bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Activation and Regulation of CXCR1 and CXCR2 by CXCL8 Monomer and Dimer
Authors: Nasser Mohd W. , Raghuwanshi Sandeep K. , Grant Delores J. , Jala Venkatakrishna R. , Rajarathnam Krishna , Richardson Ricardo M.
Published: August 2009

CXCL8 (also known as IL-8) activates CXCR1 and CXCR2 to mediate neutrophil recruitment and trigger cytotoxic effect at sites of infection. Under physiological conditions, CXCL8 could exist as monomers, dimers, or a mixture of monomers and dimers. Therefore, both forms of CXCL8 could interact with CXCR1 and CXCR2 with different affinities and potencies to mediate different cellular responses. In the present study, we have used a “trapped” nonassociating monomer (L25NMe) and a nondissociating dimer (R26C) to investigate their activities for human neutrophils that express both receptors and for RBL-2H3 cells stably expressing either CXCR1(RBL-CXCR1) or CXCR2 (RBL-CXCR2). The monomer was more active than the dimer for activities such as intracellular Ca2+ mobilization, phosphoinositide hydrolysis, chemotaxis. and exocytosis. Receptor regulation, however, is distinct for each receptor. The rate of monomer-mediated regulation of CXCR1 is greater for activities such as phosphorylation, desensitization, β-arrestin translocation, and internalization. In contrast, for CXCR2, both monomeric and dimeric CXCL8 mediate these activities to a similar extent. Interestingly, receptor-mediated signal-regulated kinase (ERK) phosphorylation in response to all three CXCL8 variants was more sustained for CXCR2 relative to CXCR1. Taken together, the results indicate that the CXCL8 monomer and dimer differentially activate and regulate CXCR1 and CXCR2 receptors. These distinct properties of the ligand and the receptors play a critical role in orchestrating neutrophil recruitment and eliciting cytotoxic activity during an inflammatory response.
A TLR2 Agonist in German Cockroach Frass Activates MMP-9 Release and Is Protective against Allergic Inflammation in Mice
Authors: Page Kristen , Ledford John R. , Zhou Ping , Wills-Karp Marsha
Published: August 2009

The role of TLR2 in modulating experimentally induced asthma is not fully understood. We recently identified that German cockroach (GC) frass contains a TLR2 ligand allowing us to investigate the role of a TLR2 agonist in a complex real world allergen in mediating allergic airway inflammation. GC frass exposure significantly increased airway inflammation, airway hyperresponsiveness and serum IgE levels in wild-type mice; however the same exposure in TLR2-deficient mice resulted in greatly exaggerated serum IgE and eosinophilia but diminished airway neutrophilia, suggesting a protective role for TLR2. Since GC frass inhalation usually induces airway neutrophilia, we queried the effect of neutrophil depletion on airway responses. Inhibition of neutrophil recruitment into the airways of naive wild-type mice before intratracheal inhalation of GC frass resulted in significantly increased levels of serum IgE and eosinophilia. Neutrophils are a rich source of MMP-9, and we found that MMP-9 levels were significantly increased in the airways of mice following exposure to GC frass. Importantly the levels of MMP-9 were significantly decreased in neutrophil-depleted and TLR2-deficient mice after exposure to GC frass, suggesting that TLR2 regulated MMP-9 release from neutrophils. Functionally, MMP-9-deficient mice had more acute allergic inflammation than wild-type mice, suggesting that MMP-9 was protective against experimentally induced asthma. These data suggest that TLR2 activation of neutrophils leads to release of MMP-9 which decreases allergic responses to GC frass. This suggests a protective role for TLR2 activation and MMP-9 release in the context of experimentally induced asthma in mice.
Renal Acid Excretion in Hypertensive Black Africans
Authors: Okpechi Ikechi G. , Kadiri Solomon , Salako Babatunde L. , Rayner Brian L.
Published: August 2009

Altered activity of the sodium-hydrogen exchanger (NHE) has been implicated in the development of hypertension. The aim of the study was to determine if the indices of urinary acid-base excretion (as markers of the NHE activity) are increased in hypertensives compared to normotensive black Africans. Sixty black African subjects (30 untreated hypertensives and 30 normotensives) were recruited for the study. All subjects collected timed 24 hour urine for quantification of the indices of acid excretion. There was no difference in all the measures of acid excretion between hyperten-sives and normotensive subjects: p=0.384 for urine pH, p=0.442 for urine ammonium, p=0.279 for urine titratable acidity and p=0.304 for total acid excretion. This suggests that there is no difference in urinary acid excretion between black hypertensives and normotensives and that the NHE may not be implicated in the genesis of hypertension in blacks.
Multidissiplinêre beskouinge op veroudering vanuit ‘n pastorale perspektief
Authors: Malan Elsona , Dreyer Yolanda
Published: August 2009

Multiprofessional aspects of ageing seen from a pastoral perspectiveThis article describes existing research on gerontology, and explores the role of pastoral care. When focusing on gerontology from a pastoral care point of view, certain multiprofessional aspects need to be considered. The article aims to highlight insights on the subject from the field of sociology, and to enable pastors to engage meaningfully with elderly persons. Reflection on the changing social environment emphasises the difficulties that retirement and the resulting loss of authenticity pose to the older person. The article considers how pastoral care as part of a multidisciplinary team could fulfil a positive role in gerontology.
Editorial for the Inaugural Issue of the International Journal of Vehicle Structures and Systems
Authors: Deb Anindya , Sahadevan Vijayakumar
Published: August 2009

