bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of horizontal gradients on GPS radio occultation observation operators. II: A Fast Atmospheric Refractivity Gradient Operator (FARGO)
Authors: Poli P.
Published: January 2005

Previous works have suggested that strong atmospheric horizontal gradients need to be accounted for in the simulation of Global Positioning System radio occultation (GPS RO) refraction measurements. The contribution of such horizontal gradients to GPS RO observables can be calculated from a background with a multi‐plane two‐dimensional (2D) ray tracer. In part I we showed that the effects of horizontal gradients can be separated into tangent point drift (TPD) and horizontal gradients along the ray (HGR). We present here a fast observation operator called FARGO. FARGO incorporates both TPD and HGR effects but presents computation times 48 times faster than 2D ray tracing for calculating bending angle and more than 250 times faster for refractivity. TPD effects are simulated using slanted profiles while the HGR correction is applied in one occultation plane only and limited to the vicinity of the tangent point.

When compared to observation operators which assume spherical symmetry, FARGO allows for reductions in the r.m.s. of the differences between observed and calculated bending angles and refractivities which are similar to those obtained with 2D ray tracing. Such reductions of the observed minus calculated refractivity can reach 80% for an occultation which occurred perpendicular to a tropospheric refractivity ridge (axis of high values) along a warm sector containing high water vapour amounts. We found that in about 5% of the cases, accounting for horizontal gradients via FARGO reduces the differences from real data by more than a half. The method used by FARGO to account for horizontal gradients can be extended for simulating refraction measurements collected by other instruments. Copyright © 2004 Royal Meteorological Society
Resolution dependence of orographic torques
Authors: R. Brown A.
Published: January 2005

An evaluation of the performance of the subgrid orography parametrization scheme in the ECMWF Integrated Forecast System is made by examining the variation with resolution of the orographic torques (resolved and parametrized) in short‐range global forecasts. As the spectral resolution is increased from T95 to T511, the magnitudes of the resolved torques increase while those of the parametrized torques decrease. In general the changes in the total orographic torques are reasonably small, but an important exception is between 20°N and 50°N in winter. Here the total orographic torque decreases significantly with increasing resolution. Through examination of errors in the modelled angular momentum budgets, it is suggested that the problems lie primarily at the low resolution end, where the parametrized orographic torques seem to be excessive. Furthermore, recent work with the NCEP reanalysis data suggests that this result may not be unique to the ECMWF system. Copyright © 2004 Royal Meteorological Society
Studies of the Selective Removal of Microquantities of Platinum(IV) Ions from Model Chloride Solutions onto Ion Exchangers Containing Functional Tertiary Amine and Polyamine Groups
Authors: Hubicki Z. , Wójcik G.
Published: January 2005

Since platinum is applied widely in industry, the recovery of noble metals from industrial wastes becomes an economic issue. Laboratory studies have been undertaken of the selective removal of microquantities of Pt(IV) ions from 0.1–6 M hydrochloric acid solutions onto ion exchangers containing functional tertiary amine groups (Amberlite IRA-67 and Amberlite IRA-93) or functional polyamine groups (Diaion CR 20). The recovery factor values [% R Pt(IV)] were determined for these ion exchangers as well as the sorption isotherms which depended on the kind of aqueous phase employed and the phase contact time. In addition, the weight and volume distribution coefficients, the number of theoretical plates as well as the working ion-exchange capacities were calculated from the Pt(IV) ion breakthrough curves. Due to their high ion-exchange capacities relative to Pt(IV) ions and their high resistance towards chemical agents, these ion exchangers may be applied both in platinum recovery technologies and in analysis of trace amounts of the noble metal.
Effect of Silanol Groups on the Acidic and Catalytic Properties of Alkylsulphoacidic Silicas and SiO2/Nafion Nanocomposites
Authors: Alekseev Sergei A. , Zaitsev V.N. , Alekseev A.N. , Kochkin Yu.N. , Evans J.
Published: January 2005

Sets of silicas covalently modified with alkylsulphoacidic groups (SiO2-SO3H) and nanocomposites of silica with superacidic Nafion® polymer (SiO2/Nafion) were synthesised. End-capping the silanol groups with trimethylsilyl groups was used to obtain surface hydrophobisation. The materials obtained were characterised by nitrogen and water adsorption measurements, MAS NMR spectroscopy and dielectric relaxation spectroscopy (DRS). The acidity of the materials was tested by 31P MAS NMR spectroscopic examination of samples with adsorbed triethylphosphine oxide (TEPO). It was demonstrated that end-capping excluded part of the surface silanol groups from interaction with acidic groups, thereby causing the sulphonic groups to exhibit an increased acidity. With SiO2-SO3H, end-capping also increased their catalytic activity in the synthesis of ethyl t-butyl ether (ETBE). However, end-capping had a negligible effect on the catalytic properties of SiO2/Nafion, probably because the catalytic reaction occurred inside the Nafion polymer nanoparticles.
Chromium(III) Removal from Wastewaters by a Weakly Acidic Resin Containing Carboxylic Groups
Authors: Kocaoba S. , Akcin G.
Published: January 2005

As a conservative technology, ion exchange allows the removal and recycling of metals from liquid effluents. A process was applied for the removal of chromium(III) from wastewaters by ion exchange. This process was based on a weakly acidic cation-exchange resin (Amberlite IRC 86) capable of removing chromium(III) from the effluent, followed by selective separation and recovery during a regeneration procedure.

