bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical entrainment of human hypoglossal motor unit activities
Authors: Laine Christopher M. , Nickerson Laura A. , Bailey E. Fiona
Published: November 2011

Output from the primary motor cortex contains oscillations that can have frequency-specific effects on the firing of motoneurons (MNs). Whereas much is known about the effects of oscillatory cortical drive on the output of spinal MN pools, considerably less is known about the effects on cranial motor nuclei, which govern speech/oromotor control. Here, we investigated cortical input to one such motor pool, the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. We recorded intramuscular genioglossus electromyogram (EMG) and scalp EEG from healthy adult subjects performing a tongue protrusion task. Cortical entrainment of HMN population activity was assessed by measuring coherence between EEG and multiunit EMG activity. In addition, cortical entrainment of individual MN firing activity was assessed by measuring phase locking between single motor unit (SMU) action potentials and EEG oscillations. We found that cortical entrainment of multiunit activity was detectable within the 15- to 40-Hz frequency range but was inconsistent across recordings. By comparison, cortical entrainment of SMU spike timing was reliable within the same frequency range. Furthermore, this effect was found to be intermittent over time. Our study represents an important step in understanding corticomuscular synchronization in the context of human oromotor control and is the first study to document SMU entrainment by cortical oscillations in vivo.
A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis
Authors: Linden David J.
Published: November 2011

Long-term synaptic depression (LTD) of cerebellar parallel fiber-Purkinje cell synapses is a form of use-dependent synaptic plasticity that may be studied in cell culture. One form of LTD is induced postsynaptically through an mGlu1/Ca influx/protein kinase Cα (PKCα) cascade, and its initial expression requires phosphorylation of ser-880 in the COOH-terminal PDZ-ligand region of GluA2 and consequent binding of PICK1. This triggers postsynaptic clathrin/dynamin-mediated endocytosis of GluA2-containing surface AMPA receptors. Cerebellar LTD also has a late phase beginning 45–60 min after induction that is blocked by transcription or translation inhibitors. Here, I have sought to determine the expression mechanism of this late phase of LTD by applying various drugs and peptides after the late phase has been established. Neither bath application of mGluR1 antagonists (JNJ-16259685, LY-456236) nor the PKC inhibitor GF-109203X starting 60–70 min after LTD induction attenuated the late phase. Similarly, achieving the whole cell configuration with a second pipette loaded with the peptide PKC inhibitor PKC(19–36) starting 60 min postinduction also failed to alter the late phase. Late internal perfusion with peptides designed to disrupt PICK1-GLUA2 interaction or PICK1 dimerization failed to impact late phase LTD expression. However, late internal perfusion with two different blockers of dynamin, the drug dynasore and a dynamin inhibitory peptide (QVPSRPNRAP), produced rapid and complete reversal of cerebellar LTD expression. These findings suggest that the protein synthesis-dependent late phase of LTD requires persistent dynamin-mediated endocytosis, but not persistent PICK1-GluA2 binding nor persistent activation of the upstream mGluR1/PKCα signaling cascade.
Expressive Animated Character Sequences Using Knowledge-Based Painterly Rendering
Authors: Seifi Hasti , DiPaola Steve , Arya Ali
Published: November 2011

We propose a technique to enhance emotional expressiveness in games and animations. Artists have used colors and painting techniques to convey emotions in their paintings for many years. Moreover, researchers have found that colors and line properties affect users' emotions. We propose using painterly rendering for character sequences in games and animations with a knowledge-based approach. This technique is especially useful for parametric facial sequences. We introduce two parametric authoring tools for animation and painterly rendering and a method to integrate them into a knowledge-based painterly rendering system. Furthermore, we present the results of a preliminary study on using this technique for facial expressions in still images. The results of the study show the effect of different color palettes on the intensity perceived for an emotion by users. The proposed technique can provide the animator with a depiction tool to enhance the emotional content of a character sequence in games and animations.
Emerging Functions of Transcription Factors in Malaria Parasite
Authors: Tuteja Renu , Ansari Abulaish , Chauhan Virander Singh
Published: November 2011

Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs) are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression. Plasmodium falciparum is responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.
Thin Filament‐Reconstituted Skinned Muscle Fibers for the Study of Muscle Physiology
Authors: Higuchi Sayaka , Tsukasaki Yoshikazu , Fukuda Norio , Kurihara Satoshi , Fujita Hideaki
Published: November 2011

