bluuebunny/crossref_metadata_2025 huggingface dataset:
Returns to Schooling and Bayesian Model Averaging: A Union of Two Literatures
Authors: Tobias Justin L. , Li Mingliang
Published: April 2004

Abstract. In this paper, we review and unite the literatures on returns to schooling and Bayesian model averaging. We observe that most studies seeking to estimate the returns to education have done so using particular (and often different across researchers) model specifications. Given this, we review Bayesian methods which formally account for uncertainty in the specification of the model itself, and apply these techniques to estimate the economic return to a college education. The approach described in this paper enables us to determine those model specifications which are most favored by the given data, and also enables us to use the predictions obtained fromallof the competing regression models to estimate the returns to schooling. The reported precision of such estimates also account for the uncertainty inherent in the model specification. Using U.S. data from the National Longitudinal Survey of Youth (NLSY), we also revisit several ‘stylized facts’ in the returns to education literature and examine if they continue to hold after formally accounting for model uncertainty.
Modified Limberg flap reconstruction compares favourably with primary repair for pilonidal sinus surgery
Authors: Cihan Alper , Mentes B. B. , Tatlicioglu E. , Ozmen S. , Leventoglu S. , Ucan B. H.
Published: April 2004

Background:  The present study analyses the results of wide excision with primary closure (PC), wide excision with classical Limberg flap reconstruction (LF) and wide excision with modified Limberg flap reconstruction (MLF) in the surgical treatment of sacrococcygeal pilonidal disease.

Methods:  One hundred and sixty‐two well‐documented patients who were operated on for pilonidal disease and followed for more than 1 year were analysed retrospectively. Group 1 was composed of patients with excision plus PC (n = 78) while group 2 included those with excision plus a LF reconstruction (n = 40), and group 3 included those with excision plus a MLF reconstruction (n = 44).

Results:  There were no significant differences among the three groups with respect to age, sex distribution, frequency of recurrent disease, or follow‐up periods (P > 0.05 for all comparisons). Significant disadvantages regarding postoperative infection rate, mobilization time, discharge from hospital, and time off work were noted for primary closure, compared with both LF and MLF reconstructions. Following a median follow‐up period of 4.2 years, 14 recurrences (17.9%) developed in the PC group, three (7.5%) in the LF group, and none (0%) in the MLF group. The zero recurrence rate in the MLF group was significantly lower than that in the PC group (P = 0.003). On the other hand, the recurrence rate in the LF was not found to differ significantly from that in the PC group (P = 0.126). Comparing the LF and MLF groups, none of the surgical end points reached a statistically significant difference (P > 0.05 for all comparisons).

Conclusions:  For the surgical treatment of sacrococcygeal pilonidal disease, excision plus a classical or modified Limberg flap reconstruction proved to be superior to excision plus primary closure in terms of infection, mobilization time, discharge from hospital and time off work. Additionally, MLF reconstruction resulted in a statistically lower recurrence rate when compared with PC.
Surgical risk management: the value of a weekly surgical radio‐pathological meeting
Authors: Wong Kenneth , Birks David
Published: April 2004

Background:  Clinical risk management in surgery involves organizational practices focused on the prevention of adverse outcomes. The present study evaluates the value of a weekly clinical meeting involving surgeons, radiologists and pathologists as a model of clinical risk management within a general surgical department.

Methods:  Data for all meetings conducted over a 6‐month period were prospectively collected. Changes to previously reported pathology and radiology results, revisions to patient diagnosis, management and recommendations for subsequent patient care arising from the meetings were recorded.

Results:  Data were collected for 18 meetings. One hundred and eleven patients were reviewed. Seventy‐six patients had previously reported radiological investigations. Sixty‐five patients had previously reported pathology specimens. Four per cent of radiology reports and 8% of pathology reports were amended at the meeting. Seven per cent of patients received a revised diagnosis. Twenty‐seven per cent of patients had suggestions for changes in management. Changes to patient care arose from pathologist input in seven patients, from radiologist input in nine patients and from clinician input in 14 patients. Four patients were recommended for an alternative surgical procedure. Five patients were recommended for cancellation of a planned procedure. Adjuvant chemo/radiotherapy was considered for four patients. Referral to specialist surgeons was suggested for two patients.

Conclusions:  Weekly multidisciplinary clinical meetings allow early revision and refinement of patient diagnosis and management. As such, they are an effective pre‐emptive incident monitoring system, facilitating regular audit and quality control as part of an overall strategy for surgical clinical risk management.
Surgical management of obesity using a soft adjustable gastric band
Authors: Greenslade Justin , Kow Lilian , Toouli James
Published: April 2004

Background:  Laparoscopically inserted adjustable gastric bands are an effective means of weight reduction for obese patients.

Methods:  The Swedish Adjustable Gastric Band was evaluated prospectively in a consecutive series of 273 patients from August 1996 to March 2003.

Results:  The first 58 patients had their band sited by the ‘peri‐gastric’ technique, with the subsequent 215 using the ‘pars flaccida’ technique, which provides better posterior fixation of the band. Results from these two groups were considered separately. Prolapse of the stomach through the band was the major complication occurring in 13 of the 58 peri‐gastric patients (22.4%). Median preoperative body mass index (BMI) was 42.1, falling below 30 by 2 years. In the pars flaccida group there were no instances of prolapse, but the major complication was three cases of band erosion (1.4%). Median preoperative BMI was 42.9 for this group, falling to 32 by 3 years. There was one death in the series due to myocardial infarction.

