bluuebunny/crossref_metadata_2025 huggingface dataset:
Lungworm outbreaks in adult dairy cows: estimating economic losses and lessons to be learned
Authors: Holzhauer M. , van Schaik G. , Saatkamp H. W. , Ploeger H. W.
Published: August 2011

Two lungworm outbreaks in dairy herds were investigated in order to estimate the resulting economic costs. On the two farms, with 110 and 95 cows, total costs were estimated at €159 and €167 per cow, respectively. Overall, milk production reduced by 15 to 20 per cent during the outbreaks. Five cows died on one farm, while on the other farm seven cows died as a result of the lungworm outbreak. On one farm, 51.7 per cent of the total costs was due to reduced milk production and 33.1 per cent was due to disposal of dead animals. On the other farm, it was 36.3 and 50.9 per cent, respectively. The remaining 13 to 15 per cent of the total costs were due to extra inseminations, laboratory diagnosis and treatments. The history and development of the outbreaks are described. One lesson from these outbreaks is that recognising that potentially lungworm‐naïve animals are to be introduced into the adult herd allows for timely measures (for example, vaccination) to prevent a lungworm outbreak.
Pattern of growth of very low birth weight preterm infants, assessed using the WHO Growth Standards, is associated with neurodevelopment
Authors: Nash Andrea , Dunn Michael , Asztalos Elizabeth , Corey Mary , Mulvihill-Jory Bridget , O’Connor Deborah L.
Published: August 2011

Several Canadian professional organizations recently recommended that the growth of preterm infants be monitored using the World Health Organization Growth Standards (WHO-GS) after hospital discharge. The WHO-GS are a prescriptive set of growth charts that describe how term infants should grow under ideal environmental conditions. Whether preterm infants following this pattern of growth have better outcomes than infants that do not has yet to be evaluated. Our aim was to determine whether the pattern of growth of very low birth weight (VLBW) infants during the first 2 years, assessed using the WHO-GS or the traditional Centers for Disease Control and Prevention reference growth charts (CDC-RGC), is associated with neurodevelopment. Pattern of weight, length, and head circumference gain of appropriate-for-gestation VLBW preterm infants (n = 289) from birth to 18–24 months corrected age was classified, using the WHO-GS and CDC-RGC, as sustained (change in Z-score ≤1 SD), decelerated (decline >1 SD), or accelerated (incline >1 SD). Development was assessed using the Bayley Scales of Infant and Toddler Development (BSID)-III at 18–24 months corrected age. Using the WHO-GS, children with a decelerated pattern of weight gain had lower cognitive (10 points), language (6 points), and motor (4 points) scores than infants with sustained weight gain (p < 0.05), even after adjustment for morbidities. No association was found using the CDC-RGC. In conclusion, a decelerated pattern of weight gain, determined with the WHO-GS, but not the CDC-GRC, is associated with poorer neurodevelopment scores on the BSID-III than a pattern of sustained growth.
DECAY PROPERTY FOR THE TIMOSHENKO SYSTEM WITH MEMORY-TYPE DISSIPATION
Authors: LIU YONGQIN , KAWASHIMA SHUICHI
Published: August 2011

In this paper we consider the initial value problem for the Timoshenko system with a memory term. We construct the fundamental solution by using the Fourier–Laplace transform and obtain the solution formula of the problem. Moreover, applying the energy method in the Fourier space, we derive the pointwise estimate of solutions in the Fourier space, which gives a sharp decay estimate of solutions. It is shown that the decay property of the system is of the regularity-loss type and is weaker than that of the Timoshenko system with a frictional dissipation.
Genetic deletion of trkB.T1 increases neuromuscular function
Authors: Dorsey Susan G. , Lovering Richard M. , Renn Cynthia L. , Leitch Carmen C. , Liu Xinyue , Tallon Luke J. , Sadzewicz Lisa DeShong , Pratap Abhishek , Ott Sandra , Sengamalay Naomi , Jones Kristie M. , Barrick Colleen , Fulgenzi Gianluca , Becker Jodi , Voelker Kevin , Talmadge Robert , Harvey Brandon K. , Wyatt Ryan M. , Vernon-Pitts Elizabeth , Zhang Chao , Shokat Kevan , Fraser-Liggett Claire , Balice-Gordon Rita J. , Tessarollo Lino , Ward Christopher W.
Published: August 2011

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.
Rho-kinase inhibition alleviates pulmonary hypertension in transgenic mice expressing a dominant-negative type II bone morphogenetic protein receptor gene
Authors: Yasuda Tadashi , Tada Yuji , Tanabe Nobuhiro , Tatsumi Koichiro , West James
Published: August 2011

