bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptualizing and Categorizing Race and Ethnicity in Health Services Research
Authors: Ford Marvella E. , Kelly P. Adam
Published: September 2005

Objectives. Veterans Affairs (VA) patient populations are becoming increasingly diverse in race and ethnicity. The purpose of this paper is to (1) document the importance of using consistent standards of conceptualizing and categorizing race and ethnicity in health services research, (2) provide an overview of different methods currently used to assess race and ethnicity in health services research, and (3) suggest assessment methods that could be incorporated into health services research to ensure accurate assessment of disease prevalence and incidence, as well as accounts of appropriate health services use, in patients with different racial and ethnic backgrounds.

Design. A critical review of published literature was used.

Principal Findings. Race is a complex, multidimensional construct. For some individuals, institutionalized racism and internalized racism are intertwined in the effects of race on health outcomes and health services use. Ethnicity is most commonly used as a social–political construct and includes shared origin, shared language, and shared cultural traditions. Acculturation appears to affect the strength of the relationships among ethnicity, health outcomes, and health services use.

Conclusions. Improved and consistent methods of data collection need to be developed for use by VA researchers across the country. VA research sites with patients representing specific population groups could use a core set of demographic items in addition to expanded modules designed to assess the ethnic diversity within these population groups. Improved and consistent methods of data collection could result in the collection of higher‐quality data, which could lead to the identification of race‐ and ethnic‐specific health services needs. These investigations could in turn lead to the development of interventions designed to reduce or eliminate these disparities.
Does Wait‐List Size at Registration Influence Time to Surgery? Analysis of a Population‐Based Cardiac Surgery Registry
Authors: Sobolev Boris , Levy Adrian , Hayden Robert , Kuramoto Lisa
Published: September 2005

Objective. To determine whether the probability of undergoing coronary bypass surgery within a certain time was related to the number of patients on the wait list at registration for the operation in a publicly funded health system.

Methods. A prospective cohort study comparing waiting times among patients registered on wait lists at the hospitals delivering adult cardiac surgery. For each calendar week, the list size, the number of new registrations, and the number of direct admissions immediately after angiography characterized the demand for surgery.

Results. The length of delay in undergoing treatment was associated with list size at registration, with shorter times for shorter lists (log‐rank test 1,198.3, p<.0001). When the list size at registration required clearance time over 1 week patients had 42 percent lower odds of undergoing surgery compared with lists with clearance time less than 1 week (odds ratio [OR] 0.58 percent, 95 percent, confidence interval [CI] 0.53–0.63), after adjustment for age, sex, comorbidity, period, and hospital. The weekly number of new registrations exceeding weekly service capacity had an independent effect toward longer service delays when the list size at registration required clearance time less than 1 week (OR 0.56 percent, 95 percent CI 0.45–0.71), but not for longer lists. Every time the operation was performed for a patient requiring surgery without registration on wait lists, the odds of surgery for listed patients were reduced by 6 percent (OR 0.94, CI 0.93–0.95).

Conclusion. For wait‐listed patients, time to surgery depends on the list size at registration, the number of new registrations, as well as on the weekly number of patients who move immediately from angiography to coronary bypass surgery without being registered on a wait list. Hospital managers may use these findings to improve resource planning and to reduce uncertainty when providing advice on expected treatment delays.
Helicobacter pylori“Rescue” Therapy After Failure of Two Eradication Treatments
Authors: Gisbert Javier P. , Pajares José María
Published: September 2005

Nowadays, apart from having to know well first‐line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final – overall – eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI–bismuth–tetracycline–metronidazole), has been generally used as the optimal second‐line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin–PPI at high doses); 2, amoxicillin plus tetracycline (PPI–bismuth–tetracycline–amoxicillin, or ranitidine–bismuth–citrate–tetracyline–amoxicillin); 3, rifabutin (rifabutin–amoxicillin–PPI); 4, levofloxacin (levofloxacin–amoxicillin–PPI); and 5, furazolidone (furazolidone–bismuth–tetracycline–PPI).
Helicobacter pylori Infection is Associated with Reduced Circulating Ghrelin Levels Independent of Body Mass Index
Authors: Shiotani Akiko , Miyanishi Teruo , Uedo Noriya , Iishi Hiroyasu
Published: September 2005

Background.  Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection.

Aim.  To investigate whether there was a relation between H. pylori infection, body mass index (BMI) and serum ghrelin or leptin levels.

Methods.  University students undergoing an annual health check‐up were invited to participate. H. pylori status was based on the presence of specific IgG H. pylori antibodies in urine. Fasting serum ghrelin, leptin levels, and pepsinogen I and II levels were measured by enzyme immunoassay (EIA).

Results.  Eight hundred and one students volunteered. There was no significant difference in the height and BMI between those with and without H. pylori infection. The population of ghrelin study consisted of 132 (66 H. pylori‐positive and 66 H. pylori‐negative) students matched for age, sex, and BMI. The ghrelin level in the H. pylori‐positive group was significantly lower (median 55 pmol/l) compared to the H. pylori‐negative group (103 pmol/l) (p < .00001). Leptin, triglyceride, total cholesterol, and HDL‐cholesterol were not different between the two groups, whereas LDL‐cholesterol levels were significantly higher (106 versus 100 mg/dl) (p = .03) in the H. pylori‐positive group. Leptin levels correlated with the BMI (r = 0.53) (p < .00001). Among H. pylori‐positive subjects, ghrelin correlated only with pepsinogen I levels (r = 0.26, p = .04).