We review the use of thin filament‐reconstituted muscle fibers in the study of muscle physiology. Thin filament extraction and reconstitution protocol is a powerful technique to study the role of each component of the thin filament. It is also useful for studying the properties of genetically modified molecules such as actin and tropomyosin. We also review the combination of this protocol with sinusoidal analysis, which will provide a solid technique for determining the effect of regulatory proteins on actomyosin interaction and concomitant cross‐bridge kinetics. We suggest that thin filament‐reconstituted muscle fibers are an ideal system for studying muscle physiology especially when gene modifications of actin or tropomyosin are involved.
Retrobulbar Hemodynamic Effects of Nipradilol in Normal and Normal-Tension Glaucoma Eyes
Authors: Fukukita Mitsushi , Ido Masashi , Osawa Syunsuke , Sasoh Mikio , Furuta Motoyasu , Ito Kunio , Sugimoto Masahiko , Uji Yukitaka
Published: November 2011

Purpose. To investigate the effects of nipradilol on retrobulbar hemodynamics.Methods. We investigated normal and normal-tension glaucoma (NTG) eyes. Topical nipradilol (one eye) and placebo eye drops (fellow eye) were instilled for 1 week in volunteers. Nipradilol was also instilled in NTG patients. Ultrasound color Doppler imaging for the posterior vessels was performed before, 2 hr, 1 week (for normal), and at 4 weeks (for NTG).Results. In normal eyes, there were significant decreases in the resistance index (RI) for the temporal short posterior ciliary arteries (PCA) at 2 hr and for the ophthalmic arteries at 1 week. There were no significant changes in the placebo-treated eyes. In the NTG eyes, there was a significant decrease in the RI for the central retinal artery, nasal, and temporal PCA at 2 hr and 4 weeks.Conclusion. Short-term observations found that nipradilol increased the ocular blood flow in normal and NTG eyes.
Imaging of Spinal Metastatic Disease
Authors: Shah Lubdha M. , Salzman Karen L.
Published: November 2011

Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis.Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease.Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.
A New Empirical Model for Short‐Term Forecasting of the Broadband Penetration: A Short Research in Greece
Authors: Konstantinos Salpasaranis , Vasilios Stylianakis
Published: November 2011

The objective of this paper is to present a short research about the overall broadband penetration in Greece. In this research, a new empirical deterministic model is proposed for the short‐term forecast of the cumulative broadband adoption. The fitting performance of the model is compared with some widely used diffusion models for the cumulative adoption of new telecommunication products, namely, Logistic, Gompertz, Flexible Logistic (FLOG), Box‐Cox, Richards, and Bass models. The fitting process is done with broadband penetration official data for Greece. In conclusion, comparing these models with the empirical model, it could be argued that the latter yields well enough statistics indicators for fitting and forecasting performance. It also stresses the need for further research and performance analysis of the model in other more mature broadband markets.
An Existence Result for Neutral Delay Integrodifferential Equations with Fractional Order and Nonlocal Conditions
Authors: Li Fang , N′Guérékata Gaston M.
Published: November 2011

We study the existence of mild solutions of a class of neutral delay integrodifferential equations with fractional order and nonlocal conditions in a Banach space X. An existence result on the mild solution is obtained by using the theory of the measures of noncompactness and the theory of condensing maps. Two examples are given to illustrate the existence theorem.
Autologous Bone Marrow Stem Cells in the Treatment of Chronic Liver Disease
Authors: Pai Madhava , Spalding Duncan , Xi Feng , Habib Nagy
Published: November 2011

Chronic liver disease (CLD) is increasing worldwide yet there has been no major advance in effective therapies for almost five decades. There is mounting evidence that adult haematopoietic stem cells (HSC) are capable of differentiating into many types of tissue, including skeletal and cardiac muscle, neuronal cells, pneumocytes and hepatocytes. These recent advances in regenerative medicine have brought hope for patients with liver cirrhosis awaiting transplantation. New findings in adult stem cell biology are transforming our understanding of tissue repair raising hopes of successful regenerative hepatology. Although all clinical trials to date have shown some improvement in liver function and CD34+cells have been used safely for BM transplantation for over 20 years, only randomised controlled clinical trials will be able to fully assess the potential clinical benefit of adult stem cell therapy for patients with CLD. This article focuses on the potential of bone marrow stem cells (BMSCs) in the management of CLD and the unresolved issues regarding their role. We also outline the different mechanisms by which stem cells may impact on liver disease.
Late Type of Bronchial Response to Milk Ingestion Challenge: A Comparison of Open and Double-Blind Challenge
Authors: Pelikan Zdenek
Published: November 2011

