bluuebunny/crossref_metadata_2025 huggingface dataset:
Significant Increase in Cytotoxic T Lymphocytes and Natural Killer Cells by Triphala: A Clinical Phase I Study
Authors: Phetkate Pratya , Kummalue Tanawan , U-pratya Yaowalak , Kietinun Somboon
Published: December 2012

Background. Searching for drugs or herbal formulations to improve the immunity of HIV/AIDS positive people is an important issue for researchers in this field. Triphala, a Thai herbal formulation, is reported to have immunomodulatory effects in mice. However, it has not yet been investigated for immunostimulatory and side effects in healthy human volunteers.Objective. To evaluate the immunostimulatory and side effects of Triphala in a clinical phase I study.Materials and Methods. All volunteers took Triphala, 3 capsules per day for 2 weeks. Complete physical examination, routine laboratory analysis, and immunological studies were performed before ingestion and after initial meeting for 4 consecutive weeks.Results. We found that Triphala demonstrated significant immunostimulatory effects on cytotoxic T cells (CD3−CD8+) and natural killer cells (CD16+CD56+). Both of them increased significantly when compared with those of the control samples. However, no significant change in cytokine secretion was detected. All volunteers were healthy and showed no adverse effects throughout the duration of the study.Conclusion. Triphala has significant immunostimulatory effects on cellular immune response, especially cytotoxic T cells and natural killer cells. Increases in the absolute number of these cells may provide a novel adjuvant therapy for HIV/AIDS positive people in terms of immunological improvement.
The Learning Curve of Gastric Intestinal Metaplasia Interpretation on the Images Obtained by Probe-Based Confocal Laser Endomicroscopy
Authors: Pittayanon Rapat , Rerknimitr Rungsun , Wisedopas Naruemon , Khemnark Suparat , Thanapirom Kessarin , Thienchanachaiya Pornpahn , Norrasetwanich Nuttaporn , Charoensuk Kriangsak , Ridtitid Wiriyaporn , Treeprasertsuk Sombat , Kongkam Pradermchai , Kullavanijaya Pinit
Published: December 2012

Background. Reading the results of gastric intestinal metaplasia (GIM) with probe-based confocal laser endomicroscopy (pCLE) by the expert was excellent. There is a lack of study on the learning curve for GIM interpretation. Therefore, we conducted a study to explore the learning curve in the beginners. Material and Method. Five GI fellows who had no experience in GIM interpretation had been trained with a set of 10 pCLE video clips of GIM and non-GIM until they were able to interpret correctly. Then they were asked to interpret another 80 video clips of GIM and non-GIM. The sensitivity, specificity, accuracy, PPV, NPV, and interobserver agreement on each session were analyzed. Results. Within 2 sessions, all beginners can achieve 80% accuracy with substantial to almost perfect level of interobserver agreement. The sensitivities and specificities among all interpreters were not different statistically. Four out of five interpreters can maintain their high quality of reading skill. Conclusion. After a short session of training on GIM interpretation of pCLE images, the beginners can achieve a high level of reading accuracy with at least substantial level of interobserver agreement. Once they achieve the high reading accuracy, almost all can maintain their high quality of reading skill.
Participation of the Third Order Optical Nonlinearities in Nanostructured Silver Doped Zinc Oxide Thin Solid Films
Authors: Torres-Torres C. , Castañeda L. , Trejo-Valdez M. , Maldonado A. , Torres-Martínez R.
Published: December 2012

We report the transmittance modulation of optical signals in a nanocomposite integrated by two different silver doped zinc oxide thin solid films. An ultrasonic spray pyrolysis approach was employed for the preparation of the samples. Measurements of the third‐order nonlinear optical response at a nonresonant 532 nm wavelength of excitation were performed using a vectorial two‐wave mixing. It seems that the separated contribution of the optical nonlinearity associated with each film noticeable differs in the resulting nonlinear effects with respect to the additive response exhibited by the bilayer system. An enhancement of the optical Kerr nonlinearity is predicted for prime number arrays of the studied nanoclusters in a two‐wave interaction. We consider that the nanostructured morphology of the thin solid films originates a strong modification of the third‐order optical phenomena exhibited by multilayer films based on zinc oxide.
Hemangioma of the Tympanic Membrane: A Case and a Review of the Literature
Authors: Mevio Emilio , Cazzaniga Marco , Mullace Mauro , Paolotti Donatella
Published: December 2012

Hemangiomas of the external auditory canal, involving the posterior bony canal and the adjacent tympanic membrane, although rare, are considered a specific disease entity of the human external auditory canal. Hemangiomas of the tympanic membrane and/or external auditory canal are rare entities; there are 16 previous case reports in the literature. It is a benign vascular tumor. It generally occurs in males in the sixth decade of life. Total surgical excision with or without tympanic membrane grafting appears to be effective in the removal of this benign neoplasm. The authors present a case and a review of the literature discussing diagnostic and surgical approaches.
Comparative Modal Analysis of Gasketed and Nongasketed Bolted Flanged Pipe Joints: FEA Approach
Authors: Abid Muhammad , Maqsood Shahid , Abdul Wajid Hafiz
Published: December 2012