Editorial forward for the inaugural issue.
Combined Applications of Test and CAE for Assessing Performance of Aircraft Windshield-Like Structures under Bird Impacts
Authors: Deb Anindya , Vijayaraju K. , Subba Reddy T.C.
Published: August 2009

The present study deals with the CAE (computer-aided engineering)-based prediction of performance of aircraft windshield-like structures under simulated bird impact following a step-by-step procedure. In the investigations carried out here, stretched polyacrylic is chosen as the windshield material. It is assumed that impact occurs at room temperature, as a majority of bird strikes would take place at low altitudes of flight. Finite element-based simulation has been carried out with the explicit code LS-DYNA. A limited number of impact tests carried out with 2 lb (0.91 kg) and 4 lb (1.82 kg) cylindrical flat-head bird specimens striking flat but inclined polyacrylic plates at 103 m/s and 173 m/s are used for validating modeling procedures. It has been found that viscoelastic modeling of gelatinous test bird using a Lagrangian mesh yields good prediction of experimentally observed bird behavior. The engineering properties of windshield material are at first verified using quasi-static plate indentation tests. These properties are further modified to account for strain rate effects under impact conditions; in particular, the expected reduction of quasi-static failure strain at high loading rates is found to be crucial in realistically predicting failure of target plate and strain time histories. The verified modeling procedure is finally used for assessing the resistance to bird strikes of polyacrylic windshield components of curved design-intent geometry.
Vibration Analysis of Composite Folded-Plate Members
Authors: Silvestre Nuno , Camotim Dinar
Published: August 2009

This paper presents the formulation of a Generalised Beam Theory (GBT) developed to analyse the vibration behaviour of composite thin-walled members made of laminated plates and displaying arbitrary orthotropy. Initially, the equilibrium equations and corresponding boundary conditions are derived and their terms are physically interpreted, i.e., related to the member mechanical properties. Then, the derived equations are used to study the local and global vibration behaviour of lipped channel members displaying cross-ply orthotropy. The GBT results are validated through a comparison with numerical values obtained from finite element analyses, which employ thin-shell elements to discretise the member. Finally, a brief investigation is carried out in order to assess the variation of the fundamental frequency value and vibration mode nature with the member length.
Dynamic Crushing Behaviour of Box Section Steel Beams
Authors: Liu Yucheng
Published: August 2009

As a popular energy absorber, steel box-sectional beams are widely used in various engineering structures. In this paper, the dynamic crushing behaviours of steel beams with box cross sections are investigated and outlined. Systematic parametric studies were conducted in order to study the effect of material properties, including strain hardening ratio and strain rate effect, length of the beam, and initial impact velocity on the crushing behaviours of the steel beams. A series of numerical models were constructed with various sets of parameters and used for crashworthiness analyses. Maximum crushing force, mean force, and specific energy absorption were recorded after analyses and compared to reveal the influences of parameters. Empirical equations were also developed based on the analyses results using nonlinear regression method, which can predict the effects of the initial impact velocity on the peak crushing forces of steel beams with box sections.
Sensing of toxic metals through pH changes using a hybrid sorbent material: Concept and experimental validation
Authors: Chatterjee Prasun K. , Sengupta Arup K.
Published: August 2009

This article reports a new hybrid sorbent material that is capable of detecting trace concentration of toxic metals, such as zinc, lead, copper, nickel, etc., through pH changes only. The material is essentially a composite granular material synthesized through rapid fusion of a mixture of amorphous hydrated ferric oxide (HFO) and akermanite or calcium magnesium silicate (Ca2MgSi2O7). When a water sample is rapidly passed through a mini‐column containing this hybrid material, effluent pH at the exit always remains alkaline (≈9.0) because of slow hydrolysis of akermanite and steady release of hydroxyl (OH−) ions. This exit solution turns pink through the addition of a phenolphthalein indicator. Commonly encountered electrolytes containing sodium, calcium, chloride, and sulfate have no impact on the exit pH from the mini‐column. However, when trace concentration of a heavy metal (say lead) is present in the sample water, a considerable drop in pH (>2 units) is observed for the exiting solution. At this point, the solution turns colorless through the addition of a phenolphthalein indicator. Moreover, the change in the slope of pH, i.e., −dpH/dBV, provides a sharp, noticeable peak for each toxic metal where BV is the bed volumes of solution fed. The technique allowed detection of zinc and lead through pH swings in synthesized samples, spiked Bethlehem City water, and also in Lehigh River water in the presence of phosphate and natural organic matter (NOM). Using a simple preconcentration technique, lower than 10 μg/l of lead was detected with a significant peak. From a mechanistic viewpoint, high sorption affinity of HFO surface sites toward toxic metal cations, ability of akermanite to maintain near‐constant alkaline pH for a prolonged period through slow hydrolysis and labile metal‐hydroxy complex formation causing dissipation of OH− ions from the aqueous phase provide a synergy that allows detection of toxic metals at concentrations well below 100 μg/l through pH changes. Nearly all previous investigations pertaining to toxic metals sensing use metal‐selective enzymes or organic chromophores. This simple‐to‐operate technique using an inexpensive hybrid material may find widespread applications in the developing world for rapid detection of toxic metals through pH changes. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Revisiting the “midtarsal break”
Authors: DeSilva Jeremy M.
Published: August 2009