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a sustained elevation in the pulmonary artery pressure and subsequent right heart failure. The activation of Rho/Rho-kinase activity and the beneficial effect of Rho-kinase inhibition have been demonstrated in several experimental models of pulmonary hypertension. However, it remains unclear whether Rho-kinase inhibitors can also be used against pulmonary hypertension associated with mutations in the type II bone morphogenetic protein receptor (BMPRII) gene. Transgenic mice expressing a dominant-negative BMPRII gene (with an arginine to termination mutation at amino acid 899) in smooth muscle by a tetracycline-gene switch system (SM22-tet-BMPR2R899X mice) were examined. They developed an elevated right ventricular systolic pressure (RVSP), right ventricular (RV) hypertrophy, muscularization of small pulmonary arteries, and an associated disturbed blood flow in their lungs. The Rho/Rho-kinase activity and Smad activity were determined by a Western blot analysis by detecting GTP-RhoA and the phosphorylation of myosin phosphatase target subunit 1, Smad1, and Smad2. In the lungs of SM22-tet-BMPR2R899X mice, the Rho/Rho-kinase activity was elevated significantly, whereas the Smad activity was almost unchanged. Fasudil, a Rho-kinase inhibitor, significantly decreased RVSP, alleviated RV hypertrophy and muscularization of small pulmonary arteries, and improved blood flow in SM22-tet-BMPR2R899X mice, although it did not alter Smad signaling. Our study demonstrates that Rho/Rho-kinase signaling is activated via a Smad-independent pathway in an animal model of pulmonary hypertension with a BMPRII mutation in the cytoplasmic tail domain. Rho-kinase inhibition is therefore a possible therapeutic approach for the treatment of PAH associated with genetic mutation.
Functional role of exercise-induced cortical organization of sensorimotor cortex after spinal transection
Authors: Kao T. , Shumsky J. S. , Knudsen E. B. , Murray M. , Moxon K. A.
Published: August 2011

Spinal cord transection silences neuronal activity in the deafferented cortex to cutaneous stimulation of the body and untreated animals show no improvement in functional outcome (weight-supported stepping) with time after lesion. However, adult rats spinalized since neonates that receive exercise therapy exhibit greater functional recovery and exhibit more cortical reorganization. This suggests that the change in the somatotopic organization of the cortex may be functionally relevant. To address this issue, we chronically implanted arrays of microwire electrodes into the infragranular layers of the hindlimb somatosensory cortex of adult rats neonatally transected at T8/T9 that received exercise training (spinalized rats) and of normal adult rats. Multiple, single neuron activity was recorded during passive sensory stimulation, when the animals were anesthetized, and during active sensorimotor stimulation during treadmill-induced locomotion when the animal was awake and free to move. Our results demonstrate that cortical neurons recorded from the spinalized rats that received exercise 1) had higher spontaneous firing rates, 2) were more likely to respond to both sensory and sensorimotor stimulations of the forelimbs, and also 3) responded with more spikes per stimulus than those recorded from normal rats, suggesting expansion of the forelimb map into the hindlimb map. During treadmill locomotion the activity of neurons recorded from neonatally spinalized rats was greater during weight-supported steps on the treadmill compared with the neuronal activity during nonweight supported steps. We hypothesize that this increased activity is related to the ability of the animal to take weight supported steps and that, therefore, these changes in cortical organization after spinal cord injury are relevant for functional recovery.
Computational Tools for Cohomology of Toric Varieties
Authors: Blumenhagen Ralph , Jurke Benjamin , Rahn Thorsten
Published: August 2011

Novel nonstandard techniques for the computation of cohomology classes on toric varieties are summarized. After an introduction of the basic definitions and properties of toric geometry, we discuss a specific computational algorithm for the determination of the dimension of line-bundle-valued cohomology groups on toric varieties. Applications to the computation of chiral massless matter spectra in string compactifications are discussed, and using the software packagecohomCalg, its utility is highlighted on a new target space dual pair of(0,2)heterotic string models.
Posttraumatic Cranial Cystic Fibrous Dysplasia
Authors: Tomiyama Arata , Aoki Kazuya , Nakayama Haruo , Izukura Hideaki , Kimura Hitoshi , Harashina Jun-ichi , Ito Keisuke , Hayashi Morito , Saito Norihiko , Sakurai Takatoshi , Oharaseki Toshiaki , Terada Hitoshi , Iwabuchi Satoshi
Published: August 2011

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested thatc-fosgene expression is a key mechanism in injury-induced FD.
On Limiting Distributions of Quantum Markov Chains
Authors: Liu Chaobin , Petulante Nelson
Published: August 2011

In a quantum Markov chain, the temporal succession of states
is modeled by the repeated action of a “bistochastic quantum operation” on
the density matrix of a quantum system. Based on this conceptual framework,
we derive some new results concerning the evolution of a quantum system,
including its long‐term behavior. Among our findings is the fact that
the Cesàro limit of any quantum Markov chain always exists and equals
the orthogonal projection of the initial state upon the eigenspace of the
unit eigenvalue of the bistochastic quantum operation. Moreover, if the
unit eigenvalue is the only eigenvalue on the unit circle, then the quantum
Markov chain converges in the conventional sense to the said orthogonal
projection. As a corollary, we offer a new derivation of the classic result
describing limiting distributions of unitary quantum walks on finite graphs
(Aharonov et al., 2001).
Association between Functional Polymorphisms of Foxp3 Gene and the Occurrence of Unexplained Recurrent Spontaneous Abortion in a Chinese Han Population
Authors: Wu Zaigui , You Zeshan , Zhang Cai , Li Zhuyu , Su Xiumei , Zhang Xiuming , Li Yinguang
Published: August 2011

