bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple, Fast, and Sensitive Method for Quantification of Tellurite in Culture Media
Authors: Molina Roberto C. , Burra Radhika , Pérez-Donoso José M. , Elías Alex O. , Muñoz Claudia , Montes Rebecca A. , Chasteen Thomas G. , Vásquez Claudio C.
Published: June 2010

A fast, simple, and reliable chemical method for tellurite quantification is described. The procedure is based on the NaBH
4
-mediated reduction of TeO
3
2−
followed by the spectrophotometric determination of elemental tellurium in solution. The method is highly reproducible, is stable at different pH values, and exhibits linearity over a broad range of tellurite concentrations.
Antibiotic Resistance Patterns and Detection ofblaDHA-1inSalmonellaSpecies Isolates from Chicken Farms in South Korea
Authors: Rayamajhi Nabin , Jung Byeong Yeal , Cha Seung Bin , Shin Min Kyung , Kim Aeran , Kang Min Su , Lee Kang Mu , Yoo Han Sang
Published: June 2010

Fifteen nonrepetitive ampicillin-resistantSalmonellaspp. were identified among 91Salmonellasp. isolates during nationwide surveillance ofSalmonellain waste from 131 chicken farms during 2006 and 2007. Additional phenotyping and genetic characterization of these 15 isolates by using indicator cephalosporins demonstrated that resistance to ampicillin and reduced susceptibility to cefoxitin in three isolates was caused by TEM-1 and DHA-1 β-lactamases. Plasmid profiling and Southern blot analysis of these three DHA-1-positiveSalmonellaserovar Indiana isolates and previously reported unrelated clinical isolates of DHA-1-positiveSalmonellaserovar Montevideo,Klebsiella pneumoniae, andEscherichia colifrom humans and swine indicated the involvement of the large-size plasmid. Restriction enzyme digestion of the plasmids from the transconjugants showed variable restriction patterns except for the twoSalmonellaserovar Indiana isolates identified in this study. To the best of our knowledge, this is the first report of the presence of the DHA-1 gene amongSalmonellaspp. of animal origin.
Contribution of SMC (Structural Maintenance of Chromosomes) and SpoIIIE to Chromosome Segregation in Staphylococci
Authors: Yu Wenqi , Herbert Silvia , Graumann Peter L. , Götz Friedrich
Published: June 2010

In contrast to rod-shaped bacteria, little is known about chromosomal maintenance and segregation in the spherical
Staphylococcus aureus
. The analysis of chromosomal segregation in
smc
(structural maintenance of chromosomes) and
spoIIIE
single and double mutants unravels differences in the chromosome dynamics in the spherical staphylococcal cells compared to the model in rods.
Carbonic Anhydrase Is Essential forStreptococcus pneumoniaeGrowth in Environmental Ambient Air
Authors: Burghout Peter , Cron Lorelei E. , Gradstedt Henrik , Quintero Beatriz , Simonetti Elles , Bijlsma Jetta J. E. , Bootsma Hester J. , Hermans Peter W. M.
Published: June 2010

The respiratory tract pathogenStreptococcus pneumoniaeneeds to adapt to the different levels of carbon dioxide (CO2) it encounters during transmission, colonization, and infection. Since CO2is important for various cellular processes, factors that allow optimal CO2sequestering are likely to be important for pneumococcal growth and survival. In this study, we showed that the putative pneumococcal carbonic anhydrase (PCA) is essential forin vitrogrowth ofS. pneumoniaeunder the CO2-poor conditions found in environmental ambient air. Enzymatic analysis showed that PCA catalyzes the reversible hydration of CO2to bicarbonate (HCO3−), an essential step to prevent the cellular release of CO2. The addition of unsaturated fatty acids (UFAs) reversed the CO2-dependentin vitrogrowth inhibition ofS. pneumoniaestrains lacking thepcagene (Δpca), indicating that PCA-mediated CO2fixation is at least associated with HCO3−-dependentde novobiosynthesis of UFAs. Besides being necessary for growth in environmental ambient conditions, PCA-mediated CO2fixation pathways appear to be required for intracellular survival in host cells. This effect was especially pronounced during invasion of human brain microvascular endothelial cells (HBMEC) and uptake by murine J774 macrophage cells but not during interaction ofS. pneumoniaewith Detroit 562 pharyngeal epithelial cells. Finally, the highly conservedpcagene was found to be invariably present in both CO2-independent and naturally circulating CO2-dependent strains, suggesting a conserved essential role for PCA and PCA-mediated CO2fixation pathways for pneumococcal growth and survival.
The MerR/NmlR Family Transcription Factor of
Streptococcus pneumoniae
Responds to Carbonyl Stress and Modulates Hydrogen Peroxide Production
Authors: Potter Adam J. , Kidd Stephen P. , McEwan Alastair G. , Paton James C.
Published: June 2010

The NmlR
sp
transcription factor of
Streptococcus pneumoniae
is shown to induce
adhC
(alcohol dehydrogenase) expression in the presence of both formaldehyde and methylglyoxal.

