bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice
Authors: Balasubramanyam Ashok , Mersmann Harry , Jahoor Farook , Phillips Terry M. , Sekhar Rajagopal V. , Schubert Ulrich , Brar Baljinder , Iyer Dinakar , Smith E. O'Brian , Takahashi Hideko , Lu Huiyan , Anderson Peter , Kino Tomoshige , Henklein Peter , Kopp Jeffrey B.
Published: August 2006

HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor and peroxisome proliferator-activated receptor-γ and affect mitochondrial function in vitro. To test the hypothesis that expression of Vpr in liver and adipocytes can alter lipid metabolism in vivo, we engineered mice to express Vpr under control of the phospho enolpyruvate carboxykinase promoter in a tissue-specific and inducible manner and investigated the effects of dietary fat, indinavir, and dexamethasone on energy metabolism and body composition. The transgenic mice expressed Vpr mRNA in white and brown adipose tissues and liver and immunoaffinity capillary electrophoresis revealed that they had free Vpr protein in the plasma. Compared with wild-type (WT) animals, Vpr mice had lower plasma triglyceride levels after 6 wk ( P < 0.05) but not after 10 wk of a high-fat diet and lower plasma cholesterol levels after 10 wk of high-fat diet ( P < 0.05). Treatment with dexamethasone obviated group differences, whereas indinavir had no significant independent effect on lipids. In the fasted state, Vpr mice had a higher respiratory quotient than WT mice ( P < 0.05). These data provide the first in vivo evidence that HIV-1 Vpr expressed at low levels in adipose tissues and liver can 1) circulate in the blood, 2) regulate lipid and fatty acid metabolism, and 3) alter fuel selection for oxidation in the fasted state.
NMDA Receptor Subtypes at Autaptic Synapses of Cerebellar Granule Neurons
Authors: Lu Congyi , Fu Zhanyan , Karavanov Irina , Yasuda Robert P. , Wolfe Barry B. , Buonanno Andres , Vicini Stefano
Published: August 2006

We studied the action potential–evoked autaptic N-methyl-d-aspartate receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) using solitary cerebellar neurons cultured in microislands from wild-type (+/+), NR2A subunit knockout (NR2A−/−), and NR2C subunit knockout (NR2C−/−) mice. The peak amplitude of autaptic NMDA-EPSCs increased for all genotypes between days in vitro 8 (DIV8) and DIV13. Compared with +/+ cells at DIV13, NR2A−/− cells had smaller and NR2C−/− cells had larger NMDA-EPSCs. The decay time of these currents were all unexpectedly fast, except in NR2A−/− neurons, and showed small but significant shortening with development. Comparison of quantal parameters during development indicated an increase in quantal content in all genotypes. The synaptic portion of NMDA receptors measured using MK-801 blockade was roughly 50% in all genotypes at DIV8, and this percentage became slightly larger in NR2A−/− and NR2C−/− neurons at DIV12. The NR2B-selective antagonists Conantokin G and CP101,606 differed in their blocking actions with development, suggesting the presence of both heterodimeric NR1/NR2B and heterotrimeric NR1/NR2A/NR2B receptors. The most striking result we obtained was the significant increase of NMDA-EPSC peak amplitude and charge transfer in NR2C−/− mice. This was mainly the result of an increase in quantal size as estimated from miniature NMDA-EPSCs. The expression of NR2C subunit containing receptors was supported by the decreased Mg2+ sensitivity of NMDA receptors at DIV13 in +/+ but not in NR2C−/− cells. Thus solitary cerebellar granule neurons provide a novel model to investigate the role of receptor subtypes in the developmental changes of synaptic NMDA receptors.
Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model
Authors: Salem Mohamed , Kenney P. Brett , Rexroad Caird E. , Yao Jianbo
Published: August 2006