Background. In some asthmatics the food allergy, for example, to milk, can participate in their bronchial complaints. The role of food allergy should be confirmed definitively by food ingestion challenge performed by an open challenge with natural foods
(OFICH) or by a double-blind placebo-controlled food challenge (DBPCFC). Objectives. To investigate the diagnostic value of these techniques for confirmation of a suspected milk allergy in bronchial
asthma patients. Methods. In 54 asthmatics with a positive history and/or positive skin tests for milk the 54 OFICH, and DBPCFC, were performed in combination with spirometry. Results. The 54 patients developed 39 positive late asthmatic responses (LAR) and 15 negative asthmatic responses to OFICH
and 40 positive LARs and 14 negative responses to DBPCFC. The overall correlation between the OFICH and DBPCFC was
statistically significant (). Conclusions. This study has confirmed the existence of LAR to milk ingestion performed by OFICH and DBPCFC in combination with spirometry. The results obtained by both the techniques did not differ significantly. The OFICH with natural food combined with monitoring of objective parameter(s), such as spirometry, seems to be a suitable method for detection of the food allergy in asthmatics. The DBPCFC can be performed as an additional check, if necessary.
Effect of Dentin Bonding Agent on the Prevention of Tooth Discoloration Produced by Mineral Trioxide Aggregate
Authors: Akbari Majid , Rouhani Armita , Samiee Sadeq , Jafarzadeh Hamid
Published: November 2011

Objective. Determination of the effect of dentin bonding agent (DBA) on the prevention of tooth discoloration produced by mineral trioxide aggregate (MTA).Methods. 50 teeth were endodontically treated and after removal of 3 mm of obturating materials were divided into five groups. In white MTA (WMTA) and grey MTA (GMTA) groups, these materials were placed in root canal below the orifice. In DBA + WMTA and DBA + GMTA groups, DBAs were applied in the access cavity. Then, 3 mm of WMTA and GMTA was placed. The last 10 teeth served as control. All of teeth were restored and color measurement was recorded for each specimen at this time and 6 months later.Results. The mean tooth discoloration in WMTA and GMTA groups was significantly more than DBA + WMTA and DBA + GMTA groups, respectively. There was no significant difference between DBA + WMTA and DBA + GMTA groups and control group.Conclusion. Application of DBA before MTA may prevent tooth discoloration.
Interest of Flow Diversion Prostheses in the Management of Unruptured Intracranial Aneurysms
Authors: Armoiry Xavier , Paysant Mélanie , Hartmann Daniel , Aulagner Gilles , Turjman Francis
Published: November 2011

Flow diversion prostheses represent a new endovascular approach aimed at treating patients with large wide-neck aneurysms. Our objective is to present this new technology, to review the clinical studies on efficacy, and to emphasize its current limits. Flow diversion prostheses consist of a cylinder made of a large number of braided microfilaments providing a large metallic surface when deployed and inducing a blood flow diversion outside the aneurysm. Two different brands are currently available. Clinical data supporting their efficacy are currently limited to six non comparative cohort studies that included between 18 and 107 patients. Procedural implantation was shown to be feasible in more than 90% and safe with a thirty-day mortality between 2.8 and 5.5%. Complete occlusion rates at twelve months varied between 85.7 and 100%. Even though promising, the current status of flow diversion prostheses needs further evaluation with randomized, prospective, clinical trials with comparison to conventional strategies including endovascular coiling or surgical clipping.
Inhibition of Aldose Reductase Activates Hepatic Peroxisome Proliferator-Activated Receptor-αand Ameliorates Hepatosteatosis in Diabetic db/db Mice
Authors: Qiu Longxin , Lin Jianhui , Xu Fangui , Gao Yuehong , Zhang Cuilin , Liu Ying , Luo Yu , Yang James Y.
Published: November 2011

We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPARα, leading to its activation and significant reductions in serum lipid levels. Herein, we report that inhibition of AR by zopolrestat or by a short-hairpin RNA (shRNA) against AR caused a significant reduction in serum and hepatic triglycerides levels in 10-week old diabetic db/db mice. Meanwhile, hyperglycemia-induced phosphorylation of hepatic ERK1/2 and PPARαwas significantly attenuated in db/db mice treated with zopolrestat or AR shRNA. Further, in comparison with the untreated db/db mice, the hepatic mRNA expression ofAcoandApoA5, two target genes for PPARα, was increased by 93% (P<0.05) and 73% (P<0.05) in zopolrestat-treated mice, respectively. Together, these data indicate that inhibition of AR might lead to significant amelioration in hyperglycemia-induced dyslipidemia and nonalcoholic fatty liver disease.
Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses
Authors: Juno Jennifer , Fowke Keith R. , Keynan Yoav
Published: November 2011

Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.
Host Cell Signalling andLeishmaniaMechanisms of Evasion
Authors: Shio Marina Tiemi , Hassani Kasra , Isnard Amandine , Ralph Benjamin , Contreras Irazu , Gomez Maria Adelaida , Abu-Dayyeh Issa , Olivier Martin
Published: November 2011

Leishmaniaparasites are able to secure their survival and propagation within their host by altering signalling pathways involved in the ability of macrophages to kill pathogens or to engage adaptive immune system. An important step in this immune evasion process is the activation of host protein tyrosine phosphatase SHP-1 byLeishmania. SHP-1 has been shown to directly inactivate JAK2 and Erk1/2 and to play a role in the negative regulation of several transcription factors involved in macrophage activation. These signalling alterations contribute to the inactivation of critical macrophage functions (e.g., Nitric oxide, IL-12, and TNF-α). Additionally, to interfere with IFN-γreceptor signalling,Leishmaniaalso alters several LPS-mediated responses. Recent findings from our laboratory revealed a pivotal role for SHP-1 in the inhibition of TLR-induced macrophage activation through binding to and inactivating IL-1-receptor-associated kinase 1 (IRAK-1). Furthermore, we identified the binding site as an evolutionarily conserved ITIM-like motif, which we named kinase tyrosine-based inhibitory motif (KTIM). Collectively, a better understanding of the evasion mechanisms utilized byLeishmaniaparasite could help to develop more efficient antileishmanial therapies in the near future.
Phenylarsine Oxide Induces Apoptosis in Bax- and Bak-Deficient Cells through Upregulation of Bim
Authors: Ni Biyun , Ma Qi , Li Baowei , Zhao Lixia , Liu Yong , Zhu Yushan , Chen Quan
Published: November 2011

Purpose: Bax and Bak are regarded as key mediators for cytochrome c (Cyt c) release and apoptosis. Loss of Bax or Bak is often reported in human cancers and renders resistance of these cancerous cells to chemotherapy. Here, we investigated that phenylarsine oxide (PAO) could induce Bax/Bak-independent apoptosis.

Experimental Design: Annexin V/propidium iodide (PI) staining, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining, and caspase activation assays were conducted to detect apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts (MEF) and HCT116 bax−/− colorectal cancer cells. Cyt c release and Bim expression were assessed by Western blotting and immunostaining. Bim was stably knocked down by short hairpin RNA. Immunoprecipitation was applied to detect the interaction between Bim and Bcl-2. Both subcutaneous and colorectal orthotopic tumor implantation models were used in nude mice to investigate the effect of PAO in vivo.

Results: PAO triggered Cyt c release and apoptosis in a Bax/Bak-independent manner. Bim and Bcl-2 were both involved in this process. PAO augmented the expression of Bim and strengthened the interaction between Bim and Bcl-2. Furthermore, PAO attenuated the growth of Bax-deficient cancer cells in vivo.

Conclusions: Our results showed that PAO induced apoptosis in chemotherapy-resistant cancer cells, which suggests that PAO has the potential to serve as a chemotherapeutic agent for Bax- and Bak-deficient cancers. Clin Cancer Res; 18(1); 140–51. ©2011 AACR.
IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma
Authors: Miyagaki Tomomitsu , Sugaya Makoto , Suga Hiraku , Kamata Masahiro , Ohmatsu Hanako , Fujita Hideki , Asano Yoshihide , Tada Yayoi , Kadono Takafumi , Sato Shinichi
Published: November 2011

Purpose: Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, TH2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22–producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of TH22- and TH17-related molecules in lesional skin and sera isolated from patients with CTCL.

Experimental Design: Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry.

Results: IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity.

Conclusions: Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6+ cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL. Clin Cancer Res; 17(24); 7529–38. ©2011 AACR.
Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma
Authors: Kirkwood John M. , Bastholt Lars , Robert Caroline , Sosman Jeff , Larkin James , Hersey Peter , Middleton Mark , Cantarini Mireille , Zazulina Victoria , Kemsley Karin , Dummer Reinhard
Published: November 2011

Purpose: To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma.

Experimental Design: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m2/d for 5 days, then 23 days off-treatment). The primary endpoint was progression-free survival.

