bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of Various Special Tests Used to Determine Elastic, Plastic, and Rupture Properties of Metals at Elevated Temperatures
Authors: Garofalo F.
Published: November 2011

Testing techniques employed in determining the elastic moduli, that is, Young’s modulus, shear modulus, and Poisson’s ratio, at room and elevated temperatures are described. These techniques depend on static or dynamic measurements. A comparison and an analysis of test results determined by these two methods are presented. The effect of composition, grain size, and various transformations on the elastic moduli or their temperature dependence is discussed. A review of techniques and experimental data on the effect of high strain rates on plastic and rupture behavior of metals, and alloys at elevated temperatures is presented. It is shown that recovery effects explain qualitatively the results obtained. A brief description of the various stages of recovery is also presented. The variation of hardness with temperature is discussed for pure metals and alloys, including a description of a typical hot-hardness tester. The relationship between hardness and tensile strength, creep, and creep-rupture behavior is briefly summarised. The use of the hot-hardness tester as a research tool for following solid-state reactions at elevated temperatures is discussed. These reactions may depend on temperature, time, or plastic strain or a combination of these.
The Role of Atmosphere in the Creep-Rupture Behavior of 80 Ni-20 Cr Alloys
Authors: Widmer Robert , Grant Nicholas J.
Published: November 2011

The microstructure of several 80 Ni-20 Cr alloys was studied after creep at 1500 and 1800 F with respect to the influence of atmosphere. In particular the propagation of intercrystalline cracks was investigated. By comparison with tests conducted in argon it can be shown that the atmosphere has a strengthening effect in all cases. The mechanism of this effect changes with the variation of minor constituents in the metals (such as silicon and Mn/S ratio). Crack propagation is strongly affected by the melting process, which influences the purity of the grain boundaries.
Heat Transfer Characteristics of Compressible Laminar Flow Through Microtubes
Authors: Hong Chungpyo , Yamamoto Takaharu , Asako Yutaka , Suzuki Koichi
Published: November 2011

This paper describes experimental results on heat transfer characteristics of gaseous flow in a microtube with constant wall temperature. The experiments were performed for nitrogen gas flow through three microtubes of 123 μm, 163 μm, and 243 μm in diameter with 50mm in length, respectively. The wall temperature was maintained at 310 K, 330 K, and 350 K by circulating water around the microtube, respectively. The stagnation pressure is chosen in such a way that the exit Mach number ranges from 0.1 to 1.0. The outlet pressure was fixed at the atmospheric condition. The total temperature at the outlet, the inlet stagnation temperature, the mass flow rate, and the inlet pressure were measured. The numerical computations based on the Arbitrary-Lagrangian-Eulerian (ALE) method were also performed with the same conditions of the experiment for validation of numerical results. Both the results are in excellent agreement. In some cases, the total temperatures obtained by the present experimental study are higher than the wall temperature. This is due to the additional heat transfer from the wall to the gas near the microtube outlet caused by the temperature fall due to the energy conversion into the kinetic energy. A quantitative correlation for the prediction of the heat transfer rate of the gaseous flow in microtubes which had been proposed in our previous study (Hong and Asako, 2007, “Heat Transfer Characteristics of Gaseous Flows in a Microchannel and a Microtube with Constant Wall Temperature,” Numer. Heat Transfer, Part A, 52, pp. 219–238) was validated.
Short RNA Duplexes Elicit RIG-I–Mediated Apoptosis in a Cell Type– and Length-Dependent Manner
Authors: Ishibashi Osamu , Ali Md. Moksed , Luo Shan-Shun , Ohba Takashi , Katabuchi Hidetaka , Takeshita Toshiyuki , Takizawa Toshihiro
Published: November 2011

Short double-stranded RNAs induce death in certain cell types without knocking down gene expression.
Setting the Clock for Recirculating Lymphocytes
Authors: Eichner Alexander , Sixt Michael
Published: November 2011

Desensitization of a sphingosine 1-phosphate receptor enables lymphocytes to leave the vascular compartment.
The Oligo-Acyl Lysyl Antimicrobial Peptide C
12
K-2β
12
Exhibits a Dual Mechanism of Action and Demonstrates Strong
In Vivo
Efficacy against Helicobacter pylori
Authors: Makobongo Morris O. , Gancz Hanan , Carpenter Beth M. , McDaniel Dennis P. , Merrell D. Scott
Published: November 2011

