bluuebunny/crossref_metadata_2025 huggingface dataset:
A pseudo‐empirical best linear unbiased prediction approach to small area estimation using survey weights
Authors: You Yong , Rao J. N. K.
Published: June 2006

The authors develop a small area estimation method using a nested error linear regression model and survey weights. In particular, they propose a pseudo‐empirical best linear unbiased prediction (pseudo‐EBLUP) estimator to estimate small area means. This estimator borrows strength across areas through the model and makes use of the survey weights to preserve the design consistency as the area sample size increases. The proposed estimator also has a nice self‐benchmarking property. The authors also obtain an approximation to the model mean squared error (MSE) of the proposed estimator and a nearly unbiased estimator of MSE. Finally, they compare the proposed estimator with the EBLUP estimator and the pseudo‐EBLUP estimator proposed by Prasad & Rao (1999), using data analyzed earlier by Battese, Harter & Fuller (1988).
Cardiovascular factors explain genetic background differences in VO2max
Authors: Roy Jane L.P. , Hunter Gary R. , Fernandez Jose R. , McCarthy John P. , Larson‐Meyer D. Enette , Blaudeau Tamilane E. , Newcomer Bradley R.
Published: June 2006

The purpose of this study was to further explore factors that may be related to ethnic differences in the maximum rate at which an individual can consume oxygen (VO2max) between 20 African American (AA) and 30 European American (EA) sedentary women who were matched for body weight (kg) and fat‐free mass (FFM). VO2max (l/min) was determined during a graded treadmill exercise test. Submaximal steady‐state heart rate and submaximal VO2 were determined at a treadmill speed of 1.3 m/sec and a 2.5% grade. Hemoglobin (Hb) was determined by the cyanide method, muscle oxidative capacity by 31P magnetic resonance spectroscopy (ADP time constant), and FFM (kg) by dual‐energy x‐ray absorptiometry. Genetic classification was self‐reported, and in a subset of the sample (N = 32), the determinants of ethnicity were measured by African genetic admixture. AA women had significantly reduced VO2max, Hb levels, and muscle oxidative capacity (longer ADP time constants, P ≤ 0.05) than EA women. Submaximal oxygen pulse (O2Psubmax), ADP time constant, Hb, and ethnic background were all significantly related to VO2max (ml/kg/min and ml/kg FFM/min, all P ≤ 0.01). By multiple regression modeling, Hb, O2Psubmax, muscle oxidative capacity, and ethnicity were found to explain 61% and 57% of the variance of VO2max in ml/kg/min and ml/kg FFM/min, respectively. Muscle oxidative capacity and O2Psubmax were both significantly and independently related to VO2max in all three models (P ≤ 0.05), whereas Hb and ethnicity were not. These results suggest that mitochondrial muscle oxidative capacity and oxygen delivery capabilities, as determined by O2Psubmax, account for most if not all of the ethnic differences in VO2max. Am. J. Hum. Biol. 18:454–460, 2006. © 2006 Wiley‐Liss, Inc.
Smoking during pregnancy and components of stature in offspring
Authors: Leary Sam , Davey Smith George , Ness Andy
Published: June 2006

The objective of this study was to examine the association between maternal smoking during pregnancy and offspring height and its components. The analysis was based on 6,340 white singletons born in 1991–1992 and enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC), who had maternal smoking data recorded for at least one trimester in pregnancy, and who had their height recorded at age 7.5. Smoking at any time in pregnancy was associated with a reduction in offspring height, trunk, and leg length, and the leg‐to‐trunk ratio, after adjustment for age and sex. After additional adjustment for maternal factors, social factors, and breastfeeding, associations with leg length and leg‐to‐trunk ratio remained, with reductions of 0.25 cm (95% confidence interval, 0.05–0.46 cm) in leg length and 0.30% (95% confidence interval, 0.03–0.57%) in leg‐to‐trunk ratio if the mother smoked. Findings were similar when the smoking data were analyzed separately for each trimester. Furthermore, in each trimester, the more a mother smoked, the greater the reduction in offspring height, leg length, and leg‐to‐trunk ratio. These dose‐response relationships remained after adjustment for all potential confounders for leg length and leg‐to‐trunk ratio. Smoking at any time in pregnancy reduces offspring height and its components, and in particular leg length and leg‐to‐trunk ratio at age 7.5. Am. J. Hum. Biol. 18:502–512, 2006. © 2006 Wiley‐Liss, Inc.
Evolution of arthropod visual systems: Development of the eyes and central visual pathways in the horseshoe crabLimulus polyphemusLinnaeus, 1758 (Chelicerata, Xiphosura)
Authors: Harzsch Steffen , Vilpoux Kathia , Blackburn David C. , Platchetzki David , Brown Nadean L. , Melzer Roland , Kempler Karen E. , Battelle Barbara A.
Published: June 2006

