bluuebunny/crossref_metadata_2025 huggingface dataset:
Regularizations of general singular integral operators
Authors: Liaw Constanze , Treil Sergei
Published: January 2013

In the theory of singular integral operators significant effort is often required to rigorously define such an operator. This is due to the fact that the kernels of such operators are not locally integrable on the diagonal

s=t

, so the integral formally defining the operator

T

or its bilinear form

\langle Tf, g \rangle

is not well defined (the integrand in not in

L^1

) even for “nice”

f

and

g

. However, since the kernel only has singularities on the “diagonal”

s=t

, the bilinear form

\langle Tf, g \rangle

is well defined, say, for bounded compactly supported functions with separated supports.

One of the standard ways to interpret the boundedness of a singular integral operators is to consider the
regularized kernel
[ K_\varepsilon(s, t) = K(s, t), m((s-t)/\varepsilon), ] where the cut-off function

m

is

0

in a neighborhood of the origin, so the integral operators

T_\varepsilon

with kernel

K_\varepsilon

are well defined (at least on a dense set). Then instead of asking about the boundedness of the operator

T

, which is not well defined, one can ask about uniform boundedness (in

\varepsilon

) of the regularized operators

T_\varepsilon

.

For the standard regularizations one usually considers
truncated
operators

T_\varepsilon

with

m(s) =\mathbf{1}_{[1, \infty)} (|s|)

, although smooth cut-off functions were also considered in the literature.

The main result of the paper is that for a wide class of singular integral operators (including the classical Calderón–Zygmund operators in nonhomogeneous two weight settings), the so called restricted

L^p

boundedness, i.e., the uniform estimate [ |\langle Tf, g \rangle| \le C ,|f|
p ,|g|
{p'} ] for bounded compactly supported

f

and

g

with separated supports implies the uniform

L^p

-boundedness of regularized operators

T_\varepsilon

for any reasonable choice of smooth cut-off function

m

. For example, any

m \in C^\infty(\mathbb{R}^N)

},

m\equiv 0

in a neighborhood of

0

, and such that

1-m

is compactly supported would work.

If the kernel

K

satisfies some additional assumptions (which are satisfied for classical singular integral operators like the Hilbert transform, Cauchy transform, Ahlfors–Beurling transform, and generalized Riesz transforms), then the restricted

L^p

boundedness also implies the uniform

L^p

boundedness of the classical truncated operators

T_\varepsilon

(

m(s) =\mathbf{1}_{[1, \infty)} (|s|)

).
Monotonicity and comparison results for conformal invariants
Authors: Baernstein II Albert , Solynin Alexander Yu.
Published: January 2013

Let

a_1,\dots,a_N

be points on the unit circle

\mathbb{T}

with

a_j=e^{i\theta_j}

, where

0=\theta_1\le\theta_2\le\dots\le \theta_N=2\pi

. Let

\Omega=\overline{\mathbb{C}}\setminus\{a_1,\dots,a_N\}

and let

\Omega^*

be

\overline{\mathbb{C}}

with the

n

-th roots of unity removed. The maximal gap

\delta(\Omega)

of

\Omega

is defined by

\delta(\Omega)=\max\{\theta_{j+1}-\theta_j:\,0\le j\le N-1\}

. How should one choose

a_1,\dots,a_N

subject to the condition

\delta(\Omega)\le 2\pi/n

so that the Poincaré metric

\lambda_\Omega(0)

of

\Omega

at the origin is as small as possible? In this paper we answer this question by showing that

\lambda_\Omega(0)

is minimal when

\Omega=\Omega^*

. Several similar problems on the extremal values of the harmonic measures and capacities are also discussed.
On symplectic and non-symplectic automorphisms of K3 surfaces
Authors: Garbagnati Alice , Sarti Alessandra
Published: January 2013

In this paper we investigate when the generic member of a family of complex K3 surfaces admitting a non-symplectic automorphism of finite order admits also a symplectic automorphism of the same order. We give a complete answer to this question if the order of the automorphism is a prime number and we provide several examples and partial results otherwise. Moreover we prove that, under certain conditions, a K3 surface admitting a non-symplectic automorphism of prime odd order,

p

, also admits a non-symplectic automorphism of order

2p

. This generalizes a previous result by J. Dillies for

p=3

.
Wavelet approach to operator-valued Hardy spaces
Authors: Hong Guixiang , Yin Zhi
Published: January 2013

This paper is devoted to the study of operator-valued Hardy spaces via the wavelet method. This approach is parallel to that in the noncommutative martingale case. We show that our Hardy spaces defined by wavelets coincide with those introduced by Tao Mei via the usual Lusin and Littlewood–Paley square functions. As a consequence, we give an explicit complete unconditional basis of the Hardy space

H_1(\mathbb{R})

when

H_1(\mathbb{R})

is equipped with an appropriate operator space structure.
Revisiting the multifractal analysis of measures
Authors: Ben Nasr Fathi , Peyrière Jacques
Published: January 2013