Unexplained recurrent spontaneous abortion (URSA) is an alloimmune disease associated with the failure of fetal-maternal immunologic tolerance in which the regulatory T lymphocytes (Treg) play a pivotal role. It is well known that Forkhead box P3 (Foxp3) is a crucial regulatory factor for the development and function of Treg cells. It has also been established that deficiency of the Foxp3 gene suppresses the regulatory function of Treg cells. To determine if functional polymorphisms at the Foxp3 loci are associated with URSA in humans, we genotyped four common polymorphisms of Foxp3 gene in 146 unrelated URSA patients and 112 healthy women. The results showed that rs3761548A/C and rs2232365A/G polymorphisms were significantly associated with URSA. Additionally, we found that the allelic distribution of rs5902434 del/ATT in URSA group was slightly different from that in the control group. We conclude that functional polymorphisms of the Foxp3 gene may confer an important susceptibility to URSA in the Chinese Han population, probably by altering Foxp3 function and/or its expression.
Effects of Photoacoustic Imaging and Photothermal Ablation Therapy Mediated by Targeted Hollow Gold Nanospheres in an Orthotopic Mouse Xenograft Model of Glioma
Authors: Lu Wei , Melancon Marites P. , Xiong Chiyi , Huang Qian , Elliott Andrew , Song Shaoli , Zhang Rui , Flores Leo G. , Gelovani Juri G. , Wang Lihong V. , Ku Geng , Stafford R. Jason , Li Chun
Published: August 2011

Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7°C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results show the feasibility of using a single nanostructure for image-guided local tumor PTA therapy with photoacoustic molecular imaging. Cancer Res; 71(19); 6116–21. ©2011 AACR.
miR-375 Is Activated by ASH1 and Inhibits YAP1 in a Lineage-Dependent Manner in Lung Cancer
Authors: Nishikawa Eri , Osada Hirotaka , Okazaki Yasumasa , Arima Chinatsu , Tomida Shuta , Tatematsu Yoshio , Taguchi Ayumu , Shimada Yukako , Yanagisawa Kiyoshi , Yatabe Yasushi , Toyokuni Shinya , Sekido Yoshitaka , Takahashi Takashi
Published: August 2011

Lung cancers with neuroendocrine (NE) features are often very aggressive but the underlying molecular mechanisms remain elusive. The transcription factor ASH1/ASCL1 is a master regulator of pulmonary NE cell development that is involved in the pathogenesis of lung cancers with NE features (NE-lung cancers). Here we report the definition of the microRNA miR-375 as a key downstream effector of ASH1 function in NE-lung cancer cells. miR-375 was markedly induced by ASH1 in lung cancer cells where it was sufficient to induce NE differentiation. miR-375 upregulation was a prerequisite for ASH1-mediated induction of NE features. The transcriptional coactivator YAP1 was determined to be a direct target of miR-375. YAP1 showed a negative correlation with miR-375 in a panel of lung cancer cell lines and growth inhibitory activities in NE-lung cancer cells. Our results elucidate an ASH1 effector axis in NE-lung cancers that is functionally pivotal in controlling NE features and the alleviation from YAP1-mediated growth inhibition. Cancer Res; 71(19); 6165–73. ©2011 AACR.
Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models
Authors: Hedley Benjamin D. , Chu Jenny E. , Ormond D. George , Beausoleil Michel S. , Boasie Alexandra , Allan Alison L. , Xenocostas Anargyros
Published: August 2011

Purpose: Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study.

Experimental Design: Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents.

Results: A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P < 0.05).

Conclusions: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy. Clin Cancer Res; 17(19); 6151–62. ©2011 AACR.
A Gene Expression–Based Predictor for Myeloma Patients at High Risk of Developing Bone Disease on Bisphosphonate Treatment
Authors: Wu Ping , Walker Brian A. , Brewer Daniel , Gregory Walter M. , Ashcroft John , Ross Fiona M. , Jackson Graham H. , Child Anthony J. , Davies Faith E. , Morgan Gareth J.
Published: August 2011

Purpose: Myeloma bone disease impairs quality of life and is associated with impaired survival. Even with effective bisphosphonate treatment, a significant proportion of patients still develop skeletal-related events (SRE). Identifying such patients at presentation would allow treatment modification.

Experimental Design: To investigate the molecular basis of bone disease at presentation and to develop a predictive signature for patients at high risk of developing SREs on bisphosphonates, 261 presenting myeloma samples were analyzed by global gene expression profiling. The derived “SRE gene signature” was complemented by the integration of associated clinical parameters to generate an optimal predictor.