Helicobacter pylori
has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-
H. pylori
therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C
12
K-2β
12
, that shows potent
in vitro
bactericidal activity against
H. pylori
. Herein, we define the mechanism of action and evaluate the
in vivo
efficacy of C
12
K-2β
12
against
H. pylori
after experimental infection of Mongolian gerbils. We demonstrate using a 1-
N
-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C
12
K-2β
12
rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C
12
K-2β
12
can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the
in vivo
efficacy of C
12
K-2β
12
,
H. pylori
-infected gerbils were orogastrically treated with increasing doses and concentrations of C
12
K-2β
12
1 day or 1 week postinfection. The efficacy of C
12
K-2β
12
was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (
P
< 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C
12
K-2β
12
. Overall, our results demonstrate a dual mode of action of C
12
K-2β
12
against the
H. pylori
membrane and cytoplasmic components. Moreover, and consistent with the previously reported
in vitro
efficacy, C
12
K-2β
12
shows significant
in vivo
efficacy against
H. pylori
when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of
H. pylori
infection.
Evaluation of Ceftobiprole Activity against a Variety of Gram-Negative Pathogens, Including Escherichia coli, Haemophilus influenzae (β-Lactamase Positive and β-Lactamase Negative), and Klebsiella pneumoniae, in a Rabbit Meningitis Model
Authors: Stucki A. , Cottagnoud M. , Acosta F. , Egerman U. , Läuffer J. , Cottagnoud P.
Published: November 2011

Ceftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an
Escherichia coli
strain, a
Klebsiella pneumoniae
strain, and a β-lactamase-negative
Haemophilus influenzae
strain. Against a β-lactamase-positive
H. influenzae
strain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.
Generic Vancomycin Enriches Resistant Subpopulations of Staphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model
Authors: Rodriguez Carlos A. , Agudelo Maria , Zuluaga Andres F. , Vesga Omar
Published: November 2011

Previous studies have shown that “bioequivalent” generic products of vancomycin are less effective
in vivo
against
Staphylococcus aureus
than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess
in vivo
the impact of exposure to innovator and generic products of vancomycin on
S. aureus
susceptibility. A clinical methicillin-resistant
S. aureus
(MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log
10
CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than
S. aureus
ATCC 29213 but without vancomycin-intermediate
S. aureus
(VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.
Pathophysiology of the Rhesus Macaque Model for Inhalational Brucellosis
Authors: Henning Lisa N. , Miller Stephen M. , Pak Dennis H. , Lindsay Amber , Fisher David A. , Barnewall Roy E. , Briscoe Crystal M. , Anderson Michael S. , Warren Richard L.
Published: November 2011

The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronicBrucella melitensisaerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+04, or 5.0E+05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E+05 CFU/animal or the unchallenged control). RMs given an aerosol challenge withB. melitensisdeveloped undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed toBrucellainfection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics againstB. melitensis.
A Protective Epitope in Type III Effector YopE Is a Major CD8 T Cell Antigen during Primary Infection with Yersinia pseudotuberculosis
Authors: Zhang Yue , Mena Patricio , Romanov Galina , Lin Jr-Shiuan , Smiley Stephen T. , Bliska James B.
Published: November 2011

Virulence in human-pathogenicYersiniaspecies is associated with a plasmid-encoded type III secretion system that translocates a set of Yop effector proteins into host cells. One effector, YopE, functions as a Rho GTPase-activating protein (GAP). In addition to acting as a virulence factor, YopE can function as a protective antigen. C57BL/6 mice infected with attenuatedYersinia pestisgenerate a dominant H2-Kb-restricted CD8 T cell response to an epitope in the N-terminal domain of YopE (YopE69-77), and intranasal vaccination with the YopE69-77peptide and the mucosal adjuvant cholera toxin (CT) elicits CD8 T cells that are protective against lethal pulmonary challenge withY. pestis. Because YopE69-77is conserved in manyYersiniastrains, we sought to determine if YopE is a protective antigen forYersinia pseudotuberculosisand if primary infection with this enteric pathogen elicits a CD8 T cell response to this epitope. Intranasal immunization with the YopE69-77peptide and CT elicited a CD8 T cell response that was protective against lethal intragastricY. pseudotuberculosischallenge. The YopE69-77epitope was a major antigen (∼30% of splenic CD8 T cells were specific for this peptide at the peak of the response) during primary infection withY. pseudotuberculosis, as shown by flow cytometry tetramer staining. Results of infections withY. pseudotuberculosisexpressing catalytically inactive YopE demonstrated that GAP activity is dispensable for a CD8 T cell response to YopE69-77. Determining the features of YopE that are important for this response will lead to a better understanding of how protective CD8 T cell immunity is generated againstYersiniaand other pathogens with type III secretion systems.
Resolving the genetic structure of striped marlin,Kajikia audax, in the Pacific Ocean through spatial and temporal sampling of adult and immature fish
Authors: Purcell Catherine M. , Edmands Suzanne
Published: November 2011

