bluuebunny/crossref_metadata_2025 huggingface dataset:
AN ANALYTICAL SOLUTION FOR OPTIMUM DESIGN OF SHRINK-FIT MULTI-LAYER COMPOUND CYLINDERS
Authors: SHARIFI M. , ARGHAVANI J. , HEMATIYAN M. R.
Published: December 2012

In this paper, employing an analytical method, optimum design of multi-layer compound cylinders is investigated. To this end, considering Tresca criterion, maximum shear stress in each layer is minimized. Analytical relations for optimum values of a layer dimension, residual pressures and radial interferences are derived. A technique for shrink-fitting of layers is also proposed and relationships for radial interferences, residual pressures and required temperature differences during the shrink-fitting process are derived. Three different examples are presented to show the effectiveness of the proposed method. It is shown that increasing the number of layers makes shear stress distribution near to uniform. As a result, with specified maximum shear stress and inner radius, the weight of compound cylinder is decreased when the number of layers is increased. Moreover, compound cylinders with more layers have lower maximum shear stress for a specified weight. It is also concluded that if the ratio of outer to inner radii be larger, increasing the number of layers is more effective.
Notes on Lower Devonian crinoids in the collections of the British Geological Survey, Keyworth
Authors: Donovan Stephen K.
Published: December 2012

Lower Devonian crinoids are poorly known from the British Isles. The British Geological Survey, Geological Survey Museum collection of Lower Devonian crinoids, mainly made by amateur collectors in the 19th century, is described for the first time. Taxa include
Hexacrinites
sp. A,
Hexacrinites
sp. B,
Floricrinus
(col.)
priscus
(Goldfuss) (probably Middle Devonian) and
Bystrowicrinus
(col.) sp.
sensu lato
; some nautiloids were misidentified as crinoids.
Hexacrinites
is moderately speciose in the Middle Devonian of SW England; columnals described herein extend this record into the Lower Devonian (Emsian).
Pentacrinus priscus
Goldfuss, erroneously included in a Mesozoic genus for over 180 years ago, is reclassified within the Devonian morphogenus
Floricrinus
(col.) Stukalina. Both
F
. (col.)
priscus
and
Bystrowicrinus
(col.) sp. represent columnal morphologies similar to some crinoids locally common in the Upper Ordovician, but unknown from the Silurian of the British Isles.
New perspectives on the globally important Ediacaran fossil discoveries in Charnwood Forest, UK: prequel to
Authors: Howe Mike P.A. , Evans Mark , Carney John N. , Wilby Philip R.
Published: December 2012

The study of latest Neoproterozoic fossils that comprise the Ediacara biota is a relatively new frontier of palaeontology. That it started when it did is due, in no small measure, to the discovery of macrofossils in Charnwood Forest in 1957, and their description in a paper to the
Proceedings of the Yorkshire Geological Society
by Trevor Ford in 1958. There is a prequel to this, however. We reveal newly found correspondence showing that as long ago as 1848 enterprising naturalists had seen these macrofossils and recognized them as such. The subsequent rejection of those finds by others mirrors the experiences of geologists elsewhere in the world, and is attributed to a previously received wisdom that macrofossils only occurred in Cambrian or younger strata.
Thermoneutrality modifies the impact of hypoxia on lipid metabolism
Authors: Jun Jonathan C. , Shin Mi-Kyung , Yao Qiaoling , Devera Ronald , Fonti-Bevans Shannon , Polotsky Vsevolod Y.
Published: December 2012

Hypoxia has been shown to rapidly increase triglycerides in mice by decreasing plasma lipoprotein clearance. However, the usual temperature of hypoxic exposure is below thermoneutrality for mice, which may increase thermogenesis and energy requirements, resulting in higher tissue lipid uptake. We hypothesize that decreased lipid clearance and ensuing hyperlipidemia are caused by hypoxic suppression of metabolism at cold temperatures and, therefore, would not occur at thermoneutrality. Twelve-week-old, male C57BL6/J mice were exposed to 6 h of 10% O2at the usual temperature (22°C) or thermoneutrality (30°C). Acclimation to 22°C increased lipid uptake in the heart, lungs, and brown adipose tissue, resulting in lower plasma triglyceride and cholesterol levels. At this temperature, hypoxia attenuated lipid uptake in most tissues, thereby raising plasma triglycerides and LDL cholesterol. Thermoneutrality decreased tissue lipid uptake, and hypoxia did not cause a further reduction in lipid uptake in any organs. Consequently, hypoxia at thermoneutrality did not affect plasma triglyceride levels. Unexpectedly, plasma HDL cholesterol increased. The effect of hypoxia on white adipose tissue lipolysis was also modified by temperature. Independent of temperature, hypoxia increased heart rate and glucose and decreased activity, body temperature, and glucose sensitivity. Our study underscores the importance of ambient temperature for hypoxia research, especially in studies of lipid metabolism.
Stability Analysis of an HIV/AIDS Dynamics Model with Drug Resistance
Authors: Li Qianqian , Cao Shengshan , Chen Xiao , Sun Guiquan , Liu Yunxi , Jia Zhongwei
Published: December 2012

