bluuebunny/crossref_metadata_2025 huggingface dataset:
Small-scale micropiles to control heave on expansive clays
Authors: Nusier O. K. , Alawneh A. S. , Abdullatit B. M.
Published: January 2009

The main purpose of this study was to examine the effectiveness of using micropiles as a technique to control upward movement of lightweight structures over expansive soils. For this purpose, smooth and roughened steel laboratory small-scale micropiles surrounded by dense sand were inserted in predrilled holes of larger diameter made in highly expansive clay. The expansive clay was compacted in a steel box (50 cm × 50 cm × 35 cm) to a final height of 20 cm. Steel plates (25 cm × 25 cm × 1 cm) were used to model footings. The heads of the model micropiles were fastened to the steel plate. Footings with zero, one, two or four micropiles were prepared then the compacted clay in the laboratory box was flooded with water then upward movement of the model footings due to compacted clay swelling was monitored with time. The results showed that the percentage reduction in heave due to micropile reinforcement was larger for roughened micropiles and increased with increasing number and diameter of micropiles. The maximum measured percentage reduction in heave was 87·2% obtained when four 18 mm diameter roughened micropiles were used. A comparison between measured and predicted percentage reduction in heave using the proposed method of Nusier and Alawneh (Geotechnical and Geological Engineering Journal, 2004, 22, No. 1, 89–104) was made, and the results of the comparison showed acceptable agreement.
Ground improvement techniques for railway embankments
Authors: Arulrajah A. , Abdullah A. , Bo M. W. , Bouazza A.
Published: January 2009

A high-speed railway project for trains of speeds of up to 160 km/h is currently being constructed between Rawang and Bidor (110 km long) in Peninsular Malaysia. The ground improvement methods adopted in the project are vibro-replacement with stone columns, dry deep soil mixing (cement columns), geogrid-reinforced piled embankments with individual pile caps and removal/replacement works. This paper provides a detailed insight into the design and implementation of vibro-replacement and the deep soil mixing treatment methods used in the project. The use of plate bearing tests and field instrumentation to monitor the performance of the stone columns and soil mixing ground treatment methods is also discussed. This paper also provides a brief overview of other treatment methods implemented in this high-speed railway project such as a pile embankment with geogrids and removal/replacement works.
Imatinib Mesylate Reduces Endoplasmic Reticulum Stress and Induces Remission of Diabetes indb/dbMice
Authors: Han Myoung Sook , Chung Kun Wook , Cheon Hyae Gyeong , Rhee Sang Dal , Yoon Chang-Hwan , Lee Moon-Kyu , Kim Kwang-Won , Lee Myung-Shik
Published: January 2009

OBJECTIVE—Imatinib has been reported to induce regression of type 2 diabetes in chronic leukemia patients. However, the mechanism of diabetes amelioration by imatinib is unknown, and it is uncertain whether imatinib has effects on type 2 diabetes itself without other confounding diseases like leukemia. We studied the effect of imatinib on diabetes in db/db mice and investigated possible mechanism's underlying improved glycemic control by imatinib.

RESEARCH DESIGN AND METHODS—Glucose tolerance and insulin tolerance tests were done after daily intraperitoneal injection of 25 mg/kg imatinib into db/db and C57BL/6 mice for 4 weeks. Insulin signaling and endoplasmic reticulum stress responses were studied by Western blotting. β-Cell mass and apoptotic β-cell number were determined by combined terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) staining and insulin immunohistochemistry. The in vitro effect of imatinib was studied using HepG2 cells.

RESULTS—Imatinib induced remission of diabetes in db/db mice and amelioration of insulin resistance. Expression of endoplasmic reticulum stress markers in the liver and adipose tissues of db/db mice, such as phospho-PERK, phospho-eIF2α, TRB3, CHOP, and phospho–c-Jun NH2-terminal kinase, was reduced by imatinib. Insulin receptor substrate-1 tyrosine phosphorylation and Akt phosphorylation after insulin administration were improved by imatinib. Serum aminotransferase levels and hepatic triglyceride contents were decreased by imatinib. Pancreatic β-cell mass was increased by imatinib, accompanied by decreased TUNEL+ β-cell and increased BrdU+ β-cell numbers. Imatinib attenuated endoplasmic reticulum stress in hepatoma cells in vitro.

CONCLUSIONS—Imatinib ameliorated endoplasmic reticulum stress and induced remission of diabetes in db/db mice. Imatinib or related compounds could be used as therapeutic agents against type 2 diabetes and metabolic syndrome.
Relationship Between Baseline Glycemic Control and Cognitive Function in Individuals With Type 2 Diabetes and Other Cardiovascular Risk Factors
Authors: Cukierman-Yaffe Tali , Gerstein Hertzel C. , Williamson Jeff D. , Lazar Ronald M. , Lovato Laura , Miller Michael E. , Coker Laura H. , Murray Anne , Sullivan Mark D. , Marcovina Santica M. , Launer Lenore J. ,   for the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Investigators
Published: January 2009

OBJECTIVE—Diabetes is associated with cognitive decline and dementia. However, the relationship between the degree of hyperglycemia and cognitive status remains unclear. This was explored using baseline cognitive measures collected in the ongoing Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

RESEARCH DESIGN AND METHODS—The relationship of A1C and fasting plasma glucose (FPG) levels to performance on four cognitive tests was assessed, adjusting for age and other determinants of cognitive status. The tests were the Digit Symbol Substitution Test (DSST), Mini Mental Status Examination (MMSE), Rey Auditory Verbal Learning Test, and Stroop Test.