nmlR
sp

and
adhC
mutant strains display altered and opposite aerobic growth phenotypes. The

nmlR
sp

strain exhibits increased resistance to high oxygen tension, attributable to decreased H
2
O
2
production, which correlated with downregulation of carbamoyl phosphate synthase (
carB
). This indicates a possible role for AdhC in aldehyde metabolism and a broader role for NmlR
sp
in the regulation of carbon metabolism.
Polar Remodeling and Histidine Kinase Activation, Which Is Essential for
Caulobacter
Cell Cycle Progression, Are Dependent on DNA Replication Initiation
Authors: Iniesta Antonio A. , Hillson Nathan J. , Shapiro Lucy
Published: June 2010

Caulobacter crescentus
initiates a single round of DNA replication during each cell cycle. Following the initiation of DNA replication, the essential CckA histidine kinase is activated by phosphorylation, which (via the ChpT phosphotransferase) enables the phosphorylation and activation of the CtrA global regulator. CtrA∼P then blocks the reinitiation of replication while regulating the transcription of a large number of cell cycle-controlled genes. It has been shown that DNA replication serves as a checkpoint for flagellar biosynthesis and cell division and that this checkpoint is mediated by the availability of active CtrA. Because CckA∼P promotes the activation of CtrA, we addressed the question of what controls the temporal activation of CckA. We found that the initiation of DNA replication is a prerequisite for remodeling the new cell pole, which includes the localization of the DivL protein kinase to that pole and, consequently, the localization, autophosphorylation, and activation of CckA at that pole. Thus, CckA activation is dependent on polar remodeling and a DNA replication initiation checkpoint that is tightly integrated with the polar phospho-signaling cascade governing cell cycle progression.
Complete Genome Sequence of
Bacillus thuringiensis
Mutant Strain BMB171
Authors: He Jin , Shao Xiaohu , Zheng Huajun , Li Mingshun , Wang Jieping , Zhang Qingye , Li Lin , Liu Ziduo , Sun Ming , Wang Shengyue , Yu Ziniu
Published: June 2010

Bacillus thuringiensis
has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of
B. thuringiensis
mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory.
Diffusion weighted imaging reversibility in the brainstem following successful recanalization of acute basilar artery occlusion
Authors: Yoo Albert J , Hakimelahi Reza , Rost Natalia S , Schaefer Pamela W , Hirsch Joshua A , González R Gilberto , Rabinov James D
Published: June 2010

Acute basilar artery occlusion (ABAO) is a devastating disease that can produce significant brainstem injury. Pretreatment diffusion weighted imaging (DWI) demonstrating extensive brainstem involvement has been shown to predict a poor outcome regardless of reperfusion. This case report describes a patient presenting with coma secondary to ABAO. MRI at presentation demonstrated significant DWI abnormality in the majority of the bilateral pons. The basilar artery was endovascularly recanalized 8 h after stroke onset, and the patient had a marked clinical recovery with no deficit at 3 months. Follow-up imaging revealed significant reversal of the pontine lesion. This finding of brainstem DWI reversibility cautions against the use of DWI to select ABAO patients for intra-arterial stroke therapy. The degree of apparent diffusion coefficient reduction on pretreatment MRI may not adequately identify which DWI abnormal brainstem tissue is potentially reversible.
A MINIMAL MODEL OF LORENTZ GAUGE GRAVITY WITH DYNAMICAL TORSION
Authors: CHO Y. M. , PAK D. G. , PARK B. S.
Published: June 2010

A new Lorentz gauge gravity model with R2-type Lagrangian is proposed. In the absence of classical torsion, the model admits a topological phase with an arbitrary metric. We analyze the equations of motion in constant curvature space–time background using the Lagrange formalism and demonstrate that the model possesses a minimal set of dynamic degrees of freedom for the torsion. Surprisingly, the number of torsion dynamic degrees of freedom equals the number of physical degrees of freedom for the metric tensor. An interesting feature of the model is that the spin-2 mode of torsion becomes dynamical essentially due to the nonlinear structure of the theory. We perform covariant one-loop quantization of the model for a special case of constant curvature space–time background. We treat the contortion as a quantum field variable whereas the metric tensor is kept as a classical object. We discuss a possible mechanism of an emergent Einstein gravity as a part of the effective theory induced due to quantum dynamics of torsion.
Concept-based partitioning for large multidomain multifunctional embedded systems
Authors: Ahmed Waseem , Myers Douglas
Published: June 2010