Results: Fifty genes were significantly associated with presenting bone disease, including the WNT signaling antagonist DKK1 and genes involved in growth factor signaling and apoptosis. Higher serum calcium level and the presence of bone disease and hyperdiploidy at presentation were associated with high risk of SRE development. A gene signature derived from the fourteen genes overexpressed in the SRE group was able to identify patients at high risk of developing an SRE on treatment. These genes either belonged to the IFN-induced family or were involved in cell signaling and mitosis. Multivariate logistic model selection yielded an optimal SRE predictor comprising seven genes and calcium level, which was validated as an effective predictor in a further set of patients.

Conclusions: The simple expression-based SRE predictor can effectively identify individuals at high risk of developing bone disease while being on bisphosphonates. This predictor could assist with developing future trials on novel therapies aimed at reducing myeloma bone disease. Clin Cancer Res; 17(19); 6347–55. ©2011 AACR.
Targeting ALDHbright Human Carcinoma–Initiating Cells with ALDH1A1-Specific CD8+ T Cells
Authors: Visus Carmen , Wang Yangyang , Lozano-Leon Antonio , Ferris Robert L. , Silver Susan , Szczepanski Miroslaw J. , Brand Randall E. , Ferrone Cristina R. , Whiteside Theresa L. , Ferrone Soldano , DeLeo Albert B. , Wang Xinhui
Published: August 2011

Purpose: Cancer-initiating cells (CIC) are considered to represent the subpopulation of tumor cells that is resistant to conventional cancer treatments, highly tumorigenic in immunodeficient mice, and responsible for tumor recurrence and metastasis. Based on an elevated aldehyde dehydrogenase (ALDH) activity attributable to ALDH1/3 isoforms, ALDHbright cells have been identified and isolated from tumors and shown to have characteristics of CIC. The ALDH1A1 isoform was previously identified as a tumor antigen recognized by CD8+ T cells. This study examines the ability of ALDH1A1-specific CD8+ T cells to eliminate ALDHbright cells and control tumor growth and metastases.

Experimental Design: ALDHbright cells were isolated by flow cytometry using ALDEFLUOR from HLA-A2+ human head and neck, breast, and pancreas carcinoma cell lines and tested for their tumorigenicity in immunodeficient mice. ALDH1A1-specific CD8+ T cells were generated in vitro and tested for their ability to eliminate CICs in vitro and in vivo by adoptive transfer to immunodeficient mice bearing human tumor xenografts.

Results: ALDHbright cells isolated by flow cytometry from HLA-A2+ breast, head and neck, and pancreas carcinoma cell lines at low numbers (500 cells) were tumorigenic in immunodeficient mice. ALDHbright cells present in these cell lines, xenografts, or surgically removed lesions were recognized by ALDH1A1-specific CD8+ T cells in vitro. Adoptive therapy with ALDH1A1-specific CD8+ T cells eliminated ALDHbright cells, inhibited tumor growth and metastases, or prolonged survival of xenograft-bearing immunodeficient mice.

Conclusions: The results of this translational study strongly support the potential of ALDH1A1-based immunotherapy to selectively target CICs in human cancer. Clin Cancer Res; 17(19); 6174–84. ©2011 AACR.
Disease Flare after Tyrosine Kinase Inhibitor Discontinuation in Patients with EGFR-Mutant Lung Cancer and Acquired Resistance to Erlotinib or Gefitinib: Implications for Clinical Trial Design
Authors: Chaft Jamie E. , Oxnard Geoffrey R. , Sima Camelia S. , Kris Mark G. , Miller Vincent A. , Riely Gregory J.
Published: August 2011

Purpose: Treatment of patients with oncogene-addicted cancers with tyrosine kinase inhibitors (TKI) is biologically and clinically different than with cytotoxic chemotherapy. We have observed that some patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib (RECIST progression after initial benefit) have accelerated progression of disease after discontinuation of TKI. To examine this observation and define the course of patients following TKI discontinuation, we systematically evaluated patients enrolled on clinical trials of agents to treat acquired resistance to erlotinib or gefitinib.

Methods: We evaluated patients with EGFR-mutant lung cancer who participated in trials for patients with acquired resistance that mandated TKI discontinuation before administration of study therapy. Disease flare was defined as hospitalization or death attributable to disease progression during the washout period.

Results: Fourteen of 61 patients (23%; 95% CI: 14–35) experienced a disease flare. The median time to disease flare after TKI discontinuation was 8 days (range 3–21). Factors associated with disease flare included shorter time to progression on initial TKI (P = 0.002) and the presence of pleural (P = 0.03) or CNS disease (P = 0.01). There was no association between disease flare and the presence of T790M at the time of acquired resistance.