Muscle atrophy is a physiological response to diverse physiological and pathological conditions that trigger muscle deterioration through specific cellular mechanisms. Despite different signals, the biochemical changes in atrophying muscle share many common cascades. Muscle deterioration as a physiological response to the energetic demands of fish vitellogenesis represents a unique model for studying the mechanisms of muscle degradation in non-mammalian animals. A salmonid microarray, containing 16,006 cDNAs, was used to study the transcriptome response to atrophy of fast-switch muscles from gravid rainbow trout compared with sterile fish. Eighty-two unique transcripts were upregulated and 120 transcripts were downregulated in atrophying muscles. Transcripts having gene ontology identifiers were grouped according to their functions. Muscle deterioration was associated with elevated expression of genes involved in the catheptic and collagenase proteolytic pathways; the aerobic production, buffering, and utilization of ATP; and growth arrest; whereas atrophying muscle showed downregulation of genes encoding a serine proteinase inhibitor, enzymes of anaerobic respiration, muscle proteins as well as genes required for RNA and protein biosynthesis/processing. Therefore, gene transcription of the trout muscle atrophy changed in a manner similar to mammalian muscle atrophy. These changes result in an arrest of normal cell growth, protein degradation, and decreased glycolytic cellular respiration that is characteristic of the fast-switch muscle. For the first time, other changes/mechanisms unique to fish were discussed including genes associated with muscle atrophy.
Temporal gene expression profiles of target-ablated olfactory epithelium in mice with disrupted expression of scavenger receptor A: impact on macrophages
Authors: Getchell M. L. , Li H. , Vaishnav R. A. , Borders A. S. , Witta J. , Subhedar N. , de Villiers W. , Stromberg A. J. , Getchell T. V.
Published: August 2006

Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of olfactory sensory neurons (OSNs) and an immune response in which activation and recruitment of macrophages (mφs) into the olfactory epithelium (OE) occupy a central role. Mφs phagocytose apoptotic neurons and secrete cytokines/growth factors that regulate subsequent progenitor cell proliferation and neurogenesis. Scavenger receptor A (SR-A) is a pattern recognition receptor that mediates binding of mφs to apoptotic cells and other relevant immune response functions. The aim of this study was to determine the impact of the absence of SR-A on the immune response to OBX. The immune response to OBX was evaluated in mice in which functional expression of the mφ scavenger receptor (MSR) was eliminated by gene disruption (MSR−/−) and wild-type (wt) mice of the same genetic background. OBX induced significant apoptotic death of mature OSNs in the two strains. However, subsequent mφ infiltration and activation and progenitor cell proliferation were significantly reduced in MSR−/−vs. wt mice. Gene expression profiling at short intervals after OBX demonstrated significant differences in temporal patterns of expression of several gene categories, including immune response genes. Many immune response genes that showed different temporal patterns of expression are related to mφ function, including cytokine and chemokine secretion, phagocytosis, and mφ maturation and activation. These studies suggest that impairment of the immune response to OBX in the OE of MSR−/−mice most likely resulted from decreased mφ adhesion and subsequent reduced infiltration and activation, with a resultant decrease in neurogenesis.
Harmless delays in a discrete ratio‐dependent periodic predator‐prey system
Authors: Fan Yong-Hong , Li Wan-Tong
Published: August 2006

Verifiable criteria are established for the existence of positive periodic solutions and permanence of a delayed discrete periodic predator‐prey model with Holling‐type II functional response N1(k + 1) = N1(k)exp⁡{b1(k) − a1(k)N1(k − [τ1]) − α1(k)N2(k)/(N1(k) + m(k)N2(k))} and N2(k + 1) = N2(k)exp⁡{−b2(k) + α2(k)N1(k − [τ2])/(N1(k − [τ2]) + m(k)N2(k − [τ2]))}. Our results show that the delays in the system are harmless for the existence of positive periodic solutions and permanence of the system. In particular our investigation confirms that if the death rate of the predator is rather small as well as the intrinsic growth rate of the prey is relatively large, then the species could coexist in the long run.
A note on discrete‐time dynamical systems under periodic perturbation
Authors: Li Huimin , Yang Xiaosong
Published: August 2006

We present some results on the existence
and the minimum period of periodic orbits for discrete‐time
dynamical systems under periodic perturbation. Some examples are
presented to illustrate these results.
Modeling of multimass systems torsionally deformed with variable inertia
Authors: Pielorz Amalia , Skóra Monika
Published: August 2006

Dynamic investigations of multimass discrete‐continuous systems
having variable moment of inertia are performed. The systems are
torsionally deformed and consist of an arbitrary number of elastic
elements connected by rigid bodies. The problem is nonlinear and
it is linearized after appropriate transformations. It is shown
that such problems can be investigated using the wave approach.
Some analytical considerations and numerical calculations are done
for a two‐mass system with a special case of boundary conditions.
Perturbation analysis of the effective equation for two coupled periodically driven oscillators
Authors: Okniński Andrzej , Kyzioł Jan
Published: August 2006

