposed cases and controls were small.

Conclusion

In elderly patients with known CHF, indomethacin and rofecoxib are associated with a greater risk of recurrent CHF compared with celecoxib. Alternatives should be considered for patients with CHF who require antiinflammatory drugs.
Social functioning and peer relationships of adolescents with juvenile fibromyalgia syndrome
Authors: Kashikar‐Zuck Susmita , Lynch Anne M. , Graham T. Brent , Swain Nicole F. , Mullen Sara M. , Noll Robert B.
Published: March 2007

Objective

To assess peer relationships of adolescents with juvenile primary fibromyalgia syndrome (JPFS) compared with matched classroom comparison peers (MCCPs) without a chronic illness. JPFS is characterized by chronic musculoskeletal pain, sleep disturbance, fatigue, and difficulty with daily functioning. Adolescents with JPFS often report problems with school and participating in peer activities, placing them at risk for social isolation from their peers and psychosocial adjustment problems.

Methods

Participants were 55 adolescents with JPFS (ages 12–18 years) from a pediatric outpatient rheumatology clinic and 55 MCCPs. Data on peer reputation and peer acceptance were collected from teachers, peers, and self report in a classroom setting with no focus on JPFS.

Results

Adolescents with JPFS were perceived (by peer and self reports) as being more isolated and withdrawn and less popular. Adolescents with JPFS were less well liked, were selected less often as a best friend, and had fewer reciprocated friendships.

Conclusion

Our findings suggest that adolescents with JPFS are experiencing problems with peer relationships. Given the central role that peer relationships play in psychological development of children, and because peer rejection and isolation have been associated with subsequent adjustment problems, these findings are concerning. Longitudinal studies of adolescents with JPFS are needed to ascertain whether these patients are at long‐term risk and will provide a foundation for the need for early interventions. Results are discussed within the context of earlier findings for other adolescents with chronic illness and rheumatic conditions, such as juvenile idiopathic arthritis, who demonstrated no social problems.
Evaluation of the preliminary definitions of minimal disease activity and remission in an early seropositive rheumatoid arthritis cohort
Authors: Khanna Dinesh , Oh Myungshin , Furst Daniel E. , Ranganath Veena , Gold Richard H. , Sharp John T. , Park Grace S. , Keystone Edward C. , Paulus Harold E. ,   Western Consortium of Practicing Rheumatologists
Published: March 2007

Objective

To evaluate published proposed definitions of minimal disease activity (MDA) and remission in patients with early rheumatoid arthritis (RA).

Methods

The cohort comprised disease‐modifying antirheumatic drug (DMARD)–naive patients with early seropositive active RA (n = 200) treated with traditional DMARDs in the prebiologic era. MDA definitions included Disease Activity Score in 28 joints (DAS28) ≤2.85, or achieving 5 of 7 World Health Organization (WHO)/International League of Associations for Rheumatology (ILAR) core set measure thresholds as proposed by the Outcome Measures in Rheumatology Clinical Trials. Other MDA definitions included Simplified Disease Activity Index (SDAI) score ≤11 and Clinical Disease Activity Index (CDAI) score ≤10. Remission definitions included American College of Rheumatology (ACR) remission, DAS28 <2.6, DAS28 <2.4, achieving all 7 WHO/ILAR core set measure thresholds, SDAI ≤3.3, and CDAI ≤2.8. Physical function was assessed using the Health Assessment Questionnaire (HAQ) disability index (DI) and radiographic progression was assessed using the Sharp score.

Results

At baseline, no patients were in MDA or remission. Depending on the MDA definition, 20–32%, 27–32%, and 30–48% were in MDA at 6, 12, and 24 months, respectively. Depending on the remission definition, 0.7–15%, 0–24%, and 0–33% were in remission at 6, 12, and 24 months, respectively. For example, at 6 months, lowest (highest) responses for MDA were seen with DAS28 ≤2.85 (SDAI ≤11) and for remission with ACR remission criteria (DAS28 <2.6). Patients who achieved either MDA or remission had lower HAQ DI and radiographic scores compared with patients who achieved neither.

