bluuebunny/crossref_metadata_2025 huggingface dataset:
Weight Change Is Associated With Change in Arterial Stiffness Among Healthy Young Adults
Authors: Wildman Rachel P. , Farhat Ghada N. , Patel Ami S. , Mackey Rachel H. , Brockwell Sarah , Thompson Trina , Sutton-Tyrrell Kim
Published: January 2005

Risk factors for arterial stiffness progression have not been well characterized. We examined the relationship between arterial stiffness progression and body weight and weight gain in a group of healthy young adults. Aortic pulse-wave velocity was assessed at 2 time points approximately 2 years apart in 152 white and black adults aged 20 to 40 years, and was standardized by the time between visits to obtain annualized pulse-wave velocity changes. Blacks had 15.5 cm/s per year larger annual pulse-wave velocity increases compared with whites (
P
=0.02), even after multivariable adjustment for weight and blood pressure changes. Larger annual pulse-wave velocity increases were also associated with larger baseline body weight (
P
=0.02), waist girth (
P
=0.003), and body mass index (
P
<0.001), and greater annual weight gain (
P
=0.02), after adjustment for baseline pulse-wave velocity. After multivariable adjustment that included blood pressure changes, larger baseline waist girth (
P
=0.009), baseline body mass index (
P
=0.001), body mass index increase (
P
=0.037), and weight gain (
P
=0.017) remained significantly associated with larger annual pulse-wave velocity progression. Weight change showed a direct relationship with pulse-wave velocity change; mean annual pulse-wave velocity changes were −29.9 cm/s per year (regression) for those with ≥4.5 kg annual weight loss and 18.2 cm/s per year (progression) for those with ≥4.5 kg annual weight gain. These data show strong associations between weight gain and arterial stiffness progression, as well as between weight loss and arterial stiffness regression. These data greatly underscore the vascular benefit of weight loss. Successful weight loss programs in young adults, particularly blacks, are needed.
The relevance of retail loyalty strategy and practice for leisure/tourism
Authors: Michels Nicolette , Bowen David
Published: January 2005

This paper reviews the concepts of loyalty and loyalty strategies both in retail and in leisure and tourism — and the increasing integration of retail concepts into leisure and tourism. Through use of case studies, the paper details management views on the strategic significance of retail and retail loyalty within a range of UK-based leisure and tourism organisations. It also details specific loyalty practices. A series of implications are derived from a cross-evaluation of the case studies.
Mineralogical and geochemical characteristics (major, minor, trace elements and REE) of detrital and authigenic clay minerals in a Cenozoic sequence from Ross Sea, Antarctica
Authors: Setti M. , Marinoni L. , López-Galindo A.
Published: January 2005

The mineralogy and geochemistry of the clay fraction of Victoria Land Basin (Ross Sea, Antarctica) sediments was investigated, to determine the origin of clay minerals and the features of authigenic smectite. The investigated core (CRP-3) is ~800 m long, mostly of Oligocene age. The clay fraction of the upper sequence consists of mica, chlorite and detrital smectite, while that of the central and lower part is largely made up of authigenic smectite. Authigenic smectites are ditrioctahedral, with a composition close to saponite, while detrital smectites such as Al-Fe beidellites are dioctahedral. Authigenic smectites have no illite mixed layers, show a higher degree of crystallization, higher MgO, Fe2O3, V, Cr, Co, Ni and Sc contents and lower SiO2, Al2O3, K2O, TiO2, Ba, Rb and Zr contents with respect to detrital clay minerals, and a clear depletion of LREE with respect to HREE. Authigenic smectite formed from the alteration of volcanic materials and clay minerals.
Identification of novel prognostic markers in cervical intraepithelial neoplasia using LDMAS (LOH Data Management and Analysis Software)
Authors: Hamoudi Rifat A , El-Hamidi Amina , Du Ming-Qing
Published: January 2005

Background

Detection of Loss of Heterozygosity (LOH) is one of the most common molecular applications in the study of human diseases, in particular cancer. The technique is commonly used to examine whether a known tumour suppressor gene is inactivated or to map unknown tumour suppressor gene(s). However, with the increasing number of samples analysed using different software, no tool is currently available to integrate and facilitate the extensive and efficient data retrieval and analyses, such as correlation of LOH data with various clinical data sets.

Results

An algorithm to identify prognostic disease markers is devised and implemented as novel software called LDMAS. LDMAS is a software suite designed for data retrieval, management and integrated analysis of the clinico-pathological data and molecular results from independent databases. LDMAS is used in stratification of disease stages according to clinical stage or histological features and correlation of various clinico-pathological features with molecular findings to obtain relevant prognostic markers such as those used in predicting the outcome of cervical intraepithelial neoplasia (CIN). This approach lead to the identification of novel prognostic cervical cancer markers and extraction of useful clinical information such as correlation of Human Papilloma Virus (HPV) status with CIN lesions.