Conclusions:  Results compare favourably with other published adjustable gastric band series. Weight loss with the SAGB appears durable overall with an acceptable complication rate once an appropriate technique is employed. Consistent life‐long follow up is necessary to achieve the best result.
High‐cycle fatigue properties in Ti–5% Al–2.5% Sn ELI alloy with large grain size at cryogenic temperatures
Authors: ONO Y. , YURI T. , SUMIYOSHI H. , MATSUOKA S. , OGATA T.
Published: April 2004

High‐cycle fatigue properties were investigated for Ti–5% Al–2.5% Sn ELI alloy with a mean α grain size of 80 μm, which had been used for liquid hydrogen turbo‐pumps of Japanese‐built launch vehicles. At cryogenic temperatures, the fatigue strength in high‐cycle region did not increase in proportion to increments of the ultimate tensile strength and the fatigue strengths at around 106 cycles were about 300 MPa independent of test temperatures. Fatigue cracks initiated in the specimen interior independent of the test temperatures of 4 K, 77 K and 293 K. At 4 K and 77 K, several crystallographic facet‐like structures were formed at crack initiation sites. On the other hand, there were no facet‐like structures that could be clearly identified at the crack initiation sites at 293 K. Low fatigue strengths in longer‐life region at cryogenic temperatures could be attributable to the formation of large sub‐surface crack initiation sites, where large facet‐like structure are formed.
Dynamic Optimal Traffic Assignment and Signal Time Optimization Using Genetic Algorithms
Authors: Varia H. R. , Dhingra S. L.
Published: April 2004

Abstract:  In this article a dynamic system‐optimal traffic assignment model is formulated for a congested urban road network with a number of signalized intersections. A simulation‐based approach is employed for the case of multiple‐origin‐multiple‐destination traffic flows. The artificial intelligence technique of genetic algorithms (GAs) is used to minimize the overall travel cost in the network with fixed signal timings and optimization of signal timings. The proposed method is applied to the example network and results are discussed. It is concluded that GAs allow the relaxation of many of the assumptions that may be needed to solve the problem analytically by traditional methods.
Co‐determination and working time accounts in the German finance industry
Authors: Croucher Richard , Singe Ingo
Published: April 2004

This article examines the workings of co‐determination in the German finance industry through two case studies examining the introduction of working time accounts. It is shown that the accounts posed important new challenges for employees and works councillors that represented variants of long‐existing negotiations around working time issues. The problems were clear and similar in both cases, giving rise to complaints to councillors, though not to managers. Councillors’ responses differed in the two companies. In one, they successfully re‐negotiated the agreement under which the accounts had been introduced. In the other, they did not succeed in doing so. The differences between the two representative bodies are analysed to reflect on a theory of employee representative influence.
Co‐existence of Philadelphia chromosome positive acute megakaryoblastic and B‐lymphoblastic mixed blast crisis of chronic myeloid leukemia with chronic lymphocytic leukemia
Authors: Colla Simona , Sammarelli Gabriella , Crugnola Monica , Ascani Stefano , Sabbatini Elena , Bonomini Sabrina , Hojden Magda , Craviotto Luisa , Celis Isabel De , Morandi Francesca , Caramatti Cecilia , Rizzoli Vittorio , Giuliani Nicola
Published: April 2004

In this study, we describe an extremely rare case of co‐existence of a Philadelphia chromosome positive acute megakaryoblastic and B‐lymphoblastic mixed blast crisis of chronic myeloid leukemia with chronic lymphocytic leukemia. A morphological, immunophenotypical and cytogenetic study has been performed to characterize the case and in order to identify the origin of two disorders. After the failure of the conventional therapy, the patient was treated with Imatinib with a complete hematological and cytogenetic response and a marked reduction of bone marrow fibrosis.
Type 3 hemochromatosis and β‐thalassemia trait
Authors: Riva Alessia , Mariani Raffaella , Bovo Giorgio , Pelucchi Sara , Arosio Cristina , Salvioni Alessandra , Vergani Anna , Piperno Alberto
Published: April 2004

Type 3 hemochromatosis is a rare autosomal recessive disorder due to mutations of the TFR2 gene. We describe clinical, biochemical and histopathologic findings of a patient with type 3 hemochromatosis at presentation and during a follow‐up of more than 20 yr and we evaluate the effect of an associated β‐thalassemia trait on phenotypic expression. At the age of 33 yr the patient showed a marked iron overload and severe iron‐related complications. After removal of 26 g of iron by subcutaneous deferoxamine infusion a marked clinical improvement was observed. Liver biopsies, performed at the age of 34 and 49 yr, indicate that in type 3 hemochromatosis there is a progressive hepatocellular iron accumulation from Rappaport's zone 1–3 and that iron loading in sinusoidal and portal macrophages occurs only in the more advanced stage. As observed in HFE hemochromatosis, the β‐thalassemia trait seems to aggravate the clinical picture of patients lacking TFR2, favoring higher rates of iron accumulation probably by activation of the erythroid iron regulator.
Serum leptin levels in patients with idiopathic thrombocytopenic purpura
Authors: Zhan Mei , Zhao Hui , Yang Renchi , Han Zhong Chao
Published: April 2004

Objectives:  The purpose of this study was to evaluate serum leptin levels in idiopathic thrombocytopenic purpura (ITP), in order to determine the influence of leptin on the pathogenesis of ITP.