Hardware-software partitioning is an important phase in embedded systems. Decisions made during this phase impact the quality, cost, performance, and the delivery date of the final product. Over the past decade or more, various partitioning approaches have been proposed. A majority operate at a relatively fine granularity and use a low-level executable specification as the starting point. This presents problems if the context is families of industrial products with frequent release of upgraded or new members. Managing complexity using a low-level specification is extremely challenging and impacts developer productivity. Designing using a high-level specification and component-based development, although a better option, imposes component integration and replacement problems during system evolution and new product release. A new approach termed Concept-Based Partitioning is presented that focuses on system evolution, product lines, and large-scale reuse when partitioning. Beginning with information from UML 2.0 sequence diagrams and a concept repository concepts are identified and used as the unit of partitioning within a specification. A methodology for the refinement of interpart communication in the system specification using sequence diagrams is also presented. Change localization during system evolution, composability during large-scale reuse, and provision for configurable feature variations for a product line are facilitated by a Generic Adaptive Layer (GAL) around selected concepts. The methodology was applied on a subsystem of an Unmanned Aerial Vehicle (UAV) using various concepts which improved the composability of concepts while keeping performance and size overhead within the 2% range.
Jinn
Authors: Lee Byeongcheol , Wiedermann Ben , Hirzel Martin , Grimm Robert , McKinley Kathryn S.
Published: June 2010

Programming language specifications mandate static and dynamic analyses to preclude syntactic and semantic errors. Although individual languages are usually well-specified, composing languages is not, and this poor specification is a source of many errors in
multilingual
programs. For example, virtually all Java programs compose Java and C using the Java Native Interface (JNI). Since JNI is informally specified, developers have difficulty using it correctly, and current Java compilers and virtual machines (VMs) inconsistently check only a subset of JNI constraints.

This paper's most significant contribution is to show how to synthesize dynamic analyses from state machines to detect foreign function interface (FFI) violations. We identify three classes of FFI constraints encoded by eleven state machines that capture thousands of JNI and Python/C FFI rules. We use a mapping function to specify which state machines, transitions, and program entities (threads, objects, references) to check at each FFI call and return. From this function, we synthesize a context-specific dynamic analysis to find FFI bugs. We build bug detection tools for JNI and Python/C using this approach. For JNI, we dynamically and transparently interpose the analysis on Java and C language transitions through the JVM tools interface. The resulting tool, called Jinn, is compiler and virtual machine
independent
. It detects and diagnoses a wide variety of FFI bugs that other tools miss. This approach greatly reduces the annotation burden by exploiting common FFI constraints: whereas the generated Jinn code is 22,000+ lines, we wrote only 1,400 lines of state machine and mapping code. Overall, this paper lays the foundation for a more principled approach to developing correct multilingual software and a more concise and automated approach to FFI specification.
Detecting inefficiently-used containers to avoid bloat
Authors: Xu Guoqing , Rountev Atanas
Published: June 2010

Runtime bloat degrades significantly the performance and scalability of software systems. An important source of bloat is the inefficient use of containers. It is expensive to create inefficiently-used containers and to invoke their associated methods, as this may ultimately execute large volumes of code, with call stacks dozens deep, and allocate many temporary objects.

This paper presents practical static and dynamic tools that can find inappropriate use of containers in Java programs. At the core of these tools is a base static analysis that identifies, for each container, the objects that are added to this container and the key statements (i.e., heap loads and stores) that achieve the semantics of common container operations such as
ADD
and
GET
. The static tool finds problematic uses of containers by considering the nesting relationships among the loops where these
semantics-achieving statements
are located, while the dynamic tool can instrument these statements and find inefficiencies by profiling their execution frequencies.

The high precision of the base analysis is achieved by taking advantage of a context-free language (CFL)-reachability formulation of points-to analysis and by accounting for container-specific properties. It is demand-driven and client-driven, facilitating refinement specific to each queried container object and increasing scalability. The tools built with the help of this analysis can be used both to avoid the creation of container-related performance problems early during development, and to help with diagnosis when problems are observed during tuning. Our experimental results show that the static tool has a low false positive rate and produces more relevant information than its dynamic counterpart. Further case studies suggest that significant optimization opportunities can be found by focusing on statically-identified containers for which high allocation frequency is observed at run time.
Composing parallel software efficiently with lithe
Authors: Pan Heidi , Hindman Benjamin , Asanović Krste
Published: June 2010

Applications composed of multiple parallel libraries perform poorly when those libraries interfere with one another by obliviously using the same physical cores, leading to destructive resource oversubscription. This paper presents the design and implementation of
Lithe
, a low-level substrate that provides the basic primitives and a standard interface for composing parallel codes efficiently. Lithe can be inserted underneath the runtimes of legacy parallel libraries to provide
bolt-on
composability without needing to change existing application code. Lithe can also serve as the foundation for building new parallel abstractions and libraries that automatically interoperate with one another.