Conclusion

Our study demonstrated that different proportions of patients were classified as MDA or remission depending on the definition used. This has implications in predefining MDA or remission for a clinical trial or to establish goals for optimum management of RA in clinical practice.
Usefulness of the disease activity scores for polymyalgia rheumatica for predicting glucocorticoid dose changes: A study of 243 scenarios
Authors: Binard Aymeric , De Bandt Michel , Berthelot Jean‐Marie , Saraux Alain ,   Inflammatory Joint Disease Working Group (CRI) of the French Society for Rheumatology
Published: March 2007

Objective

To evaluate associations linking glucocorticoid dose changes in patients with polymyalgia rheumatica (PMR) to the PMR activity score (PMR‐AS) and its components.

Methods

Nine clinical vignettes of PMR were written by a panel of experts and submitted to 35 rheumatologists, who were asked to assess disease activity using a visual analog scale (VASph) and to determine whether there was a relapse of PMR requiring an increase in the glucocorticoid dose. In 7 vignettes, >80% of the rheumatologists agreed on the diagnosis of relapse justifying the glucocorticoid dose decision. A total of 243 vignette‐physician combinations were obtained. Using these vignettes, we evaluated statistical associations linking a decision to increase the glucocorticoid dose to the value of PMR‐AS, of its components (VASph, visual analog scale for pain [VASp], C‐reactive protein level [CRP], morning stiffness [MST], and elevation of upper limbs [EUL]), or to the difference in these variables between the last 2 visits (dPMR‐AS, dVASph, dVASp, dCRP, dMST, and dEUL).

Results

The strongest associations with a decision to increase the glucocorticoid dose occurred with dPMR‐AS >4.2, dMST >10 minutes, dVASph >1.55, and dCRP >4 mg/dl (99.3% sensitivity, 100% specificity for all 4 variables); MST ≥10 minutes (100% sensitivity, 99.3% specificity); PMR‐AS ≥7 (98.1% sensitivity, 94.3% specificity); VASph ≥2.25 (94.2% sensitivity, 83.6% specificity); and CRP level ≥14.5 mg/liter (66.3% sensitivity, 99.3% specificity).

Conclusion

Despite inter‐individual variations in VASph, PMR‐AS was a good indicator of disease activity. However, MST, dMST, dVASph, dPMR‐AS, and dCRP performed better than PMR‐AS. These variables may be useful in tailoring the glucocorticoid dose to the individual needs of each patient.
Google Scholar citations and Google Web/URL citations: A multi‐discipline exploratory analysis
Authors: Kousha Kayvan , Thelwall Mike
Published: March 2007

We use a new data gathering method, “Web/URL citation,” Web/URL and Google Scholar to compare traditional and Web‐based citation patterns across multiple disciplines (biology, chemistry, physics, computing, sociology, economics, psychology, and education) based upon a sample of 1,650 articles from 108 open access (OA) journals published in 2001. A Web/URL citation of an online journal article is a Web mention of its title, URL, or both. For each discipline, except psychology, we found significant correlations between Thomson Scientific (formerly Thomson ISI, here: ISI) citations and both Google Scholar and Google Web/URL citations. Google Scholar citations correlated more highly with ISI citations than did Google Web/URL citations, indicating that the Web/URL method measures a broader type of citation phenomenon. Google Scholar citations were more numerous than ISI citations in computer science and the four social science disciplines, suggesting that Google Scholar is more comprehensive for social sciences and perhaps also when conference articles are valued and published online. We also found large disciplinary differences in the percentage overlap between ISI and Google Scholar citation sources. Finally, although we found many significant trends, there were also numerous exceptions, suggesting that replacing traditional citation sources with the Web or Google Scholar for research impact calculations would be problematic.
Phosphorus Ligands with a Large Cavity: Synthesis of Triethynylphosphines with Bulky End Caps and Application to the Rhodium‐Catalyzed Hydrosilylation of Ketones
Authors: Ochida Atsuko , Sawamura Masaya
Published: March 2007

