bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiepileptic Effects of Botulinum Neurotoxin E
Authors: Costantin Laura , Bozzi Yuri , Richichi Cristina , Viegi Alessandro , Antonucci Flavia , Funicello Marcella , Gobbi Marco , Mennini Tiziana , Rossetto Ornella , Montecucco Cesare , Maffei Lamberto , Vezzani Annamaria , Caleo Matteo
Published: February 2005

Experimental studies suggest that the delivery of antiepileptic agents into the seizure focus might be of potential utility for the treatment of focal-onset epilepsies. Botulinum neurotoxin E (BoNT/E) causes a prolonged inhibition of neurotransmitter release after its specific cleavage of the synaptic protein synaptosomal-associated protein of 25 kDa (SNAP-25). Here, we show that BoNT/E injected into the rat hippocampus inhibits glutamate release and blocks spike activity of pyramidal neurons. BoNT/E effects persist for at least 3 weeks, as determined by immunodetection of cleaved SNAP-25 and loss of intact SNAP-25. The delivery of BoNT/E to the rat hippocampus dramatically reduces both focal and generalized kainic acid-induced seizures as documented by behavioral and electrographic analysis. BoNT/E treatment also prevents neuronal loss and long-term cognitive deficits associated with kainic acid seizures. Moreover, BoNT/E-injected rats require 50% more electrical stimulations to reach stage 5 of kindling, thus indicating a delayed epileptogenesis. We conclude that BoNT/E delivery to the hippocampus is both antiictal and antiepileptogenic in experimental models of epilepsy.
Persistent Phosphorylation by Protein Kinase Mζ Maintains Late-Phase Long-Term Potentiation
Authors: Serrano Peter , Yao Yudong , Sacktor Todd Charlton
Published: February 2005

Protein kinase Mζ (PKMζ), an autonomously active atypical PKC isoform, is both necessary and sufficient for enhanced synaptic transmission during long-term potentiation (LTP) maintenance. LTP, however, evolves through several temporal phases, which may be mediated by distinct molecular mechanisms of potentiation. Here, we determined the specific phase of LTP maintained by PKMζ. Using a selective, cell-permeable ζ-pseudosubstrate inhibitor at concentrations that block potentiation produced by postsynaptic perfusion of PKMζ, we inhibited PKMζ activity at various times after tetanization of Schaffer collateral/commissural-CA1 synapses. Inhibition of PKMζ did not affect baseline AMPA receptor-mediated synaptic transmission or an early phase of LTP. In contrast, the inhibitor reversed established LTP when applied 1, 3, or 5 h after tetanic stimulation. Control nontetanized pathways within the hippocampal slices were unaffected. An inactive scrambled version of the peptide had no effect on LTP. Thus, persistent, increased phosphorylation by PKMζ specifically maintains the late phase of LTP.
Indonesia in 2004: The Rise of Susilo Bambang Yudhoyono
Authors: Liddle R. William , Mujani Saiful
Published: February 2005

Susilo Bambang Yudhoyono, a retired army officer, became Indonesia's first directly elected president, defeating incumbent Megawati Sukarnoputri in a landslide. Key positions in economic ministries were awarded both to pro-market and protectionist groups. A suicide bomb killed nine people and wounded nearly 200, intensifying the nation's search for al-Qaeda-linked terrorists.
The Philippines in 2004: New Mandate, Daunting Problems
Authors: Rivera Temario C.
Published: February 2005

National elections in the Philippines took place on May 10, 2004, providing incumbent President Gloria Macapagal Arroyo with a six-year electoral mandate and control of both houses of Congress and most of the local governmental positions. However, the Arroyo administration faced a worsening budget deficit and debt crisis, increased incidence of hunger and poverty, pervasive corruption scandals in the military, inconclusive peace negotiations with communist guerrillas and Muslim separatists, and an unexpected twist in the country's relations with the United States, provoked by a crisis in the Philippines' involvement in Iraq.
Cambodia in 2004: An Artificial Democratization Process
Authors: Beresford Melanie
Published: February 2005

Cambodia in 2004 continued its difficult labor of democratization. Elite infighting, the assassination of a prominent trade union leader, and the maneuvering of a king to ensure the safety of his dynasty dominated the political landscape during the year. Economic growth slowed, compared with previous years, and continued to be heavily concentrated in urban areas. While World Trade Organization accession in October was seen in elite circles as the key to preserving Cambodia's position in the global garment trade, few resources have trickled down to the majority rural population. The widening distribution gap may be seen as evidence for the view that barriers have been erected to substantive democratization.
Singapore in 2004: Long-Awaited Leadership Transition
Authors: Rodan Garry
Published: February 2005

With strong economic recovery, Goh Chok Tong decided the time was right for the long-anticipated handover of Singapore's prime ministership to Lee Hsien Loong. In foreign relations, the earlier leadership change in Malaysia fostered improved bilateral ties, but a visit by Lee to Taiwan generated friction with Chinese authorities.
Vietnam in 2004: Popular Authority Seeking Power?
Authors: Fforde Adam
Published: February 2005