A mathematical model of HIV/AIDS transmission incorporating treatment and drug resistance was built in this study. We firstly calculated the threshold value of the basic reproductive number (R0) by the next generation matrix and then analyzed stability of two equilibriums by constructing Lyapunov function. When R0 < 1, the system was globally asymptotically stable and converged to the disease‐free equilibrium. Otherwise, the system had a unique endemic equilibrium which was also globally asymptotically stable. While an antiretroviral drug tried to reduce the infection rate and prolong the patients’ survival, drug resistance was neutralizing the effects of treatment in fact.
Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease
Authors: Tate Barbara , McKee Timothy D. , Loureiro Robyn M. B. , Dumin Jo Ann , Xia Weiming , Pojasek Kevin , Austin Wesley F. , Fuller Nathan O. , Hubbs Jed L. , Shen Ruichao , Jonker Jeff , Ives Jeff , Bronk Brian S.
Published: December 2012

The Amyloid Hypothesis states that the cascade of events associated with Alzheimer's disease (AD)—formation of amyloid plaques, neurofibrillary tangles, synaptic loss, neurodegeneration, and cognitive decline—are triggered by Aβpeptide dysregulation (Kakuda et al., 2006, Sato et al., 2003, Qi-Takahara et al., 2005). Sinceγ-secretase is critical for Aβproduction, many in the biopharmaceutical community focused onγ-secretase as a target for therapeutic approaches for Alzheimer's disease. However, pharmacological approaches to controlγ-secretase activity are challenging because the enzyme has multiple, physiologically critical protein substrates. To lower amyloidogenic Aβpeptides without affecting otherγ-secretase substrates, the epsilon (ε) cleavage that is essential for the activity of many substrates must be preserved. Small molecule modulators ofγ-secretase activity have been discovered that spare theεcleavage of APP and other substrates while decreasing the production of Aβ42. Multiple chemical classes ofγ-secretase modulators have been identified which differ in the pattern of Aβpeptides produced. Ideally, modulators will allow theεcleavage of all substrates while shifting APP cleavage from Aβ42and other highly amyloidogenic Aβpeptides to shorter and less neurotoxic forms of the peptides without altering the total Aβpool. Here, we compare chemically distinct modulators for effects on APP processing andin vivoactivity.
New Platform Technology for Comprehensive Serological Diagnostics of Autoimmune Diseases
Authors: Willitzki Annika , Hiemann Rico , Peters Vanessa , Sack Ulrich , Schierack Peter , Rödiger Stefan , Anderer Ursula , Conrad Karsten , Bogdanos Dimitrios P. , Reinhold Dirk , Roggenbuck Dirk
Published: December 2012

Antibody assessment is an essential part in the serological diagnosis of autoimmune diseases. However, different diagnostic strategies have been proposed for the work up of sera in particular from patients with systemic autoimmune rheumatic disease (SARD). In general, screening for SARD-associated antibodies by indirect immunofluorescence (IIF) is followed by confirmatory testing covering different assay techniques. Due to lacking automation, standardization, modern data management, and human bias in IIF screening, this two-stage approach has recently been challenged by multiplex techniques particularly in laboratories with high workload. However, detection of antinuclear antibodies by IIF is still recommended to be the gold standard method for antibody screening in sera from patients with suspected SARD. To address the limitations of IIF and to meet the demand for cost-efficient autoantibody screening, automated IIF methods employing novel pattern recognition algorithms for image analysis have been introduced recently. In this respect, the AKLIDES technology has been the first commercially available platform for automated interpretation of cell-based IIF testing and provides multiplexing by addressable microbead immunoassays for confirmatory testing. This paper gives an overview of recently published studies demonstrating the advantages of this new technology for SARD serology.
The Nanofabrication and Application of Substrates for Surface-Enhanced Raman Scattering
Authors: Zhang Xian , Zhou Qin , Huang Yu , Li Zhengcao , Zhang Zhengjun
Published: December 2012

Surface-enhanced Raman scattering (SERS) was discovered in 1974 and impacted Raman spectroscopy and surface science. Although SERS has not been developed to be an applicable detection tool so far, nanotechnology has promoted its development in recent decades. The traditional SERS substrates, such as silver electrode, metal island film, and silver colloid, cannot be applied because of their enhancement factor or stability, but newly developed substrates, such as electrochemical deposition surface, Ag porous film, and surface-confined colloids, have better sensitivity and stability. Surface enhanced Raman scattering is applied in other fields such as detection of chemical pollutant, biomolecules, DNA, bacteria, and so forth. In this paper, the development of nanofabrication and application of surface-enhanced Ramans scattering substrate are discussed.
A Case of Squamous Cell Carcinoma of the Renal Pelvis in association withSchistosoma hematobium
Authors: Khan Muhammad A. A. , Kar Ashok , Walker Marjorie M. , Lloyd Jo , Vale Justin A. , Mayer Erik K.
Published: December 2012