Conclusions: In patients with EGFR-mutant lung cancer and acquired resistance to epidermal growth factor receptor TKIs, discontinuation of erlotinib or gefitinib before initiation of study treatment is associated with a clinically significant risk of accelerated disease progression. Clinical trials in this patient population must minimize protocol-mandated washout periods. Clin Cancer Res; 17(19); 6298–303. ©2011 AACR.
MT1-MMP Cooperates with KrasG12D to Promote Pancreatic Fibrosis through Increased TGF-β Signaling
Authors: Krantz Seth B. , Shields Mario A. , Dangi-Garimella Surabhi , Cheon Eric C. , Barron Morgan R. , Hwang Rosa F. , Rao M. Sambasiva , Grippo Paul J. , Bentrem David J. , Munshi Hidayatullah G.
Published: August 2011

Pancreatic cancer is associated with a pronounced fibrotic reaction that was recently shown to limit delivery of chemotherapy. To identify potential therapeutic targets to overcome this fibrosis, we examined the interplay between fibrosis and the key proteinase membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14), which is required for growth and invasion in the collagen-rich microenvironment. In this article, we show that compared with control mice (Kras+/MT1-MMP−) that express an activating KrasG12D mutation necessary for pancreatic cancer development, littermate mice that express both MT1-MMP and KrasG12D (Kras+/MT1-MMP+) developed a greater number of large, dysplastic mucin-containing papillary lesions. These lesions were associated with a significant amount of surrounding fibrosis, increased α-smooth muscle actin (+) cells in the stroma, indicative of activated myofibroblasts, and increased Smad2 phosphorylation. To further understand how MT1-MMP promotes fibrosis, we established an in vitro model to examine the effect of expressing MT1-MMP in pancreatic ductal adenocarcinoma (PDAC) cells on stellate cell collagen deposition. Conditioned media from MT1-MMP–expressing PDAC cells grown in three-dimensional collagen enhanced Smad2 nuclear translocation, promoted Smad2 phosphorylation, and increased collagen production by stellate cells. Inhibiting the activity or expression of the TGF-β type I receptor in stellate cells attenuated MT1-MMP conditioned medium–induced collagen expression by stellate cells. In addition, a function-blocking anti–TGF-β antibody also inhibited MT1-MMP conditioned medium–induced collagen expression in stellate cells. Overall, we show that the bona fide collagenase MT1-MMP paradoxically contributes to fibrosis by increasing TGF-β signaling and that targeting MT1-MMP may thus help to mitigate fibrosis. Mol Cancer Res; 9(10); 1294–304. ©2011 AACR.
Resveratrol Inhibits Proliferation and Survival of Epstein Barr Virus–Infected Burkitt's Lymphoma Cells Depending on Viral Latency Program
Authors: De Leo Alessandra , Arena Giuseppe , Stecca Claudia , Raciti Marisa , Mattia Elena
Published: August 2011

Resveratrol (3,4′,5-trihydroxy-trans-stilbene), a polyphenolic natural product, shows chemopreventive properties against several cancers, heart diseases, inflammation, and viral infections. Epstein Barr virus (EBV), a γ-herpesvirus, contributes to the development of several human cancers including Burkitt's lymphoma (BL). In this study, we asked whether treatment with resveratrol would affect the viability of EBV-positive BL cells displaying different forms of latency. We report here that resveratrol, regardless of EBV status, induces caspase-dependent apoptosis by arresting cell-cycle progression in G1 phase. However, resveratrol strongly induced apoptosis in EBV(−) and latency I EBV(+) cells, whereas latency II and latency III EBV(+) BL cells showed a survival advantage that increased with the extent of the pattern of viral gene expression. Resveratrol-induced cell-cycle arrest and apoptosis occurred in association with induction of p38 MAPK phosphorylation and suppression of ERK1/2 signaling pathway. Moreover, NF-κB DNA-binding activity was inhibited in all BL lines except EBV(+) latency III cells.

LMP1 oncogene, which is expressed in latency III phenotype, is involved with the higher resistance to the antiproliferative effect of resveratrol because siRNA-mediated inhibition of LMP1 greatly increased the sensitivity of latency III BL cells as well as that of lymphoblastoid cell lines to the polyphenol. We propose that a combined resveratrol/siRNA strategy may be a novel approach for the treatment of EBV-associated B-cell malignancies in which the viral pattern of gene expression has been defined. Mol Cancer Res; 9(10); 1346–55. ©2011 AACR.
Effect of the Inositol Polyphosphate InsP6 on DNA-PK–Dependent Phosphorylation
Authors: Hanakahi Les
Published: August 2011