Conclusions

A novel software called LDMAS is implemented and used to extract and identify prognostic disease markers. The software is used to successfully identify 4 novel prognostic markers that can be used to predict the outcome of CIN. LDMAS provides an essential platform for the extraction of useful information from large amount of data generated by LOH studies. LDMAS provides three unique and novel features for LOH analysis : (1) automatic extraction of relevant data from patient records and reports (2) correlation of LOH data with clinico-pathological data and (3) storage of complex data in flexible format. The first feature automates the creation of database of clinically relevant information from huge amount of data, the second feature extracts useful biomedical information such as prognostic markers in CIN and the third feature simplifies the statistical analyses of the data and allows non-statisticians to carry out the analysis. Additionally, LDMAS can be used to extract clinically useful markers from other diseases and interface to high throughput genotyping analysis software such as GDAS used to generate LOH data from Affymetrix® GeneChip Mapping arrays.
Assessing stability and change of four performance measures: a longitudinal study evaluating outcome following total hip and knee arthroplasty
Authors: Kennedy Deborah M , Stratford Paul W , Wessel Jean , Gollish Jeffrey D , Penney Dianne
Published: January 2005

Background

Physical performance measures play an important role in the measurement of outcome in patients undergoing hip and knee arthroplasty. However, many of the commonly used measures lack information on their psychometric properties in this population. The purposes of this study were to examine the reliability and sensitivity to change of the six minute walk test (6MWT), timed up and go test (TUG), stair measure (ST), and a fast self-paced walk test (SPWT) in patients with hip or knee osteoarthritis (OA) who subsequently underwent total joint arthroplasty.

Methods

A sample of convenience of 150 eligible patients, part of an ongoing, larger observational study, was selected. This included 69 subjects who had a diagnosis of hip OA and 81 diagnosed with knee OA with an overall mean age of 63.7 ± 10.7 years. Test-retest reliability, using Shrout and Fleiss Type 2,1 intraclass correlations (ICCs), was assessed preoperatively in a sub-sample of 21 patients at 3 time points during the waiting period prior to surgery. Error associated with the measures' scores and the minimal detectable change at the 90% confidence level was determined. A construct validation process was applied to evaluate the measures' abilities to detect deterioration and improvement at two different time points post-operatively. The standardized response mean (SRM) was used to quantify change for all measures for the two change intervals. Bootstrapping was used to estimate the 95% confidence intervals (CI) for the SRMs.

Results

The ICCs (95% CI) were as follows: 6MWT 0.94 (0.88,0.98), TUG 0.75 (0.51, 0.89), ST 0.90 (0.79, 0.96), and the SPWT 0.91 (0.81, 0.97). Standardized response means varied from .79 to 1.98, being greatest for the ST and 6MWT over the studied time intervals.

Conclusions

The test-retest estimates of the 6MWT, ST, and the SPWT met the requisite standards for making decisions at the individual patient level. All measures were responsive to detecting deterioration and improvement in the early postoperative period.
Evaluation of the Modified Fatigue Impact Scale in four different European countries
Authors: Kos D , Kerckhofs E , Carrea I , Verza R , Ramos M , Jansa J
Published: January 2005

Objective: To evaluate the psychometric properties of the Modified Fatigue Impact Scale (MFIS) in four different European countries. Methods: Individuals with definite multiple sclerosis (MS) were selected from centres in Italy (n=50), Spain (n=30), Slovenia (n=50) and Belgium (n=51) and completed the MFIS and the Fatigue Severity Scale (FSS) twice (interval ≤ 3 days). Results: In all four samples, the MFIS demonstrated a good reproducibility (intraclass correlation coefficient ≥ 0.84), with no significant differences between countries (P=0.77). Moderate correlations were found between the MFIS and FSS. No significant correlations were found between the MFIS and age, gender, type of MS, duration of the disease or EDSS score. Factor analysis of all samples (n=181) could not completely confirm the original assumptions concerning the physical, cognitive and psychosocial component. The total score, the physical and the cognitive subscale of the scale were homogeneous (Cronbach’s alpha 0.92, 0.88 and 0.92, respectively), but the psychosocial subscale had a Cronbach’s alpha of 0.65. Conclusions: No cultural or linguistic differences were found in the psychometric properties of the Belgian, Italian, Slovenian or Spanish version of the MFIS. We recommend this scale for research purposes and in clinical practice. Due to the limited value of the psychosocial subscale, we recommend interpreting this subscale with caution.
Treating learning impairments improves memory performance in multiple sclerosis: a randomized clinical trial
Authors: Chiaravalloti Nancy D , DeLuca John , Moore Nancy B , Ricker Joseph H
Published: January 2005

