bluuebunny/crossref_metadata_2025 huggingface dataset:
PDE5 inhibitor promotes melanin synthesis through the PKG pathway in B16 melanoma cells
Authors: Zhang Xiaodong , Yan Guirui , Ji Jun , Wu Jingwei , Sun Xiaoyun , Shen Jingshan , Jiang Hualiang , Wang Heyao
Published: March 2012

PDE inhibitors could increase cellular cGMP levels and are used to treat erectile dysfunction as well as pulmonary arterial hypertension. cGMP production was reported to be necessary for UVB‐induced melanin synthesis, however, the effect of PDE5 inhibitor on melanin synthesis has not been examined. We found that PDE5 inhibitor (sildenafil or vardenafil) and the cGMP analog 8‐CPT‐cGMP stimulated CREB phosphorylation, leading to increased tyrosinase expression and melanin synthesis, which was counteracted by KT5823, a selective cGMP‐dependent protein kinase (PKG) inhibitor. However, KT5823 did not affect cAMP‐elevating agent‐mediated melanin synthesis, indicating that KT5823 selectively inhibited cGMP‐induced melanin synthesis. This is the first study to find that PDE5 inhibitor can promote melanin synthesis and reveal that PKG‐dependent CREB phosphorylation and tyrosinase expression is involved in cGMP‐induced melanin synthesis. Our results suggest that PDE5 inhibitor may be beneficial for the treatment of hypopigmentation diseases. J. Cell. Biochem. 113: 2738–2743, 2012. © 2012 Wiley Periodicals, Inc.
Acetylcholine induces mesenchymal stem cell migration via Ca2+/PKC/ERK1/2 signal pathway
Authors: Tang Jun‐Ming , Yuan Jie , Li Qing , Wang Jia‐Ning , Kong Xia , Zheng Fei , Zhang Lei , Chen Long , Guo Lin‐Yun , Huang Yong‐Hang , Yang Jian‐Ye , Chen Shi‐You
Published: March 2012

Acetylcholine (ACh) plays an important role in neural and non‐neural function, but its role in mesenchymal stem cell (MSC) migration remains to be determined. In the present study, we have found that ACh induces MSC migration via muscarinic acetylcholine receptors (mAChRs). Among several mAChRs, MSCs express mAChR subtype 1 (m1AChR). ACh induces MSC migration via interaction with mAChR1. MEK1/2 inhibitor PD98059 blocks ERK1/2 phosphorylation while partially inhibiting the ACh‐induced MSC migration. InsP3Rs inhibitor 2‐APB that inhibits MAPK/ERK phosphorylation completely blocks ACh‐mediated MSC migration. Interestingly, intracellular Ca2+ ATPase‐specific inhibitor thapsigargin also completely blocks ACh‐induced MSC migration through the depletion of intracellular Ca2+ storage. PKCα or PKCβ inhibitor or their siRNAs only partially inhibit ACh‐induced MSC migration, but PKC‐ζ siRNA completely inhibits ACh‐induced MSC migration via blocking ERK1/2 phosphorylation. These results indicate that ACh induces MSC migration via Ca2+, PKC, and ERK1/2 signal pathways. J. Cell. Biochem. 113: 2704–2713, 2012. © 2012 Wiley Periodicals, Inc.
ATF5, a possible regulator of osteogenic differentiation in human adipose‐derived stem cells
Authors: Leong David Tai , Abraham Mohan Chothirakottu , Gupta Anurag , Lim Thiam‐Chye , Chew Fook Tim , Hutmacher Dietmar Werner
Published: March 2012

The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their “stem‐ness” are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose‐derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down‐regulated in a randomized time‐course study of osteogenically differentiated adipose‐derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose‐derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. J. Cell. Biochem. 113: 2744–2753, 2012. © 2012 Wiley Periodicals, Inc.
Regulation of gene expression in retrovirus vectors by X‐ray and proton beam radiation with artificially constructed promoters
Authors: Ogawa Ryohei , Morii Akihiro , Watanabe Akihiko , Cui Zheng‐Guo , Kagiya Go , Fukuda Shigekazu , Kume Kyo , Hasegawa Takashi , Hatashita Masanori , Izumi Hironori , Ishimoto Tetsuya , Feril Loreto B.
Published: March 2012

Background

We previously obtained an X‐ray responsive promoter from 11 promoters that we constructed. In the present study, we aimed to determine the efficiency of our promoter construction method. In addition, the reactivity of the promoter to X‐rays in vivo is also investigated.

Methods

Promoters constructed by linking the TATA box to randomly combined binding sequences of transcription factors activated by radiation were cloned to prepare a promoter library. Combinations of promoters and various genes were stably‐transfected into HeLa cells to establish recombinant cell lines, which were then exposed to X‐rays or a proton beam to observe gene expression enhancement with or without anti‐oxidants. Tumors of luciferase‐expressing recombinant cells on mice were exposed to X‐rays and promoter activation was evaluated by detecting bioluminescence. As a model for in vitro suicide gene therapy, fcy::fur‐expressing recombinant cells were exposed to X‐rays before incubation with 5‐fluorocytosin. Cell viability was determined with WST‐8.

