bluuebunny/crossref_metadata_2025 huggingface dataset:
Converting venous acid–base and oxygen status to arterial in patients with lung disease
Authors: Rees S. E. , Hansen A. , Toftegaard M. , Pedersen J. , Kristiensen S. R. , Harving H.
Published: January 2009

The aim of the present study was to evaluate a method for calculating arterial values of pH, carbon dioxide tension (PCO2) and oxygen tension (PO2) from peripheral venous values.

In total, 40 patients were studied. Arterial and peripheral venous blood were sampled at a department of respiratory diseases. Arterial values were calculated from venous, and measured and calculated values of arterial pH,PCO2andPO2were compared.

Measured and calculated values of pH andPCO2correlated well, with the difference between them having a very small bias and standard deviation (pH -0.001±0.013,PCO2-0.09±0.28 kPa) within those considered acceptable for laboratory equipment and clinical practice. All but four patients had peripheral oxygen saturation (Sp,O2) ≤96%, and for these measured and calculatedPO2correlated well, with a difference such that the bias and standard deviation suggested that calculated &SetFont Typeface="43" Bold="1" Italic="1";P&SetFont Typeface="43" Bold="1";O2may be clinically useful (&SetFont Typeface="43" Bold="1" Italic="1";P&SetFont Typeface="43" Bold="1";O20.11±0.53 kPa).

The present study evaluates a method for calculating arterial pH, carbon dioxide tension and oxygen tension from venous blood. It has been shown that arterial pH and carbon dioxide tension can be calculated precisely, and that oxygen tension can be calculated with reasonable precision in the vast majority of patients. This method might be useful in reducing the need for painful arterial punctures.
Nitric oxide production by the alveolar compartment of the lungs in cirrhotic patients
Authors: Degano B. , Mittaine M. , Hervé P. , Rami J. , Kamar N. , Suc B. , Rivière D. , Rostaing L.
Published: January 2009

In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V′A,NO) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measureV′A,NOand to compareV′A,NOwith pulmonary haemodynamics and gas exchange parameters.

Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration.V′A,NOwas the product of alveolar NO concentration by single breath lung transfer factor for NO.

V′A,NOwas increased in patients (median (range) 260 (177–341) nL·min−1) compared with controls (79 (60–90), p<0.0001). Alveolar–arterial oxygen tension difference failed to correlate withV′A,NO. However, cardiac index correlated positively and systemic vascular resistance correlated negatively withV′A,NO(r = 0.56, p = 0.001 and r = -0.52, p = 0.004, respectively).

In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.
Mosaic analysis of stem cell function and wound healing in the mouse corneal epithelium
Authors: Mort Richard L , Ramaesh Thaya , Kleinjan Dirk A , Morley Steven D , West John D
Published: January 2009

Background

The mouse corneal epithelium is a continuously renewing 5–6 cell thick protective layer covering the corneal surface, which regenerates rapidly when injured. It is maintained by peripherally located limbal stem cells (LSCs) that produce transient amplifying cells (TACs) which proliferate, migrate centripetally, differentiate and are eventually shed from the epithelial surface. LSC activity is required both for normal tissue maintenance and wound healing. Mosaic analysis can provide insights into LSC function, cell movement and cell mixing during tissue maintenance and repair. The present study investigates cell streaming during corneal maintenance and repair and changes in LSC function with age.

Results

The initial pattern of corneal epithelial patches in XLacZ
+/- X-inactivation mosaics was replaced after birth by radial stripes, indicating activation of LSCs. Stripe patterns (clockwise, anticlockwise or midline) were independent between paired eyes. Wound healing in organ culture was analysed by mosaic analysis of XLacZ
+/- eyes or time-lapse imaging of GFP mosaics. Both central and peripheral wounds healed clonally, with cells moving in from all around the wound circumference without significant cell mixing, to reconstitute striping patterns. Mosaic analysis revealed that wounds can heal asymmetrically. Healing of peripheral wounds produced stripe patterns that mimicked some aberrant striping patterns observed in unwounded corneas. Quantitative analysis provided no evidence for an uneven distribution of LSC clones but showed that corrected corneal epithelial stripe numbers declined with age (implying declining LSC function) but stabilised after 39 weeks.