Results: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86–1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide.

Conclusions: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors. Clin Cancer Res; 18(2); 555–67. ©2011 AACR.
The mRNA Stability Factor HuR Inhibits MicroRNA-16 Targeting of COX-2
Authors: Young Lisa E. , Moore Ashleigh E. , Sokol Lena , Meisner-Kober Nicole , Dixon Dan A.
Published: November 2011

Commonly observed in colorectal cancer is the elevated expression of the prostaglandin (PG) synthase COX-2. In normal intestinal epithelium, the COX-2 mRNA is targeted for rapid decay through the 3′-untranslated region (3′-UTR) adenylate- and uridylate (AU)-rich element (ARE), whereas in tumors ARE-mediated decay is compromised. Here we show that the COX-2 ARE can mediate degradation through microRNA (miRNA)-mediated regulation. We identified miR-16 to bind the COX-2 3′-UTR and inhibit COX-2 expression by promoting rapid mRNA decay. In colorectal cancer cells and tumors, miR-16 levels were decreased approximately twofold and miR-16 expression in cancer cells attenuated COX-2 expression and PG synthesis. The COX-2 ARE is also bound by the RNA-binding protein HuR. In colorectal cancer tumors, HuR is overexpressed and localized within the cytoplasm, where it promotes ARE-mRNA stabilization. Under conditions of HuR overexpression, miR-16 was unable to promote rapid mRNA decay through the COX-2 ARE. Ribonucleoprotein immunoprecipitation of HuR showed direct association with miR-16 that was reversed when cytoplasmic trafficking of HuR was inhibited. Furthermore, this interaction between HuR and miR-16 promoted the downregulation of miR-16. These new results identify miR-16 as a central posttranscriptional regulator of COX-2 and show the ability of elevated levels of HuR to antagonize miR-16 function. Along with insight into altered ARE-mediated mRNA decay observed in colorectal cancer, these findings provide a new explanation for tumor-derived loss of miR-16. Mol Cancer Res; 10(1); 167–80. ©2011 AACR.
How Do We Safely Get People to Stop Smoking?
Authors: Lam David C.L. , Minna John D.
Published: November 2011

Nicotine replacement therapy (NRT) is a valuable, proven, and U.S. Food and Drug Administration–approved tool for smoking cessation. However, the discoveries of functional nicotinic acetylcholine receptors (nAChR) on lung epithelial and cancer cells and of nAChR polymorphisms associated with lung cancer risk, in addition to a large number of preclinical studies indicating that nicotine may promote or facilitate cancer development and growth, have prompted concern that NRT, although important for smoking cessation, may actually augment lung carcinogenesis. Therefore, it is of great public health interest that two independent studies reported in this issue of the journal (Murphy and colleagues, beginning on page 1752, and Maier and colleagues, beginning on page 1743) showed that nicotine given in drinking water at a dose to achieve blood concentrations in mice similar to those achieved in people receiving NRT did not enhance lung carcinogenesis or tumor growth in several mouse models of lung cancer. Effective non-nicotine alternatives to NRT, such as varenicline and bupropion, are also available and perhaps better than NRT for smoking cessation therapy. In the near future, nicotine vaccines will likely be added to the smoking cessation armamentarium. However, the normal and pathophysiologic role of nicotine, nAChRs, and the signaling pathways they activate in lung epithelial cells and lung cancer still requires elucidation. Cancer Prev Res; 4(11); 1724–7. ©2011 AACR.
Long-term Nicotine Replacement Therapy: Cancer Risk in Context
Authors: Shields Peter G.
Published: November 2011

Nicotine replacement therapy (NRT) for up to 12 weeks is well established, safe and efficacious for fostering smoking cessation. Some smokers at a high risk of relapse may benefit from long-term use, and so long-term NRT safety and efficacy have become a paramount question for the FDA and others. Laboratory studies have indicated a carcinogenic potential of nicotine. Animal model studies reported in this issue of the journal by Maier and colleagues (beginning on page 1743) and Murphy and colleagues (beginning on page 1752), however, provide additional reassurance that NRT does not promote lung cancer. Very long-term studies of NRT effects do not yet exist and would be needed to definitively answer the question about NRT efficacy and cancer risk and some decision making will need to be made based on limited human data and experimental studies. The overall NRT safety question is complex and requires consideration of three contexts and comparator groups (long-term NRT/abstinence vs. smoking, long-term intermittent NRT/reduced smoking vs. smoking, and long-term NRT/abstinence vs. abstinence without long-term NRT). Although the data on these issues are insufficient, the first comparison seems intuitive and may be compelling enough to allow the FDA to approve a long-term indication for NRT. An important public health goal is to help smokers and their health care providers understand the implications of potential long-term NRT risks in the context of its potential benefits and the far greater risks of continued smoking. Cancer Prev Res; 4(11); 1719–23. ©2011 AACR.
Adipokines and Cardiovascular Risk in Cushing’s Syndrome
Authors: Valassi Elena , Biller Beverly M.K. , Klibanski Anne , Misra Madhusmita
Published: November 2011