Dynamics of two coupled periodically driven oscillators is
analyzed via approximate effective equation of motion. The
internal motion is separated off exactly and then approximate
equation of motion is derived. Perturbation analysis of the
effective equation is used to study the dynamics of the initial
dynamical system.
Comparison of Lesion Detection and Quantification in MAP Reconstruction with Gaussian and Non‐Gaussian Priors
Authors: Qi Jinyi
Published: August 2006

Statistical image reconstruction methods based on maximum a posteriori (MAP) principle have been developed for emission tomography. The prior distribution of the unknown image plays an important role in MAP reconstruction. The most commonly used prior are Gaussian priors, whose logarithm has a quadratic form. Gaussian priors are relatively easy to analyze. It has been shown that the effect of a Gaussian prior can be approximated by linear filtering a maximum likelihood (ML) reconstruction. As a result, sharp edges in reconstructed images are not preserved. To preserve sharp transitions, non‐Gaussian priors have been proposed. However, their effect on clinical tasks is less obvious. In this paper, we compare MAP reconstruction with Gaussian and non‐Gaussian priors for lesion detection and region of interest quantification using computer simulation. We evaluate three representative priors: Gaussian prior, Huber prior, and Geman‐McClure prior. We simulate imaging a prostate tumor using positron emission tomography (PET). The detectability of a known tumor in either a fixed background or a random background is measured using a channelized Hotelling observer. The bias‐variance tradeoff curves are calculated for quantification of the total tumor activity. The results show that for the detection and quantification tasks, the Gaussian prior is as effective as non‐Gaussian priors.
Extra multistep BFGS updates in quasi‐Newton methods
Authors: Moghrabi Issam A. R.
Published: August 2006

This note focuses on developing quasi‐Newton methods
that combine m + 1
multistep and single‐step updates on a
single iteration for the sake of constructing the new
approximation to the Hessian matrix to be used on the next
iteration in computing the search direction. The approach
considered here exploits the merits of the multistep methods and
those of El‐Baali (1999) to create a hybrid technique.
Our numerical results are encouraging and reveal that our proposed
approach is promising. The new methods compete well with
El‐Baali′s extra update algorithms (1999).
Classical 2‐orthogonal polynomials and differential equations
Authors: Ammar Boukhemis , Ebtissem Zerouki
Published: August 2006

We construct the linear differential equations of third order satisfied by the classical 2‐orthogonal polynomials. We show that these differential equations have the following form: , where the
coefficients are polynomials whose degrees are, respectively, less than or equal to 4, 3, 2, and 1. We also show that the coefficient R4,n(x) can be written as R4,n(x) = F1,n(x)S3(x), where S3(x) is a polynomial of degree less than or equal to 3 with coefficients independent of n and deg⁡(F1,n(x)) ≤ 1. We derive these equations in some cases and we also quote some classical 2‐orthogonal polynomials, which were the subject of a deep study.
Oscillation of solutions of impulsive neutral difference equations with continuous variable
Authors: Wei Gengping , Shen Jianhua
Published: August 2006

We obtain sufficient conditions for oscillation of all solutions of the neutral impulsive difference equation with continuous variable Δτ(y(t) + p(t)y(t − mτ)) + Q(t)y(t − lτ) = 0, t ≥ t0 − τ, t ≠ tk, y(tk + τ) − y(tk) = bky(tk), k ∈ ℕ(1), where Δτ denotes the forward difference operator, that is, Δτz(t) = z(t + τ) − z(t), p(t) ∈ C([t0 − τ, ∞), ℝ), Q(t) ∈ C([t0 − τ, ∞), (0, ∞)), m, l are positive integers, τ > 0 and bk are constants, 0 ≤ t0 < t1 < t2 < ⋯
<tk < ⋯ with limk→∞tk = ∞.
On the existence of multiple positive entire solutions for a class of quasilinear elliptic equations
Authors: Zuodong Yang
Published: August 2006

Our goal is to establish the theorems of existence
and multiple of positive entire solutions for a class quasilinear
elliptic equations in ℝN with the
Schauder‐Tychonoff fixed point theorem as the principal tool. In
many articles, the theorems of existence and multiple of
positive entire solutions for a class semilinear elliptic
equations are established. The results of the semilinear
equations are extended to the quasilinear ones and the results of
semilinear equations are developed.
On an inequality of Diananda. Part III
Authors: Gao Peng
Published: August 2006

We extend the results in parts I, II on certain inequalities
involving the generalized power means.
C0‐semigroups of linear operators on some ultrametric Banach spaces
Authors: Diagana Toka
Published: August 2006