A 72-year-old man presented with painless frank haematuria. Investigations included intravenous urogram and abdominal/pelvic CT which revealed a marked focal thickening of the wall of the inferior aspect of the left renal pelvis extending into the lower pole calyx and into the pelviureteric junction resulting in left hydronephrosis. Urine cytology demonstrated clusters of malignant keratinised squamous cells and schistosome ova. He underwent left laparoscopic radical nephroureterectomy and histology revealed moderately differentiated keratinising squamous cell carcinoma in the renal pelvis.
Fabrication of Magnetite/Silica/Titania Core‐Shell Nanoparticles
Authors: Pang Suh Cem , Kho Sze Yun , Chin Suk Fun
Published: December 2012

Fe3O4/SiO2/TiO2 core‐shell nanoparticles were synthesized via a sol‐gel method with the aid of sonication. Fe3O4 nanoparticles were being encapsulated within discrete silica nanospheres, and a layer of TiO2 shell was then coated directly onto each silica nanosphere. As‐synthesized Fe3O4/SiO2/TiO2 core‐shell nanoparticles showed enhanced photocatalytic properties as evidenced by the enhanced photodegradation of methylene blue under UV light irradiation.
Assessing the Effects of Estrogen on the Dynamics of Breast Cancer
Authors: Mufudza Chipo , Sorofa Walter , Chiyaka Edward T.
Published: December 2012

Worldwide, breast cancer has become the second most common cancer in women. The disease has currently been named the most deadly cancer in women but little is known on what causes the disease. We present the effects of estrogen as a risk factor on the dynamics of breast cancer. We develop a deterministic mathematical model showing general dynamics of breast cancer with immune response. This is a four-population model that includes tumor cells, host cells, immune cells, and estrogen. The effects of estrogen are then incorporated in the model. The results show that the presence of extra estrogen increases the risk of developing breast cancer.
Bayes Clustering and Structural Support Vector Machines for Segmentation of Carotid Artery Plaques in Multicontrast MRI
Authors: Guan Qiu , Du Bin , Teng Zhongzhao , Gillard Jonathan , Chen Shengyong
Published: December 2012

Accurate segmentation of carotid artery plaque in MR images is not only a key part but also an essential step for in vivo plaque analysis. Due to the indistinct MR images, it is very difficult to implement the automatic segmentation. Two kinds of classification models, that is, Bayes clustering and SSVM, are introduced in this paper to segment the internal lumen wall of carotid artery. The comparative experimental results show the segmentation performance of SSVM is better than Bayes.
Objective and Subjective Evaluation of Online Error Correction during P300-Based Spelling
Authors: Margaux Perrin , Emmanuel Maby , Sébastien Daligault , Olivier Bertrand , Jérémie Mattout
Published: December 2012

Error potentials (ErrP) are alterations of EEG traces following the subject’s perception of erroneous feedbacks. They provide a way to recognize misinterpreted commands in brain-computer interfaces (BCI). However, this has been evaluated online in only a couple of studies and mostly with very few subjects. In this study, we implemented a P300-based BCI, including not only online error detection but also, for the first time, automatic correction. We evaluated it in 16 healthy volunteers. Whenever an error was detected, a new decision was made based on the second best guess of a probabilistic classifier. At the group level, correction did neither improve nor deteriorate spelling accuracy. However, automatic correction yielded a higher bit rate than a respelling strategy. Furthermore, the fine examination of interindividual differences in the efficiency of error correction and spelling clearly distinguished between two groups who differed according to individual specificity in ErrP detection. The high specificity group had larger evoked responses and made fewer errors which were corrected more efficiently, yielding a 4% improvement in spelling accuracy and a higher bit rate. Altogether, our results suggest that the more the subject is engaged into the task, the more useful and well accepted the automatic error correction.
Citrus ichangensisPeel Extract Exhibits Anti-Metabolic Disorder Effects by the Inhibition of PPARγand LXR Signaling in High-Fat Diet-Induced C57BL/6 Mouse
Authors: Ding Xiaobo , Fan Shengjie , Lu Yan , Zhang Yu , Gu Ming , Zhang Lu , Liu Gaigai , Guo Lu , Jiang Dong , Lu Xiong , Li Yiming , Zhou Zhiqin , Huang Cheng
Published: December 2012