Despite ongoing interest into the architecture, biochemistry, and physiology of the visual systems of the xiphosuranLimulus polyphemus, their ontogenetic aspects have received little attention. Thus, we explored the development of the lateral eyes and associated neuropils in late embryos and larvae of these animals. The first external evidence of the lateral eyes was the appearance of white pigment spots—guanophores associated with the rudimentary photoreceptors—on the dorsolateral side of the late embryos, suggesting that these embryos can perceive light. The first brown pigment emerges in the eyes during the last (third) embryonic molt to the trilobite stage. However, ommatidia develop from this field of pigment toward the end of the larval trilobite stage so that the young larvae at hatching do not have object recognition. Double staining with the proliferation marker bromodeoxyuridine (BrdU) and an antibody againstL. polyphemusmyosin III, which is concentrated in photoreceptors of this species, confirmed previous reports that, in the trilobite larvae, new cellular material is added to the eye field from an anteriorly located proliferation zone. Pulse–chase experiments indicated that these new cells differentiate into new ommatidia. Examining larval eyes labeled for opsin showed that the new ommatidia become organized into irregular rows that give the eye field a triangular appearance. Within the eye field, the ommatidia are arranged in an imperfect hexagonal array. Myosin III immunoreactivity in trilobite larvae also revealed the architecture of the central visual pathways associated with the median eye complex and the lateral eyes. Double labeling with myosin III and BrdU showed that neurogenesis persists in the larval brain and suggested that new neurons of both the lamina and the medulla originate from a single common proliferation zone. These data are compared with eye development inDrosophila melanogasterand are discussed with regard to new ideas on eye evolution in the Euarthropoda. Developmental Dynamics 235:2641–2655, 2006. © 2006 Wiley‐Liss, Inc.
Nanostructured niobium oxide coatings influence osteoblast adhesion
Authors: Eisenbarth E. , Velten D. , Müller M. , Thull R. , Breme J.
Published: June 2006

The interaction of osteoblasts was correlated to the roughness of nanosized surface structures of Nb2O5 coatings on polished CP titanium grade 2. Nb2O5 sol–gel coatings were selected as a model surface to study the interaction of osteoblasts with nanosized surface structures. The surface roughness was quantified by determination of the average surface finish (Ra number) by means of atomic force microscopy. Surface topographies with Ra = 7, 15, and 40 nm were adjusted by means of the annealing process parameters (time and temperature) within a sol–gel coating procedure. The observed osteoblast migration was fastest on smooth surfaces with Ra = 7 nm. The adhesion strength, spreading area, and collagen‐I synthesis showed the best results on an intermediate roughness of Ra = 15 nm. The surface roughness of Ra = 40 nm was rather peaked and reduced the speed of cell reactions belonging to the adhesion process. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Biochemical modifications induced in human blood by oxygenation‐ozonation
Authors: Bocci Velio , Aldinucci Carlo
Published: June 2006

Some biochemical effects determined on human blood after addition of a gas mixture composed of oxygen (∼96%) and ozone (∼4%) have been evaluated. Ozone was used in a mild concentration ranging between 0.21 and 1.68 mM. Within few minutes after rapid mixing of the equal gas‐liquid volumes, the ozone was consumed because by instantaneously reacting with biomolecules, generating reactive oxygen species (particularly hydrogen peroxide) having very short lifetime and lipid oxidation products. The following results are oxygen‐ozone dose dependent: (1) The pO2 values have risen from about 40 up to 400 mmHg. (2) By testing the highest ozone concentration, the total antioxidant capacity of blood decreased within 1 min from 1.35 to 0.91 mM but regained its normal values within 20 min owing to the rapid reduction of oxidized antioxidants operated by erythrocytes. (3) Similarly, intraerythrocytic reduced glutathione after ozonation decreased from the initial value of 5.71 to 4.56 μmol/g Hb. (4) Both hemolysis and methemoglobin showed a negligible increase. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:133–138, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20124
Interaction of diuron and related substituted phenylureas with the Ah receptor pathway
Authors: Zhao Bin , Baston David S. , Hammock Bruce , Denison Michael S.
Published: June 2006

The aryl hydrocarbon receptor (AhR) is a ligand‐dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals, including the ubiquitous environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin. Here, we have examined the ability of diuron, a widely used herbicide, and several structurally related substituted phenylureas to bind to and activate/inhibit the AhR and AhR signal transduction. Diuron induced CYP1A1 mRNA levels in mouse hepatoma (Hepa1c1c7) cells and AhR‐dependent luciferase reporter gene expression in stably transfected mouse, rat, guinea pig, and human cell lines. In addition, ligand binding and gel retardation analysis demonstrated the ability of diuron to competitively bind to and stimulate AhR transformation and DNA binding in vitro and in intact cells. Several structurally related substituted phenylureas competitively bound to the guinea pig hepatic cytosolic AhR, inhibited 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐induced AhR‐dependent luciferase reporter gene expression in a species‐specific manner and stimulated AhR transformation and DNA binding, consistent with their role as partial AhR agonists. These results demonstrate not only that diuron and related substituted phenylureas are AhR ligands but also that exposure to these chemicals could induce/inhibit AhR‐dependent biological effects. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:103–113, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20126
Modulation of the expression of superoxide dismutase gene in lung injury by 2‐chloroethyl ethyl sulfide, a mustard analog
Authors: Mukhopadhyay Sutapa , Rajaratnam Veera , Mukherjee Shyamali , Smith Milton , Das Salil K.
Published: June 2006

