bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Clinical and Pharmacologic Study of Chronic Oral Administration of the Farnesyl Protein Transferase Inhibitor R115777 in Advanced Cancer
Authors: Crul M. , de Klerk G. J. , Swart M. , van’t Veer L. J. , de Jong D. , Boerrigter L. , Palmer P. A. , Bol C. J. , Tan H. , de Gast G. C. , Beijnen J. H. , Schellens J. H.M.
Published: October 2002

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetics of R115777, a farnesyl transferase inhibitor, when administered continuously via the oral route.

PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with R115777 using an interpatient dose escalation scheme starting at 50 mg bid. Pharmacokinetics were assessed on days 1, 28, and 56.

RESULTS: Twenty-eight patients were entered onto the study and the median duration of treatment was 55 days. The dose-limiting toxicities were myelosuppression and neurotoxicity. At a dose of 400 mg bid, grade 4 leukocytopenia and neutropenia were seen in two of four patients. Neurotoxicity grade 3 developed in one of five patients at 500 mg bid and in one of 13 at 300 mg bid after 8 weeks of treatment. Common nonhematologic toxicities were nausea, vomiting, and fatigue. The recommended dose for phase II/III testing in this scheme is 300 mg bid. The pharmacokinetic studies indicated dose proportionality. Little accumulation occurred and steady-state levels were reached within 2 to 3 days. Analyses of historic tumor material showed that five of 15 of patients had a K-ras mutation in codon 12. Three patients with pancreatic, colon, and cervix carcinomas had stable disease and one patient with a colon carcinoma had a minor response accompanied by a more than 50% decrease in carcinoembryonic antigen tumor marker. A fifth patient, with platinum-refractory non–small-cell lung cancer, showed a partial response that lasted for 5 months.

CONCLUSION: Continuous dosing of R115777 is feasible with an acceptable toxicity profile at a dose of 300 mg bid.
On some distributional properties of a first-order nonnegative bilinear time series model
Authors: Zhang Zhiqiang , Tong Howell
Published: October 2002

We study a simple first-order nonnegative bilinear time-series model and give conditions under which the model is stationary. The probability density function of the stationary distribution (when it exists) is found. We also discuss the tail behaviour of the stationary distribution and calculate the probability density function by a numerical method. Simulation is used to check the calculation.
Combinatorial techniques forM/G/1-type queues
Authors: Mercankosk G. , Nair G. M. , Soet W. J.
Published: October 2002

The application of the generalised ballot theorem to queueing theory leads to elegant results for the simpleM/G/1 queue. It is thought that such results are not possible for more generalM/G/1-type queues. We, however, derive a batch ballot theorem which can be applied to derive the first passage distribution matrix,G, for the generalM/G/1-type queue.
An asymptotic expansion for the expectation of an age-dependent branching process with a submultiplicative estimate of the remainder
Authors: Sgibnev M. S.
Published: October 2002

An asymptotic expansion for the expected number, μ(t), of particles of an age-dependent branching process is obtained with a general submultiplicative estimate for the remainder term. The influence of the roots of the characteristic equation on the asymptotic behaviour of μ(t) is taken into account.
Continuous-time Markov additive processes: Composition of large deviations principles and comparison between exponential rates of convergence
Authors: Macci Claudio
Published: October 2002

We consider a continuous-time Markov additive process (Jt,St) with (Jt) an irreducible Markov chain on E = {1,…,s}; it is known that (St/t) satisfies the large deviations principle as t → ∞. In this paper we present a variational formula H for the rate function κ∗ and, in some sense, we have a composition of two large deviations principles. Moreover, under suitable hypotheses, we can consider two other continuous-time Markov additive processes derived from (Jt,St): the averaged parameters model (Jt,St(A)) and the fluid model (Jt,St(F)). Then some results of convergence are presented and the variational formula H can be employed to show that, in some sense, the convergences for (Jt,St(A)) and (Jt,St(F)) are faster than the corresponding convergences for (Jt,St).
Exact asymptotics for a queue with fractional Brownian input and applications in ATM networks
Authors: Duncan Tyrone E. , Yan Yi , Yan Peng
Published: October 2002

In this paper, a single channel FIFO fluid queue with an infinite buffer space and a long-range dependent input is studied. The input traffic is modeled by an average input rate plus a standard fractional Brownian motion as the fluctuation. Lower and upper bounds are derived for the tail distribution of the transient queue length at timeT, which result in a logarithmic characterization of the asymptotic behavior of the tail distribution. Furthermore, the exact asymptotic is also obtained. It is observed that the transient queue length under fractional Brownian input does not suffer from the heavy-tail property as does the steady-state queue length. The results are used to compute the equivalent bandwidth requirement for ATM broadband connections with fractional Brownian traffic feed and finite connection holding time.
Quasi-renewal estimates
Authors: Piau Didier
Published: October 2002

We show that the solution of a quasi-renewal equation with an exponential distribution of the renewals converges at infinity and we compute explicitly the limit, hence generalizing the classical renewal theorem. We apply this result to a stochastic model of DNA replication introduced by Cowan and Chiu (1994).
Probabilistic aspects of the SU(2)-harmonic oscillator
Authors: Luo Shunlong
Published: October 2002