Spatial genetic structure in the highly migratory striped marlin ( Kajikia audax ) was examined using nuclear (microsatellite) and mitochondrial (control region sequences) DNA markers. While previous studies on striped marlin were limited by sampling design and sample size, this study employed a multiyear concurrent sampling scheme to collect tissue from seven locations representative of the species’ range in the Pacific: Japan, Hawaii, Southern California, Mexico, Central America, New Zealand, and Australia. Mature and immature specimens were analyzed separately to evaluate life-stage-specific population structure and movements. Microsatellite and sequence results revealed small but significant overall spatial subdivision (FST = 0.0145 and KST = 0.06995, respectively). Pairwise microsatellite analyses (n = 1199) revealed four groups: (1) Japan – Immature Hawaii – Southern California, (2) Mature Hawaii, (3) Mexico – Central America, and (4) Australia – New Zealand. Mitochondrial sequence analysis (n = 451) showed similar patterns; however, no significant differentiation was found between groups 1 and 2. This enhanced resolution of geographic genetic structure is important for understanding the complex migration patterns in this species. Moreover, the consistency among independent genetic studies on striped marlin provides strong support for management of at least three clearly delineated Pacific stocks.
Seasonal changes in depth distribution of salmon sharks (Lamna ditropis) in Alaskan waters: implications for foraging ecology
Authors: Carlisle Aaron B. , Perle Christopher R. , Goldman Kenneth J. , Block Barbara A.
Published: November 2011

The salmon shark, Lamna ditropis, is an endothermic, apex predator in the productive waters of the Gulf of Alaska (GOA). To understand their role in these productive habitats and to identify and better understand their interactions with commercially important species and fisheries, detailed information regarding the distribution of the salmon shark is required. Archival data records from eight recovered pop-up archival transmitting (PAT) tags were analyzed to examine the geographic and vertical distribution of female salmon sharks and elucidate how their distribution changes in relation to the biotic and abiotic environment. Tagged sharks used the neritic habitats of the GOA for the duration of the PAT deployments. Sharks exhibited a diel periodicity in their dive behavior. Salmon sharks exhibited three different patterns of depth distribution (behavioral modes) that occurred during distinct oceanographic seasons, likely reflecting changes in their foraging ecology in response to seasonal changes in the distribution and availability of important prey. The distribution of salmon sharks in the GOA appears to follow consistent patterns and has a high degree of geographical and vertical overlap with commercially important prey species. This information increases our understanding of interactions between salmon sharks and commercial fisheries and may assist in fostering responsible management for this species.
Fishing activity of tuna purse seiners estimated from vessel monitoring system (VMS) data
Authors: Bez Nicolas , Walker Emily , Gaertner Daniel , Rivoirard Jacques , Gaspar Philippe
Published: November 2011

In the lack of fishery-independent information, catch per unit of effort (CPUE) is the conventional abundance index. In the case of the tropical tuna purse seine fisheries, a critical difficulty lies in the definition of an effective fishing effort, because fishermen use two different fishing modes (free swimming schools versus schools under fish aggregating devices) alternatively during the same trip. In this study, vessel monitoring system (VMS) data were used in an operational level to study and quantify the spatial dynamic of the tropical tuna purse seine fishing activity. A Bayesian state–space model allowed classifying VMS steps into three activities (fishing, tracking, and cruising), which were characterized by a small set of complementary spatial indicators. The dominant activity (49%) was clearly the tracking of tuna schools within areas of aggregations. A hierarchical spatial organization of the three fishing activities was also evidenced. Fishing strategies described by the triplets of proportions of time devoted to each activity and interpreted as compositional data were modelled by the sum of a vessel effect and a seasonal effect.
Reconstruction of the Synthetic W7984 × Opata M85 wheat reference population
Authors: Sorrells Mark E. , Gustafson J. Perry , Somers Daryl , Chao Shiaoman , Benscher David , Guedira-Brown Gina , Huttner Eric , Kilian Andrezj , McGuire Patrick E. , Ross Kathleen , Tanaka James , Wenzl Peter , Williams Keith , Qualset Calvin O.
Published: November 2011