This randomized clinincal trial utilized established techniques to improve new learning and memory performance in multiple sclerosis (MS) participants with learning impairment. Participants were 29 individuals with clinincally definite MS with documented learning deficits, randomly assigned to the experimental or control group. The experimental group underwent eight sessions of the Story Memory Technique (SMT), while the control group participated in eight sessions of memory exercises. Neuropsychological assessment was conducted at baseline, immediately following treatment and 5 weeks later to assess outcome. When stratifying participants by degree of learning deficits, a significant treatment effect was noted. MS participants with moderate-severe impairment in learning showed a significant improvement in learning abilities when compared to controls, (t(19)-3.32, P<0.01) evident in 88% of participants in the experimental group. Little improvement was noted in MS participants with mild learning impairments. Significant self-reported improvements in memory were noted in MS participants that underwent treatment, but not those that did not undergo treatment (t(26)-2.55, P<0.01). Results indicate that learning and memory deficits in MS can be effectively treated through a memory rehabilitation program utilizing context and imagery to improve new learning. Appropriate patient selection is important, with moderately-severely impaired individuals showing significantly greater benefit from treatment.
Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden
Authors: Huang Yu-Min , Liu Xuan , Steffensen Knut , Sanna Alessandra , Arru Giannina , Fois Maria Laura , Rosati Giulio , Sotgiu Stefano , Link Hans
Published: January 2005

Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes. Although ethnically distant, both populations have similarly high multiple sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their receptors, signalling molecules and other immune response-associated factors might influence MS pathogenesis, though definite proof is missing. The study of populations with similar MS incidence but different genetic and environmental background could make possible the definition of factors that relate to such background differences. We selected untreated female MS patients from Sassari, Sardinia, and Stockholm, Sweden, and corresponding sexand age-matched healthy controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20 immune response-related genes considered relevant in MS, employing real-time PCR. Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and Stockholm, compared to corresponding HC. MS patients from Sassari, but not Stockholm, expressed higher TNF-a compared to corresponding HC. MS patients from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3 dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS from Stockholm compared to corresponding HC. This was not observed in Sassari. No differences were detected for other members of the IL-12 family, other Th1 and Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-a and IL-6, although the extent of expression of TNF-a, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas. This might result from genetic and/or environmental differences. They may account for some of the discrepancies regarding immune response-related molecules previously reported in MS. In conclusion, a pro-inflammatory state exists in MS patients from Sassari as well as Stockholm. The changes of pro-inflammatory and other immune response-related variables differ however between the two MS populations. This may be attributed to the genetic and/or environmental background.
Pain description in patients with isolated proximal (without distal) exercise-related lower limb arterial ischemia
Authors: Jacquinandi Vincent , Bouyé Philippe , Picquet Jean , Leftheriotis Georges , Saumet Jean-Louis , Abraham Pierre
Published: January 2005

Among the last 250 claudicants referred to the laboratory for transcutaneous oxygen pressure recording at exercise, we analyzed the symptoms reported by the 36 patients who showed isolated proximal (without distal) ischemia. Among the symptomatic proximal sites cited by these patients, the hip and thigh represent 60%, whereas the buttock is cited in fewer than 25% of cases. Buttock symptoms are reported in only 31% of symptomatic patients. ‘Buttock’ claudication is probably not the dominant symptom in isolated proximal vascular ischemia. Assessing proximal lower limb ischemia through the sole detection of ‘buttock pain’ could contribute to the underestimation of proximal vascular ischemia.
Influence of Sex on Toxicity and Treatment Outcome in Small-Cell Lung Cancer
Authors: Singh Simron , Parulekar Wendy , Murray Nevin , Feld Ronald , Evans William K. , Tu Dongsheng , Shepherd Frances A.
Published: January 2005

Purpose

Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC.

Patients and Methods

This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival.

Results

Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001).

Conclusion

Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.
Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer
Authors: Miller Kathy D. , Chap Linnea I. , Holmes Frankie A. , Cobleigh Melody A. , Marcom P. Kelly , Fehrenbacher Louis , Dickler Maura , Overmoyer Beth A. , Reimann James D. , Sing Amy P. , Langmuir Virginia , Rugo Hope S.
Published: January 2005

Purpose

This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.

Patients and Methods

Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility.

