bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Complications in Children Diagnosed With Neuroblastoma During a Screening Program
Authors: Barrette Stéphane , Bernstein Mark L. , Leclerc Jean-Marie , Champagne Martin A. , Samson Yvan , Brossard Josée , Woods William G.
Published: March 2006

Purpose

The Québec Neuroblastoma Screening Program was put in place to investigate the possibility of decreasing mortality from high-risk neuroblastoma through early screening. We assess treatment complications in the patients diagnosed during this screening program.

Patients and Methods

A total of 476,603 patients born during the screening period were eligible. Parents of 425,838 children (89%) agreed to participate in the 3-week screening, and 73% agreed to participate in the 6-month screening. Forty-five patients had neuroblastoma. We reviewed the medical and research charts for all patients diagnosed by screening. Follow-up was available from 8 to 13 years after screening.

Results

Forty-five patients were diagnosed by screening. All patients were treated according to the Pediatric Oncology Group recommendations of the time. All patients had surgery, and 29 patients received chemotherapy. No patient died from neuroblastoma. Eleven patients suffered complications from treatment. Two patients had life-threatening complications.

Conclusion

In view of the lack of impact of screening programs on neuroblastoma mortality, evidence that many of the tumors detected through screening can be observed without treatment and the serious complications that may arise from therapy, we do not support neuroblastoma screening programs for children.
Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma
Authors: Richards William G. , Zellos Lambros , Bueno Raphael , Jaklitsch Michael T. , Jänne Pasi A. , Chirieac Lucian R. , Yeap Beow Y. , Dekkers Rene J. , Hartigan Phillip M. , Capalbo Leah , Sugarbaker David J.
Published: March 2006

Purpose

To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM).

Patients and Methods

Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression.

Results

Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time.

Conclusion

Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.
Reduced Expression of Focal Adhesion Kinase Disrupts Insulin Action in Skeletal Muscle Cells
Authors: Huang Danshan , Khoe Michelle , Ilic Dusko , Bryer-Ash Michael
Published: March 2006

Integrins mediate interactions between cells and extracellular matrix proteins that modulate growth factor signaling. Focal adhesion kinase (FAK) is a key multifunctional integrin pathway protein. We recently reported that disruption of FAK impairs insulin-mediated glycogen synthesis in hepatocytes. To test the hypothesis that FAK regulates skeletal muscle insulin action, we reduced FAK expression in L6 myotubes using FAK antisense. In untransfected myotubes, insulin stimulated both FAK tyrosine phosphorylation and kinase activity. Cells treated with antisense FAK showed 78 and 53% reductions in FAK mRNA and FAK protein, respectively, whereas insulin receptor substrate 1/2 and paxillin abundance were unaffected. Insulin-stimulated U-14C-glucose incorporation into glycogen was abolished by FAK antisense, and 2-deoxy-glucose uptake and glucose transporter 4 (GLUT4) translocation were both markedly attenuated. Antisense FAK did not alter GLUT1 or GLUT3 protein abundance. Immunofluorescence staining showed decreased FAK Tyr397 phosphorylation and reduced actin stress fibers. Thus, in skeletal myotubes, FAK regulates the insulin-mediated cytoskeletal rearrangement essential for normal glucose transport and glycogen synthesis. Integrin signaling may play an important regulatory role in muscle insulin action.
Kinome Analysis Reveals Nongenomic Glucocorticoid Receptor-Dependent Inhibition of Insulin Signaling
Authors: Löwenberg Mark , Tuynman Jurriaan , Scheffer Meike , Verhaar Auke , Vermeulen Louis , van Deventer Sander , Hommes Daniel , Peppelenbosch Maikel
Published: March 2006

Glucocorticoids (GCs) are powerful immunosuppressive agents that control genomic effects through GC receptor (GR)-dependent transcriptional changes. A common complication of GC therapy is insulin resistance, but the underlying molecular mechanism remains obscure. Evidence is increasing for rapid genomic-independent GC action on cellular physiology. Here, we generate a comprehensive description of nongenomic GC effects on insulin signaling using peptide arrays containing 1176 different kinase consensus substrates. Reduced kinase activities of the insulin receptor (INSR) and several downstream INSR signaling intermediates (i.e. p70S6k, AMP-activated protein kinase, glycogen synthase kinase-3, and Fyn) were detected in adipocytes and T lymphocytes due to short-term treatment with dexamethasone (DEX), a synthetic fluorinated GC. Western blot analysis confirmed suppressed phosphorylation of the INSR and a series of downstream INSR targets (i.e. INSR substrate-1, p70S6k, protein kinase B, phosphoinositide-dependent protein kinase, Fyn, and glycogen synthase kinase-3) after DEX treatment. DEX inhibited insulin signaling through a GR-dependent (RU486 sensitive) and transcription-independent (actinomycin D insensitive) mechanism. Overall, we postulate here a molecular mechanism for GC-induced insulin resistance based on nongenomic GR-dependent inhibition of insulin signaling.
Molecular Evolution of Proadrenomedullin N-Terminal 20 Peptide (PAMP): Evidence for Gene Co-Option
Authors: Martínez Alfredo , Bengoechea José Antonio , Cuttitta Frank
Published: March 2006

