bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Aspiration Pneumonia after Percutaneous Endoscopic Gastrostomy
Authors: Kitamura Toshiro , Nakase Hajime , Iizuka Hidehiko
Published: March 2007

Background: Percutaneous endoscopic gastrostomy (PEG) is generally used for long-term enteral nutrition. Patients who require PEG placement are often very sick, and postoperative complications, especially aspiration pneumonia, can be fatal. Objective: In this study we investigated the risk factors for aspiration pneumonia after PEG using a simple two-step swallowing provocation test (S-SPT), as reported in 1999 by Teramoto et al. Methods: The study included 29 patients (10 men, 19 women; mean age 84.6 years) who underwent S-SPT before PEG. We evaluated the presence of reflux esophagitis (RE) and esophageal hiatal hernia (EHH) with PEG. According to the S-SPT results, a normal response to the 1st step S-SPT was given a score of 0, a normal response to the 2nd step S-SPT was given a score of 1, and an abnormal response to the 2nd step S-SPT was given a score of 3. In addition to S-SPT, the presence of RE was given a score of 3, the absence of RE was given a score of 0, the presence of EHH was given a score of 2, and the absence of EHH was given a score of 0. We evaluated the association between the presence of aspiration pneumonia, as an early and critical complication, up to 1 month after PEG and determined the total risk score (score of S-SPT+ score of RE+ score of EHH). Results: The group with an abnormal response to the 2nd step S-SPT and the group with RE both exhibited aspiration pneumonia. The patients with aspiration pneumonia all achieved total scores ≧3, and 8 of 13 patients without aspiration pneumonia achieved scores ≤2. Conclusions: S-SPT is particularly useful in PEG patients. The scores provided by S-SPT and endoscopic examination can be very useful for aspiration pneumonia after PEG. The patients with scores ≤2 appear to be at very low risk for aspiration pneumonia, and patients with the scores ≧3 should be carefully followed up.
Analysis of Longitudinal Strains of Cross-ply Composite Laminates using A-EFPI Optical Fiber Sensor
Authors: Woo Sung-Choong , Choi Nak-Sam , Kwon Il-Bum , Rhee Kyong Y.
Published: March 2007

The longitudinal strains (εx) of the core and the skin layers in glass fiber reinforced plastic (GFRP) cross-ply composite laminates are analyzed using embedded optical fiber sensors (OFSs) of absolute extrinsic Fabry—Perot interferometer (A-EFPI). Foil-type strain gages (SGs) bonded on both upper and lower surfaces of a specimen are employed for comparison of the strain measurement on the surface. It has been shown that the values of εx in the interior of the skin layer and the core layer measured by embedded A-EFPI sensor are lower than those of the specimen surface measured by SGs. Experimental results agree well with those from finite element analysis based on a shear lag model. Optical microscopy observation of the damage behavior around the fiber sensor by the thin-sectioning technique shows that reinforcing glass fibers protect the OFS embedded in the 0 ° skin layer, whereas the formation of transverse cracks in the 90 ° core layer substantially reduces strains at the failure of OFS embedded in the core layer.
A Discourse Analysis of Elite American Newspaper Editorials: The Case of Iran’s Nuclear Program
Authors: Izadi Foad , Saghaye-Biria Hakimeh
Published: March 2007

This study employs Said’s concept of Orientalism and van Dijk’s concept of the ideological square to analyze three elite American newspapers’ editorial coverage of Iran’s nuclear program. A critical discourse analysis of The New York Times, The Washington Post, and The Wall Street Journal editorials from 1984 to 2004 identified six Orientalist themes. The study finds that The Wall Street Journal and The Washington Post more predominantly drew on Orientalist arguments than did The New York Times.
Chemical Resistance of Sisal/Glass Reinforced Unsaturated Polyester Hybrid Composites
Authors: John K. , Naidu S. Venkata
Published: March 2007

The unsaturated polyester resin based sisal/glass hybrid composites were developed using the hand lay-up technique. Chemical resistance tests of these hybrid composites were performed in order to probe whether these composites can be used for making articles that are resistant to chemicals. The hybrid samples and the matrix have been tested for various acids, alkalis, and solvents. It is observed from the results that the developed hybrid composites are resistant to all the tested chemicals except carbon tetrachloride.
Pre-treatment of Flax Fibers for use in Rotationally Molded Biocomposites
Authors: Wang B. , Panigrahi S. , Tabil L. , Crerar W.
Published: March 2007