Because of the difficult regeneration behaviour of the metal form of the carboxylate resin, special emphasis was given to the regeneration step of the resin where most of the practical problems were found. Five different regeneration procedures were adopted: elution with 1 M NaOH; elution with 1 M H2SO4; elution with 1 M NaOH followed by 1 M H2SO4 or vice versa; elution with NaOH followed by 1 M H2SO4/Na2SO4 solution; and elution with alkaline H2O2/NaOH solutions followed by 1 M H2SO4. A non-conventional regenerant solution such as hydrogen peroxide in an alkaline medium seemed very promising. The anionic species formed (chromate) was eluted quantitatively from the cation-exchange resin and separated. The regeneration efficiency of chromium(III) was 89.5%.

Influent chromium concentrations employed during the tanning process used in the leather industry were also considered. For this purpose, influent concentrations in the range 60–100 mg/l, service flow rates of 10 and 20 l/h and appropriate retention times were selected and experiments undertaken in a column system. The exhaustion step was carried out at 250 l/h with the recovery of chromium being 95.6%. The ion-exchange capacity of Amberlite IRC 86 was found to be 1.28 equiv/l. This study undertaken under laboratory conditions demonstrated that Amberlite IRC 86 resin was suitable for the removal of chromium(III) from wastewater.
Moisture Sorption Isotherms of Whey Powder Spray in the 10–40°C Temperature Range
Authors: Stencl J.
Published: January 2005

The results of water sorption tests on whey powder spray carried out under laboratory conditions were presented together with mathematical analyses of the sorption isotherms. Moisture equilibrium data were investigated at air temperatures over the temperature range 10–40°C and water activity ranging from 0.3 to 0.99. The experimental procedure used was a gravimetric dynamic method with continuous registration of sample weight changes. A special laboratory drying device was developed for the purpose.

The sorption capacity decreased as the temperature increased. Re-hydration of the dried material resulted in hysteresis but this phenomenon was limited. Four models of equilibrium moisture content/water activity (Chung-Pfost, Halsey, Henderson and Oswin) were evaluated for their ability to fit the data for the samples tested. The Henderson equation provided a good model for moisture adsorption and desorption by whey powder spray.
Investigation of the Structure of Polyethylene Glycol (PEG) Layers Adsorbed at the Alumina-Polymer Solution Interface
Authors: Chibowski St. , Paszkiewicz M. , Mazur-Opala E.
Published: January 2005

The investigations presented were aimed at a description of the structure of the adsorbed layers of polyethylene glycol (PEG) on the surface of Al2O3. This was obtained from measurements of the adsorption heat of PEG macromolecules as well as of 1,2-dimethoxyethane (C4H10O2) and tetraethylene glycol dimethyl ether (C10H22O5), i.e. low-molecular weight compounds constituting the monomers forming the PEG chain.

The results allowed the fraction of polymer segments bonding directly to the Al2O3 surface to be estimated. Other information obtained from calculations based on the Scheutjens–Fleer theory included the distribution of chain segment conformations as trains, loops and tails, together with a determination of some structural changes and the sizes of PEG macromolecules as they moved from the bulk solution to the solid phase surface. The thickness of the adsorbed macro-molecular polymer layers on the alumina surface was also determined. All these data enabled an approximate description to be made of the polymer chain structure at the Al2O3–polymer solution interface.
Prediction of Henry's Law Constants on the Basis of the Corresponding States Theorem
Authors: Kutarov V.V. , Kats B.M.
Published: January 2005

It has been suggested that the well-known two-parameter Corresponding States Theorem for the prediction of the Henry coefficient should be broadened to the four-parameter theorem. The corresponding four-parameter theorem was used to analyze the experimental data for the adsorption of 16 organic and non-organic substances onto active carbon of the Kureha beads type. Employing this theorem to account for the form and change in position of the minimum in the potential curve, it was shown that the Corresponding States Theorem could be applied for the prediction of the Henry coefficient for molecules of arbitrary configuration under conditions requiring the introduction of quantum amendments. All the suggested amendments to the known two-parameter Corresponding States Theorem were strictly based and could be easily defined a priori.
Diethylaminoethylation of Chitin and the Adsorption of Acid Dyes onto the Resulting Polymer
Authors: Shimizu Yoshiaki , Tominaga Tsutomu , Saito Yoshihiro
Published: January 2005

Water-soluble chitin derivatives have been synthesized by the diethylaminoethylation (DEAE) reaction and the adsorption characteristics of the resulting polymeric adsorbents towards two acid dyes (CI Acid Orange 7 and CI Acid Red 88) were studied. The adsorption behaviours towards these dyes were also compared with those exhibited by two water-insoluble commercially available derivatives. The conventional water-insoluble DEAE-chitins showed a high adsorptive capacity towards CI Acid Orange 7 compared to that on untreated chitin and alkali-treated chitin. A similar trend was also found for CI Acid Red 88 dye, where the increase in adsorption was characterized more clearly. However, the adsorption capacities towards both dyes exhibited by the water-soluble DEAE-chitins were increased significantly at a particular free dye concentration, with the adsorptive power also being increased both with the degree of DEAE substitution and the hydrophobicity of the dyes.
Column Effective Length considering the Inter-Story Interaction
Authors: Tong Gengshu , Wang Jinpeng
Published: January 2005

