bluuebunny/crossref_metadata_2025 huggingface dataset:
The Canadian health care system: A model for America to emulate?
Authors: Naylor C. David
Published: May 2007

The American health care system has the world's highest per capita costs and over 30 million citizens uninsured. The neighbouring Canadian system provides coverage for all basic medical and hospital services, at costs per capita that are about US$700 lower. Single‐agency public funding allows tighter control of Canadian expenditures, and reduces administrative overheads. Hospitals are run as non‐profit private corporations, funded primarily by a fixed annual allocation for operating costs. Most physicians are in private fee‐for‐service practice, but cannot charge more than the insured tariff negotiated between their provincial government and medical association. This approach, while attractive in its decentralization, tends to separate the funding and management of clinical services. Thus, hospital information systems lag a decade behind the USA, managed care initiatives are few, health maintenance organisations do not exist, and experimentation with alternative funding or delivery systems has been sporadic.

Strengths of the system compared to the USA include: higher patient satisfaction, universal coverage, slightly better cost containment, higher hospital occupancy rates, and reduction in income‐related rationing with more equitable distribution of services. Weaknesses in common with the United States are: cost escalation consistently outstripping the consumer price index with costs per capita second highest in the world, ever rising consumption of services per capita, inadequate manpower planning and physician maldistribution, poor regional co‐ordination of services, inadequate quality assurance and provider frustration. Additional weaknesses include: an emerging funding crisis caused by the massive federal deficit, less innovation in management and delivery of care as compared to the USA, implicit rationing with long waiting lists for some services, and recurrent provider‐government conflicts that have reduced goodwill among stakeholders. Thus, while the Canadian model has important advantages, it does not offer a panacea for American health care woes.
Discounting and health benefits: Another Perspective
Authors: Cairns John
Published: May 2007

This paper reviews the argument advanced by Parsonage and Neuburger that the non‐monetary benefits of health programmes should be discounted at lower rate than that used for financial flows. The conceptual issues raised in the paper are discussed and others, such as the tradability of non‐monetary benefits and the link between individual and social discount rates are introduced. The collection and assessment of more evidence is needed before Parsonage and Neuburger's Proposition can be supported.
Lessons in long‐term care: The benefits of a northern exposure
Authors: Kane Robert L.
Published: May 2007

Canada stands as an important lesson for the United States. At the very minimum it represents the art of the possible. For those interested in long‐term care, it suggests that it is possible to include long‐term care in a programme of universally accessible care without national bankruptcy. Although Canada has brought medical and social services closer together and has brought acute and chronic care under the same aegis, not all the problems of coordinating such efforts have been solved. For others, the Canadian example shows that care can be provided to all persons who need it without creating uncontrollable expenses or removing families' motivations to care for their own. In so doing, universal coverage creates the opportunity for better coordination of services and ultimately for more efficient care.
Appraising the use of contingent valuation
Authors: Morrison Gwendolyn C. , Gyldmark Marlene
Published: May 2007

The valuation of treatments and health states has been pursued in a number of ways. Most predominant are contingent valuation (CV), QALYs, and HYEs. CV—that is, willingness to pay and willingness to accept—is the only one of these methods that can be consistent with welfare economic theory, but, as discussed by Gafni (1990), in order to do so three criteria must be met. This article argues that the fulfilment of these criteria is not sufficient to obtain useful results, and some additional criteria are suggested. Several CV studies carried out in the area of health are reviewed, and their compliance or non‐compliance, with both sets of criteria, is discussed. Finally, it is argued that, although CV is the more theoretically correct method, it is not a superior tool to QALYs and HYEs, and that the decision as to which is the appropriate valuation method depends on the policy issue at hand.
Qaly league tables: Handle with care
Authors: Gerard Karen , Mooney Gavin
Published: May 2007

This paper examines some of the difficulties in using QALY league tables in priority setting. Such tables sometimes are seen as being ‘the’ way to prioritise in health care and in particular, at present, with respect to priority setting among purchasers in the UK NHS. However the paper highlights the fact that the base on which such tables is built is small—relatively few studies in the English language using CUA have been conducted anywhere. Further, four issues which require handling with care are set out: (i) the relevant measure of cost in QALY league tables has to be restricted to health service resource use; (ii) the relevant measure of benefit in QALY league tables is clearly restricted to QALYs, thereby the utility of health gains and indeed the maximisation of the utility of health gains; (iii) in incorporating the results of CUA studies into QALY league tables there is a need for greater clarification on what the margin constitutes; and (iv) those who might use CUA results in QALY league tables need to ascertain whether the original context of the study will allow the results to be transferred to the local context of the decision maker. The paper suggests that there is a need to be quite clear what goal QALY league tables serve. The authors argue that the only legitimate (and clearly important) goal of QALY league tables is the maximisation of the utility of health gains within a health service budget.

