bluuebunny/crossref_metadata_2025 huggingface dataset:
Ice velocity from static GPS observations along the transect from Zhongshan station to Dome A, East Antarctica
Authors: Shengkai Zhang , Dongchen E , Zemin Wang , Yuansheng Li , Bo Jin , Chunxia Zhou
Published: June 2008

Dome A, the highest point on the Antarctic ice sheet at just over 4000 ma.s.l., is located near the centre of East Antarctica. Chinese National Antarctic Research Expeditions have studied ice-sheet dynamics and mass balance along a traverse route from Zhongshan station to Dome A during the austral summers from 1996/97 to 2004/05. Nineteen GPS sites were occupied on at least two occasions at approximately 50 km intervals. The purpose of the surveys was to provide accurate ice-dynamics data. A dual-frequency GPS receiver was used and each site was occupied for 1–12 hours. GPS data were processed using GAMIT/GLOBK software, and horizontal accuracies were within 0.1 m. Repeat GPS measurements provided ice velocities. The horizontal surface ice velocities increase from the summit of the ice sheet to the coast. In the Dome A area, the velocities are <10ma–1; in the plateau area, velocities range from 8 to 24 ma–1 and reach about 98.2 ma–1 at a site (LT980) near the coast. The flow directions are roughly perpendicular to the ice-sheet surface elevation contours, primarily toward the Lambert Glacier basin.
Climatic warming, glacier recession and runoff from Alpine basins after the Little Ice Age maximum
Authors: Collins David N.
Published: June 2008

Records of discharge of rivers draining Alpine basins with between 0 and ~70% ice cover, in the upper Aare and Rhône catchments, Switzerland, for the period 1894–2006 have been examined together with climatic data for 1866–2006, with a view to assessing the effects on runoff from glacierized basins of climatic warming coupled with glacier recession following the Little Ice Age maximum. Annual runoff from ice-free basins reflects precipitation variations, rising from minima between 1880 and 1910 to maxima between the late 1960s and early 1980s. The more highly glacierized the basin, the more runoff mimicked mean May–September air temperature during two periods of warming. Runoff increased gradually from the 1900s, rapidly in the 1940s, before decreasing to the late 1970s. Rising runoff levels during the second warming period failed to exceed those attained during the first, despite higher summer temperatures. Although temperatures continued to rise, discharge from glacierized basins declined after reaching maxima in the late 1980s to early 1990s. In the first warming period, rising specific melt rates augmented by increasing precipitation opposed the impact of declining glacier area on runoff. Although melt continued to increase in the second period, enhanced melting (even in the exceptionally warm summer of 2003) appears to have been insufficient to offset reducing glacier surface area exposed to melt, low or reducing levels of precipitation, and increasing evaporation. Thus runoff from glacierized basins peaked in the late 1940s to early 1950s.
Explicit iterative computation of diffusive vapour field in the 3-D snow matrix: preliminary results for low flux metamorphism
Authors: Brzoska Jean-Bruno , Flin Frédéric , Barckicke Jean
Published: June 2008

The metamorphism of seasonal snow is classically considered as limited by vapour diffusion in the pore phase. To account for the lack of knowledge of the ice–vapour reaction coefficient near 0°C, the assumption of a reaction-limited metamorphism was first tested in three-dimensional simulations at low and very low temperature gradients; however, the validity of such results is difficult to verify experimentally. By a reasoned use of traditional iterative schemes, vapour diffusion is now simulated in three dimensions on tomographic snow data, mapping the gradient of vapour pressure near the grains. Repeating this process may provide a way to simulate the isothermal metamorphism without grain packing at a reasonable expense of computation time. Preliminary results are compared with existing computations made within the reaction-limited hypothesis.
From Commission to Association: the transition of the International Commission on Snow and Ice (ICSI) to the International Association of Cryospheric Sciences (IACS)
Authors: Jones H. Gerald
Published: June 2008

The transition of the International Commission on Snow and Ice (ICSI) of the International Association of Hydrological Sciences (IAHS) to become the International Association of Cryospheric Sciences (IACS) within the International Union of Geodesy and Geophysics (IUGG) is described. IACS was accepted as the eighth Association of IUGG in 2007 and is the first new Association of the Union to be formed in over 80 years. Particular attention is paid to the reasons that prior to 1999 led to the request by the Commission to the Union for a change in status, and to the steps taken during the period 1999–2007 by the ICSI Bureaux and IUGG, that preceded the acquisition of Association status.
Incremental Entropy Relation as an Alternative to MaxEnt
Authors: Plastino Angelo , Plastino Angel R. , Curado Evaldo M. F. , Casas Montse
Published: June 2008

We show that, to generate the statistical operator appropriate for a given system, and as an alternative to Jaynes’ MaxEnt approach, that refers to the entropy S, one can use instead the increments ±S in S. To such an effect, one uses the macroscopic thermodynamic relation that links ±S to changes in i) the internal energy E and ii) the remaining M relevant extensive quantities Ai, i = 1; : : : ;M; that characterize the context one is working with.
AN ASSESSMENT OF CLIENTS’ PERFORMANCE IN HAVING AN EFFICIENT BUILDING PROCESS IN UGANDA/UŽSAKOVO DALYVAVIMO EFEKTYVIAME STATYBOS PROCESE ĮVERTINIMAS UGANDOJE
Authors: Alinaitwe Henry Mwanaki
Published: June 2008