Through an analysis of a simple two-story frame, this paper revealed that the assumptions used in conventional effective length method led to an unrealistic distribution of beam restraints among the connected columns. With three assumptions of the conventional approach discarded, a new approach is proposed by which column effective length considering inter-story interaction can be obtained in unbraced two- or three-story frames. A quadratic equation for two-story frames and a cubic equation for three-story frames are derived from which the rotational restraints provided to each column may be solved and the effective length factors can then be determined by the traditional formula or tables. For frames of more than 3 stories, the weakest story is selected and a three-story sub-assemblage including the weakest column is taken out, and the proposed method is applied, the effective length of the weakest column is thus obtained, the effective length of the remaining columns are computed through a predefined relations. Because the sub-assemblage included beams at far ends of the columns above and below the column under consideration, the far end condition (hinged or fixed) may be considered easily.
Study on Electromechanical Behavior of Unidirectional Carbon Fibre Sheet without Epoxy Resin Matrix
Authors: Li Hui , Zhou Wensong , Ou Jinping
Published: January 2005

The relationship between stress, strain and electrical resistance of carbon fibre sheet without an epoxy resin matrix has been studied. Carbon fibre sheet specimens were tested under a tensile loading condition to investigate their self-diagnostic properties, that is, the ability of the specimens to sense the strain themselves. The experimental results indicate that the electrical resistance of carbon fibre sheet changes linearly with applied strain, such that carbon fibre sheet can act as a sensor to measure strain. A parallel circuit is employed to model the electrical behavior of carbon fibre sheet. The Weibull distribution model for fibre strength is made use of to calculate change in electrical resistance as fibres break. The ratio of broken fibres not making contact with neighbouring fibres, to all broken fibres in total is identified by fitting the test data. The results calculated using the parallel circuit model agree well with the test results.
Finite Element Analysis (FEA) of Fabricated Square and Triangular Section Stub Columns Utilizing Very High Strength Steel Tubes
Authors: Van Binh Do , Al-Mahaidi Riadh , Zhao Xiao-Ling
Published: January 2005

This paper presents finite element analysis (FEA) of twenty fabricated square and triangular section (FSTS) stub columns utilizing very high strength (VHS) circular steel tubes with a nominal yield stress of 1,350 MPa. The VHS tubes are placed at each corner of the section and welded to Grade 350 steel plates. Two different nominal diameter-to-thickness ratios of 15.9 and 23.8 were chosen for the VHS tubes. Five different nominal width-to-thickness ratios ranging from 40 to 133 were chosen for the steel plates. Three different lengths of 500, 1000 and 1200mm were chosen for the specimens. The geometric imperfection and softening of heat – affected zone (HAZ) in the VHS tubes were included in the FEA along with material non-linearity and geometric non-linearity. The FEA results were compared with the experimental results and two analytical approaches proposed by the authors. Good agreement was found between the FEA, experimental and analytical results.
Over-the-Counter Medicine Use Prior to and During Hospitalization
Authors: Oborne C Alice , Luzac Michal L
Published: January 2005

BACKGROUND:

In the UK, medicines are being reclassified from prescription-only drugs to allow supply without prescription. This allows faster and easier access to medicines to treat minor ailments and allows patients to take greater responsibility for their health. However, over-the-counter (OTC) drugs may pose risks to patients; thus, it is important to understand patients' OTC medicine use.

OBJECTIVE:

To assess use of OTC drugs prior to and during hospital stay of inpatients of all ages and specialties.

METHODS:

Data were collected for 186 randomly selected patients. Patients were interviewed about OTC medicine use. Clinical notes and drug charts were examined for documentation of OTC medicine use.

RESULTS:

A total of 268 OTC medicines were used by 119 (64.0%) patients, and 117 (43.7%) were taken at least daily. Only 13 (4.9%) OTC drugs were recorded in the drug history taken at admission. Twenty-six (9.7%) OTC agents were still taken during hospitalization, but only 8 (31%) were recorded on drug charts. Patients bought 183 (68.3%) items from pharmacies, 28 (10.4%) in health food shops, and 57 (21.7%) elsewhere including supermarkets, homeopaths, or mail order. Patients had little knowledge of potential adverse effects or contraindications.

CONCLUSIONS:

Many patients use OTC medication prior to and during hospital stay, but documentation in hospital notes is poor. Healthcare professionals must pay closer attention to patients' use of OTC drugs.
Eptifibatide-Associated Acute, Profound Thrombocytopenia
Authors: Coons James C , Barcelona Robert A , Freedy Tucker , Hagerty Michael F
Published: January 2005

OBJECTIVE:

To describe 3 cases of eptifibatide-associated acute, profound thrombocytopenia.