Vietnam in 2004 saw a combination of rapid economic growth with continued evidence of weak central political authority. The ruling Vietnamese Communist Party, having granted greater freedoms in order to legitimize dissent, refused to abandon its Leninist politics that were hostile toward what appears to be a rapidly emerging “civil society.” The loss of quotas on exports of garments and footwear and slow progress toward joining the World Trade Organization suggest that 2005 could be an interesting year.
Laos in 2004: Political Stability, Economic Opening
Authors: Forbes Dean , Cutler Cecile
Published: February 2005

The Lao People's Democratic Republic made cautious progress during 2004. The socialist government does not tolerate dissent and there is continuing resistance by minorities, but generally, the year saw increased stability and greater confidence that the country is moving forward. Its economy continues to improve, albeit from a very low base. Some ambitious projects, particularly in hydroelectricity and mining, have commenced. The government is slowly building better international links within its region. However, the international community remains concerned about the lack of transparency in politics and administration, and Laos has not succeeded in normalizing trade relations with the United States.
Thailand in 2004: The “Crisis in the South”
Authors: Albritton Robert B.
Published: February 2005

News about Thailand in 2004 was dominated by the “Crisis in the South.” Daily assassinations of local police, soldiers, religious leaders, and other civilians marked a level of insurgency beyond that in other regions of Southeast Asia and one not seen in Thailand for over 30 years. The recurrent violence represents a serious challenge to the nation and at this juncture, it is unclear whether Thailand will concede to irredentism, initiate more local autonomy, or settle for a protracted period of political unrest. These events dominated the political picture in preparation for parliamentary elections scheduled for February 2005 and clouded the premise of a stabilizing economy and programs of government change unprecedented in recent Thai history.
East Timor in 2004: It Is All about Oil
Authors: Cotton James
Published: February 2005

Independent East Timor, with U.N. support until May 2005, is straining to cope with problems of institution building and development. The vital issue of hydrocarbon revenues remains unresolved because of a territorial dispute with Australia and problems with the structures proposed to manage those resources.
Papua New Guinea in 2004: Recolonization, Somare's Staying Power, and a Slight Economic Recovery
Authors: Chin James
Published: February 2005

In 2004, the key events in Papua New Guinea were the political survival of the Somare government, moves by Australia to take direct part in the country's administration, the fiasco over the election of the governor-general, and a slight economic recovery.
Japan in 2004: “Courageous” Koizumi Carries On
Authors: Hiwatari Nobuhiro
Published: February 2005

Betraying all expectations, Japanese political developments in 2004 show Prime Minister Koizumi's true colors as a reformist leader, willing to use his popularity and an empowered cabinet against the entrenched vested interests of the Liberal Democratic Party while compelling the opposition parties either to converge to his position or become marginalized.
Mongolia in 2004: Testing Politics and Economics
Authors: Tuya Nyamosor
Published: February 2005

In Mongolia, the year 2004 was marked by hotly contested parliamentary elections and a rebounding economy. During the elections, the country successfully demonstrated its commitment to pluralistic democracy. The challenge now before the new government is to ensure that economic growth reduces persistent poverty.
India in 2004: Regime Change in a Divided Democracy
Authors: Nayar Baldev Raj
Published: February 2005

The outstanding event of 2004 in India was the national election. Its unexpected results made for the ouster of the BJP-led government—despite the excellent performance of the economy—and its replacement by a coalition headed by the Congress Party, oriented toward greater state activism in economic affairs.
Sri Lanka in 2004: Enduring Political Decay and a Failing Peace Process
Authors: DeVotta Neil
Published: February 2005

With a newly formed leftist alliance headed by President Kumaratunga seizing power, and with the separatist Tamil rebels factionalized, Sri Lanka's peace talks remained suspended. And with the president seeking to change the Constitution to extend her tenure as head of state and the opposition vowing to topple her government, the island appears poised to experience even more instability and chaos.
Verdi and Sacred Revivalism in Post Unification Italy
Authors: Basini Laura
Published: February 2005

This essay sets the late sacred works of Giuseppe Verdi in the context of the late-nineteenth-century fascination for the revival, performance, and festive celebration of historical cultural figures and artworks. From the 1870s onward, certain artistic trends became prevalent in post-unification Italy: anxiety to instill a sense of nation into art and everyday life, nostalgia for a vanished golden age of Italian artistic history, and an ever more energetic revival of historical artistic forms and styles. These currents were stimulated by a nationalistic Catholic revivalism that, I argue, was the strongest influence on Verdi's late career. I outline Verdi's reception in and his personal association with the Catholic revivalist movement, developing a view of Verdi's late life and works as articulating shifting trends in the Church and conservatory. As well as revealing the impact of revivalist aesthetics on the style of works such as Verdi's Pater noster, this inquiry suggests that revivalism contributed to a "canonization" of his image that intertwined civic and religious history.
Ruthenium Indenylidene Complexes
Authors: Dragutan By Valerian , Dragutan Ileana , Verpoort Francis
Published: February 2005