Results

From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment—Breast were comparable in both treatment groups.

Conclusion

Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.
Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones
Authors: Norton Will H. , Mangoli Maryam , Lele Zsolt , Pogoda Hans-Martin , Diamond Brianne , Mercurio Sara , Russell Claire , Teraoka Hiroki , Stickney Heather L. , Rauch Gerd-Jörg , Heisenberg Carl-Philipp , Houart Corinne , Schilling Thomas F. , Frohnhoefer Hans-Georg , Rastegar Sepand , Neumann Carl J. , Gardiner R. Mark , Strähle Uwe , Geisler Robert , Rees Michelle , Talbot William S. , Wilson Stephen W.
Published: January 2005

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos,we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves.

Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphénucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.
Arxhomeobox gene is essential for development of mouse olfactory system
Authors: Yoshihara Sei-ichi , Omichi Kayo , Yanazawa Masako , Kitamura Kunio , Yoshihara Yoshihiro
Published: January 2005

The olfactory system provides an excellent model in which to study cell proliferation, migration, differentiation, axon guidance, dendritic morphogenesis, and synapse formation. We report here crucial roles of the Arx homeobox gene in the developing olfactory system by analyzing its mutant phenotypes. Arx protein was expressed strongly in the interneurons and weakly in the radial glia of the olfactory bulb, but in neither the olfactory sensory neurons nor bulbar projection neurons. Arx-deficient mice showed severe anatomical abnormalities in the developing olfactory system: (1)size reduction of the olfactory bulb, (2) reduced proliferation and impaired entry into the olfactory bulb of interneuron progenitors, (3) loss of tyrosine hydroxylase-positive periglomerular cells, (4) disorganization of the layer structure of the olfactory bulb, and (5) abnormal axonal termination of olfactory sensory neurons in an unusual axon-tangled structure, the fibrocellular mass. Thus, Arx is required for not only the proper developmental processes of Arx-expressing interneurons, but also the establishment of functional olfactory neural circuitry by affecting Arx-non-expressing sensory neurons and projection neurons. These findings suggest a likely role of Arx in regulating the expression of putative instructive signals produced in the olfactory bulb for the proper innervation of olfactory sensory axons.
bHLH-dependent and -independent modes ofAth5gene regulation during retinal development
Authors: Hutcheson David A. , Hanson Minde I. , Moore Kathryn B. , Le Tien T. , Brown Nadean L. , Vetter Monica L.
Published: January 2005

In a wide range of vertebrate species, the bHLH transcription factor Ath5 is tightly associated with both the initiation of neurogenesis in the retina and the genesis of retinal ganglion cells. Here, we describe at least two modes of regulating the expression of Ath5 during retinal development. We have found that a proximal cis-regulatory region of the Xenopus Ath5 gene (Xath5) is highly conserved across vertebrate species and is sufficient to drive retinal-specific reporter gene expression in transgenic Xenopus embryos. Xath5 proximal transgene expression depended upon two highly conserved bHLH factor binding sites (E-boxes) as well as bHLH factor activity in vivo. However, we found that bHLH activity was not required for expression of a longer Xath5transgene, suggesting that additional mechanisms contribute to Xath5expression in vivo. Consistent with this, we showed that a more distal fragment that does not include the conserved proximal region is sufficient to promote transgene expression in the developing retina. In mouse, we found that a longer fragment of the cis-regulatory region of either the mouse or Xenopus Ath5 gene was necessary for transgene expression, and that expression of a mouse Math5 (Atoh7) transgene was not dependent upon autoregulation. Thus, despite extensive conservation in the proximal region, the importance of these elements may be species dependent.
Agency Costs in a Supply Chain with Demand Uncertainty and Price Competition
Authors: Narayanan V. G. , Raman Ananth , Singh Jasjit
Published: January 2005

In this paper, we model a manufacturer that contracts with two retailers, who then choose retail prices and stocking quantities endogenously in a Bayesian Nash equilibrium. If the manufacturer designs a contract that is accepted by both retailers, it sets the wholesale price as a compromise between two conflicting roles: reducing intrabrand retail price competition and inducing retailers to stock closer to first-best levels (that is, optimum for the supply chain as a whole). In equilibrium, fill rates are less than first best. If, on the other hand, the manufacturer eliminates retail competition by designing a contract accepted by only one retailer, the assignment of consumers to retailers is inefficient. In either equilibrium, the performance of the supply chain is strictly less than first best. However, the manufacturer achieves first-best retail prices and fill rates if it can subsidize the retailers' leftover inventory. Absent such subsidies, the two-retailer equilibrium arises when the two retailers compete less intensively. In that equilibrium, numerical results indicate that the value of subsidizing unsold inventory is increasing in demand uncertainty, intensity of retail competition, and salvage value of inventory, and is decreasing in manufacturing cost and opportunity cost of shelf space.
Sell the Plant? The Impact of Contract Manufacturing on Innovation, Capacity, and Profitability
Authors: Plambeck Erica L. , Taylor Terry A.
Published: January 2005