Conclusion

Striping patterns, produced by centripetal movement, are defined independently and stochastically in individual eyes. Little cell mixing occurs during the initial phase of wound healing and the direction of cell movement is determined by the position of the wound and not by population pressure from the limbus. LSC function declines with age and this may reflect reduced LSCs numbers, more quiescent LSCs or a reduced ability of older stem cells to maintain tissue homeostasis. The later plateau of LSC function might indicate the minimum LSC function that is sufficient for corneal epithelial maintenance. Quantitative and temporal mosaic analyses provide new possibilities for studying stem cell function, tissue maintenance and repair.
Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes
Authors: Lee Kuo-Chang , Webb Richard I , Janssen Peter H , Sangwan Parveen , Romeo Tony , Staley James T , Fuerst John A
Published: January 2009

Background

The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization.

Results

The ultrastructure of cells of four members of phylum Verrucomicrobia – Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and strain Ellin514 – was examined using electron microscopy incorporating high-pressure freezing and cryosubstitution. These four members of phylum Verrucomicrobia, representing 3 class-level subdivisions within the phylum, were found to possess a compartmentalized cell plan analogous to that found in phylum Planctomycetes. Like all planctomycetes investigated, they possess a major pirellulosome compartment containing a condensed nucleoid and ribosomes surrounded by an intracytoplasmic membrane (ICM), as well as a ribosome-free paryphoplasm compartment between the ICM and cytoplasmic membrane.

Conclusion

A unique compartmentalized cell plan so far found among Domain Bacteria only within phylum Planctomycetes, and challenging our concept of prokaryote cell plans, has now been found in a second phylum of the Domain Bacteria, in members of phylum Verrucomicrobia. The planctomycete cell plan thus occurs in at least two distinct phyla of the Bacteria, phyla which have been suggested from other evidence to be related phylogenetically in the proposed PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) superphylum. This planctomycete cell plan is present in at least 3 of 6 subdivisions of Verrucomicrobia, suggesting that the common ancestor of the verrucomicrobial phylum was also compartmentalized and possessed such a plan. The presence of this compartmentalized cell plan in both phylum Planctomycetes and phylum Verrucomicrobia suggest that the last common ancestor of these phyla was also compartmentalized.
In-vivo optical detection of cancer using chlorin e6 – polyvinylpyrrolidone induced fluorescence imaging and spectroscopy
Authors: Chin William WL , Thong Patricia SP , Bhuvaneswari Ramaswamy , Soo Khee Chee , Heng Paul WS , Olivo Malini
Published: January 2009

Background

Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient.

Methods

Fluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions.

Results

Margins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient.

Conclusion

Combination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer.
The role of ENSO in understanding changes in Colombia's annual malaria burden by region, 1960–2006
Authors: Mantilla Gilma , Oliveros Hugo , Barnston Anthony G
Published: January 2009

Background

Malaria remains a serious problem in Colombia. The number of malaria cases is governed by multiple climatic and non-climatic factors. Malaria control policies, and climate controls such as rainfall and temperature variations associated with the El Niño/Southern Oscillation (ENSO), have been associated with malaria case numbers. Using historical climate data and annual malaria case number data from 1960 to 2006, statistical models are developed to isolate the effects of climate in each of Colombia's five contrasting geographical regions.

Methods

Because year to year climate variability associated with ENSO causes interannual variability in malaria case numbers, while changes in population and institutional control policy result in more gradual trends, the chosen predictors in the models are annual indices of the ENSO state (sea surface temperature [SST] in the tropical Pacific Ocean) and time reference indices keyed to two major malaria trends during the study period. Two models were used: a Poisson and a Negative Binomial regression model. Two ENSO indices, two time reference indices, and one dummy variable are chosen as candidate predictors. The analysis was conducted using the five geographical regions to match the similar aggregation used by the National Institute of Health for its official reports.

Results

The Negative Binomial regression model is found better suited to the malaria cases in Colombia. Both the trend variables and the ENSO measures are significant predictors of malaria case numbers in Colombia as a whole, and in two of the five regions. A one degree Celsius change in SST (indicating a weak to moderate ENSO event) is seen to translate to an approximate 20% increase in malaria cases, holding other variables constant.