RESULTS—A statistically significant age-adjusted association was observed between the A1C level and the score on all four cognitive tests. Specifically, a 1% higher A1C value was associated with a significant 1.75-point lower DSST score (95% CI −1.22 to −2.28; P < 0.0001), a 0.20-point lower MMSE score (−0.11 to −0.28; P < 0.0001), a 0.11-point lower memory score (−0.02 to −0.19, P = 0.0142), and a worse score (i.e., 0.75 s more) on the Stroop Test (1.31–0.19, P = 0.0094). The association between the DSST score and A1C persisted in all multiple linear regression models. FPG was not associated with test performance.

CONCLUSIONS—Higher A1C levels are associated with lower cognitive function in individuals with diabetes. The effect of glucose lowering on cognitive function will be determined by the ongoing ACCORD-MIND trial.
Age Changes in Subjective Work Ability
Authors: Solem Per Erik
Published: January 2009

This article explores the influence of psychosocial work environment on age-related subjective changes in work ability and discusses differences between work ability and job performance. The results show age and physical health to be strong predictors of subjective decline in work ability. The age effect is independent of age-associated declining health. It is not clear what it is about age that produces the subjective decline in work ability. While primary age changes may produce decline, stereotypes and self-stereotypes about ageing may also be important. Among psychosocial factors, options for learning and problems at work are robust predictors of subjective changes in work ability. One practical consequence is to ensure learning opportunities for workers, even for workers approaching retirement age. By giving learning opportunities to senior workers, subjective work ability may be maintained, and competence acquired through learning may in a direct way support stability or improvements in job performance.
Strategy for Adapting Wine Yeasts for Bioethanol Production
Authors: Ooi Beng Guat , Lankford Kevin  R.
Published: January 2009

The Saccharomyces cerevisiae wine yeast strains 71B-1122 and K1-V1116 were used to derive strains that could tolerate and produce higher ethanol yields. Respiratory-deficient mutants resistant to 500 mg/mL lycorine were isolated. Two mutants, 71B-1122 YEBr L3 and K1-V1116 YEBr L4, were shown to achieve about 10% and 18% improvement in their glucose-to-ethanol conversion efficiency compared to their respective parent strains. The K1-V1116 YEBr L4 in particular can tolerate an ethanol yield of 18.8 ± 0.8% at 3.5 weeks of fermentation and continued to consume most of the sugar until less than 1% glucose was left.
Fluorimetric Nerve Gas Sensing Based on Pyrene Imines Incorporated into Films and Sub‐Micrometer Fibers
Authors: Rathfon Jeremy M. , AL‐Badri Zoha M. , Shunmugam Raja , Berry Scott M. , Pabba Santosh , Keynton Robert S. , Cohn Robert W. , Tew Gregory N.
Published: January 2009

The chemical sensing of nerve gas agents has become an increasingly important goal due to the 1995 terrorist attack in a Tokyo subway as well as national security concerns in regard to world affairs. Chemical detection needs to be sensitive and selective while being facile, portable, and timely. In this paper, a sensing approach using a pyrene imine molecule is presented that is fluorimetric in response. The detection of a chloro‐Sarin surrogate is measured at 5 ppmv in less than 1 second and is highly selective towards halogenated organophosphates. The pyrene imine molecule is incorporated into polystyrene films as well as micrometer and sub‐micrometer fibers. Using both a direct drawing approach and electrospinning, micrometer and nanofibers can be easily manufactured. Applications for functional sensing micrometer and nanofibers are envisioned for optical devices and photonics in addition to solution and airflow sensing devices.
Upper ‐extremity musculoskeletal symptoms and physical health related quality of life among women employed in poultry processing and other low ‐wage jobs in Northeastern North Carolina
Authors: McPhee C.S. , Lipscomb H.J.
Published: January 2009

Background

The purpose of this study was to evaluate the association between upper ‐extremity musculoskeletal symptoms (MS ) and diminished physical health related quality of life (PHRQoL ) in a population of women, mostly African ‐American working in poultry processing and other low ‐wage jobs in rural northeastern North Carolina.

Methods

A cross ‐sectional analysis was performed on baseline data of self ‐reported PHRQoL and musculoskeletal symptoms for 291 poultry processing workers and 299 community comparison women. Logarithmic binomial regression was performed to assess the relationship between moderate to severe MS on low PHRQoL.

Results

Prevalence of poor PHRQoL was 35.5 % among poultry processing workers, and 14.7 % among community comparison group. Moderate to severe upper ‐extremity musculoskeletal symptoms were present in 34.4 % of the poultry workers and 10.7 % of the comparison group. After adjusting for age and other chronic conditions, moderate to severe musculoskeletal symptoms were associated with low PHRQoL in both groups. Although the observed effect was stronger among the comparison group (adjusted prevalence ratios (95 % confidence interval ): poultry workers   =  1.89 (1.36, 2.64 ), community comparison   =  4.26 (2.51, 7.24 ), the population attributable risk percent was similar (poultry workers   =  28.9, community comparison   =  31.3 % ) ) due to the higher prevalence of moderate to severe symptoms in the poultry workers.