Mustard gas exposure causes inflammatory lung diseases. Many inflammatory lung diseases are associated with oxidative stress. Reactive oxygen species (ROS) are involved in the maintenance of physiological functions. In tissues, it is therefore essential to maintain a steady‐state level of antioxidant activity to allow both for the physiological functions of ROS to proceed and at the same time preventing tissue damage. We have recently reported that mustard gas exposure decreases the overall activity of superoxide dismutase (SOD). In the present study, we investigated the effects of mustard gas on each of the three isozymes: SOD‐1 (Cu/Zn), SOD‐2 (Mn), and SOD‐3 (extracellular). Adult guinea pigs were intratracheally injected single doses of 2‐chloroethyl ethyl sulfide (CEES) (2 mg/kg body weight) in ethanol. Control animals were injected with vehicle in the same way. The animals were sacrificed after 7 days, and lungs were removed after perfusion with physiological saline. Lung injury was established by measuring the leakage of iodinated‐BSA into lung tissue. Mustard gas exposure caused a significant increase in the activity of SOD‐1 (35%). However, the SOD‐3 activity which is the predominant type in lung was significantly decreased (62%), whereas no change was observed in SOD‐2 activity. Thus the decrease in the total activity of SOD was primarily due to the SOD‐3 isozyme. Northern blot analysis indicated 3.5‐fold increased expression of SOD‐1 in mustard gas exposed lung, but no significant change in the expression of SOD‐2 and SOD‐3 was observed. Mustard gas exposure did not cause mutation in the coding region of SOD‐1 gene while causing modulation in expression levels. The protein levels of SOD‐1, SOD‐2, and SOD‐3 were not altered significantly in the mustard gas exposed lung. Our results indicate that the overall decrease in the activity of SOD by mustard gas exposure is probably mediated by direct inactivation of the SOD‐3 gene or the enzyme itself. This decrease in the activity of SOD‐3 may be due to the cleavage of active form of the protein to an inactive form. The existence of active and inactive forms of SOD‐3 as a result of shifts in Cys–Cys disulfide bonding has been described in human, recently. Studies are underway in our laboratory to investigate whether mustard gas induced inactivation of SOD‐3 in lung is similarly mediated by a change in Cys–Cys disulfide bonding. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:142–149, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20128
QM/MM modeling of compound I active species in cytochrome P450, cytochrome C peroxidase, and ascorbate peroxidase
Authors: Harvey Jeremy N. , Bathelt Christine M. , Mulholland Adrian J.
Published: June 2006

QM/MM calculations provide a means for predicting the electronic structure of the metal center in metalloproteins. Two heme peroxidases, Cytochrome c Peroxidase (CcP) and Ascorbate Peroxidase (APX), have a structurally very similar active site, yet have active intermediates with very different electronic structures. We review our recent QM/MM calculations on these systems, and present new computational data. Our results are in good agreement with experiment, and suggest that the difference in electronic structure is due to a large number of small differences in structure from one protein to another. We also discuss recent QM/MM calculations on the active species of cytochrome P450, in which a similar sensitivity of the electronic structure to the environment is found. However, this does not appear to explain different catalytic profiles of the different drug‐metabolizing isoforms of this class of enzyme. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1352–1362, 2006
On the accuracy of density functional theory for iron—sulfur clusters
Authors: Szilagyi Robert K. , Winslow Mark A.
Published: June 2006

A simple, yet powerful wave function manipulation method was introduced utilizing a generalized ionic fragment approach that allows for systematic mapping of the wave function space for multispin systems with antiferromagnetic coupling. The use of this method was demonstrated for developing ground state electronic wave function for [2Fe‐2S] and [Mo‐3Fe‐4S] clusters. Using well‐defined ionic wave functions for ferrous and ferric irons, sulfide, and thiolate fragments, the accuracy of various density functionals and basis sets including effective core potentials were evaluated on a [4Fe‐4S] cluster by comparing the calculated geometric and electronic structures with crystallographic data and experimental atomic spin densities from X‐ray absorption spectroscopy, respectively. We found that the most reasonable agreement for both geometry and atomic spin densities is obtained by a hybrid functional with 5% HF exchange and 95% density functional exchange supplemented with Perdew's 1986 correlation functional. The basis set seems to saturate only at the triple‐ζ level with polarization and diffuse functions. Reasonably preoptimized structures can be obtained by employing computationally less expensive effective core potentials, such as the Stuttgart–Dresden potential with a triple‐ζ valence basis set. The extension of the described calibration methodology to other biologically important and more complex iron–sulfur clusters, such as hydrogenase H‐cluster and nitrogenase FeMo‐co will follow. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1385–1397, 2006
High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex™ cement spacers in two‐stage revision of infected hip implants: A study of 46 patients at an average follow‐up of 107 days
Authors: Hsieh Pang‐Hsin , Chang Yu‐Han , Chen Shih‐Hao , Ueng Steve W.N. , Shih Chun‐Hsiung
Published: June 2006