The thinking underlying QALY league tables, adjusted to take account of the caveats in this paper, is the key to rational priority setting at a local level. It is this thinking that is to be emphasised rather than the use of ‘imported’ league tables or the use of results from CUA studies conducted elsewhere in the country or indeed in other countries. If results from elsewhere are to be used, the study context has to be examined carefully to establish the extent of its relevance to the local circumstances facing the purchasing authority.
Equitable access to health care: Methodological extensions to the analysis of physician utilization in Canada
Authors: Birch Stephen , Eyles John , Newbold K. Bruce
Published: May 2007

In this paper we analyse the distribution of family physician use in Canada to explore whether the stated goal of reasonable access to care has been achieved. We test hypotheses to see whether (a) variations in incidence and quantity of use are independent of need for care as proxied by self‐assessed health status and (b) any observed relationship between variations in use and need is independent of other population characteristics.

Previous research has conceptual, statistical and data limitations which bring into question the validity of the findings. These limitations are addressed by using more appropriate data, a conditional model for service utilization and correction for self‐selectivity of users in the statistical analysis.

Variations in need are identified as important and significant in explaining variations in both incidence and quantity of use with the estimated relationship between use and need being positive. Other population characteristics were found to be important and significant in explaining variations in use although household income is not among them. The relationship between use and need is associated with other variables including education, social support and region of residence.

These findings suggest that analyses of utilization based on simple multivariate techniques and aggregate data can produce a picture of utilization that conceals important, policy relevant relationships while revealing other relationships that are essentially artifacts of inappropriate aggregation in ways which provide a false sense of achievement.
A cell based approach to modelling public expenditure
Authors: Propper Carol
Published: May 2007

The paper examines the use of a cell based model to analyse the effects of demographic change on the level and distribution of public expenditure. The nature and advantages of a cell based model for this purpose are described. The level and distribution of the key components of welfare state expenditure—health, education, social security—and of direct taxes, is examined for the base year of 1985. The net transfer of resources is compared to the distribution of income across cells. The effect of demographic change on the level and distribution of health and education expenditure is analysed. Issues in the further development of this approach are then reviewed.
Convergent validity of two measures of the quality of life
Authors: Whynes David K. , Neilson Aileen R.
Published: May 2007

In the paper, a test of convergent validity is undertaken for two methods of quality of life assessment, one based on a shortened version of the Health Measurement Questionnaire and the other based on professional clinical judgement. The Nottingham Health Profile is used as the comparator, and the data derive from a sample of colorectal cancer patients. Criteria for convergent validity are established and both methods yield outcomes broadly consistent with such criteria.
Time preferences for health gains: An empirical investigation
Authors: Olsen Jan Abel
Published: May 2007

The purpose of this study was to elicit the implied discount rates to be used in economic evaluations of health care programmes. The paper presents results from two Norwegian surveys in which a random sample of the population and a sample of health planners were asked to prioritise between alternative health care programmes, and make trade‐offs between future health gains and more immediate gains. The questionnaire had four hypothetical choice situations; two for life saving and two for health improvement.
Expected social utility of life time in the presence of a chronic disease
Authors: Mulder Paul G. H. , Hempenius Anton L.
Published: May 2007

Interventive action aimed at reducing the incidence of an irreversible chronic noncommunicable disease in a population has various effects. Hopefully, it increases total longevity in the population and it causes the disease to develop later in time in a smaller portion of the population. In this paper a statistical model is built by which these effects can be estimated. A three dimensional probability density function that underlies this model is changed by the interventive action. It is shown how a three dimensional utility function can be defined to appropriately judge this change.
The contingent valuation method—appraising the appraisers
Authors: Johannesson Magnus
Published: May 2007

Morrison & Gyldmark (MG)1 in a recent issue of health economics reviewed the use of the contingent valuation (CV) method of measuring willingness to pay in the health area. Although it is useful to examine the appropriate role of the CV method in the health care field, the appraisal by MG has a number of limitations which are pointed out in this paper. These relate to some inaccuracies in the review of the literature, the limited nature of the criteria proposed by MG to evaluate CV studies, and finally I argue that the comparison between CV, QALYs, and HYEs is premature and confuses rather than clarifies the debate.
Is vaccination against hepatitis b efficient? A review of world literature
Authors: Jefferson Tom , Demicheli Vittorio
Published: May 2007

We report on the result of a study aimed at assessing the variability of assumptions upon which economic models for the introduction of vaccination against Hepatitis B are based, the conclusions reached and define a minimum set of methodological standards upon which future economic studies on vaccines should be based. We identified 116 published and unpublished works by Medline literature searches, consulting private databases and corresponding with all authors and researchers active in economic evaluation of vaccines.