New proofs of theorems on the multifractal formalism are given. They yield results even at points

q

for which Olsen’s functions

b(q)

and

B(q)

differ. Indeed, we provide an example of a measure for which the functions

b

and

B

differ and for which the Hausdorff dimensions of the sets

X_\alpha

(the level sets of the local Hölder exponent) are given by the Legendre transform of

b

and their packing dimensions by the Legendre transform of

B

.
On genuine infinite algebraic tensor products
Authors: Ng Chi-Keung
Published: January 2013

In this paper, we study genuine infinite tensor products of some algebraic structures. By a genuine infinite tensor product of vector spaces, we mean a vector space

\bigotimes_{i\in I} X_i

whose linear maps coincide with multilinear maps on an infinite family

\{X_i\}_{i\in I}

of vector spaces. After establishing its existence, we give a direct sum decomposition of

\bigotimes_{i\in I} X_i

over a set

\Omega_{I;X}

, through which we obtain a more concrete description and some properties of

\bigotimes_{i\in I} X_i

. If

\{A_i\}_{i\in I}

is a family of unital

^*

-algebras, we define, through a subgroup

\Omega^{\rm ut}_{I;A}\subseteq \Omega_{I;A}

, an interesting subalgebra

\bigotimes_{i\in I}^{\rm ut} A_i

. When all

A_i

are

C^*

-algebras or group algebras, it is the linear span of the tensor products of unitary elements of

A_i

. Moreover, it is shown that

\bigotimes_{i\in I}^{\rm ut} \mathbb{C}

is the group algebra of

\Omega^{\rm ut}_{I;\mathbb{C}}

. In general,

\bigotimes_{i\in I}^{\rm ut} A_i

can be identified with the algebraic crossed product of a cocycle twisted action of

\Omega^{\rm ut}_{I;A}

. On the other hand, if

\{H_i\}_{i\in I}

is a family of inner product spaces, we define a Hilbert

C^*(\Omega^{\rm ut}_{I;\mathbb{C}})

-module

\overline{\bigotimes}^{\rm mod}_{i\in I} H_i

, which is the completion of a subspace

\bigotimes_{i\in I}^{\rm unit} H_i

of

\bigotimes_{i\in I} H_i

. If

\chi_{\Omega^{\rm ut}_{I;\mathbb{C}}}

is the canonical tracial state on

C^*(\Omega^{\rm ut}_{I;\mathbb{C}})

, then

\overline{\bigotimes}^{\rm mod}_{i\in I} H_i\otimes_{\chi_{\Omega^{\rm ut}_{I;\mathbb{C}}}}\mathbb{C}

coincides with the Hilbert space

\overline{\bigotimes}^{\phi_1}_{i\in I} H_i

given by a very elementary algebraic construction and is a natural dilation of the infinite direct product

\prod {\otimes}_{i\in I} H_i

as defined by J. von Neumann. We will show that the canonical representation of

\bigotimes_{i\in I}^{\rm ut} \mathcal{L}(H_i)

on

\overline\bigotimes^{\phi_1}_{i\in I} H_i

is injective (note that the canonical representation of

\bigotimes_{i\in I}^{\rm ut} \mathcal{L}(H_i)

on

\prod {\otimes}_{i\in I} H_i

is not injective). We will also show that if

\{A_i\}_{i\in I}

is a family of unital Hilbert algebras, then so is

\bigotimes_{i\in I}^{\rm ut} A_i

.
Boundary asymptotic expansions of analytic self-maps of the unit disk
Authors: Bolotnikov Vladimir , Zobin Nahum
Published: January 2013

A characterization of analytic self-maps of the open unit disk in terms of their Taylor coefficients is due to I. Schur. We present a boundary analog of this result.
Measurement of low-ppm mixing ratios of water vapor in the upper troposphere and lower stratosphere using chemical ionization mass spectrometry
Authors: Thornberry T. D. , Rollins A. W. , Gao R. S. , Watts L. A. , Ciciora S. J. , McLaughlin R. J. , Voigt C. , Hall B. , Fahey D. W.
Published: January 2013

Abstract. A chemical ionization mass spectrometer (CIMS) instrument has been developed for the fast, precise, and accurate measurement of water vapor (H2O) at low mixing ratios in the upper troposphere and lower stratosphere (UT/LS). A low-pressure flow of sample air passes through an ionization volume containing an α-particle radiation source, resulting in a cascade of ion-molecule reactions that produce hydronium ions (H3O+) from ambient H2O. The production of H3O+ ions from ambient H2O depends on pressure and flow through the ion source, which were tightly controlled in order to maintain the measurement sensitivity independent of changes in the airborne sampling environment. The instrument was calibrated every 45 min in flight by introducing a series of H2O mixing ratios between 0.5 and 153 parts per million (ppm) generated by Pt-catalyzed oxidation of H2 standards while overflowing the inlet with dry synthetic air. The CIMS H2O instrument was deployed in an unpressurized payload area aboard the NASA WB-57 high altitude research aircraft during the Mid-latitude Airborne Cirrus Properties Experiment (MACPEX) mission in March and April 2011. The instrument performed successfully during seven flights, measuring H2O mixing ratios below 5 ppm in the lower stratosphere at altitudes up to 17.7 km, and as low as 3.5 ppm near the tropopause. Data were acquired at 10 Hz and reported as 1-s averages. In-flight calibrations demonstrated a typical sensitivity of 2000 Hz ppm−1 at 3 ppm with a signal to noise ratio (2σ, 1-s) greater than 32. The total measurement uncertainty was 9 to 11%, derived from the uncertainty in the in situ calibrations.
Comparative assessment of predictions in ungauged basins – Part 1: Runoff hydrograph studies
Authors: Parajka J. , Viglione A. , Rogger M. , Salinas J. L. , Sivapalan M. , Blöschl G.
Published: January 2013