In the framework of quantum probability, we present a simple geometrical mechanism which gives rise to binomial distributions, Gaussian distributions, Poisson distributions, and their interrelation. More specifically, by virtue of coherent states and a toy analogue of the Bargmann transform, we calculate the probability distributions of the position observable and the Hamiltonian arising in the representation of the classic group SU(2). This representation may be viewed as a constrained harmonic oscillator with a two-dimensional sphere as the phase space. It turns out that both the position observable and the Hamiltonian have binomial distributions, but with different asymptotic behaviours: with large radius and high spin limit, the former tends to the Gaussian while the latter tends to the Poisson.
Selecting a sequence of last successes in independent trials
Authors: Bruss F. Thomas , Paindaveine Davy
Published: October 2002

Let I1,I2,…,In be a sequence of independent indicator functions defined on a probability space (Ω, A, P). We say that index k is a success time if Ik = 1. The sequence I1,I2,…,In is observed sequentially. The objective of this article is to predict the lth last success, if any, with maximum probability at the time of its occurrence. We find the optimal rule and discuss briefly an algorithm to compute it in an efficient way. This generalizes the result of Bruss (1998) for l = 1, and is equivalent to the problem of (multiple) stopping with l stops on the last l successes. We then extend the model to a larger class allowing for an unknown number N of indicator functions, and present, in particular, a convenient method for an approximate solution if the success probabilities are small. We also discuss some applications of the results.
A generalized delta method with applications to intrinsic diversity profiles
Authors: Marcheselli Marzia
Published: October 2002

A generalization of the delta method is proposed. The asymptotic distribution of g(Yn) is obtained when g is not necessarily a differentiable function but verifies some weaker regularity conditions. An application to diversity profiles is also presented.
Explicit bounds for geometric convergence of Markov chains
Authors: Kolassa John E.
Published: October 2002

This paper presents bounds on convergence rates of Markov chains in terms of quantities calculable directly from chain transition operators. Bounds are constructed by creating a probability distribution that minorizes the transition kernel over some region, and by examining bounds on an expectation conditional on lying within and without this region. These are shown to be sharper in most cases than previous similar results. These bounds are applied to a Markov chain useful in frequentist conditional inference in canonical generalized linear models.
A best-choice problem with multiple selectors
Authors: Glickman Hagit
Published: October 2002

Consider a situation where a known number, n, of objects appear sequentially
in a random order. At each stage, the present object is presented to d ≥ 2 different selectors, who must jointly decide whether to select or reject it, irrevocably. Exactly one object must be chosen. The observation at stage j is a d-dimensional vector R(j) = (R1(j),…, Rd(j)), where Ri(j) is the relative rank of the jth object, by the criterion of the ith selector. The decision whether to stop or not at time j is based on the d-dimensional random vectors R(1),…, R(j). The criteria according to which each selector ranks the objects can either be dependent or independent. Although the goal of each selector is to maximize the probability of choosing the best object from his/her point of view, all d selectors must cooperate and chose the same object. The objective studied here is the maximization of the minimum over the d individual probabilities of choosing the best object. We exhibit the structure of the optimal rule. For independent criteria we give a full description of the rule and show that the optimal value tends to d-d/(d-1), as n → ∞. Furthermore, we show that as n → ∞, the liminf of the values under negatively associated criteria is bounded below by d-d/(d-1).
A central limit theorem for iterated random functions
Authors: Wu Wei Biao , Woodroofe Michael
Published: October 2002

A central limit theorem is established for additive functions of a Markov chain that can be constructed as an iterated random function. The result goes beyond earlier work by relaxing the continuity conditions imposed on the additive function, and by relaxing moment conditions related to the random function. It is illustrated by an application to a Markov chain related to fractals.
Poisson approximations for conditionalr-scan lengths of multiple renewal processes and application to marker arrays in biomolecular sequences
Authors: Chen Chingfer , Karlin Samuel
Published: October 2002

This study is motivated by problems of molecular sequence comparison for multiple marker arrays with correlated distributions. In this paper, the model assumes two (or more) kinds of markers, say MarkersAandB, distributed along the DNA sequence. The two primary conditions of interest are (i) many of MarkerB(say ≥m) occur, and (ii) few of MarkerB(say ≤l) occur. We title these theconditional r-scan models, and inquire on the extent to which MarkerAclusters or is over-dispersed in regions satisfying condition (i) or (ii). Limiting distributions for the extremalr-scan statistics from theAarray satisfying conditions (i) and (ii) are derived by extending the Chen-Stein Poisson approximation method.
A use of the Stein-Chen method in time series analysis
Authors: Kim Sun-Tsung
Published: October 2002

In this paper, a statistic that has been introduced to test for space-time correlation is considered in a time series context. The null hypothesis is white noise; the alternative is any kind of continuous functional dependence. For an autoregressive process close to the null hypothesis, a bound on the distance between the distribution of the statistic and a Poisson distribution is proved, using the Stein-Chen method. The main difficulty in the proof is that the dependence in the time series is not locally restricted. The result implies asymptotically certain discrimination for a reasonable choice of the thresholds.
One-dimensional branching random walks in a Markovian random environment
Authors: Machado F. P. , Popov S. Yu.
Published: October 2002