All works were assessed but we included in our review only those which were original economic analyses (90 studies). Principal epidemiological and economic variables were extracted and compared where possible. Rough manipulations were carried out to make the data comparable. We found profound variability on the main parameters of the efficiency equation (disease incidence, costing methods, use of marginal theory, discounting and study timespan, sensitivity analysis and reporting methods). We also found inconsistencies in definition and study design in 38% of a subset of studies. Although we found scarce decision‐making impact, we believe that due to uncertain or unclear methodology, few studies reach valid conclusions. In future decisions may be based on biased evidence and scarce resources committed to untested programmes. There is an urgent need to standardise study methods and define a common set of procedures.
PAR1‐mediated RhoA activation facilitates CCL2‐induced chemotaxis in PC‐3 cells
Authors: Loberg Robert D. , Tantivejkul Kwanchanit , Craig Matthew , Neeley Chris K. , Pienta Kenneth J.
Published: May 2007

Patients with advanced prostate cancer often exhibit increased activation of the coagulation system. The key activator of the coagulation cascade is the serine protease thrombin which is capable of eliciting numerous cellular responses. We previously reported that the thrombin receptor PAR1 is overexpressed in prostate cancer. To investigate further the role of PAR1 in prostate cancer metastasis, we examined the effects of thrombin activation on cell adhesion and motility in PC‐3 prostate cancer cells. Activation of PAR1‐induced dynamic cytoskeletal reorganization and reduced PC‐3 binding to collagen I, collagen IV, and laminin (P < 0.01) but not fibronectin. Expression of the cell surface integrin receptors did not change as assessed by flow cytometry. Immunofluorescence microscopy revealed that PAR1 stimulation caused reorganization of the focal adhesions, suggesting that PAR1 activation in PC‐3 cells may be modulating cell adhesion through integrin function but not expression. Furthermore, RhoA was activated upon stimulation with thrombin with subsequent cell contraction, decreased cell adhesion, and induced migration towards monocyte chemoattractant protein 1 (MCP‐1; CCL2). Thus, it appears that thrombin stimulation plays a role in prostate cancer metastasis by decreasing cell adhesion to the extracellular matrix and positioning the cell in a “ready state” for migration in response to a chemotactic signal. Further exploration is needed to determine whether PAR1 activation affects other signaling pathways involved in prostate cancer. J. Cell. Biochem. 101:1292–1300, 2007. © 2007 Wiley‐Liss, Inc.
Marfella CG, Ohkawa Y, Coles AH, Garlick DS, Jones SN, Imbalzano AN. 2006. Mutation of the SNF2 family member Chd2 affects mouse development and survival. J Cell Physiol 209:162–171.
Authors: Marfella Concetta G.A. , Ohkawa Yasuyuki , Coles Andrew H. , Garlick David S. , Jones Stephen N. , Imbalzano Anthony N.
Published: May 2007

The original article to which this erratum refers was published in J Cell Physiol 2006; 209:162–171.
Karyotype of the human insulinoma CM cell line—Beta cell model in vitro?
Authors: Jonnakuty Catherine , Gragnoli Claudia
Published: May 2007

The CM cell line is derived from a human pancreatic insulinoma and is used as a beta cell model for the study of the pathogenesis of diabetes, as it appears to maintain the characteristics of beta cells. However, a karyotype study of the CM cell line was not previously performed. We aimed at karyotyping the CM cell line to confirm its human origin, diploid karyotype, and chromosomal structure. We karyotyped the CM cells at earlier passages with the standard Giemsa technique. The karyotyping procedure confirmed the human origin of the CM cell line. However, the karyotype showed 64 chromosomes with structural abnormalities, including chromosome 11, in which the insulin gene is located. Our Medline search of other existing insulinoma cell lines of rodent, mouse and hamster origin did not show any karyotype performed. As the CM cell karyotype reveals significant structural and numerical chromosomal abnormalities, we question the use of such a cell line as an in vitro beta cell model. We suggest that insulinoma cell lines established in vitro to study beta cell function should have a karyotype performed to exclude chromosomal aberrations. J. Cell. Physiol. 213:661–662. © 2007 Wiley‐Liss, Inc.
Identification of molecular compounds critical to Alzheimer's‐like plaque formation
Authors: Gellermann Gerald P. , Ullrich Kathrin , Unger Christiane , Fändrich Marcus , Sauter Simon , Diekmann Stephan
Published: May 2007

Amyloid diseases are characterized by the formation of insoluble amyloid fibrils from previously soluble polypeptides. In Alzheimer's disease (AD), amyloid fibrils, formed from β‐amyloid peptides, are deposited as extracellular amyloid plaques only inside the brain. As previously shown, Alzheimer's‐like plaque formation in human monocyte culture recapitulates the features of in vivo amyloid plaque formation. Here we show that this cell model can be used to screen compounds that potentially influence amyloid formation in a throughput manner. We found that cellular amyloid fibril formation can be enhanced by dextran sulfate as well as heparin and can be impaired by stabilization of a micell‐like β‐amyloid conformer by using myoinositol or by inhibition of phagocytosis with cytochalasin D. Altogether, our data demonstrate the utility of this cell model for investigating pathways and molecular interactions critical to amyloidogenesis. © 2007 Wiley‐Liss, Inc.
Trophism of neural progenitor cells to embryonic stem cells: Neural induction and transplantation in a mouse ischemic stroke model
Authors: Fong Shu Pan , Tsang Kam Sze , Chan Amy Bik Wan , Lu Gang , Poon Wai Sang , Li Karen , Baum Larry William , Ng Ho Keung
Published: May 2007