Cushing’s syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or ‘cured’ CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.
Effects of Strength Training versus Power Training on Physical Performance in Prefrail Community-Dwelling Older Adults
Authors: Drey Michael , Zech Astrid , Freiberger Ellen , Bertsch Thomas , Uter Wolfgang , Sieber Cornel C. , Pfeifer Klaus , Bauer Juergen M.
Published: November 2011

Background: It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults. Objective: The purpose of the present study was to compare the effects of strength training (ST) versus power training (PT) on functional performance in prefrail older adults. This study was registered at clinicaltrials.gov as NCT00783159. Methods: 69 community-dwelling older adults (>65 years) who were prefrail according to the definition of Fried were included in a 12-week exercise program. The participants were randomized into an ST group, a PT group and a control group. All participants were supplemented with vitamin D3 orally before entering the intervention period. The primary outcome was the global score on the Short Physical Performance Battery (SPPB). Secondary outcomes were muscle power, appendicular lean mass (aLM) measured by dual energy X-ray absorptiometry and self-reported functional deficits (Short Form of the Late-Life Function and Disability Instrument, SF-LLFDI). Results: Regarding changes in the SPPB score during the intervention, significant heterogeneity between the groups was observed (p = 0.023). In pair-wise comparisons, participants in both training groups significantly (PT: p = 0.012, ST: 0.009) increased their SPPB score (PT: Δmean = 0.8, ST: Δmean = 1.0) compared to the control group, with no statistical difference among training groups (p = 0.301). No statistical differences were found in changes in aLM (p = 0.769), muscle power (p = 0.308) and SF-LLFDI (p = 0.623) between the groups. Muscle power significantly increased (p = 0.017) under vitamin D3 intake. Conclusions: In prefrail community-dwelling adults, PT is not superior to ST, although both training modes resulted in significant improvements in physical performance. With regard to dropout rates, ST appears to be advantageous compared to PT. The high prevalence of vitamin D3 deficiency and the slight improvement of physical performance under vitamin D3 supplementation among study participants underline the relevance of this approach in physical exercise interventions.
Progression from Mild to Pronounced MCI Is Not Associated with Cerebrospinal Fluid Biomarker Deviations
Authors: Wallin A. , Göthlin M. , Gustavsson M. , Zetterberg H. , Eckerström C. , Blennow K. , Edman Å. , Lind K. , Nordlund A. , Rolstad S.
Published: November 2011

Background/Aim: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. Methods: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), β-amyloid 1–42 (Aβ42) and the light subunit of neurofilament protein (NFL) were determined. Results: Patients with converting MCI and stable dementia had lower CSF Aβ42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non-progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. Conclusion: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group.
Treatment of Psoriatic Nails with Indigo Naturalis Oil Extract: A Non-Controlled Pilot Study
Authors: Lin Yin-Ku , See Lai-Chu , Chang Ya-Ching , Huang Yu-Huei , Chen Jiun-Liang , Tsou Teng-Cheng , Leu Yann-Lii , Shen Yu-Ming
Published: November 2011

Background: In the treatment of nail psoriasis, standardized therapeutic regimens are currently lacking. Objective: To evaluate the therapeutic efficacy of indigo naturalis oil extract in patients with nail psoriasis. Methods: Patients with nail psoriasis applied indigo naturalis oil extract on affected nails twice daily for 24 weeks. Efficacy was evaluated using the Nail Psoriasis Severity Index (NAPSI) and modified target NAPSI for the single most severely affected nail. Results: Twenty-eight out of 32 patients completed the study. The mean NAPSI was 36.1 ± 14.7 at baseline and decreased to 14.9 ± 11.1 at week 24 while the mean modified target NAPSI was 11.7 ± 3.9 at baseline and decreased to 3.6 ± 3.2 at week 24. Conclusions: Indigo naturalis oil extract appeared to improve nail psoriasis. Although preliminary, these results indicate that it could provide a novel therapeutic option for nail psoriasis, a disease notoriously difficult to treat.
An Exact Thickness-Weighted Average Formulation of the Boussinesq Equations
Authors: Young William R.
Published: November 2011