Subjects and methods:  Forty‐six untreated patients with chronic ITP were compared with 40 healthy people of similar age, sex and body mass index (BMI). Serum leptin levels (ng/mL) were measured by enzyme‐linked immunosorbent assay (ELISA).

Results:  We found that the mean serum leptin levels in patients with ITP (22.11 ± 15.84 ng/mL) were significantly (P < 0.001) higher than that in healthy control volunteers (5.44 ± 4.84 ng/mL). Furthermore, serum leptin levels in patients with ITP were inversely related (r = −0.86, P < 0.001) to the platelet counts and positively related to the platelet‐associated IgG (PAIgG) levels (r = 0.7, P < 0.001). The levels of PAIgG and platelet counts were significantly different between leptin‐positive (level greater than mean ± 2 SD control value) and leptin‐negative patients.

Conclusion:  These findings suggest that leptin might play an important role in the pathogenesis of ITP.
Intracellular IL‐4/IFN‐gamma producing peripheral T lymphocyte subsets in B cell non‐Hodgkin's lymphoma patients
Authors: Gergely Lajos , Aleksza Magdolna , Váróczy László , Ponyi Andrea , Sipka Sándor , Illés Árpád , Szegedi Gyula
Published: April 2004

Aim:  The availability of several biological therapy options is rapidly growing in the field of malignant lymphomas. This emphasizes the need to understand the precise interaction of the host immune system with the malignant disease. We measured the intracellular cytokine responses in lymphoma patients’ lymphocytes, to characterize the polarization changes in their immune system.

Methods:  Patients with B cell non‐Hodgkin's lymphoma were involved in the study. Peripheral lymphocytes were labeled with anti‐CD4 or anti‐CD8 antibodies and intracellular accumulation of IL‐4 or IFN‐γ was detected after in vitro incubation the cells with activating cocktail. The frequency of different T‐cell subsets were measured within the lymphocyte population.

Results:  Significantly increased CD4+, IFN‐γ producing (Th1) cell percentage were found in untreated lymphoma cases (28.8% vs. 21.8%). CD8+ IL‐4 and IFN‐γ producing (Tc0) T cell frequency is significantly higher in untreated lymphoma patients compared with normal controls (1.3% vs. 0.47%). The frequency of CD4+ IL‐4 producing (Th2) cells is significantly lower in untreated patients (0.96% vs. 1.19%). Patients in long‐term remission have lower frequency of CD4+, IL4 producing (Th2) cell ratio (0.31% vs. 1.19%) and increased CD4+ IFN‐γ producing (Th1) cell frequency (30.1% vs. 21.8%), compared with healthy normal controls.

Conclusion:  Our results demonstrate that there is a sustained increase in the CD4+ IFN‐γ producing cell frequency in lymphoma patients. The frequency of CD4+ IL‐4 producing cells is decreasing by treatment. These may contribute to strong polarization toward Th1 type response, needed for lymphoma clearance and remission.
Low‐dose amphotericin b lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies – a randomized, controlled trial
Authors: Subirà Maricel , Martino Rodrigo , Gómez Lucia , Martí Josep María , Estany Cristina , Sierra Jorge
Published: April 2004

Background:  Conventional amphotericin B (c‐AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c‐AmB is hampered by its safety profile, with frequent infusion‐related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c‐AmB.

Methods:  This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c‐AmB at 0.6 mg/kg/d for empirical antifungal therapy.

Results:  The incidence of renal toxicity was significantly lower in the ABLC group, compared with c‐AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c‐AmB). The overall response rate was 72% for ABLC compared with 48% for c‐AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c‐AmB group. The number of emergent fungal infections and overall mortality were similar in both groups.

Conclusions:  This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c‐AmB, without differences in the incidence of IRAEs and with similar efficacy.
A treatment planning study comparing HDR and AGIMRT for cervical cancer
Authors: Wahab Sasha H. , Malyapa Robert S. , Mutic Sasa , Grigsby Perry W. , Deasy Joseph O. , Miller Tom R. , Zoberi Imran , Low Daniel A.
Published: April 2004