Obesity is a common nutritional disorder associated with type 2 diabetes, cardiovascular diseases, dyslipidemia, and certain cancers. In this study, we investigated the effects ofCitrus ichangensispeel extract (CIE) in high-fat (HF) diet-induced obesity mice. Female C57BL/6 mice were fed a chow diet or an HF diet alone or supplemented with 1% w/w CIE for 8 weeks. We found that CIE treatment could lower blood glucose level and improve glucose tolerance. In the HF+CIE group, body weight gain, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels, and liver triglyceride (TG) and TC concentrations were significantly (P<0.05) decreased relative to those in the HF group. To elucidate the mechanism of CIE on the metabolism of glucose and lipid, related genes expression in liver were examined. In liver tissue, CIE significantly decreased the mRNA expression levels of peroxisome proliferator-activated receptorγ(PPARγ) and its target genes, such as fatty acid synthase (FAS) and acyl-CoA oxidase (ACO). Moreover, CIE also decreased the expression of liver X receptor (LXR)αandβwhich are involved in lipid and glucose metabolism. These results suggest that CIE administration could alleviate obesity and related metabolic disorders in HF diet-induced obesity mice through the inhibition of PPARγand LXR signaling.
Time‐Based Separation for Aircraft Landing Using Danger Value Distribution Flow Model
Authors: Wang Ta-Chung , Tsao Chih-Hsiang
Published: December 2012

This study proposes a flow model using a modified Lighthill‐Whitham‐Richards highway model. The proposed model treats each aircraft on an airway as a continuous distribution of air collision probability, which is called the danger value distribution. With the proposed flow model, collision can be easily predicted by the peak value of the overlap of the danger value distribution of each aircraft. The study further proposes a velocity adjustment method that can be used to resolve the conflict. The proposed method can be applied for aircraft separation during the landing process, in which the separation time is different for different combinations of aircraft types.
Option‐Game Approach to Analyze Technology Innovation Investment under Fuzzy Environment
Authors: Tan Yingshuang , Long Yong
Published: December 2012

Based on the model of symmetric and asymmetric duopoly option game, this paper discusses the present value of profit flows and the sunk investment costs for the trapezoidal fuzzy number. It constructs the fuzzy expressions of the investment value and investment threshold of followers and leaders under fuzzy environment and conducts numerical analysis. This offers a kind of explanation to the investment strategies under fuzzy environment.
Asymptotic Modeling of Coherent Scattering from Random Rough Layers: Application to Road Survey by GPR at Nadir
Authors: Pinel Nicolas , Le Bastard Cédric , Bourlier Christophe , Sun Meng
Published: December 2012

This paper studies the coherent scattering from random rough layers made up of two uncorrelated random rough surfaces, by considering 2D problems. The results from a rigorous electromagnetic method called PILE (propagation-inside-layer expansion) are used as a reference. Also, two asymptotic analytical approaches are presented and compared to the numerical model for comparison. The cases of surfaces with both Gaussian and exponential correlations are studied. This approach is applied to road survey by GPR at nadir.
On the Existence of Positive Periodic Solutions for Second‐Order Functional Differential Equations with Multiple Delays
Authors: Li Qiang , Li Yongxiang
Published: December 2012

The existence results of positive ω‐periodic solutions
are obtained for the second‐order functional differential equation with
multiple delays u″(t) + a(t)u(t) = f(t, u(t), u(t − τ1(t)), …, u(t − τn(t))),
where a(t) ∈ C(ℝ) is a positive ω‐periodic function, f : ℝ × [0, +∞) n+1 → [0, +∞) is a continuous function which is ω‐periodic in t, and τ1(t), …, τn(t) ∈ C(ℝ, [0, +∞)) are ω‐periodic functions. The existence conditions
concern the first eigenvalue of the associated linear periodic
boundary problem. Our discussion is based on the fixed‐point index
theory in cones.
The 19 kDaMycobacterium tuberculosisLipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor
Authors: Sánchez Alejandro , Espinosa Patricia , García Teresa , Mancilla Raúl
Published: December 2012

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDaMycobacterium tuberculosislipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.
Vouchering of Forensically Important Fly Specimens by Nondestructive DNA Extraction
Authors: Kim Seong Yoon , Park Seong Hwan , Piao Huguo , Chung Ukhee , Ko Kwang Soo , Hwang Juck-Joon
Published: December 2012

DNA extraction frequently requires destruction of whole samples. However, when the sample is very rare or has taxonomic importance, nondestructive DNA extraction is required for preservation of voucher specimens. In the case of arthropod specimens, minor anatomical structures such as a single leg or a single wing are often sacrificed instead of the whole body for DNA extraction. In an attempt to save the entire anatomical structure of specimens, several authors tried to brew the whole specimen in a lysis buffer and to extract DNA from the “soup.” We applied this nondestructive DNA extraction technique to a forensically important blowfly species,Phaenicia sericata. With nondestructive DNA extraction, a satisfactory quantity and quality of DNA for PCR amplification was obtained with only minimal anatomical disruptions that do not alter the morphologic identification. This nondestructive method may be applicable to DNA extraction of rare samples as well as vouchering of regular fly samples.
Sonodynamic Excitation of Rose Bengal for Eradication of Gram-Positive and Gram-Negative Bacteria
Authors: Nakonechny Faina , Nisnevitch Michael , Nitzan Yeshayahu , Nisnevitch Marina
Published: December 2012