It is widely known that resonance can quickly lead to failure in vibrating bolted flanged pipe joints. Condition monitoring is performed time to time in some industries for smooth operation of a system, whereas mostly trial-and-error tests are performed to control vibration. During all this process, the inherent design problems are not considered. A bolted flange joint in piping system is not a simple problem, being the combination of flange, gasket, bolts, and washers. The success of a bolted flanged pipe joint is defined by the “static mode of load” in the joint. However, it has been recognized that a “dynamic mode of load” governs in a gasketed bolted flanged pipe joint, which leads to its failure due to flange rotation, providing flange yielding, fatigue of bolts, and gasket crushing. This paper presents results of detailed 3D finite element and mathematical modal analysis under bolt up to determine natural frequencies and mode shapes of gasketed flanged joints with and without raised face in comparison to the nongasketed flange joint.
Caseous Calcification of the Mitral Annulus: A Rare Cause of Intracardiac Mass
Authors: Martinez-de-Alegria Anxo , Rubio-Alvarez Jose , Baleato-Gonzalez Sandra
Published: December 2012

Caseous calcification of the mitral annulus is a rare form of periannular calcification with a mass-like appearance, that has to be in the differential of the cardiologist and radiologist. It classically looks like a round or semilunar hyperdense mass with an even denser peripheral rim, located in the posterior mitral annulus and having in general no clinical significance.
Intramedullary Chondrosarcoma of Proximal Humerus
Authors: Yadav Pratiksha , Thakkar Dolly , Thind S. S.
Published: December 2012

Primary chondrosarcoma is the third most frequent primary malignancy of bone after myeloma and osteosarcoma. It is ranging from slow growing nonmetastasising lesions to highly aggressive lesions. We report a case of primary intramedullary chondrosarcoma of proximal humerus. A 60-year-old female presented with pain and hard swelling involving the left arm for 5 months. Radiograph showed a lucent expansile intramedullary lesion with matrix calcification and associated soft tissue mass. CT confirmed the finding. MRI showed a lobulated lesion which is hyperintense on T2WI with low signal fibrous septae. Increased tracer uptake was seen on bone scan. Histopathology confirmed the radiology diagnosis. The patient underwent wide resection and endoprosthetic reconstruction of proximal humerus.
Analytical Model for the End-Bearing Capacity of Tapered Piles Using Cavity Expansion Theory
Authors: Manandhar Suman , Yasufuku Noriyuki
Published: December 2012

On the basis of evidence from model tests on increasing the end-bearing behavior of tapered piles at the load-settlement curve, this paper proposes an analytical spherical cavity expansion theory to evaluate the end-bearing capacity. The angle of tapering is inserted in the proposed model to evaluate the end-bearing capacity. The test results of the proposed model in different types of sands and different relative densities show good effects compared to conventional straight piles. The end-bearing capacity increases with increases in the tapering angle. The paper then propounds a model for prototypes and real-type pile tests which predicts and validates to evaluate the end-bearing capacity.
Unknown Input Observer Design for Fuzzy Bilinear System: An LMI Approach
Authors: Saoudi D. , Chadli M. , Mechmeche C. , Benhadj Braiek N.
Published: December 2012

A new method to design a fuzzy bilinear observer (FBO) with unknown inputs is developed for a class of nonlinear systems. The nonlinear system is modeled as a fuzzy bilinear model (FBM). This kind of T‐S fuzzy model is especially suitable for a nonlinear system with a bilinear term. The proposed fuzzy bilinear observer subject to unknown inputs is developed to ensure the asymptotic convergence of the error dynamic using the Lyapunov method. The proposed design conditions are given in linear matrix inequality (LMI) formulation. The paper studies also the problem of fault detection and isolation. An unknown input fuzzy bilinear fault diagnosis observer design is proposed. This work is given for both continuous and discrete cases of fuzzy bilinear models. Illustrative examples are chosen to provide the effectiveness of the given methodology.
Surgical Procedures for External Auditory Canal Carcinoma and the Preservation of Postoperative Hearing
Authors: Hoshikawa Hiroshi , Miyashita Takenori , Mori Nozomu
Published: December 2012

Carcinoma of the external auditory canal (EAC) is an unusual head and neck malignancy. The pathophysiology of these tumors is different from other skin lesions because of their anatomical and functional characteristics. Early-stage carcinoma of the EAC can be generally cured by surgical treatment, and reconstruction of the EAC with a tympanoplasty can help to retain hearing, thus improving the patients’ quality of life. In this study, we present two cases of early-stage carcinoma of the EAC treated by canal reconstruction using skin grafts after lateral temporal bone resection. A rolled-up skin graft with a temporal muscle flap was useful for keeping the form and maintaining the postoperative hearing. An adequate size of the skin graft and blood supply to the graft bed are important for achieving a successful operation.
Prevalent Obstacles and Predictors for People Living with Type 2 Diabetes
Authors: Pilv L. , Rätsep A. , Oona M. , Kalda R.
Published: December 2012