Conclusion

Regional differentiation in the role of ENSO in understanding changes in Colombia's annual malaria burden during 1960–2006 was found, constituting a new approach to use ENSO as a significant predictor of the malaria cases in Colombia. These results naturally point to additional needed work: (1) refining the regional and seasonal dependence of climate on the ENSO state, and of malaria on the climate variables; (2) incorporating ENSO-related climate variability into dynamic malaria models.
Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines
Authors: Eads D , Hansen RL , Oyegunwa AO , Cecil CE , Culver CA , Scholle F , Petty ITD , Laster SM
Published: January 2009

Background

Extracts of the creosote bush,Larrea tridentata, have been used for centuries by natives of western American and Mexican deserts to treat a variety of infectious diseases and inflammatory disorders. The beneficial activity of this plant has been linked to the compound nordihydroguaiaretic acid (NDGA) and its various substituted derivatives. Recently, tetra-O-methyl NDGA or terameprocol (TMP) has been shown to inhibit the growth of certain tumor-derived cell lines and is now in clinical trials for the treatment of human cancer. In this report, we ask whether TMP also displays anti-inflammatory activity. TMP was tested for its ability to inhibit the LPS-induced production of inflammatory lipids and cytokinesin vitro. We also examined the effects of TMP on production of TNF-α in C57BL6/J mice following a sublethal challenge with LPS. Finally, we examined the molecular mechanisms underlying the effects we observed.

Methods

RAW 264.7 cells and resident peritoneal macrophages from C57BL6/J mice, stimulated with 1 μg/ml LPS, were used in experiments designed to measure the effects of TMP on the production of prostaglandins, cytokines and chemokines. Prostaglandin production was determined by ELISA. Cytokine and chemokine production were determined by antibody array and ELISA.

Western blots, q-RT-PCR, and enzyme assays were used to assess the effects of TMP on expression and activity of COX-2.

q-RT-PCR was used to assess the effects of TMP on levels of cytokine and chemokine mRNA.

C57BL6/J mice injectedi.p.with LPS were used in experiments designed to measure the effects of TMPin vivo. Serum levels of TNF-α were determined by ELISA.

Results

TMP strongly inhibited the production of prostaglandins from RAW 264.7 cells and normal peritoneal macrophages. This effect correlated with a TMP-dependent reduction in levels of COX-2 mRNA and protein, and inhibition of the enzymatic activity of COX-2.

TMP inhibited, to varying degrees, the production of several cytokines, and chemokines from RAW 264.7 macrophages and normal peritoneal macrophages. Affected molecules included TNF-α and MCP-1. Levels of cytokine mRNA were affected similarly, suggesting that TMP is acting to prevent gene expression.

TMP partially blocked the production of TNF-α and MCP-1in vivoin the serum of C57BL6/J mice that were challengedi.p. with LPS.

Conclusion

TMP inhibited the LPS-induced production of lipid mediators and several key inflammatory cytokines and chemokines, bothin vitroandin vivo, raising the possibility that TMP might be useful as a treatment for a variety of inflammatory disorders.
Removal of spermatozoa with externalized phosphatidylserine from sperm preparation in human assisted medical procreation: effects on viability, motility and mitochondrial membrane potential
Authors: de Vantéry Arrighi Corinne , Lucas Hervé , Chardonnens Didier , de Agostini Ariane
Published: January 2009

Background

Externalization of phosphatidylserine (EPS) occurs in apoptotic-like spermatozoa and could be used to remove them from sperm preparations to enhance sperm quality for assisted medical procreation. We first characterized EPS in sperms from infertile patients in terms of frequency of EPS spermatozoa as well as localization of phosphatidylserine (PS) on spermatozoa. Subsequently, we determined the impact of depleting EPS spermatozoa on sperm quality.

Methods

EPS were visualized by fluorescently-labeled annexin V binding assay. Double staining with annexin V and Hoechst differentiates apoptotic from necrotic spermatozoa. We used magnetic-activated cell sorting using annexin V-conjugated microbeads (MACS-ANMB) technique to remove EPS spermatozoa from sperm prepared by density gradient centrifugation (DGC). The impact of this technique on sperm quality was evaluated by measuring progressive motility, viability, and the integrity of the mitochondrial membrane potential (MMP) by Rhodamine 123.

Results

Mean percentages of EPS spermatozoa were 14% in DGC sperm. Four subpopulations of spermatozoa were identified: 70% alive, 3% early apoptotic, 16% necrotic and 11% late apoptotic or necrotic. PS were localized on head and/or midpiece or on the whole spermatozoa. MACS efficiently eliminates EPS spermatozoa. MACS combined with DGC allows a mean reduction of 70% in EPS and of 60% in MMP-disrupted spermatozoa with a mean increase of 50% in sperm survival at 24 h.