This paper describes a class of ruthenium indenylidene complexes which constitute robust and efficient pre-catalysts for olefin metathesis reactions, specifically ring-closing metathesis of substituted linear dienes, acyclic diene metathesis of α, ω-dienes, enyne metathesis and ring-opening metathesis polymerisation of cycloolefins. They readily allow reactions not promoted by many prior ruthenium catalysts, such as the synthesis of tri- and tetrasubstituted cycloalkenes as well as ring-closing metathesis involving highly substituted dienes. The activity and stability of these pre-catalysts can be finely tuned by adjusting both steric and electronic effects in the metal coordination sphere through an appropriate selection of ancillary ligands. Due to their accessibility, enhanced activity and good stability, this class of ruthenium complexes gratifyingly extends the scope and utility of the currently used metathesis catalysts.
The Effect of Basic Fibroblast Growth Factor on Delayed‐Replanted Monkey Teeth
Authors: Sae‐Lim Varawan , Ong Wei Yi , Li Zhimei , Neo Jennifer
Published: February 2005

Background: Basic fibroblast growth factor (bFGF; FGF‐2) has been reported to facilitate wound healing and periodontal regeneration in experimental alveolar bone defects. The purpose of this study was to evaluate histologically the effect of topically applied bFGF with or without fibrin glue on delayed‐replanted monkey teeth prone to replacement resorption.

Methods: Forty‐five roots from five monkeys were endodontically treated aseptically and then extracted as atraumatically as possible. Ten negative control roots were replanted immediately, while 12 positive control roots were allowed to bench dry for 1 hour prior to replantation, both without further treatment. Roots in the two experimental groups were bench dried for 1 hour, rinsed with saline, and then replanted into sockets filled with bFGF with (11 roots) or without (12 roots) fibrin glue. After 12 weeks, histological sections were prepared and evaluated according to morphometric analysis as complete healing or unfavorable healing composed of inflammatory resorption and replacement resorption.

Results: Kruskal‐Wallis and Mann‐Whitney U tests showed teeth in the negative control group to have significantly higher complete healing (98.88% ± 2.30%) and significantly lower unfavorable healing (1.12% ± 2.30%) than the positive control group and the experimental groups. bFGF/fibrin glue group showed higher occurrence of complete healing (39.06% ± 41.62%) compared to the bFGF group (25.28% ± 28.85%) and the positive control group (16.58% ± 19.60%), although the differences were not significant. Comparing the complete and unfavorable healing, there was no significant difference in the bFGF/fibrin glue group (P = 0.47), but the differences were significant in the other groups (P <0.05).

Conclusion: Topical application of bFGF with fibrin glue showed an insignificantly higher occurrence of complete healing in delayed‐replanted monkey teeth. J Periodontol 2004;75:1570‐1578.
Microbiological Changes With the Use of Locally Delivered Doxycycline in the Periodontal Treatment of Smokers
Authors: Machion Luciana , Andia Denise Carleto , Saito Daniel , Klein Marlize Inês , Gonçalves Reginaldo Bruno , Casati Márcio Zafallon , Nociti Francisco H. , Sallum Enilson Antonio
Published: February 2005

Background: The aim of this study was to evaluate the effect of the association of locally delivered doxycycline 10% and scaling and root planing in the subgingival plaque of smokers.

Methods: Sixteen smokers with chronic periodontitis and a minimum of four pockets ≥5 mm) on anterior teeth that bled on probing were selected. Patients were randomly assigned to one of the following groups: scaling and root planing (SRP) or scaling and root planing followed by local application of doxycycline (SRP‐D). Subgingival plaque samples were collected from initially moderate (5 to 6 mm) and deep (≥7 mm) pockets at baseline and 3 months. Polymerase chain reaction (PCR) analysis was used to detect the frequency of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythensis (Tf).

Results: No statistically significant difference was found in the reduction of Aa in either the SRP‐D or SRP group (P >0.05). The reduction in Tf, Pg, and Tf + Pg was statistically significant for SRP‐D only (P = 0.016, 0.027, and 0.027, respectively). The proportion of sites free of Tf at 3 months was 53% for SRP‐D and 9% for SRP (P = 0.02). For Pg, this proportion was 82% and 40%, respectively (P = 0.05).

Conclusion: The use of locally delivered doxycycline may promote the elimination of T. forsythensis and P. gingivalis in a greater proportion of sites compared to conventional scaling and root planing in smokers. J Periodontol 2004;75:1600‐1604.
Endothelial Dysfunction in Patients With Chronic Periodontitis and Its Improvement After Initial Periodontal Therapy
Authors: Mercanoglu Fehmi , Oflaz Hüseyin , Öz Ogün , Gökbuget Aslan Yasar , Genchellac Hakan , Sezer Murat , Nişanci Yilmaz , Umman Sabahattin
Published: February 2005

Background: Recent epidemiological data suggested that there is a relationship between periodontal health and atherosclerotic coronary heart disease. Although hypothetical models were proposed, the exact mechanism of this association has not been clarified. The aim of this study is to investigate whether there is an endothelial dysfunction in patients with chronic periodontitis and, if present, whether recovery is possible with therapy.