The objective of this study was to determine the effects of pre-treated flax fibers on the performance of the fiber-reinforced composites. Lack of good interfacial adhesion and poor resistance to moisture absorption make the use of natural fiber-reinforced composites less attractive. In order to improve fiber/matrix interfacial properties, fibers were subjected to chemical treatments, namely, mercerization, silane treatment, benzoylation, and peroxide treatment. Selective removal of non-cellulosic compounds constitutes the main objective of the chemical treatments of flax fibers to improve the performance of fiber-reinforced composites. Flax fibers were derived from Saskatchewan-grown flax straws. Composites consisting of high-density polyethylene (HDPE) or linear low-density polyethylene (LLDPE) or HDPE/LLDPE mix, chemically treated fibers and additives were prepared by the extrusion process. The test samples were prepared by rotational molding. The fiber surface morphology and the tensile fracture surfaces of the composites were characterized by scanning electron microscopy (SEM). The effects of the different chemical treatments on the mechanical and the physical properties of natural fiber-reinforced composites were investigated. The differential scanning calorimetry (DSC) was used to measure the melting point of the fiber-reinforced composites.
An Analytical Solution Procedure to Analyze Material Nonlinear Behavior of Laminated Beams
Authors: Ataş Cesim , Sayman Onur , Çallioğlu Hasan
Published: March 2007

In this study, an analytical solution procedure for elastic–plastic stress analysis of laminated beams is presented. The Bernoulli–Euler theory was used in the solution considering infinitesimal small deformations. A finite element analysis was also carried out, by using LUSAS 13.4, to compare and verify results obtained by analytical solution. Several stacking sequences such as [0°/90°]S, [90°/0°]S, [15°/–15°]S, [30°/–30°]S, and [45°/–45°]S are chosen for comparison.
Pralidoxime in carbaryl poisoning: an animal model
Authors: Mercurio-Zappala Maria , Hack Jason B. , Salvador Annabella , Hoffman Robert S.
Published: March 2007

Introduction: Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning. Methods: Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD 50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test. Results: Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%. Conclusion: When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose. Human & Experimental Toxicology (2007) 26, 125-129
Profile of poisoning admissions in Malaysia
Authors: Rajasuriar R. , Awang R. , Hashim S.B.H. , Rahmat H.R.B.H.
Published: March 2007

We retrospectively reviewed poisoning admissions to all government health facilities from 1999 to 2001, in an effort to expand our current knowledge on poisoning in Malaysia to a level that better reflects a nationwide burden. There were 21 714 admissions reported with 779 deaths. The case-fatality rate was 35.88/1000 admissions. The majority of admissions (89.7%) and deaths (98.9%) occurred in adults. Some 55.1% of all admissions were female, mostly involving pharmaceutical agents. Male poisoning admissions were more often due to chemical substances. The prevalence of poisoning and death was highest among Indians compared to all other races in Malaysia. Overall, the majority of poisoning admissions were due to pharmaceutical agents, with agents classified as non-opioid analgesics, antipyretics and anti-rheumatics the most common. Pesticides accounted for the largest number of fatalities. It was also the commonest substance reported in cases of intentional self-harm. Most cases of poisoning admissions occurred due to accidental exposure (47%), followed by cases of intentional self-harm (20.7%). Overall, this study has managed to contribute substantial additional information regarding the epidemiology of poisoning in Malaysia, highlighting important issues, such as the rampant poisonings involving pesticides and analgesics, as well as the high prevalence of poisoning among Indians in Malaysia. Human & Experimental Toxicology (2007) 26, 73- 81
Protective role of dietary fibre on N-nitrosopyrrolidine-induced toxicity in hypercholesterolemic rats
Authors: Mittal G. , Vadhera S. , Brar A.P.S. , Soni Giridhar
Published: March 2007

N-nitrosopyrrolidine (NPYR) is an important carcinogen, frequently present in the environment and food chain. Oral administration of NPYR to experimental rats evoked severe biochemical and pathological changes. In the present investigation, the protective role of dietary fibre on NPYR-induced toxicity in hypercholesterolemic rats was studied. Supplementation of chickpea seed coat fibre in the diet reduced the hepato-toxic effects of NPYR, as evident from the decreased hepatic degeneration and improved liver weight index compared to control. Administration of NPYR resulted in an increase in the osmotic fragility of erythrocytes in the experimental animals. The antioxidant potential of experimental animals decreased in the NPYR-fed group, which was evident from the increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NPYR. Administration of NPYR resulted in a substantial and significant increase in LPO in all tissues, to a varying degree, though the effect was maximum in the case of the liver. Inclusion of chickpea seed coat fibre considerably reduced the peroxidative damage caused by NPYR in all tissues. The effect of NPYR administration on antioxidant potential was variable in different tissues, but the effect was reduced considerably on inclusion of chickpea seed coat fibre in the diet, providing reasonable protection against NPYR-induced oxidative stress, and, hence, its toxicity. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups. However, the pathological effects of NPYR administration were markedly reduced with the addition of chickpea seed coat fibre in the diet. Human & Experimental Toxicology (2007) 26, 91-98
Fault Recognition Method Based on Independent Component Analysis and Hidden Markov Model
Authors: Li Zhinong , Han Jie , Sun Junjie , He Yongyong , Chu Fulei
Published: March 2007

