bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Hedging of Options with Probabilistic Haar Wavelets
Authors: Catuogno Pedro José , Ferrando Sebastián Esteban , González Alfredo Lázaro
Published: September 2012

The paper brings forward the issue of efficient representations of financial claims; in particular it addresses the problem of large transaction costs in hedging replications. Inspired by the localized properties of wavelets basis, Haar systems associated with space-time discretizations of continuous stochastic processes are proposed as a means to address the issue of efficient pathwise approximation. Theoretical developments are presented that justify the use of these approximations to construct self-financing portfolios by means of binary options. Upper bounds on the volume of transactions required to implement these portfolios are then established to illustrate the quality of the proposed approximations. The approach is applicable to general financial claims of European type, including path-dependent ones, for continuous underlying processes. Several numerical results and comparisons with delta hedging are also presented.
Important Roles of Cellular MicroRNA miR-155 in Leukemogenesis by Human T-Cell Leukemia Virus Type 1 Infection
Authors: Tomita Mariko
Published: September 2012

Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes the aggressive and lethal malignancy of CD4+ T-lymphocytes called adult T-cell leukemia/lymphoma (ATLL). MicroRNAs (miRNAs), a class of short, noncoding RNAs, regulate gene expression by targeting mRNAs for translational repression or cleavage. miRNAs are involved in many aspects of cell biology linked with formation of several cancer phenotypes. However, the relation between miRNAs and pathologic implication in ATLL is not well elucidated. Here, we evaluated the roles of cellular miRNAs in ATLL caused by HTLV-1. We found that the expression of miR-155 was increased in HTLV-1-positive T-cell lines. miR-155 expression was enhanced by Tax and binding of transcription factors, NF-κB and AP-1, on the transcription binding sites of miR-155 gene promoter region is important to increase the expression of miR-155 by Tax. Transfection of anti-miR-155 inhibitor, which inhibits the function of miR-155, inhibited the growth of HTLV-1-positive T-cell lines. On the other hand, the growth of HTLV-1-negative T-cell lines was not changed by transfection of anti-miR-155. Forced expression of miR-155 enhanced the growth of HTLV-1-positive T-cell lines. These findings indicate that targeting the functions of miRNAs is a novel approach to the prevention or treatment of ATLL.
The Roles of Southeast Asian School Managers as Instructional Leaders: An Assessment
Authors: Baliton Fructuoso C.
Published: September 2012

Schools must consciously seek principals who are instructional leaders. Principals who are comfortable with providing instructional support to teachers are likely to have been good teachers themselves (Glanz 2006). This descriptive method of research assessed the roles of Southeast Asian school managers as instructional leaders in the four domains of teaching responsibilities and explored relationships among the variables of the study namely: planning and preparation, the classroom environment, instruction, and professional responsibilities. The T-test determined the differences between the male and the female and between the Filipinos and the Non-Filipinos respondents which resulted to non-significant differences between neither of the two groups. The F-test was used to determine the significant relationships among the four domains of teaching responsibilities which established significant relationships between three pairs of domains. This research concluded that the SEA school managers are very comfortable with their level in working with teachers on content and pedagogical knowledge, knowledge of students and resources, ability to select instructional goals, and the degree to which they help teachers assess learning as well as the degree to which they encourage and create an environment of respect and caring and establish a culture for learning related to many aspects of classroom environment.   Keywords - Southeast Asian School Managers, Instructional leadership, domains of teaching responsibilities, planning and preparation, classroom environment, instruction, professional responsibilities.
Dimensions of immigrant integration and civic engagement: Issues and exemplary programs
Authors: Spruck Wrigley Heide
Published: September 2012

Immigrant integration is a multidimensional process that involves both newcomers and the receiving community. Although the United States does not have a coherent policy of immigrant integration, several city‐ and statewide efforts support immigrant integration, as do individual initiatives operating across states.
Learning from the grassroots: Exploring democratic adult learning opportunities connected to grassroots organizations
Authors: Gouthro Patricia A.
Published: September 2012

This chapter explores the challenges facing grassroots organizations and considers the opportunities they offer for adult learning connected to citizenship.
Double Stimuli‐Responsive Isoporous Membranes via Post‐Modification of pH‐Sensitive Self‐Assembled Diblock Copolymer Membranes
Authors: Clodt Juliana Isabel , Filiz Volkan , Rangou Sofia , Buhr Kristian , Abetz Clarissa , Höche Daniel , Hahn Janina , Jung Adina , Abetz Volker
Published: September 2012