Over the years researchers have paid little attention to the performance of the clients in the building industry. Much of the research on improvement of performance of the construction industry has mainly focused on contractors and the supply chain. The performance of a client is important because any decision made will affect project success. Failure on the part of the client might lead to stress factors causing significant problems in successive stages of the project. This research is an investigation into the roles of the client to find out whether clients in the building industry in Uganda are playing their part. Due to the non‐specific nature of clients, a guided questionnaire survey was carried out among architects who normally work with different types of clients. The majority of the building clients in Uganda are individuals followed by limited liability companies. It was found out that delay by clients in paying the contractors is a major factor affecting the performance of contractors. Almost all clients do not support training of the workers in its different forms. Construction works start before the designs are completed and the majority of the variations is due to incomplete briefs and designs. Many clients or their representatives do not attend meetings as regularly as would have been necessary. This study reveals information that will help clients in their future projects for ensuring successful building project implementation. Santrauka Daug metų mokslininkai mažai kreipė dėmesio į užsakovų dalyvavimą statybos pramonėje. Dauguma atliktų mokslinių tyrimų, susijusių su statybos pramonės darbų kokybės gerinimu, yra orientuoti į rangovus ir tiekimo grandinę. Užsakovo dalyvavimas yra svarbus todėl, kad kiekvienas priimtas sprendimas gali daryti įtaką projekto sėkmei. Užsakovų žlugimas gali sudaryti įtampą, kuri gali kliudyti sėkmingai vykdyti projekto stadijas. Straipsnyje buvo nagrinėjamas užsakovų vaidmuo, norint nustatyti, ar užsakovai Ugandoje aktyviai dalyvauja statybos pramonėje. Buvo atlikta apklausa architektų, kurie dirba su įvairiais užsakovais. Dauguma statybos užsakovų Ugandoje yra ribotos atsakomybės įmonės. Taip pat buvo pastebėta, kad užsakovo delsimas sumokėti rangovams yra vienas iš svarbiausių veiksnių, darančių įtaką rangovų darbui. Beveik visi užsakovai nepritaria darbuotojų kvalifikacijos tobulinimui įvairiais būdais. Dažniausiai statybos darbai yra pradedami dar nebaigus projektavimo darbų ir dauguma nukrypimų yra dėl neparengtos techninės dokumentacijos. Dauguma užsakovų ar jų atstovų nereguliariai dalyvauja svarbiuose susitikimuose. Šis tyrimas pateikia informaciją, kuri padės užsakovams ateities projektuose ir užtikrins sėkmingą statybos projektų vykdymą.
UTILIZING DATA MINING TO DISCOVER KNOWLEDGE IN CONSTRUCTION ENTERPRISE PERFORMANCE RECORDS/UTILIZUOTAS DUOMENŲ KAUPIMAS
Authors: Lee Jen-Rong , Hsueh Sung-Lin , Tseng Hung-Ping
Published: June 2008

Although Data Mining (DM) has been applied extensively in information systems and identified as a crucial tool for automatic data analysis and enterprise knowledge inference, still the practicability of DM has been little explored in the construction industry in particular. This study is conducted using data from actual practice in the customer service department of the target enterprise. Starting with data preparation, decision tree analysis and domain knowledge inference, practical verification is performed and previously unknown knowledge is discovered. Two practical barriers to enterprise information mining are found: the separation of information among various information systems and lack of key information attributes. Hence, there is a significant limitation on practical information data mining to generate new information, and only with a proper information integration one can benefit from the potential practical application of DM. Santrauka Nors duomenų ryšys buvo plačiai taikomas informacinėse sistemose ir apibrėžiamas kaip pagrindinė priemonė duomenims automatiškai analizuoti ir įmonės žinioms pateikti, tačiau praktinis jo taikymas statybos pramonėje buvo mažai nagrinėtas. Šis tyrimas atliktas naudojantis praktine informacija, surinkta Tikslinių įmonės vartotojų paslaugų departamente. Pradedant duomenų rengimu, sprendimo medžio analize ir įmonės žinių pateikimu, yra atliekamas praktinis tikrinimas ir identifikuojamos prieš tai nenustatytos žinios. Atrasti du praktiniai duomenų ryšio kliuviniai: skirtingų informacijos sistemų informacijos atskyrimas ir pagrindinių informacijos atributų trūkumas. Tai yra didelis praktinės informacijos duomenų ryšio apribojimas, trukdantis naujai informacijai kurti. Tik tinkamai integruojant informaciją, galima pasiekti naudos iš praktinio duomenų ryšio taikymo.
SELECTION OF THE EFFECTIVE DWELLING HOUSE WALLS BY APPLYING ATTRIBUTES VALUES DETERMINED AT INTERVALS
Authors: Zavadskas Edmundas Kazimieras , Kaklauskas Artūras , Turskis Zenonas , Tamošaitienė Jolanta
Published: June 2008