Conclusion

Human ejaculates contain EPS spermatozoa which can mostly be eliminated by DGC plus MACS resulting in improved sperm long term viability, motility and MMP integrity. EPS may be used as an indicator of sperm quality and removal of EPS spermatozoa may enhance fertility potential in assisted medical procreation.
Semi-allogeneic vaccines and tumor-induced immune tolerance
Authors: Yu Jin , Kindy Mark S , Gattoni-Celli Sebastiano
Published: January 2009

Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2b) before challenging the mice with a tumorigenic dose of EL-4 cells. Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2d) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology showed up-regulation of genes involved in the Th-1-type immune response and in the activation of dendritic antigen-presenting cells (APC). The results of our studies confirm the role of APC in mediating the immune protection induced by semi-allogeneic vaccines by activating a Th-1 response; these studies also reveal that semi-allogeneic vaccines are able to interfere with or even block the tumor-mediated induction of immune tolerance, a key mechanism underlying the suppression of anti-tumor immunity in the immune competent host.
Faecal shedding and strain diversity of Listeria monocytogenesin healthy ruminants and swine in Northern Spain
Authors: Esteban Jon I , Oporto Beatriz , Aduriz Gorka , Juste Ramón A , Hurtado Ana
Published: January 2009

Background

Listeria monocytogenes is among the most important foodborne bacterial pathogens due to the high mortality rate and severity of the infection. L. monocytogenes is a ubiquitous organism occasionally present in the intestinal tract of various animal species and faecal shedding by asymptomatically infected livestock poses a risk for contamination of farm environments and raw food at the pre-harvest stages. The aim of this study was to determine the prevalence and strain diversity of L. monocytogenes in healthy ruminants and swine herds.

Results

Faecal samples from 30 animals per herd were collected from 343 herds (120 sheep, 124 beef cattle, 82 dairy cattle and 17 swine) in the Basque Country and screened in pools by an automated enzyme-linked fluorescent immunoassay (VIDAS®) to estimate the prevalence of positive herds. Positive samples were subcultured onto the selective and differential agar ALOA and biochemically confirmed. L. monocytogenes was isolated from 46.3% of dairy cattle, 30.6% beef cattle and 14.2% sheep herds, but not from swine. Within-herd prevalence investigated by individually analysing 197 sheep and 221 cattle detected 1.5% of faecal shedders in sheep and 21.3% in cattle. Serotyping of 114 isolates identified complex 4b as the most prevalent (84.2%), followed by 1/2a (13.2%), and PFGE analysis of 68 isolates showed a highly diverse L. monocytogenes population in ruminant herds.

Conclusion

These results suggested that cattle represent a potentially important reservoir for L. monocytogenes in the Basque Country, and highlighted the complexity of pathogen control at the farm level.
Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity
Authors: Di Domenico Fabio , Foppoli Cesira , Blarzino Carla , Perluigi Marzia , Paolini Francesca , Morici Salvatrice , Coccia Raffaella , Cini Chiara , De Marco Federico
Published: January 2009

Background

Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype.

Methods

The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14) by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored.

Results

We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs.

Conclusion

Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these effects can modulate the cell phenotype and can induce a higher sensitivity to tyrosine related anti-blastic drugs.
Superantigen-mediated differentiation of bovine monocytes into dendritic cells
Authors: Seo Keun Seok , Park Joo Youn , Davis William C , Fox Lawrence K , McGuire Mark A , Park Yong Ho , Bohach Gregory A
Published: January 2009