CASE SUMMARIES:

A 40-year-old black female received eptifibatide 180-μg/kg double bolus followed by a continuous infusion of 2 μg/kg/min for percutaneous coronary intervention (PCI). The platelet count decreased from 308 times 103/mm3 to 2 times 103/mm3 4 hours after initiation of eptifibatide. Eptifibatide was discontinued and platelets were transfused. The patient developed a hematoma and petechiae. A 67-year-old white female received the same dosage regimen of eptifibatide for PCI with no serious adverse effects, with the treatment repeated one month later. At that time, she developed chest and back pain, dyspnea, wheezing, and hypotension after the first bolus. Her platelet count decreased from 334 times 103/mm3 to 6 times 103/mm3 24 hours after initiation. Eptifibatide was discontinued and platelets were transfused. The patient died due to shock. A 72-year-old white male received eptifibatide 180-μg/kg double bolus followed by a continuous infusion of 2 μg/kg/min for acute coronary syndrome. His platelet count decreased from 189 times 103/mm3 to 17 times 103/mm3, and eptifibatide was discontinued. Eptifibatide was readministered with bivalirudin for PCI once the platelet count increased to 94 times 103/mm3. Sixteen hours later, the platelet count decreased to 1 times 103/mm3. Eptifibatide was discontinued and platelets were transfused. The patient developed a hematoma.

DISCUSSION:

Acute, profound thrombocytopenia is a rare complication of glycoprotein IIb/IIIa inhibitor therapy characterized by a precipitous decline in platelet count to <20 times 103/mm3 within 24 hours of therapy. An objective causality assessment revealed that the adverse drug event was probable in 2 cases and possible in the other.

CONCLUSIONS:

Increasing use of the glycoprotein IIb/IIIa inhibitors and enhanced recognition of the potential for acute, profound thrombocytopenia reinforce the need for more vigilant monitoring and alternative management strategies.
Methemoglobinemia Secondary to Topical Benzocaine Use in a Lung Transplant Patient
Authors: LeClaire Aimée C , Mullett Timothy W , Jahania M Salik , Flynn Jeremy D
Published: January 2005

OBJECTIVE:

To report a case of methemoglobinemia secondary to the administration of topical benzocaine spray in an anemic patient who had previously undergone a lung transplant.

CASE SUMMARY:

A 40-year-old white man with a past medical history significant for lung transplant acutely decompensated following oropharyngeal administration of topical benzocaine spray. Subsequent blood analysis revealed a methemoglobin concentration of 51.2%. Following the administration of a single dose of methylene blue 2 mg/kg intravenously, the patient's respiratory status dramatically improved and stabilized.

DISCUSSION:

Methemoglobinemia is a rare but potentially fatal condition that may be either acquired or congenital; however, the disorder is most commonly acquired secondary to exposure to oxidizing chemicals, which are often routinely prescribed medications, including benzocaine. Benzocaine can react with hemoglobin to form methemoglobin at a rate that exceeds reduction capabilities, which may result in oxygenation difficulty and respiratory distress. In severe or symptomatic methemoglobinemia, the treatment of choice is methylene blue.

CONCLUSIONS:

Application of the Naranjo probability scale established a highly probable relationship between topical benzocaine spray and methemoglobinemia and associated respiratory compromise. The risks of palliative use of topical benzocaine in patients with preexisting disorders that compromise oxygen delivery may outweigh any benefit. In our patient, anemia and lung disease increased his risk for clinically significant adverse respiratory events secondary to deficiencies or interferences in oxygen delivery. Topical benzocaine should be administered with caution and careful monitoring in such patient populations.
Interaction Between Dexamethasone Treatment and the Corticotropin Stimulation Test in Septic Shock
Authors: Bower Amy N , Oyen Lance J
Published: January 2005

OBJECTIVE:

To review dexamethasone interaction with corticotropin stimulation testing, particularly as it applies to treating septic shock.

DATA SOURCES:

Pertinent literature was identified through MEDLINE (1966–February 2004) using combinations of the key words dexamethasone, adrenocorticotropic hormone stimulation, and pretreat. Only articles written in the English language and evaluating human subjects were considered. Reference lists of identified articles were reviewed for additional citations.

DATA SYNTHESIS:

Accurate interpretation of the corticotropin stimulation test is important to identify patients with septic shock who may benefit from corticosteroid supplementation. In healthy volunteers, short-term dexamethasone administration prior to the corticotropin stimulation test may depress the baseline cortisol level, but does not inhibit the response to the corticotropin challenge. This may result in a slight increase in the difference between baseline and post-stimulation values.

CONCLUSIONS:

In 2 small trials in healthy adults, short-term, low-dose dexamethasone pretreatment decreased baseline cortisol levels, but values following corticotropin stimulation were unaffected. Accordingly, caution in interpreting corticotropin stimulation test results is warranted. However, the application of the findings from these studies to patients with septic shock is difficult, given the important differences in physiology between normal and septic patients. As of December 29, 2004, a dexamethasone dose >2 mg or prolonged dexamethasone therapy (>2 days, totaling 4 mg) preceding corticotropin stimulation has not been studied in any population.
Health Food Stores' Recommendations for Nausea and Migraines During Pregnancy
Authors: Buckner Kaitlin D , Chavez Mary L , Raney Erin C , Stoehr James D
Published: January 2005

BACKGROUND:

Many pregnant women use dietary supplements during pregnancy; however, relatively scant information is available on the safety of these products. Consumers of dietary supplements often rely on employees of health food stores to provide recommendations.

OBJECTIVE:

To evaluate recommendations made by health food store employees in the Phoenix metropolitan area regarding treatment of nausea/vomiting and migraines during pregnancy.