In the electronics industry and others, original equipment manufacturers (OEMs) are selling their production facilities to contract manufacturers (CMs). The CMs achieve high capacity utilization through pooling (supplying many different OEMs). Meanwhile, the OEMs focus on innovation: research and development, product design, and marketing. We examine how this change in industry structure affects investment in innovation and capacity, and thus profitability. In particular, innovation is noncontractible, so OEMs will invest less in innovation than is ideal for the industry as a whole. Hence, although contract manufacturing improves capacity utilization, it may reduce the profitability of the industry as a whole by weakening the incentives for innovation. Contract manufacturing is not the only means to achieve capacity pooling. Alternatively, the OEMs can pool capacity with one another through supply contracts or a joint venture. This may result in underinvestment or overinvestment in innovation and capacity, but always increases profitability. We find that the sale of production facilities to a CM improves profitability for the industry as a whole if and only if OEMs are subsequently in a strong bargaining position vis-à-vis the CM. If the OEMs are indeed very strong, the gain from pooling capacity via contract manufacturing is maximized in industries with moderate cost of capacity.
A Principal-Agent Model for Product Specification and Production
Authors: Iyer Ananth V. , Schwarz Leroy B. , Zenios Stefanos A.
Published: January 2005

This paper develops and analyzes a principal-agent model for product specification and production motivated by “core buying” decisions at an automobile manufacturer. The model focuses on two important elements of the “core” buyer's responsibility: (1) assessing the supplier's capability, and (2) allocating some or all of a fixed level of some buyer-internal resource to help the supplier. Under the contracting scheme we model, the buyer (principal) delegates the majority of product specification and production activity to the supplier (agent), but retains the flexibility to commit a given, observable amount of an internally available, limited resource (e.g., engineering hours) to help the supplier. The supplier, in turn, allocates his resource (e.g., engineering hours) to produce the finished product. As in the motivating scenario, both the supplier's resource allocation and capability are assumed to be hidden from the buyer. Hence, the principal's problem is to determine a menu of (resource-commitment, transfer-price) contracts to minimize her total expected cost. Our analysis demonstrates that if buyer resource and supplier capability are substitutes, then the buyer's second-best involvement in the supplier's production process will be greater than first-best. The opposite is true if they are complements. Further, when the opportunity cost for the buyer's resource is zero, then in the substitutes case the buyer will commit all of its resource, while in the complements case the buyer may withhold some resources to screen the supplier type. We describe two applications of the model—one in inventory management and one in pharmaceutical drug discovery—to illustrate its applicability and versatility. Finally, we use insights from the model to suggest hypotheses for empirical study.
Salesforce Incentives, Market Information, and Production/Inventory Planning
Authors: Chen Fangruo
Published: January 2005

Salespeople are the eyes and ears of the firms they serve. They possess market knowledge that is critical for a wide range of decisions. A key question is how a firm can provide incentives to its salesforce so that it is in their interest to truthfully disclose their information about the market and to work hard. Many people have considered this question and provided solutions. Perhaps the most well-known solution is due to Gonik (1978), who proposed and implemented a clever scheme designed to elicit market information and encourage hard work. The purpose of this paper is to study Gonik's scheme and compare it with a menu of linear contracts—a solution often used in the agency literature—in a model where the market information possessed by the salesforce is important for the firm's production and inventory-planning decisions.
Decentralized Supply Chains with Competing Retailers Under Demand Uncertainty
Authors: Bernstein Fernando , Federgruen Awi
Published: January 2005

In this paper, we investigate the equilibrium behavior of decentralized supply chains with competing retailers under demand uncertainty. We also design contractual arrangements between the parties that allow the decentralized chain to perform as well as a centralized one. We address these questions in the context of two-echelon supply chains with a single supplier servicing a network of (competing) retailers, considering the following general model: Retailers face random demands, the distribution of which may depend only on its own retail price (noncompeting retailers) or on its own price as well as those of the other retailers (competing retailers), according to general stochastic demand functions.
A Smart Market for Industrial Procurement with Capacity Constraints
Authors: Gallien Jérémie , Wein Lawrence M.
Published: January 2005