Conclusions.  H. pylori infection was associated with a reduction in circulating ghrelin levels independent of sex and BMI.
Long‐Term Follow‐up after Eradication of Helicobacter pylori with Omeprazole, Clarithromycin, and Tinidazole (OCT Regimen) in a Japanese Population
Authors: Ando Takafumi , Minami Masaaki , Mizuno Tomokazu , Watanabe Osamu , Ishiguro Kazuhiro , Ina Kenji , Kusugami Kazuo , Nobata Kazuo , Nishiwaki Tsuyoshi , Tsuzuki Tomoyuki , Shimada Masaaki , El‐Omar Emad , Goto Hidemi
Published: September 2005

Background.  The long‐term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re‐infection and ulcer relapse after H. pylori eradication.

Materials and methods.  A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C‐urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy.

Results.  Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori‐positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re‐infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years.

Conclusion.  Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re‐infection rate in this population.
Immunity Markers in Patients with Helicobacter pylori Infection: Effect of Eradication
Authors: Dore Maria Pina , Fastame Laura , Tocco Andreina , Negrini Riccardo , Delitala Giuseppe , Realdi Giuseppe
Published: September 2005

Background.  Helicobacter pylori is a microorganism able to stimulate a robust inflammatory and systemic immune response.

Aim.  The aim of our study was to evaluate autoimmune markers in dyspeptic patients positive for H. pylori infection compared to a control group of non‐H. pylori‐infected subjects. The kinetics of cryoglobulins and autoantibodies was evaluated after treatment of the infection.

Patients and methods.  Dyspeptic patients with active H. pylori infection and age‐ and sex‐matched healthy H. pylori‐ negative controls were studied. Markers of immunity were compared, in H. pylori‐infected patients before, 6 months and 1 year after the end of therapy. Results were also compared between those with and without successful eradication therapy.

Results.  Eighty‐six individual were entered (43 H. pylori‐infected). H. pylori‐infected patients had higher levels of IgG and/or IgA and/or IgM (22/43 versus 2/43). Circulating immune complexes and cryoglobulins were detected in patients more often than controls (p < .05 for both). Autoantibodies were observed in 13 patients (30% versus 5% in controls) and antithyroid antibodies in 12 (p < .04 versus controls). Lower levels of C3 and/or C4 complement fractions were observed in infected patients with respect to controls (7/43 versus 1/43; p = .014). After 1 year of follow‐up, the markers of autoimmunity dramatically improved in patients eradicated for H. pylori infection compared to those in whom therapy failed. No patient developed a clinical autoimmune disorder.

Conclusions.  Additional studies are necessary to ascertain the clinical significance of the modifications of autoimmune markers in patients with H. pylori infection.
Contribution of dppA to Urease Activity in Helicobacter pylori 26695
Authors: Davis Gregg S. , Mobley Harry L.T.
Published: September 2005

Background.  The gastric pathogen Helicobacter pylori produces urease in amounts up to 10% of its cell protein. This enzyme, which catalyzes the hydrolysis of urea to ammonia and carbon dioxide, protects the bacterium from gastric acid. Urease, a nickel metalloenzyme, requires active uptake of nickel ions from the environment to maintain its activity. NixA is a nickel transport protein that resides in the cytoplasmic membrane. Mutation of nixA significantly reduces but does not abolish urease activity, strongly suggesting the presence of a second transporter. We postulated that the dipeptide permease (dpp) genes that are homologous to the nik operon of Escherichia coli could be a second nickel transporter. The predicted Dpp polypeptides DppA, DppC, and DppD of H. pylori share approximately 40%, 53%, and 56% amino acid sequence identity with their respective E. coli homologs.

Methods.  A mutation in dppA, constructed by insertional inactivation with a chloramphenicol resistance cassette, was introduced by allelic exchange into H. pylori strain 26695.

Results.  When compared to the parental strain, urease activity was not decreased in a dppA mutant.

Conclusions.  DppA does not contribute to the synthesis of catalytically active urease in H. pylori 26695 and is likely not a nickel importer in H. pylori
Helicobacter pylori Outer Membrane Protein 18 (Hp1125) Induces Dendritic Cell Maturation and Function
Authors: Rathinavelu Sivaprakash , Kao John Y. , Zavros Yana , Merchant Juanita L.
Published: September 2005

Background.  Dendritic cells (DCs) are potent antigen‐presenting cells that initiate T‐cell responses. A robust adaptive Th1 immune response is crucial to an adaptive (Th2) immune response necessary for vaccine‐induced protective immunity against Helicobacter pylori. It has been shown that several outer membrane proteins (Omps) induce a robust antibody response. However, it is also known that the antibodies generated are not protective. Moreover there is great variation in the recognition of high molecular weight H. pylori proteins by sera from infected patients. In contrast to the high molecular weight proteins, serologic responses to small molecular weight proteins provide assessment of current infection with H. pylori and also of its eradication.

Aim.  The goal of the study was to analyze the activation of the immune response by a specific low molecular weight Omp that is universally expressed by all H. pylori strains. Therefore, we studied interaction of H. pylori Omp18 with DCs.