Background. Type 2 diabetes (T2DM) is a chronic, progressive disease with serious micro- and macrovascular complications. A person affected by T2DM should learn to accept the new restricted lifestyle. Aims. The aim of the study was to identify the prevalence of obstacles in coping with daily life for people with T2DM and the magnitude of the relationships of the obstacles with various patient characteristics. Methods. Participants were recruited from randomly selected GPs’ lists in Estonia. Respondents completed the Estonian version of the Diabetes Obstacles Questionnaire (DOQ). The statements were assessed on a 5-point scale. Biomedical and clinical variables were measured. The central tendency statistics and skewness and kurtosis for all statements were computed to find out those that reflect obstacles. Then obstacles of the DOQ were stratified. Multinomial logistic regression (MLR) was computed to estimate the influences of descriptive variables on the statements. Results and Conclusions. Altogether, 138 diabetic patients were enrolled in the study. Fourteen statements were identified as obstacles. Variables such as age, type of diabetes treatment, and BMI had significant effects on five of them. Younger age, BMI, and insulin nonuse were revealed as the strongest predictive characteristics for perceiving obstacles more often in coping with daily life.
Nerium oleanderDistillate Improves Fat and Glucose Metabolism in High-Fat Diet-Fed Streptozotocin-Induced Diabetic Rats
Authors: Bas Ahmet Levent , Demirci Sule , Yazihan Nuray , Uney Kamil , Ermis Kaya Ezgi
Published: December 2012

Diabetes was induced by intraperitoneal injection of streptozotocin (35 mg/kg bw) in all rats of five groups after being fed for 2 weeks high-fat diet. Type 2 diabeticNerium-oleander-(NO-) administered groups received the NO distillate at a dose of 3.75, 37.5, and 375 μg/0.5 mL of distilled water (NO-0.1, NO-1, NO-10, resp.); positive control group had 0.6 mg glibenclamide/kg bw/d by gavage daily for 12 weeks. Type 2 diabetic negative control group had no treatment. NO distillate administration reduced fasting blood glucose, HbA1c, insulin resistance, total cholesterol, low density lipoprotein, atherogenic index, triglyceride-HDL ratio, insulin, and leptin levels. Improved beta cell function and HDL concentration were observed by NO usage. HDL percentage in total cholesterol of all NO groups was similar to healthy control. NO-10 distillate enhanced mRNA expressions of peroxisome proliferator-activated-receptor- (PPAR-)α,β, andγin adipose tissue and PPAR-α–γin liver. The findings from bothin vivoandin vitrostudies suggest that the considerable beneficial effect of NO distillate administration at a dose of 375 μg/0.5 mL of distilled water may offer new approaches to treatment strategies that target both fat and glucose metabolism in type 2 diabetes.
Damage Assessment in a SiC-fiber reinforced Ceramic Matrix Composite
Authors: Dassios Konstantinos G. , Matikas Theodore E.
Published: December 2012

Assessment of the fracture behavior of a SiC-fbre-reinforced barium osumilite (BMAS) ceramic matrix composite tested under static and cyclic tension conditions is reported herein. Notched specimens were used in order to limit material damage within a predefined gauge length. Imposition of successive unloading/reloading loops was found to result in an increase by 20% in material strength as compared to pure tension; the observed increase is attributed to energy dissipation from large-scale interfacial debonding phenomena that dominated the post-elastic tensile behaviour of the composite. Cyclic loading also helped establish the axial residual stress state of the fibres in the composite of tensile nature via a well-defined common intersection point of unloading-reloading cycles. A translation vector approach in the stress-strain plane was successful in establishing the residual stress-free properties of the composite and in reconciling the scatter noted in elastic properties of specimens with respect to theoretical expectations.
CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Authors: Saintigny Pierre , Massarelli Erminia , Lin Steven , Ahn Young-Ho , Chen Yulong , Goswami Sangeeta , Erez Baruch , O'Reilly Michael S. , Liu Diane , Lee J. Jack , Zhang Li , Ping Yuan , Behrens Carmen , Solis Soto Luisa M. , Heymach John V. , Kim Edward S. , Herbst Roy S. , Lippman Scott M. , Wistuba Ignacio I. , Hong Waun Ki , Kurie Jonathan M. , Koo Ja Seok
Published: December 2012

CXCR2 in non–small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53–mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small-molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis, and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. Cancer Res; 73(2); 571–82. ©2012 AACR.
High-Avidity T Cells Are Preferentially Tolerized in the Tumor Microenvironment
Authors: Zhu Ziqiang , Singh Vinod , Watkins Stephanie K. , Bronte Vincenzo , Shoe Jennifer L. , Feigenbaum Lionel , Hurwitz Arthur A.
Published: December 2012