Reference populations are valuable resources in genetics studies for determining marker order, marker selection, trait mapping, construction of large-insert libraries, cross-referencing marker platforms, and genome sequencing. Reference populations can be propagated indefinitely, they are polymorphic and have normal segregation. Described are two new reference populations who share the same parents of the original wheat reference population Synthetic W7984 (Altar84/ Aegilops tauschii (219) CIGM86.940) × Opata M85, an F1-derived doubled haploid population (SynOpDH) of 215 inbred lines and a recombinant inbred population (SynOpRIL) of 2039 F6lines derived by single-plant self-pollinations. A linkage map was constructed for the SynOpDH population using 1446 markers. In addition, a core set of 42 SSR markers was genotyped on SynOpRIL. A new approach to identifying a core set of markers used a step-wise selection protocol based on polymorphism, uniform chromosome distribution, and reliability to create nested sets starting with one marker per chromosome, followed by two, four, and six. It is suggested that researchers use these markers as anchors for all future mapping projects to facilitate cross-referencing markers and chromosome locations. To enhance this public resource, researchers are strongly urged to validate line identities and deposit their data in GrainGenes so that others can benefit from the accumulated information.
Transcriptomic responses to aluminum stress in soybean roots
Authors: You Jiangfeng , Zhang Hongmei , Liu Ning , Gao Lingling , Kong Lingnan , Yang Zhenming
Published: November 2011

Aluminum (Al) toxicity is the primary limitation to crop production and plant growth in acid soils. Soybean has multiple mechanisms of Al resistance including the complexing and exclusion of Al in root apices by Al-induced citrate secretion. Microarray analysis is available for the identification of genes in soybean. In the present study, Affymetrix soybean genome array was used to identify the Al-induced differentially expressed genes in Al-resistant genotype Jiyu 70. With a cutoff of >2.0-fold (p < 0.05) between non Al-treated and Al-treated root apices, 561 genes were upregulated and 78 genes were downregulated when roots were exposed to 30 µmol/L AlCl3 for 4 h. Quantitative real-time PCR was used to test the microarray data. The analysis showed that nearly half of the Al-responsive genes were of unknown biological function. A higher proportion of genes related to transcription regulation and cell wall processes were observed in Al-induced up- and downregulated genes, respectively. Some genes homologous to the citrate transporter MATE family gene or C2H2 family transcription factor gene, STOP1, were detected in our analysis. Some genes related to lignin deposition were upregulated, which might be related to Al-induced root elongation inhibition.
Mechanisms and source distances for the input of large woody debris to forested streams in British Columbia, Canada
Authors: Johnston N.T. , Bird S.A. , Hogan D.L. , MacIsaac E.A.
Published: November 2011

The geomorphic process domain concept predicts consistent associations between stream channel geomorphology and large woody debris (LWD) input mechanisms. We used synoptic surveys at 51 stream reaches adjacent to undisturbed mature or old-growth forests in central and southern British Columbia to test associations between stream geomorphology and the input processes, source distances, physical characteristics, and geomorphic functions of LWD within the bankfull channel. Standing dead tree fall was the dominant input mechanism, but bank erosion was important in low- and medium-gradient channels >3 m bankfull width. Wind-induced inputs (stem breakage and windthrow) were relatively more important in small or steep channels. LWD piece size and source distance varied among delivery processes. LWD originated at ground distances up to 65 m from the streams, but 90% of the LWD at a site originated within 18 m of the channel at 90% of the sites. Statistical models incorporating tree size and stream characteristics (bankfull width, channel type) explained 40%–64% of the variation among sites in the distances from which LWD entered streams. In general, LWD source distances increased with increasing tree height and decreased with increasing stream width; however, the strengths of these relationships were modified by channel type.
Do chestnut, northern red, and white oak germinant seedlings respond similarly to light treatments? Growth and biomass
Authors: Rebbeck Joanne , Gottschalk Kurt , Scherzer Amy
Published: November 2011