Trialkynylphosphines substituted with bulky triarylsilyl groups at the alkyne termini were synthesized. The new phosphines P(CCSiAr3)3 (Ar=3,5‐tBu2‐4‐MeOC6H2, 3,5‐(Me3Si)2C6H3) are uncrowded near the phosphorus atom but bulky in the distal region. As a result, they contain a large cavity, at the bottom of which the phosphine lone‐pair electrons are located. The compounds are stable to oxidation by air and hydrolysis. DFT calculations suggested that the triethynylphosphines are good π‐acceptor ligands, comparable with P(OAr)3. The trialkynylphosphines reacted with [{RhCl(cod)}2] (P/Rh=1.1:1) to give selectively the monophosphine–rhodium complex [RhCl(cod)P(CCSiAr3)3]. X‐ray crystal‐structure analysis revealed that the {RhCl(cod)} fragment is fully accommodated by the cavity of the phosphine ligand. Compared to the effect of analogues with smaller end caps and PPh3, the trialkynylphosphines accelerated markedly the rhodium‐catalyzed hydrosilylation of ketones with a triorganosilane. It is proposed that the higher catalytic activity observed with the holey phosphines is a result of the preferential formation of a monophosphine–rhodium species.
Iterative Anwendung zweier Rechenmodelle zur Beurteilung der Lüftungserfordernisse für eine Vermeidung von Schimmelpilzwachstum
Authors: Krus Martin , Holm Andreas , Sedlbauer Klaus
Published: March 2007

Mit Hilfe eines neu entwickelten Raumklimamodells kann der Einfluß unterschiedlicher Lüftungsvarianten auf das Raumklima berechnet werden. Die Anwendung eines biohygrothermischen Modells gestattet unter Verwendung der berechneten Oberflächentemperaturen und ‐feuchten das Schimmelpilzrisiko abzuschätzen. Für gegebene Randbedingungen ist es somit möglich, die notwendige Lüftung durch eine iterative Anwendung beider Verfahren zu ermitteln. Als Beispiele dienen unterschiedliche Baukonstruktionen, an denen der Einfluß unterschiedlicher Lüftungsstrategien (Dauerlüftung oder Stoßlüftung) auf den zur Schimmelpilzvermeidung erforderlichen mittleren Luftwechsel demonstriert wird.
Bauphysik und die technische Literatur des Neuen Bauens
Authors: Tomlow Jos
Published: March 2007

“Man könnte die Tätigkeit eines Volkes in gesundheitlicher oder hygienischer Richtung geradezu als einen Maßstab gebrauchen für die Größe seiner Fähigkeiten in der Kulturgeschichte eine Rolle zu spielen.”

Max von Pettenkofer, 1873 (zitiert nach Usemann [88], S. 38)

“Ein bekannter Architekt ging in seiner Begeisterung für einen solchen platten Internationalismus so weit, daß er die These verkündete: ‘In der Zukunft wird man im hohen Norden genau ebenso bauen wie am Mittelländischen Meer!’ In wenigen Jahren hat sich seine Forderung erfüllt; die Architektur hat eine so schwere Niederlage erlitten, dass sie sich nur sehr langsam davon erholen kann. Wäre es nur ein ästhetischer Irrtum gewesen, so wäre es vielleicht noch nicht einmal so schlimm. Aber die Natur, in diesem Fall das Klima, wird mit ihrer Rache dafür, dass sie so sträflich vernachlässigt wurde, nicht lange auf sich warten lassen.”