The higher life quality standards, the changes of habits and new well‐being requirements have led to an increase in the demand for housing. Decision‐making problems in construction management often involve a complex decision‐making process in which multiple requirements and conditions have to be taken into consideration simultaneously. However, not every attribute used in multidimensional scaling is equally and precisely weighted in the real world. Thus quantitative and qualitative assessments are often required to deal with uncertainty, subjective and imprecise data. The accuracy of performance measures in common multi-attribute methods is usually assumed to be accurate. Grey theory is a new technique for performing prediction, relational analysis and decision‐making in many areas. This paper considers the application of grey relations methodology for defining the utility of an alternative and is proposed as a method of multiple criteria COmplex PRoportional Assessment of alternatives with Grey relations (COPRAS‐G). In this model parameters of the alternatives are determined by the grey relational grade and are expressed in intervals. A case study of assessing external walls of four alternatives was used to demonstrate the applicability and the effectiveness of the proposed approach. The results show that this method can be implemented as an effective decision aid in multi‐attribute selection. Santrauka Straipsnio tikslas – pasiūlyti alternatyvią daugelio rodiklių vertinimo metodiką. Šios metodikos išskirtinumas – rodiklių reikšmės, aprašomos intervalais. Tai labiau atitinka realias aplinkos sąlygas ir galimas reikšmes. Modelis su intervaluose pateiktomis efektyvumo rodiklių reikšmėmis pritaikytas E. K. Zavadsko ir A. Kaklausko sukurtam metodui COPRAS (Complex Proportional Evaluation). Taip gautas naujas metodas COPRAS-G. Šis metodas pritaikytas daugiabučių namų išorinių sienų efektyvumo vertinimo uždaviniui spręsti. Sudaryta efektyvumo rodiklių sistema, nustatyta efektyvumo rodiklių reikšmė, rodiklių rangas. Pagal sudarytą modelį pritaikę COPRAS-G metodą, galime spręsti daugelį statybos, vadybos alternatyvų vertinimo uždavinių.
EFFECT OF BASIC MOTIVATIONAL FACTORS ON CONSTRUCTION WORKFORCE PRODUCTIVITY IN TURKEY/PAGRINDINIŲ MOTYVACIJOS VEIKSNIŲ ĮTAKA STATYBOS PRODUKTYVUMUI TURKIJOJE
Authors: Kazaz Aynur , Manisali Ekrem , Ulubeyli Serdar
Published: June 2008

Human resource today has a strategic role for productivity increase of any organization, and this makes it superior in the industrial competition. With the effective and optimum usage of it, all the advantages supplied by the productivity growth can be obtained. This usage is just possible by establishing clear and understandable criteria for the factors affecting labour. Therefore, it is aimed in this study that the factors influencing construction labour productivity in Turkey are determined, defined, and examined in detail. A survey was applied to 82 firms to obtain required data. According to results, the most effective factors group is organizational factors. Santrauka Šiuo metu vienas iš svarbiausių veiksnių, lemiančių bet kokios įmonės produktyvumo augimą ir konkurencingumą rinkoje, yra žmonių ištekliai. Produktyvumo augimas gali būti pasiektas tik efektyviai ir optimaliai naudojant šiuos išteklius. Efektyviai naudoti žmonių išteklius įmanoma nusistatant aiškius ir suprantamus kriterijus veiksniams, darantiems įtaką darbui. Šio tyrimo tikslas yra nusistatyti, apibūdinti ir išsamiai išanalizuoti veiksnius, veikiančius statybos darbo produktyvumą. Norint surinkti reikiamą informaciją, buvo ištirtos 82 įmonės. Remiantis gautais rezultatais, buvo prieita prie išvados, kad efektyviausia veiksnių grupė yra organizaciniai veiksniai.
FLEXURAL BEHAVIOUR OF CONCRETE‐FILLED STEEL HOLLOW SECTIONS BEAMS
Authors: Soundararajan Arivalagan , Shanmugasundaram Kandasamy
Published: June 2008

This paper presents an experimental study of normal mix, fly ash, quarry waste and low strength concrete (brick‐bat lime concrete) contribution to the ultimate moment capacity of square steel hollow sections. Fifteen simply supported beam specimens of 1200‐mm long steel hollow sections filled with normal mix, fly ash, quarry waste and low‐strength concrete and identical dimensions of hollow sections were experimented. Extensive measurements of such material properties, strain and deflection were carried out. Theoretical studies of ultimate moment capacity of a beam specimen were also calculated in this study for comparison's sake. These experimental investigation results showed that normal mix, fly ash, quarry waste and low‐strength concrete enhance the moment carrying capacity of steel hollow sections. Furthermore, in these studies it can be found that normal mix, fly ash and quarry waste concrete can be used in composite construction to increase the flexural capacity of steel hollow sections. Santrauka Pateikiamas normalaus, lakiųjų pelenų, akmenų skaldymo atliekų ir mažo stiprumo (skaldytųjų plytų kalkinio) betonų įtakos kvadratinio skerspjūvio plieninių vamzdžių ribinei lenkiamajai galiai eksperimentinis tyrimas. Išbandyta penkiolika dviatramių sijų bandinių iš 1 200 mm ilgio plieninių tuščiavidurių profiliuočių, pripildytų normalaus, lakiųjų pelenų, akmenų skaldymo atliekų ir mažo stiprumo betonų ir identiškų matmenų tuščiavidurių profiliuočių. Atlikti didelės apimties medžiagų savybių, santykinių deformacijų ir įlinkių matavimai. Lyginant teoriškai apskaičiuota sijų laikomoji galia. Eksperimentinio tyrimo rezultatai parodė, kad normalus, lakiųjų pelenų, akmenų skaldymo atliekų ir mažo stiprumo betonai didina plieninių tuščiavidurių profiliuočių lenkiamąją galią. Be to, iš šio tyrimo galima matyti, kad normalus, lakiųjų pelenų ir akmenų skaldymo atliekų betonus galima naudoti kompozitinių konstrukcijų plieninių tuščiavidurių profiliuočių lenkiamajai galiai didinti.
BEHAVIOUR OF SQUARE CONCRETE COLUMN CONFINED WITH GFRP COMPOSITE WARP/KOMPOZITINIAIS STIKLO PLUOŠTU ARMUOTO POLIMERO LAKŠTAIS SUSTIPRINTŲ KVADRATINIŲ BETONINIŲ KOLONŲ ELGSENA
Authors: Benzaid Riad , Chikh Nasr-Eddine , Mesbah Habib
Published: June 2008

The behaviour of fibre reinforced polymer (FRP)‐confined concrete in circular columns has been extensively studied, but much less is known about concrete in FRP‐confined square columns, in which the concrete is non‐uniformly confined and the effectiveness of confinement is much reduced. The present paper deals with the analysis of experimental results in terms of load‐carrying capacity and strains, obtained from tests on square prismatic concrete column, strengthened with external glass fibre composite. The parameters considered are the number of composite layers and the corner radius for a square shape. A total of twenty‐one prisms of size 100 × 100 × 300 mm were tested under strain control rate of loading.