Posttranslational processing of proadrenomedullin generates two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Sequence comparison of homologous proadrenomedullin genes in vertebrate evolution shows a high degree of stability in the reading frame for AM, whereas PAMP sequence changes rapidly. Here we investigate the functional significance of PAMP phylogenetic variation studying two of PAMP’s better characterized physiological activities, angiogenic potential and antimicrobial capability, with synthetic peptides carrying the predicted sequence for human, mouse, chicken, and fish PAMP. All tested peptides induced angiogenesis when compared with untreated controls, but chicken and fish PAMP, which lack terminal amidation, were apparently less angiogenic than their human and mouse homologs. Confirming the role of amidation in angiogenesis, Gly-extended and free acid variants of human PAMP produced responses similar to the natural nonamidated peptides. In contrast, antimicrobial activity was restricted to human PAMP, indicating that this function may have been acquired at a late time during the evolution of PAMP. Interestingly, free acid human PAMP retained antimicrobial activity whereas the Gly-extended form did not. This fact may reflect the need for maintaining a tightly defined structural conformation in the pore-forming mechanism proposed for these antimicrobial agents. The evolution of PAMP provides an example of an angiogenic peptide that developed antimicrobial capabilities without losing its original function.
Role of Phosphatidylinositol 3-Kinaseγ in the β-Cell: Interactions with Glucagon-Like Peptide-1
Authors: Li Li-Xin , MacDonald Patrick E. , Ahn Diane S. , Oudit Gavin Y. , Backx Peter H. , Brubaker Patricia L.
Published: March 2006

Glucagon-like peptide-1 (GLP-1) increases β-cell function and growth through protein kinase A- and phosphatidylinositol-3-kinase (PI3-K)/protein kinase B, respectively. GLP-1 acts via a G protein-coupled receptor, and PI3-Kγ is known to be activated by Gβγ. Therefore, the role of PI3-Kγ in the chronic effects of GLP-1 on the β-cell was investigated using PI3-Kγ knockout (KO) mice treated with the GLP-1 receptor agonist, exendin-4 (Ex4; 1 nmol/kg sc every 24 h for 14 d). In vivo, glucose and insulin responses were similar in PBS- and Ex4-treated KO and wild-type (WT) mice. However, glucose-stimulated insulin secretion was markedly impaired in islets from PBS-KO mice (P < 0.05), and this was partially normalized by chronic Ex4 treatment (P < 0.05). In contrast, insulin content was increased in PBS-KO islets, and this was paradoxically decreased by Ex4 treatment, compared with the stimulatory effect of Ex4 on WT islets (P < 0.05–0.01). Transfection of INS-1E β-cells with small interfering RNA for PI3-Kγ similarly decreased glucose-stimulated insulin secretion (P < 0.01) and increased insulin content. Basal values for β-cell mass, islet number and proliferation, glucose transporter 2, glucokinase, and insulin receptor substrate-2 were increased in PBS-KO mice (P < 0.05–0.001) and, although they were increased by Ex4 treatment of WT animals (P < 0.05), they were decreased in Ex4-KO mice (P < 0.05–0.01). These findings indicate that PI3-Kγ deficiency impairs insulin secretion, resulting in compensatory islet growth to maintain normoglycemia. Chronic Ex4 treatment normalizes the secretory defect, thereby relieving the pressure for expansion of β-cell mass. These studies reveal a new role for PI3-Kγ as a positive regulator of insulin secretion, and reinforce the importance of GLP-1 for the maintenance of normal β-cell function.
Angiotensin II Inhibition Reduces Stress Sensitivity of Hypothalamo-Pituitary-Adrenal Axis in Spontaneously Hypertensive Rats
Authors: Raasch Walter , Wittmershaus Christian , Dendorfer Andreas , Voges Inga , Pahlke Friedrich , Dodt Christoph , Dominiak Peter , Jöhren Olaf
Published: March 2006

Angiotensin II type 1 (AT1) receptors are expressed within organs of the hypothalamo-pituitary-adrenal (HPA) axis and seem to be important for its stress responsiveness. Secretion of CRH, ACTH, and corticosterone (CORT) is increased by stimulation of AT1 receptors. In the present study, we tested whether a blockade of the angiotensin II system attenuates the HPA axis reactivity in spontaneously hypertensive rats. Spontaneously hypertensive rats were treated with candesartan (2 mg/kg), ramipril (1 mg/kg), or mibefradil (12 mg/kg) for 5 wk. In addition to baseline levels, CORT and ACTH responses to injection of CRH (100 μg/kg) were monitored over 4 h. mRNA of CRH, proopiomelanocortin, AT1A, AT1B, and AT2 receptors was quantified by real-time PCR. All treatments induced equivalent reductions of blood pressure and had no effect on baseline levels of CORT and ACTH. However, both candesartan and ramipril significantly reduced CRH-stimulated plasma levels of ACTH (−26 and −15%) and CORT (−36 and −18%) and lowered hypothalamic CRH mRNA (−25 and −29%). Mibefradil did not affect any of these parameters. Gene expression of AT1A, AT1B, and AT2 receptors within the HPA axis was not altered by any drug. We show for the first time that antihypertensive treatment by inhibition of AT1 receptors or angiotensin-converting enzyme attenuates HPA axis reactivity independently of blood pressure reduction. This action is solely evident after CRH stimulation but not under baseline conditions. Both a reduced pituitary sensitivity to CRH and a down-regulation of hypothalamic CRH expression have the potential to reduce HPA axis activity during chronic AT1 blockade or angiotensin-converting enzyme inhibition.
Identification of Follicle-Stimulating Hormone-Selective β-Strands in the N-Terminal Hormone-Binding Exodomain of Human Gonadotropin Receptors
Authors: Vischer Henry F. , Granneman Joke C. M. , Bogerd Jan
Published: March 2006