Results

Twenty‐five of the 62 promoters in the library enhanced luciferase activity over five‐fold, 6 h after receiving 10 Gy of X‐ray irradiation, suggesting the effectiveness of our method. Luciferase activity in recombinant cells was enhanced by X‐rays and, to a lesser extent, by a proton beam. Anti‐oxidants attenuated the enhancement, suggesting the involvement of oxidative stress. Promoters were less reactive to X‐rays in tumors on mice. In our suicide gene therapy model, survival of post‐irradiated cells decreased dose‐dependently with 5‐fluorocytosin.

Conclusions

Our method was efficient in generating radiation responsive promoters. Furthermore, we have successfully shown a potential therapeutic use for one of these promoters. Copyright © 2012 John Wiley & Sons, Ltd.
Fertigation of humic substances improves yield and quality of broccoli and nutrient retention in a sandy soil
Authors: Selim El‐Metwally , Ali Mosa Ahmed
Published: March 2012

There is lack of information available concerning the effect of humic substances (HS) applied via fertigation on plant growth in sandy soils. Therefore, a field experiment was carried out at El‐Saff district (20 km southwest of Cairo), Egypt, to investigate the role of HS fertigation on water retention of a sandy soil, yield and quality of broccoli (Broccoli oleracea L.) as well as on soil nutrient concentration retained after harvest. The experiment consisted of six fertigation treatments (50%, 75%, and 100% of the recommended NPK‐fertilizer rate for broccoli combined with and without HS application at 120 L ha–1) in a complete randomized block design with three replicates. Humic substances affected spatial water distribution and improved water retention in the root zone. Furthermore, application of HS increased total marketable yield and head diameter of broccoli as well as quality parameters (i.e., total soluble solids, protein, and vitamin C). Higher nutrient concentrations were found in the broccoli heads and concentrations of plant‐available nutrients in soil after harvesting were also higher, indicating an improvement in soil fertility. In conclusion, HS fertigation can be judged as an interesting option to improve soil water and nutrient status leading to better plant growth.
Effects of biochar compared to organic and inorganic fertilizers on soil quality and plant growth in a greenhouse experiment
Authors: Schulz Hardy , Glaser Bruno
Published: March 2012

Our contemporary society is struggling with soil degradation due to overuse and climate change. Pre‐Columbian people left behind sustainably fertile soils rich in organic matter and nutrients well known as terra preta (de Indio) by adding charred residues (biochar) together with organic and inorganic wastes such as excrements and household garbage being a model for sustainable agriculture today. This is the reason why new studies on biochar effects on ecosystem services rapidly emerge. Beneficial effects of biochar amendment on plant growth, soil nutrient content, and C storage were repeatedly observed although a number of negative effects were reported, too. In addition, there is no consensus on benefits of biochar when combined with fertilizers. Therefore, the objective of this study was to test whether biochar effects on soil quality and plant growth could be improved by addition of mineral and organic fertilizers. For this purpose, two growth periods of oat (Avena sativa L.) were studied under tropical conditions (26°C and 2600 mm annual rainfall) on an infertile sandy soil in the greenhouse in fivefold replication. Treatments comprised control (only water), mineral fertilizer (111.5 kg N ha–1, 111.5 kg P ha–1, and 82.9 kg K ha–1), compost (5% by weight), biochar (5% by weight), and combinations of biochar (5% by weight) plus mineral fertilizer (111.5 kg N ha–1, 111.5 kg P ha–1, and 82.9 kg K ha–1), and biochar (2.5% by weight) plus compost (2.5% by weight). Pure compost application showed highest yield during the two growth periods, followed by the biochar + compost mixture. biochar addition to mineral fertilizer significantly increased plant growth compared to mineral fertilizer alone. During the second growth period, plant yields were significantly smaller compared to the first growth period. biochar and compost additions significantly increased total organic C content during the two growth periods. Cation‐exchange capacity (CEC) could not be increased upon biochar addition while base saturation (BS) was significantly increased due to ash addition with biochar. On the other hand, compost addition significantly increased CEC. Biochar addition significantly increased soil pH but pH value was generally lower during the second growth period probably due to leaching of base cations. Biochar addition did not reduce ammonium, nitrate, and phosphate leaching during the experiment but it reduced nitrification. The overall plant growth and soil fertility decreased in the order compost > biochar + compost > mineral fertilizer + biochar > mineral fertilizer > control. Further experiments should optimize biochar–organic fertilizer systems.
Land‐use change in subalpine grassland soils: Effect on particulate organic carbon fractions and aggregation
Authors: Meyer Stefanie , Leifeld Jens , Bahn Michael , Fuhrer Jürg
Published: March 2012

Abandonment of mountain grassland often changes vegetation composition and litter quantity and quality, but related effects on labile soil organic matter (SOM) are largely unknown. The aim of this study was to investigate the impacts of grassland management and abandonment on soil carbon distribution in light (< 1.6 g cm–3) particulate organic matter (POM) and aggregation along a gradient of management intensity including hay meadows, pastures, and abandoned grasslands. The reduction of management intensity is an interregional phenomenon throughout the European Alps. We therefore selected sites from two typical climate regions, namely at Stubai Valley, Austria (MAT: 3°C, MAP: 1097 mm) and Matsch Valley, Italy (MAT: 6.6°C, MAP: 527 mm), to evaluate effects of land‐use change in relation to climate. Free water‐floatable and free POM (wPOM, fPOM), and an occluded POM fraction (oPOM), were isolated from three water‐stable aggregate size classes (2–6.3 mm, 0.25–2 mm, < 0.25 mm) using density fractionation. Aggregate mean weight diameter slightly decreased with decreasing management intensity. In contrast to absolute POM‐C, fPOM‐C increased in aggregates at both sites with abandonment. Because the oPOM‐C was less affected by abandonment, the ratio of oPOM‐C : fPOM‐C shifted from > 1 to < 1 from meadow to abandoned grassland in aggregates at both sites and thus independent of climate. This suggests that in differently managed mountain grasslands free and occluded POM are functionally different SOM fractions. In bulk soil, the oPOM‐C : fPOM‐C ratio is better suited as an indicator for the response of SOM to management reduction in subalpine grasslands than the total soil C, absolute or relative POM‐C content.
Novel molecular screening approaches in colorectal cancer
Authors: Miller Seth , Steele Scott
Published: March 2012