Embryonic stem cell (ESC)–derived products have emerged as a promising cell source for neuroregeneration. C17.2 neural precursor cells were noted to express genes of neurotrophins and neuroprotective factors and to be enable to enhance proliferation, neuritogenesis, and differentiation of SH‐SY5Y and SK‐N‐AS neuroblasts, suggesting their neurotrophic potential. We used C17.2 cells as neurotrophic chaperones to induce ESCs, D3, and E14TG2a into neural lineage cells. Significantly greater numbers of Sox‐2+, Musashi‐1+, and nestin+ neurospheres developed in noncontact cocultures than in cultures of ESCs without C17.2 support or with 50% conditioned medium after 8 days. Immunoreactivity of the neuronal, astrocytic and oligodendrocytic markers was evident in cultures further differentiated for 10 days. Expression of Pax‐6, Otx‐1, and Nurr‐1 genes suggested neuroectodermal precursors in products encompassing neural stem cells, dopaminergic neurons, astrocytes, and oligodendrocytes. α‐Fetoprotein, GATA‐4, Brachyury, Nkx‐2.5, and Myf‐5 genes were not detected, indicating any mesodermal and endodermal cells. However, weak expression of Oct‐4 was noted. Behavioral assessment of ischemic mice 2 weeks after transplantation revealed significant improvement in cognitive function compared with that in ischemic sham‐operated mice. Tracking bromodeoxyuridine‐labeled products demonstrated that mostly implanted cells were localized along the needle track of the injection in the brain parenchyma, whereas some migrated to the striatum, cortex, nerve fiber bundle of the corpus callosum, and hippocampus in the ipsilateral hemisphere. One episode (of 22) of teratoma development was noted. Data from this study suggest a paradigm of trophism of neural progenitor cells for induction of ESCs into neural lineage cells. © 2007 Wiley‐Liss, Inc.
Long‐term delivery of FGF‐6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve
Authors: Grumbles Robert M. , Casella Gizelda T. B. , Rudinsky Michelle J. , Wood Patrick M. , Sesodia Sanjay , Bent Melissa , Thomas Christine K.
Published: May 2007

Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target‐derived trophic factor levels may limit reinnervation. Our aim was to examine whether long‐term infusion of fibroblast growth factor‐6 (FGF‐6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 μg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14–15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline‐treated muscles than in FGF‐6‐treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%–51% of non‐denervated fibers. Denervated fiber area averaged 11%. FGF‐6‐treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline‐treated muscles. FGF‐6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF‐6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF‐6 on fiber type are independent of the neuron source used for reinnervation. © 2007 Wiley‐Liss, Inc.
Role of TPH‐2 in brain function: News from behavioral and pharmacologic studies
Authors: Invernizzi Roberto W.
Published: May 2007

The recent discovery of TPH‐2, a new isoform of tryptophan hydroxylase, the enzyme that catalyses the transformation of tryptophan into 5‐hydroxytryptophan and the rate‐limiting step in brain serotonin (5‐HT) biosynthesis, has boosted new interest in the many functions of 5‐HT in the brain and non‐nervous tissues. Recent studies on TPH‐2 are reviewed with particular attention to the role of this enzyme in behavior and in response to drugs as assessed by comparing strains of mice carrying a functional polymorphism of TPH‐2. Most studies concur to indicate that 5‐HT synthesis through TPH‐2 influence nervous tissues whereas TPH‐1 is responsible for the synthesis and action of 5‐HT in peripheral organs. Partial impairment of brain 5‐HT synthesis caused by polymorphism of the gene encoding TPH‐2 causes reduced release of the neurotransmitter, increased aggressiveness, and alters the response to drugs inhibiting the reuptake of 5‐HT. Strain comparison might be a useful strategy to investigate the genotype‐dependent alterations of TPH‐2. © 2007 Wiley‐Liss, Inc.
Developmental changes in the association of NMDA receptors with lipid rafts
Authors: Besshoh Shintaro , Chen Sheng , Brown Ian R. , Gurd James W.
Published: May 2007