This study investigated the release of antibiotics in vivo, from an articulating polymethylmethacrylate (PMMA) spacer used in two‐stage revision arthroplasty of infected hip implants. Forty‐six patients who underwent two‐stage revision hip arthroplasty for infections were managed with an interim PMMA spacer loaded with a high dose of vancomycin and aztreonam. Serum and aliquots of drainage collected after the first‐stage surgery, and joint fluid obtained at the time of the second‐stage surgery were analyzed for antibiotic concentrations by high performance liquid chromatography and bioactivity by tube dilution bioassay. Following implantation, the highest levels of antibiotics were measured in aliquots of drainage on the first day (vancomycin: 1538.0 ± 243.6 µg/mL; aztreonam: 1003.5 ± 323.5 µg/mL), decreasing to 571.9 ± 169.4 µg/mL for vancomycin and 313.6 ± 88.3 µg/mL for aztreonam after 7 days. Antibiotic concentrations in serum were very low (vancomycin: 0.58 ± 0.2 µg/mL, range: 0.1–1.6 µg/mL; aztreonam: 0.46 ± 0.3 µg/mL, range: 0.1–0.9 µg/mL at 24 h) and there was no systemic adverse effect. At a mean 107 days after the first‐stage surgery, the concentrations of antibiotics in joint fluid were well above the minimal inhibitory concentration of most common microorganisms. The released antibiotics were bioactive against the test organisms. Based on the observed results, we confirmed the safety and effectiveness of in vivo drug delivery from antibiotic‐impregnated PMMA hip spacers. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1615–1621, 2006
In vivo cyclic axial compression affects bone healing in the mouse tibia
Authors: Gardner Michael J. , van der Meulen Marjolein C. H. , Demetrakopoulos Demetris , Wright Timothy M. , Myers Elizabeth R. , Bostrom Mathias P.
Published: June 2006

Abundant evidence exists that fracture healing can be influenced by mechanical loading. However, the specific loading parameters that are osteogenic remain unknown. We hypothesized that the bone healing response in mouse tibial osteotomies would be different with a short delay before loading compared to immediate load application, as well as with higher and lower load magnitudes applied. Eighty 12‐week‐old mice underwent osteotomy of the left tibia followed by intramedullary nailing. Mice were divided into six groups based on days delayed until application of load (0 days or 4 days) and amplitude of cyclic load (0.5N, 1N, or 2N). Loading regimens were applied at 1 Hz for 100 cycles per day, 5 days per week for 2 weeks, using an external device that applied axial compression to the tibia. Bone healing was assessed by both microcomputed tomography (CT) and four‐point bend testing. A short delay followed by cyclic application of a relatively low load led to improved fracture healing, as determined by increased callus strength, but this enhancement disappeared as load amplitudes increased. Load initiation immediately following fracture inhibited healing, regardless of the magnitude of load applied. MicroCT measurements of calluses in the early healing stage did not predict the mechanical strength of the fractures. These findings confirm that controlled, noninvasive cyclic loading can improve the strength of healing callus. However, application of load immediately after fracture appears to be detrimental to healing. Load magnitude also plays a critical role, and must be taken into account in future studies and clinical applications. As the loading parameters necessary to enhance fracture healing become refined, external compression may be used as a potent stimulus for treating fractures with decreased biological capacity. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1679–1686, 2006
Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital
Authors: Kato H. , Usuda J. , Okunaka T. , Furukawa K. , Honda H. , Sakaniwa N. , Suga Y. , Hirata T. , Ohtani K. , Inoue T. , Maehara S. , Kubota M. , Yamada K. , Tsuitsui H.
Published: June 2006

Background and Objectives

We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years.

Study Design/Materials and Methods

PDT for 264 centrally located early‐stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition.

Results

Recent results of interstitial PDT for peripheral‐type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter.

Conclusions

In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT. Lasers Surg. Med. 38:371–375, 2006. © 2006 Wiley‐Liss, Inc.
Endobronchial photodynamic therapy for lung cancer
Authors: Loewen Gregory M. , Pandey Ravindra , Bellnier David , Henderson Barbara , Dougherty Thomas
Published: June 2006

Background and Objective

Endobronchial photodynamic therapy (PDT) is a minimally invasive technique for the palliation of major airway obstruction from lung cancer, and for the treatment of endobronchial microinvasive lung cancer.

Study Design

Results of reported clinical trials were compared, and the author's preliminary results with second generation photosensitizers were also reviewed.

Results

A review of the clinical experience with endobronchial PDT is provided. Potential advantages of PDT include the duration of palliation achieved through the delayed cellular effects of PDT within tumor. Side‐effects from FDA‐approved photosensitizer (Photofrin, Porfimer sodium, Axcan Scandipharm, Montreal, Quebec) include skin photosensitivity. HPPH (2‐[1‐hexyloxyethyl]‐2 devinyl pyropheophorbide) is an example of a second‐generation photosensitize that shows promise in the treatment of lung cancer, and appears to be free from significant skin photosensitivity.

Conclusion

PDT is an effective tool for the palliation of endobronchial lung cancers which obstruct the central airways and is also effective for the treatment of central microinvasive carcinoma and carcinoma in situ of the central airways. Lasers Surg. Med. 38:364–370, 2006. © 2006 Wiley‐Liss, Inc.
Photodynamic therapy in the treatment of microbial infections: Basic principles and perspective applications
Authors: Jori Giulio , Fabris Clara , Soncin Marina , Ferro Stefania , Coppellotti Olimpia , Dei Donata , Fantetti Lia , Chiti Giacomo , Roncucci Gabrio
Published: June 2006

Background and Objectives

Photodynamic therapy (PDT) appears to be endowed with several favorable features for the treatment of infections originated by microbial pathogens, including a broad spectrum of action, the efficient inactivation of antibiotic‐resistant strains, the low mutagenic potential, and the lack of selection of photoresistant microbial cells. Therefore, intensive studies are being pursued in order to define the scope and field of application of this approach.