In this paper, we show versions of Threading Building Blocks (TBB) and OpenMP perform competitively with their original implementations when ported to Lithe. Furthermore, for two applications composed of multiple parallel libraries, we show that leveraging our substrate outperforms their original, even expertly tuned, implementations.
Galactic Arms Race
Authors: Hastings Erin J. , Stanley Kenneth O.
Published: June 2010

Galactic Arms Race
(GAR) is an indie video game developed by the Evolutionary Complexity Research Group (EPlex) at the University of Central Florida to demonstrate the potential for novel artificial intelligence (AI) technology to impact video games. In particular, the new technology in GAR is an evolutionary algorithm called
content-generating neuroevolution of augmenting topologies
(cgNEAT), which is designed to evolve unique game content as the game is played. GAR is a multi-player space shooter in which players fight with particle-system weapons. The unique feature of GAR is that the game continually introduces new such weapons evolved by the cgNEAT algorithm. The philosophy behind GAR is that one of the best ways to support the argument that novel AI algorithms can impact how games are made is to make a fun game that is not only an academic proof-of-concept, but also a genuinely entertaining experience for regular gamers.
eNOS is required for acute in vivo ischemic preconditioning of the heart: effects of ischemic duration and sex
Authors: Talukder M. A. Hassan , Yang Fuchun , Shimokawa Hiroaki , Zweier Jay L.
Published: June 2010

Ischemic preconditioning (IPC) is a powerful phenomenon that provides potent cardioprotection in mammalian hearts; however, the role of endothelial nitric oxide (NO) synthase (eNOS)-mediated NO in this process remains highly controversial. Questions also remain regarding this pathway as a function of sex and ischemic duration. Therefore, we performed extensive experiments in wild-type (WT) and eNOS knockout (eNOS−/−) mice to evaluate whether the infarct-limiting effect of IPC depends on eNOS, ischemic periods, and sex. Classical IPC was induced by three cycles of 5 min of regional coronary ischemia separated by 5 min of reperfusion and was followed by 30 or 60 min of sustained ischemia and 24 h of reperfusion. The control ischemia-reperfusion protocol had 30 or 60 min of ischemia followed by 24 h of reperfusion. Protection was evaluated by measuring the myocardial infarct size as a percentage of the area at risk. The major findings were that regardless of sex, WT mice exhibited robust IPC with significantly smaller myocardial infarction, whereas eNOS−/−mice did not. IPC-induced cardiac protection was absent in eNOS−/−mice of both Jackson and Harvard origin. In general, female WT mice had smaller infarctions compared with male WT mice. Although prolonged ischemia caused significantly larger infarctions in WT mice of both sexes, they were consistently protected by IPC. Importantly, prolonged myocardial ischemia was associated with increased mortality in eNOS−/−mice, and the survival rate was higher in female eNOS−/−mice compared with male eNOS−/−mice. In conclusion, IPC protects WT mice against in vivo myocardial ischemia-reperfusion injury regardless of sex and ischemic duration, but the deletion of eNOS abolishes the cardioprotective effect of classical IPC.
Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes
Authors: Alloatti Giuseppe , Arnoletti Elisa , Bassino Eleonora , Penna Claudia , Perrelli Maria Giulia , Ghé Corrado , Muccioli Giampiero
Published: June 2010

Obestatin, a newly discovered peptide encoded by the ghrelin gene, induces the expression of genes regulating pancreatic β-cell differentiation, insulin biosynthesis, and glucose metabolism. It also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase (PI3K) and ERK1/2 in pancreatic β-cells and human islets. Since these kinases have been shown to protect against myocardial injury, we sought to investigate whether obestatin would exert cardioprotective effects. Both isolated perfused rat heart and cultured cardiomyocyte models of ischemia-reperfusion (I/R) were used to measure infarct size and cell apoptosis as end points of injury. The presence of specific obestatin receptors on cardiac cells as well as the signaling pathways underlying the obestatin effect were also studied. In the isolated heart, the addition of rat obestatin-(1–23) before ischemia reduced infarct size and contractile dysfunction in a concentration-dependent manner, whereas obestatin-(23–1), a synthetic analog with an inverse aminoacid sequence, was ineffective. The cardioprotective effect of obestatin-(1–23) was observed at concentrations of 10–50 nmol/l and was abolished by inhibiting PI3K or PKC by the addition of wortmannin (100 nmol/l) or chelerythrine, (5 μmol/l), respectively. In rat H9c2 cardiac cells or isolated ventricular myocytes subjected to I/R, 50 nmol/l obestatin-(1–23) reduced cardiomyocyte apoptosis and reduced caspase-3 activation; the antiapoptotic effect was blocked by the inhibition of PKC, PI3K, or ERK1/2 pathways. In keeping with these functional findings, radioreceptor binding results revealed the presence of specific high-affinity obestatin-binding sites, mainly localized on membranes of the ventricular myocardium and cardiomyocytes. Our data suggest that, by acting on specific receptors, obestatin-(1–23) activates PI3K, PKC-ε, PKC-δ, and ERK1/2 signaling and protects cardiac cells against myocardial injury and apoptosis induced by I/R.
Elucidating mechanisms of chlorine toxicity: reaction kinetics, thermodynamics, and physiological implications
Authors: Squadrito Giuseppe L. , Postlethwait Edward M. , Matalon Sadis
Published: June 2010