We address the problem of designing multi-item procurement auctions for a monopsonistic buyer in capacity-constrained environments. Using insights from classical auction theory, we construct an optimization-based auction mechanism (“smart market”) relying on the dynamic resolution of a linear program minimizing the buyer's cost under the suppliers' capacity constraints. Suppliers can modify their offers in response to the optimal allocation corresponding to each set of bids, giving rise to a dynamic competitive bidding process. To assist suppliers, we also develop a bidding-suggestion device based on a myopic best-response (MBR) calculation that solves an associated optimization problem. Assuming linear costs for the suppliers, we study within a game-theoretic framework the sequence of bids arising in this smart market. Under a weak behavioral assumption and some symmetry requirements, an explicit upper bound for the winning bids is established. We then formulate a complete behavioral model and solution methodology based on the MBR rationale and show that the bounds derived earlier continue to hold. We analytically derive some structural and convergence properties of the MBR dynamics in the simplest nontrivial market environment, which suggests further possible design improvements, and investigate bidding dynamics and incentive compatibility issues via numerical simulations.
Using performers as tools in the creation of telematic artwork
Authors: Petersen Kjell Yngve
Published: January 2005

It is suggested how one can imaginatively use a design strategy utilizing performers as tools in the creation of augmented, performative artwork. In order to establish meaningful constructions of performative and augmentative technology, one can use the formal methodologies of advanced formal body language as a tool in the creation process, and thereby have ‘the actual experience’ present in the process as a monitor and a constructive tool. To use a human being as a design tool is a method that uses the skilled performer as a ‘super-’ or ‘extra-’ human tool to investigate through action and analysis. It is a way to test how realities occur under fluid and dynamic conditions within a controlled environment of time and space. This ‘technical’ use of the body as an extra-human behavioural entity, involves the total complex spectrum of intellect, emotions, desires, memory, actions, etc. as a formalized ‘machine’.
Thinking Liquid Thoughts: Version 2
Authors: Fraga Tania
Published: January 2005

‘Thinking liquid thoughts’ is an essay aiming at the aggregation of ideas and concepts which emerge and float when enquiring if there are characteristics related with the research of fields that artists could explore as new poetic venues for further works. Nanosciences and nanotechnologies will affect almost all features of everybody’s lives in the near future. What are the issues, either desirable or undesirable, we should try to point to considering the specific view related with art, architecture and design. We also have to ask, which are the skills and tools that artists, architects and designers will need for developing research and creating work in these new fields. Opening with the idea of thinking liquid thoughts the essay also speculates about the possibility of creating interactive responsive works of art, extremely sensitive, exploring poetic possibilities for the creation of material products aiming a bi-univocal relationship between the computer simulation and the material realm. There is also research related with educational games and the programming of poetic journeys using virtual reality technologies, pointing to the convergence of silicon with carbon, which will bring about deep implications in the mode of production of things, thoughts ands processes.modelling, animation and VRML, Java Script and Java 3D languages.
Book Reviews
Authors: Gessert George , Farley Kathryn
Published: January 2005

Art and Fear, Paul Virilio, (trans. Julie Rose), (2003) London and New York: Continuum, pp.112. Hardback, ISBN 0-8264-6080-1, $16.95.

Avatar Bodies: A Tantra for Posthumanism, Ann Weinstone, (2004) Minneapolis: University of Minnesota Press, 227
pp. Hardback, ISBN 0-8166-4146-3, $53.95. Paperback, ISBN 0-8166-4147-1, $17.95.
Contrast Adaptation in Subthreshold and Spiking Responses of Mammalian Y-Type Retinal Ganglion Cells
Authors: Zaghloul Kareem A. , Boahen Kwabena , Demb Jonathan B.
Published: January 2005

Retinal ganglion cells adapt their responses to the amplitude of fluctuations around the mean light level, or the “contrast.” But, in mammalian retina, it is not known whether adaptation arises exclusively at the level of synaptic inputs or whether there is also adaptation in the process of ganglion cell spike generation. Here, we made intracellular recordings from guinea pig Y-type ganglion cells and quantified changes in contrast sensitivity (gain) using a linear-nonlinear analysis. This analysis allowed us to measure adaptation in the presence of nonlinearities, such as the spike threshold, and to compare adaptation in subthreshold and spiking responses. At high contrast (0.30), relative to low contrast (0.10), gain reduced to 0.82 ± 0.016 (mean ± SEM) for the subthreshold response and to 0.61 ± 0.011 for the spiking response. Thus, there was an apparent reduction in gain between the subthreshold and spiking response of 0.74 ± 0.013. Control experiments suggested that the above effects could not be explained by an artifact of the intracellular recording conditions: extracellular recordings showed a gain change of 0.58 ± 0.022. For intracellular recordings, negative current reduced the spike output but did not affect the gain change in the subthreshold response: 0.80 ± 0.051. Thus, adaptation in the subthreshold response did not require spike-dependent conductances. We conclude that the contrast-dependent gain change in the spiking response can be explained by both a synaptic mechanism, as reflected by responses in the subthreshold potential, and an intrinsic mechanism in the ganglion cell related to spike generation.
Atypical Protein Kinase C Is a Novel Mediator of Dopamine-Enhanced Firing in Nucleus Accumbens Neurons
Authors: Hopf F. Woodward , Mailliard William S. , Gonzalez Gilda F. , Diamond Ivan , Bonci Antonello
Published: January 2005