Results

Optimal cytocidal activity against a large variety of bacterial, fungal, and protozoan pathogens has been found to be typical of photosensitizers that are positively charged at physiological pH values (e.g., for the presence of quaternarized amino groups or the association with polylysine moieties) and are characterized by a moderate hydrophobicity (n‐octanol/water partition coefficient around 10). These photosensitizers in a micromolar concentration can induce a >4–5 log decrease in the microbial population after incubation times as short as 5–10 minutes and irradiation under mild experimental conditions, such as fluence‐rates around 50 mW/cm2 and irradiation times shorter than 15 minutes.

Conclusions

PDT appears to represent an efficacious alternative modality for the treatment of localized microbial infections through the in situ application of the photosensitizer followed by irradiation of the photosensitizer‐loaded infected area. Proposed clinical fields of interest of antimicrobial PDT include the treatment of chronic ulcers, infected burns, acne vulgaris, and a variety of oral infections. Lasers Surg. Med. 38:468–481, 2006. © 2006 Wiley‐Liss, Inc.
Photodynamic therapy and anti‐tumor immunity
Authors: Gollnick Sandra O. , Owczarczak Barbara , Maier Patricia
Published: June 2006

Background and Objectives

Photodynamic therapy (PDT) efficacy appears to be enhanced in the presence of an intact immune system and PDT has been shown to augment anti‐tumor immunity. The mechanisms leading to the enhancement of the host immune response to tumor are unclear. Anti‐tumor immunity depends upon the presence of activated antigen presenting cells (APCs). These cells are activated by their recognition of components released by pathogens, viruses, dead cells, and the presence of pro‐inflammatory mediators. Activated APCs stimulate the generation of cytokine secreting effector cells. Therefore, we have hypothesized that PDT generated inflammatory mediators and components released from tumor cells killed by PDT results in the activation of APCs capable of stimulating effector T‐cell proliferation and cytokine secretion.

Study Design/Materials and Methods

To determine the effect of PDT on APCs, tumor draining lymph nodes (TDLNs) of EMT6 or Colo 26 tumor bearing mice were isolated 24 hours after Photofrin‐PDT and flow cytometry was used to detect the presence of APCs secreting the T cells stimulatory cytokine, IL‐12. APCs were also isolated from TDLNs and used to stimulate T‐cell proliferation and secretion of interferon‐γ (IFN‐γ).

Results

PDT results in an increase in IL‐12 expressing APCs in the TDLN. This increase was accompanied by an increase in the ability of APCs isolated from TDLNs of PDT‐treated mice to stimulate T‐cell proliferation and T‐cell secretion of IFN‐γ.

Conclusions

Our results indicate that APCs isolated from PDT‐treated mice exhibit an enhanced ability to stimulate T‐cell proliferation and IFN‐γ secretion, suggesting that PDT results in increased APC activity. Lasers Surg. Med. 38:509–515, 2006. © 2006 Wiley‐Liss, Inc.
A dose ranging study of photodynamic therapy with porfimer sodium (Photofrin®) for treatment of basal cell carcinoma
Authors: Oseroff Allan R. , Blumenson Leslie R. , Wilson B. Dale , Mang Thomas S. , Bellnier David A. , Parsons John C. , Frawley Noreen , Cooper Michele , Zeitouni Nathalie , Dougherty Thomas J.
Published: June 2006

Background and Objectives

While basal cell carcinoma (BCC) is effectively treated by several methods, many patients with numerous or frequently occurring lesions seek alternatives that can treat multiple cancers, with improved cosmetic outcome. PDT for esophageal and lung carcinomas is approved at a porfimer sodium (Photofrin®) dose of 2 mg/kg, but lower doses increase selectivity and decrease both cutaneous phototoxicity and cost. We evaluated low doses of porfimer sodium PDT for treatment of multiple BCC.

Materials and Methods

Seventy‐seven patients with 2,041 BCC were injected with 0.75, 0.875, or 1.0 mg/kg porfimer sodium and treated 2 days later with 630‐nm light. Clinical responses were determined at 6 months, then periodically to 5 years.

Results

Increasing porfimer sodium dose increased complete responses (CR), with initial CR rates of 72.7% (66–78%, 95% CI), 79.9% (73–86%, 95% CI), and 92.2% (91–93%, 95% CI), albeit with some lower selectivity at the highest dose. At 1 mg/kg, 5‐year recurrence rates were 28% (21–35%, 95% CI) and 15% (11–18%, 95% CI) for sporadic and nevoid basal cell carcinoma syndrome (NBCCS) lesions, respectively.

Conclusions

This is the largest dose‐ranging study of porfimer sodium, and the largest number of lesions treated in a single study. We found that with 1 mg/kg porfimer sodium, PDT can be a selective and durable treatment for sporadic and NBCCS‐associated BCC. Lasers Surg. Med. 38:417–426, 2006. © 2006 Wiley‐Liss, Inc.
Role of photodynamic therapy in unresectable esophageal and lung cancer
Authors: Chen Mang , Pennathur Arjun , Luketich James D.
Published: June 2006

The incidence of esophageal cancer has increased dramatically in the Western population in the last two decades. Many of these patients tend to present late in the disease course with symptoms of dysphagia and malnutrition. Thus a majority of patients at presentation may require palliation of their symptoms. Lung cancer is the most common cause of cancer related mortality in the United States. Similar to esophageal cancer, many patients present in advanced stages where surgical resection for cure may not be an option. Endobronchial obstruction from both primary and metastatic neoplasm causes significant morbidity. The modalities, which are currently available for palliation of symptoms include surgery, photodynamic therapy, dilation, external beam radiation, stents, Nd:YAG laser therapy, and brachytherapy. Each of these modalities has their specific advantages and drawbacks. In this article, we discuss the role of photodynamic therapy in the palliation of esophageal and lung cancer. Lasers Surg. Med. 38:396–402, 2006. © 2006 Wiley‐Liss, Inc.
Advances in photodynamic therapy for the treatment of head and neck cancers
Authors: Biel M.
Published: June 2006