Independent component analysis (ICA) is a powerful tool for analyzing non-Gaussian data. Through the use of ICA, invariable features embedded in multi-channel vibration measurements made in different operating modes can be extracted. The hidden Markov model (HMM) is a statistical model of the time series, and has a strong capability in pattern classification, especially for signals with abundant information quantity, non-stationary natures and poor repeatability and reproducibility. A new approach to fault recognition is proposed in this article, in which ICA is used for feature extraction, and the HMM as a classifier. Fault recognition in the speed-up and speed-down processes of rotating machinery has been successfully completed. The proposed approach is compared with another recognition approach, in which principal component analysis (PCA) is used for feature extraction, and HMM as a classifier, and is shown to be very effective.
Wave Induced Forces in Offshore Structures Using Linear and Nonlinear Forms of Morison's equation
Authors: Terro Mohamad J. , Abdel-Rohman Mohamed
Published: March 2007

Wave-induced forces applied to offshore structures can be estimated by using either the nonlinear or linear form of Morison's equation. Difficulties in using the nonlinear form of Morison's equation arise from the nonlinear relation between the wave force and the response of the structure in the drag-dominated term. The linear form of Morison's equation simplifies the estimation of the wave-induced forces in offshore structures. For this reason, engineering designers working on large-scale offshore structures rely on the modified linear Morison's equation. In this article, a comparative study of the linear and nonlinear forms of the wave-induced force from Morison's equation is presented. A parametric analysis is conducted using a numerical computer model of an offshore structure to shed light on the difference between the wave forces as estimated by the linear and nonlinear forms of Morison's equation. The difference is clarified by showing the response of a model offshore structure when subjected to these wave forces. A modification to the linear form of Morison's equation is proposed, which gives better estimates of the nonlinear wave-induced forces. Response results obtained using the proposed model are validated against those obtained using the traditional linear and nonlinear forms of the equation.
A Mixed Robust/Optimal Active Vibration Control for Uncertain Flexible Structural Systems with Nonlinear Actuators Using Genetic Algorithm
Authors: Chen Shinn-Horng , Zheng Liang-An , Chou Jyh-Horng
Published: March 2007

In this article, a mixed robust/optimal control approach is proposed to treat the active vibration control (or active vibration suppression) problems of flexible structural systems under the effects of mode truncation, linear time-varying parameter perturbations and nonlinear actuators. A new robust stability condition is derived for the flexible structural system which is controlled by an observer-based controller and is subject to mode truncation, nonlinear actuators and linear structured time-varying parameter perturbations simultaneously. Based on the robust stability constraint and the minimization of a defined H2 performance, a hybrid Taguchi-genetic algorithm (HTGA) is employed to find the optimal state feedback gain matrix and observer gain matrix for uncertain flexible structural systems. A design example of the optimal observer-based controller for a simply supported beam is given to demonstrate the combined application of the presented sufficient condition and the HTGA.
Planar Cargo Control of Elastic Ship Cranes with the “Maryland Rigging” System
Authors: Al-Sweiti Yousef M. , SÖffker Dirk
Published: March 2007

This article concerns cargo pendulation control of an elastic ship-mounted crane using the Maryland Rigging system. The boom luff angle, the length of the upper cable, and the position of its lower suspension point are used as inputs to control the planar vibrations of the elastic boom and the pendulation of the payload. The disturbances acting on the ship are represented by the rolling displacement of the ship due to sea motions and the force acting directly on the payload. The dynamic of the crane is described by a multi-model problem depending on the current values of the cable length and boom luff angle. Accordingly a variable-gain observer and a variable-gain controller are designed. The controller uses the estimated states and the measured roll angle to create the required damping and to compensate for the rolling motion of the ship. Simulation and experimental results showed that the expressed control strategy performs very well and has a significant effect in suppressing the vibrations for different operating conditions and payload masses.
Mapping discursive closings in the war on drugs
Authors: Brown Michelle
Published: March 2007

This article maps the discursive closing of the most recent war on drugs through a series of case studies drawn from popular culture. This kind of work is performed in an effort to theorize the reflexive role of structure and agency in criminological representation. Each of the three selected cases demonstrates important shifts in conventions of representation that are historically contingent and recursively embedded in developing understandings of the relationship between drugs, individual actors and larger structural forces of sovereignty, inequality, and criminality. Each highlights the nature of a protracted crisis of representation in popular narratives of the war on drugs, where individual actors, even in their most mainstream manifestations, are depicted as caught within complex institutional contradictions which often paradoxically affirm and subvert drug war contexts.
For a ruthless cultural criticism of everything existing
Authors: Ferrell Jeff
Published: March 2007