Double stimuli‐responsive membranes are prepared by modification of pH‐sensitive integral asymmetric polystyrene‐b‐poly(4‐vinylpyridine) (PS‐b‐P4VP) diblock copolymer membranes with temperature‐responsive poly(N‐isopropylacrylamide) (pNIPAM) by a surface linking reaction. PS‐b‐P4VP membranes are first functionalized with a mild mussel‐inspired polydopamine coating and then reacted via Michael addition with an amine‐terminated pNIPAM‐NH2 under slightly basic conditions. The membranes are thoroughly characterized by nuclear magnetic resonance (1H‐NMR), Fourier transform infrared spectroscopy and X‐ray‐induced photoelectron spectroscopy. Additionally dynamic contact angle measurements are performed comparing the sinking rate of water droplets at different temperatures. The pH‐ and thermo‐double sensitivities of the modified membranes are proven by determining the water flux under different temperature and pH conditions.
Biomimetic Calcium Carbonate Concentric Microgrooves with Tunable Widths for Promoting MC3T3‐E1 Cell Functions
Authors: Wu Xiaohui , Wang Shanfeng
Published: September 2012

Biomimetic, self‐assembled calcium carbonate (CaCO3) concentric microgrooves with groove widths of 5.0 and 10 μm were fabricated through simply controlling incubation temperature. Mouse pre‐osteoblastic MC3T3‐E1 cells were cultured on flat and microgrooved substrates of CaCO3 and their adhesion, spreading, proliferation, alkaline phosphatase activity, and calcium content were remarkably enhanced by the microgrooves, in particular, the narrower ones. Furthermore, focal adhesions and actin filaments of MC3T3‐E1 cells could be aligned on both 5.0‐μm and 10‐μm‐wide CaCO3 grooves. Compared with the original round nuclei on the flat substrates and expanded round nuclei on the narrower microgrooves, the MC3T3‐E1 cell nuclei on 10‐μm‐wide CaCO3 grooves demonstrated preferred entrapment in the grooves and significant alignment with a smaller area after two‐day culture.
An inherited LMNA gene mutation in atypical Progeria syndrome
Authors: Doubaj Yassamine , De Sandre‐Giovannoli Annachiara , Vera Esteves‐Vieira , Navarro Claire Laure , Elalaoui Siham Chafai , Tajir Mariam , Lévy Nicolas , Sefiani Abdelaziz
Published: September 2012

Hutchinson–Gilford Progeria syndrome (HGPS) is a rare genetic disorder, characterized by several clinical features that begin in early childhood, recalling an accelerated aging process. The diagnosis of HGPS is based on the recognition of common clinical features and detection of the recurrent heterozygous c.1824C>T (p.Gly608Gly) mutation within exon 11 in the Lamin A/C encoding gene (LMNA). Besides “typical HGPS,” several “atypical progeria” syndromes (APS) have been described, in a clinical spectrum ranging from mandibuloacral dysplasia to atypical Werner syndrome. These patients's clinical features include progeroid manifestations, such as short stature, prominent nose, premature graying of hair, partial alopecia, skin atrophy, lipodystrophy, skeletal anomalies, such as mandibular hypoplasia and acroosteolyses, and in some cases severe atherosclerosis with metabolic complications. APS are due in several cases to de novo heterozygous LMNA mutations other than the p.Gly608Gly, or due to homozygous BAFN1 mutations in Nestor–Guillermo Progeria syndrome (NGPS). We report here and discuss the observation of a non‐consanguineous Moroccan patient presenting with atypical progeria. The molecular studies showed the heterozygous mutation c.412G>A (p.Glu138Lys) of the LMNA gene. This mutation, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism. © 2012 Wiley Periodicals, Inc.
Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: Gene–phenotype correlations
Authors: Nishida Takeo , Faughnan Marie E. , Krings Timo , Chakinala Murali , Gossage James R. , Young William L. , Kim Helen , Pourmohamad Tony , Henderson Katharine J. , Schrum Stacy D. , James Melissa , Quinnine Nancy , Bharatha Aditya , terBrugge Karel G. , White Robert I.
Published: September 2012

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0–68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2–50) and 18 ± 21 (0–48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT. © 2012 Wiley Periodicals, Inc.
Environmental Requirements, Knowledge Sharing and Green Innovation: Empirical Evidence from the Electronics Industry in China
Authors: Wong Stanley Kam Sing
Published: September 2012

Building on the Porter hypothesis, which posits that regulatory stringency triggers innovation and thereby allows firms to achieve the dual purpose of environment protection and enhanced business performance, the present research develops an integrative model that explores the determinants of green innovation with a focus being placed on knowledge sharing. Data were collected from 203 green innovation project leaders from electronics manufacturers operating in China. The results indicate that knowledge sharing mediates the relationship between green requirements and new green product success as well as that between green requirements and green product and process innovations. Interestingly, the empirical analysis rejects the hypothesized positive influence of green requirements on green product and process innovations as well as that on new green product success, while confirming that there exists a direct and positive association between green requirements and knowledge sharing. The direct positive impact of knowledge sharing is the strongest on green process innovation. This study provides a theoretical basis for investigating the possible determinants in the causal links between green requirements and green innovation success and establishes that knowledge sharing and green process innovation may be the points where leverage can be applied to best secure innovation success. Implications of the findings on environmental policy and law design are also discussed to see how the regulatory role of the government can be better positioned to facilitate compliance and innovation. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment.
Clinically relevant landmarks of the frontotemporal branch of the facial nerve: A three‐dimensional study
Authors: Davies Joel C. , Fattah Adel , Ravichandiran Mayoorendra , Agur Anne M.
Published: September 2012