Industrial and transport accidents, accidental releases during recreational swimming pool water treatment, household accidents due to mixing bleach with acidic cleaners, and, in recent years, usage of chlorine during war and in acts of terror, all contribute to the general and elevated state of alert with regard to chlorine gas. We here describe chemical and physical properties of Cl2 that are relevant to its chemical reactivity with biological molecules, including water-soluble small-molecular-weight antioxidants, amino acid residues in proteins, and amino-phospholipids such as phosphatidylethanolamine and phosphatidylserine that are present in the lining fluid layers covering the airways and alveolar spaces. We further conduct a Cl2 penetration analysis to assess how far Cl2 can penetrate the surface of the lung before it reacts with water or biological substrate molecules. Our results strongly suggest that Cl2 will predominantly react directly with biological molecules in the lung epithelial lining fluid, such as low-molecular-weight antioxidants, and that the hydrolysis of Cl2 to HOCl (and HCl) can be important only when these biological molecules have been depleted by direct chemical reaction with Cl2. The results from this theoretical analysis are then used for the assessment of the potential benefits of adjuvant antioxidant therapy in the mitigation of lung injury due to inhalation of Cl2 and are compared with recent experimental results.
Sex-specific genetic dissection of diabetes in a rodent model identifies Ica1 and Ndufa4 as major candidate genes
Authors: Barkalifa Ronit , Yagil Yoram , Yagil Chana
Published: June 2010

The aim of the study was to initiate a sex-specific investigation of the molecular basis of diabetes, using a genomic approach in the Cohen Diabetic rat model of diet-induced Type 2 diabetes. We used an F2 population resulting from a cross between Cohen Diabetic susceptible (CDs) and resistant (CDr) and consisting of 132 males and 159 females to detect relevant QTLs by linkage and cosegregation analyses. To confirm the functional relevance of the QTL, we applied the “chromosome substitution” strategy. We identified candidate genes within the quantitative trait locus (QTL) and studied their differential expression. We sequenced the differentially expressed candidate genes to account for differences in their expression. We confirmed in this new cross in males a previously detected major QTL on rat chromosome 4 (RNO4); we identified in females this major QTL as well. We found three additional diabetes-related QTLs on RNO11, 13, and 20 in females only. We pursued the investigation of the QTL on RNO4 and generated a CDs.4CDr consomic strain, which provided us with functional confirmation for the contribution of the QTL to the diabetic phenotype in both sexes. We successfully narrowed the QTL span to 2.6 cM and identified within it six candidate genes, but only two of which, Ica1 (islet cell autoantigen 1) and Ndufa4 (NADH dehydrogenase ubiquinone) were differentially expressed between CDs and CDr. We sequenced the exons and promoter regions of Ica1 and Ndufa4 but did not identify sequence variations between the strains. The detection of the QTL on RNO4 in both sexes suggests involvement of Ica1, Ndufa4, the Golgi apparatus, the mitochondria and genetic susceptibility to dietary-environmental factors in the pathophysiology of diabetes in our model. The additional sex-specific QTLs are likely to account for differences in the diabetic phenotype between the sexes.
Aspirin resistance with genetic dyslipidemia: contribution of vascular thromboxane generation
Authors: Frisbee Jefferson C. , Goodwill Adam G. , Stapleton Phoebe A. , Frisbee Stephanie J. , d'Audiffret Alexandre C.
Published: June 2010

One clinical intervention against the negative outcomes associated with atherothrombotic vascular disease (AVD) is low-dose, chronic aspirin therapy. However, epidemiological studies suggest that recurrence of adverse vascular events with aspirin therapy is growing and associated with therapy duration. The contributors to this outcome are unclear and include poor patient compliance and aspirin-resistant platelet thromboxane A2 (TxA2) production. Based on previous results in hypercholesterolemic mice, we hypothesized that elevated aspirin-insensitive arachidonic acid (AA)-induced TxA2 production by the vascular endothelium contributes to aspirin resistance in AVD independent of platelet behavior. AA-induced dilation was blunted in aortic rings and in arterioles from apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) gene deletion mice (vs. C57/Bl6/J), partially due to elevated TxA2 production. Acute inhibition of cyclooxygenases or TxA2 synthase attenuated the increased TxA2 production in ApoE and LDLR and improved AA-induced dilation, responses that were mirrored by chronic treatment with low-dose aspirin of 16 wk duration. However, this effect was not temporally stable, and, with longer-duration therapy, the beneficial impact of aspirin on outcomes diminished. A similar, though less robust, pattern to the impact of chronic aspirin therapy on vascular outcomes was identified with chronic antioxidant treatment (TEMPOL). These results suggest that in dyslipidemic mice, the beneficial impact of chronic aspirin therapy on improving vascular outcomes decay with time and that a contributing element to subsequent negative vascular events may be the development of aspirin-resistant TxA2 production by the vasculature itself.
Image-Based Framework for Concrete Surface Crack Monitoring and Quantification
Authors: Chen ZhiQiang , Hutchinson Tara C.
Published: June 2010