Methods.  Activation of murine bone marrow‐derived DCs and production of cytokines by Omp18 was assessed by fluorescence‐activated cell sorter (FACS) for costimulatory markers and ELISA, respectively. The ability of Omp18 stimulated DCs to induce lymphocyte proliferation was measured in a mixed leukocyte reaction.

Results.  Omp18 induced higher expression of the B7 (CD80 and CD86) costimulatory molecule after 18 hours indicating processing and presentation of the antigen on the surface by bone marrow‐derived DCs. The maturing DCs also secreted significant levels of IL‐12, but was 4‐fold less than that stimulated by whole bacteria. Omp18‐primed DCs induced proliferation and release of IFNγ by syngeneic splenocytes.

Conclusion.  We concluded that Omp18 is capable of activating DCs initiating a Th1 immune response.
Equilibrium in a Dynamic Limit Order Market
Authors: GOETTLER RONALD L. , PARLOUR CHRISTINE A. , RAJAN UDAY
Published: September 2005

We model a dynamic limit order market as a stochastic sequential game with rational traders. Since the model is analytically intractable, we provide an algorithm based on Pakes and McGuire (2001) to find a stationary Markov‐perfect equilibrium. We then generate artificial time series and perform comparative dynamics. Conditional on a transaction, the midpoint of the quoted prices is not a good proxy for the true value. Further, transaction costs paid by market order submitters are negative on average, and negatively correlated with the effective spread. Reducing the tick size is not Pareto improving but increases total investor surplus.
The Optimal Concentration of Creditors
Authors: BRIS ARTURO , WELCH IVO
Published: September 2005

Our model assumes that creditors need to expend resources to collect on claims. Consequently, because diffuse creditors suffer from mutual free‐riding (Holmstrom (1982)), they fare worse than concentrated creditors (e.g., a house bank). The model predicts that measures of debt concentration relate positively to creditors' (aggregate) debt collection expenditures and positively to management's chosen expenditures to resist paying. However, collection activity is purely redistributive, so social waste is larger when creditors are concentrated. If borrower quality is not known, the best firms choose the most concentrated creditors and pay higher expected yields.
Managerial Stock Ownership and the Maturity Structure of Corporate Debt
Authors: DATTA SUDIP , ISKANDAR‐DATTA MAI , RAMAN KARTIK
Published: September 2005

This study documents that managerial stock ownership plays an important role in determining corporate debt maturity. Controlling for previously identified determinants of debt maturity and modeling leverage and debt maturity as jointly endogenous, we document a significant and robust inverse relation between managerial stock ownership and corporate debt maturity. We also show that managerial stock ownership influences the relation between credit quality and debt maturity and between growth opportunities and debt maturity.
Methods of Payment in Asset Sales: Contracting with Equity versus Cash
Authors: SLOVIN MYRON B. , SUSHKA MARIE E. , POLONCHEK JOHN A.
Published: September 2005

We analyze intercorporate asset sales where equity is the means of payment, and compare the results to cash asset sales. Equity deals are value‐enhancing for both buyers, 10%, and sellers, 3%, while cash sales generate seller returns of 1.9% and buyer returns that are not significant. Combined wealth gains are large for equity deals, but modest for cash deals. Equity‐based asset sales are not a precursor to consolidations between buyers and sellers, and do not affect buyer openness to the takeover market. We conclude that the use of buyer equity conveys favorable information about the value of assets and buyers.
Information and Control in Ventures and Alliances
Authors: DESSEIN WOUTER
Published: September 2005

This paper develops a theory of control as a signal of congruence of objectives, and applies it to financial contracting between an investor and a privately informed entrepreneur. We show that formal investor control is (i) increasing in the information asymmetries ex ante, (ii) increasing in the uncertainty surrounding the venture ex post, (iii) decreasing in the entrepreneur's resources, and (iv) increasing in the entrepreneur's incentive conflict. In contrast, real investor control—that is, actual investor interference—is decreasing in information asymmetries. Control rights are further such that control shifts to the investor in bad states of nature.
Maxillary sinus floor grafting with β‐tricalcium phosphate in humans: density and microarchitecture of the newly formed bone
Authors: Suba Zsuzsanna , Takács Daniel , Matusovits Danica , Barabás József , Fazekas András , Szabó György
Published: September 2005

Objectives: Graft insertion can effectively enhance the regeneration of debilitated bone. The effects of an alloplastic bone‐replacing material, β‐tricalcium phosphate (Cerasorb), and of autogenous bone graft were compared.

Materials and methods: In 17 edentulous patients, the maxillary sinus floor was extremely atrophied to such an extent that implant placement was impossible. The Schneiderian membrane was surgically elevated bilaterally by insertion of Cerasorb (experimental side) and autogenous bone graft (control side). After surgery, the recovery was followed clinically and radiologically. After 6 months, 68 bone cylinders were excised from the grafted areas and implants were inserted into their places. The bone samples were embedded into resin, and the osteointegration of the grafts was studied histologically. Trabecular bone volume (TBV) and trabecular bone pattern factor (TBPf) were quantified by histomorphometry.