Traditional methods for colorectal cancer (CRC) screening have reduced rates of malignancy and death; however, low compliance and morbidities associated with invasive techniques have encouraged efforts for establishing equally effective, less invasive novel screening approaches. We review the current state of novel screening approaches in CRC to include CT colonography, fecal DNA, DNA methylation, micro‐RNA, and protein and molecular markers. J. Surg. Oncol. 2012; 105:459–467. © 2012 Wiley Periodicals, Inc.
Clinical decision support systems: Potential with pitfalls
Authors: Eberhardt John , Bilchik Anton , Stojadinovic Alexander
Published: March 2012

Clinical Decision Support Systems (CDSS), an important part of clinical practice, are comprised of a: knowledge base; program for integrating patient‐specific information with the knowledge‐base; and, user‐interface to allow clinicians to interact with the system and get the right information needed to make the right decision for the right patient at the right time. We review the common approaches to CDSS, their strengths and weaknesses and how they are evaluated and developed for clinical use. J. Surg. Oncol. 2012; 105:502–510. © 2012 Wiley Periodicals, Inc.
Irregular osteotomy in limb salvage for juxta‐articular osteosarcoma under computer‐assisted navigation
Authors: Li Jing , Wang Zhen , Guo Zheng , Chen Guo‐jing , Yang Ming , Pei Guo‐Xian
Published: March 2012

Background

Joint‐preserving limb salvage surgery has been expected to have good functional outcomes. However, it is still a unsolved problem to perform a joint preserving resection for patients with juxta‐articular osteosarcoma invading epiphyseal line. We determined whether irregular osteotomy under image‐guided navigation make joint‐saving resection possible for juxta‐articular osteosarcoma while adhering oncological principles.

Methods

We performed joint‐preserving limb salvage surgeries on six patients with juxta‐articular osteosarcoma of the long bone. Three lesions located in humerus, two in tibia and one in femur. Two tumors extend to and four beyond the epiphyseal line. CT and MRI data fusion images were applied for intraoperative navigation. Planned irregular osteotomy under image‐guided navigation was employed for obtaining clear surgical margin while maximizing host tissue preservation. All tumors were en bloc removed and intercalary defect were reconstructed by allograft in one and combination of allograft with vascularized fibula graft in five patients. All specimens were examined for resection margin. Patients were followed up for average of 17.5 months for evaluating of functional and oncology outcomes.

Result

Entire joint were preserved in three patients and part of joint were saved in another three patients. Clear surgical margin was obtained in all specimens with a minimum of 6‐mm distance between tumor and osteotomy line. No patient experienced a local recurrence. One patient developed lung metastasis and had no evidence of disease at the most recent follow‐up. All allografts but one healed during the study period. The MSTS average score was 88.8% at final follow‐up.

Conclusions

With careful patient selection, the irregular osteotomy under navigation guidance was proved to be an effective and safe technique for precise tumor resection in joint preserving limb salvage procedures for treating patients with juxta‐articular osteosarcomas. J. Surg. Oncol. 2012; 106:411–416. © 2012 Wiley Periodicals, Inc.
Solvolysis of 2‐chloro‐2(3,4‐disubstituted) phenylpropanes: Validity of Hammett–Brown σ+ constants in assessing additive effects of substituents
Authors: Taha Ahmed A.
Published: March 2012

The objective of this study is to test the suitability of the extended Hammett–Brown equation, log (kXX/kHH) = ρ+Σσ+, in depicting satisfactorily additive effects of electronegative atom‐bearing substituents, which are known to possess diverse and multicomponent influences on the side chain reactions of polysubstituted benzenes. The equation has been used to correlate, for the first time, the additive effect of substituents in the specific rates of solvolysis of 2‐chloro‐2‐phenylpropanes (3b–3f) having 3‐F,4‐Me, 3‐Br,4‐Me, 3‐I,4‐Me, 3‐Me,4‐Me, or 3‐MeO,4‐Me substituents. The rates were determined titrimetrically at 288, 298, and 308 K using 90% aqueous acetone as solvent. Measured additive effects of these substituents on the solvolysis rate and activation parameters of the parent cumyl chloride (2‐chloro‐2‐phenylpropane) are found to be well correlated using the equation given above. Plots of log (kXX/kHH) of 3b–3f together with mainly di‐, but also tri‐ and mono‐substituted cumyl chlorides from previous studies against Σσ+ give a linear correlation coefficient of 0.990 as a measure of the validity of the equation to depict such systems. The halogen substituents' extent of conformity with additivity reflected in their relative (kobsd/kcalcd) rate ratios is found to correlate with the steric size of substituents. Plots of rate ratios against Taft's steric factor of each halogen give a linear correlation coefficient of 0.994 for the 3‐halo substituents. The 3,4‐dimethyl substituents' relative rate ratio of 1.03 shows excellent additivity, whereas the 3‐methoxy‐4‐methyl ratio of 1.43 shows the methoxy group to be far less deactivating than predicted. Similar trends were found for the free energy of activation (ΔG‡ – ΔG0‡) differences, which correlated linearly with a coefficient of 0.983 with Taft's steric factor of halogen atoms. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 514–523, 2012
Bevacizumab in hereditary hemorrhagic telangiectasia‐associated epistaxis: Effectiveness of an injection protocol based on the vascular anatomy of the nose
Authors: Dheyauldeen Sinan , Østertun Geirdal Amy , Osnes Terje , Vartdal Liv Sofie , Dollner Ralph
Published: March 2012