In the engineering community, nondestructive imaging has been widely used for damage identification by capturing anomalies on the surface or inside of structural elements. In this paper, we focus on one of the most common damage types observed in civil engineering, namely, concrete surface cracks. To identify this type of damage, we propose an image-based framework, whereby optical cameras provide the source images. The framework involves several advanced image processing methods, including: (i) the determination of damage occurrence using time-series images, (ii) the localization of damage at each image frame, and (iii) the geometric quantification of damage. Challenges that may arise when images are obtained in the laboratory or field environment are addressed. Two application examples are provided to demonstrate the use and effectiveness of the proposed approach.
Eosinophilic Panniculitis and Insect Bite‐Like Eruption in a Patient with Chronic Lymphocytic Leukaemia: A Spectrum of the Same Entity
Authors: Rodríguez-Lojo R. , Almagro M. , Piñeyro F. , Pérez-Varela L. , Fernández-Jorge B. , Del Pozo J. , Sacristán F. , Fonseca E.
Published: June 2010

Background. Eosinophilic dermatosis of hematologic disorders is a reactive process that may cause a variety of clinical manifestations. Methods. We report a patient who had outbreaks of skin lesions since the onset of chronic lymphocytic leukaemia. Results. The cutaneous eruptions began as eosinophilic panniculitis and after changed to insect bite‐like lesions. Conclusion. We think that eosinophilic panniculitis and insect bite‐like lesions may be part of the spectrum of the same entity in patients with hematologic disorders.
Therapeutic Management of Hypothenar Hammer Syndrome Causing Ulnar Nerve Entrapment
Authors: Cigna Emanuele , Spagnoli Anna Maria , Tarallo Mauro , De Santo Liliana , Monacelli Giampaolo , Scuderi Nicolò
Published: June 2010

Introduction. The hypothenar hammer syndrome is a rare traumatic vascular disease of the hand.Method and Materials. We report the case of a 43-years-old man with a painful tumefaction of the left hypothenar region. The ulnar artery appeared thrombosed clinically and radiologically. The patient underwent surgery to resolve the ulnar nerve compression and revascularise the artery.Results. The symptoms disappeared immediately after surgery. The arterial flow was reestablished. Postoperatively on day 20, a new thrombosis of the ulnar artery occurred.Conclusion. Hypothenar hammer syndrome is caused by repetitive trauma to the heel of the hand. The alterations of the vessel due to its chronic inflammation caused an acute compression of the ulnar nerve at the Guyon's canal and, in our case, do not allow a permanent revascularisation of the ulnar artery.
Synthesis and Structural Characterization of a Metal Cluster and a Coordination Polymer Based on the [Mn6(μ4-O)2] 10+ Unit
Authors: Moushi Eleni E. , Tasiopoulos Anastasios J. , Manos Manolis J.
Published: June 2010

A new 1‐D coordination polymer {[Mn6O2(O2CMe) 10(H2O) 4]·2.5H2O} ∞ (1·2.5H2O) ∞ and the cluster [Mn6O2(O2(O2CPh) 10 (py) 2(MeCN)(H2O)]·2MeCN (2·2MeCN) are reported. Both compounds were synthesized by room temperature reactions of [Mn3(μ3‐O)(O2CR) 6(L) 2(L′)] (R = Me, L = L′ = py, (1·2.5H2O) ∞; R = Ph, L = py, L′ = H2O, 2·2MeCN) in the presence of 3‐hydroxymethylpyridine (3hmpH) in acetonitrile. The structures of these complexes are based on hexanuclear mixed‐valent manganese carboxylate clusters containing the [(μ4‐O) 2] 10+ structural core. (1·2.5H2O) ∞ consists of zigzag chain polymers constructed from [Mn6O2(O2CMe) 10(H2O) 4] repeating units linked through acetate ligands, whereas 2·2MeCN comprises a discrete Mn6‐benzoate cluster.
Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations
Authors: Amico Paolo , Lanzafame Salvatore , Li Destri Giovanni , Greco Paolo , Caltabiano Rosario , Vecchio Giada Maria , Magro Gaetano
Published: June 2010

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.
Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells
Authors: Ruvolo Vivian R. , Karanjeet Kul B. , Schuster Todd F. , Brown Rhoderick , Deng Yibin , Hinchcliffe Edward , Ruvolo Peter P.
Published: June 2010

The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC cleavage and protected cells from fenretinide. Suppression of PKC expression by shRNA sensitized cells to fenretinide-induced apoptosis possibly by a mechanism involving ROS production. A previous study demonstrated that fenretinide promotes degradation of antiapoptotic MCL-1 in ALL cells via JNK. Now we have found that fenretinide-induced MCL-1 degradation may involve PKC as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. These results suggest that PKC may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide.
Inflammatory Markers in Middle-Aged Obese Subjects: Does Obstructive Sleep Apnea Syndrome Play a Role?
Authors: Steiropoulos Paschalis , Papanas Nikolaos , Nena Evangelia , Antoniadou Maria , Serasli Evangelia , Papoti Sophia , Hatzizisi Olga , Kyriazis Georgios , Tzouvelekis Argyris , Maltezos Efstratios , Tsara Venetia , Bouros Demosthenes
Published: June 2010