Results: Cerasorb proved to be an effective bone‐replacing material with osteoconductivity; it was capable of gradual disintegration, thereby providing space for the regenerating bone. The new bone density was not significantly different on the experimental and control sides (32.4±10.9% and 34.7±11.9%, respectively). However, the graft biodegradation was significantly slower on the experimental side than the control side. The TBPf value was lower on the control side than on the experimental side (−0.53±1.7 and −0.11±1.4 mm−1, respectively), but this difference was not significant.

Conclusions: Six months after insertion of the grafts, the bone of the augmented sinus floor was strong and suitable for anchorage of dental implants, irrespective of whether autogenous bone or Cerasorb particles had been applied.
Human ex vivo bone tissue strains around immediately loaded implants supporting maxillary overdentures
Authors: Akça Kıvanç , Akkocaoğlu Murat , Cömert Ayhan , Tekdemir İbrahim , Çehreli Murat Cavit
Published: September 2005

Purpose: To evaluate ex vivo bone tissue strains around maxillary implants supporting immediately loaded bar‐retained overdentures.

Material and methods: Ninety degree two‐element rosette strain gauges were bonded on the labial bone of four ITI® dental implants placed in the maxillary anterior region of four completely edentulous maxilla of fresh human cadavers. The installation torque value (ITV) of each implant was measured by a custom‐made torque wrench and resonance frequency analyses (RFAs) were undertaken. A bar‐retained overdenture was fabricated for each cadaver, and two miniature load cells were integrated in the first molar region of the overdentures for controlled loading experiments. Strain measurements were performed at a sample rate of 10 kHz and under a maximum load of 100 N, simultaneously monitored from a computer connected to a data acquisition system. Finally, removal torque values (RTVs) of the implants were measured.

Results: RFA values did not mirror ITVs, while RTVs of implants were slightly lower than the ITVs. Any correlation could not be obtained between RFA values and ITVs or RTVs. Maximum strains around loaded implants ranged between −100 and −550 μɛ under 25–100 N. The axial and lateral strain values of posterior implants of both sides were higher than those of anterior implants under all loads (P<0.05).

Conclusion: Because occlusal forces in humans tend to decrease because of age‐related factors, maximum strains around immediately loaded implants supporting maxillary overdentures fall within physiologic levels.
A distinguishable observation between survival and success rate outcome of hydroxyapatite‐coated implants in 5–10 years in function
Authors: Artzi Zvi , Carmeli Guy , Kozlovsky Avital
Published: September 2005

Purpose: To differentiate between the survival and success definitions of functional hydroxyapatite (HA)‐coated implant prosthesis.

Methods: A total of 248 implants (62 patients), 5–10 years in function, were evaluated. The implant distribution length was 8 mm (6.5%), 10 mm (29.4%), 13 mm (30.2%) and 15 mm (33.9%). The diameter was 3.25 mm (60.1%) and 4 mm (39.9%). Probing depth (PD), gingival index (GI), height of keratinized mucosa (KM) and recession (REC) were measured. Periapical radiographs were taken to estimate the amount of crestal bone resorption (BL), mesially and distally, with the aid of a millimetric‐scaled magnifying glass (× 8). Only implants that fulfilled the success rate criteria were considered as successful. All other functional implants were assigned to the non‐successful group. All functional implant prostheses were defined as survival ones.

Results: The accumulative survival rate after 5 and 10 years was 94.4% and 92.8%, respectively. Accumulative success rates were 89.9% and 54%, respectively. Implants 13 and 15 mm in length (97.9% and 96.4%, respectively) had the highest survival rate, which was higher over implants 8 and 10 mm in length (75%, P<0.01 and 88.2%, respectively). The survival rate of 4 mm diameter implants compared with 3.25 mm was 96.5% and 90.3%, respectively (P=0.019). The average BL was 1.7, 0.92 and 2.79 mm for the survival, successful and non‐successful defined implant groups. PD was 3.26, 2.79 and 4 mm and GI was 0.96, 0.75 and 1.57, respectively. These measurements were statistically different between implant groups. KM and REC measurements showed similar scoring for all groups. A correlation was shown between successful and non‐successful implants on the score of GI and PD (P<0.001 in both).

Conclusion: A distinguishable observation between survival and success rate was noted particularly in long‐term observations. Implant length and diameter have an influence on the survival rate. Clinical parameter scores expressed an influence on the defined implant status.
The predictive value of exercise testing for survival among 75‐year‐old men and women
Authors: Kallinen M. , Kauppinen M. , Era P. , Heikkinen E.
Published: September 2005

All 75‐year‐olds born in 1914 and living in the city of Jyväskylä, central Finland (n=388) were invited to study the predictive value of exercise test for mortality. Subjects who entered the laboratory (n=295) were to have a standard pre‐test evaluation and perform a cycle ergometer exercise test. Subjects with complete background, exercise‐test status and mortality data (n=282) were divided into three groups according to exercise‐test status: a non‐exercise test group (n=79), an exercise‐test termination group (n=95), and an exercise‐test completion group (n=108). Mortality was followed up for 9 years. The multivariate hazard ratio (HR) for death among the non‐exercise test group compared with exercise‐test completion group was 1.87 (CI 1.19–2.94). The multivariate HR for death among the exercise‐test termination group compared with the exercise‐test completion group was 0.95 (CI 0.58–1.54). High cycling power (W/kg body weight) in the exercise‐test completion group was associated with a decreased risk for death with a multivariate HR 0.14 (CI 0.05–0.38). Performing an exercise test serves information on the risk of death that is incremental to clinical data and traditional risk factors of death in elderly people.
Enhanced apoptosis through farnesol inhibition of phospholipase D signal transduction
Authors: Taylor Marcia M. , MacDonald Kendra , Morris Andrew J. , McMaster Christopher R.
Published: September 2005