We study a one-dimensional supercritical branching random walk in a non-i.i.d. random environment, which considers both the branching mechanism and the step transition. This random environment is constructed using a recurrent Markov chain on a finite or countable state space. Criteria of (strong) recurrence and transience are presented for this model.
Conditional law of a branching process observing a subpopulation
Authors: Ceci Claudia , Gerardi Anna
Published: October 2002

The paper is concerned with filtering the cardinality of a branching process observing the cardinality of a subpopulation. In this model, both the processes, state and observation are pure jump processes and may have common jump times. Preliminary properties are studied in the tree framework. A recursive structure for the filtering equation is proved in the supercritical case.
Output analysis of a single-buffer multiclass queue: FCFS service
Authors: Kulkarni V. G. , Glazebrook K. D.
Published: October 2002

We consider an infinite capacity buffer where the incoming fluid traffic belongs to K different types modulated by K independent Markovian on-off processes. The kth input process is described by three parameters: (λk, μk, rk), where 1/λk is the mean off time, 1/μk is the mean on time, and rk is the constant peak rate during the on time. The buffer empties the fluid at rate c according to a first come first served (FCFS) discipline. The output process of type k fluid is neither Markovian, nor on-off. We approximate it by an on-off process by defining the process to be off if no fluid of type k is leaving the buffer, and on otherwise. We compute the mean on time τkon and mean off time τkoff. We approximate the peak output rate by a constant rko so as to conserve the fluid. We approximate the output process by the three parameters (λko, μko, rko), where λko = 1/τkoff, and μko = 1/τkon. In this paper we derive methods of computing τkon, τkoff and rko for k = 1, 2,…, K. They are based on the results for the computation of expected reward in a fluid queueing system during a first passage time. We illustrate the methodology by a numerical example. In the last section we conduct a similar output analysis for a standard M/G/1 queue with K types of customers arriving according to independent Poisson processes and requiring independent generally distributed service times, and following a FCFS service discipline. For this case we are able to get analytical results.
Waiting times for patterns in a sequence of multistate trials
Authors: Antzoulakos Demetrios L.
Published: October 2002

LetXn,n≥ 1 be a sequence of trials taking values in a given setA, let ∊ be a pattern (simple or compound), and letXr,∊be a random variable denoting the waiting time for therth occurrence of ∊. In the present article a finite Markov chain imbedding method is developed for the study ofXr,∊in the case of the non-overlapping and overlapping way of counting runs and patterns. Several extensions and generalizations are also discussed.
Sufficient conditions for long-range count dependence of stationary point processes on the real line
Authors: Kulik Rafał , Szekli Ryszard
Published: October 2002

Daley and Vesilo (1997) introduced long-range count dependence (LRcD) for stationary point processes on the real line as a natural augmentation of the classical long-range dependence of the corresponding interpoint sequence. They studied LRcD for some renewal processes and some output processes of queueing systems, continuing the previous research on such processes of Daley (1968), (1975). Subsequently, Daley (1999) showed that a necessary and sufficient condition for a stationary renewal process to be LRcD is that under its Palm measure the generic lifetime distribution has infinite second moment. We show that point processes dominating, in a sense of stochastic ordering, LRcD point processes are LRcD, and as a corollary we obtain that for arbitrary stationary point processes with finite intensity a sufficient condition for LRcD is that under Palm measure the interpoint distances are positively dependent (associated) with infinite second moment. We give many examples of LRcD point processes, among them exchangeable, cluster, moving average, Wold, semi-Markov processes and some examples of LRcD point processes with finite second Palm moment of interpoint distances. These examples show that, in general, the condition of infiniteness of the second moment is not necessary for LRcD. It is an open question whether the infinite second Palm moment of interpoint distances suffices to make a stationary point process LRcD.
Trisomy 18 in a 20‐year‐old woman
Authors: Kelly Michael , Robinson Bradley W. , Moore John W.
Published: October 2002

A 20‐year‐old female with trisomy 18 is described. Survival past infancy is rare in this disorder. Little is known concerning the factors that contribute to prolonged survival with this syndrome. This case provides an opportunity to review the management of older children and young adults with trisomy 18. © 2002 Wiley‐Liss, Inc.
Partial deletions of the long arm of chromosome 13 associated with holoprosencephaly and the Dandy‐Walker malformation
Authors: McCormack W. Michael , Shen Joseph J. , Curry Stacey M. , Berend Sue Ann , Kashork Catherine , Pinar Halit , Potocki Lorraine , Bejjani Bassem A.
Published: October 2002

Two patients with partial deletions of the long arm of chromosome 13, del(13)(13q21‐q34) and del(13)(13q22‐q33), respectively, multiple congenital anomalies including holoprosencephaly (HPE) and the Dandy‐Walker malformation (DWM) are described. The occurrence of HPE and the DWM in both of these patients suggests that, in addition to ZIC2, which is important for normal development of the forebrain, there is at least one other dosage‐sensitive gene in 13q22‐q33 that plays an important role in brain development. The DWM is anatomically and developmentally distinct from HPE. The presence of a DWM in each of these two patients with partial deletions of the long arm of chromosome 13 suggests that haploinsufficiency at a locus in 13q22‐q33 may cause this anomaly. These findings suggest that microdeletions in 13q22‐q33 may be found in a proportion of patients with an apparently isolated DWM. Therefore, careful high‐resolution cytogenetic analysis (550 band level or greater) of 13q22‐q33 may be considered in these patients. Furthermore, future molecular studies of this region may reveal candidate gene loci for the DWM. © 2002 Wiley‐Liss, Inc.
Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation
Authors: Turner Gillian , Partington Michael , Kerr Bronwyn , Mangelsdorf Marie , Gecz Jozef
Published: October 2002