Abstract. The objective of this assessment is to compare studies predicting runoff hydrographs in ungauged catchments. The aim is to learn from the differences and similarities between catchments in different locations, and to interpret the differences in performance in terms of the underlying climate and landscape controls. The assessment is performed at two levels. The Level 1 assessment is a meta-analysis of 34 studies reported in the literature involving 3874 catchments. The Level 2 assessment consists of a more focused and detailed analysis of individual basins from selected studies from Level 1 in terms of how the leave-one-out cross-validation performance depends on climate and catchment characteristics as well as on the chosen regionalisation method. The results indicate that runoff hydrograph predictions in ungauged catchments tend to be more accurate in humid than in arid catchments and more accurate in large than in small catchments. The dependence of performance on elevation differs by regions and depends on how aridity varies with elevation and air temperature. The effect of parameter regionalisation method on model performance differs between studies. However, there is a tendency towards a somewhat lower performance of regressions than other methods in those studies that apply different methods in the same region. In humid catchments spatial proximity and similarity methods perform best while in arid catchments similarity and parameter regression methods perform slightly better. For studies with a large number of catchments (dense stream gauge network) there is a tendency for spatial proximity and geostatistics to perform better than regression or regionalisation based on simple averaging of model parameters from gauged catchments. There was no clear relationship between predictive performance and the number of regionalised model parameters. The implications of the findings are discussed in the context of model building.
Human Resource Dvelopment and Poverty Reduction in Nigeria: A Symbiotic Relationship
Authors: Asaju Kayode
Published: January 2013

ABSRACTHuman Capital development through education is a long time investment made by the state to enhance the well being of her citizenry. By investing in education, well educated individuals bring to bear their talents, knowledge, skills and experiences as they function in the various sectors of the economy. Human Capital development is therefore a prerequisite for economic growth and development, as well as a necessary and sufficient condition for poverty reduction in Nigeria. Unfortunately, successive governments in Nigeria have continued to pay lip services to the issue of investment in education. The author is of the view that poverty is synonymous with underdevelopment. Therefore, investing in human capital through education is the best strategy for overcoming the developmental challenges in the country, especially poverty reduction. This will be achieve by ensuring an effective educational system that is well funded, equipped, science and technology focus, dynamic, and innovative. Development   Education   Human Capital   Poverty   Poverty Reduction
Quality Management System for Contemporary Public Administration: A case study of e-Governance
Authors: Vasista T. G. K.
Published: January 2013

The quality movement in Public Administration is a part of reform and modernisation efforts aimed at replacing the bureaucratic model by a more citizen-oriented paradigm. Governments are considered organisations that are capable enough to quickly adopt new technologies to engage and serve constituents. While eGovernment embraces the use of information and communication technologies in public administration (combined with organisational change) to improve public services, e-governance on the other hand focuses on the idea of creating a government that is closer to the citizens it serves and more open to their participation at several levels. Research is needed on how the dynamic, competitive web culture affects citizen (and other user) demands for electronic service quality in the process of achieving customer satisfaction. The main theoretical argument behind this paper is that governments in the process of establishing quality management system in public administration should focus on working towards                             e-governance, which is citizen centric so as to create right organisational environment to achieve the effectiveness, efficiency and equity.
Technocratic Structures of Climate Policy: Dead-end Debates, Neat Narratives and Manipulative Machiavellianism
Authors: Murray Taylor A.
Published: January 2013

The contemporary models of climate change policy-making in the United States are particular to this decade. The increased role for experts and expert-led policymaking is unprecedented. However this power has been paradoxical. This paper argues that an excessive role for science in discussions of climate change has undermined the public’s role, and has thus undermined the efforts on behalf of policymakers to pass comprehensive climate change policy. Two main aspects of the excessive role for science in the formation of climate policy were found to be 1. the large influence of dissenting scientists on the debate, and 2. the alienation of the public from the discourse. Further, possible scenarios for policymaking, which better balance the roles of experts, the public, and policymakers, are discussed and frameworks for the future are outlined.
Apresentação do processo de formação da estratégia: um estudo de caso em empresa inovadora
Authors: Gomes Daniel Teodoro , Muniz Reynaldo Maia , Dias Alexandre Teixeira , Gonçalves Carlos Alberto
Published: January 2013