Farnesol is a catabolite of the cholesterol biosynthetic pathway that preferentially causes apoptosis in tumorigenic cells. Phosphatidylcholine (PC), phosphatidic acid (PA), and diacylglycerol (DAG) were able to prevent induction of apoptosis by farnesol. Primary alcohol inhibition of PC catabolism by phospholipase D augmented farnesol‐induced apoptosis. Exogenous PC was unable to prevent the increase in farnesol‐induced apoptosis by primary alcohols, whereas DAG was protective. Farnesol‐mediated apoptosis was prevented by transformation with a plasmid coding for the PA phosphatase LPP3, but not by an inactive LPP3 point mutant. Farnesol did not directly inhibit LPP3 PA phosphatase enzyme activity in an in vitro mixed micelle assay. We propose that farnesol inhibits the action of a DAG pool generated by phospholipase D signal transduction that normally activates an antiapoptotic/pro‐proliferative target.
Structural function of C‐terminal amidation of endomorphin
Authors: In Yasuko , Minoura Katsuhiko , Tomoo Koji , Sasaki Yusuke , Lazarus Lawrence H. , Okada Yoshio , Ishida Toshimasa
Published: September 2005

To investigate the structural function of the C‐terminal amide group of endomorphin‐2 (EM2, H‐Tyr‐Pro‐Phe‐Phe‐NH2), an endogenous µ‐opioid receptor ligand, the solution conformations of EM2 and its C‐terminal free acid (EM2OH, H‐Tyr‐Pro‐Phe‐Phe‐OH) in TFE (trifluoroethanol), water (pH 2.7 and 5.2), and aqueous DPC (dodecylphosphocholine) micelles (pH 3.5 and 5.2) were investigated by the combination of 2D 1H‐NMR measurement and molecular modelling calculation. Both peptides were in equilibrium between the cis and trans rotamers around the Tyr‐‐Pro w bond with population ratios of 1 : 1 to 1 : 2 in dimethyl sulfoxide, TFE and water, whereas they predominantly took the trans rotamer in DPC micelle, except in EM2OH at pH 5.2, which had a trans/cis rotamer ratio of 2 : 1. Fifty possible 3D conformers were generated for each peptide, taking different electronic states depending on the type of solvent and pH (neutral and monocationic forms for EM2, and zwitterionic and monocation forms for EM2OH) by the dynamical simulated annealing method, under the proton‐proton distance constraints derived from the ROE cross‐peak intensities. These conformers were then roughly classified into four groups of two open [reverse S (rS)‐ and numerical 7 (n7)‐type] and two folded (F1‐ and F2‐type) conformers according to the conformational pattern of the backbone structure. Most EM2 conformers in neutral (in TFE) and monocationic (in water and DPC micelles) forms adopted the open structure (mixture of major rS‐type and minor n7‐type conformers) despite the trans/cis rotamer form. On the other hand, the zwitterionic EM2OH in TFE, water and DPC micelles showed an increased population of F1‐ and F2‐type folded conformers, the population of which varied depending on their electronic state and pH. Most of these folded conformers took an F1‐type structure similar to that stabilized by an intramolecular hydrogen bond of (Tyr1)NH3+...COO–(Phe4), observed in its crystal structure. These results show that the substitution of a carboxyl group for the C‐terminal amide group makes the peptide structure more flexible and leads to the ensemble of folded and open conformers. The conformational requirement of EM2 for binding to the µ‐opioid receptor and the structural function of the C‐terminal amide group are discussed on the basis of the present conformational features of EM2 and EM2OH and a possible model for binding to the µ‐opioid receptor, constructed from the template structure of rhodopsin.
Association of MHC class I chain related gene‐A microsatellite polymorphism with the susceptibility to T1DM and LADA in Czech adult patients
Authors: Novota P. , Kolostova K. , Pinterova D. , Novak J. , Weber P. , Treslova L. , Kovar J. , Andel M. , Cerna M.
Published: September 2005

The results in this study suggest that microsatellite polymorphism within the transmembrane region of MIC‐A gene is associated with genetic susceptibility to adult‐onset of type 1 diabetes mellitus (T1DM), MIC‐A5.1 allele, corrected P = 0.001, whereas it is not associated with latent autoimmune diabetes in adults (LADA) in Czech population. According to our findings, we can hypothesize that adult‐onset T1DM and LADA may have partly different immunogenetic aetiopathogenesis.
A case–control study of tyrosine phosphatase (PTPN22) confirms the lack of association with Crohn's disease
Authors: Wagenleiter S. E. N. , Klein W. , Griga T. , Schmiegel W. , Epplen J. T. , Jagiello P.
Published: September 2005

In Crohn's disease (CD), the whole gastrointestinal tract can be affected by discontinuous and transmural inflammation. The terminal ileum and colon are especially prone to inflammation that comprises granulomata and later intestinal and perianal fistulas. Genome‐wide linkage and epidemiological studies established genetic predisposition factors to CD.