Santrauka

Pluoštu armuotu polimeru sustiprintų apskritų betoninių kolonų elgsena yra išsamiai išnagrinėta. Daug mažiau žinoma apie polimero pluoštu sustiprintų kvadratinių betoninių kolonų elgseną. Tokiuose elementuose betono deformacijos suvaržomos nevienodai. Dėl to mažėja sustiprinimo efektyvumas. Straipsnyje pateikiami išoriniais stiklo pluošto lakštais sustiprintų kvadratinių betoninių kolonų laikomosios galios, deformacijų eksperimentinių tyrimų rezultatai ir jų analizė. Eksperimentiniuose tyrimuose nagrinėta kompozitinių pluoštų sluoksnių skaičiaus, skerspjūvio kampo spindulio įtaka sustiprintų kolonų elgsenai. Iš viso išbandytos dvidešimt viena 100×100× 300 mm matmenų prizmės. Bandymai atlikti kontroliuojant apkrovimo greitį pagal deformacijas.
SENSITIVITY OF DYNAMIC BEHAVIOUR OF THE FE MODEL: CASE STUDY FOR THE IGNALINA NPP REACTOR BUILDING
Authors: Baušys Romualdas , Dundulis Gintautas , Kačianauskas Rimantas , Markauskas Darius , Rimkevičius Sigitas , Stupak Eugeniuš , Stupak Stanislav , Šliaupa Saulius
Published: June 2008

The 3D thin‐walled finite element model of Ignalina NPP Unit 2 reactor building was developed aimed at the evaluation of the global dynamic behaviour with a focus on the seismic response. The model comprises description of the monolithic structures, while prefabricated frame structures are ignored and replaced by external masses. Sensitivity study of the selected dynamic characteristics of the model with respect to data uncertainties is considered. Uncertainty of the model is considered in terms of masses of removed structures and wall stiffness. Seismic input is represented by the site specific free‐field ground response acceleration spectra. The sensitivity study concerns variations of frequencies and acceleration of in‐structure horizontal response spectra at specified points. Maximal bending moments are also considered. It was obtained that the reactor level is not sensitive to the uncertainties considered, while discernable sensitivity was detected at the top level of the structure. Santrauka Pateikta Ignalinos atominės elektrinės pastato erdvinio baigtinių elementų dinaminio modelio kūrimo koncepcija, išnagrinėtas šio modelio jautrumas keičiamoms masėms ir sienų standumui. Parodyta, kaip šie keičiami dydžiai turi įtaką dažniams, horizontaliems tam tikrų nagrinėjamų taškų atsako spektrams, lenkimo momentų persiskirstymui ir jų didžiui.
TENSION STIFFENING BOND MODELLING OF CRACKED FLEXURAL REINFORCED CONCRETE BEAMS/SUPLEIŠĖJUSIŲ GELŽBETONINIŲ SIJŲ ARMATŪROS IR BETONO SANKIBOS MODELIAVIMAS
Authors: Khalfallah Salah
Published: June 2008

This paper deals with the analysis of cracked flexural reinforced concrete structures with special highlighting of modelling the interaction between concrete and reinforcement. A new approach based on the bond stress distribution through the transfer length between the zero‐slip and the cracked sections is proposed. Since the cracking phenomenon of concrete occurs, the fracture energy changes in order to appeal to the interaction between concrete and steel. The increment of stresses is evaluated by the bond‐slip distribution by means of one‐dimensional problem. Besides, the 2D nonlinear description of components behaviour, concrete and steel are considered.

On numerical modelling level, the interaction property is obtained from a variety of fundamental pull out and push out tests, for the most part this phenomenon does not very well represent the bending members. For this object, this study presents a numerical approach, which can compute the distribution stresses at the steel‐concrete interface near flexural crack in reinforced concrete beams. Finally, predictions made by the non‐linear finite element analysis program and the non‐linear material models for concrete, reinforcing bars and bond slip are in good agreement with the experimental results.