This paper presents a study of strategy formation process with the following starting question: "How the strategy is shaped in an innovative company and how the factors manifesting in the process?". The research builds on a case study of a company considered innovative leader in its industry and a pioneer in providing various services in the area of mobile phone in Brazil. Data collection was through interviews semi-structured with directors and managers involved in strategy formation, supplemented by documents and direct observation. Data analysis is based on the techniques of discourse analysis, from the persuasion strategies suggested by Linhares and Faria (1993). The company's strategy studied can be defined as an entrepreneurial vision, focused on growth supported by a process of diversification of product lines from a new direction composed of three elements: (i) componentization; (ii) segmentation by products chain and; (iii) external to finance leverage in order to resumption of innovative projects. It was concluded that the company's strategy focused on these three factors, supported by a deliberate vision of the future, conditions its historical trajectory type standard cultural, its core values, which acts as a motivator and guide for members of the organization decisions and actions.
Escolarização de jovens e adultos com deficiência intelectual: considerações sobre as pesquisas em dissertações e teses no período de 1988 a 2008
Authors: Brito Jéssica De , Campos Juliane Ap. de Paula Perez
Published: January 2013

http://dx.doi.org/10.5902/1984686X4848 O objetivo deste estudo foi investigar produções científicas sobre a temática da educação de jovens e adultos com deficiência intelectual, presentes em dissertações e teses no período de 1988 a 2008. Para isso, realizou-se o levantamento no banco de teses da Capes, por meio de busca com descritores específicos que contemplassem a educação de jovens e adultos, educação especial, e deficiência intelectual e mental. Foram selecionadas dez produções distribuídas em seis Instituições de Ensino Superior (IES), a maioria oriundas de IES públicas, relativas ao Programa de Pós-Graduação em Educação, e defendidas na década de 2000. A maior parte dos estudos incidiu sobre a alfabetização e sinalizou a necessidade de aprimoramento das práticas pedagógicas, bem como a importância da interação dos jovens e adultos portadores de deficiência intelectual com seus professores. Verificou-se ainda a existência de poucos estudos pertinentes a essa população em questão; apontando para um campo de conhecimento a ser devidamente desvendado.Palavras-chave: Alunos com deficiência intelectual; Educação de jovens e adultos; Educação Especial.
Inclusão escolar e Educação Infantil: um estudo de caso
Authors: Pereira Paulo Celso , Matsukura Thelma Simões
Published: January 2013

http://dx.doi.org/10.5902/1984686X5471A inclusão escolar surgiu na década de 80, pautada no movimento de inclusão social, propondo um novo paradigma para o atendimento de crianças com necessidades educacionais especiais. A literatura aponta uma grande dificuldade para a implantação de projetos de inclusão escolar e, na literatura nacional são poucos os estudos sobre a inserção de crianças com necessidades educacionais especiais em creches (Educação Infantil). O objetivo deste estudo foi realizar um levantamento, segundo a perspectiva das professoras, das crianças com necessidades especiais inseridas em creches da rede municipal da cidade de Catanduva, estado de São Paulo, e identificar a concepção das diretoras de creche sobre inclusão escolar. Participaram da pesquisa 54 professoras e 15 diretoras; que preencheram o Instrumento de Identificação de Crianças com Necessidades Educacionais Especiais e responderam a uma entrevista, respectivamente. Os resultados mostraram que, na concepção das professoras, nas creches da referida cidade estavam inseridas 40 crianças com necessidades especiais, na maioria meninos, com maior incidência na faixa etária de dois a três anos, sendo que 27,5% foram identificadas em situação de risco. O estudo revelou ainda que as diretoras tinham conhecimento superficial sobre inclusão escolar, priorizando seus aspectos práticos.Palavras-chave: Educação infantil; Inclusão escolar; Creche.
Práticas de leitura e compreensão para o desempenho do aluno surdo no ensino regular
Authors: Pinheiro Lucineide Machado
Published: January 2013

http://dx.doi.org/10.5902/1984686X6469 A leitura é fundamental para a formação dos alunos, é por meio dela que se dá a abordagem dos conteúdos escolares. Por isso, é preciso ensinar os alunos a lerem com competência, para que tenham um desempenho escolar satisfatório. Constata-se que as escolas não têm oferecido aos alunos, e entre eles, os surdos oralizados, práticas de leitura significativas, provocando assim, um baixo desempenho e um quadro de fracasso escolar. De forma contrária, práticas de leitura e compreensão desenvolvidas por profissionais da saúde em núcleos ou clínicas fonoaudiológicas, relatadas por vários autores, tem contribuído para minimizar a problemática que o ensino de leitura incipiente provoca na vida escolar desses alunos. Diante desse contexto, este estudo teve como objetivo, investigar a contribuição das práticas de leitura e compreensão de texto desenvolvidas por profissionais da saúde, para o desempenho do aluno surdo oralizado inserido no ensino regular. Trata-se de um estudo de caso, em que se utilizou como procedimento para coleta de dados, a observação na escola, na qual o aluno surdo encontra-se matriculado, e no Núcleo de Atuação Interdisciplinar de Audição, Linguagem e Educação (NAIALE), onde ele participa do atendimento voltado às dificuldades de leitura e compreensão. Os resultados demonstraram que as práticas de leitura e compreensão desenvolvidas no NAIALE, contribuem para um desempenho escolar satisfatório, pois atendem as especificidades de aprendizagem dos alunos surdos oralizados.Palavras-chave: Desempenho escolar; Leitura; Língua portuguesa; Surdos.
Xenakis et le sérialisme : l’apport d’une analyse génétique de Metastasis
Authors: Barthel-Calvet Anne-Sylvie
Published: January 2013