The customization of brachytherapy dose distributions for gynecologic malignancies is limited by the spatial positioning of the applicators. We tested the hypothesis that applicator‐guided intensity modulated radiation therapy (AGIMRT) has the potential to deliver highly conformal dose distributions to cervical tumors, representing improvement over distributions obtained with intracavitary brachytherapy. A commercial three‐dimensional (3‐D) treatment planning system was used to create plans for ten cervical cancer patients treated at our institution. Dose distributions of conventionally designed high dose rate (HDR) plans were compared against those of AGIMRT. Tumor delineation was based on a previously published binary threshold technique, using image intensity on positron emission tomography (PET) scans. AGIMRT treatment schedules were designed using two fraction sizes: 6.5 Gy, to directly reproduce the HDR fractionation, and 1.8 Gy, to simulate traditional external beam fractionation. The average minimum tumor dose was significantly greater for the AGIMRT dose distributions than for the HDR distributions (64.2 Gy vs 33.6 Gy; The mean percent tumor volume at the prescription dose was higher for the AGIMRT plans (90.0% vs 58.2%; Using AGIMRT, the mean percent volume at the tolerance limit was decreased for the bladder (6.1% vs 16.6%; but increased for the rectum (4.1% vs 2.2%; Our study suggests that there may be conceptual and dosimetric advantages to replacing HDR with AGIMRT for patients with large‐volume cervical tumors. This investigation is being expanded using sequential PET images to model tumor regression and compare brachytherapy and AGIMRT throughout the course of therapy.
Investigation of physical image quality indices of a bone densitometry system
Authors: Wilkie Joel R. , Giger Maryellen L. , Chinander Michael R. , Vokes Tamara J. , Nishikawa Robert M. , Carlin Michael D.
Published: April 2004

Osteoporosis is a disease characterized by a loss of bone mass and a deterioration of bone structure. Bone mineral density (BMD) measures bone mass and is currently the method used to diagnose osteoporosis, while computerized radiographic texture analysis (RTA) is being investigated as a measure of bone structure. The GE/Lunar PIXI peripheral bone densitometer (PD) system, which uses dual‐energy subtraction to measure BMD, also provides a digital image of the heel or forearm. The goal of our current research was to evaluate the physical imaging properties of the PIXI system (pixel size of 0.2 mm) compared to a Fuji computed radiography (CR) system (pixel size of 0.1 mm) to determine its suitability for texture analysis from image data. Contrast was measured using a series of uniform images covering the useful clinical exposure range. Spatial resolution was characterized by the presampling modulation transfer function (MTF) determined by an edge method. Noise power spectra (NPS) for different exposures were calculated using a two‐dimensional Fourier analysis method. The expectation modulation transfer function was measured and combined with the NPS data to calculate the noise‐equivalent number of quanta. The slope of the characteristic curve of the peripheral densitometer (PD) system was found to be position dependent across the image, although this dependence was substantially reduced by use of the system's clinical‐settings corrections. An MTF value of 0.5 was found at 0.5 cycles/mm for the densitometry system compared to the same value at 1.6 cycles/mm for the CR system. Unlike the CR system, the NPS of the densitometry system was found not to be directionally dependent and did not drop off at higher spatial frequencies.
AAPM TG‐43 formalism for brachytherapy dose calculation of a 137Cs tube source
Authors: Zhang Pengpeng , Beddar A. Sam , Sibata Claudio H.
Published: April 2004

We present a development of the use of the AAPM TG‐43 dose formalism applied to gynecological implant sources. The geometry factor, radial dose function, and anisotropy function of a source modeled after the Nuclear Associates 67‐809 series stainless steel jacketed tube source were derived following the AAPM TG‐43 formalism. The dose rate distribution through the center of the source using the AAPM TG‐43 dose formalism is calculated and compared with the calculations obtained using the Sievert summation and Monte Carlo simulation. The three methods resulted in an agreement within less than 5%, or an isodose rate line agreement within 2 mm. We demonstrate that the AAPM TG‐43 formalism can be applied to linear sources and is capable of serving as a dose calculation algorithm that can be used for treatment planning purpose.
Optimization in intensity modulated radiation therapy
Authors: Gaede Stewart
Published: April 2004

Intensity modulated radiation therapy (IMRT) uses nonuniform intensity distributions to conform high dose to a tumor and low dose to surrounding sensitive structures. Because of the large number of beams (5–11) and the wide range of intensities, treatment planning is typically an inverse problem in which the intensity distributions are optimized. Three areas addressed in this thesis are plan complexity, beam directions, and dose–volume constraints. Inverse treatment planning is flexible and can deliver complex dose distributions that are sometimes not warranted. The first goal of this thesis is to demonstrate simple alternatives to inverse planning that use just enough degrees of freedom for the problem so that the solution is not overly sensitive to a slight change in dose constraints and patient geometry. With the addition of simple beam direction optimization, a suitable IMRT plan can be created while maintaining clinical practicality. The second goal of the thesis is to introduce and analyze a new algorithm which systematically analyzes and selects beam directions in the fewest number of beams possible. In IMRT, the optimization of beam directions is complicated due to the interdependence with beam intensities. Our beam direction algorithm has the capability of achieving plans that are better than standard IMRT techniques, often with a fewer number of beams. The third goal of this thesis is to propose a new formulation of the inverse treatment planning optimization problems that include dose–volume constraints which are known to destroy convexity. This is compared to a formulation that has been addressed in the literature. We solve both formulations with a new technique based on direct search optimization with a systematic search region reduction. This is compared to a standard fast simulated annealing technique. The results of using the new formulation show a direct correspondence between the minimum objective function values and the resulting dose distributions and dose–volume histograms. The research of this thesis is performed using examples of lung, prostate, and brain stem radiotherapy. We provide evidence that dose–volume based formulations of inverse treatment planning optimization for IMRT have the ability to achieve optimal plans that are clinically relevant.
Accurate determination of dose‐point‐kernel functions close to the origin using Monte Carlo simulations
Authors: Janicki Christian , Seuntjens Jan
Published: April 2004