One obstacle in eliciting potent antitumor immune responses is the induction of tolerance to tumor antigens. TCRlo mice bearing a TCR transgene specific for the melanoma antigen tyrosinase-related protein-2 (TRP-2, Dct) harbor T cells that maintain tumor antigen responsiveness but lack the ability to control melanoma outgrowth. We used this model to determine whether higher avidity T cells could control tumor growth without becoming tolerized. As a part of the current study, we developed a second TRP-2–specific TCR transgenic mouse line (TCRhi) that bears higher avidity T cells and spontaneously developed autoimmune depigmentation. In contrast to TCRlo T cells, which were ignorant of tumor-derived antigen, TCRhi T cells initially delayed subcutaneous B16 melanoma tumor growth. However, persistence in the tumor microenvironment resulted in reduced IFN-γ production and CD107a (Lamp1) mobilization, hallmarks of T-cell tolerization. IFN-γ expression by TCRhi T cells was critical for upregulation of MHC-I on tumor cells and control of tumor growth. Blockade of PD-1 signals prevented T-cell tolerization and restored tumor immunity. Depletion of tumor-associated dendritic cells (TADC) reduced tolerization of TCRhi T cells and enhanced their antitumor activity. In addition, TADCs tolerized TCRhi T cells but not TCRlo T cells in vitro. Our findings show that T-cell avidity is a critical determinant of not only tumor control but also susceptibility to tolerization in the tumor microenvironment. For this reason, care should be exercised when considering T-cell avidity in designing cancer immunotherapeutics. Cancer Res; 73(2); 595–604. ©2012 AACR.
Clonal Progression of Prostate Cancers from Gleason Grade 3 to Grade 4
Authors: Sowalsky Adam G. , Ye Huihui , Bubley Glenn J. , Balk Steven P.
Published: December 2012

Low-grade prostate cancers (Gleason pattern 3, G3) detected on needle biopsies are generally viewed as indolent and suitable for conservative management with only interval repeat biopsies to monitor by watchful waiting. Higher grade tumors eventually emerge in 20% to 30% of these cases, but this process may only reflect incomplete sampling on the initial biopsy, such that it remains unknown whether G3 tumors generally progress to higher grades. In this study, we examined a series of adjacent G3 and Gleason pattern 4 (G4) tumors in radical prostatectomy specimens and found that all were concordant for the TMPRSS2:ERG gene fusion. Using hybrid-capture and deep sequencing in four fusion-positive cases, we found that adjacent laser-capture microdissected G3 and G4 tumors had identical TMPRSS2:ERG fusion breakpoints, confirming their clonal origin. Two of these G3 tumors had deletion of a single PTEN gene that was also deleted in the adjacent G4, while the G4 tumors in two cases had additional PTEN losses. These findings establish that a subset of G3 tumors progress to G4 or emerge from a common precursor. Further, they show that G3 tumors that progress to G4 may have molecular features distinguishing them from G3 tumors that do not progress. Thus, determining the spectrum of these genetic or epigenetic features may allow for the identification of G3 tumors on needle biopsies that are truly indolent versus those that have the potential to progress or that may already be associated with a G4 tumor that was not sampled at the initial biopsy, therefore, requiring more aggressive surveillance or intervention. Cancer Res; 73(3); 1050–5. ©2012 AACR.
Disruption of Wild-Type IDH1 Suppresses D-2-Hydroxyglutarate Production in IDH1-Mutated Gliomas
Authors: Jin Genglin , Reitman Zachary J. , Duncan Christopher G. , Spasojevic Ivan , Gooden David M. , Rasheed B. Ahmed , Yang Rui , Lopez Giselle Y. , He Yiping , McLendon Roger E. , Bigner Darell D. , Yan Hai
Published: December 2012

Point mutations at Arg132 of the cytoplasmic NADP+-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the “oncometabolite” D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually associated with a wild-type IDH1 allele (heterozygous) in cancer. Here, we identify 2 gliomas that underwent loss of the wild-type IDH1 allele but retained the mutant IDH1 allele following tumor progression from World Health Organization (WHO) grade III anaplastic astrocytomas to WHO grade IV glioblastomas. Intratumoral D-2HG was 14-fold lower in the glioblastomas lacking wild-type IDH1 than in glioblastomas with heterozygous IDH1 mutations. To characterize the contribution of wild-type IDH1 to cancer cell D-2HG production, we established an IDH1-mutated astrocytoma (IMA) cell line from a WHO grade III anaplastic astrocytoma. Disruption of the wild-type IDH1 allele in IMA cells by gene targeting resulted in an 87-fold decrease in cellular D-2HG levels, showing that both wild-type and mutant IDH1 alleles are required for D-2HG production in glioma cells. Expression of wild-type IDH1 was also critical for mutant IDH1-associated D-2HG production in the colorectal cancer cell line HCT116. These insights may aid in the development of therapeutic strategies to target IDH1-mutated cancers. Cancer Res; 73(2); 496–501. ©2012 AACR.
BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Antitumor Activity of Adoptive Immunotherapy in Mice
Authors: Liu Chengwen , Peng Weiyi , Xu Chunyu , Lou Yanyan , Zhang Minying , Wargo Jennifer A. , Chen Jie Qing , Li Haiyan S. , Watowich Stephanie S. , Yang Yan , Frederick Dennie Tompers , Cooper Zachary A. , Mbofung Rina M. , Whittington Mayra , Flaherty Keith T. , Woodman Scott E. , Davies Michael A. , Radvanyi Laszlo G. , Overwijk Willem W. , Lizée Gregory , Hwu Patrick
Published: December 2012

Purpose: Treatment of melanoma patients with selective BRAF inhibitors results in objective clinical responses in the majority of patients with BRAF-mutant tumors. However, resistance to these inhibitors develops within a few months. In this study, we test the hypothesis that BRAF inhibition in combination with adoptive T-cell transfer (ACT) will be more effective at inducing long-term clinical regressions of BRAF-mutant tumors.