Inositol hexakisphosphate (InsP6) is a member of the inositol polyphosphate group that participates in numerous intracellular signaling pathways. Cheung and colleagues previously reported that InsP6 stimulated double-strand break repair by nonhomologous end joining (NHEJ) in cell-free extracts and that InsP6 binding by the Ku70/80 subunit of the DNA-dependent protein kinase (DNA-PK) was required for stimulation of NHEJ in vitro. This report describes InsP6-dependent phosphorylation of two NHEJ factors, XRCC4 and XLF, in partially purified human cell extracts. XRCC4 and XLF are known substrates for DNA-PK, which does not require InsP6 for protein kinase activity. Consistent with a role for DNA-PK in these reactions, InsP6-dependent phosphorylation of XRCC4 and XLF was DNA dependent and not observed in the presence of DNA-PK inhibitors. Depletion of the Ku70/80 DNA-, InsP6-binding subunit of DNA-PK resulted in loss of InsP6-dependent phosphorylation and showed a requirement for Ku70/80 in these reactions. Complementation of Ku70/80-depleted reactions with recombinant wild-type Ku70/80 restored InsP6-dependent phosphorylation of XRCC4 and XLF. In contrast, addition of a Ku70/80 mutant with reduced InsP6 binding failed to restore InsP6-dependent phosphorylation. While additional protein kinases may participate in InsP6-dependent phosphorylation of XRCC4 and XLF, data presented here describe a clear requirement for DNA-PK in these phosphorylation events. Furthermore, these data suggest that binding of the inositol polyphosphate InsP6 by Ku70/80 may modulate the substrate specificity of the phosphoinositide-3-kinase–related protein kinase DNA-PK. Mol Cancer Res; 9(10); 1366–76. ©2011 AACR.
Arrhythmia Type After Persistent Atrial Fibrillation Ablation Predicts Success of the Repeat Procedure
Authors: Ammar Sonia , Hessling Gabriele , Reents Tilko , Fichtner Stephanie , Wu Jinjin , Zhu Pinjun , Kathan Susanne , Estner Heidi Louise , Jilek Clemens , Kolb Christof , Haller Bernhard , Deisenhofer Isabel
Published: August 2011

Background—

The aim of the study was to investigate whether the type of arrhythmia recurrence after ablation of persistent atrial fibrillation (AF) has an impact on the maintenance of sinus rhythm after the repeat ablation procedure.

Methods and Results—

Included were 78 consecutive patients (82% men; mean age, 61±10 years; mean left atrial diameter, 47±4 mm) with persistent AF who underwent ≥1 repeat ablation. The initial ablation procedure had consisted of pulmonary vein isolation with additional substrate modification (ablation of complex fractionated atrial electrograms [n=63] or linear lesions [n=15]). Patients presented for reablation either with persistent atrial tachycardia (AT) (group 1, n=36), persistent AF (group 2, n=37), or paroxysmal AF (group 3, n=5). The primary end point was freedom from any arrhythmia off antiarrhythmic drugs 6 and 9 months after the reablation procedure. Estimated proportions of patients reaching the primary end point were 59% for group 1, 28% for group 2, and 100% for group 3 at 6 months and 51%, 23%, and 100%, for groups 1, 2, and 3, respectively, at 9 months (
P
=0.002).

Conclusions—

In patients presenting for a repeat procedure after ablation of persistent AF, the occurrence of AT is associated with a significantly better outcome compared with recurrent persistent AF. These results suggest that AT might be considered as a step toward sinus rhythm.
Parent-Reported Reasons for Nonreceipt of Recommended Adolescent Vaccinations, National Immunization Survey—Teen, 2009
Authors: Dorell Christina , Yankey David , Strasser Sheryl
Published: August 2011

Objectives: To identify parent-reported reasons for non-receipt of adolescent vaccinations by provider recommendation status. Methods: Parental reasons for non-receipt of adolescent vaccines were analyzed among adolescents 13-17 years using data from the 2009 National Immunization Survey-Teen (n=20,066). Results: Among unvaccinated adolescents, 87.9% (Td/Tdap), 90.9% (MenACWY), and 66.0% (HPV) of parents reported that they did not receive a healthcare provider recommendation for their adolescent to receive the vaccine. Among those without a provider recommendation, the most common reasons for not receiving the vaccines were ‘vaccine not recommended’ [Td/Tdap, MenACWY] and ‘not needed’ [HPV]. Among those with a recommendation, the most common parental reasons were ‘lack of knowledge’ [Td/Tdap], ‘vaccine not needed’ [MenACWY], and ‘lack of knowledge’ [HPV]. Conclusions: Non-receipt of provider recommendations was a main parent-reported reason for not getting vaccinated. Increasing parental knowledge and vaccination coverage through increased provider-parent communication about disease risk and vaccine benefits is needed.
Barriers to Care for Children and Youth With Special Health Care Needs
Authors: Agrawal Rishi , Shah Parag , Zebracki Kathy , Sanabria Kathy , Kohrman Claire , Kohrman Arthur F.
Published: August 2011

Objective. To assess primary care pediatricians’ (PCPs’) perceptions of caring for children and youth with special health care needs (CYSHCN). Methods. Cross-sectional survey of Illinois pediatricians. Results. Thirty-five percent of surveys were returned and 26% were analyzed. The top 3 perceived barriers were insufficient time (72%), insufficient reimbursement (68%), and lack of support services (59%). Insufficient interest was the least cited barrier (19%). Preparedness to perform tasks related to care of CYSHCN ranged from 89% for accessing early intervention services to 24% for billing and coding. The percentage of PCPs somewhat or very comfortable providing primary care to patients with technology dependence ranged from 75% for blood glucose monitoring to 12% for dialysis. Conclusions. The issues of time, reimbursement, billing, and coding are perceived as significant barriers to the care CYSHCN. There is substantial variation in PCPs’ comfort in the care of CYSHCN who require the assistance of medical technologies.
Expression and Possible Immune-regulatory Function of Ghrelin in Oral Epithelium
Authors: Ohta K. , Laborde N.J. , Kajiya M. , Shin J. , Zhu T. , Thondukolam A.K. , Min C. , Kamata N. , Karimbux N.Y. , Stashenko P. , Kawai T.
Published: August 2011