Glycoprotein hormone receptors contain large N-terminal extracellular domains (ECDs) that distinguish these receptors from most other G protein-coupled receptors. Each glycoprotein hormone receptor ECD consists of a curved leucine-rich repeat domain flanked by N- and C-terminal cysteine-rich regions. Selectivity of the different glycoprotein hormone receptors for their cognate hormones is exclusively determined by their ECDs and, in particular, their leucine-rich repeat domain. To identify human (h)FSH-selective determinants we used a gain-of-function mutagenesis strategy in which β-strands of the hLH receptor (hLH-R) were substituted with their hFSH receptor (hFSH-R) counterparts. Introduction of hFSH-R β-strand 1 into hLH-R conferred responsiveness to hFSH, whereas hLH-R mutants harboring one of the other hFSH-R β-strands displayed none or very limited sensitivity to hFSH. However, combined substitution of hFSH-R β-strand 1 and some of the other hFSH-R β-strands further increased the sensitivity of the mutant hLH-R to hFSH. The apparent contribution of multiple hFSH-R β-strands in providing a selective hormone binding interface corresponds well with their position in relation to hFSH as recently determined in the crystal structure of hFSH in complex with part of the hFSH-R ECD.
Calcitonin Increases Tumorigenicity of Prostate Cancer Cells: Evidence for the Role of Protein Kinase A and Urokinase-Type Plasminogen Receptor
Authors: Thomas Shibu , Chigurupati Srinivasulu , Anbalagan Muralidharan , Shah Girish
Published: March 2006

The expression of human (h) calcitonin (CT) and its receptor (CTR) is localized to basal epithelium in benign prostates but is distributed in whole epithelium of malignant prostates. Moreover, the abundance of hCT and CTR mRNA in primary prostate tumors positively correlates with the tumor grade. We tested the hypothesis that the modulation of endogenous hCT expression of prostate cancer (PC) cell lines alters their oncogenicity. The effect of modulation of hCT expression on oncogenic characteristics was examined in LNCaP and PC-3M cell lines. The endogenous hCT expression was modulated using either constitutively active expression vector containing hCT cDNA or anti-hCT hammerhead ribozymes. The changes in the oncogenicity of cell sublines was assessed with cell proliferation assays, invasion assays, colony formation assays, and in vivo growth in athymic nude mice. Up-regulation of hCT in PC-3M cells and or enforced hCT expression in LNCaP cells dramatically enhanced their oncogenic characteristics. In contrast, the down-regulation of hCT in PC-3M cells led to a dramatic decline in their oncogenicity. These results, when combined with our other results, that the expression of hCT in primary PCs increase with tumor grade, suggest an important role for hCT in the progression of PC to a metastatic phenotype.
Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling
Authors: Mazie Abigail R. , Spix Julie K. , Block Ethan R. , Achebe Hewa B. , Klarlund Jes K.
Published: March 2006

Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid, and there is currently much interest in elucidating messenger functions for this molecule. We report here that wounding sheets of corneal epithelial and Madin Darby canine kidney cells induces strong activation of phospholipase D, and we provide evidence that activation is amplified through a positive feed-back loop. Short-chain analogues of phosphatidic acid induce motility robustly in corneal and other epithelial cell types. The effects of these analogues were not the result of their conversion to the corresponding diacylglycerol or lysophosphatidic acid, implying that phosphatidic acid acts directly on one or more cellular targets. Strikingly, phosphatidic acid signaling was found to stimulate the epidermal growth factor receptor (EGFR) through a transactivation process. Healing of wounds in sheets of corneal epithelial cells is absolutely dependent on epidermal growth factor receptor signaling, and the present data suggest that its activation is a result of wound-induced phospholipase D activation.
Twinfilin is an actin-filament-severing protein and promotes rapid turnover of actin structures in vivo
Authors: Moseley James B. , Okada Kyoko , Balcer Heath I. , Kovar David R. , Pollard Thomas D. , Goode Bruce L.
Published: March 2006