Lipid rafts (LR) are lipid microdomains present in the cell surface membrane that are organizational platforms involved in protein trafficking and formation of cell signaling complexes. In the adult brain, NMDA receptors (NMDAR) and receptor‐associated proteins such as membrane‐associated guanylate kinases (PSD‐95 and SAP102), are distributed between the postsynaptic density (PSD) and lipid rafts. However, the time course of the association of NMDAR with LR during neural development is not known. We therefore investigated the effect of development on the association of NMDAR with LR prepared from rat brains ranging in postnatal age from 1–35 days and compared this with their expression in PSDs. LR and PSD fractions were prepared by extraction of P2 membranes with Tx‐100 followed by sucrose density gradient centrifugation. The yield of LR, as reflected by levels of protein, Thy‐1, and flotillin‐1 increased during postnatal development. NR2A was associated predominantly with the lipid raft fraction at all ages examined whereas NR2B underwent a gradual shift from PSDs to lipid rafts during the first 3 weeks after birth. These changes in the distribution of NR2A and NR2B were paralleled by changes in the distribution of PSD‐95 and SAP102 respectively. Tyrosine‐phosphorylated proteins, including NR2A and NR2B, were preferentially associated with lipid rafts in older, as compared to younger, animals. These results show that the association of NMDAR with LR is regulated developmentally. © 2007 Wiley‐Liss, Inc.
Origin identification on the commercial samples of Aurantii Fructus
Authors: Chuang Ching‐Ching , Wen Wu‐Che , Sheu Shuenn‐Jyi
Published: May 2007

A total of 50 commercial samples of Aurantii Fructus, originating from Poncitrus trifoliata for Aurantii Fructus Immaturus, Citrus aurantium, and C. wilsonii for Aurantii Fructus Maturus, respectively, were collected from Taiwan and China herbal markets. Contents of the constituents in the samples were determined within 60 min using a developed HPLC method, which had been validated in terms of precision, repeatability, and accuracy. The results of the analyses showed that the constituents were closely related to the species and also the degree of maturity of the fruits, especially in the case of hesperidin (HE), naringin (NG), neohesperidin (NE), naringenin‐7‐glucoside (NGC), narirutin (NR), and quercetin (QU). The mature fruits (C. aurantium and C. wilsonii) contained chiefly NG, HE, and NE and the immature ones (P. trifoliata) had NG, NR, and QU majorly. Within the mature samples, the ratios of HE/NE and NGC/NE values were higher than 2.94 and 0.21 in C. aurantium and lower than 1.31 and 0.02 in C. wilsonii, respectively. A flowchart that is useful for identifying Aurantii Fractus was devised, based on the various chemical identification methods.
Development of SPE for recovery of polysaccharides and its application to the determination of monosaccharides composition of the polysaccharide sample of a lactobacillus KLB 58
Authors: Baik Yoon Suk , Cheong Won Jo
Published: May 2007

A new SPE cartridge has been prepared in this study to purify polysaccharides of high molecular weights. A porous nonpolar styrene–divinylbenzene copolymer phase (Hamilton PRP‐1) was used to make the new cartridge. The cartridge was conditioned with methanol, water, and ACN in sequence, and the sample dissolved in a small amount of water was loaded. Impurities of low molecular weights were removed first by elution of 80:20 or 90:10 v/v% ACN/water, and polysaccharides were quantitatively recovered by elution of 50:50 v/v% ACN/water or pure water. The recovery of pure dextran 10000 was 90–95%. The SPE method was applied to purification of the polysaccharide sample of KLB58, a new lactobacillus discovered in Korea. The purified KLB 58 sample (weight recovery after SPE purification; 60%) was hydrolyzed for analysis of composition of monosaccharides. The hydrolysate was found to be composed primarily of fructose, glucose, galactose, rhamnose, mannose with small amounts of fucose and ribose.
Protein sequence information by matrix‐assisted laser desorption/ionization in‐source decay mass spectrometry
Authors: Hardouin Julie
Published: May 2007

Proteins from biological samples are often identified by mass spectrometry (MS) with the two following “bottom‐up” approaches: peptide mass fingerprinting or peptide sequence tag. Nevertheless, these strategies are time‐consuming (digestion, liquid chromatography step, desalting step), the N‐ (or C‐) terminal information often lacks and post‐translational modifications (PTMs) are hardly observed. The in‐source decay (ISD) occurring in a matrix assisted laser desorption/ionization (MALDI) source appears an interesting analytical tool to obtain N‐terminal sequence, to identify proteins and to characterize PTMs by a “top‐down” strategy. The goal of this review deals with the usefulness of the ISD technique in MALDI source in proteomics fields. In the first part, the ISD principle is explained and in the second part, the use of ISD in proteomic studies is discussed for protein identification and sequence characterization. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 26:672–682, 2007
Molecular modeling of adenosine receptors: new results and trends
Authors: Martinelli Adriano , Tuccinardi Tiziano
Published: May 2007

Adenosine is a ubiquitous neuromodulator, which carries out its biological task by stimulating four cell surface receptors (A1, A2A, A2B, and A3). Adenosine receptors (ARs) are members of the superfamily of G protein‐coupled receptors (GPCRs). Their discovery opened up new avenues for potential drug treatment of a variety of conditions such as asthma, neurodegenerative disorders, chronic inflammatory diseases, and many other physiopathological states that are believed to be associated with changes in adenosine levels. Knowledge of the 3D structure of ARs could be of great help in the task of understanding their function and in the rational design of specific ligands. However, since GPCRs are membrane‐bound proteins, high‐resolution structural characterization is still an extremely difficult task. For this reason, great importance has been placed on molecular modeling studies and, particularly in the last few years, on homology modeling (HM) techniques. The publication of the first high‐resolution crystal structure for bovine rhodopsin (bRh), a GPCR superfamily member, provides the option of utilizing HM to generate 3D models based on detailed structural information. In this review we report, analyze, and compare the main experimental data, computational HM procedures and validation methods used for ARs, describing in detail the most successful results. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 247–277, 2008
DNA methylation and chromatin accessibility of the proximal Cyp19 promoter region 1.5/2 correlate with expression levels in sheep placentomes
Authors: Fürbass Rainer , Selimyan Roza , Vanselow Jens
Published: May 2007