Objective/Hypothesis:

To evaluate the effectiveness of a standardized intranasal bevacizumab injection in treating hereditary hemorrhagic telangiectasia (HHT)‐associated epistaxis.

Study Design:

Prospective pilot study.

Methods:

A total dose of 100 mg bevacizumab (25 mg/mL Avastin) was injected submucosally, 50 mg on each side. A total of 0.5 mL was injected in the sphenopalatine area, upper part of bony septum, upper part of the later nasal wall, and the anterior part of nasal floor. No cauterizations or laser therapy were done during or after the procedure. The hemoglobin level and grades of epistaxis were recorded before and monthly after the procedure. The IFT grading system (intensity [I], frequency [F] of epistaxis, and the amount of blood transfusion [T]) and epistaxis severity score (ESS) for hereditary hemorrhagic telangiectasia system were used. Quality of life (QoL) was evaluated before and 4 weeks after the procedure using the Short Form‐36 Health Survey questionnaire, Cantril's Self‐Anchoring Ladder questionnaire, and Slotosch disease‐specific QoL questionnaire.

Results:

A significant improvement was found in IFT grading (P = .007), ESS grading (P = .001), and hemoglobin level (P = .01). The QoL differences were statistically not significant.

Conclusions:

The four‐injection site technique of intranasal administration of bevacizumab is an effective treatment option in HHT‐associated epistaxis, at least on the short‐term effect. Long‐term and comparative studies are needed to further evaluate the significance of this treatment modality. Laryngoscope, 2012
Unsedated transnasal endoscopy with ultrathin endoscope as a screening tool for research studies
Authors: Siwiec Robert M. , Dua Kulwinder , Surapaneni Sri Naveen , Hafeezullah Mohammed , Massey Benson , Shaker Reza
Published: March 2012

Objectives/Hypothesis:

Asymptomatic subjects volunteering for research studies are generally stratified as healthy based on a questionnaire, medical interviewing, and physical examination. The aim of this study was to evaluate the prevalence of upper gastrointestinal (GI) abnormalities in healthy asymptomatic volunteers using unsedated transnasal esophagogastroduodenoscopy (T‐EGD) with an ultrathin endoscope as an additional screening tool.

Study Design:

A prospective study from one academic medical center with extensive experience in T‐EGD.

Methods:

Consecutive 150 subjects volunteering for research studies were initially screened by using a gastroesophageal reflux disease (GERD) questionnaire, interviewing, and examination. Based on these, they were stratified as healthy asymptomatic volunteers or with GERD. Unsedated T‐EGD was then performed by a faculty member who was blinded to the results of the initial assessment.

Results:

On initial assessment using GERD questionnaire, medical interviewing, and physical examination, of the total 150 consecutive research volunteers, 83 (average age 33 ± 16 years; 46 females, 37 males) subjects were healthy asymptomatic volunteers and 67 (average age 36 ± 15 years; 35 females, 32 males) had symptoms of GERD. On T‐EGD, GI pathology was found in 15 of 83 (18%) healthy asymptomatic volunteers as compared to 24 of 67 (36%) stratified as having GERD (P < .01). The esophageal abnormalities found in healthy asymptomatic volunteers were esophagitis (13.3%), Barrett's esophagus (2.4%), hiatus hernia (2.4%), and gastritis (2.4%).

Conclusions:

A small but significant number of asymptomatic subjects have abnormal upper GI findings. Hence, transnasal unsedated endoscopy can be considered as a screening tool to stratify subjects as healthy, especially when considering them for research studies. Laryngoscope, 2012
Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells
Authors: Johnston Nikki , Yan Justin C. , Hoekzema Craig R. , Samuels Tina L. , Stoner Gary D. , Blumin Joel H. , Bock Jonathan M.
Published: March 2012

Objective/Hypothesis:

Laryngopharyngeal reflux (LPR) is thought to be a significant risk factor for laryngeal squamous cell carcinoma (SCC), but causality has never been proven. It is accepted that chronic reflux into the esophagus can induce metaplastic changes in esophageal mucosa with subsequent increased risk of esophageal adenocarcinoma, but no similar associations have been established for LPR and laryngopharyngeal SCC. The objective of this study was to test the hypothesis that reflux of pepsin into the laryngopharynx can promote carcinogenesis.

Study Design:

Translational research study.