Working in concert, multiple actin-binding proteins regulate the dynamic turnover of actin networks. Here, we define a novel function for the conserved actin-binding protein twinfilin, which until now was thought to function primarily as a monomer-sequestering protein. We show that purified budding yeast twinfilin (Twf1) binds to and severs actin filaments in vitro at pH below 6.0 in bulk kinetic and fluorescence microscopy assays. Further, we use total internal reflection fluorescence (TIRF) microscopy to demonstrate that Twf1 severs individual actin filaments in real time. It has been shown that capping protein directly binds to Twf1 and is required for Twf1 localization to cortical actin patches in vivo. We demonstrate that capping protein directly inhibits the severing activity of Twf1, the first biochemical function ascribed to this interaction. In addition, phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] inhibits Twf1 filament-severing activity. Consistent with these biochemical activities, a twf1Δ mutation causes reduced rates of cortical actin patch turnover in living cells. Together, our data suggest that twinfilin coordinates filament severing and monomer sequestering at sites of rapid actin turnover and is controlled by multiple regulatory inputs.
TRAF6 activation of PI 3-kinase-dependent cytoskeletal changes is cooperative with Ras and is mediated by an interaction with cytoplasmic Src
Authors: Wang Kent Z. Q. , Wara-Aswapati Nawarat , Boch Jason A. , Yoshida Yasuhiro , Hu Chang-Deng , Galson Deborah L. , Auron Philip E.
Published: March 2006

Interleukin 1 (IL-1) has been implicated in the reorganization of the actin cytoskeleton. An expression vector encoding a PKB/Akt pleckstrin-homology domain fused to a fluorescent protein was used to detect phosphoinositide 3-kinase (PI 3-kinase) products. It was observed that PI 3-kinase was activated either by treatment with IL-1 or by expression of either TRAF6, Src, MyD88 or dominant-positive PI 3-kinase, and resulted in the formation of long filopodia-like cellular protrusions that appeared to branch at membrane sites consisting of clusters of phosphoinositide. This depended upon a TRAF6 polyproline motif and Src catalytic activity, and was blocked by inhibitors of PI 3-kinase, Src and Ras. Using both conventional and split fluorescent protein probes fused to expressed TRAF6 and Src in living cells, the polyproline sequence of TRAF6 and the Src-homology 3 (SH3) domain of Src were shown to be required for interaction between these two proteins. Interaction occurred within the cytoplasm, and not at either the cell membrane or cytoplasmic sequestosomes. In addition, co-transfection of vectors expressing fluorescent-protein-fused TRAF6 and non-fluorescent MyD88, IRAK1 and IRAK2 revealed an inverse correlation between increased sequestosome formation and activation of both PI 3-kinase and NF-κB. Although a key factor in TRAF6-dependent activation of PI 3-kinase, ectopic expression of Src was insufficient for NF-κB activation and, in contrast to NF-κB, was not inhibited by IRAK2.
Structural basis for altering the stability of homologous RNAs from a mesophilic and a thermophilic bacterium
Authors: BAIRD NATHAN J. , SRIVIDYA NARAYANAN , KRASILNIKOV ANDREY S. , MONDRAGÓN ALFONSO , SOSNICK TOBIN R. , PAN TAO
Published: March 2006

Tertiary RNA structures from thermophilic bacteria generally are more stable than their mesophilic homologs. To understand the structural basis of the increase in stability, we investigated equilibrium folding of the specificity domain (S-domain) of RNase P RNA from a mesophilic (Escherichia coli) and a thermophilic (Thermus thermophilus) bacterium. Equilibrium folding of both S-domains is described by a minimal, three-state folding scheme, U-to-I-to-N. In the I-to-N transition of the thermophilic S-domain, more structure forms and protections are stronger against T1 nuclease and hydroxyl radical reactions. Phylogenetic comparison in the context of the native structure reveals that among 39 nucleotide differences between these S-domains, 12 likely contribute to higher stability. These residues participate in extensive networks of hydrogen bonding, stacking, and metal ion coordination throughout the molecule. The thermophilic S-domain achieves higher stability by mutating strategic base pairs to G-C, decreasing surface accessibility of the native state, and increasing the amount of structure formation in the native folding transition. An E. coli S-domain mutant containing these 12 nt has the same stability and folding cooperativity as the T. thermophilus S-domain. E. coli S-domain mutants containing a subset of 4 or 6 nt have the same stability as the T. thermophilus S-domain but the same folding cooperativity as the E. coli S-domain. These results show that increasing stability can be accomplished by mutations within a local structure, but increasing folding cooperativity needs concerted changes among multiple structural units.
Transcriptional termination sequences in the mouse serum albumin gene
Authors: WEST STEVEN , ZARET KENNETH , PROUDFOOT NICK J.
Published: March 2006