The midtarsal break was first described in this journal nearly 75 years ago to explain the ability of non‐human primates to lift their heel independently of the rest of the foot. Since the initial description of the midtarsal break, the calcaneocuboid joint has been assumed to be the anatomical source of this motion. Recently, however, it has been suggested that the midtarsal break may occur at the cuboid‐metatarsal joint, rather than at the calcaneocuboid joint. Data compiled from X‐rays, dissections, manual manipulation of living primate feet, video of captive catarrhines, and osteological specimens concur that the midtarsal break is a complex motion caused by dorsiflexion at both joints with the cuboid‐metatarsal joint contributing roughly 2/3 of total midfoot dorsiflexion, and the calcaneocuboid joint only about 1/3 of total midfoot dorsiflexion. The convexity of the proximal articular surface of the fourth and fifth metatarsals and corresponding concave cuboid facets provide skeletal correlates for the presence of midfoot dorsiflexion at the cuboid‐metatarsal joint. Study of hominin metatarsals from Australopithecus afarensis, A. africanus, Homo erectus, and the metatarsals and a cuboid from the OH 8 foot show little capacity for dorsiflexion at the cuboid‐metatarsal joint. These results suggest that hominins may have already evolved a stable midfoot region well adapted for the push‐off phase of bipedalism by at least 3.2 million years ago. These data illuminate the evolution of the longitudinal arch and show further evidence of constraints on the arboreal capacity in early hominins. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.
Hierarchical modeling of genome‐wide Short Tandem Repeat (STR) markers infers native American prehistory
Authors: Lewis Cecil M.
Published: August 2009

This study examines a genome‐wide dataset of 678 Short Tandem Repeat loci characterized in 444 individuals representing 29 Native American populations as well as the Tundra Netsi and Yakut populations from Siberia. Using these data, the study tests four current hypotheses regarding the hierarchical distribution of neutral genetic variation in native South American populations: (1) the western region of South America harbors more variation than the eastern region of South America, (2) Central American and western South American populations cluster exclusively, (3) populations speaking the Chibchan‐Paezan and Equatorial‐Tucanoan language stock emerge as a group within an otherwise South American clade, (4) Chibchan‐Paezan populations in Central America emerge together at the tips of the Chibchan‐Paezan cluster. This study finds that hierarchical models with the best fit place Central American populations, and populations speaking the Chibchan‐Paezan language stock, at a basal position or separated from the South American group, which is more consistent with a serial founder effect into South America than that previously described. Western (Andean) South America is found to harbor similar levels of variation as eastern (Equatorial‐Tucanoan and Ge‐Pano‐Carib) South America, which is inconsistent with an initial west coast migration into South America. Moreover, in all relevant models, the estimates of genetic diversity within geographic regions suggest a major bottleneck or founder effect occurring within the North American subcontinent, before the peopling of Central and South America. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.
Long‐term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma
Authors: Juergens Annika , Pels Hendrik , Rogowski Sabine , Fliessbach Klaus , Glasmacher Axel , Engert Andreas , Reiser Marcel , Diehl Volker , Vogt‐Schaden Marlies , Egerer Gerlinde , Schackert Gabriele , Reichmann Heinz , Kroschinsky Frank , Bode Udo , Herrlinger Ulrich , Linnebank Michael , Deckert Martina , Fimmers Rolf , Schmidt‐Wolf Ingo G. H. , Schlegel Uwe
Published: August 2009

Objective

To evaluate long‐term progression‐free survival and overall survival, quality of life, and cognitive function in primary central nervous system lymphoma after systemic and intraventricular chemotherapy without radiotherapy.

Methods

A long‐term follow‐up was conducted on surviving primary central nervous system lymphoma patients having been enrolled in a pilot/phase II trial between September 1995 and December 2001. Initially, 65 patients (median age, 62 years) had been treated with systemic and intraventricular chemotherapy without radiotherapy. All living patients were contacted, and a neurological examination, comprehensive neuropsychological testing, quality‐of‐life assessment, and imaging were performed.

Results

Twenty‐one of all 65 patients (32 %) and 17 of 30 patients 60 years or younger (57%), respectively, were still alive at median follow‐up of 100 months (range, 77–149 months). Nineteen of 21 patients completed all investigations; 1 was lost to follow‐up. In three patients, an exclusively extraneural relapse of a high‐grade non‐Hodgkin's lymphoma was diagnosed after 9, 31, and 40 months, respectively. All of them experienced complete remission to high dose. Neither late neurotoxicity nor compromise of quality of life was found in any of the patients examined.

Interpretation

Primary polychemotherapy based on high‐dose methotrexate (MTX) and cytarabine (Ara‐C) is highly efficient in treatment of primary central nervous system lymphoma. About half of patients 60 years or younger can obviously be cured with this regimen without long‐term neurotoxic sequelae or quality‐of‐life compromise. ANN NEUROL 2010;67:182–189
Second and third hepatectomies for recurrent hepatocellular carcinoma are justified
Authors: Wu C-C , Cheng S-B , Yeh D-C , Wang J , P'eng F-K
Published: August 2009

Background

Liver resection is the main curative treatment for hepatocellular carcinoma (HCC), but recurrence rates are high. The remnant liver is the most common site of recurrence, but the role of repeat hepatectomy in the treatment of recurrent HCC is controversial.