Some scholars contend that cultural criminology has abandoned the critical analysis of capitalism’s criminogenic tendencies, resorting instead to a myopic subjectivism that romanticizes transgression and misses broader structures of inequality. On the contrary, cultural criminology can be seen to incorporate a constellation of critiques designed to expose the distinctly cultural dynamics of late capitalism and its crimes. From this view, cultural criminological analysis overcomes the dichotomization of structure and agency by locating structural arrangements within moments of lived experience, and by exploring in these moments the often confounded possibilities of agency, subversion, and control. In this way cultural criminology calls into question dismissive distinctions between crimes large and small, and continues to investigate the complex process by which crime and transgression are invested with collective meaning.
NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells
Authors: Miller Claudia P. , Ban Kechen , Dujka Melanie E. , McConkey David J. , Munsell Mark , Palladino Michael , Chandra Joya
Published: March 2007

The proteasome has been successfully targeted for the treatment of multiple myeloma and mantle cell lymphoma; however, in other hematologic malignancies, bortezomib has been less effective as a single agent. Here, we describe effects of NPI-0052, a novel proteasome inhibitor, in leukemia model systems. In cell lines, NPI-0052 inhibits all 3 proteolytic activities associated with the proteasome: chymotrypsin-, trypsin-, and caspase-like. NPI-0052 also induces DNA fragmentation in leukemia lines and in mononuclear cells from a Ph + acute lymphoblastic leukemia (ALL) patient. Caspase-3 activation by NPI-0052 was seen in wild-type Jurkat cells, but was significantly lessened in Fas-associated death domain (FADD)–deficient or caspase-8–deficient counterparts. NPI-0052–induced apoptosis was further probed using caspase-8 inhibitors, which were more protective than caspase-9 inhibitors. N-acetyl cysteine (NAC) also conferred protection against NPI-0052–induced apoptosis, indicating a role for oxidative stress by NPI-0052. In support of the drug's in vitro activities, biweekly treatment with NPI-0052 lessened total white blood cell (WBC) burden over 35 days in leukemic mice. Interestingly, combining NPI-0052 with either MS-275 or valproic acid (VPA) induced greater levels of cell death than the combination of bortezomib with these histone deacetylase inhibitors (HDACi). These effects of NPI-0052, alone and in combination with HDACi, warrant further testing to determine the compound's clinical efficacy in leukemia.
Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation
Authors: Boulland Marie-Laure , Marquet Jeanine , Molinier-Frenkel Valérie , Möller Peter , Guiter Chrystelle , Lasoudris Fanette , Copie-Bergman Christiane , Baia Maryse , Gaulard Philippe , Leroy Karen , Castellano Flavia
Published: March 2007

Interleukin-4–induced gene 1 (IL4I1) was first described as a B-cell IL4-inducible gene and is highly expressed in primary mediastinal B-cell lymphomas. We established stable HEK293 clones expressing human and mouse IL4I1 to examine their biochemical properties and function. Both proteins were secreted into the culture medium, and we observed the secretion of endogenous human IL4I1 (hIL4I1) protein in a mediastinal lymphoma B-cell line, MedB-1. We showed that IL4I1 has l-amino acid oxidase activity, optimal at physiological pH and primarily directed toward phenylalanine. Immunohistochemical analysis of secondary lymphoid organs showed staining of germinal center macrophages and inflammatory myeloid cells. In vitro, functional enzyme was highest in mature dendritic cells (DCs), suggesting a role in antigen-presenting cell/T-lymphocyte cross-talk. Indeed, hIL4I1 inhibited the proliferation of CD3-stimulated T lymphocytes with a similar effect on CD4+ and CD8+ T cells. In contrast, memory T cells were more strongly affected by hIL4I1 and its catabolite H2O2 than naive T cells. hIL4I1 inhibitory effect was dependent on enzymatic activity and H2O2 production and associated with a transient down-regulation of TCRζ expression. Altogether these data suggest IL4I1 as a new immunomodulatory enzyme produced by DCs.
Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper
Authors: Hamdi Haifa , Godot Véronique , Maillot Marie-Christine , Prejean Maria Victoria , Cohen Nicolas , Krzysiek Roman , Lemoine François M. , Zou Weiping , Emilie Dominique
Published: March 2007

Dendritic cells (DCs) determine whether antigen presentation leads to immune activation or to tolerance. Tolerance-inducing DCs (also called regulatory DCs) act partly by generating regulatory T lymphocytes (Tregs). The mechanism used by DCs to switch toward regulatory DCs during their differentiation is unclear. We show here that human DCs treated in vitro with glucocorticoids produce the glucocorticoid-induced leucine zipper (GILZ). Antigen presentation by GILZ-expressing DCs generates CD25highFOXP3+CTLA-4/CD152+ and interleukin-10–producing Tregs inhibiting the response of CD4+ and CD8+ T lymphocytes. This inhibition is specific to the antigen presented, and only proliferating CD4+ T lymphocytes express the Treg markers. Interleukin-10 is required for Treg induction by GILZ-expressing DCs. It is also needed for the suppressive function of Tregs. Antigen-presenting cells from patients treated with glucocorticoids generate interleukin-10–secreting Tregs ex vivo. These antigen-presenting cells produce GILZ, which is needed for Treg induction. Therefore, GILZ is critical for commitment of DCs to differentiate into regulatory DCs and to the generation of antigen-specific Tregs. This mechanism may contribute to the therapeutic effects of glucocorticoids.
Daytime sleepiness and polysomnographic variables in sleep apnoea patients
Authors: Mediano O. , Barceló A. , de la Peña M. , Gozal D. , Agustí A. , Barbé F.
Published: March 2007

Excessive daytime sleepiness (EDS) is not invariably present in patients with obstructive sleep apnoea syndrome (OSAS). The aim of the present study was to investigate polysomnographic determinants of EDS in patients with OSAS.