Poly(A) signals are required for efficient 3′ end formation and transcriptional termination of most protein-encoding genes transcribed by RNA polymerase II. However, transcription can extend far beyond the poly(A) site before termination occurs. This implies the existence of further downstream termination signals. In mammals, a variety of sequence elements, in addition to the poly(A) site, have been implicated in the termination process. For example, termination of the human β- and ε-globin genes is mediated by a sequence downstream of the poly(A) site that promotes an RNA cotranscriptional cleavage (CoTC). Here we report the identification of multiple termination sequences in the mouse serum albumin (MSA) 3′ flanking region. Many transcripts from this region are cleaved cotranscriptionally, implying that such cleavage of pre-mRNA may be a more general feature of transcriptional termination.
The La protein functions redundantly with tRNA modification enzymes to ensure tRNA structural stability
Authors: COPELA LAURA A. , CHAKSHUSMATHI GHADIYARAM , SHERRER R. LYNN , WOLIN SANDRA L.
Published: March 2006

Although the La protein stabilizes nascent pre-tRNAs from nucleases, influences the pathway of pre-tRNA maturation, and assists correct folding of certain pre-tRNAs, it is dispensable for growth in both budding and fission yeast. Here we show that the Saccharomyces cerevisiae La shares functional redundancy with both tRNA modification enzymes and other proteins that contact tRNAs during their biogenesis. La is important for growth in the presence of mutations in either the arginyl tRNA synthetase or the tRNA modification enzyme Trm1p. In addition, two pseudouridine synthases, PUS3 and PUS4, are important for growth in strains carrying a mutation in tRNAArgCCG and are essential when La is deleted in these strains. Depletion of Pus3p results in accumulation of the aminoacylated mutant tRNAArgCCG in nuclei, while depletion of Pus4p results in decreased stability of the mutant tRNA. Interestingly, the degradation of mutant unstable forms of tRNAArgCCG does not require the Trf4p poly(A) polymerase, suggesting that yeast cells possess multiple pathways for tRNA decay. These data demonstrate that La functions redundantly with both tRNA modifications and proteins that associate with tRNAs to achieve tRNA structural stability and efficient biogenesis.
Dynamic-Programming Approximations for Stochastic Time-Staged Integer Multicommodity-Flow Problems
Authors: Topaloglu Huseyin , Powell Warren B.
Published: March 2006

In this paper, we consider a stochastic and time-dependent version of the min-cost integer multicommodity-flow problem that arises in the dynamic resource allocation context. In this problem class, tasks arriving over time have to be covered by a set of indivisible and reusable resources of different types. The assignment of a resource to a task removes the task from the system, modifies the resource, and generates a profit. When serving a task, resources of different types can serve as substitutes of each other, possibly yielding different revenues. We propose an iterative, adaptive dynamic-programming-based methodology that makes use of linear or nonlinear approximations of the value function. Our numerical work shows that the proposed method provides high-quality solutions and is computationally attractive for large problems.
A Computational Study of Cost Reoptimization for Min-Cost Flow Problems
Authors: Frangioni Antonio , Manca Antonio
Published: March 2006

In the last two decades, a number of algorithms for the linear single-commodity min-cost flow (MCF) problem have been proposed, and several efficient codes are available that implement different variants of the algorithms. The practical significance of the algorithms has been tested by comparing the time required by their implementations for solving “from-scratch” instances of MCF, of different classes, as the size of the problem (number of nodes and arcs) increases. However, in many applications several closely related instances of MCF have to be sequentially solved, so that reoptimization techniques can be used to speed up computations, and the most attractive algorithm is the one that minimizes the total time required to solve all the instances in the sequence. In this paper we compare the performances of four different efficient implementations of algorithms for MCF under cost reoptimization in the context of decomposition algorithms for the multicommodity min-cost flow (MMCF) problem, showing that for some classes of instances the relative performances of the codes doing “from-scratch” optimization do not accurately predict the relative performances when reoptimization is used. Because the best solver depends both on the class and on the size of the instance, this work also shows the usefulness of a standard interface for MCF problem solvers that we have proposed and implemented.
A Set-Covering-Based Heuristic Approach for Bin-Packing Problems
Authors: Monaci Michele , Toth Paolo
Published: March 2006

Several combinatorial optimization problems can be formulated as large set-covering problems. In this work, we use the set-covering formulation to obtain a general heuristic algorithm for this type of problem, and describe our implementation of the algorithm for solving two variants of the well-known (one-dimensional) bin-packing problem: the two-constraint bin-packing problem and the basic version of the two-dimensional bin-packing problem, where the objects cannot be rotated and no additional requirements are imposed. In our approach, both the “column-generation” and the “column-optimization” phases are heuristically performed. In particular, in the first phase, we do not generate the entire set of columns, but only a small subset of it, by using greedy procedures and fast constructive heuristic algorithms from the literature. In the second phase, we solve the associated set-covering instance by means of a Lagrangian-based heuristic algorithm. Extensive computational results on test instances from the literature show that, for the two considered problems, this approach is competitive, with respect to both the quality of the solution and the computing time, with the best heuristic and metaheuristic algorithms proposed so far.
Early Estimates of the Size of Branch-and-Bound Trees
Authors: Cornuéjols Gérard , Karamanov Miroslav , Li Yanjun
Published: March 2006