Northern red oak ( Quercus rubra L.) seedling growth has been extensively studied. White oak ( Quercus alba L.) and chestnut oak ( Quercus prinus L.), however, are far less investigated despite their importance among upland oak species in eastern North American forests. We characterized white and chestnut oak seedling response to light and available soil nutrients while using northern red oak as a benchmark. Germinants were grown within one of three shade treatments (25%, 18%, and 6% of full sun) in one of two native forest soil mixes over two growing seasons. Leaf area, shoot mass, and root mass of all three species showed positive growth responses to increasing light. Growth and biomass were higher for all species grown in the more nutrient-rich forest soil, but chestnut oak displayed the greatest positive responses to the higher nutrient levels. White oak seedlings were the slowest growers and demonstrated the most root-centered growth, with root to shoot ratios almost twice that of either chestnut or northern red oak seedlings. The oak species evaluated here responded differently to changes in resource availability. Our study demonstrates the differential response of upland oaks to low light and nutrients. These differences need consideration when developing oak management prescriptions for specific oaks.
Comparing growth and mortality of a spruce budworm (Choristoneura fumiferana) inspired harvest versus a spruce budworm outbreak
Authors: Spence C. Eiry , MacLean David A.
Published: November 2011

Many current forest management regimes stress emulation of natural disturbance events, e.g., spruce budworm (SBW; Choristoneura fumiferana (Clemens)) outbreaks in a balsam fir (Abies balsamea (L.) Mill.) dominated forest, as the preferred method for ensuring sustainability of forest ecosystems. This study compared a SBW-inspired harvest treatment in 25 plots in northern New Brunswick with an uncontrolled SBW outbreak in 30 plots in the Cape Breton Highlands, Nova Scotia. Stand-level measurements before, during, and after each disturbance indicated similar reduction of living stand volume (70% reduction in emulation harvest versus 83% in SBW outbreak), mortality patterns, and lengths of disturbance (4 years of >10% mortality by density of predisturbance stand). Differences for the harvest treatment included higher cumulative postdisturbance blowdown (43% versus 8% of postdisturbance stand density), conversion to hardwood-dominated stands immediately after the disturbance, and faster growth response (immediate release of all species in the harvest treatment versus decreased balsam fir and white spruce (Picea glauca [Moench] Voss) growth and increased white birch (Betula papyrifera Marshall) growth in the SBW outbreak). There were significant differences in stand dynamics following the two disturbances. Results suggest that instead of emulating SBW disturbances, forest managers should be inspired by the spatial and temporal characteristics of SBW-defoliated stands and use significant key features of them to design harvest plans that satisfy management goals.
Changes in ash tree demography associated with emerald ash borer invasion, indicated by regional forest inventory data from the Great Lakes States
Authors: Pugh Scott A. , Liebhold Andrew M. , Morin Randall S.
Published: November 2011

The emerald ash borer (EAB) ( Agrilus planipennis Fairmaire) is a nonnative phloem-feeding beetle that was accidentally introduced near Detroit, Michigan, two to three decades ago. North American ash ( Fraxinus spp.) exhibit little or no resistance, and as this insect species expands its range, extensive mortality results. Previous studies of the impacts of EAB, typical of most insect and disease impact studies, utilized data acquired from sites with known infestations and cannot be used to make regional estimates of change on forest land. By contrast, this study investigated the regional impacts of EAB on the affected resource using information from a large-scale forest inventory (Forest Inventory and Analysis program of the US Department of Agriculture, Forest Service) previously implemented to estimate regional forest resources. Results indicate that since 1980, ash has been increasing throughout many of the Great Lakes States but EAB is reversing this trend in recently invaded areas. Within 50 km of the epicenter of the EAB invasion, a major decline was observed after 2004. For growing stock (trees at least 12.7 cm diameter at breast height), average ash volume decreased from 12.7 to 3.2 m3·ha–1and mortality increased from 0.1 to 1.4 m3·ha–1·year–1on timberland between the 2004 and 2009 inventories.
A cognitive approach for effective coding and transmission of 3D video
Authors: Milani Simone , Calvagno Giancarlo
Published: November 2011