The frontotemporal branch of the facial nerve (FTN) is vulnerable during craniofacial surgeries due to its superficial course and variable distribution. Surface landmarks that correlate with the underlying course of the FTN can assist in surgical planning. Estimates of the course of FTN commonly rely on Pitanguy's line (PL), which utilizes variable soft‐tissue landmarks. The purpose of this study was to evaluate palpable surface landmarks to predict the course and distribution of FTN using 3D modeling. Fifteen half‐heads were used. In five formalin‐embalmed specimens, surface topography was obtained using a FARO® scanner and landmarks corresponding to PL, porion, supraorbital notch, frontozygomatic and zygomaticotemporal sutures, and supraorbitomeatal line (SOML) and infraorbitomeatal line (IOML) were demarcated/digitized using a Microscribe™ digitizer. A preauricular flap was raised, and branches of FTN were isolated and digitized. The data were reconstructed into 3D models (Geomagic®/Maya®) to quantify landmarks. In 10 Thiel‐embalmed specimens, four independent raters identified/palpated and pinned the frontozygomatic and zygomaticotemporal sutures and PL. Data were collected and analyzed using the same protocol as in the first part of the study. Landmarking of PL was inconsistent between raters and not representative of FTN distribution. The easily identifiable surface landmarks defined in this study, a line 12 mm anterior to the porion along the SOML and IOML and a line joining the zygomaticotemporal and frontozygomatic sutures, comprehensively captured the distribution of FTN. The raters found a mean of 21 ± 2 branches between the lines out of a total of 22 ± 2 branches. These landmarks may be used clinically to avoid injury to FTN. Clin. Anat. 25:858–865, 2012. © 2012 Wiley Periodicals, Inc.
Conformational Analysis of Fluorinated Pyrrolidines Using 19F–1H Scalar Couplings and Heteronuclear NOEs
Authors: Combettes Lorraine E. , Clausen‐Thue Philip , King Michael A. , Odell Barbara , Thompson Amber L. , Gouverneur Véronique , Claridge Tim D. W.
Published: September 2012

A series of 3‐fluoropyrrolidines have been studied to investigate the influence of the stereoelectronic fluorine gauche effect on ring conformations in the solid state by single‐crystal X‐ray analysis and in solution phase by NMR spectroscopy. As part of these studies 1D 19F–1H heteronuclear NOE (HOESY) experiments have been optimised for applications to small molecules and are described in detail. These have been employed to estimate 19F–1H internuclear distances and were combined with vicinal 3J(F,H) and 3J(H,H) scalar coupling constants to analyse the ring conformations. Where possible the derived solution‐phase structural data have been compared with those of the crystalline state. The results demonstrate the influence of the gauche effect in stabilising Cγ‐exo conformations of the fluorinated pyrrolidines. It was further shown that when steric interactions were also present, this conformational bias was diminished and the contribution of the alternative Cγ‐endo conformation was seen to increase in solution at lower sample temperatures.
Labour Arbitration of Co‐Worker Sexual Harassment Cases in Canada
Authors: Hart Susan M.
Published: September 2012

Women have the right to a workplace free from sexual harassment under Canadian provincial and federal human rights legislation. Canadian labour laws incorporate the right to a grievance procedure including binding arbitration where arbitrators must interpret and apply human rights legislation. This paper analyzes co‐worker sexual harassment cases in order to assess how well arbitrations protect the right of unionized women to a harassment free workplace. Results indicate that women complainants were often subjected to aggressive gendered cross‐examinations and the application of gendered jurisprudence that largely ignored the impact of gendered power relations in the workplace. The conclusion is that women's experiences in arbitrations are likely a deterrent to filing formal complaints, effectively undermining rather than protecting their rights. Copyright © 2012 ASAC. Published by John Wiley & Sons, Ltd.
UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors
Authors: Zage Peter E. , Sirisaengtaksin Natalie , Liu Yin , Gireud Monica , Brown Brandon S. , Palla Shana , Richards Kristen N. , Hughes Dennis P. M. , Bean Andrew J.
Published: September 2012

BACKGROUND:

The UBE4B gene, which is located on chromosome 1p36, encodes a ubiquitin ligase that interacts with hepatocyte growth factor‐regulated tyrosine kinase substrate (Hrs), a protein involved in epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. The authors analyzed the roles of UBE4B in the outcomes of patients with neuroblastoma and in neuroblastoma tumor cell proliferation, EGFR trafficking, and response to EGFR inhibition.

METHODS:

The association between UBE4B expression and the survival of patients with neuroblastoma was examined using available microarray data sets. UBE4B and EGFR protein levels were measured in patient tumor samples, EGFR degradation rates were measured in neuroblastoma cell lines, and the effects of UBE4B on neuroblastoma tumor cell growth were analyzed. The effects of the EGFR inhibitor cetuximab were examined in neuroblastoma cells that expressed wild‐type and mutant UBE4B.