Experimental Design: BRAF-mutated human melanoma tumor cell lines transduced to express gp100 and H-2Db to allow recognition by gp100-specific pmel-1 T cells were used as xenograft models to assess melanocyte differentiation antigen–independent enhancement of immune responses by BRAF inhibitor PLX4720. Luciferase-expressing pmel-1 T cells were generated to monitor T-cell migration in vivo. The expression of VEGF was determined by ELISA, protein array, and immunohistochemistry. Importantly, VEGF expression after BRAF inhibition was tested in a set of patient samples.

Results: We found that administration of PLX4720 significantly increased tumor infiltration of adoptively transferred T cells in vivo and enhanced the antitumor activity of ACT. This increased T-cell infiltration was primarily mediated by the ability of PLX4720 to inhibit melanoma tumor cell production of VEGF by reducing the binding of c-myc to the VEGF promoter. Furthermore, analysis of human melanoma patient tumor biopsies before and during BRAF inhibitor treatment showed downregulation of VEGF consistent with the preclinical murine model.

Conclusion: These findings provide a strong rationale to evaluate the potential clinical application of combining BRAF inhibition with T-cell–based immunotherapy for the treatment of patients with melanoma. Clin Cancer Res; 19(2); 393–403. ©2012 AACR.
It's About Time: Lessons for Solid Tumors from Chronic Myelogenous Leukemia Therapy
Authors: Westin Jason R. , Kurzrock Razelle
Published: December 2012

The use of imatinib in chronic myelogenous leukemia (CML) transformed the disease, rapidly changing the median survival from 4 years to at least 20 years. In this review, we outline the causes of this revolution, including the identification of a critical driving molecular aberration, BCR-ABL, and the development of a potent and specific inhibitor, imatinib. Equally important was the timing of the targeted therapy, specifically its administration to patients with newly diagnosed disease. In solid tumors, targeted therapies are often both developed and used in metastatic malignancies after conventional approaches have failed. We postulate that this strategy is similar to using imatinib in blast-crisis CML, in which response rates are less than 15%, all patients relapse, and median survival remains only about 1 year. We hypothesize that the imatinib-led revolution in CML, including the critically important factor of timing, may be applicable to other cancers as well. Therefore, it will be important to use promising targeted therapies in the earliest phases of biomarker-defined solid tumors, before metastatic progression, to determine if outcomes can be significantly improved and, thus, establish if the success of imatinib in CML is an anomaly or a paradigm. Mol Cancer Ther; 11(12); 2549–55. ©2012 AACR.
CLT1 Targets Bladder Cancer through Integrin α5β1 and CLIC3
Authors: Knowles Lynn M. , Zewe James , Malik Gunjan , Parwani Anil V. , Gingrich Jeffrey R. , Pilch Jan
Published: December 2012

High-grade non–muscle-invasive bladder cancer is commonly treated with Bacillus Calmette-Guérin, an immunotherapeutic that depends on fibronectin and tumor cell integrin α5β1 for internalization into bladder cancer cells. We previously showed that the anti-angiogenic peptide CLT1 forms cytotoxic complexes with fibronectin that are cooperatively internalized into proliferating endothelium through ligation of integrins and chloride intracellular channel 1. While CLT1 has no effect on mature, differentiated cells, we show here that CLT1 is highly cytotoxic for a panel of bladder tumor cell lines as well as a variety of cell lines derived from kidney, lung, breast, and prostate cancer. Paralleling our previous results, we found CLT1-induced tumor cell death to be increased in the presence of fibronectin, which mediated CLT1 internalization and subsequent autophagic cell death in a mechanism that depends on tumor cell integrin α5β1 and chloride intracellular channel 3 (CLIC3). This mechanistic link was further supported by our results showing upregulation of α5β1 and CLIC3 in CLT1-responsive tumor cell lines and colocalization with CLT1 in tumor tissues. Incubating tumor tissue from patients with bladder cancer with fluorescein-conjugated CLT1 resulted in a strong and specific fluorescence whereas normal bladder tissue remained negative. On the basis of its affinity for bladder tumor tissue and strong antitumor effects, we propose that CLT1 could be useful for targeting bladder cancer. Mol Cancer Res; 11(2); 194–203. ©2012 AACR.
Effects of the Tumor Necrosis Factor-α Antagonist Adalimumab on Arterial Inflammation Assessed by Positron Emission Tomography in Patients With Psoriasis
Authors: Bissonnette Robert , Tardif Jean-Claude , Harel François , Pressacco Joséphine , Bolduc Chantal , Guertin Marie-Claude
Published: December 2012

Background—

Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown.