Methods: The study groups consisted of 28 patients (mean age: 45.5 ± 8.6 years) with chronic periodontitis and without any atherosclerotic vascular disease, and 26 healthy controls (mean age: 43.7 ± 6.8 years). Cardiovascular risk factors were investigated in both groups. Brachial artery responses to reactive hyperemia (endothelium‐dependent dilatation [EDD]) and sublingual nitroglycerin (endothelium‐independent dilatation [EID]) were measured using high‐resolution vascular ultrasound in both groups. Measurements were taken before and after initial periodontal therapy in the periodontal patients.

Results: There was no significant difference between the groups with regard to cardiovascular risk factors. In the baseline measurements, EDD and EID were significantly impaired in patients with chronic periodontitis when compared with the controls (8.4% ± 4.0% versus 19.4% ± 8.1%, P <0.0001; 13.3% ± 6.3% versus 29.5% ± 10.0%, P <0.0001 for EDD and EID, respectively). After non‐surgical periodontal therapy, EDD and EID improved significantly (from 8.4% ± 4.0% to 17.7% ± 5.7%, P <0.0001; and from 13.3% ± 6.3% to 24.9% ± 7.3%, P <0.0001 for FMD and EID, respectively). The EDD and EID changes in the controls were insignificant.

Conclusion: This study showed that endothelial functions were impaired in patients with chronic periodontitis and that they improve following initial periodontal therapy. J Periodontol 2004;75:1694‐1700.
Particle sizing in dense suspensions with multiwavelength photon migration measurements
Authors: Dali Sarabjyot Singh , Rasmussen John C. , Huang Yingqing , Roy Ranadhir , Sevick‐Muraca Eva M.
Published: February 2005

Characterization of dense polydisperse suspensions, with mean diameters 143 and 226 nm and volume fractions ranging from 0.03 to 0.27, was conducted using time‐dependent measurements of multiply scattered light. Frequency‐domain photon migration measurements of isotropic scattering coefficients at wavelengths between 488 and 828 nm were found to agree with those predicted from the Mie theory and the polydisperse hard‐sphere Percus–Yevick model. The wavelength‐dependent isotropic scattering data were then used to successfully recover the particle size distribution and volume fraction of the suspensions, by minimizing a nonlinear least‐squares problem. The mean particle size and volume fractions were recovered within an error range of 0–15.53 and 0–24%, respectively, compared with dynamic light scattering results and experimentally measured volume fractions. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Computational issues in hybrid multizonal/computational fluid dynamics models
Authors: Bezzo F. , Macchietto S. , Pantelides C. C.
Published: February 2005

Hybrid multizonal/computational fluid dynamics (CFD) models provide a means of introducing a more realistic description of fluid mechanics and mixing phenomena within process models. The solution of the CFD submodel implicitly defines a function relating one or more of the variables in the multizonal model (the function outputs) in terms of another subset of the variables (the function inputs). This paper is concerned with the accurate and efficient evaluation of this function using local approximate models (LAMs) that may have a general mathematical structure, or be based on physical correlations. Practical issues relating to the robustness of the solution of hybrid models are also considered, and a general architecture for the software interface between the multizonal and CFD submodels is presented. The effectiveness and efficiency of the overall approach are tested by two applications relating, respectively, to a stirred‐tank chemical reactor fitted with a cooling jacket and to a stirred‐tank bioreactor. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Rheometry of aging of colloidal melamine–urea–formaldehyde polycondensates
Authors: Pizzi A. , George B. , Zanetti M. , Meausoone P.‐J.
Published: February 2005

Aged and whitened melamine–urea–formaldehyde (MUF) resins in a colloidal state were tested with parallel‐plate rheometry to determine the extent of their viscoelastic behavior. Only in advanced colloidal states, and so only when aggregated colloidal clusters occurred, did the resins present clear indications of viscoelastic responses, as illustrated by the crossover of elastic modulus and viscous modulus curves at lower strain percentages. These colloidal clusters were labile microstructures, which, broken by applied shear, justified the known thixotropic behavior of these resins sufficiently advanced by aging or other means. MUF resins already in the colloidal state, but for which colloidal clustering had not yet occurred, behaved exclusively as viscous liquids. Two different cases of physical gelation were observed, reversible physical gelation and irreversible physical gelation, underlying which a true gel situation possibly occurred. Physical gelation due to colloidal superstructures occurred in both, but the difference in the resin average molecular masses revealed if the physical gelation was reversible or irreversible and, therefore, if the liquid/cluster separation was defined as the terminal phase of physical gelation. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 655–659, 2005
Quantifying maintenance requirements from the steady‐state operation of a two‐phase partitioning bioscrubber
Authors: Nielsen David R. , Daugulis Andrew J. , McLellan P. James
Published: February 2005