RESULTS:

Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma. UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B expression was inversely related to EGFR expression in tumor samples. EGFR degradation rates correlated with cellular UBE4B levels. Enhanced expression of catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition.

CONCLUSIONS:

The current study demonstrates associations between UBE4B expression and the outcomes of patients with neuroblastoma and between UBE4B and EGFR expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influence neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR inhibition. These results suggest UBE4B‐mediated growth factor receptor trafficking may contribute to the poor prognosis of patients who have neuroblastoma tumors with 1p36 deletions and that UBE4B expression may be a marker that can predict responses of neuroblastoma tumors to treatment. Cancer 2013. © 2012 American Cancer Society.
Trait‐level and momentary correlates of bulimia nervosa with a history of anorexia nervosa
Authors: Goldschmidt Andrea B. , Peterson Carol B. , Wonderlich Stephen A. , Crosby Ross D. , Engel Scott G. , Mitchell James E. , Crow Scott J. , Cao Li , Berg Kelly C.
Published: September 2012

Objective:

Some investigators have suggested subtyping bulimia nervosa (BN) by anorexia nervosa (AN) history. We examined trait‐level and momentary eating‐related and psychosocial factors in BN with and without an AN history.

Method:

Interview, questionnaire, and ecological momentary assessment data of eating‐related and psychological symptoms were collected from 122 women with BN, including 43 with (BN+) and 79 without an AN history (BN−).

Results:

Body mass index (kg/m2) was lower in BN+ than BN− (p = 0.001). Groups did not differ on trait‐level anxiety, shape/weight concerns, psychiatric comorbidity, or dietary restraint; or on momentary anxiety, dietary restriction, binge eating, purging, or exercise frequency, or affective patterns surrounding binge/purge behaviors. Negative affect increased prior to exercise and decreased thereafter in BN+ but not BN−, although groups did not statistically differ.

Discussion:

Results do not support formally subtyping BN by AN history. Exercise in BN+ may modulate negative affect, which could have important treatment implications. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Water‐use response to climate factors at whole tree and branch scale for a dominant desert species in central Asia: Haloxylon ammodendron
Authors: Zheng Chaolei , Wang Quan
Published: September 2012

Water use of a dominant desert species, Haloxylon ammodendron, growing in the southern edge of Gurbantünggüt Desert in northwest China, was measured using sap flow technologies at both tree and branch scales. Daily sap flow at whole‐tree scale showed a good relationship with atmospheric evaporation demand (P < 0·001), whereas daily sap flow at branch scale showed good relationships with the variable of transpiration rate (P < 0·01). Hysteresis in hourly sap flow at both scales was observed as a function of micro‐meteorological variables, in which the hysteresis between sap flow and vapour pressure deficit was clockwise rotation, suggesting that the water use of H. ammodendron was related to not just the stomatal behaviour but also use of stored plant water. The hysteresis between sap flow and photosynthetic photon flux density was counter‐clockwise after precipitation, but turned to be clockwise under dry conditions, which was ever clearer at whole‐tree scale. Different responses of sap flows at branch and whole‐tree scale to climate factors were identified, which strongly indicated that H. ammodendron had some mechanisms to reduce whole‐tree water use at high transpiration demand, while maintaining part of canopy under relatively high water use, which resulted in canopy scale patchiness. Copyright © 2012 John Wiley & Sons, Ltd.
Hexagonal Supramolecular Assemblies Based on a RuII(DMSO)3‐ or OsII(DMSO)3‐Capped {HW9O33} Isopolyanion with Potassium Cations as Linkers
Authors: Barats‐Damatov Delina , Shimon Linda J. W. , Neumann Ronny
Published: September 2012

Crystallization of the {HW9O33} isopolyanion in the presence of MII(DMSO)4Cl2 (where M = Ru, Os) and Na and K cations yielded one‐dimensional chains, {K[HW9O33M2(C2H6SO)6]6–}n. The {HW9O33} isopolyanion is capped by MII(DMSO)3 moieties, which are, in turn, linked by potassium cations. The chains for the RuII‐based compound show a prismatic coordination around the K+ linker and {HW9O33} moieties that are eclipsed relative to each other along the chain, while the OsII‐based compound has an octahedral coordination around the K+ linker and {HW9O33} moieties that are staggered relative to each other along the chain. The three‐dimensional arrangement of the two compounds is quite different. For the RuII compound, channels are obtained by the arrangement of six {K[HW9O33Ru2(C2H6SO)6]6–}n chains along the c axis. The channel is stabilized by the binding of sodium cations, which interlock the chains through coordination of different oxygen atoms and leads to a tight staggered arrangement between the chains of {K[HW9O33Ru2(C2H6SO)6]6–}n. The channels have an approximate diameter of 8 Å and are occupied by layers of six sodium cations that form chair‐like hexagons with Na–Na interatomic distances of 2.807 Å. There are five water molecules that separate the layers of the Na+ cations. For the osmium compound, two different types of channels, defined by the arrangement three {K[HW9O33Os2(C2H6SO)6]6–}n chains, are formed. The channels are formed through interchain bonding through a bridge formed by connecting sodium atoms to the terminal atoms of the {HW9O33} unit. Here, the {K[HW9O33Os2(C2H6SO)6]6–}n chains are eclipsed relative to one another. Water molecules occupy one channel, while the other channel is occupied by K+ cations hexacoordinated to aqua ligands. The approximate diameter of the channels is 5.5 Å.
Siloxane‐Crown Ether Polyamide Based Electrode for Electrochemical Determination of Lead(II) in Aqueous Solution
Authors: Simionca Ioana‐Maria , Arvinte Adina , Ardeleanu Rodinel , Pinteala Mariana
Published: September 2012