Bruno Taut, 1936 (zitiert nach Medina Warmburg [47], S. 392)
eLearning als Weiterbildungschance für Ingenieure
Authors: Gorges Karin , Bröker Thomas , Kornadt Oliver
Published: March 2007

Im Memorandum des Ingenieurdialogs “Zukunftssicherung des Ingenieurwesens in Deutschland” wurde 2001 angesichts sinkender Absolventenzahlen und ständig wachsender Anforderungen gefordert, neben der grundständigen Ausbildung auch die wissenschaftliche Weiterbildung an den Universitäten und Hochschulen stärker zu etablieren. Zeitgleich ist in den letzten Jahren eine rasante Entwicklung von Computer‐ und Netzwerktechnologien zu verzeichnen. Diese neuen Technologien nicht als technische Spielerei, sondern in didaktisch sinnvollen Szenarien zielgerichtet einzusetzen ist eine Aufgabe, der sich die Universitäten und Hochschulen stellen sollten. Über die Vermittlung fachlicher Inhalte hinaus, sollen bei den Lernenden Schlüsselqualifikationen wie Lern‐, Kommunikations‐ und Medienkompetenzen ausgebaut werden. Die Bund‐Länder‐Kommission für Bildungsplanung und Forschungsförderung fördert seit 2005 das Projekt eLBau – eLearning Bauphysik, das sich diesen Anforderungen stellt und die Projektergebnisse in ein berufsbegleitendes Masterkonzept umsetzt.
Erinnerung an Leonhard Euler (1707–1783)
Authors: Lehmann Günter
Published: March 2007

Leonhard Euler (15. 4. 1707–18. 9. 1783) war nicht nur der größte Mathematiker seiner Zeit, sondern zugleich einer der schöpferischsten Menschen überhaupt. Seine wissenschaftliche Tätigkeit, die nicht einmal durch nahezu völlige Erblindung in den letzten 14 Lebensjahren beeinträchtigt werden konnte, umfaßt außer der Mathematik und Physik auch die Ingenieurwissenschaften, die Astronomie und die Philosophie. Seine Leistungen auf diesen Gebieten sollen und können hier nicht behandelt werden, doch soviel sei gesagt, Euler war der erste, der für die Kreiszahl den Buchstaben π und als Summenzeichen das große griechische Sigma Σ einführte. Für die Basis der natürlichen Logarithmen benutzte er den Buchstaben e. Dies geschah wohl aus praktischen Gründen und nicht in Anlehnung an seinen Namen, denn die Buchstaben a, b, c und d wurden schon damals in der Mathematik häufig benutzt, und so war es naheliegend, das e zu wählen. Der Buchstabe e könnte aber auch eine Abkürzung für “exponential” sein. Nachfolgende Mathematiker bezeichneten dann die Zahl e = 2,7 18 28 18 28 … als die Eulersche Zahl. Nicht zu verwechseln mit der Euler‐Zahl Eu = Δp/(ρ · c2), einer Kennzahl für reibungsbehaftete Strömungen. So gibt es nachweislich mindestens 30 Begriffe, die alle mit dem Namen Euler in Beziehung stehen. Zu seinen Ehren sind der “Krater Euler” auf dem Mond und der 2002 entdeckte “Asteroid Euler” benannt worden. In diesem Beitrag werden dagegen der Mensch Leonhard Euler und seine Lebensumstände im Mittelpunkt stehen.
Mezzanine participations
Authors: Leonard Carson
Published: March 2007

In April of 2005, one of the architectural icons of the New York City skyline, the Met Life Building, on Park Avenue above Grand Central Terminal, was purchased by an affiliate of one of the leading real estate companies in the USA, Tishman–Speyer. Designed by Emery Roth and Walter Gropius, the building now boasts some of the highest asking rents in Manhattan. The acquisition financing for this transaction was originated by a leading investment bank and was structured to include a mortgage loan and three mezzanine loans. The mortgage loan was carved into a number of pieces and sold in several securitization transactions. Through participation and servicing agreements put in place by the originator, the mezzanine loans were each carved into participations and sold off in a series of transactions to a variety of institutional investors. This transaction is an example of the critical role that mezzanine financing has come to play in large real estate financings over the past half‐decade. Copyright © 2005 John Wiley & Sons, Ltd.
Renewed interest in hotel investment: white paper
Authors: Lee Brian
Published: March 2007

As the world's largest industry, tourism is becoming increasingly global and places greater demands on the hotel trade.