Photodynamic antimicrobial chemotherapy based on photosensitizers activated by illumination is limited by poor penetration of visible light through skin and tissues. In order to overcome this problem, Rose Bengal was excited in the dark by 28 kHz ultrasound and was applied for inactivation of bacteria. It is demonstrated, for the first time, that the sonodynamic technique is effective for eradication of Gram-positiveStaphylococcus aureusand Gram-negativeEscherichia coli. The net sonodynamic effect was calculated as a 3-4 log10reduction in bacteria concentration, depending on the cell and the Rose Bengal concentration and the treatment time. Sonodynamic treatment may become a novel and effective form of antimicrobial therapy and can be used for low-temperature sterilization of medical instruments and surgical accessories.
Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl β-Cyclodextrin Inclusion Complexes
Authors: Jagdale Swati C. , Mohanty Prachyasuman , Chabukswar Aniruddha R. , Kuchekar Bhanudas S.
Published: December 2012

Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15–19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpβ-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpβ-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin.
Development and Characterization of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Tumorgrafts
Authors: Kimple Randall J. , Harari Paul M. , Torres Alexandra D. , Yang Robert Z. , Soriano Benjamin J. , Yu Menggang , Armstrong Eric A. , Blitzer Grace C. , Smith Molly A. , Lorenz Laurel D. , Lee Denis , Yang David T. , McCulloch Timothy M. , Hartig Gregory K. , Lambert Paul F.
Published: December 2012

Purpose: To develop a clinically relevant model system to study head and neck squamous cell carcinoma (HNSCC), we have established and characterized a direct-from-patient tumorgraft model of human papillomavirus (HPV)–positive and HPV-negative cancers.

Experimental Design: Patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor specimens. Surgically obtained tissue was implanted subcutaneously into immunodeficient mice. During subsequent passages, both formalin-fixed/paraffin-embedded as well as flash-frozen tissues were harvested. Tumors were analyzed for a variety of relevant tumor markers. Tumor growth rates and response to radiation, cisplatin, or cetuximab were assessed and early passage cell strains were developed for rapid testing of drug sensitivity.

Results: Tumorgrafts have been established in 22 of 26 patients to date. Significant diversity in tumorgraft tumor differentiation was observed with good agreement in degree of differentiation between patient tumor and tumorgraft (Kappa 0.72). Six tumorgrafts were HPV-positive on the basis of p16 staining. A strong inverse correlation between tumorgraft p16 and p53 or Rb was identified (Spearman correlations P = 0.085 and P = 0.002, respectively). Significant growth inhibition of representative tumorgrafts was shown with cisplatin, cetuximab, or radiation treatment delivered over a two-week period. Early passage cell strains showed high consistency in response to cancer therapy between tumorgraft and cell strain.

Conclusions: We have established a robust human tumorgraft model system for investigating HPV-positive and HPV-negative HNSCC. These tumorgrafts show strong correlation with the original tumor specimens and provide a powerful resource for investigating mechanisms of therapeutic response as well as preclinical testing. Clin Cancer Res; 19(4); 855–64. ©2012 AACR.
Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer
Authors: Rao Guanhua , Wang Hongyi , Li Baowei , Huang Li , Xue Danfeng , Wang Xiaohui , Jin Haijing , Wang Jun , Zhu Yushan , Lu Youyong , Du Lei , Chen Quan
Published: December 2012

Purpose: CD44 is of functional importance for tumor initiation and progression in colorectal cancer, but how this molecule benefits cancer cells from the tumor microenvironment, especially tumor-associated macrophages (TAM), remains poorly defined.

Experimental Design: In vivo tumorigenic assays were conducted to assess the role of murine TAMs in the tumorigenesis of human colorectal cancer cells. Both in vitro and in vivo osteopontin (OPN) expression levels in TAMs were examined by immunohistochemistry, quantitative PCR, and Western blotting. Soft agar colony formation assays were used to estimate the clonogenicity of colorectal cancer cells that had received different treatments. The relationships between the expression levels of OPN, CD44v6, and CD68 and clinical prognosis were evaluated by tissue microarray analysis.

Results: We found that macrophages, when coinjected or cocultured with CD44-positive colorectal cancer cells, were able to produce higher levels of OPN, which in turn facilitated the tumorigenicity and clonogenicity of the colorectal cancer cells. The knockdown of CD44 or treatment with blocking antibodies to CD44 attenuated OPN secretion. OPN, through binding to its receptor CD44, activated c-jun-NH2-kinase signaling and promoted the clonogenicity of colorectal cancer cells. Moreover, tissue microarray data have shown that OPN expression, in combination with CD44v6, has a negative correlation with colorectal cancer patient survival.