EDS was assessed using the Epworth Sleepiness Scale (ESS) and the multiple sleep latency test (MSLT). Patients showed EDS whenever the ESS score was >10 and the MSLT score <5 min. Absence of EDS was defined as having an ESS score of <10 and an MSLT score of >10 min.

In total, 23 male patients with EDS (mean±sdESS and MSLT score 17±3 and 4±1 min, respectively) and 17 without EDS (ESS and MSLT score 5±2 and 16±3 min, respectively), were studied. Both groups exhibited a similar apnoea/hypopnoea index (62±18versus60±20 events·h−1). Patients with EDS exhibited shorter sleep latency (11±16versus18±18 min) and greater sleep efficiency (90±7versus82±13%) than those without EDS. Patients with EDS showed lower oxygenation (lowest arterial oxygen saturation 69±12versus79±8%; mean arterial oxygen saturation 87±6versus90±5%). Sleep stage distribution and arousal index did not differ between the groups.

Patients with obstructive sleep apnoea syndrome and excessive daytime sleepiness are characterised by shorter sleep latency, increased sleep efficiency and worse nocturnal oxygenation than those without excessive daytime sleepiness. Nocturnal hypoxaemia can be a major determinant of excessive daytime sleepiness in patients with obstructive sleep apnoea syndrome.
An epidemiological study of pulmonary arterial hypertension
Authors: Peacock A. J. , Murphy N. F. , McMurray J. J. V. , Caballero L. , Stewart S.
Published: March 2007

All hospitalisations for pulmonary arterial hypertension (PAH) in the Scottish population were examined to determine the epidemiological features of PAH. These data were compared with expert data from the Scottish Pulmonary Vascular Unit (SPVU).

Using the linked Scottish Morbidity Record scheme, data from all adults aged 16–65 yrs admitted with PAH (idiopathic PAH, pulmonary hypertension associated with congenital heart abnormalities and pulmonary hypertension associated with connective tissue disorders) during the period 1986–2001 were identified. These data were compared with the most recent data in the SPVU database (2005).

Overall, 374 Scottish males and females aged 16–65 yrs were hospitalised with incident PAH during 1986–2001. The annual incidence of PAH was 7.1 cases per million population. On December 31, 2002, there were 165 surviving cases, giving a prevalence of PAH of 52 cases per million population. Data from the SPVU were available for 1997–2006. In 2005, the last year with a complete data set, the incidence of PAH was 7.6 cases per million population and the corresponding prevalence was 26 cases per million population.

Hospitalisation data from the Scottish Morbidity Record scheme gave higher prevalences of pulmonary arterial hypertension than data from the expert centres (Scotland and France). The hospitalisation data may overestimate the true frequency of pulmonary arterial hypertension in the population, but it is also possible that the expert centres underestimate the true frequency.
Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics
Authors: Tgavalekos N. T. , Musch G. , Harris R. S. , Vidal Melo M. F. , Winkler T. , Schroeder T. , Callahan R. , Lutchen K. R. , Venegas J. G.
Published: March 2007

Bronchoconstriction in asthma results in patchy ventilation forming ventilation defects (VDefs). Patchy ventilation is clinically important because it affects obstructive symptoms and impairs both gas exchange and the distribution of inhaled medications. The current study combined functional imaging, oscillatory mechanics and theoretical modelling to test whether the degrees of constriction of airways feeding those units outside VDefs were related to the extent of VDefs in bronchoconstricted asthmatic subjects.

Positron emission tomography was used to quantify the regional distribution of ventilation and oscillatory mechanics were measured in asthmatic subjects before and after bronchoconstriction. For each subject, ventilation data was mapped into an anatomically based lung model that was used to evaluate whether airway constriction patterns, consistent with the imaging data, were capable of matching the measured changes in airflow obstruction.

The degree and heterogeneity of constriction of the airways feeding alveolar units outside VDefs was similar among the subjects studied despite large inter-subject variability in airflow obstruction and the extent of the ventilation defects. Analysis of the data amongst the subjects showed an inverse relationship between the reduction in mean airway conductance, measured in the breathing frequency range during bronchoconstriction, and the fraction of lung involved in ventilation defects.

The current data supports the concept that patchy ventilation is an expression of the integrated system and not just the sum of independent responses of individual airways.
Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions
Authors: Makris D. , Scherpereel A. , Leroy S. , Bouchindhomme B. , Faivre J-B. , Remy J. , Ramon P. , Marquette C-H.
Published: March 2007

The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic.