Dose‐point‐kernel (DPK) functions are used extensively for the dosimetry of gamma and beta emitters in many physical problems. These functions are usually obtained from Monte Carlo simulations where the energy deposited in concentric spherical shells around a point source is tallied. The energy scored in a spherical shell divided by the shell mass is taken as the dose at some effective radiusof the shell. The effective radiusdefined as the distance of a hypothetical zero‐thickness scoring region from the source, can be evaluated in different ways for a finite thickness scoring region. For a shell thickness that is very small compared to the distance from the origin, this exact evaluation method becomes unimportant and the arithmetic mean is usually an accurate estimator forHowever, accurately determiningcan be problematic for the innermost regions when the radial dose functionvaries considerably over the finite spherical shell thickness. In this work, a new method for determiningis introduced which yields consistent results for any shell thickness, thus improving on previous Monte Carlo calculations for DPKs at or near the origin. Dimensionless DPK functions for monoenergetic electrons were reevaluated using EGSnrc with an emphasis on accuracy and consistency near the origin using our new method for determiningThese improved functions were implemented in a software code to calculate the DPKs for an exhaustive list of 546 beta emitters, thus extending the compilation from previous works.
The stability of liquid‐filled matrix ionization chamber electronic portal imaging devices for dosimetry purposes
Authors: Louwe R. J. W. , Tielenburg R. , van Ingen K. M. , Mijnheer B. J. , van Herk M. B.
Published: April 2004

This study was performed to determine the stability of liquid‐filled matrix ionization chamber (LiFi‐type) electronic portal imaging devices (EPID) for dosimetric purposes. The short‐ and long‐term stability of the response was investigated, as well as the importance of factors influencing the response (e.g., temperature fluctuations, radiation damage, and the performance of the electronic hardware). It was shown that testing the performance of the electronic hardware as well as the short‐term stability of the imagers may reveal the cause of a poor long‐term stability of the imager response. In addition, the short‐term stability was measured to verify the validity of the fitted dose–response curve immediately after beam startup. The long‐term stability of these imagers could be considerably improved by correcting for room temperature fluctuations and gradual changes in response due to radiation damage. As a result, the reproducibility was better than 1% (1 SD) over a period of two years. The results of this study were used to formulate recommendations for a quality control program for portal dosimetry. The effect of such a program was assessed by comparing the results of portal dosimetry and in vivo dosimetry using diodes during the treatment of 31 prostate patients. The improvement of the results for portal dosimetry was consistent with the deviations observed with the reproducibility tests in that particular period. After a correction for the variation in response of the imager, the average difference between the measured and prescribed dose during the treatment of prostate patients was −0.7%±1.5% (1 SD), and −0.6%±1.1% (1 SD) for EPID and diode in vivo dosimetry, respectively. It can be concluded that a high stability of the response can be achieved for this type of EPID by applying a rigorous quality control program.
SUMO Modification of Huntingtin and Huntington's Disease Pathology
Authors: Steffan Joan S. , Agrawal Namita , Pallos Judit , Rockabrand Erica , Trotman Lloyd C. , Slepko Natalia , Illes Katalin , Lukacsovich Tamas , Zhu Ya-Zhen , Cattaneo Elena , Pandolfi Pier Paolo , Thompson Leslie Michels , Marsh J. Lawrence
Published: April 2004

Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)–1 or by ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes its capacity to repress transcription. In a
Drosophila
model of HD, SUMOylation of Httex1p exacerbates neurodegeneration, whereas ubiquitination of Httex1p abrogates neurodegeneration. Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation.
The Early Evolution of the Tetrapod Humerus
Authors: Shubin Neil H. , Daeschler Edward B. , Coates Michael I.
Published: April 2004

A tetrapod humerus from the Late Devonian of Pennsylvania has a novel mix of primitive and derived characters. A comparative analysis of this fossil and other relevant humeri from the Devonian shows that the role of the limb in propping the body arose first in fish fins, not tetrapod limbs. The functional diversity of the earliest known limbs includes several different kinds of appendage design. This functional diversity was achieved with a humeral architecture that was remarkably conserved during the Devonian.
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Authors: Bouret Sebastien G. , Draper Shin J. , Simerly Richard B.
Published: April 2004

In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient (Lep
ob
/Lep
ob
) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lep
ob
/Lep
ob
neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.
The recognition and catalytic hydrolysis of ATP by protonated phenanthroline-bridged polyamine and (or) Ca(II), Mg(II), Zn(II), and La(III) ions
Authors: Guo Yan-He , Ge Qing-Chun , Lin Hai , Lin Hua-Kuan , Zhu Shou-Rong
Published: April 2004