Current concepts suggest that nucleus accumbens (NAcb) dopamine mediates several motivated and addictive behaviors. Although the role of protein kinase A (PKA) and dopamine and cyclic adenosine 3′,5′ monophosphate-regulated phosphoprotein 32 kDa in NAcb dopamine receptor throughput has been studied extensively, the contribution of protein kinase C (PKC) to NAcb firing is poorly understood. Here we show that dopamine-mediated enhancement of spike firing in NAcb shell medium spiny neurons was prevented by the PKC inhibitor bisindolylmaleimide but not by the phospholipase C inhibitor 1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione, suggesting a role for a diacylglycerol-independent atypical PKC (aPKC) isoform. In this regard, modulation of firing by dopamine was prevented by intracellular perfusion of a pseudosubstrate peptide inhibitor for aPKCs. We also provide evidence, using anin vitrokinase assay, that dopamine receptor activation increased aPKC activity in striatal membranes. Finally, direct activation of PKA with forskolin enhanced firing even during inhibition of aPKCs, suggesting that aPKCs acted upstream of PKA activation. Thus, aPKCs appear to mediate dopaminergic enhancement of spike firing in the NAcb shell, and may therefore play a critical role in NAcb- and dopamine-dependent goal-directed behaviors.
Evidence That Disinhibition Is Associated with a Decrease in Number of Vesicles Available for Release at Inhibitory Synapses
Authors: Ledoux Veronica A. , Woolley Catherine S.
Published: January 2005

We used three-dimensional reconstruction from serial electron micrographs to investigate two structural changes that could underlie estrogen-induced disinhibition of hippocampal CA1 pyramidal cells: a decrease in the number of inhibitory inputs per neuron and/or a change in inhibitory boutons that could limit GABA release. We analyzed 373 boutons forming 510 inhibitory synapses in estrogentreated and control animals. Our results show that estrogen specifically decreases the number of synaptic vesicles adjacent to the presynaptic membrane of inhibitory synapses without affecting the overall number of vesicles. We detected no difference in the density of inhibitory inputs. These findings provide a novel mechanism for the functional effects of estrogen on synaptic inhibition and represent the firstin vivoevidence that the number of presynaptic vesicles available for release is a regulated property of synapses that affects synaptic physiology.
Altered Behavioral Responses to Noxious Stimuli and Fear in Glutamate Receptor 5 (GluR5)- or GluR6-Deficient Mice
Authors: Ko Shanelle , Zhao Ming-Gao , Toyoda Hiroki , Qiu Chang-Shen , Zhuo Min
Published: January 2005

Different kainate receptor (KAR) subtypes contribute to the regulation of both excitatory and inhibitory transmission. However, no study has reported a role for KAR subtypes in behavioral responses to persistent pain and fear memory. Here we show that responses to capsaicin or inflammatory pain were significantly reduced in mice lacking glutamate receptor 5 (GluR5) but not GluR6 subunits. In classic fear-memory tests, mice lacking GluR6 but not GluR5 showed a significant reduction in fear memory when measured 3, 7, or 14 d after training. Additionally, synaptic potentiation was significantly reduced in the lateral amygdala of GluR6 but not GluR5 knock-out mice. Our findings provide evidence that distinct KAR subtypes contribute to chemical/inflammatory pain and fear memory. Selectively targeting different KAR subtypes may provide a useful strategy for treating persistent pain and fear-related mental disorders.
Angular Path Integration by Moving “Hill of Activity”: A Spiking Neuron Model without Recurrent Excitation of the Head-Direction System
Authors: Song Pengcheng , Wang Xiao-Jing
Published: January 2005