Methods:

Normal human laryngeal primary epithelial cell cultures and hypopharyngeal FaDu SCC cells were exposed to human pepsin and analyzed by Human Cancer PathwayFinder and miRNA Superarrays, flow cytometry, and Western blot to determine the effect of pepsin on carcinogenesis. Laryngeal biopsy specimens taken from cancer patients and normal control subjects were analyzed for the presence of pepsin by Western blot.

Results:

Microarray analysis demonstrated that pepsin significantly altered the expression of 27 genes implicated in carcinogenesis and also affected the expression of 22 microRNAs known to be altered in human head and neck cancers. Pepsin increased proliferation in both FaDu SCC cells and cultured normal laryngeal epithelial primary cells by increasing S phase distribution on flow cytometry analysis in a time‐ and dose‐dependent manner. Furthermore, pepsin was detected in 60% (3/5) human laryngeal cancer biopsies, absent in all (0/5) normal control specimens.

Conclusions:

These data support a role for refluxed pepsin in the promotion of epithelial proliferation and carcinogenesis of the larynx and pharynx. Laryngoscope, 2012
Readability assessment of internet‐based patient education materials related to endoscopic sinus surgery
Authors: Cherla Deepa V. , Sanghvi Saurin , Choudhry Osamah J. , Liu James K. , Eloy Jean Anderson
Published: March 2012

Objectives/Hypothesis:

Numerous professional societies, clinical practices, and hospitals provide Internet‐based patient education materials (PEMs) to the general public, but not all of this information is written at a reading level appropriate for the average patient. The National Institutes of Health and the US Department of Health and Human Services recommend that PEMs be written at or below the sixth‐grade level. Our purpose was to assess the readability of endoscopic sinus surgery (ESS)‐related PEMs available on the Internet and compare readability levels of PEMs provided by three sources: professional societies, clinical practices, and hospitals.

Study Design:

A descriptive and correlational design was used for this study.

Methods:

The readability of 31 ESS‐related PEMs was assessed with four different readability indices: Flesch‐Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG), and Gunning Frequency of Gobbledygook (Gunning FOG). Averages were evaluated against national recommendations and between each source using analysis of variance and t tests.

Results:

The majority of PEMs (96.8%) were written above the recommended sixth‐grade reading level, based on FKGL (P < .001). Only one article (3.2%) had an FKGL at or below the sixth‐grade level. The mean readability values were: FRES 47.1 ± 13.4, FKGL 10.7 ± 2.4, SMOG 13.7 ± 1.6, and Gunning FOG 12.4 ± 2.7.

Conclusions:

Current Internet‐based PEMs related to ESS, regardless of source type, were written well above the recommended sixth‐grade level. Materials from the hospitals/university‐affiliated websites had lower readability scores, but were still above recommended levels. Web‐based PEMs pertaining to ESS should be written with the average patient in mind. Laryngoscope, 2012
Immunohistochemical expression patterns of the HER4 receptors in normal mucosa and in laryngeal squamous cell carcinomas: Antioncogenic significance of the HER4 protein in laryngeal squamous cell carcinoma
Authors: Bussu Francesco , Ranelletti Franco O. , Gessi Marco , Graziani Cristina , Lanza Paola , Lauriola Libero , Paludetti Gaetano , Almadori Giovanni
Published: March 2012

Objectives/Hypothesis.

The prognosis for laryngeal squamous cell carcinoma (LSCC) has not shown any improvement in the last 30 years because of inadequate prognostic stratification. Therefore, the detection of reliable molecular markers may have a significant impact on clinical practice. As promising data regarding HER1/EGFR have been published, the purpose of the present study was to elucidate the role of the other receptors of the HER family.

Study Design:

Retrospective.

Methods.

We used quantitative immunohistochemistry to evaluate the expression pattern of the HER4 receptors cytokeratin (CK)‐14, CK‐17, and proliferating cell nuclear antigen in 67 LSCCs and assessed correlations with various prognostic parameters.

Results.

HER1 levels inversely correlated with those of HER2–4. The negative prognostic value of HER1 was confirmed, and a protective role for HER2–4 was found. Specifically, the overexpression of HER4 and its nuclear localization are protective and are associated with a better prognosis.

Conclusions.

Semiquantitative evaluation of HER2–4 provides predictive information that can be combined with HER1 expression data for molecular characterization of LSCC. The pattern of localization of HER4 is an easily evaluable qualitative parameter with a clear correlation with prognosis. The immunohistochemical methods described in this article are reliable, reproducible, and potentially translatable to clinical practice. Laryngoscope, 2012
Effects of the electrode location on tonal discrimination and speech perception of mandarin‐speaking patients with a cochlear implant
Authors: Lee Fei‐Peng , Hsu Hsin‐Te , Lin Yung‐Song , Hung Su‐Chen
Published: March 2012

Objectives/Hypothesis:

This study assessed the effects of varying the electrode location on tonal discrimination and speech perception in Mandarin Chinese‐speaking patients.

Study Design:

A controlled study with six experimental conditions.

Methods:

Seven Mandarin‐speaking listeners who received a MED‐EL cochlear implant (CI), ranging in age from 12.88 to 36.43 years (mean, 25.51 years), with an average of 5.28 years of device experience, participated this study. To evaluate the effects of electrode location, six experimental conditions each with the switch off at six different electrodes were designed. Identification tests of Mandarin lexical tones and words were performed.