Placental oestrogens play an important role as local regulators of placental growth and differentiation during gestation, and toward term they are also involved in the preparation of parturition. They are synthesized within the fetal cotyledons of placentomes by aromatase cytochrome P450 (P450arom; EC 1.14.14.1), the product of the Cyp19 gene. The first step of regulation of P450arom expression, and hence enzyme activity and oestrogen production, takes place at the level of Cyp19 transcription, which is driven by a proximal promoter region, P1.5/2, in the sheep placenta. The aim of the present study was to find out if different Cyp19 expression levels, which previously had been observed in ovine placentome tissues, correlate with the tissue‐specific chromatin structure of the promoter. To this end, we investigated the chromatin structure across the P1.5/2 region in caruncles and cotyledons from 100 and 125 days pregnant ewes, and in term placentae, respectively, by analyzing the DNA methylation and the accessibility to restriction digestion. Our data show that: (1) cotyledonal DNA was significantly lower methylated than caruncular DNA; (2) methylation of cotyledonal DNA was low at 100 and 125 days of pregnancy, and increased to a significant higher level in term placentae; and (3) concurrently, cotyledonal chromatin became inaccessible to restriction digestion at term of gestation. The results imply that DNA methylation and chromatin accessibility of the P1.5/2 promoter region correlate with expression levels of the Cyp19 gene. Mol. Reprod. Dev. 75: 1–7, 2008. © 2007 Wiley‐Liss, Inc.
Optimal dispatching strategies for vehicles having exponentially distributed trip times
Authors: Asgharzadeh Kamran , Newell G. F.
Published: May 2007

A transportation system has N vehicles with no capacity constraint which take passengers from a depot to various destinations and return to the depot. The trip times are considered to be independent and identically distributed random variables. The dispatch strategy at the depot is to dispatch immediately, or to hold any returning vehicles with the objective of minimizing the average wait per passenger at the depot, if passengers arrive at a uniform rate.

Optimal control strategies and resulting waits are determined in the special case of exponentially distributed trip time for various N up to N = 15. For N ≫ 1, the nature of the solution is always to keep a reservoir of vehicles in the depot, and to decrease (increase) the time headway between dispatches as the size of the reservoir gets larger (smaller). For sufficiently large N, one can approximate the number of vehicles in the reservoir by a continuum and obtain analytic experession for the optimal dispatch rate as a function of the number of vehicles in the reservoir. For the optimal strategy, it is shown that the average number of vehicles in the depot is of order N1/3. These limit properties are expected to be quite insensitive to the actual trip time distribution, but the convergence of the exact properties to the continuum approximation as N → ∞ is very slow.
Probabilistic formulations of the multifacility weber problem
Authors: Aly Adel A. , White John A.
Published: May 2007

The problem considered is to locate one or more new facilities relative to a number of existing facilities when both the locations of the existing facilities, the weights between new facilities, and the weights between new and existing facilities are random variables. The new facilities are to be located such that expected distance traveled is minimized. Euclidean distance measure is considered; both unconstrained and chance‐constrained formulations are treated.
The constrained shortest path problem
Authors: Aneja Y. P. , Nair K. P. K.
Published: May 2007

The shortest path problem between two specified nodes in a general network possesses the unimodularity property and, therefore, can be solved by efficient labelling algorithms. However, the introduction of an additional linear constraint would, in general, destroy this property and the existing algorithms are not applicable in this case. This paper presents a parametric approach for solving this problem. The algorithm presented would require, on the average, a number of iterations which is polynomially bounded. The similarity of this approach to that of the generalized Lagrange multiplier technique is demonstrated and a numerical example is presented.
An algorithm for 0‐1 multiple‐knapsack problems
Authors: Hung Ming S. , Fisk John C.
Published: May 2007

The 0‐1 multiple‐knapsack problem is an extension of the well‐known 0‐1 knapsack problem. It is a problem of assigning m objects, each having a value and a weight, to n knapsacks in such a way that the total weight in each knapsack is less than its capacity limit and the total value in the knapsacks is maximized.