During spatial navigation, the head orientation of an animal is encoded internally by neural persistent activity in the head-direction (HD) system. In computational models, such a bell-shaped “hill of activity” is commonly assumed to be generated by recurrent excitation in a continuous attractor network. Recent experimental evidence, however, indicates that HD signal in rodents originates in a reciprocal loop between the lateral mammillary nucleus (LMN) and the dorsal tegmental nucleus (DTN), which is characterized by a paucity of local excitatory axonal collaterals. Moreover, when the animal turns its head to a new direction, the heading information is updated by a time integration of angular head velocity (AHV) signals; the underlying mechanism remains unresolved. To investigate these issues, we built and investigated an LMN-DTN network model that consists of three populations of noisy and spiking neurons coupled by biophysically realistic synapses. We found that a combination of uniform external excitation and recurrent cross-inhibition can give rise to direction-selective persistent activity. The model reproduces the experimentally observed three types of HD tuning curves differentially modulated by AHV and anticipatory firing activity in LMN HD cells. Time integration is assessed by using constant or sinusoidal angular velocity stimuli, as well as naturalistic AHV inputs (from rodent recordings). Furthermore, the internal representation of head direction is shown to be calibrated or reset by strong external cues. We identify microcircuit properties that determine the ability of our model network to subserve time integration function.
Differential Transport and Local Translation of Cytoskeletal, Injury-Response, and Neurodegeneration Protein mRNAs in Axons
Authors: Willis Dianna , Li Ka Wan , Zheng Jun-Qi , Chang Jay H. , Smit August , Kelly Theresa , Merianda Tanuja T. , Sylvester James , van Minnen Jan , Twiss Jeffery L.
Published: January 2005

Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ganglion (DRG) neurons and proteomics methodology to identify axonally synthesized proteins. Reverse transcription (RT)-PCR from axonal preparations was used to confirm that the mRNA for each identified protein extended into the DRG axons. Proteins and the encoding mRNAs for the cytoskeletal proteins β-actin, peripherin, vimentin, γ-tropomyosin 3, and cofilin 1 were present in the axonal preparations. In addition to the cytoskeletal elements, several heat shock proteins (HSP27, HSP60, HSP70, grp75, αB crystallin), resident endoplasmic reticulum (ER) proteins (calreticulin, grp78/BiP, ERp29), proteins associated with neurodegenerative diseases (ubiquitin C-terminal hydrolase L1, rat ortholog of human DJ-1/Park7, γ-synuclein, superoxide dismutase 1), anti-oxidant proteins (peroxiredoxins 1 and 6), and metabolic proteins (e.g., phosphoglycerate kinase 1 (PGK 1), α enolase, aldolase C/Zebrin II) were included among the axonally synthesized proteins. Detection of the mRNAs encoding each of the axonally synthesized proteins identified by mass spectrometry in the axonal compartment indicates that the DRG axons have the potential to synthesize a complex population of proteins. Local treatment of the DRG axons with NGF or BDNF increased levels of cytoskeletal mRNAs into the axonal compartment by twofold to fivefold but had no effect on levels of the other axonal mRNAs studied. Neurotrophins selectively increased transport of β-actin, peripherin, and vimentin mRNAs from the cell body into the axons rather than changing transcription or mRNA survival in the axonal compartment.
A Novel Substrate of Receptor Tyrosine Phosphatase PTPRO Is Required for Nerve Growth Factor-Induced Process Outgrowth
Authors: Chen Bo , Bixby John L.
Published: January 2005

The receptor protein tyrosine phosphatase PTPRO may be involved in axon guidance both as a ligand and as a neuronal receptor. We have begun to characterize signaling by PTPRO as a receptor by screening for proteins interacting with the intracellular domain of PTPRO. In a yeast-two hybrid screen, we identified a novel class of protein, which we named neuronal pentraxin with chromo domain (NPCD), as a PTPRO-interacting protein. We have shown recently that NPCD has multiple cytoplasmic isoforms as a result of alternative splicing and that these proteins are present in many neurons, mainly associated with the inner side of the plasma membrane. Through additional two-hybrid experiments, cotransfection and reciprocal coprecipitation, glutathioneS-transferase pulldown, and immunoprecipitationin vivo, we confirm that NPCD isoforms interact with the catalytic phosphatase domain of PTPRO. We also find that at least one NPCD isoform is tyrosine phosphorylatedin vivoand can serve as a substrate for PTPROin vitro. Analysis of PTPRO knock-out mice demonstrates that normal localization of NPCD at the plasma membrane requires PTPRO expression, suggesting a physiological role for the NPCD/PTPRO interaction. NPCD is likely to be relevant to axon growth and/or guidance, because RNA interference mediated knock-down of NPCD expression in pheochromocytoma cells inhibits NGF-induced neuronal process outgrowth without affecting NGF-dependent survival or initial NGF signaling.