A siloxane‐crown ether polyamide copolymer (PDMS‐PA‐DB18C6) was electrochemically investigated for fabrication of lead‐sensitive electrodes for trace analysis in aqueous solutions. The PDMS‐PA‐DB18C6 electrodes were successfully evaluated for anodic stripping voltammetric determination of lead(II) as a promising alternative for the detection of lead at ppb levels. By a judicious choice of the deposition time, electrolyte concentration and pulse amplitude, good analytical performance of the developed sensor could be achieved, with a linear response in the range of 20–700 ppb, when LOD of 3.5 ppb could be attained. This method showed a good degree of selectivity and sensitivity for lead, suitable for the determination of Pb2+ in wastewater sample.
All Solid State Nickel(II)‐Selective Potentiometric Sensor Based on an Upper Rim Substituted Calixarene
Authors: Kumar Pankaj
Published: September 2012

A new ionophore, i.e. p‐(2‐thiazolazo)calix[4]arene (I) has been explored for its selective behavior towards Ni(II) ions. A poly(vinyl chloride) based membrane containing (I) as an electroactive material along with sodiumtetraphenylborate (NaTPB), and nitrophenyloctyl ether in the ratio 10 : 100 : 3 : 150 (I:PVC:NaTPB:NPOE) (w/w) was used to fabricate an all solid state nickel(II)‐selective sensor. The developed sensor exhibited a working concentration range of 1.0×10−6–1.0×10−1 M, with a Nernstian slope of 28.9±1.0 mV/decade of activity and a response time of 10–15 s. This sensor shows a detection limit of 9.0×10−7 M. Its potential response remains unaffected of pH in the range 3.0–7.6, and the cell assembly could be used successfully in partially nonaqueous medium (up to 10 % v/v) without any significant change in the slope value or the working concentration range. The sensor worked satisfactorily for about ten weeks and exhibited excellent selectivity over a number of mono‐, bi‐, and tri‐valent cations including alkali, alkaline earth metal, and transition metal ions. It could be used as an indicator electrode for the end point determination in the potentiometric titration of nickel ions against ethylenediaminetetraacetic acid (EDTA) as well as for the determination of nickel ion concentration in real samples.
Hybrid E‐Tongue for the Evaluation of Sweetness and Bitterness of Soft Drinks Fortified with Epigallocatechin Gallate
Authors: Bulbarello Andrea , Cuenca Martha , Schweikert Loni , Mannino Saverio , Scampicchio Matteo
Published: September 2012

A home‐made hybrid electronic tongue was set up, validated and applied to discriminate soft drinks fortified with plant extracts of green tea. The e‐tongue consists of a flow injection system equipped with two electrochemical and one optical sensors. Different formulations of soft drinks composed of glucose and epigallocatechin gallate were then discriminated by principal component analysis. Furthermore, two partial least squares regression models were developed to estimate the “sweetness” (r2 of 0.992) and “bitterness” (r2 of 0.993) of the model solutions and commercial soft drinks, before and after their fortification with epigallocatechin gallate.
Determination of Salbutamol in Pharmaceutical and Serum Samples by Adsorptive Stripping Voltammetry on a Carbon Paste Electrode Modified by Iron Titanate Nanopowders
Authors: Attaran Abdol Mohammad , Javanbakht Mehran , Fathollahi Fatemeh , Enhessari Morteza
Published: September 2012

This study introduces a fast and direct electrochemical method for the determination of salbutamol using an iron titanate nanopowder‐modified carbon paste electrode. The electrochemical behavior of salbutamol was studied by differential pulse adsorptive stripping voltammetry. Factors affecting the performance of the adsorptive stripping such as the modifier percent, the electrolyte pH and accumulation time and potential were optimized. The resulting electrode exhibited a linear response in the range of 0.2–25 nM of salbutamol with a detection limit of 90 pM. The proposed method was successfully applied to determine salbutamol in pharmaceutical formulations and human blood plasma.
Identification of upregulated genes in oral squamous cell carcinomas
Authors: Lessa Roberta C. , Campos Antonio Hugo J. F. M. , de Freitas Carlos Elias , da Silva Felipe Rodrigues , Kowalski Luiz Paulo , Carvalho André Lopes , Vettore André Luiz
Published: September 2012

Background

Oral cancer is the most common subset of head and neck squamous cell carcinomas (HNSCC). These tumors often have an aggressive clinical outcome hallmarked by a propensity for local invasion and regional nodal metastasis. Upregulated genes could be useful as markers for diagnosis, prognosis, and as new drug targets for these tumors.