Par rapport à l’article de Xenakis « Métastassis-Analyse » (2003), le matériau particulièrement abondant d’esquisses de Metastasis conservé au Département de la Musique de la Bibliothèque Nationale de France permet d’affiner la compréhension de l’écriture sérielle qui y est développée. À travers les multiples aspects que le compositeur y met en jeu, celle-ci apparaît comme une véritable maïeutique au cours de laquelle il va prendre conscience qu’il lui faut se tourner vers un autre mode d’organisation musicale, plus adapté à son projet esthétique.
Performance Strategies in Three Recordings of Bach’s Invention No. 1 in C Major: A Comparative Study
Authors: Dodson Alan
Published: January 2013

After a brief introduction to the field of empirical performance studies and its goals and methods, recordings of the titular work by pianists Harold Bauer, Glenn Gould, and Angela Hewitt are discussed. It is suggested that these recordings demonstrate three distinct performance strategies for the piece: Bauer highlights the boundaries of each phrase and projects a teleological design within each phrase and at the level of the entire piece; Gould conveys an arch-shaped design tied to harmonic tension; and Hewitt draws attention not only to the three structural cadences (mm. 7, 15, and 22) but also to a subsidiary V-I motion at m. 11, thereby hinting that it might have structural importance. Parallels between these performance strategies and analyses by Howard Cinnamon, Steve Larson, and Roy Travis are briefly considered. The emphasis on multiplicity in this study distinguishes it from most earlier scholarship on structure and performance.
Le Prisonnier de Luigi Dallapiccola : derrière le politique, le religieux
Authors: Ginot-Slacik Charlotte
Published: January 2013

Composé pendant la seconde guerre mondiale, Le Prisonnier de Luigi Dallapiccola constitue un tournant pour la musique italienne : premier opéra sériel italien en un temps de réaction esthétique et charge contre le fascisme, il est un modèle pour des compositeurs engagés tels que Luigi Nono et Bruno Maderna. Par-delà sa charge politique, Le Prisonnier est également l’expression d’une crise religieuse et d’un doute existentiel. L’Inquisition, institution religieuse par excellence est aussi celle qui torture le croyant au nom de la foi. Le retournement diabolique fait par le Grand Inquisiteur des principales thématiques chrétiennes vise à détruire le libre arbitre de l’autre. La manipulation du prisonnier, Christ contemporain, démontre la vacuité, voire la dangerosité de l’espérance, au nom de laquelle a été abjuré le libre arbitre. Dans l’affrontement entre le geôlier et son prisonnier s’esquisse enfin une sombre définition de la liberté car la parole de celui qui enferme n’est pas plus libre que celle de celui qui est enfermé. La mère seule, unique personnage clairvoyant de l’opéra a pu conserver sa liberté, mais à quel prix : celui de ne pas entrer dans l’action. Le doute qui émerge du Prisonnier est aussi celui de Luigi Dallapiccola, en individu directement touché par la guerre et les lois raciales, et en compositeur humaniste. L’objet de ce texte sera d’étudier la façon dont le musicien décline les thématiques religieuses mais pour les retourner totalement. Car Le Prisonnier, immense oeuvre politique, est aussi celle de l’errance et du questionnement religieux.
Skin regenerative potentials of curcumin
Authors: Thangapazham Rajesh L. , Sharad Shashwat , Maheshwari Radha K.
Published: January 2013

Curcumin, an active constituent of the spice turmeric, is well known for its chemopreventive properties and is found to be beneficial in treating various disorders including skin diseases. Curcumin protects skin by quenching free radicals and reducing inflammation through the inhibition of nuclear factor‐kappa B. Curcumin also affects other signaling pathways including transforming growth factor‐β and mitogen‐activated protein kinase pathway. Curcumin also modulates the phase II detoxification enzymes which are crucial in detoxification reactions and for protection against oxidative stress. In the present review, the biological mechanisms of the chemopreventive potential of curcumin in various skin diseases like psoriasis, vitiligo, and melanoma is discussed. The application of curcumin in skin regeneration and wound healing is also elucidated. We also explored the recent innovations and advances involved in the development of transdermal delivery systems to enhance the bioavailability of curcumin, particularly in the skin. Recent clinical trials pertaining to the use of curumin in skin diseases establishes its benefits and also the need for additional clinical trials in other diseases are discussed. © 2013 BioFactors, 39(1):141–149, 2013
Curcumin (diferuloylmethane) delivery methods: A review
Authors: Helson Lawrence
Published: January 2013