The supramolecular interactions of 2,9-di(((2′-phenylamino)ethyleneamino)methyl)-1,10-phenanthroline (L) and (or) metal ions (M = Ca2+, Mg2+, Zn2+, or La3+) with nucleotides were investigated. Furthermore, the hydrolysis of ATP catalyzed by a protonated ligand and (or) a metal ion (M = Ca2+, Mg2+, Zn2+, or La3+) was studied at pH 7.6 using 31P NMR spectra. Kinetics studies show that at pH 7.6 the protonated ligand, with a rate constant of 2.9 × 104 min1, does not significantly promote ATP hydrolysis. However, in the presence of Ca2+, Mg2+, Zn2+, or La3+ ions, L can accelerate the hydrolysis of ATP, with corresponding rate constants of 5.73, 1.48, 6.76, and 31.7 × 103 min1, respectively, which are about 29-, 7.5-, 34-, and 159-fold faster than the hydrolysis rate of free ATP. By comparison with MATP (M = Ca2+, Mg2+, and La3+) systems, the rates of MLATP were also promoted. This has been achieved through the effective recognition of ATP and the availability of a good intramolecular nucleophile, i.e., a free amino nitrogen atom of L. Compared with the Zn2+ATP system, the decrease in the rate of the Zn2+LATP system at pH 7.6 may be attributed to the competition between the mixed ligands in binding Zn2+. Similar to LATP, the hydrolysis reactions in the Zn2+LATP or MLATP (M = Ca2+, Mg2+, and La3+) systems occur through an additionelimination type mechanism, in which phosphoramidate intermediates were observed at 2.88 and 4.06 parts per million (ppm) in the LATP and Mg2+LATP systems, respectively. Here, metal ions add control or regulation to the hydrolysis reaction. Key words: recognition, ATP hydrolysis, metal ions, phenanthroline-bridged polyamine.
Group selection management in conifer forests: relationships between opening size and tree growth
Authors: York Robert A , Heald Robert C , Battles John J , York Jennifer D
Published: April 2004

Replicated circular openings ranging in size from 0.1 to 1 ha were cleared in 1996 at Blodgett Forest Research Station, California, and planted with seedlings of six native species. After 5 years of postharvest growth, heights were measured and analyzed according to species, opening size, and location within opening. The sequence of mean height from tallest to shortest, according to species, was as follows: giant sequoia (Sequoiadendron giganteum (Lindl.) Buchholz) > incense-cedar (Calocedrus decurrens (Torr.) Florin) > Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) ≈ ponderosa pine (Pinus ponderosa Dougl. ex Laws.) > sugar pine (Pinus lambertiana Dougl.) ≈ white fir (Abies concolor (Gord. & Glend.) Lindl.). To describe the influence of openings size on seedling height, we use an information-theoretic approach to select from competing models that predicted fifth-year height from group selection opening size. Asymptotic fits (modeled with MichaelisMenton curves) were selected for giant sequoia, ponderosa pine, sugar pine, and incense-cedar. Quadratic fits were selected for white fir and Douglas-fir. Linear models predicting increasing growth with opening size were consistently ruled out for all species. Although a marked depression in seedling-height growth occurred along the edges within the openings, mean annual radial increment of the 90-year-old border trees surrounding the openings increased by 30%, compared with other canopy trees in the forested matrix between openings.
The effect of interspecific competition on conifer seedling growth and nitrogen availability measured using ion-exchange membranes
Authors: Hangs Ryan D , Greer Ken J , Sulewski Catharine A
Published: April 2004

During the early establishment phase, outplanted white spruce (Picea glauca (Moench) Voss) and jack pine (Pinus banksiana Lamb.) seedlings are vulnerable to lethargic growth or mortality because of interspecific competition for soil nutrients, particularly N. Accurately quantifying the degree of N competition is essential for supporting effective vegetation management (VM) decisions. This study evaluated the use of in situ burials of ion-exchange membrane (IEM; Plant Root SimulatorTM-probes) for quantifying differences in soil N supply rate between different VM treatments and the relationship of this N availability index to early growth of conifer seedlings at four boreal forest sites. At most sites, the effect of noncrop N uptake on soil N availability was apparent, with smaller NH4+-N, NO3-N, and total dissolved inorganic N (DIN) supply rates in control plots than in VM plots. Total DIN supply rate was correlated (R2 = 0.60 to 0.73, P < 0.01) with seedling height, root-collar diameter, and stem volume growth. Ammonium-N supply rate was better correlated than NO3-N supply rate with conifer seedling growth, which is in agreement with preferential NH4+-N uptake by conifer species. The results of this study support the use of in situ burials of IEM for measuring soil N availability during the early establishment phase.
Efficacy of 4-allylanisole-based products for protecting individual loblolly pines from Dendroctonus frontalis Zimmermann (Coleoptera: Scolytidae)
Authors: Strom B L , Clarke S R , Shea P J
Published: April 2004