Conclusions

Significant upper‐extremity musculoskeletal symptoms were associated with poor PHRQoL among both groups of women employed in low ‐wage jobs. Nationwide, poultry work is over ‐represented by minorities and immigrants. Though challenging, we need to search for ways to improve the conditions of these women as a matter of social justice. Am. J. Ind. Med. 52:331–340, 2009. © 2009 Wiley‐Liss, Inc.
Synthesis of Pure Phosphorus Nanostructures
Authors: Winchester Richard A. L. , Whitby Max , Shaffer Milo S. P.
Published: January 2009

Mit oder ohne Katalysator: Die Synthese von Phosphornanostäben mit zwei unterschiedlichen Morphologien – mit oder ohne Bismutkatalysator – wird vorgestellt. Diese Materialien repräsentieren nicht nur eine neue Klasse elementarer Nanostäbe, sondern eröffnen auch Einblicke in die komplexe Allotropie des Phosphors.

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Synthesis of Pure Phosphorus Nanostructures
Authors: Winchester Richard A. L. , Whitby Max , Shaffer Milo S. P.
Published: January 2009

To Bi or not to Bi? The synthesis of phosphorus nanorods of two differing morphologies is reported, in both the presence and absence of a bismuth catalyst. Not only do these materials represent a new class of elemental nanorods but they also give valuable insight into the complex allotropy of phosphorus.

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Iridium‐Catalyzed Reactions of Trifluoromethylated Compounds with Alkenes: A CH Bond Activation α to the Trifluoromethyl Group
Authors: Guo Yong , Zhao Xiaming , Zhang Dazhi , Murahashi Shun‐Ichi
Published: January 2009

Catalytic convenience: The use of iridium or ruthenium catalysts for CH bond activation has led to the addition reaction of trifluoromethylated compounds to alkenes (see scheme). This atom‐economical reaction occurs under neutral reaction conditions and without the formation of undesired defluorinated by‐products, even at high temperature.

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Improved function from progressive strengthening interventions after total knee arthroplasty: A randomized clinical trial with an imbedded prospective cohort
Authors: Petterson Stephanie C. , Mizner Ryan L. , Stevens Jennifer E. , Raisis Leo , Bodenstab Alex , Newcomb William , Snyder‐Mackler Lynn
Published: January 2009

Objective

To determine the effectiveness of progressive quadriceps strengthening with or without neuromuscular electrical stimulation (NMES) on quadriceps strength, activation, and functional recovery after total knee arthroplasty (TKA), and to compare progressive strengthening with conventional rehabilitation.

Methods

A randomized controlled trial was conducted between July 2000 and November 2005 in an academic outpatient physical therapy clinic. Two hundred patients who had undergone primary, unilateral TKA for knee osteoarthritis were randomized to 1 of 2 interventions 4 weeks after surgery, and 41 patients eligible for enrollment who did not participate in the intervention were tested 12 months after surgery (standard of care group). All randomized patients received 6 weeks of outpatient physical therapy 2 or 3 times per week through 1 of 2 intervention protocols: an exercise group (volitional strength training) or an exercise‐NMES group (volitional strength training and NMES). Treatment effects were evaluated by a burst superimposition test to assess quadriceps strength and volitional activation 3 and 12 months postoperatively. The Medical Outcomes Study Short Form 36 and Knee Outcome Survey were completed. Knee range of motion, Timed Up and Go, Stair‐Climbing Test, and 6‐Minute Walk were also measured.

Results

Strength, activation, and function were similar between the exercise and exercise‐NMES groups at 3 and 12 months. The standard of care group was weaker and exhibited worse function at 12 months compared with both treatment groups.

Conclusion

Progressive quadriceps strengthening with or without NMES enhances clinical improvement after TKA, achieving similar short‐ and long‐term functional recovery and approaching the functional level of healthy older adults. Conventional rehabilitation does not yield similar outcomes.
Health‐related quality of life for patients with vasculitis and their spouses
Authors: Carpenter Delesha M. , Thorpe Carolyn T. , Lewis Megan , Devellis Robert F. , Hogan Susan L.
Published: January 2009

Objective

Chronic disease affects both patients and spouses, yet the effect of vasculitis on the spouses of patients has not been systematically examined. We addressed this research gap by describing 8 dimensions of health‐related quality of life (HRQOL) for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) patients and their spouses and compared patients and spouses with norms for the general US population. We also determined whether the impact of AAV on HRQOL differs by sex for patients or their spouses.

Methods

Ninety‐seven patients with AAV and their spouses completed a mailed questionnaire that included demographic information and a measure of HRQOL (Medical Outcomes Study Short Form 36.) Using the RAND method, we calculated 8 HRQOL dimensions: general health, physical functioning, emotional role limitations, physical role limitations, social functioning, mental health, bodily pain, and energy/vitality. Using norm‐based scores, we compared the HRQOL of patients and spouses with the general US population. We then used multivariate analysis of covariance (MANCOVA) test for sex differences in HRQOL for patients and spouses.