Methods and Results—

This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by
18
F-fluorodeoxyglucose uptake on positron emission tomography. The change in target:background ratio in the vessel with highest baseline target:background ratio (primary end point) was significant at week 15 compared with baseline for patients randomized to adalimumab (–0.23 [95% CI, –0.39 to –0.08];
P
=0.004) but not for the control group (–0.10 [95% CI, –0.32 to 0.12];
P
=0.35). The difference between study arms for this primary end point did not reach statistical significance (–0.13 [95% CI, –0.01 to 0.14];
P
=0.32). The change in target:background ratio at week 15 improved with adalimumab compared with controls both in the ascending aorta (–0.26±0.11,
P
=0.021) and in carotid arteries (–0.32±0.15,
P
=0.037) when analyzed separately (secondary end points). Changes in other positron emission tomography indices also improved significantly with adalimumab compared with controls in the ascending aorta and carotids. High-sensitivity C-reactive protein decreased by 51% at week 16 with adalimumab compared with 5% in controls (
P
=0·002).

Conclusions—

The study did not meet its primary end point because the change in target:background ratio in patients randomized to adalimumab was not different from controls. Although adalimumab may reduce vascular inflammation in patients with moderate to severe psoriasis, this effect is not large enough to be demonstrated in a study with a small sample size.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NTC00940862.
CXC-Chemokine Receptor 4 Antagonist AMD3100 Promotes Cardiac Functional Recovery After Ischemia/Reperfusion Injury via Endothelial Nitric Oxide Synthase–Dependent Mechanism
Authors: Jujo Kentaro , Ii Masaaki , Sekiguchi Haruki , Klyachko Ekaterina , Misener Sol , Tanaka Toshikazu , Tongers Jörn , Roncalli Jérôme , Renault Marie-Ange , Thorne Tina , Ito Aiko , Clarke Trevor , Kamide Christine , Tsurumi Yukio , Hagiwara Nobuhisa , Qin Gangjian , Asahi Michio , Losordo Douglas W.
Published: December 2012

Background—

CXC-chemokine receptor 4 (CXCR4) regulates the retention of stem/progenitor cells in the bone marrow (BM), and the CXCR4 antagonist AMD3100 improves recovery from coronary ligation injury by mobilizing stem/progenitor cells from the BM to the peripheral blood. Thus, we investigated whether AMD3100 also improves recovery from ischemia/reperfusion injury, which more closely mimics myocardial infarction in patients, because blood flow is only temporarily obstructed.

Methods and Results—

Mice were treated with single subcutaneous injections of AMD3100 (5 mg/kg) or saline after ischemia/reperfusion injury. Three days later, histological measurements of the ratio of infarct area to area at risk were smaller in AMD3100-treated mice than in mice administered saline, and echocardiographic measurements of left ventricular function were greater in the AMD3100-treated mice at week 4. CXCR4
+
cells were mobilized for just 1 day in both groups, but the mobilization of sca1
+
/flk1
+
cells endured for 7 days in AMD3100-treated mice compared with just 1 day in the saline-treated mice. AMD3100 upregulated BM levels of endothelial nitric oxide synthase (eNOS) and 2 targets of eNOS signaling, matrix metalloproteinase-9 and soluble Kit ligand. Furthermore, the loss of BM eNOS expression abolished the benefit of AMD3100 on sca1
+
/flk1
+
cell mobilization without altering the mobilization of CXCR4
+
cells, and the cardioprotective effects of AMD3100 were retained in eNOS-knockout mice that had been transplanted with BM from wild-type mice but not in wild-type mice with eNOS-knockout BM.

Conclusions—

AMD3100 prolongs BM progenitor mobilization and improves recovery from ischemia/reperfusion injury, and these benefits appear to occur through a previously unidentified link between AMD3100 and BM eNOS expression.
Cell Selective Cardiovascular Biology of Microsomal Prostaglandin E Synthase-1
Authors: Chen Lihong , Yang Guangrui , Xu Xiufeng , Grant Gregory , Lawson John A. , Bohlooly-Y Mohammad , FitzGerald Garret A.
Published: December 2012

Background—

Global deletion of microsomal prostaglandin E synthase 1 (mPGES-1) in mice attenuates the response to vascular injury without a predisposition to thrombogenesis or hypertension. However, enzyme deletion results in cell-specific differential use by prostaglandin synthases of the accumulated prostaglandin H
2
substrate. Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells, endothelial cells, and myeloid cells further to elucidate the cardiovascular function of this enzyme.

Methods and Results—

Vascular smooth muscle cell and endothelial cell mPGES-1 deletion did not alter blood pressure at baseline or in response to a high-salt diet. The propensity to evoked macrovascular and microvascular thrombogenesis was also unaltered. However, both vascular smooth muscle cell and endothelial cell mPGES-1–deficient mice exhibited a markedly exaggerated neointimal hyperplastic response to wire injury of the femoral artery in comparison to their littermate controls. The hyperplasia was associated with increased proliferating cell nuclear antigen and tenascin-C expression. In contrast, the response to injury was markedly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltration, and expression of proliferating cell nuclear antigen and tenascin-C. Conditioned medium derived from mPGES-1–deficient macrophages less potently induced vascular smooth muscle cell proliferation and migration than that from wild-type macrophages.