Originally found in stomach mucosa, ghrelin is a peptide appetite hormone that has been implicated as an immuno-modulatory factor. Ghrelin has also been found in salivary glands and saliva; however, its expression patterns and biological properties in the oral cavity remain unclear. Therefore, we investigated the expression patterns of ghrelin in saliva, gingival crevicular fluid (GCF), and gingival tissue, as well as its in vitro effects on IL-8 production by TNF-α or LPS-stimulated oral epithelial cells. In the clinical samples obtained from 12 healthy volunteers, the concentration of ghrelin in GCF remarkably exceeded that detected in saliva. The expression of ghrelin mRNAs and growth hormone secretagogue (GHS) receptors could be detected in human oral epithelial cells. Immunohistochemical analysis revealed the expression of ghrelin in gingival epithelium, as well as in fibroblasts in the lamina propria. Ghrelin increased intracellular calcium mobilization and cAMP levels in oral epithelial cells, suggesting that ghrelin acts on epithelial cells to induce cell signaling. Furthermore, synthetic ghrelin inhibited the production of IL-8 from TNF-α or LPS-stimulated oral epithelial cells. These results indicate that ghrelin produced in the oral cavity appears to play a regulatory role in innate immune responses to inflammatory infection.
Double Edge
Authors: Wong D.T.W. , Kim J.J. , Khalid O. , Sun H.-H. , Kim Y.
Published: August 2011

Cancer research has been devoted toward an understanding of the molecular regulation and functional significance of cell-cycle regulators in the pathogenesis and development of cancers. Cyclin-dependent Kinase 2-associated Protein 1 (CDK2AP1) is one such cell-cycle regulator, originally identified as a growth suppressor and a prognostic marker for human oral/head and neck cancers. Functional importance and the molecular mechanism of CDK2AP1-mediated cell-cycle regulation have been documented over the years. Recent progress has shown that CDK2AP1 is a competency factor in embryonic stem cell differentiation. Deletion of CDK2AP1 leads to early embryonic lethality, potentially through altered differentiation capability of embryonic stem cells. More intriguingly, CDK2AP1 exerts its effect on stem cell maintenance/differentiation through epigenetic regulation. Cancer cells and stem cells share common cellular characteristics, most prominently in maintaining high proliferative potential through an unconventional cell-cycle regulatory mechanism. Cross-talk between cellular processes and molecular signaling pathways is frequent in any biological system. Currently, it remains largely elusive how cell-cycle regulation is mechanistically linked to epigenetic control. Understanding the molecular mechanism underlying CDK2AP1-mediated cell-cycle regulation and epigenetic control will set an example for establishing a novel and effective molecular link between these two important regulatory mechanisms.
Kindergarten Children’s Growth Trajectories in Reading and Mathematics
Authors: Morgan Paul L. , Farkas George , Wu Qiong
Published: August 2011

The authors used a large sample of children ( N ≈ 7,400) participating in the Early Childhood Longitudinal Study–Kindergarten Cohort (ECLS-K) to estimate kindergarten children’s academic achievement growth trajectories in reading and mathematics. The authors were particularly interested in whether the growth trajectories of children with learning disabilities (LD) or speech language impairments (SLI)—as well as those of other groups of children—were consistent with a cumulative or compensatory developmental cycle. Both LD and SLI children displayed significantly lower levels of kindergarten reading achievement than nondisabled children. However, and over the subsequent 5 years of elementary school, only children with SLI lagged increasingly behind nondisabled peers in their reading skills growth. The authors observed a different pattern for mathematics achievement. Children with LD, but not SLI, lagged increasingly behind nondisabled children in their mathematics skills growth. The authors also observed some consistency in “poor-get-poorer” effects across reading and mathematic achievement for additional population subgroups. Those kindergarten children who were from lower socioeconomic status families, who were African American, and who more frequently displayed learning-related behavior problems initially had lower levels of reading and mathematics achievement and also lagged increasingly behind in their acquisition of these skills over time. Some groups of children, including those with SLI, experience a cumulative rather than a compensatory cycle of achievement growth.
Matthew Effects in Reading Comprehension
Authors: Protopapas Athanassios , Sideridis Georgios D. , Mouzaki Angeliki , Simos Panagiotis G.
Published: August 2011