Photodynamic therapy (PDT) is an FDA‐approved minimally invasive medical treatment modality that utilizes light in the presence of oxygen to activate photosensitizing agents that are relatively selectively concentrated in abnormal or neoplastic cells resulting in cell death. At the present time, PDT has been approved for clinical treatment in the United States, European Union, Canada, Russia, and Japan. In the United States, US Food and Drug administration approval has been given for the use of PDT in the treatment of Barrett's esophagus, obstructing esophageal carcinoma and early and obstructing tracheobronchial carcinoma using the photosensitizer Photofrin; actinic keratosis using the photosensitizer Levulan (aminolevulinic acid); and macular degeneration using the photosensitizer BPD. In the EU the above noted indications have also been approved in addition to the treatment of early head and neck cancers and palliative treatment of head and neck cancer using the photosensitizer Foscan; and treatment of basal and squamous cell skin cancers using the photosensitizer Metvix. Lasers Surg. Med. 38:349–355, 2006. © 2006 Wiley‐Liss, Inc.
Targeted disruption of the mouse Asna1 gene results in embryonic lethality
Authors: Mukhopadhyay Rita , Ho Ye-Shih , Swiatek Pamela J. , Rosen Barry P. , Bhattacharjee Hiranmoy
Published: June 2006

The bacterial ArsA ATPase is the catalytic component of an oxyanion pump that is responsible for resistance to arsenicals and antimonials. Homologues of the bacterial ArsA ATPase are widespread in nature. We had earlier identified the mouse homologue (Asna1) that exhibits 27% identity to the bacterial ArsA ATPase. To identify the physiological role of the protein, heterozygous Asna1 knockout mice (Asna1
+/−) were generated by homologous recombination. The Asna1
+/− mice displayed similar phenotype as the wild‐type mice. However, early embryonic lethality was observed in homozygous Asna1 knockout embryos, between E3.5 (E = embryonic day) and E8.5 stage. These findings indicate that Asna1 plays a crucial role during early embryonic development.
The role of the N‐terminal domain of chloroplast targeting peptides in organellar protein import and miss‐sorting
Authors: Bhushan Shashi , Kuhn Claus , Berglund Anna-Karin , Roth Christian , Glaser Elzbieta
Published: June 2006

We have analysed 385 mitochondrial and 567 chloroplastic signal sequences of proteins found in the organellar proteomes ofArabidopsis thaliana. Despite overall similarities, the first 16 residues of transit peptides differ remarkably. To test the hypothesis that the N‐terminally truncated transit peptides would redirect chloroplastic precursor proteins to mitochondria, we studied import of the N‐terminal deletion mutants of ELIP, PetC and Lhcb2.1. The results show that the deletion mutants were neither imported into chloroplasts nor miss‐targeted to mitochondriain vitroandin vivo, showing that the entire transit peptide is necessary for correct targeting as well as miss‐sorting.
Asp‐196 → Ala mutant of Leuconostoc mesenteroides sucrose phosphorylase exhibits altered stereochemical course and kinetic mechanism of glucosyl transfer to and from phosphate
Authors: Schwarz Alexandra , Nidetzky Bernd
Published: June 2006

Mutagenesis of Asp‐196 into Ala yielded an inactive variant of Leuconostoc mesenteroides sucrose phosphorylase (D196A). External azide partly complemented the catalytic defect in D196A with a second‐order rate constant of 0.031 M−1
s−1 (pH 5, 30 °C) while formate, acetate and halides could not restore activity. The mutant utilized azide to convert α‐d‐glucose 1‐phosphate into β‐d‐glucose 1‐azide, reflecting a change in stereochemical course of glucosyl transfer from α‐retaining in wild‐type to inverting in D196A. Phosphorolysis of β‐d‐glucose 1‐azide by D196A occurred through a ternary complex kinetic mechanism, in marked contrast to the wild‐type whose reactions feature a common glucosyl enzyme intermediate and Ping‐Pong kinetics. Therefore, Asp‐196 is identified unambiguously as the catalytic nucleophile of sucrose phosphorylase, and its substitution by Ala forces the reaction to proceed via single nucleophilic displacement. D196A is not detectably active as α‐glucosynthase.
Alopecia areata: pathogenesis and potential for therapy
Authors: Lu Wei , Shapiro Jerry , Yu Mei , Barekatain Armin , Lo Blanche , Finner Andreas , McElwee Kevin
Published: June 2006

Although the complete picture for alopecia areata (AA) pathogenesis has yet to be determined, recent research has made much progress in our understanding of the disease mechanism. Numerous circumstantial evidence supports the notion that AA is fundamentally a disease mediated by inflammatory cells and may be autoimmune in nature. Recent research has shown the hair-loss phenotype is precipitated predominantly by CD8+ lymphocytes, but the disease mechanism is driven by CD4+ lymphocytes. Although genetic susceptibility is a key contributor to disease development, disease onset and phenotypic presentation are probably modified by complex environmental interplay. On the basis of our current understanding of AA disease pathogenesis, several experimental and theoretical therapeutic approaches might be possible. However, the pathogenetic disease mechanism is particularly robust and the development of a cure for AA will be a significant challenge.
Detachment shear zone of the Atlantis Massif core complex, Mid‐Atlantic Ridge, 30°N
Authors: Karson J. A. , Früh‐Green G. L. , Kelley D. S. , Williams E. A. , Yoerger D. R. , Jakuba M.
Published: June 2006