Two families, originally diagnosed as having nonsyndromic X‐linked mental retardation (NSXLMR), were reviewed when it was shown that they had a 24‐bp duplication (428‐45 1dup(24bp)) in the ARX gene [Stromme et al., 2002: Nat Genet 30:441–445]. This same duplication had also been found in three other families: one with X‐linked infantile spasms and hypsarrhythmia (X‐linked West syndrome, MIM 308350) and two with XLMR and dystonic movements of the hands (Partington syndrome, MIM 309510). On review, manifestations of both West and Partington syndromes were found in some individuals from both families. In addition, it was found that one individual had autism and two had autistic behavior, one of whom had epilepsy. The degree of mental retardation ranged from mild to severe. A GCG trinucleotide expansion (GCG)10+7 and a deletion of 1,517 bp in the ARX gene have also been found in association with the West syndrome, and a missense mutation (1058C>T) in a family with a newly recognized form of myoclonic epilepsy, severe mental retardation, and spastic paraplegia [Scheffer et al., 2002: Neurology, in press]. Evidently all these disorders are expressions of mutations in the same gene. It remains to be seen what proportions of patients with infantile spasms, focal dystonia, autism, epilepsy, and nonsyndromic mental retardation are accounted for by mutations in the ARX gene. © 2002 Wiley‐Liss, Inc.
Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes simplex virus 1 mutant that expresses the CYP2B1 transgene
Authors: Pawlik Timothy M. , Nakamura Hideo , Mullen John T. , Kasuya Hideki , Yoon Sam S. , Chandrasekhar Soundararajalu , Chiocca E. Antonio , Tanabe Kenneth K.
Published: October 2002

BACKGROUND

Herpes simplex virus 1 (HSV‐1) infection of cancer cells results in viral replication with cell destruction and liberation of progeny virion that infect adjacent tumor cells. rRp450 is a novel replication‐conditional HSV‐1 mutant that expresses both the endogenous herpes viral thymidine kinase gene and the rat p450 CYP2B1 transgene; p450 bioactivates such cancer prodrugs as cyclophosphamide.

METHODS

Viral cytotoxicity and replication assays were performed in colon carcinoma cells as well as primary human hepatocytes. For in vivo studies, diffuse liver metastases were generated by inoculating MC26 cells into the portal system of BALB/c mice. Mice were treated with control media, rRp450, or rRp450 plus cyclophosphamide.

RESULTS

Cytopathic effects induced by rRp450 replication in colon carcinoma cells were equivalent to those induced by wild type HSV‐1 in vitro. Assays developed to separate cytotoxicity mediated by viral replication from cytotoxicity mediated by chemotherapy confirmed that HSV‐1 thymidine kinase bioactivates ganciclovir and CYP2B1 bioactivates cyclophosphamide in rRp450‐infected cells. rRp450 mediated cytotoxicity in the presence of cyclophosphamide was increased by 21% to 30% above that achieved by viral replication alone. Cyclophosphamide bioactivation produced bystander killing of colon carcinoma cells but not hepatocytes. In contrast to these effects of cyclophosphamide, rRp450 mediated cytotoxicity was reduced in the presence of ganciclovir. These findings are explained by further experiments showing that bioactivation of cyclophosphamide only minimally affected HSV‐1 replication in colon carcinoma cells, whereas bioactivation of ganciclovir markedly attenuated HSV‐1 replication. In vivo studies revealed a substantial decrease in hepatic tumor burden in all rRp450‐treated animals compared to controls. The addition of cyclophosphamide augmented rRp450's in vivo anti‐neoplastic effect.

CONCLUSIONS

The rRp450 mutant HSV‐1 is highly oncolytic against colon carcinoma cells both in vitro and in vivo. rRp450 displays preferential replication in colon carcinoma cells compared to normal hepatocytes. Activation of cyclophosphamide by the p450 transgene augmented the anti‐neoplastic effects of rRp450 without simultaneously decreasing viral replication. Oncolysis induced by HSV‐1 replication combined with cyclophosphamide prodrug activation warrants further investigation as a potential therapy for colon carcinoma liver metastases. Cancer 2002;95:1171–81. © 2002 American Cancer Society.

DOI 10.1002/cncr.10776
Technical Note: Reduction of rational integrals related to linear and convex quadrilateral finite elements
Authors: Rathod H.T. , Islam Md. Shafiqul
Published: October 2002

We reduce a rational function of bivariate nth degree polynomial numerator with a linear denominator to a simple bivariate polynomial of degree (n − 1) and a rational function of a single variate nth degree polynomial numerator with the same bivariate linear denominator. This has very greatly contributed to the evaluation of (n + 1)(n + 2)/2 rational integrals in bivariates to mere (n + 1) rational integral of a single variate and an integration of simple polynomial in bivariates. Thus the effort of integration is reduced several times and leads to simple analytical expressions in terms of the nodal coordinates. In order to illustrate the numerical process two examples are considered. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 759–770, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/num.10026.
A lot sizing and sequencing algorithm for dynamic demands upon a single facility
Authors: Aras Ömer A. , Swanson Lloyd A.
Published: October 2002

A heuristic algorithm is developed and applied to determine lot sizes and production sequence on a single facility. The various product demands are treated as deterministic and time varying (dynamic) over a finite planning horizon, such as that generated from a material requirements planning (MRP) system.