The author shows that a systematic application of thickness-weighted averaging to the Boussinesq equations of motion results in averaged equations of motion written entirely in terms of the thickness-weighted velocity; that is, the unweighted average velocity and the eddy-induced velocity do not appear in the averaged equations of motion. This thickness-weighted average (TWA) formulation is identical to the unaveraged equations, apart from eddy forcing by the divergence of three-dimensional Eliassen–Palm (EP) vectors in the two horizontal momentum equations. These EP vectors are second order in eddy amplitude and, moreover, the EP divergences can be expressed in terms of the eddy flux of the Rossby–Ertel potential vorticity derived from the TWA equations of motion. That is, there is a fully nonlinear and three-dimensional generalization of the one- and two-dimensional identities found by Taylor and Bretherton. The only assumption required to obtain this exact TWA formulation is that the buoyancy field is stacked vertically; that is, that the buoyancy frequency is never zero. Thus, the TWA formulation applies to nonrotating stably stratified turbulent flows, as well as to large-scale rapidly rotating flows. Though the TWA formulation is obtained by working on the equations of motion in buoyancy coordinates, the averaged equations of motion can then be translated into Cartesian coordinates, which is the most useful representation for many purposes.
Analysis of Tidal Straining as Driver for Estuarine Circulation in Well-Mixed Estuaries
Authors: Burchard Hans , Schuttelaars Henk M.
Published: November 2011

Tidal straining, which can mathematically be described as the covariance between eddy viscosity and vertical shear of the along-channel velocity component, has been acknowledged as one of the major drivers for estuarine circulation in channelized tidally energetic estuaries. In this paper, the authors investigate the role of lateral circulation for generating this covariance. Five numerical experiments are carried out, starting with a reference scenario including the full physics and four scenarios in which specific key physical processes are neglected. These processes are longitudinal internal pressure gradient forcing, lateral internal pressure gradient forcing, lateral advection, and the neglect of temporal variation of eddy viscosity. The results for the viscosity–shear covariance are correlated across different experiments to quantify the change due to neglect of these key processes. It is found that the lateral advection of vertical shear of the along-channel velocity component and its interaction with the tidally asymmetric eddy viscosity (which is also modified by the lateral circulation) is the major driving force for estuarine circulation in well-mixed tidal estuaries.
Annual Cycle and Depth Penetration of Wind-Generated Near-Inertial Internal Waves at Ocean Station Papa in the Northeast Pacific
Authors: Alford Matthew H. , Cronin Meghan F. , Klymak Jody M.
Published: November 2011

The downward propagation of near-inertial internal waves following winter storms is examined in the context of a 2-yr record of velocity in the upper 800 m at Ocean Station Papa. The long time series allow accurate estimation of wave frequency, whereas the continuous data in depth allow separation into upward- and downward-propagating components. Near-inertial kinetic energy (KEin) dominates the record. At all measured depths, energy in downgoing motions exceeds that of upward-propagating motions by factors of 3–7, whereas KEin is elevated by a factor of 3–5 in winter relative to summer. The two successive winters are qualitatively similar but show important differences in timing and depth penetration. Energy is seen radiating downward in a finite number of wave groups, which are tagged and catalogued to determine the vertical group velocity cgz, which has a mean of about 1.5 × 10−4 m s−1 (13 m day−1). Case studies of three of these are presented in detail.

Downward energy flux is estimated as cgz × KEin (i) by summing over the set of events, (ii) from time series near the bottom of the record, and (iii) from the wavenumber–frequency spectrum and the dispersion relationship. These estimates are compared to the work done on near-inertial motions in the mixed layer by the wind, which is directly estimated from mixed layer near-inertial currents and winds measured from a surface buoy 10 km away. All three methods yield similar values, indicating that 12%–33% of the energy input into the mixed layer transits 800 m toward the deep sea. This simple picture neglects lateral energy flux carried by the first few vertical modes, which was not measured. The substantial deep penetration implies that near-inertial motions may play a role in mixing the deep ocean, but the strong observed variability calls for a need to better understand the role of lateral mesoscale structures in modulating the vertical propagation.
A Political Ecology of “Water in Mind”: Attributing Perceptions in the Era of Global Climate Change
Authors: Crate Susan A.
Published: November 2011