Methods

Patients who underwent curative hepatectomy for HCC and subsequent repeat hepatectomy for recurrent HCC between 1990 and 2007 were reviewed retrospectively. Clinicopathological characteristics, and early- and long-term outcomes of patients who had a first, second, third and fourth hepatectomy were compared.

Results

Some 1177 patients underwent a first hepatectomy for HCC, and 149, 35 and eight patients respectively had a second, third and fourth hepatectomies for recurrence. There were no significant differences in early postoperative outcomes after first and repeat hepatectomies. Five-year disease-free and overall survival rates after first, second and third hepatectomies were 43·6, 31·8 and 33·8 per cent (P = 0·772), and 52·4, 56·4 and 59·4 per cent (P = 0·879), respectively. Patients undergoing second and third hepatectomies for recurrence had better survival rates than those who did not have a repeat hepatectomy, but not those after fourth hepatectomy.

Conclusion

Second and third hepatectomies seem justified for hepatic recurrence of HCC. The role of fourth hepatectomy needs further investigation.
Diagnosis and management of coagulopathy after major trauma
Authors: Brohi K
Published: August 2009

This is the third leading article in the Journal's series on major trauma. In it Karim Brohi, Professor of Trauma Sciences at Queen Mary University of London, deals with the important topic of the defects in blood coagulation that are often encountered after serious injury.
Liver regeneration and platelets
Authors: Clavien P A , Graf R
Published: August 2009

The presence of platelets is crucial
Conquer the Net: An educational computer game to learn the basic configuration of networking components
Authors: Arevalillo‐Herráez Miguel , Morán‐Gómez Raúl , Claver José M.
Published: August 2009

Advanced networking equipment is relatively expensive and student access to it is usually limited to scheduled times at computer laboratories within the university premises. Hence, it is important to make the most effective use of the time assigned and minimize the time that students spend in activities which can be performed outside the laboratory sessions. Familiarizing with the basic configuration commands is one such activity. We have developed a computer game to allow students to learn these in a motivating and pleasant environment. This game has been designed so that rules are easily learned and both cooperative and competitive learning are promoted. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 20: 72–77, 2012
Clewlike ZnV2O4 Hollow Spheres: Nonaqueous Sol–Gel Synthesis, Formation Mechanism, and Lithium Storage Properties
Authors: Xiao Lifen , Zhao Yanqiang , Yin Jia , Zhang Lizhi
Published: August 2009

Hollow ZnV2O4 microspheres with a clewlike feature were synthesized by reacting zinc nitrate hexahydrate and ammonium metavanadate in benzyl alcohol at 180 °C for the first time. GC–MS analysis revealed that the organic reactions that occurred in this study were rather different from those in benzyl alcohol based nonaqueous sol–gel systems with metal alkoxides, acetylacetonates, and acetates as the precursors. Time‐dependent experiments revealed that the growth mechanism of the clewlike ZnV2O4 hollow microspheres might involve a unique multistep pathway. First, the generation and self‐assembly of ZnO nanosheets into metastable hierarchical microspheres as well as the generation of VO2 particles took place quickly. Then, clewlike ZnV2O4 hollow spheres were gradually produced by means of a repeating reaction–dissolution (RD) process. In this process, the outside ZnO nanosheets of hierarchical microspheres would first react with neighboring vanadium ions and benzyl alcohol and also serve as the secondary nucleation sites for the subsequently formed ZnV2O4 nanocrystals. With the reaction proceeding, the interior ZnO would dissolve and then spontaneously diffuse outwards to nucleate as ZnO nanocrystals on the preformed ZnV2O4 nanowires. These renascent ZnO nanocrystals would further react with VO2 and benzyl alcohol, ultimately resulting in the final formation of a hollow spatial structure. The lithium storage ability of clewlike ZnV2O4 hollow microspheres was studied. When cycled at 50 mA g−1 in the voltage range of 0.01–3 V, this peculiarly structured ZnV2O4 electrode delivered an initial reversible capacity of 548 mAh g−1 and exhibited almost stable cycling performance to maintain a capacity of 524 mAh g−1 over 50 cycles. This attractive lithium storage performance suggests that the resulting clewlike ZnV2O4 hollow spheres are promising for lithium‐ion batteries.
Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma
Authors: Abdeen Ayesha , Chou Alexander J. , Healey John H. , Khanna Chand , Osborne Tanasa S. , Hewitt Stephen M. , Kim Mimi , Wang Dan , Moody Karen , Gorlick Richard
Published: August 2009

BACKGROUND:

Multiple cell‐signaling ligands and receptors—including vascular endothelial growth factor (VEGF), insulin‐like growth factor (IGF), endothelial growth factor (EGF), v‐akt murine thymoma viral oncogene homolog (AKT), platelet‐derived growth factor (PDGF), mitogen‐activated protein kinase (MAPK), and 70‐kilodalton (kD) protein S6 kinase (p70S6 kinase)—reportedly are variably expressed in osteogenic sarcoma. Expression of these proteins may have future implications for prognostication and targeted therapy. The objective of the current study was to determine the relation between clinical outcome and the expression of these proteins.