We evaluated the effectiveness of 4-allylanisole (4AA) as a protective treatment for loblolly pines threatened by the southern pine beetle, Dendroctonus frontalis Zimmermann. Three products were evaluated in combination with two methods that promoted attack of trees by D. frontalis. One method used attractive semiochemicals and the other decreased host resistance, both of which are important scenarios for implementing protective treatments of individual trees. Each method promoted mass attack of unprotected control trees, thus providing a statistically verifiable challenge to the candidate protectants. In trees with increased susceptibility, mortality ranged from 63% (untreated) to 77% (4AA applied in paintball formulation), and two products appeared to alter the relative composition of scolytid species that attacked at two heights; however, tree mortality was unaffected. In trees challenged with semiochemical attractants, mortality ranged from 54% (4AA released from vials) to 82% (untreated and paintball application of 4AA). Although 4AA consistently reduces catch of D. frontalis in traps, it was not efficacious for protecting individual loblolly pines over a period of 30 or 60 days in this experiment.
HOW DO CORPORATE CHAMPIONS PROMOTE INNOVATIONS?
Authors: JENSSEN JAN INGE , JØRGENSEN GEIR
Published: April 2004

The aim of this paper is to discuss which factors influence the impact of innovation champions on organisations. This is done by means of a systematic review of existing research. Many of the studies do not have a solid theoretical base. However, we find that resource dependency theory provides a theoretical framework in which innovation champions can be understood. We also show explicitly how other theories such as network theory, agency theory, and personal trait theory are needed in order to explain certain elements of the champions' behaviour. We propose an overall model, discuss theoretical and managerial implications of previous research, and suggest areas for future research.
Role of a PDZ1 domain of NHERF1 in the binding of airway epithelial RACK1 to NHERF1
Authors: Liedtke Carole M. , Raghuram Viswanathan , Yun C. Chris , Wang Xiangyun
Published: April 2004

In past studies, we demonstrated regulation of CFTR Cl channel function by protein kinase C (PKC)-ϵ through the binding of PKC-ϵ to RACK1 (a receptor for activated C-kinase) and of RACK1 to human Na+/H+ exchanger regulatory factor (NHERF1). In this study, we investigated the site of RACK1 binding on NHERF1 using solid-phase and solution binding assays and pulldown, immunoprecipitation, and 36Cl efflux experiments. Recombinant RACK1 binding to glutathione S-transferase (GST)-tagged PDZ1 domain of NHERF1 was 10-fold higher than its binding to GST-tagged PDZ2 domain of NHERF1. PDZ1 binds to RACK1 in a dose-dependent manner and vice versa, with similar binding constants of 1.67 and 1.26 μg, respectively. Interaction of the PDZ1 domain with RACK1 was not blocked by binding of activated PKC-ϵ to RACK1. A GST-tagged PDZ1 domain pulled down endogenous RACK1 from Calu-3 cell lysate. An internal 11-amino acid motif embedding the GYGF carboxylate binding loop of PDZ1 binds to RACK1, inhibits binding of recombinant NHERF1 and RACK1, pulls down endogenous RACK1 from Calu-3 cell lysate, and blocks coimmunoprecipitation of endogenous RACK1 with endogenous NHERF1 but does not affect cAMP-dependent activation of CFTR. A similar amino acid sequence in the PDZ2 domain did not bind RACK1. Our results indicate binding of Calu-3 RACK1 predominantly to the PDZ1 domain of NHERF1 at a site encompassing the GYGF loop of the PDZ1 domain and a site on RACK1 distinct from a PKC-ϵ binding site. CFTR activation by cAMP-generating agent is not affected by loss of RACK1-NHERF1 interaction.
Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner
Authors: Oba Toshiharu , Maeno Yoshitaka
Published: April 2004

We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to ∼50–200 μM acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modified channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 μM acetaldehyde to frog fibers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of fibers to 50 and 200 μM acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200–400 μM acetaldehyde induced Ca2+ release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by ∼12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca2+ release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1–30 μM) are unlikely to mediate alcohol-induced acute muscle dysfunction.
Acid-base effects on intestinal Cl- absorption and vesicular trafficking
Authors: Charney Alan N. , Egnor Richard W. , Henner David , Rashid Haroon , Cassai Nicholas , Sidhu Gurdip S.
Published: April 2004

In rat ileum and colon, apical membrane [Formula: see text] exchange and net Cl- absorption are stimulated by increases in Pco2 or [Formula: see text]. Because changes in Pco2 stimulate colonic Na+ absorption, in part, by modulating vesicular trafficking of the Na+/H+ exchanger type 3 isoform to and from the apical membrane, we examined whether changes in Pco2 affect net Cl- absorption by modulating vesicular trafficking of the [Formula: see text] exchanger anion exchanger (AE)1. Cl- transport across rat distal ileum and colon was measured in the Ussing chamber, and apical membrane protein biotinylation of these segments and Western blots of recovered proteins were performed. In colonic epithelial apical membranes, AE1 protein content was greater at Pco2 70 mmHg than at Pco2 21 mmHg but was not affected by pH changes in the absence of CO2. AE1 was internalized when Pco2 was reduced and exocytosed when Pco2 was increased, and both mucosal wortmannin and methazolamide inhibited exocytosis. Wortmannin also inhibited the increase in colonic Cl- absorption caused by an increase in Pco2. Increases in Pco2 stimulated ileal Cl- absorption, but wortmannin was without effect. Ileal epithelial apical membrane AE1 content was not affected by Pco2. We conclude that CO2 modulation of colonic, but not ileal, Cl- absorption involves effects on vesicular trafficking of AE1.
cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts
Authors: Liu Xiaoqiu , Ostrom Rennolds S. , Insel Paul A.
Published: April 2004