This article explores how researchers can apply social science methods and theoretical frames to capture how place-based communities are perceiving and responding to the immediate effects of global climate change. The study focuses on research with Viliui Sakha—native horse and cattle breeders of northeastern Siberia, Russia, who are increasingly challenged by one of global climate change’s most prevalent effects: altered water regimes. By applying the theoretical framework of political ecology, the article shows how researchers can better understand how affected peoples have, in this case, “water in mind” via their histories, cosmologies, and management practices of water. Such awareness can inform research activities and findings, facilitate effective adaptation, and, ultimately, affect policy. Given the widespread emphasis on adaptation, including the urgent need for, increasing interest in, and funding support for transdisciplinary research projects on adaptation, and the facilitative role researchers and policymakers can play in adaptation, this move to understanding and integrating a population’s shifting perceptions—in this case, of water in mind—into research is fundamental.
Voices of Early Career Psychologists in Division 17, the Society of Counseling Psychology
Authors: Smith Nathan Grant , Keller Briana K. , Mollen Debra , Bledsoe Meredith L. , Buhin Larisa , Edwards Lisa M. , Levy Jacob J. , Magyar-Moe Jeana L. , Yakushko Oksana
Published: November 2011

This article reports on a survey of early career members of the Society of Counseling Psychology (SCP). Seventy early career psychologists completed a survey assessing the usefulness and climate of SCP, barriers to and facilitative factors for involvement in SCP, inclusiveness of SCP regarding cultural diversity and professional interests, degree of involvement in various aspects of SCP, and their areas of satisfaction and dissatisfaction with SCP membership. In general, participants were split on the degree to which they were satisfied with SCP, with participants in faculty positions reporting significantly more positive views of SCP than their practitioner counterparts did. Faculty members viewed SCP as more useful to their careers and reported more positive social interactions within SCP than did non–faculty members. Open-ended responses suggested that satisfaction with SCP was related to availability of mentorship and opportunities for involvement in SCP. Suggestions for engaging new professionals in SCP are offered.
Language Brokering Among Mexican-Immigrant Families in the Midwest
Authors: Morales Alejandro , Yakushko Oksana F. , Castro Antonio J.
Published: November 2011

Language brokering (LB) is the act of translating and interpreting within immigrant families by children and adolescents for their parents, other family members, and other adults. Although LB is a common phenomenon among immigrant families in the United States, research regarding its impact on immigrant families mainly focuses on the experiences of language brokers only and not on their parents or immediate families. Thus, the purpose of this in-depth multiple qualitative case study was to understand how the demands of LB affected relationships within Mexican immigrant families living in the Midwestern United States. Six two-parent Mexican immigrant families with an identified child language broker participated in this study. Parents and child brokers were interviewed separately and participated in an LB simulation. The data were analyzed case by case through thematic analysis followed by cross-case analysis. Four themes emerged as pertinent across all cases and included family relationships, feelings about brokering, language brokering situations, and challenges of language brokering.
Rotary ultrasonic machining of carbon fiber-reinforced plastic composites: using cutting fluid vs. cold air as coolant
Authors: Cong WL , Feng Q , Pei ZJ , Deines TW , Treadwell C
Published: November 2011

Drilling is involved in many applications of carbon fiber-reinforced plastic (CFRP) composites. Rotary ultrasonic machining (RUM) has been successfully employed to drill holes in CFRP using either cutting fluid or cold air as coolant. However, there are no reported studies to compare the results in RUM of CFRP using these two types of coolant. This article, for the first time, presents an experimental study to compare cutting force, torque, surface roughness, burning of machined surface, and tool wear in RUM of CFRP using these two types of coolant. This study will result in knowledge about machining conditions under which it is feasible to use cold air instead of cutting fluid and differences in machined hole quality produced using cold air vs. cutting fluid.
Prospects for the UK Economy
Authors: Kirby Simon , Whitworth Rachel
Published: November 2011

The economic news flow since the publication of our JulyReviewhas been predominately negative, focusing on the deteriorating Euro Area sovereign debt crisis. This has added to further disappointing data on UK domestic activity. Quarterly economic growth has averaged just 0.3 per cent in the first three quarters of 2011 (see figure 1). Anaemic GDP growth is due to both the public and private sectors simultaneously consolidating their balance sheets. Looking ahead, the crisis in the Euro Area will play a central role. We expect the UK economy to expand by 0.9 per cent this year and 0.8 per cent in 2012, before increasing by 2.6 per cent in 2013. This will be the most protracted recovery since the end of the First World War (see figure 2).