The presence of Matthew effects was tested in students of varying reading, spelling, and vocabulary skills. A cross-sequential design was implemented, following 587 Grade 2 through 4 students across five measurement points (waves) over 2 years. Students were administered standardized assessments of reading, spelling, and vocabulary. Results indicated that the hypothesized fan-spread pattern for Matthew effects was not evident. Low and high ability groups were formed based on 25th and 75th percentile cutoffs on initial measures of spelling, reading accuracy and fluency, vocabulary, and reading comprehension. Multilevel modeling suggested that low and high ability groups had significantly different starting points (intercepts) and their pattern of growth on passage comprehension did not indicate that the gap would increase over time. Instead, some analyses, especially of the youngest cohorts, showed significant convergence. However, there was no evidence of eventually closing the gap. Thus, although the poor students may not be getting poorer, they do not get sufficiently richer either.
On the Use of As If, As Though, and Like in Present-Day English Complementation Structures
Authors: López-Couso María José , Méndez-Naya Belén
Published: August 2011

This investigation is part of the authors’ larger research project on so-called minor declarative complementizers in the history of English, that is, connectives recruited mostly in the adverbial domain that are occasionally used in complementation. The present study sheds light on the complementizer use of the three originally comparative links as if, as though, and like in Present-Day English complement structures. In the theoretical part of the article, the authors argue for the complement analysis of certain clauses depending on as if, as though, and like (e.g., It seemed as if the strange little man had never been there). The empirical part of the study analyzes data drawn from the Brown family of corpora (LOB, Brown, FLOB, and Frown), the Diachronic Corpus of Present-day Spoken English (DCPSE), and the Toronto English Archive (TEA), which are representative of both written and spoken language at different time periods (1960s, 1990s, and early 2000s) and in different varieties of English (British English, American English, and Canadian English). Taking the corpus data as a starting point, and with the aim of revealing what ongoing change is observable in the contemporary language, the authors attend to the following issues: (a) the predicates and construction types associated with these minor links, (b) the factors determining the variation between the three comparative complementizers, and (c) the variation between as if, as though, and like and the default declarative complementizer that.
Reflecting on the Role of Literature in Qualitative Public Administration Research
Authors: Tummers Lars , Karsten Niels
Published: August 2011

When undertaking qualitative research, public administration scholars must walk a thin line between being theoretically sensitive and imposing preconceived ideas on their work. This article identifies opportunities and pitfalls in using literature in qualitative public administration research. Although the opportunities are already well known within the discipline, the pitfalls remain underexposed. The authors identify potential pitfalls by using insights from the grounded theory approach. To illustrate how opportunities can be optimally exploited, and pitfalls avoided, they provide examples of high-quality public administration research. Finally, the authors derive recommendations for public administration scholars when using literature in their qualitative research. These recommendations can help improve qualitative methods in the public administration discipline.
Improving reverse cycle defrosting performance of air source heat pumps using thermal storage-based refrigerant sub-cooling energy
Authors: Jiankai Dong , Yiqiang Jiang , Shiming Deng , Yang Yao , Minglu Qu
Published: August 2011

When an air source heat pump (ASHP) unit is used for space heating at a low ambient temperature in winter, frost may be formed on its outdoor coil surface. Over time, frost accumulation on coil surface may become sufficient to restrict air passage through the coil and increase the heat transfer resistance between ambient air and coil surface, leading to performance degradation for the outdoor coil, or even the shutdown of the ASHP unit. Therefore, periodic defrosting is necessary. Currently, the most widely used standard defrosting method for an ASHP unit is reverse cycle defrosting. During a standard reverse cycle defrosting (SRCD) operation, the indoor coil in an ASHP unit actually acts as an evaporator. Because the indoor fan is usually turned off during defrosting, there is an insignificant amount of energy from indoor coil, leading to a number of associated operational problems such as a longer defrosting duration and the risk of having a lower air temperature inside a heated space during defrosting, etc. To solve the fundamental problem of insufficient heat available during defrosting while ensuring the efficient and safe system operation, a novel reverse cycle defrosting (NRCD) method which is thermal energy storage-based using sub-cooling energy of refrigerant for ASHPs has been developed. Comparative experiments using both the SRCD method and the NRCD method were carried out on an experimental ASHP unit with a nominal 2.5 kW heating capacity. Experimental results clearly suggested that when using the NRCD method, the discharge and suction pressures were increased by 0.56 and 0.12 MPa, respectively. Furthermore, the defrosting duration and heating-resumption duration were shortened by 30.8% and 25.0%, respectively, and the defrosting energy consumption was reduced by 13.9%, compared to those when using the SRCD method.

Practical application: ASHPs have been widely used worldwide due to their significant energy-saving potentials. However, frost can be formed on the outdoor coil surface when an ASHP unit operates for space heating. Frost accumulation on coil surface reduces the coil’s efficiency, or causes even the shutdown of the ASHP unit. Reverse cycle defrosting is the most widely used standard defrosting method. This paper presents the reverse cycle defrosting performance for an ASHP unit with a PCM-HE acting as both a sub-cooler during heating operation and a heat source during defrosting operation, which could help to ensure the safe operation and achieve a higher defrosting efficiency of the ASHP unit.