Background. Obstructive Sleep Apnea Syndrome (OSAS) is associated with inflammation, but obesity may be a confounding factor. Thus, the aim of this study was to explore differences in serum levels of inflammation markers between obese individuals with or without OSAS.Methods. Healthy individuals (n=61) from an outpatient obesity clinic were examined by polysomnography and blood analysis, for measurement of TNF-α, IL-6, CRP, and fibrinogen levels. According to Apnea-Hypopnea Index (AHI), participants were divided into two BMI-matched groups: controls (AHI < 15/h,n=23) and OSAS patients (AHI ≥ 15/h,n=38).Results. OSAS patients had significantly higher TNF-αlevels (P<.001) while no other difference in the examined inflammation markers was recorded between groups. Overall, TNF-αlevels were correlated with neck circumference (P<.001), AHI (P=.002), and Oxygen Desaturation Index (P=.002).Conclusions. Obese OSAS patients have elevated TNF-αlevels compared to BMI-matched controls, suggesting a role of OSAS in promoting inflammation, possibly mediated by TNF-a.
Bandwidth Enhancement of Antenna Arrays Utilizing Mutual Coupling between Antenna Elements
Authors: Wang Min , Wu Wen , Shen Zhongxiang
Published: June 2010

The mutual coupling effect between antenna elements on an array's bandwidth is investigated using scattering parameters instead of the mutual impedance. First, an approximate expression is derived for matched voltage standing wave ratio (VSWR) bandwidth of a tuned antenna, which reveals that the bandwidth is inversely proportional to the magnitude|Γ0'(ω0)|of the frequency derivative of the reflection coefficient. Next, considering linear antenna arrays with corporate feed as an example, closed-form expressions of the reflection coefficient are derived at the input port of the feeding network, which shows that the active reflection coefficient of an array is the linear superposition of elements' passive reflection coefficientS11and the mutual coupling coefficientS12from adjacent elements. The VSWR bandwidth expressions for an array imply that bandwidth enhancement of the overall array can be achieved when the element passive reflection coefficientS11and mutual couplingS12are cancelled, as well as the frequency derivativesS11'andS12'also cancel each other. Slot arrays and a two-element Vivaldi array are investigated to verify the validity of our theoretical analysis. Numerical and experimental results are presented to successfully demonstrate the bandwidth enhancement of antenna arrays utilizing mutual coupling effect.
Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis
Authors: Sreekanthreddy Peddagangannagari , Srinivasan Harish , Kumar Durairaj Mohan , Nijaguna Mamatha Bangalore , Sridevi Sambandam , Vrinda Marigowda , Arivazhagan Arimappamagan , Balasubramaniam Anandh , Hegde Alangar Sathyaranjandas , Chandramouli Bangalore A. , Santosh Vani , Rao Manchanahalli R.S. , Kondaiah Paturu , Somasundaram Kumaravel
Published: June 2010

Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM).

Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients.

Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis.

Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs.

Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis. Cancer Epidemiol Biomarkers Prev; 19(6); 1409–22. ©2010 AACR.
Serum Adiponectin, Leptin, C-Peptide, Homocysteine, and Colorectal Adenoma Recurrence in the Polyp Prevention Trial
Authors: Bobe Gerd , Murphy Gwen , Rogers Connie J. , Hance Kenneth W. , Albert Paul S. , Laiyemo Adeyinka O. , Sansbury Leah B. , Lanza Elaine , Schatzkin Arthur , Cross Amanda J.
Published: June 2010

Background: Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer.

Aims: To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit and vegetable, flavonol, or dry bean intake and colorectal adenoma recurrence.

Methods: Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence.

Results: Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruit and vegetable, and flavonol intake and positively related to percentage of calories from fat (all Ptrend ≤0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile: OR, 2.26; 95% CI, 1.30-3.94) and more than one adenoma recurrence (OR, 2.11; 95% CI, 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR, 0.22; 95% CI, 0.06-0.79).

Conclusion: Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, high-fruit and vegetable, and high-flavonol diet, as well as colorectal adenoma recurrence.

Impact: Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence. Cancer Epidemiol Biomarkers Prev; 19(6); 1441–52. ©2010 AACR.
Esophageal Adenocarcinoma Incidence: Are We Reaching the Peak?
Authors: Pohl Heiko , Sirovich Brenda , Welch H. Gilbert
Published: June 2010

Background: A steep increase in the incidence of esophageal adenocarcinoma has been observed between 1973 and 2001, but recent trends have not been reported. Our aim was to examine recent trends in esophageal adenocarcinoma incidence.

Methods: We used the Surveillance Epidemiology and End Results database of the National Cancer Institute to identify all patients who were diagnosed with esophageal adenocarcinoma between 1973 and 2006. Incidence trends were analyzed for esophageal adenocarcinoma overall and by stage using joinpoint regression.