METHODS:

A paraffin‐embedded microarray of 48 human osteogenic sarcoma tissue specimens was stained with the antibodies against VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase. Staining for each protein included the total protein and, when applicable, the phosphorylated version of the protein. Immunohistochemical staining was then correlated with patient survival (overall survival [OS] and event‐free survival [EFS]), histologic response to chemotherapy, and serum markers.

RESULTS:

There was a negative correlation between VEGF receptor 3 (VEGF‐R3) and both OS and EFS. VEGF‐B was correlated with a poor histologic response to chemotherapy. Serum markers were not correlated with any specific proteins. When using a P value of .05, multiple correlations were observed between proteins of various pathways.

CONCLUSIONS:

The current results suggested that the VEGF pathway is a critical signaling pathway in osteogenic sarcoma. These data have identified specific proteins within these pathways toward which future investigations should be directed to further clarify their prognostic potential. Cancer 2009. Published 2009 by the American Cancer Society.
Sequential adjuvant chemotherapy after surgical resection of high‐risk urothelial carcinoma
Authors: Gallagher David J. , Milowsky Matthew I. , Iasonos Alexia , Maluf Fernando C. , Russo Paul , Dalbagni Guido , Donat Machele S. , Boyle Mary G. , Zheng Junting , Riches Jamie , Bajorin Dean F.
Published: August 2009

BACKGROUND:

Despite definitive surgery, the survival of patients with high‐risk urothelial carcinoma (UC) is poor. Adjuvant cisplatin‐based chemotherapy may be beneficial, but it is restricted by the need for normal renal function (RF). Sequential administration of adjuvant chemotherapy facilitates drug delivery and improves survival in patients with breast cancer. The objective of this study was to evaluate the feasibility and survival impact of adjuvant, sequential chemotherapy in patients with high‐risk UC.

METHODS:

Fifty patients were treated on 2 simultaneous protocols between 1997 and 2004. The patients on Protocol A (normal RF) received doxorubicin and gemcitabine (AG) followed by paclitaxel and cisplatin. The patients on Protocol B (impaired RF) received AG followed by paclitaxel plus carboplatin. Overall survival (OS) and disease‐specific survival (DSS) were compared with a group of 203 contemporary control patients who had similar pathology and RF and who underwent surgery alone.

RESULTS:

The median follow‐up of protocol patients was 6.5 years (range, 0.9‐8.6 years), and 25 patients remained alive. The median follow‐up of the control group was 4.7 years (0.0‐9.2), and 68 patients remained alive. The median OS for patients on Protocol A was greater than that for controls who had good RF (4.6 years vs 2.5 years; P = .03). The median OS for patients on Protocol B was greater than that for controls who had impaired RF (3.4 years vs 2 years; P = .04). DSS for the protocol and matched control groups was similar (good RF: 4.6 years vs 3 years; P = .24; impaired RF: 3.4 years vs 3.3 years; P = .40).

CONCLUSIONS:

In this nonrandomized study, adjuvant, sequential chemotherapy for patients with high‐risk UC did not improve DSS over that observed with surgery alone. Cancer 2009. © 2009 American Cancer Society.
Obesity as a predictor of adverse outcome across black and white race
Authors: Jayachandran Jayakrishnan , Bañez Lionel L. , Aronson William J. , Terris Martha K. , Presti Joseph C. , Amling Christopher L. , Kane Christopher J. , Freedland Stephen J. ,   the SEARCH Database Study Group
Published: August 2009

BACKGROUND:

Across multiple studies, obesity has been associated with an increased risk of higher grade disease and prostate‐specific antigen (PSA) recurrence after radical prostatectomy (RP). Whether these associations vary by race is unknown. In the current study, the authors examined the association between obesity and outcome after RP stratified by race.

METHODS:

A retrospective analysis was performed on 1415 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1989 and 2008. The association between increased body mass index (BMI) and adverse pathology and biochemical recurrence was examined using multivariate logistic regression and Cox models, respectively. Data were examined stratified by race.

RESULTS:

After adjusting for preoperative clinical characteristics, higher BMI was associated with higher tumor grade (P = .008) and positive surgical margins (P < .001) in white men, and similar but statistically nonsignificant trends were observed in black men. No significant interaction was noted between race and BMI for associations with adverse pathology (Pinteraction≥.12). After adjusting for preoperative clinical characteristics, higher BMI was associated with an increased risk of recurrence in both white men (P = .001) and black men (P = .03). After further adjusting for pathologic variables, higher BMI was associated with significantly increased risk of recurrence in white men (P = .002) and black men (P = .01). No significant interactions were observed between race and BMI for predicting biochemical progression adjusting either for preoperative factors (Pinteraction = .35) or for preoperative and pathologic features (Pinteraction = .47).

CONCLUSIONS:

Obesity was associated with a greater risk of recurrence among both black men and white men. Obesity did not appear to be more or less influential in 1 race than another but, rather, was identified as a risk factor for aggressive cancer regardless of race. Cancer 2009. © 2009 American Cancer Society.
How cancer at the primary site and in the lymph nodes contributes to the risk of cancer death
Authors: Michaelson James S. , Chen L. Leon , Silverstein Melvin J. , Mihm Martin C. , Sober Arthur J. , Tanabe Kenneth K. , Smith Barbara L. , Younger Jerry
Published: August 2009

BACKGROUND:

It has long been appreciated that tumor size, lymph node status, and patient survival are related qualities, although how to isolate their interactions has not been obvious, nor has it been obvious how to integrate tumor size and lymph node status into predictions of the risk of death for individual patients.