Santrauka

Straipsnyje atlikta supleišėjusių lenkiamųjų gelžbetoninių elementų analizė armatūros ir betono sąveikos modeliavimo aspektu. Pasiūlytas naujas modelis, pagrįstas sukibimo įtempių pasiskirstymu sąveikos zonos ilgiu nuo nulinio praslydimo iki plyšio pjūvio. Supleišėjus betonui dėl jo sąveikos su armatūra keičiasi irimo energija. Įtempių didėjimas sukibimo ir praslydimo zonoje įvertinamas taikant vienmatį (1D) modelį. Sąveikos komponentų (betono ir armatūros) elgsena aprašoma pasitelkiant dvimačius (2D) modelius. Atliekant skaitinį modeliavimą, betono ir armatūros sąveikos parametrai dažniausiai nustatomi pagal klasikinius ištraukimo ir išstūmimo bandymus. Tačiau lenkiamiesiems elementams taip nustatyti parametrai netinka. Pasiūlytas skaitinis supleišėjusių lenkiamų gelžbetoninių sijų skaičiavimo algoritmas, kurį taikant gali būti nustatytas įtempių pasiskirstymas plieno ir betono sąveikos paviršiuje pjūvyje ties plyšiu. Skaičiavimo rezultatai, gauti taikant netiesinės analizės baigtinių elementų programą kartu su betono, armatūros ir sankibos modeliais, gerai sutapo su eksperimentinių tyrimų rezultatais.
A MONUMENT OF HISTORICAL HERITAGE ‐ VILNIUS ARCHCATHEDRAL BELFRY: THE DYNAMIC INVESTIGATION/VILNIAUS ISTORINIO PAVELDO PAMINKLO − ARKIKATEDROS VARPINĖS − DINAMINIAI TYRIMAI
Authors: Kliukas Romualdas , Kačianauskas Rimantas , Jaras Arūnas
Published: June 2008

The dynamic investigation of a monument of historical heritage ‐ Vilnius Archcathedral Belfry ‐ is investigated. In 2002 six new bells were installed in Vilnius Archcathedral Belfry according to a modern location scheme and their ringing order was changed. Evidently, they caused different dynamic loads which were not completely controlled and their effect on historical buildings of the Old Town of Vilnius could hardly be predictable. The paper presents the results of dynamic investigation of the Archcathedral Belfry, subject to the influence of the bell system operation. The dynamic impact was evaluated by measuring the acceleration history under the conditions, when different combinations of bells were used. A contribution of the dynamic effects was assessed in terms of response spectra. The obtained results have been thoroughly analysed and the appropriate findings and conclusions provided. Santrauka Nagrinėjamas Vilniaus arkikatedros varpinės eksperimentinis tyrimas nuo dinaminių apkrovų, sukeltų veikiant varpams. Preliminaraus tyrimo metu varpinės sienų konstrukcijose buvo pastebėta irimo požymių, daugybinių plyšių. Tai sukėlė ilgalaikis statinio eksploatavimas. Tačiau 2002 m. pagal naują schemą varpinėje pakabinus 6 naujus varpus labai pasikeitė jų poveikis statinio konstrukcijoms. Skambant varpams sukeliamos dinaminės apkrovos varpinės konstrukcijoms iki šiol dar nebuvo tyrinėtos. Atliktas dinaminis eksperimentas, kurio metu ištirti varpinės charakteringųjų vietų masių pagreičiai nuo įvairiais režimais skambančių varpų: varpai skamba vienas paskui kitą iš eilės; skamba visi varpai kartu; keturi mažieji varpai skamba kartu; skamba tik du didieji varpai. Dinaminis poveikis statinio konstrukcijoms įvertinamas pagreičių atsako spektrais. Gauti rezultatai kruopščiai apdoroti ir pateiktos išvados.
Full Recovery of Fracture Toughness Using a Nontoxic Solvent‐Based Self‐Healing System
Authors: Caruso Mary M. , Blaiszik Benjamin J. , White Scott R. , Sottos Nancy R. , Moore Jeffrey S.
Published: June 2008

Two significant advances are reported for solvent‐based self‐healing of epoxy materials. First, an autonomic system yielding complete recovery of fracture toughness after crack propagation was achieved by embedding microcapsules containing a mixture of epoxy monomer and solvent into an epoxy matrix. Healing with epoxy‐solvent microcapsules is superior to capsules that contain solvent alone, and multiple healing events are reported for this system. Second, efficient healing is reported for new solvents, including aromatic esters, which are significantly less toxic than the previously employed solvent, chlorobenzene. Preliminary aging studies using either chlorobenzene or ethyl phenylacetate as the solvent demonstrate the stability of the epoxy‐solvent system under ambient conditions for at least one month.
Synthesis and Biological Evaluation of Some 2,4,5‐Trisubstituted Thiazole Derivatives as Potential Antimicrobial and Anticancer Agents
Authors: Al‐Saadi Mohammed S. , Faidallah Hassan M. , Rostom Sherif A. F.
Published: June 2008

We report on the synthesis and biological evaluation of two series of 2,4,5‐polysubstituted thiazoles comprising the acid hydrazide functionality and some derived pharmacophores known to contribute to various chemotherapeutic activities. All newly synthesized compounds were subjected to in‐vitro antibacterial and antifungal screening. Of the compounds tested, 13 derivatives displayed inhibitory effect on the growth of three Gram‐positive strains while they lack activity against Gram‐negative bacteria. Moreover, four compounds were able to exert antifungal activity against C. albicans. Potential antibacterial and antifungal activities were linked to the thiosemicarbazide function 6a–f and those substituted with both the thioureido and thiosemicarbazide moieties 12a–f. Compounds 6f and 12f (R = 4‐F‐C6H4) could be considered as the most active members in this investigation with a broad spectrum of antibacterial activity against three types of Gram‐positive bacteria, together with an appreciable antifungal activity against C. albicans. Compounds 6d, 6f, and 12f were twice as active as ampicillin against B. subtilis. The best antifungal activity was shown by compound 6d 50% less active than clotrimazole. 17 compounds were selected and tested for their preliminary in‐vitro anticancer activity according to the current one‐dose protocol of the NCI. Three cell lines, non‐small cell lung cancer Hop‐92, ovarian cancer IGROV1, and melanoma SK‐MEL‐2, exhibited some sensitivity against most of the tested compounds. Compound 12f proved to be the most active anticancer member with a broad spectrum of activity against most of the tested subpanel tumor cell lines. Consequently, 12f was carried over to be tested in the five‐dose assay.
Syntheses and Cytotoxic Properties of the Curcumin Analogs 2,6‐Bis(benzylidene)‐4‐phenylcyclohexanones
Authors: Davis Ryan , Das Umashankar , Mackay Hilary , Brown Toni , Mooberry Susan L. , Dimmock Jonathan R. , Lee Moses , Pati Hari
Published: June 2008