In contrast to other approaches available, the algorithm considers the sequencing decision in each period by realistically assuming inventory holding cost occurrence in the period of production, and in addition, it is capable of considering set‐up times where such set‐up times consume available productive capacity. The ability to handle numerous products, and the capability of being able to specify maintenance time and holidays is an integral aspect of the algorithm.

The results of an application of the algorithm in a medium size bearing company have shown very significant reduction in the controllable inventory holding cost while eliminating late deliveries. In an effort to cope with potential realistic schedule alterations, different solutions were developed for managerial evaluation providing greater flexibility but at a higher cost.
A dynamic priority rule for scheduling against due‐dates
Authors: Baker Kenneth R. , Bertrand J.W.M.
Published: October 2002

We simulate the performance of a simple production system in which due‐dates are set internally. We investigate priority rules aimed at minimizing tardiness, emphasizing a “modified duedate rule” which functions effectively in conjunction with internally‐set deadlines and which adapts to both tight and loose conditions in the due‐dates. This rule is simple and logical, and shows considerable promise for application in complex production systems.
EOQ application in a pharmaceutical environment: A case study
Authors: Ouellet Roch , Roy Jacques , Cardinal Claude , Rosconi Yves
Published: October 2002

This paper describes a successful application of classical inventory theory at a drug manufacturing plant located in Montreal that has resulted in annual savings in the order of $110,800 and assisted management in its decision to invest in larger production equipment. The basic assumptions underlying EOQ models are reviewed and dealt with. For instance, an algorithm was devised to handle the peaks in the demand of many A class items. Following the implementation of this algorithm, buffer stocks were reduced signifi cantly while maintaining the same high levels of service.
Short interval forecasting of emergency phone call (911) work loads
Authors: Mabert Vincent A.
Published: October 2002

There has been an increasing emphasis over the last 5 to 10 years to improve productivity in the Service Sector of the U.S. economy. Much of the improvement obtained by these managers has come about through better scheduling of the work force in these organizations. Effective scheduling of this personnel requires good estimates of demand, which may exhibit substantial variations between days for certain times of the year. The Indianapolis Police Department (IPD) Communications area is one such organization that exhibits varying workloads and is interested in improving staff scheduling of dispatch operators.

This article explores the use of six different forecasting techniques for predicting daily emergency call workloads for the IPD's communications area. Historical call volume data are used to estimate the model parameters. A hold‐out sample of five months compares forecasts and actual daily call levels. The forecast system utilizes a rolling horizon approach, where daily forecasts are made for the coming month from the end of the prior month. The forecast origin is then advanced to the end of the month, where the current month's actual call data are added to the historical database, new parameters are estimated, and then the next month's daily estimates are generated. Error measures of residual standard deviation, mean absolute percent error, and bias are used to measure performance. Statistical analyses are conducted to evaluate if significant differences in performance are present among the six models.

The research presented in this article indicates that there are clearly significant differences in performance for the six models analyzed. These models were tailored to the specific structure and this work suggests that the short interval forecasting problems faced by many service organizations has several structural differences compared to the typical manufacturing firm in a made‐to‐stock environment. The results also suggests two other points. First, simple modeling approaches can perform well in complex environments that are present in many service organizations. Second, special tailoring of the forecasting model is necessary for many service firms. Historical data patterns for these organizations tend to be more complex than just trend and seasonal elements, which are normally tracked in smoothing models. These are important conclusions for both managers of operating systems and staff analysts supporting these operating systems. The design of an appropriate forecasting system to support effective staff planning must consider the nature, scope, and complexity of these environments.
Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA‐binding proteins in activation of LPA receptors
Authors: Hama Kotaro , Bandoh Koji , Kakehi Yoshiyuki , Aoki Junken , Arai Hiroyuki
Published: October 2002

Lysophosphatidic acid (LPA) exerts multiple biological functions through G protein‐coupled receptors (EDG2/LPA1, EDG4/LPA2, and EDG7/LPA3) and is present in serum where it is associated with albumin. In this study we examined LPA activity in various biological fluids by measuring the LPA‐induced increase in the intracellular concentration of calcium ion in three types of Sf9 insect cells, each expressing one of the LPA receptors. Using this system, we found that EDG2 and EDG4, but not EDG7, were activated strongly by addition of incubated plasma. By contrast, LPA detected in seminal plasma, which contains a low concentration of albumin, selectively activated EDG7. After LPA in these samples was extracted and reconstituted, it activated all three receptors. We also found that serum albumin readily inhibits the activation of EDG7 but not the activation of EDG2 or EDG4. In addition, plasma from Nagase analbuminemic rats but not plasma from control Sprague–Dawley rats was found to strongly activate EDG7, although the plasma of these two types of rats contained equal amounts of LPA and activated both EDG2 and EDG4. The present study shows that serum albumin can negatively regulate EDG7 but not EDG2 or EDG4, and suggests that protein factors are present in seminal plasma and deliver LPA efficiently to EDG7 but not to EDG2 or EDG4.
Modification of rRNA as a ‘quality control mechanism’ in ribosome biogenesis
Authors: Song Xinyu , Nazar Ross N
Published: October 2002