Results

Patients with AAV scored lower than the US norm on all HRQOL subscales with the exception of bodily pain. In contrast, spouses scored similarly to national norms. When age, education, race, illness duration, and disease severity were controlled, there were no significant sex differences in HRQOL for patients or spouses.

Conclusion

AAV negatively impacts HRQOL for patients; whereas, spouses do not appear to be as negatively impacted. Long‐term marriages may attenuate the effect of sex on HRQOL. Quality of life should be assessed throughout the disease course for both patients and spouses.
Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt‐induced signaling protein 1
Authors: Blom Arjen B. , Brockbank Sarah M. , van Lent Peter L. , van Beuningen Henk M. , Geurts Jeroen , Takahashi Nozomi , van der Kraan Peter M. , van de Loo Fons A. , Schreurs B. Wim , Clements Kristen , Newham Peter , van den Berg Wim B.
Published: January 2009

Objective

Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA.

Methods

Longitudinal expression analysis was performed in 2 models of OA. Levels of messenger RNA for genes from the Wnt/β‐catenin pathway were determined in synovium and cartilage, and the results were validated using immunohistochemistry. Effects of selected genes were assessed in vitro using recombinant protein, and in vivo by adenoviral overexpression.

Results

Wnt‐induced signaling protein 1 (WISP‐1) expression was strongly increased in the synovium and cartilage of mice with experimental OA. Wnt‐16 and Wnt‐2B were also markedly up‐regulated during the course of disease. Interestingly, increased WISP‐1 expression was also found in human OA cartilage and synovium. Stimulation of macrophages and chondrocytes with recombinant WISP‐1 resulted in interleukin‐1–independent induction of several matrix metalloproteinases (MMPs) and aggrecanase. Adenoviral overexpression of WISP‐1 in murine knee joints induced MMP and aggrecanase expression and resulted in cartilage damage.

Conclusion

This study included a comprehensive characterization of Wnt and Frizzled gene expression in experimental and human OA articular joint tissue. The data demonstrate, for the first time, that WISP‐1 expression is a feature of experimental and human OA and that WISP‐1 regulates chondrocyte and macrophage MMP and aggrecanase expression and is capable of inducing articular cartilage damage in models of OA.
Long‐term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two‐year, randomized, double‐blind, placebo‐controlled trial
Authors: Kahan André , Uebelhart Daniel , De Vathaire Florent , Delmas Pierre D. , Reginster Jean‐Yves
Published: January 2009

Objective

To assess the long‐term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA).

Methods

We performed an international, randomized, double‐blind, placebo‐controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years.

Results

The intent‐to‐treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean ± SEM −0.07 ± 0.03 mm) as compared with the placebo group (−0.31 ± 0.04 mm). The percentage of patients with radiographic progression ≥0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16–46%]). The number of patients needed to treat was 8 (95% confidence interval 5–17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups.

Conclusion

The long‐term combined structure‐modifying and symptom‐modifying effects of CS suggest that it could be a disease‐modifying agent in patients with knee OA.
Prostaglandin E2and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis
Authors: Li Xin , Ellman Michael , Muddasani Prasuna , Wang James H.‐C. , Cs‐Szabo Gabriella , van Wijnen Andre J. , Im Hee‐Jeong
Published: January 2009

Objective

To elucidate the pathophysiologic links between prostaglandin E2(PGE2) and osteoarthritis (OA) by characterizing the catabolic effects of PGE2and its unique receptors in human adult articular chondrocytes.

Methods

Human adult articular chondrocytes were cultured in monolayer or alginate beads with and without PGE2and/or agonists of EP receptors, antagonists of EP receptors, and cytokines. Cell survival, proliferation, and total proteoglycan synthesis and accumulation were measured in alginate beads. Chondrocyte‐related gene expression and phosphatidylinositol 3‐kinase/Akt signaling were assessed by real‐time reverse transcription–polymerase chain reaction and Western blotting, respectively, using a monolayer cell culture model.

Results

Stimulation of human articular chondrocytes with PGE2through the EP2 receptor suppressed proteoglycan accumulation and synthesis, suppressed aggrecan gene expression, did not appreciably affect expression of matrix‐degrading enzymes, and decreased the type II collagen:type I collagen ratio. EP2 and EP4 receptors were expressed at higher levels in knee cartilage than in ankle cartilage and in a grade‐dependent manner. PGE2titration combined with interleukin‐1 (IL‐1) synergistically accelerated expression of pain‐associated molecules such as inducible nitric oxide synthase and IL‐6. Finally, stimulation with exogenous PGE2or an EP2 receptor–specific agonist inhibited activation of Akt that was induced by insulin‐like growth factor 1.

Conclusion

PGE2exerts an antianabolic effect on human adult articular cartilage in vitro, and EP2 and EP4 receptor antagonists may represent effective therapeutic agents for the treatment of OA.
In vitro stage‐specific chondrogenesis of mesenchymal stem cells committed to chondrocytes
Authors: Chen Wei‐Hong , Lai Ming‐Tang , Wu Alexander T. H. , Wu Chia‐Che , Gelovani Juri G. , Lin Che‐Tong , Hung Shih‐Chieh , Chiu Wen‐Ta , Deng Win‐Ping
Published: January 2009

Objective

Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)–based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration.