Near‐bottom investigations of the cross section of the Atlantis Massif exposed in a major tectonic escarpment provide an unprecedented view of the internal structure of the footwall domain of this oceanic core complex. Integrated direct observations, sampling, photogeology, and imaging define a mylonitic, low‐angle detachment shear zone (DSZ) along the crest of the massif. The shear zone may project beneath the nearby, corrugated upper surface of the massif. The DSZ and related structures are inferred to be responsible for the unroofing of upper mantle peridotites and lower crustal gabbroic rocks by extreme, localized tectonic extension during seafloor spreading over the past 2 m.y. The DSZ is characterized by strongly foliated to mylonitic serpentinites and talc‐amphibole schists. It is about 100 m thick and can be traced continuously for at least 3 km in the tectonic transport direction. The DSZ foliation arches over the top of the massif in a convex‐upward trajectory mimicking the morphology of the top of the massif. Kinematic indicators show consistent top‐to‐east (toward the MAR axis) tectonic transport directions. Foliated DSZ rocks grade structurally downward into more massive basement rocks that lack a pervasive outcrop‐scale foliation. The DSZ and underlying basement rocks are cut by discrete, anastomosing, normal‐slip, shear zones. Widely spaced, steeply dipping, normal faults cut all the older structures and localize serpentinization‐driven hydrothermal outflow at the Lost City Hydrothermal Field. A thin (few meters) sequence of sedimentary breccias grading upward into pelagic limestones directly overlies the DSZ and may record a history of progressive rotation of the shear zone from a moderately dipping attitude into its present, gently dipping orientation during lateral spreading and uplift.
Summertime pollution events in the Arctic and potential implications
Authors: Iziomon M. G. , Lohmann U. , Quinn P. K.
Published: June 2006

Arctic summertime aerosols are examined here on the basis of column integrated and surface aerosol measurements made at Barrow (North Slope of Alaska) between 1998 and 2003. Although the site generally exhibits low aerosol burden in the summer, events of high loadings occur 8 days per summer. During the pollution episodes, the potential source contribution function from Russia is dominant (being about 40%). The source locations in Russia are mainly situated in the central and eastern parts. South Asia, Europe and North America each contribute 6% to the observed high aerosol loading. Source locations in south Asia lie in northern China and northern Japan, while those in Europe lie mainly in northern U.K. and Estonia. The North American sources are situated in northern Canada and Alaska. Over the 6‐year period, 10 ± 4 days per summer season show elevated levels of surface aerosol absorption. The pollution events with the highest aerosol absorption appear to be associated with smoke from wild fires burning in northwest Canada. Diurnally averaged top of the atmosphere direct radiative forcing ΔFTOA (550 nm) at Barrow lie between −1.50 W m−2 and 1.19 W m−2 in summer with an annual mean of −0.53 ± 0.11 W m−2. Given low Arctic summertime surface albedo (<30%), a positive ΔFTOA results when the single scattering albedo is 0.85 or lower. Summertime direct surface radiative forcing (550 nm) ranges between −3.2 W m−2 and −29 W m−2 for observed cases of aerosol optical depth at the site.
Phase equilibrium in the system CO2‐H2O: Application to Mars
Authors: Longhi John
Published: June 2006

Thermodynamic analysis of the system CO2‐H2O shows that although CO2clathrate and liquid CO2are stable over most of the pressure and temperature range expected for the Martian regolith, hydraulic equilibrium of the regolith pore gas with the overlying atmosphere, a condition most likely in equatorial regions, will destabilize both phases. Condensation on Mars comes in four predictable assemblages: pure H2O ice, CO2clathrate (hydrate), a eutectic mixture of solid CO2and either clathrate or H2O ice (if the clathrate fails to nucleate), and under limited conditions, pure solid CO2. Seasonal frosts are likely to consist of thin layers of water ice and/or clathrate, overlain by the eutectic assemblage. Growing ice caps are also likely to be layered, with sets of ice (lower) and eutectic (upper) layers interspersed with pure solid CO2layers. The saturated water content of a 1‐bar CO2atmosphere with surface temperatures >273 K would have reached 20 precipitable millimeters. Basal melting, triggered by trapped heat flow from the interior, limits the thickness and composition of the polar ice caps and is to be expected during periods of low obliquity, when there is extensive cooling and condensation at the poles. Introduction of liquid CO2into the Martian regolith by basal melting at the poles may be a major mechanism for loss of the ancient greenhouse atmosphere and its long‐term sequestration. Explosive release of CO2fluid coexisting with groundwater may trigger outflow channel floods and reset atmospheric isotope ratios.
Tree species and moisture effects on soil sources of N2O: Quantifying contributions from nitrification and denitrification with 18O isotopes
Authors: Menyailo Oleg V. , Hungate Bruce A.
Published: June 2006