Conclusions: These results suggest that the OPN–CD44 interaction is important for colorectal cancer progression and could serve as a potential therapeutic target for the treatment of colorectal cancer. Clin Cancer Res; 19(4); 785–97. ©2012 AACR.
A Focus on PD-L1 in Human Melanoma
Authors: Hersey Peter , Gallagher Stuart
Published: December 2012

Treatment of metastatic melanoma with inhibitors of the BRAF V600 oncogene in melanoma has been limited by the development of resistance. Combining the BRAF inhibitors with immunotherapy may prolong the response, but will acquisition of resistance to BRAF inhibitors also make melanoma cells resistant to immunotherapy? Clin Cancer Res; 19(3); 514–6. ©2012 AACR.
Incremental Diagnostic and Prognostic Value of Contemporary Stress Echocardiography in a Chest Pain Unit
Authors: Shah Benoy N. , Balaji Gothandaraman , Alhajiri Abdalla , Ramzy Ihab S. , Ahmadvazir Shahram , Senior Roxy
Published: December 2012

Background—

Clinical assessment often cannot reliably or rapidly risk stratify patients hospitalized with suspected acute coronary syndrome. The real-world clinical value of stress echocardiography (SE) in these patients is unknown. Thus, we undertook this study to assess the feasibility, safety, ability for early triaging, and prediction of hard events of SE incorporated into a chest pain unit for patients admitted with acute chest pain, nondiagnostic ECG, and negative 12-hour troponin.

Methods and Results—

Accordingly, 839 consecutive patients who underwent clinical, ECG, and SE assessments within 24 hours of admission were assessed for feasibility, safety, impact on triaging and discharge, and 30-day readmission rate and were followed up for hard events (all-cause mortality and acute myocardial infarction). Of the 839 patients, 811 (96.7%) had diagnostic SE results. Median time to SE and median length of stay for normal SE patients (77%) were both 1 day. The 30-day readmission rate was 0.5%. During long-term follow-up of 27±11 months, 39 hard events (30 deaths and 9 acute myocardial infarctions) occurred. Kaplan-Meier estimates of hard events were 0.5% versus 6.6% in the normal versus abnormal SE groups, respectively, in the first year of follow-up (15 events in the first year). Among all prognostic variables, only abnormal SE (hazard ratio, 4.08; 95% confidence interval, 2.15–7.72;
P
<0.001) and advancing age (hazard ratio, 1.78; 95% confidence interval, 1.39–2.37;
P
<0.001) predicted hard events in multivariable regression analysis.

Conclusions—

SE incorporated into a chest pain unit has excellent feasibility and provides rapid assessment and discharge with accurate risk stratification of patients with suspected acute coronary syndrome but nondiagnostic ECG and negative 12-hour troponin.
Survival Trends in Pediatric In-Hospital Cardiac Arrests
Authors: Girotra Saket , Spertus John A. , Li Yan , Berg Robert A. , Nadkarni Vinay M. , Chan Paul S. ,   for the American Heart Association Get With the Guidelines–Resuscitation Investigators
Published: December 2012

Background—

Despite ongoing efforts to improve the quality of pediatric resuscitation, it remains unknown whether survival in children with in-hospital cardiac arrest has improved.

Methods and Results—

Between 2000 and 2009, we identified children (<18 years of age) with an in-hospital cardiac arrest at hospitals with >3 years of participation and >5 cases annually within the national Get With The Guidelines–Resuscitation registry. Multivariable logistic regression was used to examine temporal trends in survival to discharge. We also explored whether trends in survival were attributable to improvement in acute resuscitation or postresuscitation care and examined trends in neurological disability among survivors. Among 1031 children at 12 hospitals, the initial cardiac arrest rhythm was asystole and pulseless electrical activity in 874 children (84.8%) and ventricular fibrillation and pulseless ventricular tachycardia in 157 children (15.2%), with an increase in cardiac arrests due to pulseless electrical activity over time (
P
for trend <0.001). Risk-adjusted rates of survival to discharge increased from 14.3% in 2000 to 43.4% in 2009 (adjusted rate ratio per year, 1.08; 95% confidence interval, 1.01–1.16;
P
for trend=0.02). Improvement in survival was driven largely by an improvement in acute resuscitation survival (risk-adjusted rates: 42.9% in 2000, 81.2% in 2009; adjusted rate ratio per year: 1.04; 95% confidence interval, 1.01–1.08;
P
for trend=0.006). Moreover, survival trends were not accompanied by higher rates of neurological disability among survivors over time (unadjusted
P
for trend=0.32), suggesting an overall increase in the number of survivors without neurological disability over time.

Conclusions—

Rates of survival to hospital discharge in children with in-hospital cardiac arrests have improved over the past decade without higher rates of neurological disability among survivors.
Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7
Authors: Vergani Andrea , Tezza Sara , D’Addio Francesca , Fotino Carmen , Liu Kaifeng , Niewczas Monika , Bassi Roberto , Molano R. Damaris , Kleffel Sonja , Petrelli Alessandra , Soleti Antonio , Ammirati Enrico , Frigerio Maria , Visner Gary , Grassi Fabio , Ferrero Maria E. , Corradi Domenico , Abdi Reza , Ricordi Camillo , Sayegh Mohamed H. , Pileggi Antonello , Fiorina Paolo
Published: December 2012

Background—

Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation.

Methods and Results—

We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well.