METHODS:

The authors describe a mathematical method, the binary‐biological model of cancer metastasis, based on the spread of cancer cells, in which the equations capture the relations between tumor size, lymph node status, and cancer lethality.

RESULTS:

For melanoma, renal cell carcinoma, and breast carcinoma, the relation between tumor size and the risk of cancer death was captured by the SizeOnly equation. For melanoma and breast carcinoma, the relation between tumor size and the presence of cancer in the lymph nodes was captured by using the NodalSizeOnly equation. For lymph node‐negative melanoma and breast carcinoma, the relation between tumor size and risk of death was captured by the PrimarySizeOnly equation. For breast carcinoma, the model indicated that each positive lymph node contributed ∼6% extra risk of death, whereas each millimeter of greatest primary tumor dimension contributed ∼1% risk of death. For melanoma, each positive lymph node contributed ∼23% risk of death, whereas each millimeter of primary melanoma thickness contributed ∼8% risk of death. This information was captured by a pair of linked equations, the Size+Nodes method.

CONCLUSIONS:

Both tumor size and the number of positive lymph nodes made independent contributions to the risk of cancer death, as estimated by using the Size+Nodes method. Cancer 2009. © 2009 American Cancer Society.
The dual dopamine‐glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain
Authors: Bérubé‐Carrière Noémie , Riad Mustapha , Dal Bo Grégory , Lévesque Daniel , Trudeau Louis‐Éric , Descarries Laurent
Published: August 2009

Coexpression of tyrosine hydroxylase (TH) and vesicular glutamate transporter 2 (VGLUT2) mRNAs in the ventral tegmental area (VTA) and colocalization of these proteins in axon terminals of the nucleus accumbens (nAcb) have recently been demonstrated in immature (15‐day‐old) rat. After neonatal 6‐hydroxydopamine (6‐OHDA) lesion, the proportion of VTA neurons expressing both mRNAs and of nAcb terminals displaying the two proteins was enhanced. To determine the fate of this dual phenotype in adults, double in situ hybridization and dual immunolabeling for TH and VGLUT2 were performed in 90‐day‐old rats subjected or not to the neonatal 6‐OHDA lesion. Very few neurons expressed both mRNAs in the VTA and substantia nigra (SN) of P90 rats, even after neonatal 6‐OHDA. Dually immunolabeled terminals were no longer found in the nAcb of normal P90 rats and were exceedingly rare in the nAcb of 6‐OHDA‐lesioned rats, although they had represented 28% and 37% of all TH terminals at P15. Similarly, 17% of all TH terminals in normal neostriatum and 46% in the dopamine neoinnervation of SN in 6‐OHDA‐lesioned rats were also immunoreactive for VGLUT2 at P15, but none at P90. In these three regions, all dually labeled terminals made synapse, in contradistinction to those immunolabeled for only TH or VGLUT2 at P15. These results suggest a regression of the VGLUT2 phenotype of dopamine neurons with age, following normal development, lesion, or sprouting after injury, and a role for glutamate in the establishment of synapses by these neurons. J. Comp. Neurol. 517:873–891, 2009. © 2009 Wiley‐Liss, Inc.
The Lee‐Yang and Pólya‐Schur programs. II. Theory of stable polynomials and applications
Authors: Borcea Julius , Brändén Petter
Published: August 2009

In the first part of this series we characterized all linear operators on spaces of multivariate polynomials preserving the property of being nonvanishing in products of open circular domains. For such sets this completes the multivariate generalization of the classification program initiated by Pólya and Schur for univariate real polynomials. We build on these classification theorems to develop here a theory of multivariate stable polynomials. Applications and examples show that this theory provides a natural framework for dealing in a uniform way with Lee‐Yang type problems in statistical mechanics, combinatorics, and geometric function theory in one or several variables. In particular, we answer a question of Hinkkanen on multivariate apolarity. © 2009 Wiley Periodicals, Inc.
Scheduling dense linear algebra operations on multicore processors
Authors: Kurzak Jakub , Ltaief Hatem , Dongarra Jack , Badia Rosa M.
Published: August 2009

State‐of‐the‐art dense linear algebra software, such as the LAPACK and ScaLAPACK libraries, suffers performance losses on multicore processors due to their inability to fully exploit thread‐level parallelism. At the same time, the coarse–grain dataflow model gains popularity as a paradigm for programming multicore architectures. This work looks at implementing classic dense linear algebra workloads, the Cholesky factorization, the QR factorization and the LU factorization, using dynamic data‐driven execution. Two emerging approaches to implementing coarse–grain dataflow are examined, the model of nested parallelism, represented by the Cilk framework, and the model of parallelism expressed through an arbitrary Direct Acyclic Graph, represented by the SMP Superscalar framework. Performance and coding effort are analyzed and compared against code manually parallelized at the thread level. Copyright © 2009 John Wiley & Sons, Ltd.
Vascular endothelial growth factor prevents G93A‐SOD1‐induced motor neuron degeneration
Authors: Lunn J. Simon , Sakowski Stacey A. , Kim Bhumsoo , Rosenberg Andrew A. , Feldman Eva L.
Published: August 2009