An innovative method for directly and explicitly quantifying the maintenance energy requirements of pure cultures growing on volatile organic compound (VOC) substrates in a two‐phase partitioning bioscrubber is described. Direct evidence of maintenance energy requirements of Achromobacter xylosoxidans Y234 is provided both through observed reductions in the macroscopic biomass‐to‐substrate yield with decreasing specific growth rates, but more remarkably through achievement of steady‐state operation. The data conclusively show that maintenance activities do occur in the two‐phase partitioning bioscrubber and clearly illustrate the importance of this phenomenon to the operation of this process, and similar bioreactor systems. While benzene was selected as the principal, sole substrate of interest in this study, ethylbenzene degradation experiments were also subsequently performed to illustrate and confirm the general applicability of the proposed technique, as well as the potential capabilities of the two‐phase partitioning bioscrubber for the continuous treatment of waste gases containing various VOCs. The proposed method has been shown to generate maintenance energy estimates that are consistent with those obtained while employing more widely recognized estimation strategies, further validating its capabilities. The proposed steady‐state mode also offers key operational advantages in terms of decreased disposal requirements in two‐phase partitioning bioscrubbers. © 2005 Wiley Periodicals, Inc.
Zur Modellierung von Zerkleinerungsprozessen
Authors: Husemann K.
Published: February 2005

Die Bedeutung der Zerkleinerung für die industrielle Stoffwandlung ist groß und die Angebotspalette an Zerkleinerungsmaschinen – angepasst an die Festigkeit/Härte des Mahlgutes, die Ausgangsmaterial‐ und Mahlproduktfeinheit, den notwendigen Durchsatz u. a. – breit. Die Beschreibung der Zerkleinerung ist auch heute trotz der erreichten Fortschritte bei den Grundlagen der Zerkleinerung und den Kenntnissen der Vorgänge in Zerkleinerungsmaschinen nur eingeschränkt möglich. Vor diesem Hintergrund ist die Modellierung der Zerkleinerung von der Modellvorstellung bis zum mathematischen Algorithmus notwendig und hilfreich. Im Beitrag werden verschiedene Modellierungsmöglichkeiten dargestellt und dabei zwischen Regressionsmodellen für die Prozesse in Zerkleinerungsmaschinen, Modellvorstellungen aus den Grundlagen der Zerkleinerung und Modellen für die Zerkleinerung aus der allgemeinen Prozessgleichung der mechanischen Verfahrenstechnik unterschieden.
Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5‐fluorouracil in patients with unresectable biliary tract tumors
Authors: Cantore Maurizio , Mambrini Andrea , Fiorentini Giammaria , Rabbi Carla , Zamagni Donatella , Caudana Roberto , Pennucci Cristina , Sanguinetti Franco , Lombardi Mirko , Nicoli Nicola
Published: February 2005

BACKGROUND

Patients with unresectable biliary tract carcinomas have a very poor prognosis. To improve the efficacy and tolerance of the ECF regimen (epirubicin at a dose of 50 mg/m2, cisplatin at a dose of 60 mg/m2, and 5‐fluorouracil [5‐FU] at a dose of 200 mg/m2 per day by continuous infusion), the authors designed a novel approach that combined locoregional and systemic chemotherapy with the same agents at the same dosages.

METHODS

Thirty consecutive patients with advanced or metastatic biliary tumors were treated with epirubicin at a dose of 50 mg/m2 and cisplatin at a dose of 60 mg/m2 administered as a bolus in the hepatic artery on Day 1, combined with systemic continuous infusion of 5‐FU at a dose of 200 mg/m2 per day, from Day 1 to Day 14, every 3 weeks.

RESULTS

Tumor sites were the intrahepatic bile ducts in 25 patients and the gallbladder in 5 patients. The overall response rate was 40% (12 of 30 patients), including 1 complete response and 11 partial responses. Stable disease was observed in 12 of 30 patients (40%) and progressive disease in 6 of 30 patients (20%). The median progression‐free and overall survival periods were 7.1 and 13.2 months, respectively, and the 1‐year and 2‐year survival rates were 54% and 20%, respectively. Performance status improved in 9 of 30 patients (30%) and a weight gain of > 7% was observed in 4 of 30 patients (13%). The treatment was well tolerated with minimal hematologic toxicity. The major clinical problem was the deep venous thrombosis related to the central venous catheter, which occurred in 5 patients (17%).