Results:

Among experimental conditions with electrode lengths of 31, 23.8, and 16.6 mm, the CI subjects exhibited improved vowel and consonant identification in the condition of 31 mm, reflecting the apical location of electrodes. Specifically, the improvement was observed in the identification score for the vowel backness and height, as well as for the consonant place of articulation. Comparison among three settings with a same electrode length of 12.6 mm and the setting with stimulation to the midregion of the cochlea produces better words as well as the vowel and consonant identification compared with stimulation to basal and apical regions. However, no significant difference was observed for the lexical tone identification among conditions with different electrode location and stimulating region.

Conclusions:

Less mismatch of the frequency‐to‐place alignment may account for the improvement of word identification in conditions with electrodes coverage to more apical location; and in conditions where the mid‐region of the cochlea were stimulated. Laryngoscope, 2012
Extension of the notion of a gap to differential operators defined on different open sets
Authors: Burenkov Victor I. , Feleqi Ermal
Published: March 2012

In this paper the notion of a gap between two linear operators is extended to the case of linear differential operators defined on different open sets. Estimates of the gap between second order uniformly elliptic partial differential operators subject to homogeneous Dirichlet boundary conditions defined on different open sets Ω1 and Ω2 are obtained in terms of the geometrical characteristics of vicinity of Ω1 and Ω2. These estimates can be used for obtaining spectral stability estimates for the eigenvalues and eigenfunctions of the aforementioned operators.
Suggested immobilization test for diagnosis of restless legs syndrome in Parkinson's disease
Authors: De Cock Valérie Cochen , Bayard Sophie , Yu Huan , Grini Magda , Carlander Bertrand , Postuma Ron , Charif Mahmoud , Dauvilliers Yves
Published: March 2012

Diagnosis of restless leg syndrome (RLS) in Parkinson's disease (PD) is difficult because of clinical confounds. The suggested immobilization test (SIT) is validated for diagnosis of primary RLS. This study evaluated the usefulness of the SIT for diagnosis of RLS in PD. We compared SIT scores, as well as polysomnography measures in 50 patients with PD (25 with RLS, 25 without), 25 patients with primary RLS, and 25 age/sex matched controls. Mean leg discomfort score was increased in patients with PD and RLS compared to PD without RLS, and also in patients with primary RLS compared to controls. Leg discomfort was significantly higher at the end of the test in patients with RLS compared to patients without RLS. Intensity of leg discomfort was similar between patients with RLS, with or without PD. Using a mean leg discomfort cutoff of 11, we showed sensitivity of 91% and specificity of 72% for RLS diagnosis in PD during symptomatic time intervals. Periodic leg movements index during the SIT did not differ between groups. Periodic leg movements index during sleep and wakefulness was increased in patients with primary RLS compared to controls, but did not differ between patients with PD, with and without RLS. The sensory SIT is a simple test that may help diagnose RLS in patients with PD. © 2012 Movement Disorder Society
Hexafluorobenzene in comparison with perfluoro‐15‐crown‐5‐ether for repeated monitoring of oxygenation using 19F MRI in a mouse model
Authors: Mignion Lionel , Magat Julie , Schakman Olivier , Marbaix Etienne , Gallez Bernard , Jordan Bénédicte F.
Published: March 2012

Hexafluorobenzene (HFB) and perfluoro‐15‐crown‐5‐ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using 19F MRI for dynamic assessment of muscle oxygenation, with special focus on muscle tissue toxicity of the probes, and consecutive alteration of animal behavior. The latter were also compared in terms of sensitivity to changes in oxygenation as well as of signal‐to‐noise ratio for accurate pO2 measurements. For that purpose, mouse muscles were imaged at 11.7 T, at 2‐ and 36‐h after intramuscular injection of HFB or 15C5. Histological analysis of the muscle tissue revealed a lack of toxicity for 15C5 from 2 up to 36‐h postinjection, whereas HFB induced tissue necrosis, blood clots and thrombosis as soon as 24‐h postinjection. This muscle toxicity led to a limitation in mice mobility 24‐h after injection of HFB as evidenced by behavioral testing (open‐field, grip strength, and catwalk tests), which was not the case after 15C5 intramuscular injection. Finally, pO2 measurements assessed 2‐h postinjection showed consistent values with both probes, evidencing cross‐validation of the 19F MRI oximetry technique for acute measurements. However, the measurement at 36‐h was hampered for HFB, which showed significant lower values of muscle pO2, whereas 15C5 was able to reliably assess muscle pO2 at 36‐h postinjection. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
In vivo measurement of gadolinium diffusivity by dynamic contrast‐enhanced MRI: A preclinical study of human xenografts
Authors: Koh T. S. , Hartono S. , Thng C. H. , Lim T. K. H. , Martarello L. , Ng Q. S.
Published: March 2012