Although many effects of staphylococcal superantigens (SAg) on T cells are well established, less is known about their effects on APC. In this study, bovine PBMC were stimulated with a low dose of staphylococcal enterotoxin C1 (SEC1). The phenotype of adherent cells (Ac) derived from bovine PBMC cultured with SEC1 [SEC1-stimulated Ac (sAc)] for 192 h was CD14−, CD68−, CD163−, dendritic cell (DC)-specific ICAM-3-grabbing nonintegrin+, MHC class II (MHC II)high, CD11alow, CD11bhigh, CD11chigh, and CD1bhigh, suggesting these cells were dendritic cells (DC). SEC1 also induced transcription of the CXCL1, -2, and -3 family, CXCL6, CCL2, and CCL5 genes in sAc, which increased rapidly but returned to basal levels by 48 h. In contrast, increased transcription of CCL3, CCL8, and CXCL12, responsible for mononuclear cell migration and chronic inflammation, was sustained. In vitro cell migration assays showed vigorous migration of granulocytes, followed by migration of mononuclear cells. The autologous MLR showed that sAc induced a dose-dependent proliferation of CD4+ T cells and an even stronger proliferation of CD8+ T cells. This effect was inhibited or reduced by pretreatment with mAb to CD11b, MHC II, or MHC II plus CD18. These results indicate that stimulation of bovine PBMC by SAg induces differentiation of monocytes into DC.
Financing as a Marketing Strategy
Authors: Seog S. Hun , Hyun Yong J.
Published: January 2009

This paper investigates the issues concerning a film producer that finances production costs not only by the conventional funding from an institutional investor, but also by “Internet funding,” financing through the Internet from so-called netizen investors. In Internet funding, netizen investors engage in word-of-mouth activities. Assuming that information asymmetry exists between the producer and investors, we investigate how the Internet funding size varies with the word-of-mouth effect, the monitoring effect of the institutional investor, and the bargaining power of the producer over investors. When the producer has no bargaining power, the Internet funding size is determined by balancing the word-of-mouth effect with the monitoring effect by the institutional investment. If there is no word-of-mouth effect, there may be no Internet funding, because netizen investors interpret Internet funding as an indicator of a negative profit. When the producer has high bargaining power, full Internet funding is possible if the information asymmetry of the film quality is resolved. We discuss how information asymmetry can be resolved by the monitoring of the film quality, the producer's reputation, or the insurance on investment returns. Our model helps to capture several interesting aspects of Internet funding in the Korean film industry.
Market Structure Across Retail Formats
Authors: Hansen Karsten , Singh Vishal
Published: January 2009

We study how market structure within a product category varies across retail formats. Building on the literature on internal market structure, we estimate a joint store and brand choice model where the loading matrix of brand attributes are allowed to be retail format specific. The approach allows us to recover brand maps for different retail formats while controlling for the short-term marketing mix activities at these stores and the self-selection of households that frequent a particular format. The model is applied to consumer panel data from two product categories, where households are observed to make purchases across three store types: high-end grocery store, traditional supermarket, and large everyday low pricing (EDLP) formats. Our results show strong correlations between the marketing mix sensitivities, store format preference, and unobserved brand attributes. These correlations translate into significant differences in market structure across retail formats and in the direction and size of preference vectors for unobservable brand attributes. We find a tight clustering of brands at the EDLP format, whereas brands are found to compete in distinct subgroups at other stores. Results show that failure to account for retail format effects can substantially bias the understanding of underlying market structure and could lead to incorrect implications in applications such as new product entry.
Sales Growth of New Pharmaceuticals Across the Globe: The Role of Regulatory Regimes
Authors: Stremersch Stefan , Lemmens Aurélie
Published: January 2009

Prior marketing literature has overlooked the role of regulatory regimes in explaining international sales growth of new products. This paper addresses this gap in the context of new pharmaceuticals (15 new molecules in 34 countries) and sheds light on the effects of regulatory regimes on new drug sales across the globe.

Based on a time-varying coefficient model, we find that differences in regulation substantially contribute to cross-country variation in sales. One of the regulatory constraints investigated, i.e., manufacturer price controls, has a positive effect on drug sales. The other forms of regulation such as restrictions of physician prescription budgets and the prohibition of direct-to-consumer advertising (DTCA) tend to hurt sales. The effect of manufacturer price controls is similar for newly launched and mature drugs. By contrast, regulations on physician prescription budgets and DTCA have a differential effect for newly launched and mature drugs. Whereas the former hurts mature drugs more, the latter has a larger effect on newly launched drugs. In addition to these regulatory effects, we find that national culture, economic wealth, and lagged sales also affect drug sales.