CONCLUSIONS

This novel combined locoregional and systemic chemotherapeutic regimen was found to be active and safe for patients with advanced biliary tract carcinoma. Cancer 2005. © 2005 American Cancer Society.
Enterprise JavaBeans caching in clustered environments
Authors: Leff Avraham , Rayfield James T.
Published: February 2005

We present the design of an Enterprise JavaBeans (EJBs) caching architecture, and show that EJB caching can greatly improve application throughput in clustered environments. Throughput is improved because data serving is offloaded from the database server to the cache‐enabled application server. EJB caching is successful because it exploits the low‐latency connections between the database server and application servers that exist in a clustered environment. An important feature of our architecture is that the caching function is transparent to applications that use it. The cache‐enabled application server uses the same (EJB) programming model, and the same transactional semantics, as provided by non‐caching architectures. Copyright © 2005 John Wiley & Sons, Ltd.
Features from functional programming for a C++ skeleton library
Authors: Kuchen H. , Striegnitz J.
Published: February 2005

Message passing based on libraries such as MPI is typically used to program parallel machines with distributed memory. This is efficient, but error prone. Algorithmic skeletons are intended to simplify parallel programming by increasing expressive power. The idea is to offer typical parallel programming patterns as polymorphic higher‐order functions which are efficiently implemented in parallel. The present paper describes how C++ templates and operator overloading can be used in order to provide the main features needed for algorithmic skeletons, namely higher‐order functions, partial applications and parametric polymorphism. Experimental results based on a draft implementation of our C++ skeleton library show that higher expressive power can be gained without a significant performance penalty. Copyright © 2005 John Wiley & Sons, Ltd.
Advanced eager scheduling for Java‐based adaptive parallel computing
Authors: Neary Michael O. , Cappello Peter
Published: February 2005

Javelin 3 is a software system for developing large‐scale, fault‐tolerant, adaptively parallel applications. When all or part of their application can be cast as a master–worker or branch‐and‐bound computation, Javelin 3 frees application developers from concerns about inter‐processor communication and fault tolerance among networked hosts, allowing them to focus on the underlying application. The paper describes a fault‐tolerant task scheduler and its performance analysis. The task scheduler integrates work stealing with an advanced form of eager scheduling. It enables dynamic task decomposition, which improves host load‐balancing in the presence of tasks whose non‐uniform computational load is evident only at execution time. Speedup measurements are presented of actual performance on up to 1000 hosts. We analyze the expected performance degradation due to unresponsive hosts, and measure actual performance degradation due to unresponsive hosts. Copyright © 2005 John Wiley & Sons, Ltd.
On the conditions necessary for removing abstraction penalties in OOLALA
Authors: Luján Mikel , Freeman T. L. , Gurd John R.
Published: February 2005

OOLALA is an object‐oriented linear algebra library designed to reduce the effort of software development and maintenance. In contrast with traditional (Fortran‐based) libraries, it provides two high abstraction levels that significantly reduce the number of implementations necessary for particular linear algebra operations. Initial performance evaluations of a Java implementation of OOLALA show that the two high abstraction levels are not competitive with the low abstraction level of traditional libraries. These initial performance results motivate the present contribution—the characterization of a set of storage formats (data structures) and matrix properties (special features) for which implementations at the two high abstraction levels can be transformed into implementations at the low (more efficient) abstraction level. Copyright © 2005 John Wiley & Sons, Ltd.
Ibis: a flexible and efficient Java‐based Grid programming environment
Authors: van Nieuwpoort Rob V. , Maassen Jason , Wrzesińska Gosia , Hofman Rutger F. H. , Jacobs Ceriel J. H. , Kielmann Thilo , Bal Henri E.
Published: February 2005

In computational Grids, performance‐hungry applications need to simultaneously tap the computational power of multiple, dynamically available sites. The crux of designing Grid programming environments stems exactly from the dynamic availability of compute cycles: Grid programming environments (a) need to beportableto run on as many sites as possible, (b) they need to beflexibleto cope with different network protocols and dynamically changing groups of compute nodes, while (c) they need to provideefficient(local) communication that enables high‐performance computing in the first place. Existing programming environments are either portable (Java), or flexible (Jini, Java Remote Method Invocation or (RMI)), or they are highly efficient (Message Passing Interface). No system combines all three properties that are necessary for Grid computing. In this paper, we present Ibis, a new programming environment that combines Java's ‘run everywhere’ portability both with flexible treatment of dynamically available networks and processor pools, and with highly efficient, object‐based communication. Ibis can transfer Java objects very efficiently by combining streaming object serialization with a zero‐copy protocol. Using RMI as a simple test case, we show that Ibis outperforms existing RMI implementations, achieving up to nine times higher throughputs with trees of objects. Copyright © 2005 John Wiley & Sons, Ltd.
Identification of B and T cells in human spleen sections by infrared microspectroscopic imaging
Authors: Krafft Christoph , Salzer Reiner , Soff Gerhard , Meyer‐Hermann Michael
Published: February 2005

Background

Infrared spectroscopy probes the chemical composition and molecular structure of complex systems such as tissue and cells. Infrared spectroscopic imaging combines this spectral information with lateral resolution near the single‐cell level. We analyzed whether this method is competitive with classic immunohistochemical methods for immunologic tissue and cells.

Methods

We recorded infrared microspectroscopic mapping datasets with a 90‐ × 90‐μm2 aperture from a 3‐ × 3‐mm2 unstained tissue area of human spleen. A secondary follicle containing a germinal center and a T zone were studied in more detail by infrared microspectroscopic imaging with lateral resolution near 5 μm. The results were compared with consecutive sections stained by immunoglobulin D antibodies. T and B lymphocytes were extracted from human blood and served as independent test samples.