Methods

To identify upregulated genes in oral squamous cell carcinomas (OSSCs), we examined the ORESTES public database and used a quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) approach to determine the expression level of selected genes in tumor samples.

Results and Conclusions

The ORESTES data mining analysis indicated 40 upregulated genes in HNSCC. Nine of these candidate genes were selected for further qRT‐PCR validation and 3 of them (ALDOA, AHSA1, and POLQ) were frequently found upregulated in OSCC samples, which may indicate an association of these genes with the carcinogenesis process in this tumor site and they can constitute potential new targets for therapy. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1475–1481, 2013
Differentiation capacity of hepatic stem/progenitor cells isolated from d-galactosamine-treated rat livers
Authors: Ichinohe Norihisa , Tanimizu Naoki , Ooe Hidekazu , Nakamura Yukio , Mizuguchi Toru , Kon Junko , Hirata Koichi , Mitaka Toshihiro
Published: September 2012

Oval cells and small hepatocytes (SHs) are known to be hepatic stem and progenitor cells. Although oval cells are believed to differentiate into mature hepatocytes (MHs) through SHs, the details of their differentiation process are not well understood. Furthermore, it is not certain whether the induced cells possess fully mature functions as MHs. In the present experiment, we used Thy1 and CD44 to isolate oval and progenitor cells, respectively, from d-galactosamine-treated rat livers. Epidermal growth factor, basic fibroblast growth factor, or hepatocyte growth factor could trigger the hepatocytic differentiation of sorted Thy1+ cells to form epithelial cell colonies, and the combination of the factors stimulated the emergence and expansion of the colonies. Cells in the Thy1+-derived colonies grew more slowly than those in the CD44+-derived ones

in vitro

and

in vivo

and the degree of their hepatocytic differentiation increased with CD44 expression. Although the induced hepatocytes derived from Thy1+ and CD44+ cells showed similar morphology to MHs and formed organoids from the colonies similar to those from SHs, many hepatic differentiated functions of the induced hepatocytes were less well performed than those of mature SHs derived from the healthy liver. The gene expression of cytochrome P450 1A2, tryptophan 2,3-dioxygenase, and carbamoylphosphate synthetase I was lower in the induced hepatocytes than in mature SHs. In addition, the protein expression of CCAAT/enhancer-binding protein alpha and bile canalicular formation could not reach the levels of production of mature SHs.

Conclusion
: The results suggest that, although Thy1+ and CD44+ cells are able to differentiate into hepatocytes, the degree of maturation of the induced hepatocytes may not be equal to that of healthy resident hepatocytes. (Hepatology 2013)
Intestinal mucus-derived nanoparticle–mediated activation of Wnt/β-catenin signaling plays a role in induction of liver natural killer T cell anergy in mice
Authors: Deng Zhong-Bin , Zhuang Xiaoying , Ju Songwen , Xiang Xiaoyu , Mu Jingyao , Wang Qilong , Jiang Hong , Zhang Lifeng , Kronenberg Mitchell , Yan Jun , Miller Donald , Zhang Huang-Ge
Published: September 2012

The Wnt/β-catenin pathway has been known to play a role in induction of immune tolerance, but its role in the induction and maintenance of natural killer T (NKT) cell anergy is unknown. We found that activation of the Wnt pathways in the liver microenvironment is important for induction of NKT cell anergy. We identified a number of stimuli triggering Wnt/β-catenin pathway activation, including exogenous NKT cell activator, glycolipid α-GalCer, and endogenous prostaglandin E2 (PGE2). Glycolipid α-GalCer treatment of mice induced the expression of wnt3a and wnt5a in the liver and subsequently resulted in a liver microenvironment that induced NKT cell anergy to α-GalCer restimulation. We also found that circulating PGE2 carried by nanoparticles is stable, and that these nanoparticles are A33+. A33+ is a marker of intestinal epithelial cells, which suggests that the nanoparticles are derived from the intestine. Mice treated with PGE2 associated with intestinal mucus-derived exosome-like nanoparticles (IDENs) induced NKT cell anergy. PGE2 treatment leads to activation of the Wnt/β-catenin pathway by inactivation of glycogen synthase kinase 3β of NKT cells. IDEN-associated PGE2 also induces NKT cell anergy through modification of the ability of dendritic cells to induce interleukin-12 and interferon-β in the context of both glycolipid presentation and Toll-like receptor–mediated pathways.