Amyotrophic lateral sclerosis (ALS) is an adult‐onset neurodegenerative disorder characterized by selective loss of motor neurons (MNs). Twenty percent of familial ALS cases are associated with mutations in Cu2+/Zn2+ superoxide dismutase (SOD1). To specifically understand the cellular mechanisms underlying mutant SOD1 toxicity, we have established an in vitro model of ALS using rat primary MN cultures transfected with an adenoviral vector encoding a mutant SOD1, G93A‐SOD1. Transfected cells undergo axonal degeneration and alterations in biochemical responses characteristic of cell death such as activation of caspase‐3. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can increase axonal outgrowth, block neuronal apoptosis, and promote neurogenesis. Decreased VEGF gene expression in mice results in a phenotype similar to that seen in patients with ALS, thus linking loss of VEGF to the pathogenesis of MN degeneration. Decreased neurotrophic signals prior to and during disease progression may increase MN susceptibility to mutant SOD1‐induced toxicity. In this study, we demonstrate a decrease in VEGF and VEGFR2 levels in the spinal cord of G93A‐SOD1 ALS mice. Furthermore, in isolated MN cultures, VEGF alleviates the effects of G93A‐SOD1 toxicity and neuroprotection involves phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt) signaling. Overall, these studies validate the usefulness of VEGF as a potential therapeutic factor for the treatment of ALS and give valuable insight into the responsible signaling pathways and mechanisms involved. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009
A clinical perspective of rheumatoid arthritis
Authors: Scherer Hans Ulrich , Burmester Gerd R.
Published: August 2009

In recent years, factors potentially involved in pathogenesis of rheumatoid arthritis have mostly been identified by studying well‐defined patient cohorts. Characterization of antibodies from sera of affected patients, family‐based heritability studies, genome‐wide association scans, the analysis of environmental factors and data from clinical trials have contributed largely to a thorough reassembly of our perception of rheumatoid arthritis. Modified animal models are now crucial to obtain experimental evidence for suggested pathogenetic pathways based on these observations and are currently being developed and explored. Some of the novel pathogenetic aspects, however, already influence decision making in the clinic.
The road not taken: A path to curing type 1 diabetes?
Authors: Haller Michael J. , Atkinson Mark A. , Schatz Desmond A.
Published: August 2009

The past quarter century has seen a rapid increase in our knowledge about the natural history of autoimmune type 1 diabetes. However, we stand unable to achieve our ultimate goal of preventing or reversing this disease. This viewpoint discusses controversies in current management of type 1 diabetes, the challenges in translating promising studies from mouse models of the disease to humans, hurdles faced in designing optimal prevention and intervention studies, and potential strategies to overcome these obstacles.

“....Two roads diverged in a wood, and I‐I took the one less traveled by, And that has made all the difference.”

 ‐The Road Not Taken

 Robert Frost, 1920
Animal models of tuberculosis
Authors: Young Douglas
Published: August 2009

There is a wide range of animal models of tuberculosis; which is fortunate, given that there is a wide range of complex biological phenomena to model. Nonetheless, the inadequacy of animal models is a chronic grievance amongst researchers, often expressed in the conclusion that the mouse is not a good model of human tuberculosis. There clearly are major differences between experimental infection of mice and natural infection of humans, but this overarching dogma is inconducive to fruitful research.
EAE: An immunologist's magic eye
Authors: Krishnamoorthy Gurumoorthy , Wekerle Hartmut
Published: August 2009

EAE comes in many shapes and colors. Individual variants of EAE present a baffling complexity of different aspects and traits, clinical, immunological, and structural. But, embedded in this seemingly chaotic image, the educated eye will discern patterns that retrace fundamental features of immune response, in particular, autoimmunity and self‐tolerance. EAE and its variants thus can be likened to an autostereogram, i.e. they are an immunologist's magic eye.
Clinical aspects of inflammatory bowel disease
Authors: Siegmund Britta , Zeitz Martin
Published: August 2009

Inflammatory bowel disease (IBD) accompanies its patients throughout life. Current treatment options do not lead to a cure and are accompanied by significant toxicities. Numerous animal models contributed to the understanding of the pathogenesis of the disease and led to the development of novel treatment strategies. Genome‐wide association analysis added a novel dimension. Here, we discuss how characterization of mutated genes in animal models supports the identification of future therapeutic targets.
Cover Picture: Eur. J. Immunol. 8/09
Authors: Hohlfeld Reinhard
Published: August 2009

The set of scales characterising the differing, but balanced perspectives, of Viewpoint articles forms a distinctive component of the cover image. Combined with the scales is an image taken from the Viewpoint article by Hohlfeld (pp. 2036–2039) that depicts, in cartoon form, the immunopathogenesis of multiple sclerosis. The cartoon portrays activated autoreactive T cells crossing the blood‐brain barrier where, following re‐stimulation, these cells stimulate processes leading to myelin and axon damage. The cartoon is modified from Gijbels K. PhD thesis University of Louvain, 1995 and Hohlfeld, R. Brain 1997. 120: 865–916 and reprinted with permission.
Syntheses and Structures of Tris‐β‐Diketiminate Lanthanide Complexes and Their High Activity for Ring‐Opening Polymerization of ϵ‐Caprolactone and L‐Lactide
Authors: Xue Mingqiang , Jiao Rui , Zhang Yong , Yao Yingming , Shen Qi
Published: August 2009