Curcumin interacts with a large number of extra‐ and intracellular targets in a biphasic dose‐dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation‐based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion‐oriented delivery methods, representatives of which are here reviewed. © 2013 BioFactors, 39(1):21–26, 2013
Dietary n‐3 long‐chain polyunsaturated fatty acids modify phosphoenolpyruvate carboxykinase activity and lipid synthesis from glucose in adipose tissue of rats fed a high‐sucrose diet
Authors: Londero Lisiane G. , Rieger Débora K. , Hansen Fernanda , Silveira Simone L. , Martins Tiago L. , Lulhier Francisco , da Silva Roselis S. , Souza Diogo O. , Perry Marcos L. S. , de Assis Adriano M.
Published: January 2013

Long‐chain polyunsaturated n‐3 fatty acids (n‐3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep‐AT) and liver were investigated. Male rats were fed a high‐sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU–FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n‐3 LCPUFAs prevented sucrose‐induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n‐3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep‐AT of rats fed the SU–FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n‐3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases. Copyright © 2013 John Wiley & Sons, Ltd.
Human omentum fat‐derived mesenchymal stem cells transdifferentiates into pancreatic islet‐like cluster
Authors: Dhanasekaran M , Indumathi S , Harikrishnan R , Mishra Rashmi , Lissa RP , Rajkumar J S , Sudarsanam D
Published: January 2013

Current protocols of islet cell transplantation for the treatment of diabetes mellitus have been hampered by islet availability and allograft rejection. Although bone marrow and subcutaneous adipose tissue stem cells feature their tissue repair efficacy, applicability of stem cells from various sources is being researched to develop a promising therapy for diabetes mellitus. Although omentum fat has emerged as an innovative source of stem cells, the dearth of researches confirming its transdifferentiation potential limits its applicability as a regenerative tool in diabetic therapy. Thus, this work is a maiden attempt to explore the colossal potency of omentum fat‐derived stem cells on its lucrative differentiation ability. The plasticity of omentum fat stem cells was substantiated by transdifferentiation into pancreatic islet‐like clusters, which was confirmed by dithizone staining and immunocytochemistry for insulin. It was also confirmed by the expression of pancreatic endocrine markers nestin and pancreatic duodenal homeobox 1 (Pdx 1) using Fluorescence‐activated cell sorting (FACS), neurogenic 3, islet‐1 transcription factor, paired box gene 4, Pdx 1 and insulin using quantitative real‐time polymerase chain reaction and through insulin secretion assay. This study revealed the in vitro differentiation potency of omentum fat stem cells into pancreatic islet‐like clusters. However, further research pursuits exploring its in vivo endocrine efficacy would make omentum fat stem cells a superior source for β‐cell replacement therapy. Copyright © 2013 John Wiley & Sons, Ltd.
Novel aspects of parenchymal–mesenchymal interactions: from cell types to molecules and beyond
Authors: Bluguermann Carolina , Wu Ling , Petrigliano Frank , McAllister David , Miriuka Santiago , Evseenko Denis A.
Published: January 2013

Mesenchymal stem or stromal cells (MSCs) were initially isolated from the bone marrow and received their name on the basis of their ability to differentiate into multiple lineages such as bone, cartilage, fat and muscle. However, more recent studies suggest that MSCs residing in perivascular compartments of the small and large blood vessels play a regulatory function supporting physiologic and pathologic responses of parenchymal cells, which define the functional representation of an organ or tissue. MSCs secrete or express factors that reach neighbouring parenchymal cells via either a paracrine effect or a direct cell‐to‐cell interaction promoting functional activity, survival and proliferation of the parenchymal cells. Previous concept of ‘epithelial–stromal’ interactions can now be widened. Given that MSC can also support hematopoietic, neuronal and other non‐epithelial parenchymal lineages, terms ‘parenchymal–stromal’ or ‘parenchymal–mesenchymal’ interactions may better describe the supportive or ‘trophic’ functions of MSC. Importantly, in many cases, MSCs specifically provide supportive microenvironment for the most primitive stem or progenitor populations and therefore can play a role as ‘stem/progenitor niche’ forming cells. So far, regulatory roles of MSCs have been reported in many tissues. In this review article, we summarize the latest studies that focused on the supportive function of MSC. This thread of research leads to a new perspective on the interactions between parenchymal and mesenchymal cells and justifies a principally novel approach for regenerative medicine based on co‐application of MSC and parenchymal cell for the most efficient tissue repair. Copyright © 2013 John Wiley & Sons, Ltd.
An integrated modelling framework of catchment‐scale ecohydrological processes: 1. Model description and tests over an energy‐limited watershed
Authors: Niu Guo‐Yue , Paniconi Claudio , Troch Peter A. , Scott Russell L. , Durcik Matej , Zeng Xubin , Huxman Travis , Goodrich David C.
Published: January 2013

The interactions between atmospheric, hydrological, and ecological processes at various spatial and temporal scales are not fully represented in most ecohydrological models. This first of a two‐part paper documents a fully integrated catchment‐scale ecohydrological model consisting of a three‐dimensional physically based hydrological model and a land surface model. This first part also presents a first application to test the model over an energy‐limited catchment (8.4 km2) of the Sleepers River watershed in Vermont.