METHODS:

Phone calls were made by a disguised shopper to 155 health food stores in the greater Phoenix area. The caller posed as a woman 8 weeks' pregnant asking for recommendations for treatment of nausea/vomiting and migraines. Responses and recommendations were recorded and then compared with current scientific evidence obtained during a search of the literature using MEDLINE (1966–September 2004) as to whether or not the supplements and the methods of their use during pregnancy were contraindicated.

RESULTS:

Eighty-nine percent of stores offered recommendations for nausea/vomiting, and 82% provided recommendations for migraines. The use of ginger was the most recommended therapy for nausea/vomiting. Only 3.6% of respondents recommended correct usage, but failed to supply the correct dosage and duration. A total of 15 of 278 (5%) recommendations, for both nausea/vomiting and migraines, were for products contraindicated in pregnancy.

CONCLUSIONS:

In light of the increased use of dietary supplements by women during pregnancy, the willingness of personnel in health food stores to make any recommendations should foster concerns by patients and healthcare providers alike. Use of dietary supplements contraindicated in pregnancy could cause significant harm to the mother and/or fetus. Studies are needed to address the need for more stringent guidelines regarding health food stores and their recommendations.
Dystonia Induced by Gabapentin
Authors: Pina Miguel A , Modrego Pedro J
Published: January 2005

OBJECTIVE:

To report a case of dystonia as an adverse effect of gabapentin.

CASE SUMMARY:

A 72-year-old woman was diagnosed with essential tremor and treated with propranolol 120 mg daily. The drug was withdrawn because of bradycardia, and gabapentin was prescribed 3 times a day at escalating doses to reach 2100 mg daily. The woman developed a dystonic reaction involving muscles of the neck and both arms that resolved rapidly after drug withdrawal. She was restarted on gabapentin with slow titration to 1800 mg daily, but the same dystonic reaction appeared, which led to definitive withdrawal of the drug. An objective causality assessment revealed that this adverse effect was highly probable.

DISCUSSION:

There have been only a few previous reports of gabapentin-induced dystonia. Other movement disorders reported with gabapentin include myoclonus, ataxia, and choreoathetosis. Gabapentin has been used to treat dystonias with variable results.

CONCLUSIONS:

Although gabapentin is widely used and well tolerated, it can cause dystonic reactions, which are reversible after drug withdrawal.
Possible Warfarin Interaction with Menthol Cough Drops
Authors: Kassebaum Paul J , Shaw Don L , Tomich Dave J
Published: January 2005

OBJECTIVE:

To report a case of possible interaction of menthol cough drops (Halls) with warfarin in a patient awaiting cardioversion.

CASE SUMMARY:

A 57-year-old white male awaiting cardioversion for atrial fibrillation was prescribed warfarin. His dosage was adjusted to 7 mg daily to provide stable international normalized ratio (INR) values of 2.28–2.68. Approximately one week later, his INR fell to 1.45. During a follow-up interview, the patient reported that he experienced a flu-like illness during the previous week and had been using menthol cough drops. No other potential causes for the decreased INR were found. Illness will most often elevate the INR; we therefore concluded that the cough drops were the likely cause of this reaction, and the warfarin dose was increased to 53 mg/wk. After discontinuing use of menthol cough drops, the warfarin dose was returned to the previous amount and the INR remained stabilized.

DISCUSSION:

An objective causality assessment suggests that the decreased INR was possibly related to the use of menthol cough drops during warfarin therapy. The active ingredient in these cough drops is menthol. Menthol has been shown to affect the pharmacokinetics of other drugs by inducing or inhibiting cytochrome P450 isoenzymes and slowing drug absorption. It is not clear whether these mechanisms played a role in this case. As of January 5, 2005 this is the first case report documenting an interaction between warfarin and cough drops containing menthol.

CONCLUSIONS:

This case documents a significant decrease in the INR following the use of menthol cough drops. Patients who are ill have several factors that can potentially affect their INR and should be monitored closely.
Retailer, Manufacturers, and Individual Consumers: Modeling the Supply Side in the Ketchup Marketplace
Authors: Villas-Boas J. Miguel , Zhao Ying
Published: January 2005

The authors construct a model of the local ketchup market in a Texas city that accounts for household, manufacturer, and retailer decisions. That is, the model develops both demand and supply sides of the market. The authors model the demand side through a latent utility framework that allows for a no-purchase option. Accounting for both sides of the market enables the authors to check for any endogeneity problems on the demand side. They model the supply side through the profit-maximizing decisions of the manufacturers and a multiproduct retailer. Accounting for both the retailer and the manufacturer decisions enables the authors to evaluate the degree of manufacturer competition, retailer–manufacturer interactions, and retailer product-category pricing. Given the model assumptions and the market being studied, the authors find that not accounting for demand endogeneity can create bias in the estimation, the retailer seems to price below the static profit-maximizing prices for two of the three brands, and the inferred marginal wholesale prices are below the equilibrium uniform wholesale prices for two brands. The authors discuss the results with regard to channel bargaining, quantity discounts, and retailer category pricing.
Longer Forms of Amyloid β Protein: Implications for the Mechanism of Intramembrane Cleavage by γ-Secretase
Authors: Qi-Takahara Yue , Morishima-Kawashima Maho , Tanimura Yu , Dolios Georgia , Hirotani Naoko , Horikoshi Yuko , Kametani Fuyuki , Maeda Masahiro , Saido Takaomi C. , Wang Rong , Ihara Yasuo
Published: January 2005