Conclusions—

Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.
Youthful Memory Capacity in Old Brains: Anatomic and Genetic Clues from the Northwestern SuperAging Project
Authors: Rogalski Emily J. , Gefen Tamar , Shi Junzi , Samimi Mehrnoosh , Bigio Eileen , Weintraub Sandra , Geula Changiz , Mesulam M.-Marsel
Published: December 2012

The Northwestern University SuperAging Project recruits community dwellers over the age of 80 who have unusually high performance on tests of episodic memory. In a previous report, a small cohort of SuperAgers was found to have higher cortical thickness on structural MRI than a group of age-matched but cognitively average peers. SuperAgers also displayed a patch of ACC where cortical thickness was higher than in 50- to 60-year-old younger cognitively healthy adults. In additional analyses, some SuperAgers had unusually low densities of age-related Alzheimer pathology and unusually high numbers of von Economo neurons in the anterior cingulate gyrus. SuperAgers were also found to have a lower frequency of the ɛ4 allele of apolipoprotein E than the general population. These preliminary results show that above-average memory capacity can be encountered in advanced age. They also offer clues to potential biological factors that may promote resistance to age-related involutional changes in the structure and function of the brain.
Spatial Cognition and the Hippocampus: The Anterior–Posterior Axis
Authors: Nadel Lynn , Hoscheidt Siobhan , Ryan Lee R.
Published: December 2012

We discuss the question of differentiation along the anterior–posterior longitudinal axis of the hippocampus. Data from a recent fMRI study are reanalyzed to determine whether activations in these hippocampal regions are affected by the nature of the information being accessed during a scanning session in which participants thought about episodes from their lives. Retrieving detailed spatial relational information preferentially activated the posterior hippocampus, whereas retrieving information about locales (or contexts) preferentially activated the anterior hippocampus. These data support the view that there is functional differentiation along the longitudinal axis in humans that matches what has been seen in rats, namely, that the posterior (dorsal) hippocampus is crucial for precise spatial behavior, and the anterior (ventral) hippocampus is crucial for context coding.
Neocortical Correlates of Vibrotactile Detection in Humans
Authors: Moore Christopher I. , Crosier Emilie , Greve Douglas N. , Savoy Robert , Merzenich Michael M. , Dale Anders M.
Published: December 2012

This study examined the cortical representation of vibrotactile detection in humans using event-related fMRI paired with psychophysics. Suprathreshold vibrotactile stimulation activated several areas, including primary (SI) and second somatosensory cortices (SII/PV). For threshold-level stimuli, poststimulus activity in contralateral and ipsilateral SII/PV was the best correlate of detection success. In these areas, evoked signals on hit trials were significantly greater than on missed trials in all participants, and the relative activity level across stimulation amplitudes matched perceptual performance. Activity in the anterior insula and superior temporal gyrus also correlated with hits and misses, suggesting that a “ventral stream” of somatosensory representations may play a crucial role in detection. In contrast, poststimulus activity in Area SI was not well correlated with perception and showed an overall negative response profile for threshold-level stimulation. A different correlate of detection success was, however, observed in SI. Activity in this representation immediately before stimulus onset predicted performance, a finding that was unique to SI. These findings emphasize the potential role of SII/PV in detection, the importance of state dynamics in SI for perception, and the possibility that changes in the temporal and spatial pattern of SI activity may be essential to the optimal representation of threshold-level stimuli for detection.
Evaluation of Wearable Simulation Interface for Military Training
Authors: Taylor Grant S. , Barnett John S.
Published: December 2012

Objective:

This research evaluated the training effectiveness of a novel simulation interface, a wearable computer integrated into a soldier’s load-bearing equipment.

Background:

Military teams often use game-based simulators on desktop computers to train squad-level procedures. A wearable computer interface that mimics the soldier’s equipment was expected to provide better training through increased realism and immersion.

Method:

A heuristic usability evaluation and two experiments were conducted. Eight evaluators interacted with both wearable and desktop interfaces and completed a usability survey. The first experiment compared the training retention of the wearable interface with a desktop simulator and interactive training video. The second experiment compared the training transfer of the wearable and desktop simulators with a live training environment.

Results:

Results indicated the wearable interface was more difficult to use and elicited stronger symptoms of simulator sickness. There was no significant difference in training retention between the wearable, desktop, or interactive video training methods. The live training used in the second experiment provided superior training transfer than the simulator conditions, with no difference between the desktop and wearable.

Conclusion:

The wearable simulator interface did not provide better training than the desktop computer interface. It also had poorer usability and caused worse simulator sickness. Therefore, it was a less effective training tool.

Application:

This research illustrates the importance of conducting empirical evaluations of novel training technologies. New and innovative technologies are always coveted by users, but new does not always guarantee improvement.
The Application of Reduced-Processing Decision Support Systems to Facilitate the Acquisition of Decision-Making Skills
Authors: Perry Nathan C. , Wiggins Mark W. , Childs Merilyn , Fogarty Gerard
Published: December 2012

Objective:

The study was designed to examine whether the availability of reduced-processing decision support system interfaces could improve the decision making of inexperienced personnel in the context of firefighting.

Background:

Although research into reduced-processing decision support systems has demonstrated benefits in minimizing cognitive load, these benefits have not typically translated into direct improvements in decision accuracy because of the tendency for inexperienced personnel to focus on less-critical information. The authors investigated whether reduced-processing interfaces that direct users’ attention toward the most critical cues for decision making can produce improvements in decision-making performance.