Metathesis of {[(4–XC6H4)NC(Me)]2CH}Li with anhydrous lanthanide trichlorides (LnCl3) in a 3:1 molar ratio yielded a series of tris‐β‐diketiminate complexes with the general formula [LnLX3] [X = Cl, LCl: Ln = Pr (1), Nd (2), Sm (3); X = H, L: Ln = Nd (4); X = Me, LMe: Ln = Nd (5)]. Reaction of sodium salt of β‐diketiminate with anhydrous LnCl3 in a 1:1 molar ratio in thf afforded the corresponding β‐diketiminate lanthanide dichlorides [LClPrCl2(thf)2] (6), [LMeNdCl2(thf)2] (7), and [LNdCl2(thf)2] {L = [(2,6‐iPr2C6H3)NC(Me)]2CH–} (8), respectively. Each of these complexes was characterized, and the molecular structures of complexes 1–5 and 8 were determined by X‐ray single‐crystal structure analysis. Complexes 1–5 were found to be very active single‐component initiators for the ring‐opening polymerization of ϵ‐caprolactone (ϵ‐CL) and L‐lactide (L‐LA) under mild conditions, giving polymers with high molecular weight and moderate polydispersities, whereas complexes 6–8 displayed no activity under the same polymerization conditions. The high catalytic activity shown by tris‐β‐diketiminate lanthanide complexes may be attributed to the activated Ln–β‐diketiminate bond caused by the crowded coordination sphere around the central metal.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Temporary Protection of H‐Phosphinic Acids as a Synthetic Strategy
Authors: Coudray Laëtitia , Montchamp Jean‐Luc
Published: August 2009

H‐Phosphinates obtained through various methodologies are protected directly by the reaction with triethyl orthoacetate. The resulting products can be manipulated easily, andvarious synthetic reactions are presented. For example, application to the synthesis of aspartate transcarbamoylase (ATCase) or kynureninase inhibitors are illustrated. Other reactions, such as Sharpless' asymmetric dihydroxylation, or Grubbs' olefin cross‐metathesis are also demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Numerical study of the turbulent flow in strongly curved stationary and rotating U‐ducts
Authors: Guleren K. Melih
Published: August 2009

A large‐eddy simulation (LES) study is undertaken to explore the complex flow of developing turbulent flow through stationary and rotating U‐ducts with strong curvature. Three flow cases are investigated: stationary (non‐rotating), positive and negative rotational cases. Stationary and positive rotational cases are shown to have similar flow characteristics in terms of the mean velocity variations, although the predicted separation zone is nearly doubled in size for positive rotational case. Unlike the positive rotation for which the laminarization effects are observed, turbulence is significantly enhanced for the negative rotation mainly due to the existence of strong secondary flow. Turbulence is found to be highly anisotropic throughout the duct apart from the far downstream regions of the bend for the negative rotational case. The stress–strain relation seems to be completely invalid in the U‐duct apart from the bend region. Copyright © 2009 John Wiley & Sons, Ltd.
Rearrangement of upstream sequences of the hTERT gene during cellular immortalization
Authors: Zhao Yuanjun , Wang Shuwen , Popova Evgenya Y. , Grigoryev Sergei A. , Zhu Jiyue
Published: August 2009

Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase‐negative (Tel−) and ‐positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental precrisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. © 2009 Wiley‐Liss, Inc.
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Authors: Zhao Weihua , Beers David R. , Henkel Jenny S. , Zhang Wei , Urushitani Makoto , Julien Jean‐Pierre , Appel Stanley H.
Published: August 2009

Through undefined mechanisms, dominant mutations in (Cu/Zn) superoxide dismutase‐1 (mSOD1) cause the non‐cell‐autonomous death of motoneurons in inherited amyotrophic lateral sclerosis (ALS). Microgliosis at sites of motoneuron injury is a neuropathological hallmark of ALS. Extracellular mutant SOD1 (mSOD1) causes motoneuron injury and triggers microgliosis in spinal cord cultures, but it is unclear whether the injury results from extracellular mSOD1 directly interacting with motoneurons or is mediated through mSOD1‐activated microglia. To dissociate these potential mSOD1‐mediated neurotoxic mechanisms, the effects of extracellular human mSOD1G93A or mSOD1G85R were assayed using primary cultures of motoneurons and microglia. The data demonstrate that exogenous mSOD1G93A did not cause detectable direct killing of motoneurons. In contrast, mSOD1G93A or mSOD1G85R did induce the morphological and functional activation of microglia, increasing their release of pro‐inflammatory cytokines and free radicals. Furthermore, only when microglia was co‐cultured with motoneurons did extracellular mSOD1G93A injure motoneurons. The microglial activation mediated by mSOD1G93A was attenuated using toll‐like receptors (TLR) 2, TLR4 and CD14 blocking antibodies, or when microglia lacked CD14 expression. These data suggest that extracellular mSOD1G93A is not directly toxic to motoneurons but requires microglial activation for toxicity, utilizing CD14 and TLR pathways. This link between mSOD1 and innate immunity may offer novel therapeutic targets in ALS. © 2009 Wiley‐Liss, Inc.