Tourist traffic had increased by 30% over the last five years, according to the World Tourism Organisation, and will shortly exceed one billion tourist arrivals per annum.

Greater demand for hotel accommodation coupled with increasing separation of ownership and management has placed the hotel sector firmly in the investment spotlight.

The following article explains why. Copyright © 2005 John Wiley & Sons, Ltd.
Photocaged Agonist for an Analogue‐Specific form of the Vitamin D Receptor
Authors: Biggins John B. , Hashimoto Atsushi , Koh John T.
Published: March 2007

Nuclear hormone receptors (NHRs) represent a diverse class of ligand‐dependent transcriptional regulators. NHRs that have been rendered functionally inactive due to mutations that abrogate proper ligand binding can often be rescued by appropriately designed hormone analogues. The analogue‐specific receptor–ligand pairs provide an ideal platform from which to develop new chemogenomic tools for the spatial and temporal control of gene expression. Here, we describe the synthesis and in vitro assessment of a photocaged VDR agonist specific to a mutant NHR that is associated with vitamin D‐resistant rickets. The results provide insight into the utility of the agonist as a potential tool for photoinduced gene patterning.
Hybrid Peptides: Expanding the β Turn in Peptide Hairpins by the Insertion of β‐, γ‐, and δ‐Residues
Authors: Rai Rajkishor , Vasudev Prema G. , Ananda Kuppanna , Raghothama Srinivasarao , Shamala Narayanaswamy , Karle Isabella L. , Balaram Padmanabhan
Published: March 2007

The β turn segment in designed peptide hairpins has been expanded by the insertion of β‐, γ‐ and δ‐amino acids at the i+2 position. The model octapeptides Boc‐Leu‐Phe‐Val‐DPro‐Ac6c‐Leu‐Phe‐Val‐OMe (1), Boc‐Leu‐Phe‐Val‐DPro‐β3‐Ac6c‐Leu‐Phe‐Val‐OMe (2), and Boc‐Leu‐Phe‐Val‐DPro‐Gpn‐Leu‐Phe‐Val‐OMe (3) have been shown to adopt β hairpin conformations in methanol by the observation of key diagnostic nuclear Overhauser effects. Boc‐Leu‐Val‐Val‐DPro‐δ‐Ava‐Leu‐Val‐Val‐OMe (4) adopts a β hairpin conformation in crystals; this is stabilized by three cross‐strand hydrogen bonds as demonstrated by X‐ray diffraction. The canonical C10 turn in an α–α segment is expanded to C11, C12, and C13 turns in α–β, α–γ, and α–δ segments, respectively. The crystal structures of Piv‐LPro‐β3‐Ac6c‐NHMe (5) and Boc‐Ac6c‐Gpn‐Ac6c‐OMe (6) reveal intramolecularly hydrogen‐bonded C11 and C12 conformations, respectively. Computer modeling of octapeptide sequences that contain centrally positioned hybrid‐turn segments, by using turn parameters derived from the structures of peptides 5 and 6, establishes the stereochemical acceptability of the β hairpins in the cases of peptides 2 and 3. Accommodation of ω‐amino acids into the turn segments is achieved by the adoption of gauche conformations around the backbone CC bonds.
DNA‐Directed Immobilization of Horseradish Peroxidase–DNA Conjugates on Microelectrode Arrays: Towards Electrochemical Screening of Enzyme Libraries
Authors: Fruk Ljiljana , Müller Joachim , Weber Günther , Narváez Arántzazu , Domínguez Elena , Niemeyer Christof M.
Published: March 2007