The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean±sem23.5±1.5 mm and the depth from the visceral-costal pleura was 14.9±2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy.

All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25–40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was ≤4 mm. Three pneumothoraces occurred and chest drainage was required in one case.

Electromagnetic navigation-guided bronchoscopy has the potential to improve the diagnostic yield of transbronchial biopsies without additional fluoroscopic guidance, and may be useful in the early diagnosis of lung cancer, particularly in nonoperable patients.
Peroxisome Proliferator-Activated Receptor-γ C190S Mutation Causes Partial Lipodystrophy
Authors: Lüdtke Angelika , Buettner Janine , Wu Wei , Muchir Antoine , Schroeter Andreas , Zinn-Justin Sophie , Spuler Simone , Schmidt Hartmut H.-J. , Worman Howard J.
Published: March 2007

Context: Mutations in PPARG are associated with insulin resistance and familial partial lipodystrophy, a disease characterized by altered distribution of sc fat and symptoms of the metabolic syndrome. The encoded protein, peroxisome proliferator-activated receptor (PPAR)-γ, plays a pivotal role in regulating lipid and glucose metabolism, the differentiation of adipocytes, and other cellular regulatory processes.

Objectives: The objective of the study was to detect a novel PPARG mutation in a kindred with partial lipodystrophy and analyze the functional characteristics of the mutant protein.

Patients and Methods: In three subjects with partial lipodystrophy, one unaffected family member, and 124 unaffected subjects, PPARG was screened for mutations by direct sequencing. Body composition, laboratory abnormalities, and hepatic steatosis were assessed in each affected subject. Transcriptional activity was determined, and EMSA was performed to investigate DNA binding capacity of the mutant protein.

Results: We identified a PPARG mutation, C190S, causing partial lipodystrophy with metabolic alterations in three affected family members. The mutation was absent in the unaffected family member and unaffected controls. The mutation is located within zinc-finger 2 of the DNA binding domain. C190S PPARγ has a significantly lower ability to activate a reporter gene than wild-type PPARγ in absence and presence of rosiglitazone. A dominant-negative effect was not observed. Compared with wild-type PPARγ, C190S PPARγ shows a reduced capacity to bind DNA.

Conclusion: Mutation of a zinc-binding amino acid of PPARγ leads to an altered protein-DNA binding pattern, resulting in a partial loss of function, which in turn is associated with partial lipodystrophy.
Dysregulation of Placental Endothelial Lipase and Lipoprotein Lipase in Intrauterine Growth-Restricted Pregnancies
Authors: Gauster M. , Hiden U. , Blaschitz A. , Frank S. , Lang U. , Alvino G. , Cetin I. , Desoye G. , Wadsack C.
Published: March 2007

Context: Fetal supply of maternally derived fatty acids requires lipase-mediated hydrolysis of lipoprotein-borne triglycerides and phospholipids at the placental surface.

Objective: The objective of the study was to test the hypothesis that members of the triglyceride lipase gene (TLG) family are expressed in the human placenta at the maternoplacental (syncytiotrophoblast) and fetoplacental (endothelial cells) interface and that their expression is altered in pregnancy pathologies.

Design and Setting: Expression of TLG family members in primary placental cells (trophoblast and endothelial cells) and tissues of first-trimester and term human placenta was analyzed by microarrays, RT-PCR, Western blotting, and immunohistochemistry. Their expression was compared between normal pregnancies and those complicated with intrauterine growth restriction (IUGR).

Participants: Participants included women with uncomplicated pregnancies and pregnancies complicated by IUGR.

Results: Endothelial lipase (EL) and lipoprotein lipase (LPL) were the only lipases among the TLG family expressed in key cells of the human placenta. In first trimester, EL and LPL were expressed in trophoblasts. At term, EL was detected in trophoblasts and endothelial cells, whereas LPL was absent in these cells. Both lipases were found at placental blood vessels, EL in vascular endothelial cells and LPL in the surrounding smooth muscle cells. In total placental tissue EL expression prevails in first trimester and at term. Compared with normal placentas, EL mRNA was decreased (30%; P < 0.02), whereas LPL mRNA expression was increased (2.4-fold; P < 0.015) in IUGR.

Conclusion: EL is the predominant TLG family member in the human placenta present at both interfaces. EL and LPL are dysregulated in IUGR.
Relative Potencies of Anastrozole and Letrozole to Suppress Estradiol in Breast Cancer Patients Undergoing Ovarian Stimulation before in Vitro Fertilization
Authors: Azim Amr A. , Costantini-Ferrando Maria , Lostritto K. , Oktay Kutluk
Published: March 2007

Context: Breast cancer patients undergoing controlled ovarian hyperstimulation (COH) for embryo or oocyte cryopreservation should be induced by the method that leads to the least increase in estradiol (E2) levels.