This paper intends to show that the time needed to solve mixed-integer-programming problems by branch and bound can be roughly predicted early in the solution process. We construct a procedure that can be implemented as part of an MIP solver. It is based on analyzing the partial tree resulting from running the algorithm for a short period of time and predicting the shape of the whole tree. The procedure is tested on instances from the literature. This work was inspired by the practical applicability of such a result.
An Improved Augmented Neural-Network Approach for Scheduling Problems
Authors: Agarwal Anurag , Jacob Varghese S. , Pirkul Hasan
Published: March 2006

For the task-scheduling problem, we propose an augmented neural-network approach, which allows the integration of greedy as well as nongreedy heuristics (AugNN-GNG), to give improved solutions in a small number of iterations. The problem we address is that of minimizing the makespan of n tasks on m identical machines (or processors), where tasks are nonpreemptive and follow a precedence order. The proposed approach exploits the observation that a nongreedy search heuristic often finds better solutions than do their greedy counterparts. We hypothesize that combinations of nongreedy and greedy heuristics when integrated with an augmented neural-network approach can lead to better solutions than can either one alone. We show the formulation of such integration and provide empirical results on over a thousand problems. This approach is found to be very robust in that the results were not very sensitive to the type of greedy heuristic chosen. The new approach is able to find solutions, on average, within 1.8% to 2.8% of the lower bound compared to 2.0% to 8.3% for the greedy-only AugNN approach. This improvement is obtained without any increase in computational complexity. In fact the number of iterations used to find the solution decreased.
An Automated Multiresolution Procedure for Modeling Complex Arrival Processes
Authors: Kuhl Michael E. , Sumant Sachin G. , Wilson James R.
Published: March 2006

To automate the multiresolution procedure of Kuhl et al. for modeling and simulating arrival processes that may exhibit a long-term trend, nested periodic phenomena (such as daily and weekly cycles), or both types of effects, we formulate a statistical-estimation method that involves the following steps at each resolution level corresponding to a basic cycle: (a) transforming the cumulative relative frequency of arrivals within the cycle (for example, the percentage of all arrivals as a function of the time of day within the daily cycle) to obtain a statistical model with approximately normal, constant-variance responses; (b) fitting a specially formulated polynomial to the transformed responses; (c) performing a likelihood ratio test to determine the degree of the fitted polynomial; and (d) fitting to the original (untransformed) responses a polynomial of the same form as in (b) with the degree determined in (c). A comprehensive experimental performance evaluation involving 100 independent replications of eight selected test processes demonstrates the accuracy and flexibility of the automated multiresolution procedure.
Optimal Inventory Policy with Two Suppliers
Authors: Fox Edward J. , Metters Richard , Semple John
Published: March 2006

We analyze a periodic-review inventory model where the decision maker can buy from either of two suppliers. With the first supplier, the buyer incurs a high variable cost but negligible fixed cost; with the second supplier, the buyer incurs a lower variable cost but a substantial fixed cost. Consequently, ordering costs are piecewise linear and concave. We show that a reduced form of generalized (s, S) policy is optimal for both finite and (discounted) infinite-horizon problems, provided that the demand density is log-concave. This condition on the distribution is much less restrictive than in previous models. In particular, it applies to the normal, truncated normal, gamma, and beta distributions, which were previously excluded. We concentrate on the situation in which sales are lost, but explain how the policy, cost assumptions, and proofs can be altered for the case where excess demand is backordered. In the lost sales case, the optimal policy will have one of three possible forms: a base stock policy for purchasing exclusively at the high variable cost (HVC) supplier; an (sLVC, SLVC) policy for buying exclusively from the low variable cost (LVC) supplier; or a hybrid (s, SHVC, SLVC) policy for buying from both suppliers.
Book Reviews
Authors: Mansell Warren
Published: March 2006

Psychological treatment of bipolar disorder Edited by Sheri L. Johnson & Robert L. Leahy

New York, USA: The Guilford Press, 2004, Pp. 340, Paperback £30.95, ISBN 1572309245.
Book Reviews
Authors: Smith Keren
Published: March 2006

Anxiety (2nd edn)

ByRachman S. Hove: Psychology Press, 2004, Pp. 207,£12.95, ISBN 1‐84169‐516‐5
Book Reviews
Authors: De Silva P.
Published: March 2006

Disgust: The gatekeeper emotion Edited by Susan Miller Hillsdale, NJ: The Analytic Press, 2004, Pp 213. ISBN 0‐88163‐387‐9
Anti-Cardiolipin Antibodies and Overall Survival in a Large Cohort: Preliminary Report
Authors: Endler Georg , Marsik Claudia , Jilma Bernd , Schickbauer Thomas , Vormittag Rainer , Wagner Oswald , Mannhalter Christine , Rumpold Helmut , Pabinger Ingrid
Published: March 2006

Background: Anti-cardiolipin antibodies have been associated with both arterial and venous thrombosis, but their overall impact on all-cause or vascular mortality is unknown. In this study, we evaluated the influence of anti-cardiolipin antibodies on all-cause and vascular mortality.