This work is aimed towards the generation of enzyme arrays on electrochemically active surfaces by taking advantage of the DNA‐directed immobilization (DDI) technique. To this end, two different types of horseradish peroxidase (HRP)–DNA conjugates were prepared, either by covalent coupling with a bifunctional cross‐linker or by the reconstitution of apo‐HRP, that is, HRP lacking its prosthetic heme (protoporphyrin IX) group, with a covalently DNA‐modified heme cofactor. Both conjugates were characterized in bulk and also subsequent to their immobilization on gold electrodes through specific DNA hybridization. Electrochemical measurements by using the phenolic mediator ortho‐phenylendiamine indicated that, due to the high degree of conformational orientation, the apparent Michaelis–Menten constants of the reconstituted HRP conjugate were lower than those of the covalent conjugate. Due to the reversible nature of DDI, both conjugates could be readily removed from the electrode surface by simple washing and, subsequently, the electrodes could be reloaded with fresh enzymes, thereby restoring the initial amperometric‐response activity. Moreover, the specific DNA hybridization allowed us to direct the two conjugates to distinct sites on a microelectrode array. Therefore, the self‐assembly and regeneration capabilities of this approach should open the door to the generation of arrays of redox‐enzyme devices for the screening of enzymes and their effectors.
Heparin‐binding epidermal growth factor‐like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcome
Authors: Kramer Christopher , Klasmeyer Kai , Bojar Hans , Schulz Wolfgang A. , Ackermann Rolf , Grimm Marc‐Oliver
Published: March 2007

BACKGROUND.

Cleavage of membrane‐anchored heparin‐binding epidermal growth factor‐like growth factor (proHB‐EGF) yields a soluble HB‐EGF isoform (sHB‐EGF), which is an activating epidermal growth factor receptor (EGFR) ligand and a C‐terminal fragment HB‐EGF‐C acting directly in the nucleus. In bladder cancer, overexpression of both HB‐EGF and EGFR have been observed, but to the authors' knowledge the prognostic significance of different modes of HB‐EGF signaling have remained unclear.

METHODS.

Expression and intracellular localization of HB‐EGF and EGFR were examined by immunohistochemistry in paraffin‐embedded specimens from 121 patients who underwent cystectomy for bladder cancer. Tumor stage was pTis/pT1 in 7 patients, pT2 in 41 patients, pT3 in 55 patients, and pT4 in 18 patients. Lymph node metastases were present in 32 patients.

RESULTS.

Using an antibody directed against the C‐terminal domain, HB‐EGF expression was detected in the cytoplasm or in the nucleus of tumor cells. EGFR staining was uniform at the plasma membrane. The actuarial 5‐year cancer‐specific survival of patients with tumors with predominant nuclear HB‐EGF staining was 28% compared with 57% if HB‐EGF staining was predominantly cytoplasmic (P = .027). Disease outcome of patients with a ‘mixed’ HB‐EGF staining pattern was found to be between that of the 2 former groups. In agreement with previous studies, strong EGFR expression was associated with poor prognosis. Despite strong EGFR expression, predominant cytoplasmic HB‐EGF staining was associated with a more favorable outcome, whereas a predominant nuclear pattern defined a subgroup with extremely poor prognosis (5‐year tumor‐specific survival of 55% vs 13%, respectively; P = .026).

CONCLUSIONS.

The current study results confirm that EGFR expression is significantly correlated with disease‐specific mortality but that the outcome is also influenced by the mode of HB‐EGF signaling. Additional nuclear HB‐EGF signaling, indicative of increased cleavage of proHB‐EGF, appears to enhance the adverse activities. Cytoplasmic HB‐EGF staining likely reflects proHB‐EGF, which may also exert antiproliferative effects. Cancer 2007. © 2007 American Cancer Society.