An efficiently expressed rDNA plasmid was used to quantitatively analyze the effect of base changes in modified positions associated with the peptidyl transferase center of the 25S rRNA from the yeast Schizosaccharomyces pombe. The results show that, unlike normal RNA and relative to a less conserved modified position outside the center, these mutant RNAs are highly unstable and rapidly degraded with little or no effect on cell growth. These results provide direct evidence that the positions of modification can be critical sites for nuclease attack. Taken together with previous genetic analyses of rRNA modification, they raise the possibility that rRNA modification may act, at least in part, as a quality control mechanism to help ensure that only functional RNA is incorporated into active ribosomes.
Aluminium fluoride associates with the small guanine nucleotide binding proteins
Authors: Ahmadian Mohammad Reza , Mittal Rohit , Hall Alan , Wittinghofer Alfred
Published: October 2002

AlF4
− has long been known to associate with and activate the GDP‐bound alpha subunits of heterotrimeric G‐proteins. Recently the small guanine nucleotide binding protein Ras has also been shown to associate with AlF4
− in the presence of stoichiometric amounts of its
TPase
ctivating
rotein (GAP). Here we present the isolation of a stable Ras·GDP·AlF4
−·GAP ternary complex by gel filtration. In addition, we generalise the association of AlF4
− with the small GTP‐binding proteins by demonstrating ternary complex formation for the Cdc42, Rap and Ran proteins in the presence of their respective GAP proteins.
Kinetics of apolipoprotein E isoforms‐binding to the major glycosaminoglycans of the extracellular matrix
Authors: Shuvaev Vladimir V , Laffont Isabelle , Siest Gérard
Published: October 2002

Apolipoprotein E (apoE), a key lipid transport protein, displays a heparin‐binding property that is critical in several apoE functions. The kinetics of the interaction between apoE isoforms and glycosaminoglycans (GAGs) were studied using surface plasmon resonance. The dissociation constant of equilibrium K
D for apoE3‐heparin interaction was estimated to be 12 nM for apoE3 and three common apoE isoforms revealed similar affinities for heparin. ApoE binds to GAGs in the following order: heparin>heparan sulfate>dermatan sulfate>chondroitin sulfate. The affinity parameter of the binding of low molecular weight heparins to apoE is correlated with the chain length. The effective number Z of electrostatic interactions between plasma apoE3 and heparin was assessed to be three. Metal chelators were able to diminish apoE‐binding to heparin, suggesting some stabilizing effect of metal ions while reconstitution with lipids did not affect binding affinities for heparin, suggesting that the N‐terminal heparin‐binding site is responsible for apoE‐containing lipoprotein interactions with heparin.
Risk factors for salmonella food poisoning in the domestic kitchen – a case control study
Authors: PARRY S. M. , PALMER S. R. , SLADER J. , HUMPHREY T. , THE SOUTH EAST WALES INFECTIOUS DISEASE LIAISON GROUP
Published: October 2002

Domestic kitchen food handling risk factors for sporadic salmonella food poisoning are largely unknown. We compared food consumption and food handling practices, opportunities for cross contamination and refrigerator temperature control, in 99 households in South East Wales in 1997/8 with a case of salmonella food poisoning, and control households matched for electoral ward. On univariate analyses, cases were significantly more likely than control respondents to have purchased free-range eggs in the preceding week, and more likely than control households to have handled frozen whole chicken in the previous week, and to handle raw chicken portions at least weekly. In multivariate analysis, only consumption of raw eggs and handling free-range eggs were significant risk factors, independent of the age structure of the family and of the season.
Epidemiology of Sindbis virus infections in Finland 1981–96: possible factors explaining a peculiar disease pattern
Authors: BRUMMER-KORVENKONTIO M. , VAPALAHTI O. , KUUSISTO P. , SAIKKU P. , MANNI T. , KOSKELA P. , NYGREN T. , BRUMMER-KORVENKONTIO H. , VAHERI A.
Published: October 2002

Pogosta disease (PD), an epidemic rash-arthritis occurring in late summer is caused by Sindbis virus (SINV) and is transmitted to humans by mosquitoes. Altogether 2183 PD cases were serologically confirmed 1981–96 in Finland, with an annual incidence of 2.7/100000 (18 in the most endemic area of Northern Karelia). The annual average was 136 (varying from 1 to 1282) with epidemics occurring in August–September with a 7-year interval. Studies on 6320 patients with suspected rubella (1973–89) revealed 107 PD cases. The depth of snow cover and the temperature in May–July seemed to predict the number of cases. The morbidity was highest in 45- to 65-year-old females and lowest in children. Subclinical SINV infections were 17 times more common than the clinical ones. The SINV-antibody prevalence in fertile-age females was 0.6% in 1992; the estimated seroprevalence in Finland is about 2%. Among game animals the tetraonids (black grouse and capercaillie) had the highest seroprevalence (65%) in the epidemic year of 1981.
I spy with my little eye: interpreting seventeenth-century Venetian spy reports
Authors: Walker Jonathan
Published: October 2002