Methods: All individuals who fulfilled the inclusion criteria (completeness of data, no admission from an intensive care unit, unique identification with name and date of birth) and whose anti-cardiolipin antibodies were measured between October 2002 and February 2004 were included in this study (n = 4756; 64% female; median age, 46 years). Death/survival and cause of death were obtained from the Austrian Death Registry. The median observation period was 1.5 years, and the study comprised 7189 person-years.

Results: During the study period, 184 patients (3.9%) died. There were no associations between either anti-cardiolipin IgM or IgG antibodies and both vascular death and noncancer mortality as outcome variables in a Cox regression analysis adjusted for age and sex. In contrast, the risk of cancer-related mortality was increased 2.6-fold.

Conclusions: Anti-cardiolipin antibodies are associated with cancer mortality, likely as an epiphenomenon of malignancy, but they are not predictive of vascular mortality or noncancer mortality. Hence, although a clear association between anti-cardiolipin antibodies and (mostly nonfatal) vascular events has been described in the literature, our data indicate that this finding is not necessarily associated with an increase in vascular mortality.
Gap Junctions among Dendrites of Cortical GABAergic Neurons Establish a Dense and Widespread Intercolumnar Network
Authors: Fukuda Takaichi , Kosaka Toshio , Singer Wolf , Galuske Ralf A. W.
Published: March 2006

Gap junctions are common between cortical GABAergic interneurons but little is known about their quantitative distribution along dendritic profiles. Here, we provide direct morphological evidence that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions. Gap junction-coupled networks of parvalbumin neurons were visualized using connexin36 immunohistochemistry and confocal laser-scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve puncta and gap junctions was confirmed by examining the same structures in both CLSM and electron microscopy. Single parvalbumin neurons with large somata (≥200 μm2) formed 60.3 ± 12.2 (mean ± SD) gap junctions with other cells whereby these contacts were not restricted to proximal dendrites but occurred at distances of up to 380 μm from the soma. In a Sholl analysis of large-type parvalbumin neurons, 21.9 ± 7.9 gap junctions were within 50 μm of the soma, 21.7 ± 7.6 gap junctions in a segment between 50 and 100 μm, 11.2 ± 4.7 junctions between 100 and 150 μm, and 5.6 ± 3.6 junctions were in more distal segments. Serially interconnected neurons could be traced laterally in a boundless manner through multiple gap junctions. Comparison to the orientation-preference columns revealed that parvalbumin-immunoreactive cells distribute randomly whereby their large dendritic fields overlap considerably and cover different orientation columns. It is proposed that this dense and homogeneous electrical coupling of interneurons supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.
Rostral Elements of Sympatho-motor Circuitry: A Virally Mediated Transsynaptic Tracing Study
Authors: Kerman Ilan A. , Akil Huda , Watson Stanley J.
Published: March 2006

Numerous physiological and emotionally motivated behaviors, including locomotion, exercise, escape, and attack behaviors as well as passive coping responses, require concomitant activation of motor and sympathetic efferents. Such functional heterogeneity suggests the existence of dual function neurons that can simultaneously coordinate motor and sympathetic output. Because previous physiological investigations have implicated a number of mesencephalic and telencephalic regions in mediating these behaviors, we hypothesized the presence of dual function sympatho-motor neurons in these neural structures. To test this hypothesis, we used recombinant strains of the pseudorabies virus (PRV) for transsynaptic tract-tracing. PRV-152, a strain that expresses enhanced green fluorescent protein, was injected into sympathectomized gastrocnemius muscle, whereas PRV-BaBlu, which expresses β-galactosidase, was injected into the adrenal gland in the same animals. Although coinfected neurons were detected in a number of mesencephalic and telencephalic regions, >50% of such neurons were located within specific subdivisions of two general areas: the hypothalamus and periaqueductal gray. These subdivisions included the ventrolateral periaqueductal gray, dorsomedial hypothalamus, dorsolateral lateral hypothalamus, and ventral portion of the medial parvocellular subdivision of the paraventricular nucleus of the hypothalamus (PVN). A subset of the sympatho-motor neurons within the PVN also contained either arginine vasopressin or oxytocin. This sympatho-motor circuitry likely plays an important role in mediating different aspects of stress responses and emotionally motivated behaviors.
What Are They Doing in There? Case Studies of Volunteer Tutors and Adult Literacy Learners
Authors: Belzer Alisa
Published: March 2006

Through case studies of adult literacy learners and the volunteer tutors who instructed them, this article illustrates the strengths and challenges faced by these kinds of instructional pairs. The descriptions help to reveal critical issues that can inform researchers' and practitioners' thinking and practice with regard to tutor training and ongoing support of instructional pairs. These issues are meant to serve as a starting point for rethinking commonly accepted tutor training practices. Findings indicate the importance of providing tutors with ongoing, situated assistance based on the particular needs of tutors and their students.
Using Open‐Book Tests to Strengthen the Study Skills of Community‐College Biology Students
Authors: Phillips Gregory
Published: March 2006