Results: Overall esophageal adenocarcinoma incidence increased from 3.6 per million in 1973 to 25.6 per million in 2006. Incidence trend analysis, however, suggests that the increase has slowed, from an 8.2% annual increase prior to 1996 to 1.3% increase in subsequent years (P = 0.03). Stage-specific trend analyses suggest that the change in overall esophageal adenocarcinoma incidence largely reflects a plateau in the incidence of early stage disease. Its slope has changed direction, from a 10% annual increase prior to 1999 to a 1.6% decline in subsequent years (P = 0.01).

Conclusions: The incidence of early stage esophageal adenocarcinoma seems to have plateaued.

Impact: Although definitive conclusions will require additional years of data, the plateau in early stage disease might portend stabilization in the overall incidence of esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 19(6); 1468–70. ©2010 AACR.
Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of the Combination of Sorafenib and Tanespimycin
Authors: Vaishampayan Ulka N. , Burger Angelika M. , Sausville Edward A. , Heilbrun Lance K. , Li Jing , Horiba M. Naomi , Egorin Merrill J. , Ivy Percy , Pacey Simon , LoRusso Patricia M.
Published: June 2010

Purpose: Heat shock protein (Hsp) 90 inhibition affects the Raf kinase signaling pathway and could enhance antitumor effects of sorafenib, a Raf kinase inhibitor. The combination of sorafenib and tanespimycin [17-allyl-amino-geldanamycin (17-AAG); NSC 330507/KOS-953] was evaluated in a phase I trial with the primary objective of defining a phase II dose.

Patients and Methods: The dose cohorts consisted of fixed continuous oral dosing of 400 mg sorafenib twice daily, starting at 14 days before tanespimycin, which was administered intravenously at escalating doses (starting at 300 mg/m,2 with 50 mg/m2 increments), on days 1, 8, and 15 in a 28-day cycle. Toxicity was assessed weekly, and response was evaluated every two cycles.

Results: Twenty-seven toxicity-evaluable patients were enrolled and treated at four dose levels. Predominant primary malignancies were renal cancer (12), melanoma (6), and colorectal cancer (4). Dose-limiting toxicities of grade 4 transaminitis and grade 3 hand-foot syndrome in one patient each were observed at 450 mg/m2 of tanespimycin. One hundred fourteen cycles were administered with a median of four cycles (range 1–17 cycles). Plasma concentrations of sorafenib and metabolites reached steady state after 7 days. Tanespimycin did not alter sorafenib concentrations. Pharmacodynamics showed a decrease in Hsp90 levels and induction of Hsp70. Clinical efficacy was observed in 9 of 12 renal cancer patients and 4 of 6 melanoma patients

Conclusions: Recommended phase II doses of this combination are 400 mg sorafenib twice daily and 400 mg/m2 tanespimycin on days 1, 8, and 15, every 28 days. Clinical and pharmacodynamic activity was observed in kidney cancer and melanoma. Clin Cancer Res; 16(14); 3795–804. ©2010 AACR.
Patients with Advanced Head and Neck Cancers Have Similar Progression-Free Survival on Phase I Trials and Their Last Food and Drug Administration–Approved Treatment
Authors: Garrido-Laguna Ignacio , Janku Filip , Falchook Gerald S. , Fu Siqing , Hong David S. , Naing Aung , Aaron Joanne , Wang Xuemei , Kies Merrill , Kurzrock Razelle
Published: June 2010

Purpose: To compare clinical outcomes of metastatic head and neck cancer patients treated in phase I clinical trials with clinical outcomes of those patients who had their last Food and Drug Administration (FDA)–approved therapy in the setting of metastatic disease.

Experimental Design: We retrospectively reviewed the outcomes of 61 consecutive patients with head and neck tumors treated in 36 phase I trials at The University of Texas M.D. Anderson Cancer Center between July 2004 and September 2009.

Results: The most common histology was head and neck squamous cell carcinoma (62%). Median age was 55 years (range, 26-80). Eastern Cooperative Oncology Group performance status was 0 to 1 for 95% of patients. Fifty-nine patients had received FDA-approved drugs as the backbone of their last systemic therapy before inclusion in phase I trials (median, 2 systemic therapies). Progression-free survival (PFS) on phase I trials was not inferior to PFS on their last FDA-approved therapies (12 versus 10.7 weeks, log-rank P = 0.87). Fifty-three patients were evaluable for response by Response Evaluation Criteria in Solid Tumors criteria. Four (7%) had partial responses and 16 (26%) had stable disease for ≥4 months. In univariate analysis, number of metastatic sites, lactate dehydrogenase (LDH) levels at baseline, and Royal Marsden Hospital prognosis scores were significant predictors of survival. Only LDH was significant in multivariate analysis (hazard ratio, 6.35; P ≤ 0.0001).

Conclusions: For patients with heavily pretreated advanced head and neck tumors, PFS on phase I trials is not inferior to PFS with their last FDA-approved therapy. The only significant predictor of survival in the multivariate analysis was baseline LDH. Clin Cancer Res; 16(15); 4031–7. ©2010 AACR.