Objective: The aim of the study was to determine the potency of anastrozole to suppress serum E2 levels in breast cancer patients undergoing COH.

Design and Setting: A prospective sequential cohort study was conducted in an academic center for reproductive medicine between May 2003 and November 2005 for letrozole and between December 2005 and April 2006 for anastrozole.

Patients: Breast cancer patients presenting for fertility preservation participated in the study.

Intervention: COH using FSH and letrozole (n = 47) or anastrozole (n = 7) was followed by oocyte retrieval and embryo cryopreservation.

Main Outcome Measures: Serum E2 levels, area under the curve for E2, and outcomes of COH cycles were measured.

Results: There were no significant differences between the two groups regarding length of stimulation, total gonadotropin dose, number of follicles larger than 17 mm, and the lead follicle size on human chorionic gonadotropin (hCG) day and number of embryos cryopreserved. The mean E2 levels on the day of hCG and post-hCG days were higher in the anastrozole group compared to the letrozole group (1325.89 ± 833.17 and 2515.07 ± 1368.52 vs. 427.78 ± 278.24 and 714.38 ± 440.83 pg·d/ml; P ≤ 0.01), respectively, even when anastrozole dose was increased up to 10 mg/d. The mean area under the curve was significantly higher in the anastrozole group compared to the letrozole group (4402.93 ± 1526.7 vs. 1287.48 ± 732.17 pg·d/ml; P <0.004).

Conclusions: Breast cancer patients who underwent ovarian stimulation with anastrozole had a significantly higher exposure to E2 than those who were stimulated with letrozole.
Endofin acts as a Smad anchor for receptor activation in BMP signaling
Authors: Shi Weibin , Chang Chenbei , Nie Shuyi , Xie Shutao , Wan Mei , Cao Xu
Published: March 2007

Signaling through receptors of the transforming growth factor β (TGFβ) superfamily is mediated by cytoplasmic Smad proteins. It has been demonstrated that Smad anchor for receptor activation (SARA) facilitates TGFβ and activin/nodal signaling by recruiting and presenting Smad2/3 to the receptor complex. SARA does not bind Smad1 and hence does not enhance bone morphogenetic protein (BMP) signaling. Here we report for the first time that the endosome-associated FYVE-domain protein endofin acts as a Smad anchor for receptor activation in BMP signaling. We demonstrate that endofin binds Smad1 preferentially and enhances Smad1 phosphorylation and nuclear localization upon BMP stimulation. Silencing of endofin by RNAi resulted in a reduction in BMP-dependent Smad1 phosphorylation. Moreover, disruption of the membrane-anchoring FYVE motif by point mutation led to a reduction of BMP-responsive gene expression in cell culture and Xenopus ectodermal explants. Furthermore, we demonstrate that endofin contains a protein-phosphatase-binding motif, which functions to negatively modulate BMP signals through receptor dephosphorylation. Taken together, our results suggest that endofin plays an important role in both positive and negative feedback regulation of the BMP signaling pathway.
Analogs of the Golgi complex in microsporidia: structure and avesicular mechanisms of function
Authors: Beznoussenko Galina V. , Dolgikh Viacheslav V. , Seliverstova Elena V. , Semenov Petr B. , Tokarev Yuri S. , Trucco Alvar , Micaroni Massimo , Di Giandomenico Daniele , Auinger Peter , Senderskiy Igor V. , Skarlato Sergei O. , Snigirevskaya Ekaterina S. , Komissarchik Yan Yu. , Pavelka Margit , De Matteis Maria A. , Luini Alberto , Sokolova Yuliya Ya. , Mironov Alexander A.
Published: March 2007

Microsporidia are obligatory intracellular parasites, most species of which live in the host cell cytosol. They synthesize and then transport secretory proteins from the endoplasmic reticulum to the plasma membrane for formation of the spore wall and the polar tube for cell invasion. However, microsporidia do not have a typical Golgi complex. Here, using quick-freezing cryosubstitution and chemical fixation, we demonstrate that the Golgi analogs of the microsporidia Paranosema (Antonospora) grylli and Paranosema locustae appear as 300-nm networks of thin (25- to 40-nm diameter), branching or varicose tubules that display histochemical features of a Golgi, but that do not have vesicles. Vesicles are not formed even if membrane fusion is inhibited. These tubular networks are connected to the endoplasmic reticulum, the plasma membrane and the forming polar tube, and are positive for Sec13, γCOP and analogs of giantin and GM130. The spore-wall and polar-tube proteins are transported from the endoplasmic reticulum to the target membranes through these tubular networks, within which they undergo concentration and glycosylation. We suggest that the intracellular transport of secreted proteins in microsporidia occurs by a progression mechanism that does not involve the participation of vesicles generated by coat proteins I and II.
Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks
Authors: Jing Runfeng , Wilhelmsson Ulrika , Goodwill William , Li Lizhen , Pan Yihang , Pekny Milos , Skalli Omar
Published: March 2007