γ-Cleavage of β-amyloid precursor protein (APP) in the middle of the cell membrane generates amyloid β protein (Aβ), and ϵ-cleavage, ∼10 residues downstream of the γ-cleavage site, releases the APP intracellular domain (AICD). A significant link between generation of Aβ and AICD and failure to detect AICD41-99 led us to hypothesize that ϵ-cleavage generates longer Aβs, which are then processed to Aβ40/42. Using newly developed gel systems and an N-end-specific monoclonal antibody, we have identified the longer Aβs (Aβ1-43, Aβ1-45, Aβ1-46, and Aβ1-48) within the cells and in brain tissues. The production of these longer Aβs as well as Aβ40/42 is presenilin dependent and is suppressed by {1S-benzyl-4R-[1S-carbamoyl-2-phenylethylcarbamoyl-1S-3-methylbutylcarbamoyl]-2R-hydroxy-5-phenylpentyl}carbamic acid tert-butyl ester, a transition state analog inhibitor for aspartyl protease. In contrast,N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, a potent dipeptide γ-secretase inhibitor, builds up Aβ1-43 and Aβ1-46 intracellularly, which was also confirmed by mass spectrometry. Notably, suppression of Aβ40 appeared to lead to an increase in Aβ43, which in turn brings an increase in Aβ46, in a dose-dependent manner. We therefore propose an α-helical model in which longer Aβ species generated by ϵ-cleavage is cleaved at every three residues in its carboxyl portion.
3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses
Authors: Cordle Andrew , Landreth Gary
Published: January 2005

Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar β-amyloid (Aβ) in the brain, a fulminant microglial-mediated inflammatory reaction, and neuronal death. The use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) is associated with a reduced risk of AD, which has been attributed to the cholesterol-lowering actions of these drugs. Statins have been reported recently to have anti-inflammatory actions in addition to their classic lipid-lowering effects. We report that statins robustly inhibited the Aβ-stimulated expression of interleukin-1β and inducible nitric oxide synthase and the production of nitric oxide by microglia and monocytes. Statin treatment also blocked the rac1-dependent activation of NADPH oxidase and superoxide production. The anti-inflammatory actions of the statins were attributable to their ability to reduce the levels of isoprenyl intermediates in the cholesterol biosynthetic pathway. The effect of statins could not be reversed by exogenous cholesterol supplementation, indicating that the anti-inflammatory actions are distinct from their cholesterol-lowering actions. The addition of the isoprenyl precursors, mevalonic acid, and geranylgeranyl pyrophosphate (GGpp) attenuated the statin-mediated downregulation of inflammatory markers. Prevention of protein isoprenylation by the GGpp transferase inhibitor (GGTI-286) or inhibition of Rho-family function withClostridium difficileToxin A blocked the inflammatory response similar to the effect of statin treatment. We argue that the statin-mediated decrease in AD risk arises from their pleiotropic actions, effecting a reduction in neuronal Aβ production and microglia-directed inflammation.
Postsynaptic Shank Antagonizes Dendrite Branching Induced by the Leucine-Rich Repeat Protein Densin-180
Authors: Quitsch Arne , Berhörster Kerstin , Liew Chong Wee , Richter Dietmar , Kreienkamp Hans-Jürgen
Published: January 2005

Leucine-rich repeat and PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domain proteins such as scribble and Densin-180 have been implicated in the establishment of cell-cell contacts. Here, we show that Densin-180, which has been identified as a constituent of the postsynaptic density in excitatory synapses interacts with the postsynaptic scaffold protein shank (shank1-3). The interaction involves a two-point attachment of the C-terminal region of Densin-180 with the Src homology 3 domain and the N-terminal part of the proline-rich region of shank proteins. The N-terminal leucine-rich repeat region, which is not involved in binding shank, targets Densin-180 to the plasma membrane in transfected cells and to the basolateral membrane of epithelial cells. Nevertheless, coexpression of shank leads to a redirection of Densin-180 into intracellular clusters. In cultured hippocampal neurons, Densin-180 overexpression induces excessive branching of neuronal dendrites, which occurs at the expense of clusters for the postsynaptic marker PSD-95. Coexpression of shank3 abrogates branch formation and targets Densin-180 into postsynaptic clusters instead. Shank blocks binding of δ-catenin but not αCaM kinase II to Densin-180; because δ-catenin has been shown to induce branching and neurite formation, our data suggest a mechanism where shank could block the activation of a Densin-180-dependent signaling pathway by δ-catenin.
Glutamatergic Innervation of the Heart Initiates Retrograde Contractions in AdultDrosophila melanogaster
Authors: Dulcis Davide , Levine Richard B.
Published: January 2005

The adult abdominal heart ofDrosophila melanogasterreceives extensive innervation from glutamatergic neurons at specific cardiac regions during metamorphosis. Here, we show that the neurons form presynaptic specializations, as indicated by the localization of synaptotagmin and active zone markers, adjacent to postsynaptic sites that have aggregates of glutamate IIA receptors. To determine the role of this innervation in cardiac function, we developed an optical technique, based on the movement of green fluorescent protein-labeled nerve terminals, to monitor heart beat in intact and semi-intact preparations. Simultaneous monitoring of adjacent cardiac chambers revealed the direction of contractions and allowed correlation with volume changes. The cardiac cycle is composed of an anterograde beat in alternation with a retrograde beat, which correlate respectively with systole and diastole of this multichambered heart. The periodic change in hemolymph direction is referred to as cardiac reversal.