Methods

A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp‐hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage‐forming ability.

Results

Coculture of hPi‐GFP chondrocytes with Kp‐hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor β superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin‐like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp‐hMSCs acquired neocartilage‐forming potential within the collagen scaffold.

Conclusion

These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell‐based transplantation for future clinical use.
Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: Impact of interstitial lung disease
Authors: Mathai Stephen C. , Hummers Laura K. , Champion Hunter C. , Wigley Fredrick M. , Zaiman Ari , Hassoun Paul M. , Girgis Reda E.
Published: January 2009

Objective

Pulmonary hypertension (PH) is an important cause of mortality in systemic sclerosis (SSc), where it can be isolated (pulmonary arterial hypertension [PAH]) or associated with interstitial lung disease (ILD). This study was undertaken to characterize determinants of survival among SSc patients with either type of PH who received PAH‐specific therapy.

Methods

Consecutive SSc patients with PAH or ILD‐associated PH confirmed by right heart catheterization were included in the study. Kaplan‐Meier and Cox proportional hazards models were used to compare survival between SSc patients with PAH and those with ILD‐associated PH and to identify predictors of survival.

Results

Fifty‐nine patients (39 with PAH and 20 with ILD‐associated PH) were identified. The majority (15 of 20 with ILD‐associated PH and 27 of 39 with PAH) received an endothelin receptor antagonist as initial therapy. Median followup time was 4.4 years (range 2.7–7.4 years). Survival was significantly worse in SSc patients with ILD‐associated PH than in those with PAH (1‐, 2‐, and 3‐year survival rates 82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank test). In a multivariable analysis, ILD‐associated PH was associated with a 5‐fold increase in risk of death compared with PAH. Pulmonary vascular resistance index was also an independent predictor of mortality in the overall cohort (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in each group separately. Type of initial PAH therapy and the use of warfarin were not related to survival.

Conclusion

Survival in SSc complicated by PH remains poor despite currently available treatment options. While therapy may be associated with improved survival in PAH compared with historical controls, the prognosis for patients with ILD‐associated PH is particularly grim. Early diagnosis and treatment may improve outcomes since worsening hemodynamic factors were associated with reduced survival.
Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis factor receptor–associated periodic syndrome
Authors: Nedjai Belinda , Hitman Graham A. , Quillinan Niamh , Coughlan Robert J. , Church Leigh , McDermott Michael F. , Turner Mark D.
Published: January 2009

Objective

Tumor necrosis factor receptor (TNFR)–associated periodic syndrome (TRAPS) is an autosomal‐dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene. Unlike other autoinflammatory diseases in which anti‐TNF therapy is largely a successful treatment option, therapy with the anti‐TNF drug infliximab is often ineffective in patients with TRAPS. Moreover, in certain cases, infliximab actually triggers severe episodes of inflammation. The aim of this study was to elucidate the mechanisms underlying such a reaction.

Methods

Peripheral blood mononuclear cells (PBMCs) were obtained from patients with TRAPS. Both caspase 3 activity and NF‐κB subunit activity were determined by enzyme‐linked immunosorbent assay. Cytokine secretion was assessed using a specific customized human multiplex bead immunoassay kit.

Results

Unlike findings in controls, cells from a family of 9 patients, all of whom carried the T50M mutation in TNFRSF1A, failed to respond to infliximab through proapoptotic induction of caspase 3 activity. Instead, we observed enhanced antiapoptotic c‐Rel subunit activity, accompanied by a significant increase in secretion of the proinflammatory cytokines interleukin‐ 1β (IL‐1β), IL‐1 receptor, IL‐6, IL‐8, and IL‐12.

Conclusion

Altered extracellular conformation of TNFRI, resulting from the T50M mutation in TNFRSF1A, results in failure of PBMCs to induce an apoptotic response to infliximab. We hypothesize that failure to shed infliximab‐bound TNF/TNFRI from the cell surface of cells from patients with the T50M mutation triggers c‐Rel activation, and that this leads to a marked increase in cytokine secretion and an increased proinflammatory response. In light of these findings, we strongly advise caution when prescribing infliximab as anti‐TNF therapy to patients with TRAPS.
Prognostic factors in adults with knee pain in general practice
Authors: Belo J. N. , Berger M. Y. , Koes B. W. , Bierma‐Zeinstra S. M. A.
Published: January 2009

Objective

To predict the 1‐year outcome of incident nontraumatic knee symptoms in adults presenting in general practice.

Methods

Adults age >35 years with nontraumatic knee symptoms (n = 480) were followed for 1 year. At baseline, data on knee symptoms and demographics were collected and a physical examination performed. Knee symptoms were assessed by self‐report questionnaires at 3‐month intervals. After 1 year the physical examination was repeated. Multivariate prognostic regression models of patient characteristics, symptom characteristics, and physical examination were used to predict persisting knee symptoms after 1 year. Areas under receiving operating characteristic curves (AUCs) were used to determine the predictive value of the model. To assess the added predictive value of symptom characteristics and physical examination, these models were added to the model of patient characteristics. The improvement was expressed as the difference between the 2 AUCs.