The physically based hydrological model (CATchment HYdrology, CATHY) describes three‐dimensional subsurface flow in variably saturated porous media and surface routing on hillslopes and in stream channels, whereas the land surface model (LSM), an augmented version of Noah LSM with multiple parameterization schemes (NoahMP), accounts for energy, water, and carbon flux exchanges between various land surface elements and the atmosphere. CATHY and NoahMP are coupled through exchanges of water fluxes and states. In the energy‐limited catchment of the Sleepers River watershed, where snowmelt runoff generation is the dominant hydrologic flux, the coupled CATHY/NoahMP model at both 90 and 30‐m surface grid resolutions, with minimal calibration, performs well in simulating the observed snow accumulation, and melt and subsequent snowmelt discharge. The Nash–Sutcliffe model efficiency of daily discharge is above 0.82 for both resolutions. The simulation at 90‐m resolution shows a marginal improvement over that at 30‐m resolution because of more elaborate calibration of model parameters. The coupled CATHY/NoahMP also shows a capability of simulating surface‐inundated area and distributed surface water height, although the accuracy of these simulations needs further evaluation. The CATHY/NoahMP model is thus also a potentially useful research tool for predicting flash flood and lake dynamics under climatic change. Copyright © 2013 John Wiley & Sons, Ltd.
A global view of hepatitis C: Physician knowledge, opinions, and perceived barriers to care
Authors: McGowan Christopher E. , Monis Ali , Bacon Bruce R. , Mallolas Josep , Goncales Fernando L. , Goulis Ioannis , Poordad Fred , Afdhal Nezam , Zeuzem Stefan , Piratvisuth Teerha , Marcellin Patrick , Fried Michael W.
Published: January 2013

Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community.

Conclusion:

Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed.
Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice
Authors: Mouralidarane Angelina , Soeda Junpei , Visconti-Pugmire Clara , Samuelsson Anne-Maj , Pombo Joaquim , Maragkoudaki Xanthi , Butt Adil , Saraswati Ruma , Novelli Marco , Fusai Guiseppe , Poston Lucilla , Taylor Paul D. , Oben Jude A.
Published: January 2013

The global prevalence of obesity-induced liver disease (nonalcoholic fatty liver disease; NAFLD) is rising. Suggested causes include a role for in utero influences of maternal obesity compounded by the availability of energy-dense foods throughout postnatal life. Using a physiologically relevant model, we investigated the role of the innate immune system in liver injury induced by maternal obesity followed by a postnatal obesogenic diet. Female C57BL/6J mice were fed a standard or obesogenic diet before and throughout pregnancy and during lactation. Female offspring were weaned onto a standard or obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis, analysis of profibrotic pathways, liver innate immune cells, and reactive oxygen species (ROS) were investigated at 3, 6, and 12 months. Female offspring exposed to a postweaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury, which was exacerbated by previous exposure to maternal obesity (OffOb-OD), as demonstrated by raised alanine aminotransferase, hepatic triglycerides, and hepatic expression of interleukin (IL)-6, tumor necrosis factor alpha, transforming growth factor beta, alpha smooth muscle actin, and collagen (P < 0.01). Histological evidence of hepatosteatosis and a more-robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell numbers with impaired phagocytic function and raised ROS synthesis (P < 0.01), together with reduced natural killer T cells and raised interleukin (IL)-12 and IL-18. Conclusion: Maternal obesity in the context of a postnatal hypercalorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease. (HEPATOLOGY 2013)
Hepatocyte nuclear factor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular carcinoma in rodents
Authors: Walesky Chad , Edwards Genea , Borude Prachi , Gunewardena Sumedha , O'Neil Maura , Yoo Byunggil , Apte Udayan
Published: January 2013