Intracellular recordings from muscles of the first abdominal cardiac chamber, the conical chamber, revealed pacemaker action potentials and the excitatory effect of local glutamate application, which initiated retrograde contractions in semi-intact preparations. Unilateral electrical stimulation of the transverse nerve containing the glutamatergic neuron that serves the conical chamber caused a chronotropic effect and initiation of retrograde contractions. This effect is distinct from that of peripheral crustacean cardioactive peptide (CCAP) neurons, which potentiate the anterograde beat. Cardiac reversal was evoked pharmacologically by sequentially applying CCAP and glutamate to the heart.
Axonal Protein Synthesis and Degradation Are Necessary for Efficient Growth Cone Regeneration
Authors: Verma Poonam , Chierzi Sabrina , Codd Amanda M. , Campbell Douglas S. , Meyer Ronald L. , Holt Christine E. , Fawcett James W.
Published: January 2005

Axonal regeneration can occur within hours of injury, the first step being the formation of a new growth cone. For sensory and retinal axons, regenerative abilityin vivocorrelates with the potential to form a new growth cone after axotomyin vitro. We show that this ability to regenerate a new growth cone depends on local protein synthesis and degradation within the axon. Axotomyin vitroleads to a fourfold to sixfold increase in3H-leucine incorporation in both neurones and axons, starting within 10 min and peaking 1 h after axotomy. Application of protein synthesis inhibitors (cycloheximide and anisomycin) to cut axons, including axons whose cell bodies were removed, or proteasome inhibitors (lactacystin andN-acetyl-Nor-Leu-Leu-Al) all result in a reduction in the proportion of transected axons able to reform growth cones. Similar inhibition of growth cone formation was observed on addition of target of rapamycin (TOR), p38 MAPK (mitogen-activated protein kinase), and caspase-3 inhibitors. Comparing retinal and sensory axons of different developmental stages, levels of ribosomal protein P0 and phosphorylated translation initiation factor are high in sensory axons, lower in embryonic axons, and absent in adult retinal axons. Conditioning lesions, which increase the regenerative ability of sensory axons, lead to increases in intra-axonal protein synthetic and degradative machinery bothin vitroandin vivo. Collectively, these findings suggest that local protein synthesis and degradation, controlled by various TOR-, p38 MAPK-, and caspase-dependent pathways, underlie growth cone initiation after axotomy.
Morphine-Induced Chemotaxis and Brain-Derived Neurotrophic Factor Expression in Microglia
Authors: Takayama Naoko , Ueda Hiroshi
Published: January 2005

The addition of morphine at 1 μminduced morphological changes of cultured microglia such that they changed from having globular or bipolar rod-like shapes to being flat and lamellipodial, with membrane ruffling at the edge, which was stained with phalloidin. The membrane ruffling was clearly colocalized withRac. Morphine also induced chemotaxis in Boyden chamber analysis at concentrations of 1 μmor more in microglia and the microglial cell line EOC 2. All of these changes were abolishable by naloxone, antisense oligodeoxynucleotide for μ-opioid receptor (MOR), pertussis toxin (PTx), and wortmannin, but not genistein or 1,10-phenanthroline. The addition of morphine to microglia stimulated the gene expression of brain-derived neurotrophic factor (BDNF) as early as the 1 hr point, and this lasted for >12 hr. Morphine induced BDNF gene expression and ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation, and these were abolishable by naloxone, wortmannin, PD98059, genistein, and 1,10-phenanthroline. The addition of conditioned medium derived from the culture of morphine-treated microglia also increased the phosphorylation of ERK1/2. All of these findings suggest that morphine induces significant changes in both morphology and gene expression at relatively high concentrations, but the underlying signaling pathways downstream of MOR and Gi/oappear to be different from each other. Phosphoinositide 3-kinase γ activation andRacactivation are involved in chemotaxis, whereas indirect pathways through ERK1/2 phosphorylation induced by unknown growth factors generated through an MOR-mediated metalloprotease activation are linked to the enhanced BDNF gene expression.
Activity-Dependent Presynaptic Regulation of Quantal Size at the Mammalian Neuromuscular JunctionIn Vivo
Authors: Wang Xueyong , Li Yingjie , Engisch Kathrin L. , Nakanishi Stan T. , Dodson Sara E. , Miller Gary W. , Cope Timothy C. , Pinter Martin J. , Rich Mark M.
Published: January 2005