Fifteen curcumin analogs were synthesized and tested for in‐vitro cytotoxicity towards B16 and L1210 murine cancer cell lines using an MTT assay. Significant activity was discovered for two analogs: 8 (B16 IC50 = 1.6 μM; L1210 IC50 = 0.35 μM) and 9 (B16 IC50 = 0.51 μM; L1210 IC50 = 1.2 μM). Several other analogs exhibited notable cytotoxicity. The data from quantitative structure‐activity relationships suggest that large electron‐withdrawing substituents placed in the meta‐position of the arylidene aryl rings enhance potencies. Compounds 8 and 9 were found using a cell‐based assay to have virtually no effects on microtubules at concentrations up to 40 μM. These results suggest that tubulin inhibition is not the principal mechanism by which the curcumin analogs act.
Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population
Authors: Kobayashi Shu , Ikari Katsunori , Kaneko Hirotaka , Kochi Yuta , Yamamoto Kazuhiko , Shimane Kenichi , Nakamura Yusuke , Toyama Yoshiaki , Mochizuki Takeshi , Tsukahara So , Kawaguchi Yasushi , Terai Chihiro , Hara Masako , Tomatsu Taisuke , Yamanaka Hisashi , Horiuchi Takahiko , Tao Kayoko , Yasutomo Koji , Hamada Daisuke , Yasui Natsuo , Inoue Hiroshi , Itakura Mitsuo , Okamoto Hiroshi , Kamatani Naoyuki , Momohara Shigeki
Published: June 2008

Objective

STAT4 encodes a transcriptional factor that transmits signals induced by several key cytokines, and it might be a key molecule in the development of autoimmune diseases. Recently, a STAT4 haplotype was reported to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in Caucasian populations. This was replicated in a Korean RA population. Interestingly, the degree of risk of RA susceptibility with the STAT4 haplotype was similar in the Caucasian and Korean populations. The present study was undertaken to investigate the effect of STAT4 on susceptibility to RA and SLE in the Japanese.

Methods

We performed an association study using 3 independent Japanese RA case–control populations (total 3,567 cases and 2,199 controls) and 3 independent Japanese SLE populations (total 591 cases). All samples were genotyped using the TaqMan fluorogenic 5′ nuclease assay for single‐nucleotide polymorphism (SNP) rs7574865, which tags the susceptibility haplotype. The association of the SNP with disease susceptibility in each case–control study was calculated using Fisher's exact test, and the results were combined, using the Mantel‐Haenszel method, to obtain combined odds ratios (ORs).

Results

We observed a significant association of the STAT4 polymorphism with susceptibility to both RA and SLE. The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 × 10−9) and 1.61 (P = 2.1 × 10−11) for allele frequency distribution; these ORs were quite similar to those previously observed in the Caucasian population.

Conclusion

We conclude that STAT4 is associated with RA and SLE in the Japanese. Our results indicate that STAT4 is a common genetic risk factor for autoimmune diseases, with similar strength across major racial groups.
Differential expression of GADD45β in normal and osteoarthritic cartilage: Potential role in homeostasis of articular chondrocytes
Authors: Ijiri Kosei , Zerbini Luiz F. , Peng Haibing , Otu Hasan H. , Tsuchimochi Kaneyuki , Otero Miguel , Dragomir Cecilia , Walsh Nicole , Bierbaum Benjamin E. , Mattingly David , van Flandern Geoff , Komiya Setsuro , Aigner Thomas , Libermann Towia A. , Goldring Mary B.
Published: June 2008

Objective

Our previous study suggested that growth arrest and DNA damage–inducible protein 45β (GADD45β) prolonged the survival of hypertrophic chondrocytes in the developing mouse embryo. This study was undertaken, therefore, to investigate whether GADD45β plays a role in adult articular cartilage.

Methods

Gene expression profiles of cartilage from patients with late‐stage osteoarthritis (OA) were compared with those from patients with early OA and normal controls in 2 separate microarray analyses. Histologic features of cartilage were graded using the Mankin scale, and GADD45β was localized by immunohistochemistry. Human chondrocytes were transduced with small interfering RNA (siRNA)–GADD45β or GADD45β‐FLAG. GADD45β and COL2A1 messenger RNA (mRNA) levels were analyzed by real‐time reverse transcriptase–polymerase chain reaction, and promoter activities were analyzed by transient transfection. Cell death was detected by Hoechst 33342 staining of condensed chromatin.

Results

GADD45β was expressed at higher levels in cartilage from normal donors and patients with early OA than in cartilage from patients with late‐stage OA. All chondrocyte nuclei in normal cartilage immunostained for GADD45β. In early OA cartilage, GADD45β was distributed variably in chondrocyte clusters, in middle and deep zone cells, and in osteophytes. In contrast, COL2A1, other collagen genes, and factors associated with skeletal development were up‐regulated in late OA, compared with early OA or normal cartilage. In overexpression and knockdown experiments, GADD45β down‐regulated COL2A1 mRNA and promoter activity. NF‐κB overexpression increased GADD45β promoter activity, and siRNA‐GADD45β decreased cell survival per se and enhanced tumor necrosis factor α–induced cell death in human articular chondrocytes.