The author observed that students enrolled in first‐year college biology courses often had weak study skills. This longitudinal study examined the use of open‐book tests to encourage reading and to assess the improvement of college students' study skills. There was a statistically significant improvement from the initial test to the final test given for the entire sample. This study also examined students with weaker study skills, as determined by their performance on the first open‐book test, and found that they benefited more from open‐book tests than did the overall sample. The entire sample had an average improvement of 4.47 points over the first test, which was statistically significant. However, the students with weaker study skills had an average improvement of 23.79 points.
Representations of Critical Media Literacy in the Film Pump Up the Volume
Authors: Trier James
Published: March 2006

One of the main aspects of critical media literacy is taking as objects of critique both the mass media (television, film, music) and the commodities they produce. The purpose of engaging students in this activity is to develop within them an awareness of the social, political, and economic messages emanating from popular fiction, music, movies, and so on. Along with critically examining media systems and popular culture texts, two other main aspects of critical media literacy involve producing media texts and taking up (using, consuming) media texts for critical purposes. An excellent text about the production and use of media texts for critical purposes is the school film Pump Up the Volume, which is the focus of this article.
Building on theoretical principles gleaned from Reading Recovery to inform classroom practice
Authors: COX BEVERLY E. , HOPKINS CAROL J.
Published: March 2006

The authors, both of whom are outside the network of scholars and practitioners typically associated with Reading Recovery, describe the instructional and teacher professional development components of the program and review related research. They then explore the theory and instructional assumptions on which RR is based, positing that both have implications for effective classroom instruction. In fact, they argue that the theory and assumptions of RR can be considered as core to good literacy instruction for all children.
SEARCHing for an Answer: The Critical Role of New Literacies While Reading on the Internet
Authors: Henry Laurie A.
Published: March 2006

It is increasingly clear that the Internet will be the defining technology for reading, writing, and communication in the 21st century. But without the ability to locate information in an efficient and effective manner, students' access to information on the Internet is limited. This article introduces SEARCH, a strategy classroom teachers can use to assist students in becoming better searchers. SEARCH includes setting a purpose, employing effective search strategies, analyzing search engine results, reading critically and synthesizing information, citing sources, and a reflective component in which students ask “How successful was the search?” in order to review the success of the techniques implemented.

Additional resources that provide practice in searching for information on the Internet are also presented.
What if They Can Say the Words but Don't Know What They Mean?
Authors: Cunningham Pat
Published: March 2006

Vocabulary is critical to reading comprehension. Children differ greatly in the size of their meaning vocabularies at school entrance, and those with small vocabularies tend to add fewer words than those with larger vocabularies. Included in this column are some strategies to add more meaning‐vocabulary development to classroom instruction.
Fostering Flexibility and Comprehension in Elementary Students
Authors: Cartwright Kelly B.
Published: March 2006

Skilled reading requires attention to many aspects of print at the same time. Some children demonstrate difficulty in attending flexibly to multiple features of print, often focusing solely on decoding or word‐level information. These children often lack the insight that reading is more than decoding; they have a difficult time thinking about words as having both meaning and sound.

This article reviews work that shows how children can be taught to think more about both words' sounds and their meanings, resulting in increased flexibility and comprehension for these children. Further, the article provides teachers with a simple strategy for helping students achieve increased flexibility in reading processes to aid them in making the transition to more fluent reading.
Yes, There Is Room for Soup in the Curriculum: Achieving Accountability in a Collaboratively Planned Writing Program
Authors: Engel Trudie , Streich Russell
Published: March 2006

This article describes how one U.S. school district created a planned writing curriculum to provide strong, cohesive instruction for all students. Because of teacher preferences, some children received little instruction in expository writing, and scores on the state writing assessment fluctuated widely. The authors focus on how all teachers came together and hammered out a systematic writing program that took long‐taught, favorite projects (such as making soup) and put them into a process writing format. Teachers agreed to take each workshop at least through the revision step, and rubrics in student‐friendly language were created. Uniformity in content, instructional strategies, time spent on writing, and assessment was thus achieved.

Key points in developing the curriculum were inclusiveness, with all teachers participating, and flexibility of implementation. A teacher survey indicated a high degree of satisfaction with the program, and writing samples showed a noticeable improvement in targeted areas. Student writing included in the article demonstrates proficiency in previously neglected organizational skills at all grade levels. The authors also give suggestions for adapting the collaborative process described.
What Do the Kids Think?
Authors: Pachtman Andrew B. , Wilson Karen A.
Published: March 2006

Can students identify the practices that motivate them to read? If asked to evaluate which components of a reading program are beneficial in motivating them, can they identify a particular practice and explain why it was helpful? These were the two major questions asked of 22 fifth‐grade students reflecting on their fourth‐grade experience. A survey was developed to elicit students' reflections and opinions on 18 components of a fourth‐grade reading program.

These components fell into five categories:

Proximity and access to books

Routines and procedures

Reading strategies

Individual preferences

Student accountability and record‐keeping

The students rated each practice as “very important,” “important,” “not very important,” or “not important,” based on how much each influenced their reading attitudes and habits. According to the students, “proximity and access to books” was the most valued component of the reading program. Eighty‐six percent of the students ranked having a lot of books in the classroom library as “most important.” They appreciated being able to find books immediately.