Immature astrocytes and astrocytoma cells contain synemin and three other intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), vimentin and nestin. Here, we show that, after neurotrauma, reactive astrocytes produce synemin and thus propose synemin as a new marker of reactive astrocytes. Comparison of synemin mRNA and protein levels in brain tissues and astrocyte cultures from wild-type, Vim-/- and Gfap-/-Vim-/- mice showed that in the absence of vimentin, synemin protein was undetectable although synemin mRNA was present at wild-type levels. By contrast, in Gfap-/- astrocytes, synemin protein and mRNA levels, as well as synemin incorporation into vimentin IFs, were unaltered. Biochemical assays with purified proteins suggested that synemin interacts with GFAP IFs like an IF-associated protein rather than like a polymerization partner, whereas the opposite was true for synemin interaction with vimentin. In transfection experiments, synemin did not incorporate into normal, filamentous GFAP networks, but integrated into vimentin and GFAP heteropolymeric networks. Thus, alongside GFAP, vimentin and nestin, reactive astrocytes contain synemin, whose accumulation is suppressed post-transcriptionally in the absence of a polymerization partner. In astrocytes, this partner is vimentin and not GFAP, which implies a functional difference between these two type III IF proteins.
Modulation of Nod2-dependent NF-κB signaling by the actin cytoskeleton
Authors: Legrand-Poels Sylvie , Kustermans Gaelle , Bex Françoise , Kremmer Elisabeth , Kufer Thomas A. , Piette Jacques
Published: March 2007

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-κB activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-κB activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-κB signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co-immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF-κB signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-κB signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection.
Bureaucrats or Politicians? Part I: A Single Policy Task
Authors: Alesina Alberto , Tabellini Guido
Published: March 2007

This paper investigates the normative criteria that guide the allocation of a policy task to an elected politician versus an independent bureaucrat. The bureaucrat is preferable for technical tasks for which ability is more important than effort, or if there is great uncertainty about whether the policymaker has the required abilities. The optimal allocation of redistributive tasks is ambiguous, and depends on how the bureaucrat can be instructed. But irrespective of the normative conclusion, the politician prefers not to delegate redistributive policies. (JEL D72, D73, D82)
The Motivation and Bias of Bureaucrats
Authors: Prendergast Canice
Published: March 2007

Many individuals are motivated to exert effort because they care about their jobs, rather than because there are monetary consequences to their actions. The intrinsic motivation of bureaucrats is the focus of this paper, and three primary results are shown. First, bureaucrats should be biased. Second, sometimes this bias takes the form of advocating for their clients more than would their principal, while in other cases, they are more hostile to their interests. For a range of bureaucracies, those who are biased against clients lead to more efficient outcomes. Third, self-selection need not produce the desired bias. Instead, selection to bureaucracies is likely to be bifurcated, in the sense that it becomes composed of those who are most preferred by the principal, and those who are least preferred. (JEL D64, D73, D82)
Imprecision as an Account of the Preference Reversal Phenomenon
Authors: Butler David J , Loomes Graham C
Published: March 2007

Many individuals' choices and valuations involve a degree of uncertainty/imprecision. This paper reports an experiment designed to obtain some measure of imprecision and to examine the extent to which it can explain preference reversals of two opposite forms, one of which appears not to have been reported previously. The model of imprecision we examine not only predicts both patterns but also provides an account of earlier results that are otherwise not well explained. The results suggest that any successful descriptive theory of choice and valuation will need to allow in some way for the imprecision surrounding people's decisions. (JEL C91, D11, D81)
Do Workers Work More if Wages Are High? Evidence from a Randomized Field Experiment
Authors: Fehr Ernst , Goette Lorenz
Published: March 2007

Most previous studies on intertemporal labor supply found very small or insignificant substitution effects. It is possible that these results are due to constraints on workers' labor supply choices. We conducted a field experiment in a setting in which workers were free to choose hours worked and effort per hour. We document a large positive elasticity of overall labor supply and an even larger elasticity of hours, which implies that the elasticity of effort per hour is negative. We examine two candidate models to explain these findings: a modified neoclassical model with preference spillovers across periods, and a model with reference dependent, loss-averse preferences. With the help of a further experiment, we can show that only loss-averse individuals exhibit a negative effort response to the wage increase. (JEL J22, J31)
The Effect of Court-Ordered Hiring Quotas on the Composition and Quality of Police
Authors: McCrary Justin
Published: March 2007

Arguably the most aggressive affirmative action program ever implemented in the United States was a series of court-ordered racial hiring quotas imposed on municipal police departments. My best estimate of the effect of court-ordered affirmative action on work-force composition is a 14-percentage-point gain in the fraction African American among newly hired officers. Evidence on police performance is mixed. Despite substantial black-white test score differences on police department entrance examinations, city crime rates appear unaffected by litigation. However, litigation lowers slightly both arrests per crime and the fraction black among serious arrestees. (JEL H76, J15, J78, K31)