Future multimedia applications will rely on the transmission of 3D video contents within heterogeneous fruition scenarios, and as a matter of fact, the reliable delivery of 3D video signals proves to be a crucial issue in such communications. To this purpose, multimedia communication experts have been designing cross-layer strategies to improve the quality of the perceived 3D experience. This article presents a new cross-layer strategy, called Cognitive Source Coding (CSC), that defines a new 3D video system able to identify the different elements of the 3D scene and choose the most appropriate coding strategy.
Targeting Tumor-Associated Endothelial Cells: Anti-VEGFR2 Immunoliposomes Mediate Tumor Vessel Disruption and Inhibit Tumor Growth
Authors: Wicki Andreas , Rochlitz Christoph , Orleth Annette , Ritschard Reto , Albrecht Imke , Herrmann Richard , Christofori Gerhard , Mamot Christoph
Published: November 2011

Purpose: Angiogenesis is a key process in tumor progression. By binding VEGF, VEGF receptor-2 (VEGFR2) is a main signaling transducer in tumor-associated angiogenesis. Accordingly, therapeutic approaches against the VEGF/VEGFR2 signaling axis have been designed. However, an efficient and specific chemotherapeutic targeting of tumor-associated endothelial cells has not yet been achieved.

Experimental Design: We have employed anti-VEGFR2 antibodies covalently linked to pegylated liposomal doxorubicin (PLD) to specifically ablate tumor-associated endothelial cells in the Rip1Tag2 mouse model of insulinoma, in the MMTV-PyMT mouse model of breast cancer, and in the HT-29 human colon cancer xenograft transplantation model.

Results: In each model, anti-VEGFR2–targeted immunoliposomes (ILs) loaded with doxorubicin (anti-VEGFR2-ILs-dox) were superior in therapeutic efficacy to empty liposomes, empty anti-VEGFR2-ILs, antibodies alone, and PLD. Efficacy was similar to that of the oral VEGFR1, -2, and -3 inhibitor PTK787. Detailed histopathologic and molecular analysis revealed a strong antiangiogenic effect of anti-VEGFR2-ILs-dox, and the observed antiangiogenic therapy was significantly more efficient in reducing tumor burden in well-vascularized transgenic mouse models as compared with the less-vascularized xenograft model.

Conclusions: Anti-VEGFR2 ILs provide a highly efficient approach to selectively deplete VEGFR2-expressing tumor vasculature. They offer a novel and promising anticancer strategy. Clin Cancer Res; 18(2); 454–64. ©2011 AACR.
Concurrent Temozolomide and Dose-Escalated Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma
Authors: Tsien Christina I. , Brown Doris , Normolle Daniel , Schipper Matthew , Piert Morand , Junck Larry , Heth Jason , Gomez-Hassan Diana , Ten Haken Randall K. , Chenevert Thomas , Cao Yue , Lawrence Theodore
Published: November 2011

Purpose: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of 11C methionine PET (MET-PET) imaging in predicting recurrence.

Experimental Design: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m2) followed by adjuvant cyclic temozolomide (200 mg/m2 d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure.

Results: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0–32.5) and 9.0 (6.0–11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001).

Conclusions: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions. Clin Cancer Res; 18(1); 273–9. ©2011 AACR.
Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma
Authors: Carbone Michele , Yang Haining
Published: November 2011

Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-κB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16INK4a and p14ARF are frequently inactivated in human mesothelioma, and ∼50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1β and TNF-α secretion and NF-κB activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection. Clin Cancer Res; 18(3); 598–604. ©2011 AACR.
Lung Cancer in Mice Induced by the Jaagsiekte Sheep Retrovirus Envelope Protein Is Not Maintained by Rare Cancer Stem Cells, but Tumorigenicity Does Correlate with Wnt Pathway Activation
Authors: Vaughan Andrew E. , Halbert Christine L. , Wootton Sarah K. , Miller A. Dusty
Published: November 2011