Results

In the multivariate prognostic model of patient characteristics, age >60 years, educational level, kinesophobia, and comorbidity of the skeletal system were associated with persistent knee symptoms after 1 year (AUC 0.67). Of the symptom characteristics, history of nontraumatic knee symptoms, bilateral symptoms, and duration of symptoms >3 months were associated (AUC 0.73). For determinants of physical examination, crepitus of passive extension was associated (AUC 0.55). The added value of the symptom characteristics model to the patient characteristics model was 0.09 (AUC 0.76). Physical examination added no further value.

Conclusion

Symptom characteristics are the strongest predictors of persisting knee symptoms at 1‐year followup. Physical examination has no added value in predicting persistent knee symptoms in general practice.
Conformational requirement on peptides to exert laminin's activities and search for protein segments with laminin's activities
Authors: Umezawa Koji , Ikebe Jinzen , Nomizu Motoyoshi , Nakamura Haruki , Higo Junichi
Published: January 2009

The human laminin α3 chain LG4 module has biological activities of cell adhesion, heparin binding, migration, and neurite outgrowth. The authors had previously identified that the active site of this protein is in residues 1411–1429 (amino‐acid sequence = KNSFMALYLSKGRLVFALG called A3G756) and that a three‐amino‐acid sequence KGR in A3G756 is crucial for exerting the activities. An experiment has shown that a cyclo‐hEF3A peptide (a cyclic analog of A3G756) exhibits stronger activities than a linear‐hEF3A peptide (a linearized peptide of the cyclo‐hEF3A peptide). This experiment implies that adopting a loop conformation may be important for exerting the activities. In this study, the authors first computed the solution structures of the cyclo‐hEF3A and linear‐hEF3A peptides by molecular dynamics simulations. The obtained conformational ensembles consisted of a variety of conformations, which is a usual property of short peptides in solution. The ensembles involved a fraction where the peptide adopted β‐hairpins and KGR was located at the hairpin head. If there are protein segments that adopt β‐hairpins similar to those sampled from the simulation and have the KGR sequence at the hairpin head, these segments may have some activities. Then, the authors searched a database for segments satisfying these requirements and detected six functional segments. Three of them had laminin's activity, and the remaining three had activities similar to laminin's activities. Analyses on the conformational ensembles of cyclo‐ and linear‐hEF3A peptides suggest that not only the KGR position in the hairpin but also the inter‐strand packing is important for exerting laminin's activities. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 124–131, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Compositions of Essential Oils and Trichomes of Teucrium chamaedrys L. subsp. trapezunticumRech. fil. and subsp. syspirense (C. Koch) Rech. fil.
Authors: Kaya Ayla , Demirci Betül , Başer K. Hüsnü C.
Published: January 2009

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Teucrium chamaedrys L. is a member of the Lamiaceae family and is represented in the Flora of Turkey by six subspecies. The aerial organs of T. chamaedrys L. subsp. trapezunticum Rech. fil. and subsp. syspirense (C. Koch) Rech. fil. bears numerous eglandular and glandular trichomes. Eglandular trichomes are simple, long‐multicellular with cuticular micropapillae, and glandular hairs are of peltate and capitate types. The peltate hairs consist of a basal cell, a short unicellular stalk, and multicellular secretory head, and the capitate ones possess 1–2 stalk cells and one glandular head cell. The aerial parts were subjected to microdistillation for the isolation of volatiles. The analysis was simultaneously performed by using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The major components were characterized as β‐caryophyllene (18%), nonacosane (12%), germacrene D (11%), caryophyllene oxide (7%), and α‐pinene (7%) for subsp. trapezunticum, and caryophyllene oxide (23%), α‐pinene (11%), and caryophyllenol II (5%) for subsp. syspirense.
A Simple and ‘Green’ Synthesis of Polymer‐Based Silver Colloids and Their Antibacterial Properties
Authors: Bo Lili , Yang Wu , Chen Miao , Gao Jinzhang , Xue Qunji
Published: January 2009

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Stable silver colloids were prepared using polyethylene glycol (PEG) as an environment friendly reduction agent and stabilizer, and with H2O as solvent. The Ag colloids were characterized by UV/VIS spectroscopy, transmission electron microscopy (TEM), and atom force microscopy (AFM). TEM and AFM of the sample showed uniform and monodispersive particle distribution in the colloids. The particle size is found to be less than 10 nm. The antibacterial activity of the Ag colloids was also studied. The results showed that the sample had high antibacterial activity toward Gram‐positive and Gram‐negative bacteria, and fungi.
Deterministic and Probabilistic Estimation of Appropriate Distances: Motivation for Considering the Consequences for Industrial Sites
Authors: Gawlowski M. , Hailwood M. , Vela I. , Schönbucher A.
Published: January 2009