Results

Cluster analysis of infrared datasets produced images that distinguished anatomical features such as primary and secondary follicles, T zones, arteries, and spleen red pulp. The assignments could be confirmed in consecutive sections by immunohistochemical staining. Main spectral variances between T and B lymphocytes in high‐resolution measurements were attributed to specific spectral contributions of DNA and cytosol.

Conclusions

Sensitivity and specificity of the infrared based methods are comparable to those of standard staining procedures for identification of B and T cells. However, infrared spectroscopic imaging can offer advantages in velocity, data throughput, and standardization because of minimal sample preparation. The results emphasize the potential of infrared spectroscopy as an innovative tool for the distinction of cell types, in particular in immunologic tissue. © 2005 Wiley‐Liss, Inc.
Synthesis of the Salicylihalamide Core Structure from Epichlorohydrin– Laying the Foundation to Macrolactone Collections
Authors: Herb Christian , Dettner Frank , Maier Martin E.
Published: February 2005

Starting from (R)‐epichlorohydrin, two successive carbon–carbon bond formations, one with acetylide and the other with cyanide, led to the 3‐hydroxynitrile 20. This compound was further elaborated to the enynol 29 via an Evans aldol reaction of the derived aldehyde 22 with the pentenoyloxazolidinone 23 and conversion of the carboxyl to a methyl group after the aldol reaction. Mitsunobu esterification of the enynol 29 with the benzoic acid 5 gave rise to the ester 30 with two double bonds and one triple bond. After protection of the terminal triple bond with a TIPS group, the ring closing metathesis proceeded in good yield. The macrolactone E‐33 was converted into the vinyl iodide 34 and the pyridin containing salicylihalamide analog 36. The described sequence, the two‐sided elongation of epichlorohydrin appears as a general route to secondary alcohols that can be further elaborated to functionalized macrolactones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Clear cell hidradenoma of the skin—a third tumor type with a t(11;19)‐associated TORC1–MAML2 gene fusion
Authors: Behboudi Afrouz , Winnes Marta , Gorunova Ludmila , van den Oord Joost J. , Mertens Fredrik , Enlund Fredrik , Stenman Göran
Published: February 2005

Recent studies have shown that the t(11;19)(q21;p13) translocation in mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the N‐terminal CREB‐binding domain of the cAMP coactivator TORC1 (a.k.a. MECT1 and WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type, clear cell hidradenoma of the skin, also expresses this gene fusion. RT‐PCR analysis of a clear cell hidradenoma with a t(11;19)(q21;p13) translocation revealed expression of a TORC1–MAML2 fusion transcript consisting of exon 1 of TORC1 fused to exons 2–5 of MAML2. Because the fusion was only detected in a single case, the frequency of this aberration in clear cell hidradenomas remains unknown. These results demonstrate that the t(11;19) in mucoepidermoid carcinoma, Warthin's tumor, and clear cell hidradenoma targets the same genes and results in identical gene fusions, indicating that at least subgroups of these glandular tumors evolve through activation of the same molecular pathways. © 2005 Wiley‐Liss, Inc.
The analysis of incomplete cost data due to dropout
Authors: Oostenbrink Jan B. , Al Maiwenn J.
Published: February 2005

Incomplete data due to premature withdrawal (dropout) constitute a serious problem in prospective economic evaluations that has received only little attention to date. The aim of this simulation study was to investigate how standard methods for dealing with incomplete data perform when applied to cost data with various distributions and various types of dropout. Selected methods included the product‐limit estimator of Linet al. the expectation maximisation (EM‐) algorithm, several types of multiple imputation (MI) and various simple methods like complete case analysis and mean imputation. Almost all methods were unbiased in the case of dropout completely at random (DCAR), but only the product‐limit estimator, the EM‐algorithm and the MI approaches provided adequate estimates of the standard error (SE). The best estimates of the mean and SE for dropout at random (DAR) were provided by the bootstrap EM‐algorithm, MI regression and MI Monte Carlo Markov chain. These methods were able to deal with skewed cost data in combination with DAR and only became biased when costs also included the costs of expensive events. None of the methods were able to deal adequately with informative dropout. In conclusion, the EM‐algorithm with bootstrap, MI regression and MI MCMC are robust to the multivariate normal assumption and are the preferred methods for the analysis of incomplete cost data when the assumption of DCAR is not justified. Copyright © 2005 John Wiley & Sons, Ltd.
Development of the vasculature in “pushing‐type” liver metastases of an experimental colorectal cancer
Authors: Paku Sándor , Kopper László , Nagy Péter
Published: February 2005