A branch‐and‐bound algorithm for solving the problem is developed and tested. Branching rules that avoid the search of redundant partial solutions are used in the algorithm. Various bounding techniques, including Lagrangean and surrogate relaxations, are investigated and compared.
Estimating value in a uniform auction
Authors: Samaniego Francisco J. , Kaiser Lee D.
Published: May 2007

Consider an auction in which increasing bids are made in sequence on an object whose value θ is known to each bidder. Suppose n bids are received, and the distribution of each bid is conditionally uniform. More specifically, suppose the first bid X1 is uniformly distributed on [0, θ], and the ith bid is uniformly distributed on [Xi−1, θ] for i = 2, …︁, n. A scenario in which this auction model is appropriate is described. We assume that the value θ is un known to the statistician and must be esimated from the sample X1, X2, …︁, Xn. The best linear unbiased estimate of θ is derived. The invariance of the estimation problem under scale transformations in noted, and the best invariant estimation problem under scale transformations is noted, and the best invariant estimate of θ under loss L(θ, a) = [(a/θ) − 1]2 is derived. It is shown that this best invariant estimate has uniformly smaller mean‐squared error than the best linear unbiased estimate, and the ratio of the mean‐squared errors is estimated from simulation experiments. A Bayesian formulation of the estimation problem is also considered, and a class of Bayes estimates is explicitly derived.
A generalized‐indices transportation problem
Authors: Bammi Deepak
Published: May 2007

A generalized‐indices transportation problem is formulated and an algorithm is presented for its solution. The algorithm is an extension of the modi‐method. A theorem on the number of independent variables in the generalized‐indices transportation problem is proved. An example problem is solved for the four‐indices transportation problem. A computer program has been written to solve any four‐indices problem.
A problem in network interdiction
Authors: Golden Bruce
Published: May 2007

Suppose we are given a network G=(V,E) with arc distances and a linear cost function for lengthening arcs. In this note, we consider a network‐interdiction problem in which the shortest path from source node s to sink node t is to be increased to at least τ units via a least‐cost investment strategy. This problem is shown to reduce to a simple minimum‐cost‐flow problem. Applications and generalizations are discussed, including the multiple‐destination case.
Convex/stochastic programming and multilocation inventory problems
Authors: Karmarkar Uday S.
Published: May 2007

This paper examines a convex programming problem that arises in several contexts. In particular, the formulation was motivated by a generalization of the stochastic multilocation problem of inventory theory. The formulation also subsumes some “active” models of stochastic programming. A qualititative analysis of the problem is presented and it is shown that optimal policies have a certain geometric form. Properties of the optimal policy and of the optimal value function are described.
Adaptive disposal models
Authors: Derman C. , Lieberman G. J. , Ross S. M.
Published: May 2007

This paper reconsiders the classical model for selling an asset in which offers come in daily and a decision must then be made as to whether or not to sell. For each day the item remains unsold a continuation (or maintenance cost)cis incurred. The successive offers are assumed to be independent and identically distributed random variables having an unknown distributionF. The model is considered both in the case where once an offer is rejected it may not be recalled at a later time and in the case where such recall of previous offers is allowed.
Least‐absolute‐value estimators for one‐way and two‐way tables
Authors: Armstrong R. D. , Frome E. L.
Published: May 2007

This paper concerns itself with the problem of estimating the parameters of one‐way and two‐way classification models by minimization of the sum of the absolute deviations of the regression function from the observed points. The one‐way model reduces to obtaining a set of medians from which optimal parameters can be obtained by simple arithmetic manipulations. The two‐way model is transformed into a specially structured linear programming problem, and two algorithms are presented to solve this problem. The occurrence of alternative optimal solutions in both models is discussed, and numerical examples are presented.
The next decade of logistics research
Authors: Wagner Harvey M.
Published: May 2007

Pathbreaking logistics research over the next 10 years will focus on systems problems. Whereas past research generally has taken a “bottom‐up” approach, future investigations are likely to pursue a “top‐down” philosophy. Specifically, attention will concentrate on diagnosis of systems' improvement potentials; easy‐to‐use analytic approaches, inherently approximative, will be devised for quickly ascertaining whether a complex operating system can be substantially and effectively improved. Theories to assist in overall systems design, particularly the setting of boundaries and buffers among systems components, will be developed. At the same time, techniques for accurately forecasting future systems performance will be investigated.

Underlying such research will be efforts to gain better understanding of management information requirements, including approaches for monitoring systems performance and providing early warning detection of systems degradation Improved management information systems will have to be coupled with appropriate design of managerial organizations and assignment of decision making responsibilities. Important avenues of research will he development of robust approaches, that is, both mathematical techniques and organizational approaches that are not too adversely affected by limited data, a changing environment, and human frailly.