Our findings may be used as input by managers for international launch and marketing decisions. They may also be used by public policy administrators to assess the role of regulatory regimes in pharmaceutical sales growth.
Firm-Created Word-of-Mouth Communication: Evidence from a Field Test
Authors: Godes David , Mayzlin Dina
Published: January 2009

In this paper, we investigate the effectiveness of a firm's proactive management of customer-to-customer communication. We are particularly interested in understanding how, if at all, the firm should go about effecting meaningful word-of-mouth (WOM) communications. To tackle this problem, we collect data from two sources: (1) we implement a large-scale field test in which a national firm created word of mouth through two populations: customers and noncustomers, and (2) we collect data from an online experiment. We break our theoretical problem into two subproblems. First, we ask: “What kind of WOM drives sales?” Motivated by previous research, we hypothesize that for a product with a low initial awareness level, WOM that is most effective at driving sales is created by less loyal (not highly loyal) customers and occurs between acquaintances (not friends). We find support for this in the field test as well as in an experimental setting. Hence, we demonstrate the potential usefulness of exogenously created WOM: conversations are created where none would naturally have occured otherwise. Then, we ask: “Which agents are most effective at creating this kind of WOM?” In particular, we are interested in evaluating the effectiveness of the commonly used opinion leader designation. We find that although opinion leadership is useful in identifying potentially effective spreaders of WOM among very loyal customers, it is less useful for the sample of less loyal customers.
Findings—Retailer Promotion Pass-Through: A Measure, Its Magnitude, and Its Determinants
Authors: Ailawadi Kusum L. , Harlam Bari A.
Published: January 2009

We use data on all manufacturer funding and promotion activity by a major U.S. retailer during a two-year period to compute promotion pass-through and assess its magnitude. Then, we estimate a two-tiered probit and lognormal regression model to study drivers of the large variation we observe in pass-through rates.

Although our analysis is based on data from a single retailer, it provides a much more complete picture of the magnitude and variability of pass-through than has been available to date. Some key insights from our work are as follows. First, the retailer passes through more than 100% of the total manufacturer funding it receives in aggregate, but the median pass-through rate for individual manufacturers is much lower than 100%. Second, some manufacturers are promoted even without funding. This is more likely for private label and high-share manufacturers in high-lift and high-margin categories. Third, a small number of manufacturer and category characteristics explain a significant amount of the variation in pass-through. In particular, pass-through is higher for private label. It increases with the share of the manufacturer in the focal category but also with the sales of that manufacturer in other categories. Categories with high sales, high promotion lift, low concentration, and low margin get more pass-through.

We corroborate some recent conclusions in the literature, e.g., that some pass-through rates are much higher than 100% and that high-share manufacturers get more pass-through. We add several new insights, e.g., on the magnitude of aggregate pass-through, on cross-pass-through across and within categories, on pass-through for private label, and on the category drivers of pass-through.
Cold stress regulation of a bi-functional 3-dehydroquinate dehydratase/shikimate dehydrogenase (DHQ/SDH)-like gene in the freshwater green alga Spirogyra varians
Authors: Han Jong Won , Lee Key Pyoung , Yoon Minchul , Kang Sung Ho , Kim Gwang Hoon
Published: January 2009

A low temperature up-regulated gene was isolated from Spirogyra varians using the differentially expressed gene method. The full cDNA sequence consisted of 1798 bp with an open reading frame of 1560 bp encoding 520 amino acid residues, which had neither a cleavage site nor a signal peptide. The deduced amino acid sequence was highly similar to the bi-functional 3-dehydroquinate dehydratase/shikimate dehydrogenase (DHQ/SDH) gene of higher plants. As the gene was cold regulated, we named it SVCR3 (Spirogyra varians cold regulated gene). SVCR3 had two conserved domains of DHQase I and SDH (AroE), as well as a shikimate-binding site as found in other DHQ/SDH genes. Northern blot analysis showed that SVCR3 was up-regulated at 4°C. When combined with light (>50 μmol photon m-2 s-1) the expression of SVCR3 increased more at 4°C, but the expression was not affected by light intensity alone up to 200 μmol photon m-2 s-1 at temperatures higher than 10°C. Using the zymogram method (which is a visualization method for gel areas containing specific enzymes based on chromogenic reactions), we showed that there were three isozymes of DHQ/SDH in Spirogyra varians. This is the first report of DHQ/SDH-like gene regulation by cold stress.
Roller Coasters, Mental Models, and Product Safety
Authors: Nemire Kenneth
Published: January 2009