A mechanism for stroma formation (development of vasculature and supportive connective tissue) is suggested in an experimental “pushing‐type” colorectal carcinoma liver metastasis model. The key element is the appearance of smooth muscle actin (SMA)‐positive cells and the sinusoidal lakes at the border of the metastases. These lakes are the consequence of the disappearance (‘stepping back’ of hepatocytes from the border zone, resulting in the fusion of partially capillarized sinusoids. The growing tumor incorporates SMA‐expressing cells and sinusoidal lakes. SMA‐positive cells produce collagenous matrix, whereas the lakes become the central vessels within the connective tissue columns. Formation of these columns within the tumor is a consequence of the compression atrophy of the base of the incorporated liver tissue, leading to partial separation of the innermost part of the invagination containing functional vessel(s) from the surrounding liver. © 2005 Wiley‐Liss, Inc.
XPC polymorphisms and lung cancer risk
Authors: Lee Ga Young , Jang Jin‐Sung , Lee Sin Yeob , Jeon Hyo‐Sung , Kim Kyung Mee , Choi Jin Eun , Park Jung Min , Chae Myung Hwa , Lee Won Kee , Kam Sin , Kim In‐San , Lee Jae‐Tae , Jung Tae Hoon , Park Jae Yong
Published: February 2005

Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smoking‐related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (–449G→C, –371G→A, –27G→C, Val499Arg, PAT–/+, IVS11‐5C→A and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequency‐matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined –27CG+CC genotype was associated with a significantly increased risk for overall lung cancer compared to the –27GG genotype (adjusted OR = 1.97, 95% CI 1.22–3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the –371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined –371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09–4.00, p = 0.03). The PAT–/+, IVS11‐5C→A and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29–0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36–1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35–0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11‐5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37–0.85, p = 0.007 and Bonferroni‐corrected p = 0.049), whereas haplotype 5 (1122111) containing the –27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41–5.87, p = 0.004 and Bonferroni‐corrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer. © 2005 Wiley‐Liss, Inc.
Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks
Authors: Muzio Lorenzo Lo , D'Angelo Matteo , Procaccini Maurizio , Bambini Fabrizio , Calvino Francesco , Florena Ada Maria , Franco Vito , Giovannelli Lucia , Ammatuna Pietro , Campisi Giuseppina
Published: February 2005

Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB‐1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09‐MY11/GP5‐GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered (p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV‐positive vs. 100% HPV‐negative subjects (p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV‐negative than in HPV‐positive OSCC [root mean‐square error (RMSE) = 5.89 × 10–6, % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV‐positive cases (OR = 0.019, 95%CI 0.001–0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV‐positive vs. HPV‐negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV‐negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers. © 2005 Wiley‐Liss, Inc.
Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1
Authors: Correa Isabel , Plunkett Timothy , Coleman Julia , Galani Eleni , Windmill Elisabeth , Burchell Joy M. , Taylor‐Papdimitriou Joyce
Published: February 2005

The epithelial mucin MUC1 is one of the few tumour‐associated antigens identified for breast cancer. Several MUC1‐derived peptides binding HLA‐A*0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA‐A*0201‐binding peptide has been identified in a human system. We have evaluated the CD8+ T‐cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8+ T‐cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA‐A*0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA‐A*0201+ breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system. © 2005 Wiley‐Liss, Inc.
Achieving strategy with scorecarding
Authors: Lawson Raef , Stratton William , Hatch Toby
Published: February 2005

There are four key factors to achieving strategy through implementation of a scorecarding system. The first of these is clear communication of strategy to employees. Second is tracking results and providing visual feedback, such as through scorecards with traffic lights, trend indicators, benchmarks, and scores. Third is having people with the right skills doing the things necessary to push the strategy forward. Fourth is having a strategy champion to keep the scorecard system initiative visible and to encourage communication. © 2005 Wiley Periodicals, Inc.
A personal computer based implementation of the maximum‐likelihood method of analysis of electron microscope autoradiographs
Authors: Roysam Badrinath , Maffitt David R. , Miller Michael I. , Saffitz Jeffrey E. , Thomas Lewis J.
Published: February 2005

The maximum‐likelihood (ML) method for the quantitative analysis of electron‐microscopic autoradiographs has been shown to be substantially superior to the conventional crossfire (CF) method. It can generate reliable and accurate tracer concentration estimates with far fewer micrographs and produce valid estimates even at counts low enough to preclude the use of the crossfire method while eliminating the need for special ad hoc treatment of narrow membranous structures as well as the secondary verification of the tracer concentration estimates.

Despite these significant advantages, the large computational requirements of the ML method has to date hampered its widespread use. In this paper, we present a new line‐integration method that allows us to reduce the computational requirements of the ML method to a point where it becomes feasible to implement it on a small computer system of the type typically available to a laboratory user of EM autoradiography. We present the complete line‐integration method for the particular case of EM autoradiography with tritium, and show how it can be adapted to other isotopes.

We have constructed a software package that implements the complete maximum‐likelihood method on the IBM PC class of machines using our line‐integration method. Features of this software package which are of particular importance to the research community are device independence, which makes it usable with a large variety of currently available laboratory equipment, and easy portability of the software and data between different computer systems.