Pulmonary fibroblasts are recruited to sites of lung injury, where they are activated to produce extracellular matrix proteins and to facilitate repair. However, these cells become dysregulated in pulmonary fibrosis, producing excess collagen at sites of injury and forming fibrotic loci that impair lung function. In this study, we used WI-38 human lung fibroblasts and evaluated the ability of G protein-coupled receptor agonists to increase cAMP production and regulate cell proliferation and collagen synthesis. WI-38 cells increase cAMP in response to the β-adrenergic agonist isoproterenol (Iso), prostaglandin E2 (PGE2), certain prostanoid receptor-selective agonists (beraprost, butaprost), an adenosine receptor agonist, and the direct adenylyl cyclase (AC) activator forskolin (Fsk). Responses to Iso, PGE2, and Fsk were studied in more detail. Each induced a dose-dependent inhibition of serum-stimulated cell proliferation (as measured by [3H]thymidine incorporation) and collagen synthesis (as measured by [3H]proline incorporation, collagenase-sensitive [3H]proline incorporation, or levels of procollagen type 1 C-peptide). Quantitative RT-PCR analyses indicated that elevation in cellular cAMP levels decreases expression of collagen types 1α(II) and 5α(I) and increases expression and activity of matrix metalloproteinase 2 (MMP-2). Overexpression of AC type 6 or inhibition of cyclic nucleotide phosphodiesterases also increased cellular cAMP levels and decreased cell proliferation and collagen synthesis. Thus multiple approaches that increase cAMP signaling reduce proliferation and differentiated function in human pulmonary fibroblasts. These results suggest that therapies that raise cAMP levels may prove useful in the treatment of pulmonary fibrosis.
Characterization of T-type calcium current and its contribution to electrical activity in rabbit urethra
Authors: Bradley J. E. , Anderson U. A. , Woolsey S. M. , Thornbury K. D. , McHale N. G. , Hollywood M. A.
Published: April 2004

Rabbit urethral smooth muscle cells were studied at 37°C by using the amphotericin B perforated-patch configuration of the patch-clamp technique, using Cs+-rich pipette solutions. Two components of current, with electrophysiological and pharmacological properties typical of T- and L-type Ca2+ currents, were recorded. Fitting steady-state inactivation curves for the L current with a Boltzmann equation yielded a V1/2 of -41 ± 3 mV. In contrast, the T current inactivated with a V1/2 of -76 ± 2 mV. The L currents were reduced by nifedipine (IC50 = 225 ± 84 nM), Ni2+ (IC50 = 324 ± 74 μM), and mibefradil (IC50 = 2.6 ± 1.1 μM) but were enhanced when external Ca2+ was substituted with Ba2+. The T current was little affected by nifedipine at concentrations <300 nM but was increased in amplitude when external Ca2+ was substituted with Ba2+. Both Ni2+ and mibefradil reduced the T current with an IC50 = 7 ± 1 μM and ∼40 nM, respectively. Spontaneous electrical activity recorded with intracellular electrodes from strips of rabbit urethra consisted of complexes comprising a series of spikes superimposed on a slow spontaneous depolarization (SD). Inhibition of T current reduced the frequency of these SDs but had no effect on either the number of spikes per complex or the amplitude of the spikes. In contrast, application of nifedipine failed to significantly alter the frequency of the SD but reduced the number and amplitude of the spikes in each complex.
VE-cadherin: adhesion at arm's length
Authors: Vincent Peter A. , Xiao Kanyan , Buckley Kathleen M. , Kowalczyk Andrew P.
Published: April 2004

VE-cadherin was first identified in the early 1990s and quickly emerged as an important endothelial cell adhesion molecule. The past decade of research has revealed key roles for VE-cadherin in vascular permeability and in the morphogenic events associated with vascular remodeling. The details of how VE-cadherin functions in adhesion became apparent with structure-function analysis of the cadherin extracellular domain and with the identification of the catenins, a series of cytoplasmic proteins that bind to the cadherin tail and mediate interactions between cadherins and the cytoskeleton. Whereas early work focused on the armadillo family proteins β-catenin and plakoglobin, more recent investigations have identified p120-catenin (p120 ctn) and a related group of armadillo family members as key binding partners for the cadherin tail. Furthermore, a series of new studies indicate a key role for p120 ctn in regulating cadherin membrane trafficking in mammalian cells. These recent studies place p120 ctn at the hub of a cadherin-catenin regulatory mechanism that controls cadherin plasma membrane levels in cells of both epithelial and endothelial origin.
On Cauchy‐type functional equations
Authors: Elhoucien Elqorachi , Akkouchi Mohamed
Published: April 2004

Let G be a Hausdorff topological locally compact group. Let M(G) denote the Banach algebra of all complex and bounded measures on G. For all integers n ≥ 1 and all μ ∈ M(G), we consider the functional equations , x, y ∈ G, where the functions f, {gi}, {hi}: G → ℂ to be determined are bounded and continuous functions on G. We show how the solutions of these equations are closely related to the solutions of the μ‐spherical matrix functions. When G is a compact group and μ is a Gelfand measure, we give the set of continuous solutions of these equations.