Changes in synaptic activity alter quantal size, but the relative roles of presynaptic and postsynaptic cells in these changes are only beginning to be understood. We examined the mechanism underlying increased quantal size after block of synaptic activity at the mammalian neuromuscular junctionin vivo. We found that changes in neither acetylcholinesterase activity nor acetylcholine receptor density could account for the increase. By elimination, it appears likely that the site of increased quantal size after chronic block of activity is presynaptic and involves increased release of acetylcholine. We used mice with muscle hyperexcitability caused by mutation of the ClC-1 muscle chloride channel to examine the role of postsynaptic activity in controlling quantal size. Surprisingly, quantal size was increased in ClC mice before block of synaptic activity. We examined the mechanism underlying increased quantal size in ClC mice and found that it also appeared to be located presynaptically. When presynaptic activity was completely blocked in both control and ClC mice, quantal size was large in both groups despite the higher level of postsynaptic activity in ClC mice. This suggests that postsynaptic activity does not regulate quantal size at the neuromuscular junction. We propose that presynaptic activity modulates quantal size at the neuromuscular junction by modulating the amount of acetylcholine released from vesicles.
Regulation of Gephyrin and GABAAReceptor Binding within the Amygdala after Fear Acquisition and Extinction
Authors: Chhatwal Jasmeer P. , Myers Karyn M. , Ressler Kerry J. , Davis Michael
Published: January 2005

Both the acquisition and extinction of conditioned fear appear to require the basolateral amygdala (BLA). Because these two forms of learning have opposing effects on the expression of conditioned fear, we hypothesized that they may modulate GABAergic tone differentially within the BLA. Previously, we reported that gene expression for the GABAAreceptor clustering protein gephyrin was significantly downregulated in the BLA after fear acquisition (Ressler et al., 2002). Here we demonstrate an analogous decrease in BLA gephyrin protein levels, together with a decrease in the surface expression of GABAAreceptors in the BLA after fear acquisition, as evidenced by decreased binding of H3-flunitrazepam. In marked contrast, gephyrin mRNA and protein levels in the BLA significantly increased after extinction training, as did H3-flunitrazepam binding. These results implicate the protein gephyrin in both fear acquisition and extinction and suggest that the modulation of gephyrin and GABAAreceptor expression in the BLA may play a role in the experience-dependent plasticity underlying both of these types of learning. Furthermore, these results demonstrate that physiologically relevant, dynamic alterations of GABAergic synapses occur during the consolidation phase of BLA-dependent learning and may interact with previously described alterations in glutamatergic transmission to initiate and stabilize memory formationin vivo.
Roles for Pain Modulatory Cells during Micturition and Continence
Authors: Baez Madelyn A. , Brink Thaddeus S. , Mason Peggy
Published: January 2005

We studied how the nervous system selects between noxious stimulus-evoked withdrawals and micturition, movements that are necessary for survival but use overlapping muscles and therefore cannot occur simultaneously. In lightly anesthetized rats, micturition was favored, because noxious stimulation never interrupted micturition, whereas withdrawals were suppressed during voiding. Neurons in the ventromedial medulla (VMM) are a major source of descending antinociceptive signals. To test whether VMM neurons support withdrawal suppression during micturition, the discharge of VMM neurons was recorded during continence and micturition. VMM cells that were inhibited (M-inh) or excited (M-exc) during micturition were observed. M-inh cells were excited by noxious cutaneous stimulation and thus are likely nociception facilitating, whereas M-exc cells were inhibited by noxious heat and are likely nociception inhibiting. The excitation of nociception-inhibiting M-exc and inhibition of nociception-facilitating M-inh cells predicts suppression of withdrawals during micturition. M-exc cells were typically silent before micturition, whereas most M-inh cells fired before micturition, suggesting that these cells may also play a preparatory role for micturition. To test this idea, we examined manipulations that either advanced or delayed the onset of micturition. Hypothalamic stimulation and noxious paw heat advanced micturition while exciting M-inh cells and inhibiting M-exc cells. In contrast, colorectal distension, a stimulus that delays micturition, inhibited M-inh cells and excited M-exc cells. These results suggest a model in which, during continence, VMM M-inh cells facilitate and M-exc cells inhibit bladder afferents, advancing micturition onset when M-inh cells are activated and delaying onset when M-exc cells are activated.
Prefrontal Serotonin Depletion Affects Reversal Learning But Not Attentional Set Shifting
Authors: Clarke H. F. , Walker S. C. , Crofts H. S. , Dalley J. W. , Robbins T. W. , Roberts A. C.
Published: January 2005

Recently, we have shown that serotonin (5-HT) depletion from the prefrontal cortex (PFC) of the marmoset monkey impairs performance on a serial discrimination reversal (SDR) task, resulting in perseverative responding to the previously correct stimulus (Clarke et al., 2004). This pattern of impairment is just one example of inflexible responding seen after damage to the PFC, with performance on the SDR task being dependent on the integrity of the orbitofrontal cortex. However, the contribution of 5-HT to other forms of flexible responding, such as attentional set shifting, an ability dependent on lateral PFC (Dias et al., 1996a), is unknown. The present study addresses this issue by examining the effects of 5,7-dihydroxytryptamine-induced PFC 5-HT depletions on the ability to shift attention between two perceptual dimensions of a compound visual stimulus (extradimensional shift).

Monkeys with selective PFC 5-HT lesions, despite being impaired in their ability to reverse a stimulus-reward association, were unimpaired in their ability to make an extradimensional shift when compared with sham-operated controls. These findings suggest that 5-HT is critical for flexible responding at the level of changing stimulus-reward contingencies but is not essential for the higher-order shifting of attentional set. Thus, psychological functions dependent on different loci within the PFC are differentially sensitive to serotonergic modulation, a finding of relevance to our understanding of cognitive inflexibility apparent in disorders such as obsessive-compulsive disorder and schizophrenia.