Mental models – internal representations of the external world – influence perception and decision making. An inappropriate mental model of a roller coaster contributed to one injury and one death in a roller coaster incident. This study revealed that participants' mental models represented the oldest and most prevalent type of roller coaster, despite the existence of several different types. Investigating mental models of users involved in injury incidents often reveals how such incidents occur. To prevent inaccurate mental models from leading users into hazardous situations, product and system designers should follow product safety guidelines to eliminate or reduce the hazards.
Text Entry Interface Design Requirements at a Glance
Authors: O'Brien Marita A. , Rogers Wendy A. , Fisk Arthur D.
Published: January 2009

A critical challenge in creating text entry interfaces for noncomputer-based devices is to devise a highly usable solution that blends aesthetic and functional concerns. As psychologists, we study user and environmental factors that facilitate usability, although this research often is not presented in a format that designers can use. This article presents a framework for guiding the systematic and comprehensive analysis of design requirements through the assessment of critical psychological components. We highlight several solutions from typing and mobile devices that can be directly transferred into a new system and note those areas that typically call for customized solutions.
Wheelchair Postural Support Solutions for Low-Income Countries
Authors: Mines Ray
Published: January 2009

An estimated 80% of the world's disabled people live in low-income countries. The majority of them are poor and do not have access to basic services, including rehabilitation facilities. Motivation is an international organization working in low-income countries to improve opportunities for disabled people by positively influencing their physical, social, and economic situations to enable their full participation in society. Providing good-quality, low-cost, ergonomic wheelchairs in low-income countries is extremely challenging. These complex issues are best addressed by establishing comprehensive services with trained staff and a range of innovative product solutions.
Dilatometric Analysis for Investigating Age Hardening in a Commercial Precious Metal Dental Alloy
Authors: Rivolta B. , Gerosa R. , Pinasco M. R. , Pellati G.
Published: January 2009

Age hardening in a commercial precious metal dental alloy based on the Au–Cu–Ag system with platinum addition was investigated by light optical microscope, scanning electron microscope, energy dispersion x-ray system microanalysis, image analysis, hardness measurements, and dilatometric tests. Dilatometric tests are known to give important information for optimizing the heat treatment parameters of metallic materials but are seldom used in studying the hardening of precious alloys. Nonisothermal dilatometric tests were used to point out the temperature range within which the microstructural hardening transformations occur, while isothermal tests were adopted to study the kinetics of each transformation. The macrohardness and microhardness measurements contributed to the understanding of the nature of the observed transformations, together with the microstructural analysis. We concluded that hardening is mainly due to order-disorder transformations taking place in the matrix. The identified optimal parameters were used for the heat treatment of a lost wax casting alloy prepared according to the traditional procedures for prosthesis manufacturing.
One More Discussion “What is Intensive Quenching Process?”
Authors: Kobasko N. I. , Aronov M. A. , Powell J. A. , Totten G. E.
Published: January 2009

Three intensive quenching processes known as IQ-1, IQ-2, and IQ-3 are considered. In contrast to IQ-2 and IQ-3, processes that use water as a quenchant, the two-step IQ-1 technique is actually a combination of a conventional quench (in oil or polymer/water solution) as the first step, followed by intensive quenching in water (the second step). Similar to the IQ-2 and IQ-3 methods, the IQ-1 process provides residual surface compressive stresses, optimum hardened depth, and additional strengthening (superstrengthening) of the material. A database and a method of calculating the IQ-1 process parameters are considered. The authors underlined that IQ processes are green environmentally friendly methods that significantly reduce CO2 emissions and energy consumption. Also examples of the use of IQ-2 and IQ-3 methods for quenching different kinds of steel parts (such as shafts, pinions, crosses, etc.) are provided. It is shown that the IQ technology’s rapid and uniform cooling rates increase service life of steel parts due to the creation of high residual compressive stresses at the surface of steel parts and due to additional strengthening (superstrengthening) of the material.
Optimierung der Regelung zwischen Brennstoffzelle und Batterie in Bezug auf KomponentenalterungOptimization of Fuel Cell and Battery Control in Relation to Component Aging of Fuel Cell Power Train
Authors: Herb Frieder , Frank Achim , Nitsche Christof , Jossen Andreas
Published: January 2009