Finally, critical research will be directed at the implementation process, especially the interaction among initiation, design, testing and ultimate adoption

This prognosis will explore the above themes in the context of large‐scale, complex systems. The decision areas will encompass inventory replenishment, multiechelon hierarchies for stockage and maintenance, procurement, transportation, scheduling, facilities planning, budgeting, reliability and personnel management.
The asymptotic distribution of order statistics
Authors: Weiss Lionel
Published: May 2007

For each n., X1(n), X2(n), …, Xn(n) are IID, with common pdf fn(x). y1(n) < … < Yn (n) are the ordered values of X1 (n), …, Xn(n). Kn is a positive integer, with lim Kn = ∞. Under certain conditions on Kn and fn (x), it was shown in an earlier paper that the joint distribution of a special set of Kn + 1 of the variables Y1 (n), …, Yn (n) can be assumed to be normal for all asymptotic probability calculations. In another paper, it was shown that if fn (x) approaches the pdf which is uniform over (0, 1) at a certain rate as n increases, then the conditional distribution of the order statistics not in the special set can be assumed to be uniform for all asymptotic probability calculations. The present paper shows that even if fn (x) does not approach the uniform distribution as n increases, the distribution of the order statistics contained between order statistics in the special set can be assumed to be the distribution of a quadratic function of uniform random variables, for all asymptotic probability calculations. Applications to statistical inference are given.
Nonextreme point solution strategies for linear programs
Authors: Cooper Leon , Kennington Jeff
Published: May 2007

This exposition presents two algorithms for linear programs which allow a value change in more than one nonbasic variable at each iteration. The computational formulae are developed and errors which have appeared in the literature are noted. One algorithm is a multiple basis exchange procedure while the second is a feasible direction method. There remain many computational challenges in the area of linear programming and we hope that this investigation will encourage additional work in the directions indicated in this exposition.
On n/1/F̄ dynamic deterministic problems
Authors: Chandra Ramesh
Published: May 2007

We consider sequencing of n jobs which will arrive intermittently and are to be processed on a single machine; the arrival and the processing times of each jobs are assumed known. A schedule is to be developed that minimizes the mean flow time. Two models are considered: (i) when no pre‐emption or inserted idle time is allowed in the schedule, and (ii) when pre‐emption is allowed but the jobs follow a pre‐empt‐repeat discipline We illustrate that Cobham's and Phipp's SPT dispatching rule does not guarantee the optimum F̄ even for the non‐preemptive model We propose a branch and bound algorithm for both models and discuss our computational experience We also examine the relative performances of the optimum nonpre‐emptive sequence, and the optimum pre‐empt‐repeat sequence over that resulting from SPT dispatching rule on a large number of sets of jobs of varying sizes and tightness.
Damage calculations for unreliable warheads
Authors: Curran R. T. , Jaquette S. C. , Politzer J. L.
Published: May 2007

For large numbers of perfectly reliable, optimally targeted warheads the square‐root law approximates the expected fraction damage achieved on an area target. In this paper a more exact expression is derived for this damage fraction which Holds for all numbers of warheads. This expression is shown to converge to the square‐root law when a large number of warheads are fired. The more exact expression is used in a procedure to calculate expected damage when warheads are unreliable, and this procedure is shown to be superior to a modified square‐root approximation which has been used previously.
Test selection for a mass screeening program
Authors: Voelker John A. , Pierskalla William P.
Published: May 2007

Periodic mass screening is the scheduled application of a test to all members of a population to provide early detection of a randomly occurring defect or disease. This paper considers periodic mass screening with particular reference to the imperfect capacity of the test to detect an existing defect and the associated problem of selecting the kind of test to use. Alternative kinds of tests differ with respect to their reliability characteristics and their cost per application.

Two kinds of imperfect test reliability are considered. In the first case, the probability that the test will detect an existing defect is constant over all values of elapsed time since the incidence of the defect. In the second case, the test will detect the defect if, and only if, the lapsed time since incidence exceeds a critical threshold T which characterizes the test.

The cost of delayed detection is an arbitrary increasing function (the “disutility function”) of the duration of the delay. Expressions for the long‐run expected disutility per unit time are derived for the above two cases along with results concerning the best choice of type of test (where the decision rules make reference to characteristics of the disutility function).
The use of dynamic programming methodology for the solution of a class of nonlinear programming problems
Authors: Cooper Mary W.
Published: May 2007

This paper presents an application of a method for finding the global solution to a problem in integers with a separable objective function of a very general form. This report shows that there is a relationship between an integer problem with a separable nonlinear objective function and many constraints and a series of nonlinear problems with only a single constraint, each of which can be solved sequentially using dynamic programming. The first solution to any of the individual smaller problems that satisfies the original constraints in addition, will be the optimal solution to the multiply‐constrained problem.
The U.S. versus the Soviet incentive models
Authors: Hildebrandt Gregory G.
Published: May 2007

This paper is concerned with models of the use of performance incentives in the Soviet Union and United States. The principal analytical result is an extension of an analysis of the methods whereby Soviet planners make the decision about production targets a variable under control of the producer, who is the only one possessing a knowledge of the uncertain condition of production. It is shown that this device can be viewed as a classical inventory problem. There is also an examination of the “U.S. incentive program” referring to multi‐incentive contracts in which the profits received by the private producers are related to performance, outcome and cost. The analysis describes how this device can be extended to solve the target output selection problem of the Soviet planning system.