This article examines the reports written by Gerolamo Vano, a spy working in early seventeenth-century Venice. It concentrates on their form rather than their content in a attempt to assess Vano's story-telling skills. It is also an experiment in historical story-telling, which departs from some of the conventions of academic writing and embraces the melodramatic qualities of Vano's writing. In short, the article's form is used to comment allegorically upon its content.
Chinese urban history: four cheers
Authors: Bun Kwan Man
Published: October 2002

These four exciting books fill in what Sir Peter Hall's monumental Cities in Civilization left undone. To be sure, they do not tell the entire story of China's five (possibly six or more according to the latest archaeological findings) thousand years of uninterrupted urban experience, but together they are a flying start, especially from the perspective of one kind of elite or another.
The Role of T‐Lymphocytes in Hypercholesterolemia‐Induced Leukocyte‐Endothelial Interactions
Authors: STOKES KAREN Y. , CLANTON E. CHRIS , BOWLES KIMBERLY S. , FUSELER JOHN W. , CHERVENAK DEBORAH , CHERVENAK ROBERT , JENNINGS STEPHEN R. , GRANGER D. NEIL
Published: October 2002

Objective: Hypercholesterolemia promotes the adhesion of leukocytes to vascular endothelium in large and microscopic blood vessels. Lymphocytes that can modulate endothelial cell adhesion molecule expression have been implicated in the altered structure and function of large arterial vessels associated with chronic hypercholesterolemia. This study assesses the contribution of CD4+ and CD8+ T‐cells to acute inflammatory responses observed in the microcirculation of hypercholesterolemic mice.

Methods: Intravital microscopy was used to quantify baseline leukocyte‐endothelial cell interactions in cremasteric postcapillary venules of wild‐type (WT) and severe combined immunodeficient (SCID) mice placed on a normal (ND) or high‐cholesterol (HC) diet for 2 weeks. A group of SCID‐HC mice received splenocytes from WT‐HC mice (WT→SCID). Separate WT‐HC groups were depleted of neutrophils or CD4+ and/or CD8+ T‐cells.

Results: WT‐HC mice, compared with WT‐ND, exhibited exaggerated leukocyte adherence and emigration. These leukocytes were predominantly granulocytes. These responses were absent in neutropenic WT‐HC mice. SCID‐HC mice also showed significantly less leukocyte adherence and emigration than WT‐HC mice. Elevated leukocyte adherence and emigration were restored in WT→SCID mice, despite a continued absence of circulating blood lymphocytes. Selective depletion of either CD4+ or CD8+ cell populations attenuated HC‐induced leukocyte adhesion but not emigration. However, simultaneous depletion of both CD4+ and CD8+ cells attenuated both leukocyte adhesion and emigration to ND levels.

Discussion: These findings indicate that both CD4+ and CD8+ T‐cells contribute to granulocyte adhesion and emigration elicited in postcapillary venules by hypercholesterolemia.
The role of negative ions in the propagation of discharges across insulating surfaces
Authors: N L Allen  , A A R Hashem
Published: October 2002

The relative importance of atmospheric negative ions in corona formation and breakdown in a radial electric field has been investigated, with special reference to effects occurring at an insulating surface of a cycloaliphatic polyurethane with dolomite filler. The inception times, corona charge, light emission (by UV photography) and sparkover voltages under lightning impulses have been recorded under natural atmospheric conditions and under the influence of negative ions introduced from an auxiliary corona. The presence of excess negative ions on the surface is shown to increase both the charge injected and the mean radius of the corona, attributable to an augmentation of streamer discharges. In similar experiments in air, the excess ions cause a transition to a `glow' discharge. Effects of negative ions on sparkover are not significant on the insulator surface, but they cause a small increase in air. Comparisons between the two cases lead to the conclusion that the most important effect of the ions on the surface is to provide `seed' electrons for streamer propagation, following ion detachment in the field of advancing streamer tips.
Transcription Factor CBF4 Is a Regulator of Drought Adaptation in Arabidopsis
Authors: Haake Volker , Cook Daniel , Riechmann JoséLuis , Pineda Omaira , Thomashow Michael F. , Zhang James Z.
Published: October 2002

In plants, low temperature and dehydration activate a set of genes containing C-repeat/dehydration-responsive elements in their promoter. It has been shown previously that the Arabidopsis CBF/DREB1 transcription activators are critical regulators of gene expression in the signal transduction of cold acclimation. Here, we report the isolation of an apparent homolog of the CBF/DREB1 proteins (CBF4) that plays the equivalent role during drought adaptation. In contrast to the three already identified CBF/DREB1 homologs, which are induced under cold stress, CBF4 gene expression is up-regulated by drought stress, but not by low temperature. Overexpression of CBF4 in transgenic Arabidopsis plants results in the activation of C-repeat/dehydration-responsive element containing downstream genes that are involved in cold acclimation and drought adaptation. As a result, the transgenic plants are more tolerant to freezing and drought stress. Because of the physiological similarity between freezing and drought stress, and the sequence and structural similarity of the CBF/DREB1 and the CBF4 proteins, we propose that the plant's response to cold and drought evolved from a common CBF-like transcription factor, first through gene duplication and then through promoter evolution.
ACTCAT, a Novel cis-Acting Element for Proline- and Hypoosmolarity-Responsive Expression of theProDHGene Encoding Proline Dehydrogenase in Arabidopsis
Authors: Satoh Rie , Nakashima Kazuo , Seki Motoaki , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko
Published: October 2002