Der Beitrag untersucht die Einflüsse unterschiedlicher Hybridisierungsstrategien für Brennstoffzellen-Hybrid-Fahrzeuge auf die Lebensdauer der Brennstoffzelle und der Hybrid-Batterie. Hierbei wurde der Wasserstoffverbrauch bei verschiedener Fahrzyklen mit betrachtet. Die Hybridisierungsstrategien konzentrieren sich alleine auf die Regelung der Leistungsverteilung von Brennstoffzelle und Batterie. Die Untersuchung wurde anhand eines erarbeiteten Fahrzeugsimulationsmodells und Fahrzeugdaten aus dem Advisor-Modell durchgeführt. Für die Lebensdauer der Brennstoffzelle und der Batterie wurden Güteparameter definiert und in einem Netz-Diagramm dargestellt. Des Weiteren wurde der Einfluss einer degradierten Brennstoffzelle auf die Regelung untersucht. Dafür wurde ein Brennstoffzellenmodell, auf der Basis künstlicher neuronaler Netze, anhand von realen Fahrdaten erstellt und in das Gesamtfahrzeugmodell eingebunden. Die Veränderung wird mittels der Abhängigkeit der Güteparameter vom Regelungsparameter diskutiert.
Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis
Authors: Ponce Carlos , Torres Marisa , Galleguillos Carolina , Sovino Hugo , Boric M Angélica , Fuentes Ariel , Johnson M Cecilia
Published: January 2009

In order to investigate the role of the nuclear factor κB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IκB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysedRELA,CHUK,NFKBIAandIL6mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) inNFKBIAmRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) inIL6mRNA and protein (61%),NFKBIAmRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.
Meiotic maturation failure induced by DICER1 deficiency is derived from primary oocyte ooplasm
Authors: Mattiske Deidre M , Han Li , Mann Jeffrey R
Published: January 2009

RNA interference (RNAi) has diverse functions across cellular processes, including a role in the development of the mammalian oocyte. Mouse primary oocytes deficient in the key RNAi enzyme DICER1 exhibit pronounced defects in chromosome congression and spindle formation during meiotic maturation. The cause of this meiotic maturation failure is unknown. In this study, observations of chromosomes and spindle microtubules during prometaphase in DICER1-deficient oocytes indicate that chromosome congression and spindle formation are overtly normal. Spindle breakdown and chromosome displacement occur after the metaphase plate has formed, during the metaphase to anaphase transition. We hypothesised that this defect could be attributed to either RNAi-mediated regulation of nuclear factors, such as the regulation of centromere chromatin assembly, or the regulation of mRNA expression within the cytoplasm. By transplanting germinal vesicles between DICER1-deficient and wild-type primary oocytes, we show that, unexpectedly, the meiotic failure is not caused by a deficiency derived from the germinal vesicle component. Instead, we reveal that the ooplasm of primary oocytes contains DICER1-dependent factors that are crucial for chromosome segregation and meiotic maturation.
Predictors of Outcomes in Pediatric Enteritis: A Prospective Cohort Study
Authors: Freedman Stephen B. , Powell Elizabeth , Seshadri Roopa
Published: January 2009

OBJECTIVES. Oral rehydration therapy is underused by physicians treating children with acute infectious enteritis. To guide management, we hypothesized that clinical variables available at the initial assessment could be identified that will predict the need for intravenous fluid administration.

PATIENTS AND METHODS. Clinical data were prospectively collected on a cohort of 214 children, aged 6 months to 10 years, treated in an emergency department for dehydration secondary to acute enteritis. All of the children performed supervised oral rehydration therapy for a minimum of 60 minutes according to protocol. Outcomes assessed were intravenous rehydration, return visits after discharge, and successful oral rehydration therapy. The latter variable was defined as the consumption of ≥12.5 mL/kg per hour of oral rehydration solution. Variables individually associated with outcomes of interest were evaluated by using multiple logistic regression analysis.

RESULTS. Forty-eight(22%) of 214 children received intravenous rehydration. In multivariate analysis, the 2 clinical predictors of intravenous rehydration were large urinary ketones and altered mental status. Significant predictors of repeat emergency department visits within 3 days included ≥10 episodes of vomiting over the 24 hours before presentation and a higher heart rate at discharge from the emergency department.

CONCLUSIONS. Among children with enteritis and mild-to-moderate dehydration, the presence of large urine ketones or an altered mental status is associated with intravenous rehydration after a 60-minute oral rehydration therapy period. Caution should be exercised before discharging children with either tachycardia or a history of significant vomiting before presentation, because they are more likely to require future emergency department care.