Conclusion:

These findings demonstrate that IDEN-associated PGE2 serves as an endogenous immune modulator between the liver and intestines and maintains liver NKT cell homeostasis. This finding has implications for development of NKT cell–based immunotherapies. (Hepatology 2013)
Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C
Authors: Arase Yasuji , Kobayashi Mariko , Suzuki Fumitaka , Suzuki Yoshiyuki , Kawamura Yusuke , Akuta Norio , Kobayashi Masahiro , Sezaki Hitomi , Saito Satoshi , Hosaka Tetsuya , Ikeda Kenji , Kumada Hiromitsu , Kobayashi Tetsuro
Published: September 2012

The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for malignancies after the termination of interferon (IFN) therapy in Japanese patients for hepatitis C virus (HCV). A total of 4,302 HCV-positive patients treated with IFN were enrolled. The mean observation period was 8.1 years. The primary outcome was the first onset of malignancies. Evaluation was performed using the Kaplan-Meier method and Cox proportional hazard analysis. A total of 606 patients developed malignancies: 393 developed hepatocellular carcinoma (HCC) and 213 developed malignancies other than HCC. The cumulative development rate of HCC was 4.3% at 5 years, 10.5% at 10 years, and 19.7% at 15 years. HCC occurred significantly (
P

< 0.05) when the following characteristics were present: advanced histological staging, sustained virological response not achieved, male sex, advanced age of ≥50 years, total alcohol intake of ≥200 kg, and presence of type 2 diabetes (T2DM). T2DM caused a 1.73-fold enhancement in HCC development. In patients with T2DM, HCC decreased when patients had a mean hemoglobin A1c (HbA1c) level of <7.0% during follow-up (hazard ratio, 0.56; 95% confidence interval, 0.33–0.89;

P

= 0.015). The cumulative development rate of malignancy other than HCC was 2.4% at 5 years, 5.1% at 10 years, and 9.8% at 15 years. Malignancies other than HCC occurred significantly when patients were of advanced age of ≤50 years, smoking index (package per day × year) was ≥ 20, and T2DM was present. T2DM caused a 1.70-fold enhancement in the development of malignancies other than HCC.

Conclusion:

T2DM causes an approximately 1.7-fold enhancement in the development of HCC and malignancies other than HCC in HCV-positive patients treated with IFN. In T2DM patients, maintaining a mean HbA1c level of <7.0% reduces the development of HCC. (Hepatology 2013)
The HPV test has similar sensitivity but more overdiagnosis than the Pap test—A randomised health services study on cervical cancer screening in Finland
Authors: Malila Nea , Leinonen Maarit , Kotaniemi‐Talonen Laura , Laurila Pekka , Tarkkanen Jussi , Hakama Matti
Published: September 2012

We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non‐progressive pre‐invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person‐years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/105 person‐years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.
Direct medical resource utilization associated with osteoporosis-related nonvertebral fractures in postmenopausal women
Authors: Jean Sonia , Bessette Louis , Belzile Étienne L , Davison K Shawn , Candas Bernard , Morin Suzanne , Dodin Sylvie , Brown Jacques P
Published: September 2012

The purposes of this study were to assess direct medical resource utilization related to the treatment of nonvertebral osteoporotic fractures within 1 year postfracture and to evaluate whether age impacts resource utilization. A previously-validated algorithm for physician claims databases identified 15,327 women aged 50 years or older with incident fracture at nonvertebral osteoporotic sites between January 1, 2004 and December 31, 2005. Administrative databases of the health services available to all residents in Quebec served to study fracture-related health resource utilization in the year after fracture. Data were linked by a unique personal identifier, creating a longitudinal cohort of all fracture cases for health resource utilization. The proportions of fractures treated by open reduction, closed reduction, immobilization or follow-up by an orthopedic surgeon (OS) were evaluated. The mean number of claims for consultation with an OS or other clinicians in inpatient and outpatient visits, the hospitalization rate and length of stay (LOS) were assessed. Hip/femur fractures represented the highest rate of resource utilization because the majority of them required surgery (91.1%) and hospitalization (94.5%) with a mean (median) LOS of 39.2 (31) days. However, other nonvertebral fracture types needed significant clinical care related to surgery (27.9%), follow-up consultation with an OS (77.6%), and hospitalization (27.3% of total LOS). Even pelvic fractures, which often do not require surgical treatment, commanded high resource utilization due to the high hospitalization rate (67.4%) with mean (median) LOS of 34.2 (26) days. Moreover, age was an important determinant of health resource utilization, being associated with an increased number of visits to other physicians, hospitalization, and length of hospitalization (LOS), admissions to long term care (LTC), and death. Osteoporosis-related fractures accounted for substantial healthcare resource utilization. With an aging population and increased prevalence of fractures, strategies for osteoporosis management need to be introduced to reduce the healthcare burden. © 2013 American Society for Bone and Mineral Research
Meta-analysis of vertebral augmentation compared with conservative treatment for osteoporotic spinal fractures
Authors: Anderson Paul A , Froyshteter Alexander B , Tontz William L
Published: September 2012

Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF). Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points? We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Searches were performed from Medical Subject Headings. Terms “vertebroplasty” and “compression fracture” were used. The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed. A random effects model was chosen. Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group. New vertebral fracture risk was calculated using log odds ratio. Six studies met the criteria. The pain visual analog scale (VAS) mean difference was 0.73 (confidence interval [CI] 0.35, 1.10) for early (<12 weeks) and 0.58 (CI 0.19, 0.97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0.001). The functional outcomes at early and late time points were statistically significant with 1.08 (CI 0.33, 1.82) and 1.16 (CI 0.14, 2.18), respectively. The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0.39 (CI 0.16, 0.62) and 0.33 (CI 0.16, 0.51), respectively. Secondary fractures were not statistically different between the groups, 0.065 (CI −0.57, 0.70). This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls. Cement augmentation results were significant in the early (<12 weeks) and the late time points (6 to 12 months). This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic VCF fractures. © 2013 American Society for Bone and Mineral Research
PTH-enhanced structural allograft healing is associated with decreased angiopoietin-2–mediated arteriogenesis, mast cell accumulation, and fibrosis
Authors: Dhillon Robinder S , Xie Chao , Tyler Wakenda , Calvi Laura M , Awad Hani A , Zuscik Michael J , O'Keefe Regis J , Schwarz Edward M
Published: September 2012

Recombinant parathyroid hormone (rPTH) therapy has been evaluated for skeletal repair in animal studies and clinical trials based on its known anabolic effects, but its effects on angiogenesis and fibrosis remain poorly understood. We examined the effects of rPTH therapy on blood vessel formation and osseous integration in a murine femoral allograft model, which caused a significant increase in small vessel numbers, and decreased large vessel formation (p < 0.05). Histology showed that rPTH also reduced fibrosis around the allografts to similar levels observed in live autografts, and decreased mast cells at the graft-host junction. Similar effects on vasculogenesis and fibrosis were observed in femoral allografts from Col1caPTHR transgenic mice. Gene expression profiling revealed rPTH-induced angiopoietin-1 (8-fold), while decreasing angiopoietin-2 (70-fold) at day 7 of allograft healing. Finally, we show anti-angiopoietin-2 peptibody (L1-10) treatment mimics rPTH effects on angiogenesis and fibrosis. Collectively, these findings show that intermittent rPTH treatment enhances structural allograft healing by two processes: (1) anabolic effects on new bone formation via small vessel angiogenesis, and (2) inhibition of angiopoietin-2–mediated arteriogenesis. The latter effect may function as a vascular sieve to limit mast cell access to the site of tissue repair, which decreases fibrosis around and between the fractured ends of bone. Thus, rPTH therapy may be generalizable to all forms of tissue repair that suffer from limited biointegration and excessive fibrosis. © 2013 American Society for Bone and Mineral Research.
Tooth root dentin mineralization defects in a mouse model of hypophosphatasia
Authors: Foster BL , Nagatomo KJ , Tso HW , Tran AB , Nociti FH , Narisawa S , Yadav MC , McKee MD , Millán JL , Somerman MJ
Published: September 2012

Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in mineralizing tissues and functions to reduce pyrophosphate (PPi), a potent inhibitor of mineralization. Loss of TNAP function causes hypophosphatasia (HPP), a heritable disorder marked by increased PPi, resulting in rickets and osteomalacia. Tooth root cementum defects are well described in both HPP patients and in Alpl−/− mice, a model for infantile HPP. In Alpl−/− mice, dentin mineralization is specifically delayed in the root; however, reports from human HPP patients are variable and inconsistent regarding dentin defects. In the current study, we aimed to define the molecular basis for changes in dentinogenesis observed in Alpl−/− mice. TNAP was found to be highly expressed by mature odontoblasts, and Alpl−/− molar and incisor roots featured defective dentin mineralization, ranging from a mild delay to severely disturbed root dentinogenesis. Lack of mantle dentin mineralization was associated with disordered and dysmorphic odontoblasts having disrupted expression of marker genes osteocalcin and dentin sialophosphoprotein. The formation of, initiation of mineralization within, and rupture of matrix vesicles in Alpl−/− dentin matrix was not affected. Osteopontin (OPN), an inhibitor of mineralization that contributes to the skeletal pathology in Alpl−/− mice, was present in the generally unmineralized Alpl−/− mantle dentin at ruptured mineralizing matrix vesicles, as detected by immunohistochemistry and by immunogold labeling. However, ablating the OPN-encoding Spp1 gene in Alpl−/− mice was insufficient to rescue the dentin mineralization defect. Administration of bioengineered mineral-targeting human TNAP (ENB-0040) to Alpl−/− mice corrected defective dentin mineralization in the molar roots. These studies reveal that TNAP participates in root dentin formation and confirm that reduction of PPi during dentinogenesis is necessary for odontoblast differentiation, dentin matrix secretion, and mineralization. Furthermore, these results elucidate developmental mechanisms underlying dentin pathology in HPP patients, and begin to explain the reported variability in the dentin/pulp complex pathology in these patients. © 2013 American Society for Bone and Mineral Research