Conclusions—

P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.
Measurement Methods Affect the Observed Global Dimming and Brightening
Authors: Wang Kaicun , Dickinson Robert E. , Ma Qian , Augustine John A. , Wild Martin
Published: December 2012

Surface incident solar radiation G determines our climate and environment, and has been widely observed with a single pyranometer since the late 1950s. Such observations have suggested a widespread decrease between the 1950s and 1980s (global dimming), that is, at a rate of −3.5 W m−2 decade−1 (or −2% decade−1) from 1960 to 1990. Since the early 1990s, the diffuse and direct components of G have been measured independently, and a more accurate G has been calculated by summing these two measurements. Data from this summation method suggest that G increased at a rate of 6.6 W m−2 decade−1 (3.6% decade−1) from 1992 to 2002 (brightening) at selected sites. The brightening rates from these studies were also higher than those from a single pyranometer. In this paper, the authors used 17 years (1995–2011) of parallel measurements by the two methods from nearly 50 stations to test whether these two measurement methods of G provide similar long-term trends. The results show that although measurements of G by the two methods agree very well on a monthly time scale, the long-term trend from 1995 to 2011 determined by the single pyranometer is 2–4 W m−2 decade−1 less than that from the summation method. This difference of trends in the observed G is statistically significant. The dependence of trends of G on measurement methods uncovered here has an important implication for the widely reported global dimming and brightening based on datasets collected by different measurement methods; that is, the dimming might have been less if measured with current summation methods.
From model to practice: Researching and representing Rwanda’s ‘modernized’ gacaca courts
Authors: Ingelaere Bert
Published: December 2012

The publications on the modernized gacaca courts dealing with the legacy of the Rwandan genocide are abundant and they often seem to be rife with diverging analysis and conclusions. This article argues that the seeming lack of consensus does not signal the impossibility of adequately representing the gacaca courts. This article does not dwell on the crisis of representation. Instead, an effort is made to provide clarity in a disorder of representations in the context of a political anthropology that works across localized, national and international networks and dynamics. The process of establishing a representation of the gacaca courts is scrutinized. Numerical legibility, magic syllogisms and performative speech lie at the heart of the process that generates an ideological representation of the modern gacaca courts upheld by the Rwandan regime and its agents. In addition, a first generation of academic studies on gacaca is characterized by magical legalism: they depict a theoretical model that is primarily based on law or law talk. A second generation of gacaca studies mainly adopt a bottom-up perspective that is often ethnographically informed. A focus on actual gacaca practice not only constitutes an alternative research approach but also unmasks and destabilizes the process of ‘making models’. But dangers exist regarding these alternative types of representational strategies as well, especially due to uncritical blurring of reigning models and actual practice. The analysis suggests new avenues of investigation and reflection in the fields of the anthropology of transitional justice, international relations and peace-building.
Learning the knacks of actually existing capitalism: Young Beijing migrants and the problem of value
Authors: Hansen Anders Sybrandt
Published: December 2012

Chinese migrant workers make up the key manual workforce of global capitalist production, but they are barely integrated into either Chinese state narratives or global capitalism’s self-representation. In Chinese they are known as the floating population because they dwell outside the modernist state grid and remain largely unrecognised by the state. This article addresses the labour experiences and developmental aspirations of young Beijing migrants. While they are shown to frame development in the terminology used in state policies, I argue that state conceptions of ideal citizenship are in fact felt to be of little relevance. Their struggle to develop is better understood in relation to a materialist logic of sale of labour, imprinting upon them that their wages equal their worth. To appreciate their aspirations, I argue, we should realise that migrant workers were never successfully integrated into state ideology and therefore restore attention to the subjectivising effects of the labour market.
An epistemological turn: Cheating the death ray of bathos by building an anthropology of hypocrisy (using Foucault)
Authors: Reyna Stephen P
Published: December 2012

This article takes an epistemological turn, warning that certain areas of social and cultural anthropology face the death ray of bathos, due to deference to an essentialist skepticism. An approximating skepticism is suggested as a means of cheating the death ray. Foucault’s regimes of truth (RoT) standpoint is investigated using such skepticism, and shown to be made more politically relevant if transformed into an anthropology of hypocrisy. In the process of doing this, notions of epistemic practice as well as those of asserted and approximate truth are explicated. The anthropology of hypocrisy approach is formulated through an exploration of Foucault’s understanding of RoTs. The approach is applied through consideration of the work of four anthropologists who interrogate different aspects of imperial and liberal RoTs. Finally, it suggests how an anthropology of hypocrisy both makes anthropology more politically valuable, while cheating the death ray of bathos.
Reconstructing the citizen: Disaster, citizenship, and expertise in racial Guyana
Authors: Vaughn Sarah E
Published: December 2012