Hepatocyte nuclear factor 4 alpha (HNF4α), the master regulator of hepatocyte differentiation, has been recently shown to inhibit hepatocyte proliferation by way of unknown mechanisms. We investigated the mechanisms of HNF4α-induced inhibition of hepatocyte proliferation using a novel tamoxifen (TAM)-inducible, hepatocyte-specific HNF4α knockdown mouse model. Hepatocyte-specific deletion of HNF4α in adult mice resulted in increased hepatocyte proliferation, with a significant increase in liver-to-body-weight ratio. We determined global gene expression changes using Illumina HiSeq-based RNA sequencing, which revealed that a significant number of up-regulated genes following deletion of HNF4α were associated with cancer pathogenesis, cell cycle control, and cell proliferation. The pathway analysis further revealed that c-Myc-regulated gene expression network was highly activated following HNF4α deletion. To determine whether deletion of HNF4α affects cancer pathogenesis, HNF4α knockdown was induced in mice treated with the known hepatic carcinogen diethylnitrosamine (DEN). Deletion of HNF4α significantly increased the number and size of DEN-induced hepatic tumors. Pathological analysis revealed that tumors in HNF4α-deleted mice were well-differentiated hepatocellular carcinoma (HCC) and mixed HCC-cholangiocarcinoma. Analysis of tumors and surrounding normal liver tissue in DEN-treated HNF4α knockout mice showed significant induction in c-Myc expression. Taken together, deletion of HNF4α in adult hepatocytes results in increased hepatocyte proliferation and promotion of DEN-induced hepatic tumors secondary to aberrant c-Myc activation.
Genome-wide microRNA and messenger RNA profiling in rodent liver development implicates mir302b and mir20a in repressing transforming growth factor-beta signaling
Authors: Wei Wei , Hou Juan , Alder Olivia , Ye Xin , Lee Sam , Cullum Rebecca , Chu Andy , Zhao Yongjun , Warner Stephanie M. , Knight Darryl A. , Yang Decheng , Jones Steven J.M. , Marra Marco A. , Hoodless Pamela A.
Published: January 2013

MicroRNAs (miRNAs) are recently discovered small RNA molecules that regulate developmental processes, such as proliferation, differentiation, and apoptosis; however, the identity of miRNAs and their functions during liver development are largely unknown. Here we investigated the miRNA and gene expression profiles for embryonic day (E)8.5 endoderm, E14.5 Dlk1+ liver cells (hepatoblasts), and adult liver by employing Illumina sequencing. We found that miRNAs were abundantly expressed at all three stages. Using K-means clustering analysis, 13 miRNA clusters with distinct temporal expression patterns were identified. mir302b, an endoderm-enriched miRNA, was identified as an miRNA whose predicted targets are expressed highly in E14.5 hepatoblasts but low in the endoderm. We validated the expression of mir302b in the endoderm by whole-mount

in situ

hybridization. Interestingly, mir20a, the most highly expressed miRNA in the endoderm library, was also predicted to regulate some of the same targets as mir302b. We found that through targeting

Tgfbr2

, mir302b and mir20a are able to regulate transforming growth factor beta (TGFβ) signal transduction. Moreover, mir302b can repress liver markers in an embryonic stem cell differentiation model. Collectively, we uncovered dynamic patterns of individual miRNAs during liver development, as well as miRNA networks that could be essential for the specification and differentiation of liver progenitors.
The ART of decision making: Retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma
Authors: Sieghart Wolfgang , Hucke Florian , Pinter Matthias , Graziadei Ivo , Vogel Wolfgang , Müller Christian , Heinzl Harald , Trauner Michael , Peck-Radosavljevic Markus
Published: January 2013

We aimed to establish an objective point score to guide the decision for retreatment with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). In all, 222 patients diagnosed with HCC and treated with multiple TACE cycles between January 1999 and December 2009 at the Departments of Gastroenterology/Hepatology of the Medical Universities of Vienna (training cohort) and Innsbruck (validation cohort) were included. We investigated the effect of the first TACE on parameters of liver function and tumor response and their impact on overall survival (OS, log rank test) and developed a point score (ART score: Assessment for Retreatment with TACE) in the training cohort (n = 107, Vienna) by using a stepwise Cox regression model. The ART score was externally validated in an independent validation cohort (n = 115, Innsbruck). The increase of aspartate aminotransferase (AST) by >25% (hazard ratio [HR] 8.4;

P

< 0.001), an increase of Child-Pugh score of 1 (HR 2.0) or ≥2 points (HR 4.4) (

P

< 0.001) from baseline, and the absence of radiologic tumor response (HR 1.7;

P

= 0.026) remained independent negative prognostic factors for OS and were used to create the ART score. The ART score differentiated two groups (0-1.5 points; ≥2.5 points) with distinct prognosis (median OS: 23.7 versus 6.6 months;

P

< 0.001) and a higher ART score was associated with major adverse events after the second TACE (

P

= 0.011). These results were confirmed in the external validation cohort and remained significant irrespective of Child-Pugh stage and the presence of ascites prior the second TACE.

Conclusion:

An ART score of ≥2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions.
Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: Role of the S100A4-miR155-SOCS1-MMP9 axis
Authors: Yan Xin-Long , Jia Ya-Li , Chen Lin , Zeng Quan , Zhou Jun-Nian , Fu Chun-Jiang , Chen Hai-Xu , Yuan Hong-Feng , Li Zhi-Wei , Shi Lei , Xu Ying-Chen , Wang Jing-Xue , Zhang Xiao-Mei , He Li-Juan , Zhai Chao , Yue Wen , Pei Xue-Tao
Published: January 2013

Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth

in vivo

and promoted tumor sphere formation

in vitro

. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness.

Conclusion:

S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target.