Accidents and disruptions in chemical process installations can, in principle, lead to the rare events in which the release of flammable and/or toxic substances occurs, and which at particular distances from the installation can result in a hazard potential due to thermal radiation, blast wave effects or the concentration of toxic substances. The possibilities and limits of deterministic and probabilistic estimation methods for appropriate distances from hazardous installations, based on the example of an ammonia release and a large surface fire, are shown. In this, it is demonstrated that the deterministic and probabilistic approaches are in no way conflicting or unnecessary, but rather that they are complementary. The use of a deterministic estimation method leads to a maximum set radius of effects which only take account of the damage impact. Depending on the selection of the appropriate and suitable consequence models, critical distances are calculated which are in some cases much larger than the current standardised distances, as is shown by the example of large‐scale fires. The use of a probabilistic estimation method leads to a range of distances for which the individual risk can be given in addition. In principle, iso‐contours joining points of same risk or areas of same risk may be defined through the use of such estimations.
Protonation of 2H‐Azaphosphirene Complexes: PN Bond Activation and Ring‐Expansion Reactions
Authors: Helten Holger , Engeser Marianne , Gudat Dietrich , Schilling Reinhold , Schnakenburg Gregor , Nieger Martin , Streubel Rainer
Published: January 2009

PN bond activation of 2H‐azaphosphirene complexes 1 and 2 by using triflic acid led to ring expansion in the presence of nitriles. In the absence of nitriles, the reaction surprisingly afforded two haptomeric N‐protonated 1‐aza‐3‐phospha‐butadiene complexes in the case of complex 1, whereas the N‐protonated 2H‐azaphosphirene complex [H‐2]+ was characterized by NMR spectroscopy.

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Protonation of 2H‐azaphosphirene complexes 1 and 2 using trifluoromethanesulfonic acid in the presence and in the absence of nitriles was studied. Reactions with nitrile derivatives of different nucleophilicity and steric demand (3 a–f) led to highly bond‐ and regioselective ring‐expansion reactions of complexes 1 and 2 and yielded 2H‐1,4,2‐diazaphosphole complexes 4 a–f and 5 a after deprotonation with NEt3. Upon protonation of complex 1 in the absence of nitriles a mixture of two haptomeric N‐protonated 1‐aza‐3‐phosphabuta‐1,3‐diene complexes 13 and 14 was obtained, which upon addition of Me2NCN (3 a) and NEt3 afforded 2H‐1,4,2‐diazaphosphole complex 16 a bearing a P‐substituent with only one SiMe3 group. Protonation of complex 2 led to the 2H‐azaphosphirenium complex [H‐2]+, unambiguously identified by NMR spectroscopy at low temperature. All isolated products were characterized by multinuclear NMR spectroscopy, IR, MS, and single‐crystal X‐ray crystallography in the cases of complexes 4 a, 4 e, 6 a, and 16 a. Furthermore, ESI‐MS/MS studies on primarily formed reactive intermediates and DFT studies on the reaction mechanism are presented.
Stereoselective Synthesis of 2,6‐Disubstituted Piperidines Using the Iridium‐Catalyzed Allylic Cyclization as Configurational Switch: Asymmetric Total Synthesis of (+)‐241 D and Related Piperidine Alkaloids
Authors: Gnamm Christian , Krauter Caroline M. , Brödner Kerstin , Helmchen Günter
Published: January 2009

Pressing the configurational switch: Use of enantiomeric Ir catalysts allows the vinylpiperidine building blocks 2 a and 2 b to be synthesized with high selectivity. Total syntheses of the dendrobate alkaloid (+)‐241 D, its C6‐epimer, and a spruce alkaloid are presented as applications.

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ortho‐Selective Phenol‐Coupling Reaction by Anodic Treatment on Boron‐Doped Diamond Electrode Using Fluorinated Alcohols
Authors: Kirste Axel , Nieger Martin , Malkowsky Itamar M. , Stecker Florian , Fischer Andreas , Waldvogel Siegfried R.
Published: January 2009

Enlarged scope by fluorinated mediators: Oxyl radicals are easily formed on boron‐doped diamond (BDD) electrodes and can be exploited for the ortho‐selective coupling to the corresponding biphenols (see scheme). At partial conversion, a clean transformation is achieved that can be applied to electron‐rich as well as fluorinated phenols.

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Helical Hairpin Structure of a Potent Antimicrobial Peptide MSI‐594 in Lipopolysaccharide Micelles by NMR Spectroscopy
Authors: Bhunia Anirban , Ramamoorthy Ayyalusamy , Bhattacharjya Surajit
Published: January 2009

Essential understanding: Elucidation of structural requirements and interactions of antimicrobial peptides with lipopolysaccharide (LPS) are essential to understand the mechanism of action of antimicrobial peptides. The highly active antimicrobial peptide MSI‐594 (see figure for electrostatic potential surface) acquires a novel helical hairpin structure in complex with LPS. The structure and interactions of MSI‐594 with LPS presented here provide important insights into the mechanism of outer membrane permeabilization by antimicrobial peptides.