Compartmental tracer kinetic models currently used for analysis of dynamic contrast‐enhanced MRI data yield poor fittings or parameter values that are unphysiological in necrotic regions of the tumor, as these models only describe microcirculation in perfused tissue. In this study, we explore the use of Fick's law of diffusion as an alternative method for analysis of dynamic contrast‐enhanced MRI data in the necrotic regions. Xenografts of various human cancer cell lines were implanted in 14 mice that were subjected to dynamic contrast‐enhanced MRI performed using a spoiled gradient recalled sequence. Tracer concentration was estimated using the variable flip angle technique. Poorly perfused and necrotic tumor regions exhibiting delayed and slow enhancement were identified using a k‐means clustering algorithm. Tracer behavior in necrotic regions was shown to be consistent with Fick's diffusion equation and the in vivo gadolinium diffusivity was estimated to be 2.08 (±0.88) × 10−4 mm2/s. This study proposes the use of gadolinium diffusivity as an alternative parameter for quantifying tracer transport within necrotic tumor regions. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Simultaneous noncontrast angiography and intraPlaque hemorrhage (SNAP) imaging for carotid atherosclerotic disease evaluation
Authors: Wang Jinnan , Börnert Peter , Zhao Huilin , Hippe Daniel S. , Zhao Xihai , Balu Niranjan , Ferguson Marina S. , Hatsukami Thomas S. , Xu Jianrong , Yuan Chun , Kerwin William S.
Published: March 2012

A simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MR imaging technique is proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. Thirteen patients with diagnosed carotid atherosclerotic plaque were admitted after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time‐of‐flight and magnetization‐prepared 3D rapid acquisition gradient echo sequences. The SNAP sequence utilized a phase sensitive acquisition, and was designed to provide positive signals corresponding to intraplaque hemorrhage and negative signals corresponding to lumen. SNAP images were compared to time‐of‐flight images to evaluate lumen size measurements using linear mixed models and the intraclass correlation coefficient. Intraplaque hemorrhage identification accuracy was evaluated by comparing to magnetization‐prepared 3D rapid acquisition gradient echo images using Cohen's Kappa. Diagnostic quality SNAP images were generated from all subjects. Quantitatively, the lumen size measurements by SNAP were strongly correlated (intraclass correlation coefficient = 0.96,P< 0.001) with those measured by time‐of‐flight. For intraplaque hemorrhage detection, strong agreement (κ = 0.82,P< 0.001) was also identified between SNAP and magnetization‐prepared 3D rapid acquisition gradient echo images. In conclusion, a SNAP imaging technique was proposed and shows great promise for imaging both lumen size and carotid intraplaque hemorrhage with a single scan. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
An efficient analyse phase for element problems
Authors: Hogg Jonathan D. , Scott Jennifer A.
Published: March 2012

The analyse phase of a sparse direct solver for symmetrically structured linear systems of equations is used to determine the sparsity pattern of the matrix factor. This allows the subsequent numerical factorisation and solve phases to be executed efficiently. Many direct solvers require the system matrix to be in assembled form. For problems arising from finite element applications, assembling and then using the system matrix can be costly in terms of both time and memory. This paper describes and implements a variant of the work of Gilbert, Ng and Peyton for matrices in elemental form. The proposed variant works with an equivalent matrix that avoids explicitly assembling the system matrix and exploits supervariables. Numerical experiments using problems from practical applications are used to demonstrate the significant advantages of working directly with the elemental form. Copyright © 2012 John Wiley & Sons, Ltd.
Granular control of photovoltaic arrays by means of a multi‐output Maximum Power Point Tracking algorithm
Authors: Petrone Giovanni , Ramos‐Paja Carlos Andrés , Spagnuolo Giovanni , Vitelli Massimo
Published: March 2012

In this paper, a Distributed Maximum Power Point Tracking (D‐MPPT) approach in photovoltaic (PV) applications is discussed. The proposed control method is suitable for the granular control of the PV generator at a module level or even at a sub‐module level. D‐MPPT is usually implemented by means of independent converters, each one of them running its own MPPT algorithm. Instead, the architecture proposed in this paper consists of only one digital controller, implementing a multivariable MPPT algorithm based on the Perturb and Observe approach, acting on a number of dc/dc converters, each one of them dedicated to a single PV module. The proposed control strategy reduces the number of current sensors with respect to the classical D‐MPPT architecture and tracks the maximum power evaluated at the dc/dc converters' output. Planar solid immersion mirror simulations and experimental results confirm the validity of the approach and of the design guidelines proposed in the paper. Copyright © 2012 John Wiley & Sons, Ltd.
Assessment of domestic photovoltaic systems based on real options theory
Authors: Martinez‐Cesena Eduardo Alejandro , Azzopardi Brian , Mutale Joseph
Published: March 2012

In the last decade, the financial attractiveness of photovoltaic (PV) systems has been increasing due to the rapid and constant improvements of PV technologies and the introduction of renewable energy support mechanisms. Under these circumstances, residential electricity consumers can benefit from investments in domestic PV systems. Investment decisions in PV systems can be assessed with well‐known discounted cash flows criteria such as the cost of energy and the net present value. These types of analyses either recommend abandoning the project or investing immediately. However, due to fast improvements in PV technologies, especially in the last few years, options to postpone investments in PV systems can be valuable. These options can be assessed with real options theory. This paper proposes a real options methodology for the assessment of domestic PV systems, considering the expected evolution of PV technologies and the option to delay investment. The methodology employs a normalization technique to illustrate, in a simple and intuitive manner, the convenience of the delay option. Two case studies based on real aggregated data for the UK are presented. The first case study illustrates the methodology, whereas the second is an extensive study meant to provide insights about investments in domestic PV systems in the UK. The results indicate the circumstances that drive and disincentivize investments in different PV technologies. Additionally, it is shown that the option to delay investment is a potential driver for investments in emerging organic‐based PV technologies. Copyright © 2012 John Wiley & Sons, Ltd.
Analysis of the Mean Diameters and Particle‐Size Distribution in Powders
Authors: González‐Tello Pedro , Camacho Fernando , Vicaria José. M. , González Pedro A.
Published: March 2012