Recently, a variation of the intracellular protein tyrosine phosphatase nonreceptor‐type 22 (PTPN22) was associated with several autoimmune diseases. Here, we analysed the functionally relevant polymorphism R620W (rs 2476601) of the PTPN22 gene in 146 patients suffering from CD using restriction fragment length polymorphism (RFLP) analyses. This study revealed evidence that PTPN22 variation may have no influence in the genetic predisposition to CD, at least not in another well‐characterized Caucasian cohort.
A radial velocity survey of low Galactic latitude structures – II. The Monoceros Ring behind the Canis Major dwarf galaxy
Authors: Conn Blair C. , Martin Nicolas F. , Lewis Geraint F. , Ibata Rodrigo A. , Bellazzini Michele , Irwin Mike J.
Published: September 2005

An AAT/2dF Spectrograph Survey of low Galactic latitudes targeting the putative Canis Major dwarf galaxy and the (possibly) associated tidal debris of stars known as the Monoceros Ring, covering Galactic coordinates and , has revealed the presence of the Monoceros Ring in the background of the Canis Major dwarf galaxy. This detection resides at a Galactocentric distance of ∼18.9 ± 0.3 kpc (13.5 ± 0.3 kpc heliocentric), exhibiting a velocity of ∼132.8 ± 1.3kms−1 with a dispersion of ∼22.7 ± 1.7kms−1, both of these comparable to previous measurements of the Monoceros Ring in nearby fields. This detection highlights the increasing complexity of structure being revealed in recent surveys of the Milky Way thick disc and halo.
The progenitor of SN 2005cs in the Whirlpool Galaxy
Authors: Maund Justyn R. , Smartt Stephen J. , Danziger I. John
Published: September 2005

The progenitor of SN 2005cs, in the galaxy M51, is identified in pre-explosion Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) Wide Field Channel (WFC) imaging. Differential astrometry, with post-explosion ACS High Resolution Channel (HRC) F555W images, permitted the identification of the progenitor with an accuracy of 0.006 arcsec. The progenitor was detected in the F814W pre-explosion image with I= 23.3 ± 0.2, but was below the detection thresholds of the F435W and F555W images, with B < 24.8 and V < 25 at 5σ. Limits were also placed on the U- and R-band fluxes of the progenitor from pre-explosion HST Wide Field Planetary Camera 2 (WFPC2) F336W and F675W images. Deep images in the infrared from the Near Infra-red Imager (NIRI) on the Gemini North Telescope were taken 2 months prior to explosion, but the progenitor is not clearly detected on these. The upper limits for the JHK magnitudes of the progenitor were J < 21.9, H < 21.1 and K < 20.7. Despite having a detection in only one band, a restrictive spectral energy distribution of the progenitor star can be constructed and a robust case is made that the progenitor was a red supergiant with spectral type between mid-K and late-M. The spectral energy distribution allows a region in the theoretical Hertzsprung–Russell diagram to be determined that must contain the progenitor star. The initial mass of the star is constrained to be MZAMS= 9+3−2M⊙, which is very similar to the identified progenitor of the Type II-P SN 2003gd, and also consistent with upper mass limits placed on five other similar supernovae. The upper limit in the deep K-band image is significant in that it allows us to rule out the possibility that the progenitor was a significantly higher mass object enshrouded in a dust cocoon before core collapse. This is further evidence that the trend for Type II-P supernovae to arise in low- to moderate-mass red supergiants is real.
Organization of common synaptic drive to motoneurones during fictive locomotion in the spinal cat
Authors: Nielsen J. B. , Conway B. A. , Halliday D. M. , Perreault M.‐C. , Hultborn H.
Published: September 2005

The basic locomotor rhythm in the cat is generated by a neuronal network in the spinal cord. The exact organization of this network and its drive to the spinal motoneurones is unknown. The purpose of the present study was to use time (cumulant density) and frequency domain (coherence) analysis to examine the organization of the last order drive to motoneurones during fictive locomotion (evoked by application of nialamide and dihydroxyphenylalanine (DOPA)) in the spinal cat. In all cats, narrow central synchronization peaks (half‐width < 3 ms) were observed in cumulants estimated between electroneurograms (ENGs) of close synergists, but not between nerves belonging to muscles acting on different joints or to antagonistic muscles. Coherence was not observed at frequencies above 100 Hz and was mainly observed between synergists. Intracellular recording was obtained from a population of 70 lumbar motoneurones. Significant short‐term synchronization was observed between the individual intracellular recordings and the ENGs recorded from nerves of the same pool and of close synergists. Recordings from 34 pairs of motoneurones (10 pairs belonged to the same motor pool, 11 pairs to close synergists and 13 pairs to antagonistic pools) failed to reveal any short‐lasting synchronization. These data demonstrate that short‐term synchronization during fictive locomotion is relatively weak and is restricted to close synergists. In addition, coherence analysis failed to identify any specific rhythmic component in the locomotor drive that could be associated with this synchronization. These results resemble findings obtained during human treadmill walking and imply that the spinal interneurones participating in the generation of the locomotor rhythm are themselves weakly synchronized. The restricted synchronization within the locomotor drive to motoneuronal pools may be a feature of the locomotor generating networks that is related to the ability of these networks to produce highly adaptive patterns of muscle activity during locomotion.
ATP sensitivity of ATP‐sensitive K+ channels: role of the γ phosphate group of ATP and the R50 residue of mouse Kir6.2
Authors: John Scott A. , Weiss James N. , Ribalet Bernard
Published: September 2005