Conclusion

These observations suggest that GADD45β might play an important role in regulating chondrocyte homeostasis by modulating collagen gene expression and promoting cell survival in normal adult cartilage and in early OA.
Association ofSTAT4with rheumatoid arthritis: A replication study in three European populations
Authors: Orozco Gisela , Alizadeh Behrooz Z. , Delgado‐Vega Angélica M. , González‐Gay Miguel Á. , Balsa Alejandro , Pascual‐Salcedo Dora , Fernández‐Gutierrez Benjamín , González‐Escribano María F. , Petersson Ingemar F. , van Riel Piet L. C. M. , Barrera Pilar , Coenen Marieke J. H. , Radstake Timothy R. D. J. , van Leeuwen Miek A. , Wijmenga Cisca , Koeleman Bobby P. C. , Alarcón‐Riquelme Marta , Martín Javier
Published: June 2008

Objective

This study was undertaken to investigate the previously reported association of theSTAT4polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls.

Methods

Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for theSTAT4single‐nucleotide polymorphism rs7574865 using a TaqMan 5′‐allele discrimination assay. The chi‐square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%;P= 0.001, OR 1.26 [95% CI 1.09–1.45]). This association was confirmed in both the Swedish population (P= 0.03, OR 1.35 [95% CI 1.03–1.77]) and the Dutch population (P= 0.03, OR 1.45 [95% CI 1.21–1.73]). The overallPvalue for all 3 populations was 9.79 × 10−6(OR 1.25 [95% CI 1.13–1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti–cyclic citrullinated peptide autoantibodies was observed. A meta‐analysis of all publishedSTAT4associations revealed an OR of 1.25 (95% CI 1.19–1.33) (P= 1 × 10−5).

Conclusion

Our findings indicate an association between theSTAT4polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.
Regulation of B cell tolerance by 129‐derived chromosome 1 loci in C57BL/6 mice
Authors: Fossati‐Jimack Liliane , Cortes‐Hernandez Josefina , Norsworthy Peter J. , Cook H. Terence , Walport Mark J. , Botto Marina
Published: June 2008

Objective

Systemic lupus erythematosus is a multifactorial disease with a strong genetic component. Previous studies have shown that a 129‐derived chromosome 1 interval (Sle16) on the C57BL/6 (B6) background is sufficient to induce humoral autoimmunity. The aim of the present study was to elucidate the mechanisms by which this locus contributes to the loss of peripheral tolerance.

Methods

Anti–single‐stranded DNA (anti‐ssDNA)–knockin transgenic mice (VH3H9R/Vκ8R and VH3H9R) were crossed with a B6 congenic line named B6.129chr1b that carries the Sle16 locus. A parallel study of a gene‐targeted animal, whose mutated gene is located within the 129chr1b interval on chromosome 1, was also performed.

Results

The combination of VH3H9R/Vκ8R with the 129chr1b interval resulted in impaired B cell anergy, and transgenic IgM and IgG anti‐ssDNA antibodies were found in the circulation. The presence of IgG2aa anti‐ssDNA and IgMa anti‐Sm antibodies in sera indicated that the autoreactive transgenic B cells underwent class switching and epitope spreading. The 129chr1b locus appeared to have a dominant effect, since transgenic antibodies were also detected in mice carrying a single allele. The gene‐targeted animals showed a similar phenotype.

Conclusion

The presence of a single 129chr1b locus on the B6 background impaired B cell anergy, prevented deletion of anti‐DNA transgenic B cells, and induced receptor revision. The findings of this study also emphasize that the autoimmune phenotype observed in mice with targeted genes located on chromosome 1 may simply arise from epistatic interactions between the 129 and B6 parental strains.
Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (Prognostic Index for Nailfold Capillaroscopic Examination)
Authors: Ingegnoli Francesca , Boracchi Patrizia , Gualtierotti Roberta , Lubatti Chiara , Meani Laura , Zahalkova Lenka , Zeni Silvana , Fantini Flavio
Published: June 2008

Objective

To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5‐year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs).

Methods

The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1–8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries).

Results

The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm‐based prognostic index. The model was internally and externally validated.

Conclusion

Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.
Modulation of CCR2 in rheumatoid arthritis: A double‐blind, randomized, placebo‐controlled clinical trial
Authors: Vergunst Clarissa E. , Gerlag Daniëlle M. , Lopatinskaya Luba , Klareskog L. , Smith M. D. , van den Bosch F. , Dinant Huib J. , Lee Yih , Wyant Timothy , Jacobson Eric W. , Baeten Dominique , Tak Paul P.
Published: June 2008

Objective

CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2‐mediated chemotaxis in vitro and modulates arthritis in animal models of RA. In this study we examined the effects of CCR2 blockade on synovial inflammation in RA.

Methods

The study was designed as a phase IIa clinical trial with a human CCR2 blocking antibody (MLN1202) in patients with active RA. Thirty‐two patients received 3 infusions, over a period of 6 weeks, with either placebo (n = 9) or anti‐CCR2 monoclonal antibody at 0.5 mg/kg (n = 7), 1.5 mg/kg (n = 7), or 4.0 mg/kg (n = 9). Safety was monitored with laboratory tests, immunotoxicity assessments, and documenting of adverse events, and European League Against Rheumatism and American College of Rheumatology response criteria were used to assess clinical improvement. Synovial tissue was obtained at baseline and after 43 days of treatment, for pharmacodynamic analysis using immunohistochemistry and digital image analysis. The Kruskal‐Wallis test was used to compare groups, and the Wilcoxon signed rank test was used to assess changes within the groups.