The granulometric characterization of a pulverulent material requires quantification of the particle size and its distribution frequency. From these primary data, the mean size (mean diameters) of the pulverulent material is calculated and the data are adjusted to the distribution functions. In this study, the most frequent mean diameters are defined and calculated, and the application of the distribution functions to the experimental results is discussed. It is concluded that the Rosin‐Rammler distribution function and a modified Nukiyama‐Tanasawa function are the most suitable equations to fit the differential and the cumulative undersize distribution frequencies. This review is accompanied by calculations that illustrate the application of the equations related to this work.
Formation of a disorderd hetero‐junction by diffusion of CuI from CuSCN into In2S3 layers: A surface photovoltage study
Authors: Juma Albert , Kavalakkatt Jaison , Pistor Paul , Latzel Björn , Schwarzburg Klaus , Dittrich Thomas
Published: March 2012

Charge‐selective disordered hetero‐junctions were formed in evaporated In2S3 layers by diffusing at 200 °C CuI from a CuSCN source. The thicknesses of In2S3 layers and diffusion times were varied between 5 and 80 nm and between 2 and 19 min, respectively. In some cases CuSCN layers were etched back with pyridine. Spectral and time‐dependent surface photovoltage measurements were carried out in the capacitor arrangement. It was observed that a competing process of charge separation and relaxation was initiated together with the formation of the charge‐selective In2S3/In2S3:Cu hetero‐junction.

Modulated SPV amplitude for different annealing times and thicknesses of the evaporated In2S3 layers.

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Vertically stacked and laterally ordered InP and In(Ga)As quantum dots for quantum gate applications
Authors: Koroknay Elisabeth , Schulz Wolfgang‐Michael , Richter Daniel , Rengstl Ulrich , Reischle Matthias , Bommer Moritz , Kessler Christian Alexander , Roßbach Robert , Schweizer Heinz , Jetter Michael , Michler Peter
Published: March 2012

We report on the epitaxial growth of vertically stacked InP and In(Ga)As quantum dot (QD) layers to realize a triple dot quantum gate structure consisting of an asymmetric control double dot and a single target dot suitable for a CNOT gate structure. Structural analysis as well as studies on the optical properties are presented. For studies on control dot structures we analyze the growth of InP islands in a GaInP barrier on (100) GaAs substrates. By stacking InP QD layers with intentional asymmetric design in QD size of each layer and adjustment of the barrier width between the double dots, coupling and control of the coupling via barrier layer width‐design can be demonstrated. For defined gate action single dot spectra of aligned dots are indispensable. Therefore QD density reduction is studied. We study two possibilities to affect the QD density and control the dot site by manipulating the surface potential of InP island nucleation. (i) Growth of InP islands on top of a low density In(Ga)As QD seed layer (ii) Growth of InP islands on patterned (100) GaAs substrates. We present microsphere photolithography in combination with wet chemical etching as a fast and low‐cost method to produce regular hole arrays in a GaAs surface, which are suitable for controlled nucleation of self‐assembled InP islands.
The Marine AlgaGelidium amansiiPromotes the Development and Complexity of Neuronal Cytoarchitecture
Authors: Hannan Md. Abdul , Kang Ji‐Young , Hong Yong‐Ki , Lee HyunSook , Choi Jae‐Suk , Choi In Soon , Moon Il Soo
Published: March 2012

Neurotrophic factors are vital not only to support neuronal development but also to protect mature neurons from atrophy in neurodegenerative diseases. As an effort to explore natural sources that possess neurotrophic activity, we screened common marine algae for their neuritogenic activity in the developing rat hippocampal neurons in culture. Of the 22 seaweed species examined, ethanol extracts ofGelidium amansii(GAE) exhibited potent neuritogenic activity, followed byUndaria pinnatifidaandSargassum fulvellumextracts. The effects of GAE were dose dependent with an optimum concentration of 15 µg/mL. The GAE significantly promoted the initial neuronal differentiation from the stage I into the stage II and increased the indices of axonal and dendritic development such as the length, the numbers of primary processes, and branching frequencies by a minimum of twofold compared with the vehicle control. These results show that marine algae are promising candidates for neurotrophic potentials. Copyright © 2012 John Wiley & Sons, Ltd.
A bias‐corrected decomposition of the Brier score
Authors: Ferro C. A. T. , Fricker T. E.
Published: March 2012

The Brier score is a widely used measure of performance for probabilistic forecasts of event occurrences and is often decomposed additively into three terms that quantify the reliability and resolution of the forecasts and the uncertainty of the forecast events. The standard decomposition yields biased estimates of the large‐sample values of these three quantities: reliability is overestimated and uncertainty is underestimated, while resolution may be either overestimated or underestimated. An unbiased decomposition is shown to be unattainable but a new decomposition is proposed that has smaller biases and therefore provides a more accurate measure of forecast performance. The implications for the Brier skill score and the attributes diagram are discussed and results are illustrated with seasonal forecasts of sea‐surface temperatures. Copyright © 2012 Royal Meteorological Society