Proline (Pro) is one of the most widely distributed osmolytes in water-stressed plants. We previously isolated from Arabidopsis a gene encoding Pro dehydrogenase (ProDH), a mitochondrial enzyme involved in the first step of the conversion of Pro to glutamic acid. The ProDH gene in Arabidopsis is up-regulated by rehydration after dehydration but is down-regulated by dehydration.ProDH is also induced by l-Pro and hypoosmolarity. The induction of ProDH expression under rehydration seems to be caused by both accumulated Pro and hypoosmolarity. We analyzed a DNA region that is located 5′ to the transcription start site (a promoter region) of ProDH to identify cis-acting elements involved in l-Pro-induced and hypoosmolarity-induced expression in transgenic tobacco (Nicotiana tabacum) and Arabidopsis plants. We found that a 9-bp sequence, ACTCATCCT, in the ProDH promoter is necessary for the efficient expression of ProDH in response to l-Pro and hypoosmolarity. Moreover, ACTCAT is a core cis-acting element, which we have called Pro- or hypoosmolarity-responsive element (PRE), that is necessary forl-Pro-responsive and hypoosmolarity-responsive expression of ProDH. Microarray and RNA gel-blot analyses showed that 21 l-Pro-inducible genes have the PRE sequences in their promoter regions. These results indicate that the PRE sequence play an important role in the l-Pro-responsive gene expression.
Perceived risks as barriers to Internet and e‐commerce usage
Authors: Liebermann Yehoshua , Stashevsky Shmuel
Published: October 2002

Previous research suggests that perceived risk is an important ingredient in the consumer decision‐making process. The purpose of the present study is to investigate what are the perceived barriers to Internet usage and e‐marketing by both users and non‐users. By understanding these potential obstacles, more efficient marketing strategies will become available that will drive Internet use and e‐commerce. A detailed perceived risks map has been developed using a qualitative research paradigm. We suggest a model with the factors affecting the Internet’s perceived risk elements. The factors are demographic traits and usage behavior characteristics. The model is tested against a sample of 465 employed adults.
SIMULATION OF THE CASIMIR–POLDER EFFECT FOR VARIOUS GEOMETRIES
Authors: TAŞCI EMRE S. , ERKOÇ ŞAKIR
Published: October 2002

We have investigated the Casimir–Polder effect for various geometries such as concentric spherical shells, a spherical shell within a cubic shell and spherical shell within a pyramidal shell. Simulations have been performed by static calculations. Simulation results agreed with theoretical predictions.
BARYON MASSES AND WILSON LOOPS FOR FRACTIONAL D3-BRANE ON THE RESOLVED CONIFOLD
Authors: RYANG SHIJONG
Published: October 2002

We study the ir dynamics of the type IIB supergravity solution describing N D3-branes and M fractional D3-branes on the resolved conifold. The baryon mass and the tension of domain wall in the dual gauge theory are evaluated and compared with those for the deformed conifold. The ir behavior of the solution for the general conifold is also discussed. We show that the area law behavior of the Wilson loop is attributed to the existence of the locus in the ir where the D3-brane charge vanishes.
Coupling an aVLSI Neuromorphic Vision Chip to a Neurotrophic Model of Synaptic Plasticity: The Development of Topography
Authors: Elliott Terry , Kramer Jörg
Published: October 2002

We couple a previously studied, biologically inspired neurotrophic model of activity-dependent competitive synaptic plasticity and neuronal development to a neuromorphic retina chip. Using this system, we examine the development and refinement of a topographic mapping between an array of afferent neurons (the retinal ganglion cells) and an array of target neurons. We find that the plasticity model can indeed drive topographic refinement in the presence of afferent activity patterns generated by a real-world device. We examine the resilience of the developing system to the presence of high levels of noise by adjusting the spontaneous firing rate of the silicon neurons.
Nature and mechanism of ilmenite alteration: a Mössbauer and X-ray diffraction study of oxidized ilmenite from the Beja-Acebuches Ophiolite Complex (SE Portugal)
Authors: Waerenborgh J. C. , Figueiras J. , Mateus A. , Gonçalves M.
Published: October 2002

Ilmenites from the least-altered rocks of the Beja-Acebuches Ophiolite Complex (SE Portugal), with low Ti values and excess Fe, despite rare optical evidence of hematite exsolution, were studied by 57Fe Mössbauer spectroscopy and X-ray diffraction. According to single-crystal XRD the sequence of alternate layers characteristic of the ideal ilmenite structure is preserved, the excess Fe being accommodated in the Ti layers. No superparamagnetic oxides were detected by 57Fe Mössbauer spectroscopy. The typical spectra of bulk αFe2O3 and of Fe3+-containing ilmenite, in the paramagnetic state above 49 K and magnetically ordered at 6 K, are observed. The average degree of oxidation of the ilmenites, estimated from the chemical analysis assuming ideally stoichiometric full cation site occupancies, is also confirmed by 57Fe Mössbauer data. Since our crystal chemistry study gave no evidence of crypto-exsolution textures within the ilmenite with the observed compositions, fast cooling from magmatic temperatures and decomposition of ilmenite in supergene conditions is suggested.