ATP‐sensitive K (KATP) channels are composed of Kir6, the pore‐forming protein, and the sulphonylurea receptor SUR, a regulatory protein. We and others have previously shown that positively charged residues in the C terminus of Kir6.2, including R201 and K185, interact with the α and β phosphate groups of ATP, respectively, to induce channel closure. A positively charged residue in the N terminus, R50, is also important, and has been proposed to interact with either the γ or β phosphate group of ATP. To examine this issue, we systematically mutated R50 to residues of different size, charge and hydropathy, and examined the effects on adenine nucleotide sensitivity in the absence and presence of SUR1. In the absence of SUR1, only the size of residue 50 significantly altered ATP sensitivity, with smaller side chains decreasing ATP sensitivity. In the presence of SUR1, however, hydrophathy and charge also played a role. Hydrophilic residues decreased ATP sensitivity more than hydrophobic residues for small size residues, and, surprisingly, negatively charged residues E and D preserved ATP sensitivity and increased ADP sensitivity relative to the wild‐type residue R. These observations suggest that a negative charge near position 50, due to either mutation of R50 or the interaction of the γ phosphate group of ATP with R50, facilitates closure of the ATP‐dependent gate. Mutation of the nearby positively charged residue R54, known to be involved in stabilizing channel opening via electrostatic interactions with phosphatidylinositol 4,5‐bisphosphate (PIP2), also caused increased ADP sensitivity as compared with ATP, suggesting a loss of function of ATP's γ phosphate. Based on these results, we propose that a phosphate group or a negative charge at position 50 initiates channel closure by destabilizing the electrostatic interactions between negative phosphate groups of PIP2 and residues such as R54.
Spike coding during osmotic stimulation of the rat supraoptic nucleus
Authors: Bhumbra G. S. , Inyushkin A. N. , Syrimi M. , Dyball R. E. J.
Published: September 2005

Novel measures of coding based on interspike intervals were used to characterize the responses of supraoptic cells to osmotic stimulation. Infusion of hypertonic NaCl in vivo increased the firing rate of continuous (putative oxytocin) cells (Wilcoxon z= 3.84, P= 0.001) and phasic (putative vasopressin) cells (z= 2.14, P= 0.032). The irregularity of activity, quantified by the log interval entropy, was decreased for continuous (Student's t= 3.06, P= 0.003) but not phasic cells (t= 1.34, P= 0.181). For continuous cells, the increase in frequency and decrease in entropy was significantly greater (t= 2.61, P= 0.036 and t= 3.06, P= 0.007, respectively) than for phasic cells. Spike patterning, quantified using the mutual information between intervals, was decreased for phasic (z=−2.64, P= 0.008) but not continuous cells (z=−1.14, P= 0.256). Although continuous cells showed similar osmotic responses to mannitol infusion, phasic cells showed differences: spike frequency decreased (z=−3.70, P < 0.001) and entropy increased (t=−3.41, P < 0.001). Considering both cell types together, osmotic stimulation in vitro using 40 mm NaCl had little effect on firing rate (z=−0.319, P= 0.750), but increased both entropy (t= 2.75, P= 0.010) and mutual information (z=−2.73, P= 0.006) in contrast to the decreases (t= 2.92, P= 0.004 and z=−2.40, P= 0.017) seen in vivo. Responses to less severe osmotic stimulation with NaCl or mannitol were not significant. Potassium‐induced depolarization in vitro increased firing rate (r= 0.195, P= 0.034), but the correlation with decreased entropy was not significant (r=−0.097, P= 0.412). Intracellular recordings showed a small depolarization and decrease in input resistance during osmotic stimulation with NaCl or mannitol, and membrane depolarization following addition of potassium. Differences in responses of oxytocin and vasopressin cells in vivo, suggest differences in the balance between the synaptic and membrane properties involved in coding their osmotic responses. The osmotic responses in vivo constrasted with those seen in vitro, which suggests that, in vivo, they depend on extrinsic circuitry. Differences in responses to osmolality and direct depolarization in vitro indicate that the mechanism of osmoresponsiveness within a physiological range is unlikely to be fully explained by depolarization.
Fibroblast growth factor 14 is an intracellular modulator of voltage‐gated sodium channels
Authors: Lou Jun‐Yang , Laezza Fernanda , Gerber Benjamin R. , Xiao Maolei , Yamada Kathryn A. , Hartmann Hali , Craig Ann Marie , Nerbonne Jeanne M. , Ornitz David M.
Published: September 2005