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Dependency and self‐criticism in post‐partum depression and anxiety: a case control study
Authors: Vliegen Nicole , Luyten Patrick
Published: January 2009

This study investigates the role of self‐criticism and dependency in inpatient post‐partum depressed women (n = 55) and non‐depressed controls (n = 37) as well as the relationship between both personality dimensions and severity of depression and anxiety. As expected, mothers with post‐partum depression showed not only increased levels of depression but also anxiety compared with non‐depressed mothers. Furthermore, they had significantly higher levels of self‐criticism, but not of dependency. In the post‐partum depressed mothers, both personality dimensions were positively associated with severity of depression. However, in non‐depressed mothers, self‐criticism was positively associated with depression, while there was an inverse relationship between dependency and severity of depression. In both samples, self‐criticism, but not dependency, was related to state anxiety. The cross‐sectional nature of this study limits the ability to draw causal conclusions. The study was based on self‐report and conducted in relatively small samples. Copyright © 2009 John Wiley & Sons, Ltd.
Adult attachment as mediator between recollections of childhood and satisfaction with life
Authors: Hinnen Chris , Sanderman Robbert , Sprangers Mirjam A. G.
Published: January 2009

In accordance with attachment theory, the present study investigates whether internal working models of attachment mediated the association between childhood memories and satisfaction about life in adulthood. A convenient sample of 437 participants completed questionnaires assessing a broad range of childhood memories, working models of attachment and life satisfaction. After controlling for demographics, relational status and living condition, Baron and Kenny's mediation criteria were met for the association between memories about childhood, adult attachment and life satisfaction. That is, family warmth and harmony and parental support were associated with attachment security while parental rejection and adverse childhood events (e.g., abuse, parental psychopathology) were associated with an insecure attachment style. More securely attached individuals were in turn more satisfied about their current life than insecurely attached individuals. Sobel test confirmed these findings. These finding are in accordance with attachment theory and highlight the importance of this theory for understanding how early childhood experiences may impact adult life. Copyright © 2008 John Wiley & Sons, Ltd.
Proliferation of weakly suppressive regulatory CD4+ T cells is associated with over‐active CD4+ T‐cell responses in HIV‐positive patients with mycobacterial immune restoration disease
Authors: Seddiki Nabila , Sasson Sarah C. , Santner‐Nanan Brigitte , Munier Meeling , van Bockel David , Ip Susanna , Marriott Debbie , Pett Sarah , Nanan Ralph , Cooper David A. , Zaunders John J. , Kelleher Anthony D.
Published: January 2009

The role of Treg in patients with late‐stage HIV disease, who commence combination antiretroviral therapy (cART) and develop pathogen‐specific immunopathology manifesting as immune restoration disease (IRD) remains unclear. We hypothesised that Treg could be defective in either numbers and/or function and therefore unable to ensure the physiological equilibrium of the immune system in patients with IRD. Phenotypic and functional CD4+ T‐cell subsets of eight late‐stage HIV patients with nadir CD4 count <50 cells/μL, who developed mycobacterial IRD upon commencing cART were compared with six therapy naive HIV+ patients (nadir CD4 count <50 cells/μL), who did not develop an IRD after cART. Mycobacterium‐avium‐specific CD4+ T cells from IRD patients produced high levels of IFN‐γ and IL‐2 compared with controls (p<0.001). Surprisingly, we found a significant expansion of CD127loFoxp3+CD25+ Treg in IRD patients and a higher ratio of Treg to effector/memory subsets (p<0.001). In vitro suppression assays demonstrated reduced functional capacity of suppressor cells and diminished IL‐10 secretion in IRD patients. Plasma levels of IL‐7 were increased in patients and, interestingly, exogenous IL‐7 and other cytokines strongly inhibited Treg suppression. These data suggest that despite substantial Treg expansion in IRD, their ability to induce suppression, and thereby downregulate aberrant immune responses, is compromised.
A Study of the Influence of Composition on the Microstructural Properties of ZnO/Al2O3 Mixed Oxides
Authors: Miao Shaojun , d'Alnoncourt Raoul Naumann , Reinecke Thomas , Kasatkin Igor , Behrens Malte , Schlögl Robert , Muhler Martin
Published: January 2009

A series of ZnO/Al2O3 mixed oxide samples with varyingZn/Al ratio is prepared by coprecipitation, ageing, drying, and calcination. Samples are investigated in the state after drying and calcination. The applied methods include X‐ray diffraction, solid‐state 27Al magic‐angle spinning nuclear magnetic resonance spectroscopy, transmission electron microscopy and thermogravimetric experiments coupled with evolved gas analysis. Phases present in the dried precursor samples include hydrozincite, zaccagnaite, and an unknown phase. After calcination zinc oxide and spinel can be found. All results indicate the substitution of Al ions for Zn ions in zinc oxide of zinc‐rich samples. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Low‐Barrier Pathway for endo‐Cleavage Induced Anomerization of Pyranosides with N‐Benzyl‐2,3‐trans‐oxazolidinone Groups
Authors: Satoh Hiroko , Hutter Jürg , Lüthi Hans Peter , Manabe Shino , Ishii Kazuyuki , Ito Yukishige
Published: January 2009

Pyranosides with N‐benzyl‐2,3‐trans‐oxazolidinone undergo anomerization from the β form to the α form even in the presence of a weak Lewis acid. Experimental evidence for endo‐cleavage, the breaking of the bond between the pyran‐oxygen and anomeric carbon atoms, in the anomerization reactions was obtained. This unexpected phenomenon was investigated by quantum mechanical calculations, which found clear differences in the transition states between anomerized and non‐anomerized substrates. The computations suggest that BF3 induces endo‐cleavage followed by rotation of the C1–C2 bond to give the α form via lower‐energy transition states. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)