Results

All patients completed the study. Treatment with CCR2 blocking antibody reduced the levels of free CCR2 on CD14+ monocytes by at least 57% and up to 94% (P < 0.001), demonstrating the biologic activity of the compound. However, there was no reduction in the levels or expression of any of the synovial biomarkers. Accordingly, no clinical improvement was observed.

Conclusion

Treatment with anti‐CCR2 blocking antibody did not result in amelioration of synovial inflammation in active RA. The results do not support the notion that blockade of CCR2 may be sufficient to induce clinical improvement in RA.
A broad analysis of IL1 polymorphism and rheumatoid arthritis
Authors: Johnsen Alyssa K. , Plenge Robert M. , Butty Vincent , Campbell Christopher , Dieguez‐Gonzalez Rebeca , Gomez‐Reino Juan J. , Shadick Nancy , Weinblatt Michael , Gonzalez Antonio , Gregersen Peter K. , Benoist Christophe , Mathis Diane
Published: June 2008

Objective

It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well‐powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA.

Methods

Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single‐nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case–control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects.

Results

No fully significant associations were observed. Analysis of the discovery case–control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case–control samples. No association with rheumatoid factor, anti–cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here.

Conclusion

In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.
CXCR2‐specific chemokines mediate leukotriene B4–dependent recruitment of neutrophils to inflamed joints in mice with antigen‐induced arthritis
Authors: Grespan Renata , Fukada Sandra Y. , Lemos Henrique P. , Vieira Silvio M. , Napimoga Marcelo H. , Teixeira Mauro M. , Fraser Alasdair R. , Liew Foo Y. , McInnes Iain B. , Cunha Fernando Q.
Published: June 2008

Objective

To investigate the mechanism underlying neutrophil migration into the articular cavity in experimental arthritis and, by extension, human inflammatory synovitis.

Methods

Antigen‐induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Migration assays and histologic analysis were used to evaluate neutrophil recruitment to knee joints. Levels of inflammatory mediators were measured by enzyme‐linked immunosorbent assay. Antibodies and pharmacologic inhibitors were used in vivo to determine the role of specific disease mediators. Samples of synovial tissue and synovial fluid from rheumatoid arthritis (RA) or osteoarthritis patients were evaluated for CXCL1 and CXCL5 expression.

Results

High levels of CXCL1, CXCL5, and leukotriene B4 (LTB4) were expressed in the joints of arthritic mice. Confirming their respective functional roles, repertaxin (a CXCR1/CXCR2 receptor antagonist), anti‐CXCL1 antibody, anti‐CXCL5 antibody, and MK886 (a leukotriene synthesis inhibitor) reduced mBSA‐induced neutrophil migration to knee joints. Repertaxin reduced LTB4 production in joint tissue, and neutrophil recruitment induced by CXCL1 or CXCL5 was inhibited by MK886, suggesting a sequential mechanism. Levels of both CXCL1 and CXCL5 were elevated in synovial fluid and were released in vitro by RA synovial tissues. Moreover, RA synovial fluid neutrophils stimulated with CXCL1 or CXCL5 released significant amounts of LTB4.

Conclusion

Our data implicate CXCL1, CXCL5, and LTB4, acting sequentially, in neutrophil migration in AIA. Elevated levels of CXCL1 and CXCL5 in the synovial compartment of RA patients provide robust comparative data indicating that this mechanism plays a role in inflammatory joint disease. Together, these results suggest that inhibition of CXCL1, CXCL5, or LTB4 may represent a potential therapeutic strategy in RA.
Failure of oral atorvastatin to modulate a murine model of systemic lupus erythematosus
Authors: Graham Kareem L. , Lee Lowen Y. , Higgins John P. , Steinman Lawrence , Utz Paul J. , Ho Peggy P.
Published: June 2008

Objective

Inhibitors of the 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase enzyme (statins) are cholesterol‐lowering drugs that have shown promise as therapeutic agents in various animal models of autoimmune disease. The results of initial clinical trials with statins in multiple sclerosis and rheumatoid arthritis have also been encouraging. In this study, we attempted to treat a widely studied murine model of spontaneous systemic lupus erythematosus (SLE) with atorvastatin.

Methods

(NZB × NZW)F1 (NZB/NZW) mice received daily oral doses of atorvastatin for 20 weeks. The mice were monitored weekly for survival and proteinuria. Anti–double‐stranded DNA (anti‐dsDNA) antibody levels in sera were determined by enzyme‐linked immunosorbent assay (ELISA). T lymphocyte cytokine production in vitro, as well as cytokine levels in vivo, were measured by ELISA. T cell proliferation was assessed by thymidine incorporation assay. Serum cholesterol levels were determined using a standard fluorometric assay. Kidney tissue was harvested and evaluated for pathologic changes.

Results

In NZB/NZW mice, oral atorvastatin had significant effects on T cell proliferation and cytokine production in vitro. Atorvastatin also induced significant increases in serum levels of interleukin‐4. However, atorvastatin treatment in NZB/NZW mice had no significant impact on proteinuria, survival, serum anti‐dsDNA antibody and cholesterol levels, or extent of renal disease.

Conclusion

Monotherapy with oral atorvastatin has no protective effects in a murine model of spontaneous SLE. The efficacy of atorvastatin in human SLE remains to be determined.