Method:

Novice participants made incident command-related decisions in experimental conditions that differed according to the amount of information that was available within the interface, the level of control that they could exert over the presentation of information, and whether they had received decision training.

Results:

The results revealed that despite receiving training, participants improved in decision accuracy only when they were provided with an interface that restricted information access to the most critical cues.

Conclusion:

It was concluded that an interface that restricts information access to only the most critical cues in the scenario can facilitate improvements in decision performance.

Application:

Decision support system interfaces that encourage the processing of the most critical cues have the potential to improve the accuracy and timeliness of decisions made by inexperienced personnel.
From Crime to Recovery
Authors: Duke Karen
Published: December 2012

During the last 5 years, there has been an important shift in the policy discourse around drugs issues. This article reviews the key changes and continuities in British drugs policy since the mid 1990s. It examines the crime reduction focus of the previous Labour government and the processes by which the recovery discourse came to dominate the current policy framework under the coalition government in 2010. The shifts in policy and practice will be explored in relation to how the drugs problem was framed and reframed over time and how shifts within the wider social, political, and economic contexts have impacted these developments. It is argued that although the moves toward a recovery-based policy represent significant changes, there are powerful continuities and remnants of previous policies and structures, which have endured and set the parameters for the current policy framework, particularly in relation to crime reduction priorities.
Development and Use of Curricular Adaptations for Students Receiving Special Education Services
Authors: Kurth Jennifer A. , Keegan Lissa
Published: December 2012

This study is a quasi-experimental descriptive design, with existing educator-made adaptations evaluated. The goals of this study were to (a) describe how educators develop adaptations and (b) evaluate the effectiveness of educator-made adaptations in facilitating the learning of students with disabilities. Findings suggest that (a) most adaptations were made in core general education classes; (b) experienced educators created more simplified curricular adaptations, whereas novice educators created more functional alternative adaptations; (c) educators are generally satisfied with the adaptation they have created and believe it was effective in teaching the student; (d) educators spent on average 59.1 min creating the adaptation; (e) educators in rural areas and novice educators provided adaptations that were rated lower in quality and clarity than experienced and urban educators; and (f) general education teachers provided adaptations that were of lower quality and clarity than special education teachers and paraeducators. Recommendations for practice are provided.
Social Relationships and Delinquency
Authors: Brauer Jonathan R. , De Coster Stacy
Published: December 2012

Scholars interested in delinquency have focused much attention on the influence of parent and peer relationships. Prior research has assumed that parents control delinquency because they value convention, whereas peers promote delinquency because they value and model nonconvention. We argue that it is important to assess the normative and behavioral orientations of those to whom adolescents feel close to accurately model how relationships operate. Drawing on social control, social learning, and a prominent developmental perspective, we derive and test alternative hypotheses about the manner in which attachments to significant others and the normative and behavioral orientations of these others operate either independently or in tandem to influence delinquency. Empirical findings based on tobit regressions and National Youth Survey (NYS) data suggest that social learning theory is best equipped to explain peer influence; however, the developmental perspective appears more applicable to parent influence.
The Cultural Dimensions of Urban Fragmentation
Authors: Bayón María Cristina , Saraví Gonzalo A.
Published: December 2012

In the past few decades, Mexico City has experienced the continuity of traditional patterns of urbanization and the emergence of new urban processes after globalization and neoliberal reforms. The result of this confluence of persistent and emerging trends is not wholly transparent, and the social and urban fragmentation of the city is under debate. Structural trends are not enough to understand these processes; sociocultural dimensions should also be addressed. The experience of the city and the patterns of sociability in the privileged and disadvantaged classes are characterized by contrasting urban lifestyles, as well as social homogeneity, reciprocal isolation and closure, mutual indifference, stigmatization, and fear. The scale of urban segregation is decreasing; the rich and the poor may live physically closer, but the spaces for interaction and encounter are becoming increasingly homogeneous and distant in social terms. These sociocultural dimensions shed light on a new Latin American geography of urban inequality that undermines social cohesion and the experience of citizenship.

En las ultimas décadas la Ciudad de México ha experimentado tanto la continuación de su patrón tradicional de urbanización como la aparición de nuevos procesos urbanos como consecuencia de la globalización y las reformas neoliberales. El resultado de esta confluencia de corrientes persistentes y emergentes no es del todo transparente, y se debate la fragmentación social y urbana de la ciudad. No basta con examinar tendencias estructurales, también se tiene que dirigir atención a las dimensiones socioculturales. La experiencia de la ciudad y el patrón de sociabilidad dentro de las clases privilegiadas y desventajadas se contrastan por sus formas de vida urbana, como por su respectiva homogeneidad social, su aislamiento reciproco y cierre, su indiferencia mutua, su estigmatización, y sus temores. Se va disminuyendo la escala de la segregación; los ricos y pobres pueden vivir mas cercanos físicamente, pero los espacios para la interacción y encuentro se tornan cada vez mas homogéneos y distantes en términos sociales. Estas dimensiones socioculturales iluminan una nueva geografía latinoamericana de desigualdad urbana que mina la cohesión social y la experiencia de la ciudadanía.