JSRV, a simple beta-retrovirus, is the etiologic agent of ovine pulmonary adenocarcinoma, a form of non–small cell lung cancer in sheep and goats. It has been shown that the envelope protein alone is sufficient to induce tumorigenesis in the lungs of mice when delivered via an adeno-associated viral vector. Here, we tested the hypothesis that JSRV envelope–induced tumors are maintained by a small population of tumor-initiating cells, termed cancer stem cells. To test this hypothesis, dissociated cancer cells were sorted from envelope-induced tumors in mouse lung based on the putative stem cell markers Sca-1, CD34, and CD133, the pluripotency-associated transcription factor Oct4, and the level of Wnt signaling. No association with increased tumor-initiating capacity was found with any of the cell-surface markers. In addition, we were unable to detect any evidence of Oct4 expression in tumor-bearing mouse lung. However, tumor cells possessing an active Wnt signaling pathway did show a significant correlation with increased tumor formation upon transplantation. Limiting dilution transplant analysis suggests the existence of a large fraction of cells with the ability to propagate tumor growth, with increasing tumor initiation potential correlating with activated Wnt signaling. Mol Cancer Res; 10(1); 86–95. ©2011 AACR.
Learning Curve and Surgical Outcome for Single-Port Access Total Laparoscopic Hysterectomy in 100 Consecutive Cases
Authors: Paek Jiheum , Kim Sang-Wun , Lee San-Hui , Lee Maria , Yim Ga-Won , Nam Eun-Ji , Kim Young-Tae
Published: November 2011

Aims: To define the learning curve for single-port access (SPA) total laparoscopic hysterectomy (TLH) and evaluate the surgical outcomes. Methods: Patient demographics and segmental operating times of all 100 patients who underwent SPA-TLH by a single surgeon were analyzed. Patients were arranged in order based on surgery date. Results: 100 patients underwent SPA-TLH. There was no conversion to conventional laparoscopy or laparotomy. The median time until the removal of a specimen (TR) was 45 min and the median time for closure of the vaginal cuff (TC) was 18 min. The median total operating time from skin opening to closure (TO) was 80 min. TR, TC, and TO decreased significantly over the study period. The TC decreased significantly from the first 20 cases to the next 20 (p = 0.028) and the TO from the second 20 cases to the next 20 (p = 0.029). Conclusions: Proficiency for SPA-TLH was achieved after 40 cases. Operating time and postoperative hemoglobin drop decreased with experience, without increasing complication.
Sarcoglycans in the Normal and Pathological Breast Tissue of Humans: An Immunohistochemical and Molecular Study
Authors: Arco Alba , Favaloro Angelo , Gioffrè Mara , Santoro Giuseppe , Speciale Francesco , Vermiglio Giovanna , Cutroneo Giuseppina
Published: November 2011

The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant.
Dental Caries Area of Rat Molar Expanded by Cigarette Smoke Exposure
Authors: Fujinami Y. , Nakano K. , Ueda O. , Ara T. , Hattori T. , Kawakami T. , Wang P.-L.
Published: November 2011

Objectives: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on caries risk and experimental dental caries. Methods: Experimental dental caries was induced in rat maxillary molars which were inoculated orally with Streptococcus mutans MT8148 and maintained on a cariogenic diet (diet 2000) and high sucrose water during the experimental period. CS-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (day 0) and for 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. Maxillary molars were harvested on day 31. Results: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rate, concentration of S. mutans in the stimulated saliva and caries activity score did not significantly differ between 0 and 30 days after the start of CS exposure. Histological examination of the caries-affected area on maxillary molars 30 days after CS exposure showed expansion compared to control rats. In the electron probe microanalysis, no differences were observed between the mineral components of the CS-exposed teeth and the control teeth. Conclusion: These results suggest that CS exposure expands the caries-affected area in the maxillary molars of the rat.
Does Surgery for Breast Cancer Induce Angiogenesis and Thus Promote Metastasis?
Authors: Park Youngjin , Kitahara Tomoaki , Takagi Ryuichi , Kato Ryoji
Published: November 2011