This article examines the interlocking of nature and race within the overarching framework of the turn toward an idiom of ‘preparedness’ in disaster expertise in Guyana. Tracking the question of racial insecurity following disastrous floods in 2005, the article discusses disaster preparedness interventions as working against the country’s process toward postsocialist racial democratization. In this respect, disaster preparedness has had contradictory effects on security and has enacted a sort of public critique and humor about its inaptness. On the basis of this ethnographic case, the article argues that a practice and language of preparedness is as much about technocratic know-how as it is a style of political humor itself. In this theorization, preparedness is more than contingent, and so is a necessary temporal moment in which people work to imagine a new relationship to nature in recognition of their everyday life molded to environmental and racial-political vulnerability.
The Diversity and Complexity of the Everyday Lives of Mixed Racial and Ethnic Families
Authors: Caballero Chamion , Edwards Rosalind , Goodyer Annabel , Okitikpi Toyin
Published: December 2012

Recent research on mixed racial and ethnic couples and lone parents in Britain indicates that not only are they a diverse group, but they also have a diversity of ways of understanding their difference and creating a sense of belonging for their children (Caballero et al, 2008; Caballero, 2010, 2011). Such research strongly challenges the idea that there is - or should be - a single benchmark of how to raise children from mixed racial and ethnic backgrounds. Nevertheless, placement decisions for this broad group of children are often still rooted in longstanding and politicised assumptions about their identities and how best to instil a positive and healthy sense of self (Phoenix, 1999; Okitikpi, 2005; Goodyer and Okitikpi, 2007; Patel, 2008). Drawing on three recent studies exploring the everyday experiences of lone and couple parents of mixed racial and ethnic children, Chamion Caballero, Rosalind Edwards, Annabel Goodyer and Toyin Okitikpi discuss the ways in which mixed racial and ethnic children who are not in the care system experience difference and belonging within their families, and how they negotiate and manage these factors. In particular, this article illustrates the types of strategies and supports that parents draw on to give their children a positive sense of identity and belonging, as well as the ways in which other issues can be more significant for mixed racial and ethnic children and their parents than what they often see as ‘ordinary’ internal family difference. Arguing that the demographics and experiences of mixed racial and ethnic families are much more diverse and complex than is commonly imagined, the authors ask to what extent policies and practice around the placement of mixed racial and ethnic children reflect the lives of those families outside the care system. Moreover, in what ways can or should the experiences of these families inform policy and practice for those within it? Implications for adoption and fostering practice and policies emerging from this more multifaceted understanding of the everyday lives of racially and ethnically mixed families are also discussed.
Transracial Adoption in Britain
Authors: Barn Ravinder , Kirton Derek
Published: December 2012

Transracial adoptions by white parents are situated at the intersections of family and public policy. Debates on racial integration are juxtaposed with child rights and the private sphere of the family. In Britain, the practices of transracial adoption and ‘racial matching’ continue to invite fierce debate and discussion. Several factors, including the ongoing disproportionate representation of minority ethnic children in the public care system, the ‘unavailability’ of suitable minority ethnic adoptive parents, concerns about adoptees' racial/cultural identity and the ‘suitability’ of white parents to raise racially competent children, form the backdrop for such debates. For the last decade or so, political attention has been focused on permanence for children in care and adoption in particular. Within these wider debates, the allegedly low adoption rates of minority ethnic children, the ‘delay’ in finding suitable adoptive families, the ‘rejection’ of suitable white adoptive couples, and ‘ethnic matching’ are presented as some of the key concerns. Ravinder Barn and Derek Kirton seek to unravel the evidence base around transracial adoption and ‘racial matching’ in the symbolic representational battle being fought in the ‘best interests’ of minority ethnic children.
Transracial Adoption Policies and Practices
Authors: McRoy Ruth , Griffin Amy
Published: December 2012

The over-representation of African American children placed in out-of-home care and in need of adoption continues to be a major problem in the United States. Many believed that the passage of the controversial Multiethnic Placement Act and subsequent Interethnic Provisions would address the problem by increasing the number of African American children adopted. However, the problem still remains years later. Ruth McRoy and Amy Griffin examine the factors associated with US practice and policy initiatives, which aimed to increase the number of adoptions of minority ethnic (especially African American) children in care. The lessons from these experiences may be particularly relevant as the UK develops a new legal, policy and practice framework for transracial adoption to increase permanency for minority ethnic children.
‘As Swedish as Anybody Else’ or ‘Swedish, but Also Something Else’?
Authors: Lind Judith
Published: December 2012

The consequences of looking visibly ‘non-white’ are a recurrent theme in the accounts of many transnational adoptees in Sweden, who frequently find their Swedishness challenged in everyday life. The guidance and education material published by the Swedish Intercountry Adoption Authority (MIA) suggests a strategy of dealing with this by developing pride in the adoptees' non-Swedish origin. The implicit message is that the Swedishness they are excluded from is not worth aspiring to and having additional national origins is more desirable. While this might seem to be a plausible strategy, it raises various problems. For example, despite official discourse on the value of multiculturalism, non-Swedishness in Sweden continues to have predominantly negative connotations. Further, it is a strategy that requires certain cultural and language competencies that are difficult to acquire. Judith Lind analyses the accounts of 22 young adult transnational adoptees in nine focus group discussions in relation to the recommendations made by the MIA. In so doing, she contextualises the Swedish recommendations by considering the background in which they were produced.