Nitrous oxide (N2O) is an important greenhouse gas and participates in the destruction of stratospheric ozone. Soil bacteria produce N2O through denitrification and nitrification, but these processes differ radically in substrate requirements and responses to the environment. Understanding the controls over N2O efflux from soils, and how N2O emissions may change with climate warming and altered precipitation, require quantifying the relative contributions from these groups of soil bacteria to the total N2O flux. Here we used ammonium nitrate (NH4NO3, including substrates for both processes) in which the nitrate has been enriched in the stable isotope of oxygen, 18O, to partition microbial sources of N2O, arguing that a molecule of N2O carrying the 18O labeled will have been produced by denitrification. We compared the influences of six common tree species on the relative contributions of nitrification and denitrification to N2O flux from soils, using soils from the Siberian afforestation experiment. We also altered soil water content, to test whether denitrification becomes a dominant source of N2O when soil water content increases. Tree species altered the proportion of nitrifier and denitrifier‐derived N2O. Wetter soils produced more N2O from denitrification, though the magnitude of this effect varied among tree species. This indicates that the roles of denitrification and nitrification vary with tree species, and, that tree species influence soil responses to increased water content.
Effect of tree line advance on carbon storage in NW Alaska
Authors: Wilmking M. , Harden J. , Tape K.
Published: June 2006

We investigated the size, distribution, and temporal dynamics of ecosystem carbon (C) pools in an area of recent tree line advance, northwest Alaska. Repeat aerial photographs show forest cover increased ∼10% in our study area since 1949. We sampled C pools of four principal ecosystem types, tussock tundra, shrub tundra, woodland, and forest, all located on a 600–800 year old river terrace. Significant differences between ecosystem C pools, both above ground and below ground existed. Tundra sites store >22.2 kg C/m2, shrub tundra sites and woodland sites store 9.7 kg C/m2 and 14.3 kg C/m2, respectively, and forest sites store 14.4 kg C/m2. Landscape variation of total ecosystem C was primarily due to organic soil C and was secondarily due to C stored in trees. Soil C/N profiles of shrub tundra sites and woodland sites showed similarities with forest site soils at surface and tundra site soils at depth. We hypothesize that tundra systems transformed to forest systems in this area under a progression of permafrost degradation and enhanced drainage. On the basis of C pool estimates for the different ecosystem types, conversion of tundra sites to forest may have resulted in a net loss of >7.8 kg C/m2, since aboveground C gains were more than offset by belowground C losses to decomposition in the tundra sites. Tree line advance therefore might not increase C storage in high‐latitude ecosystems and thus might not, as previously suggested, act as a negative feedback to warming. Key to this hypothesis and to its projection to future climate response is the fate of soil carbon upon warming and permafrost drainage.
Development of a forecasting system for supporting remediation design and process control based on NAPL‐biodegradation simulation and stepwise‐cluster analysis
Authors: Huang G. H. , Huang Y. F. , Wang G. Q. , Xiao H. N.
Published: June 2006

Effective process control is crucial in implementing remediation actions for petroleum‐contaminated sites. However, in dealing with in situ bioremediation practices, difficulties exist in incorporating numerical simulation models that are needed for process forecasting within real‐time non‐linear optimization frameworks that are critical for supporting the process control. With such difficulties, it is desired that a statistical relationship between remediation system performance and operating condition be established. Nevertheless, in the remediation systems, many variables can be either continuous or discrete, and the relations among them can be either linear or non‐linear. These lead to complexities in the related multivaraite analyses. In this study, a forecasting system has been developed for supporting remediation design and process control based on techniques of NAPL‐biodegradation (non‐aqueous phase liquid biodegradation) simulation and stepwise‐cluster analysis (SCA). The results indicate that the developed system is effective in forecasting the effects of multiple cleanup actions under various conditions. The predicted benzene concentrations have acceptable error levels compared with the outputs of numerical simulation. An optimization model for obtaining optimum operating conditions is then proposed to illustrate how the SCA method can be used for supporting optimization of bioremediation operations. A unique contribution of this research is the development of a multivariate inference system associated with simulation and optimization efforts for tackling the complex in situ bioremediation practices.
Sediment supply and local scouring at bed sills in high‐gradient streams
Authors: Marion Andrea , Tregnaghi Matteo , Tait Simon
Published: June 2006

This paper presents the results of an experimental study about the pattern of local scouring generated at the toe of bed sills, which are commonly built in steep, gravel bed mountain streams. The aim of this study is to evaluate the effect of upstream sediment supply on the scour depth and shape. The experiments simulated conditions of a steady upstream sediment supply which had the same grain size composition as the sediment deposit placed on the bed of the flume. The geometric characteristics of three scour holes developed under conditions of steady flow discharge and steady upstream sediment supply were measured during 48 different tests. This provided a data set containing measurements of 144 scour holes. Three different sediment feed rates were used, and tests were also performed with clear water conditions. Geometric interference between sills was not observed. A natural river gravel with a limited grain size was used. The collected data were analyzed using nondimensional groups developed in previous clear water studies. It is shown that the imposed sediment transport does not require the introduction of new dimensionless parameters into existing scour depth and length prediction formula. The effects of sediment feed are shown to be incorporated in the existing dimensionless parameters. The new data set was used to recalibrate existing scour depth formula. The influence of jet erosion on scour geometry is also discussed. Inspection of the data indicates a possible two‐stage behavior, with the threshold between behaviors related to the ratio of the value of the morphological jump created at a scour hole and the flow specific energy at the bed sill.