At the time of surgery for breast cancer, cancer cells released from the primary tumor have most likely entered blood or lymphatic vessels, leading to the development of micrometastases. Cancer cells directly produce angiogenesis stimulators, provoke the release of stimulators bound to the surrounding extracellular matrix and induce macrophages to secrete angiogenesis stimulators, thereby promoting angiogenesis. Metastasis dormancy is characterized by a balance between cell proliferation and apoptosis and is thought to be controlled by increased apoptosis, indirectly induced by angiogenesis inhibitors. Many patients with solid tumors already have micrometastases at the time of detection and surgical removal of their primary tumors. Primary tumor resection is believed to stimulate angiogenesis, initiating the proliferation of latent micrometastases. Latent micrometastases have already acquired angiogenic potential. The provision of additional therapy to inhibit angiogenesis after surgery is therefore considered a rational approach. The effectiveness of dormancy therapy should be evaluated in the prospective clinical trials of chemotherapy with drugs such as cyclophosphamide and UFT, which have been reported to inhibit angiogenesis as demonstrated by the numbers of circulating endothelial cells and circulating endothelial progenitors in peripheral blood before and after surgery in women with primary breast cancer.
Remote-Controlled Magnetic Navigation and Ablation With 3D Image Integration as an Alternative Approach in Patients With Intra-Atrial Baffle Anatomy
Authors: Ernst Sabine , Babu-Narayan Sonya V. , Keegan Jennifer , Horduna Irina , Lyne Jonathan , Till Janice , Kilner Philip J. , Pennell Dudley , Rigby Michael L. , Gatzoulis Michael A.
Published: November 2011

Background—

Improvement in outcome of infants born with congenital heart defects has been accompanied by an increasing frequency of late arrhythmias. Ablation is difficult because of multiple tachycardias in the presence of complex anatomy with limited accessibility. We report on remote-controlled ablation using magnetic navigation in conjunction with 3D image integration in patients with previous intra-atrial baffle procedures.

Methods and Results—

Thirteen patients (8 male; age, 30.5±8 years) with supraventricular tachycardia (SVT) underwent catheter ablation. Group A had a medical history of a Mustard or Senning operation, whereas group B had undergone total cavopulmonary connection. A total of 26 tachycardias were treated in 17 procedures (median cycle length of 280 ms). Group A patients had more inducible SVTs than group B, and all index SVTs were located in the remainder of the morphological right atrium in all but 1 patient. Retrograde access through the aorta was performed and led to successful ablation, using magnetic navigation with a very low total radiation exposure (median of 3.8 minutes in group A versus 5.9 minutes in group B). Only 1 of 13 patients continued to have short-lasting SVTs despite 3 ablation procedures during a median follow-up time of >200 days.

Conclusions—

Remote-controlled catheter ablation by magnetic navigation in combination with accurate 3D image integration allowed safe and successful elimination of SVTs, using an exclusively retrograde approach, resulting in low radiation exposure for patients after intra-atrial baffle procedures (Mustard, Senning, or total cavopulmonary connection).
Statin Use in Outpatients With Obstructive Coronary Artery Disease
Authors: Arnold Suzanne V. , Spertus John A. , Tang Fengming , Krumholz Harlan M. , Borden William B. , Farmer Steven A. , Ting Henry H. , Chan Paul S.
Published: November 2011

Background—

Clinical trials have shown that statin therapy reduces cardiovascular morbidity and mortality in patients with coronary artery disease (CAD), even among patients with low-density lipoprotein cholesterol levels <100 mg/dL. We sought to determine the extent to which patients with obstructive CAD in routine outpatient care are treated with statins, nonstatins, or no lipid-lowering therapy.

Methods and Results—

Within the American College of Cardiology's Practice Innovation and Clinical Excellence (PINNACLE) outpatient registry, we examined rates of treatment with statin and nonstatin medications in 38 775 outpatients with obstructive CAD (history of myocardial infarction or coronary revascularization) and without documented contraindications to statin therapy. Among these patients, 30 160 (77.8%) were prescribed statins, 2042 (5.3%) were treated only with nonstatin lipid-lowering medications, and 6573 (17.0%) were untreated. Lack of medical insurance was associated with no statin treatment, and male sex, coexisting hypertension, and a recent coronary revascularization were associated with statin treatment. Among those not on any lipid-lowering therapy, low-density lipoprotein cholesterol levels were available for 51.2% (3365/6573). Among these untreated patients, low-density lipoprotein cholesterol levels were <100 mg/dL in 1794 patients (53.3%) and ≥100 mg/dL in 1571 patients (46.7%).

Conclusions—

Despite robust clinical trial evidence, a substantial number of patients with obstructive CAD remain untreated with statins. A small proportion were treated with nonstatin therapy, and 1 in 6 patients was simply untreated; half of the untreated patients had low-density lipoprotein cholesterol values <100 mg/dL. These findings illustrate important opportunities to improve lipid management in outpatients with obstructive CAD.