Genetic ablation of the fibroblast growth factor (Fgf) 14 gene in mice or a missense mutation in Fgf14 in humans causes ataxia and cognitive deficits. These phenotypes suggest that the neuronally expressed Fgf14 gene is essential for regulating normal neuronal activity. Here, we demonstrate that FGF14 interacts directly with multiple voltage‐gated Na+ (Nav) channel α subunits heterologously expressed in non‐neuronal cells or natively expressed in a murine neuroblastoma cell line. Functional studies reveal that these interactions result in the potent inhibition of Nav channel currents (INa) and in changes in the voltage dependence of channel activation and inactivation. Deletion of the unique amino terminus of the splice variant of Fgf14, Fgf14‐1b, or expression of the splice variant Fgf14‐1a modifies the modulatory effects on INa, suggesting an important role for the amino terminus domain of FGF14 in the regulation of Nav channels. To investigate the function of FGF14 in neurones, we directly expressed Fgf14 in freshly isolated primary rat hippocampal neurones. In these cells, the addition of FGF14‐1a–GFP or FGF14‐1b–GFP increased INa density and shifted the voltage dependence of channel activation and inactivation. In fully differentiated neurones, FGF14‐1a–GFP or FGF14‐1b–GFP preferentially colocalized with endogenous Nav channels at the axonal initial segment, a critical region for action potential generation. Together, these findings implicate FGF14 as a unique modulator of Nav channel activity in the CNS and provide a possible mechanism to explain the neurological phenotypes observed in mice and humans with mutations in Fgf14.
Oxytocin stimulates secretory processes in lactating rabbit mammary epithelial cells
Authors: Lollivier Vanessa , Marnet Pierre‐Guy , Delpal Serge , Rainteau Dominique , Achard Caroline , Rabot Aline , Ollivier‐Bousquet Michèle
Published: September 2005

Oxytocin plays a major role in lactation mainly by its action on milk ejection via the contraction of myoepithelial cells. The effect of oxytocin on milk production and the presence of oxytocin receptors on different epithelial cells suggest that this hormone may play a role in mammary epithelial cells. To determine precisely the various roles of oxytocin, we studied localization of oxytocin receptors in lactating rabbit and rat mammary tissue and the influence of oxytocin on secretory processes in lactating rabbit mammary epithelial cells. Immunolocalization of oxytocin receptors on mammary epithelial cells by immunofluorescence and in mammary tissue by immunogold in addition to in situ hybridization showed that lactating rat and rabbit mammary epithelial cells expressed oxytocin receptors. Moreover, oxytocin bound specifically to epithelial cells. To determine whether oxytocin had an effect on lactating rabbit mammary epithelial cells, isolated mammary fragments were incubated in the presence or absence of 10−6 i.u. ml−1 of oxytocin. After 1 min of incubation with oxytocin, the morphology of epithelial cells and the localization of caseins and proteins associated with the secretory traffic suggested a striking acceleration of the transport leading to exocytosis, whereas the contraction of myoepithelial cells was only detectable after 7 min. Addition of 10−8 g ml−1 of atosiban before the addition of oxytocin prevented the oxytocin effect on secretory processes and on myoepithelial cell contraction. Addition of 10−6 i.u. ml−1 of vasopressin to the incubation medium did not mimic the stimulating effect of oxytocin on secretory traffic. These results show that lactating rabbit and rat mammary epithelial cells express oxytocin receptors and that oxytocin binds to these receptors. They strongly suggest that oxytocin has a dual effect on lactating mammary tissue: an acceleration of the intracellular transfer of caseins in mammary epithelial cells followed by the contraction of myoepithelial cells.
Illustrations of the relativistic conservation law for the center of energy
Authors: Boyer Timothy H.
Published: September 2005

The relativistic conservation law involving the center of energy is reviewed and illustrated using simple examples from classical electromagnetic theory. It is emphasized that this conservation law is parallel to the conservation laws for energy, linear momentum, and angular momentum, because it arises from the generators of the Poincare group for electromagnetic theory; yet this relativistic law reflecting the continuous flow of energy is not mentioned in text books. The illustrations include situations where external forces are present and are absent. A parallel plate capacitor, a flattened slip-joint solenoid, and two interacting charges are treated.
An entangled web of crime: Bell’s theorem as a short story
Authors: Jacobs Kurt , Wiseman Howard M.
Published: September 2005

Nonlocality of the type first elucidated by Bell in 1964 is a difficult concept to explain to nonspecialists and undergraduates. We attempt to do so by showing how nonlocality can be used to solve a problem in which someone might find themselves as the result of a series of normal, even if somewhat unlikely, events. Our story is told in the style of a Sherlock Holmes mystery, and is based on Mermin’s formulation of the “paradoxical” illustration of quantum nonlocality discovered by Greenberger, Horne, and Zeilinger.
A note on Dolby and Gull on radar time and the twin “paradox”
Authors: Eagle Antony
Published: September 2005

Recently a suggestion was made that standard textbook representations of hypersurfaces of simultaneity for the traveling twin in the twin “paradox” are incorrect. This suggestion is false: The textbooks are in agreement with a correct understanding of the relativity of simultaneity.
Calculation of band structures by a discrete variable representation based on Bloch functions
Authors: Le Rouzo Hervé
Published: September 2005

The propagation of waves in periodic media is restricted to allowed bands of energy or frequencies separated by forbidden gaps. We propose a discrete variable representation, based on Bloch functions, that is suitable for the calculation of band structures in one-dimensional systems. The solutions are obtained by a single diagonalization without any integration. The method only needs the values of the potential at grid points. Applications to the standard Krönig-Penney and Mathieu potentials, and to the nonanalytical case of a soft Coulomb potential, show that very good accuracy is achieved with moderate grid sizes.