C0‐semigroups of linear operators play a crucial role in the solvability of evolution equations in the classical context. This paper is concerned with a brief conceptualization of C0‐semigroups on (ultrametric) free Banach spaces . In contrast with the classical setting, the parameter of a given C0‐semigroup belongs to a clopen ball Ωr of the ground field . As an illustration, we will discuss the solvability of some homogeneous p‐adic differential equations.
On an extension of singular integrals along manifolds of finite type
Authors: Al-Hasan Abdelnaser , Fan Dashan
Published: August 2006

We extend the Lp‐boundedness of a class of singular integral operators
under the H1 kernel condition on a compact manifold from the homogeneous
Sobolev space to the Lebesgue space
Lp(ℝn).
On the biharmonicity of product maps
Authors: Todjihounde Leonard
Published: August 2006

We introduce the warped product of maps defined between Riemannian
warped product spaces and we give necessary and sufficient
conditions for warped product maps to be (bi)harmonic. We obtain
then some characterizations of nontrivial harmonic metrics and
nonharmonic biharmonic metrics on warped product spaces.
Common fixed point theorems in Menger spaces
Authors: Chen Chi-Ming , Chang Tong-Huei
Published: August 2006

We proved two common fixed point theorems for four self‐mappings
and two set‐valued mappings with φ‐contractive condition in a Menger space.
ℂ‐convexity in infinite‐dimensional Banach spaces andapplications to Kergin interpolation
Authors: Filipsson Lars
Published: August 2006

We investigate the concepts of linear convexity and ℂ‐convexity
in complex Banach spaces. The main result is that any
ℂ‐convex domain is necessarily linearly convex. This is a
complex version of the Hahn‐Banach theorem, since it means the
following: given a ℂ‐convex domain Ω
in the Banach space
X
and a point p ∉ Ω, there is a complex hyperplane
through p
that does not intersect Ω. We also prove that
linearly convex domains are holomorphically convex, and that
Kergin interpolation can be performed on holomorphic mappings
defined in ℂ‐convex domains.
Filters of R0‐algebras
Authors: Jun Young Bae , Lianzhen Liu
Published: August 2006

The notion of fated filters in R0‐algebras is introduced.
Characterizations of (fated) filters are given. A filter generated
by a set is established. By introducing the notion of finite
⊙‐property, we show that if F is a nonempty subset of an
R0‐algebra L that has the finite ⊙‐property, then there
exists a maximal filter of L
containing F.
Effects of solar radiation on collagen‐based biomaterials
Authors: Sionkowska Alina , Wisniewski Marcin , Skopinska Joanna , Mantovani Diego
Published: August 2006

The effect of solar radiation on collagen and collagen/synthetic polymer blends in the form of thin films and solutions has been studied by UV‐VIS and FTIR spectroscopies. Films and solutions of collagen blended with poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) were irradiated by solar light. It was found that UV‐VIS spectra, which characterize collagen, collagen/PVA, and collagen/PVP blended films, were significantly altered by solar radiation. FTIR spectra of collagen, collagen/PVA, and collagen/PVP films showed that after solar irradiation, the positions of Amide A bands were shifted to lower wavenumbers. There was not any significant alteration in the position of Amide I and Amide II bands of collagen and its blends after solar radiation. The effect of solar UV radiation in comparison with artificial UV radiation has been discussed.
Intronic MicroRNA (miRNA)
Authors: Lin Shi-Lung , Miller Joseph D. , Ying Shao-Yao
Published: August 2006

Nearly 97% of the human genome is composed of noncoding DNA,
which varies from one species to another. Changes in these
sequences often manifest themselves in clinical and circumstantial
malfunction. Numerous genes in these non‐protein‐coding regions
encode microRNAs, which are responsible for RNA‐mediated
gene silencing through RNA interference (RNAi)‐like pathways.
MicroRNAs (miRNAs), small single‐stranded regulatory RNAs capable
of interfering with intracellular messenger RNAs (mRNAs) with
complete or partial complementarity, are useful for the design of
new therapies against cancer polymorphisms and viral mutations. Currently, many varieties of miRNA are widely reported in plants, animals, and even
microbes. Intron‐derived microRNA (Id‐miRNA) is a new class of
miRNA derived from the processing of gene introns. The intronic
miRNA requires type‐II RNA polymerases (Pol‐II) and spliceosomal
components for their biogenesis. Several kinds of Id‐miRNA have
been identified in C elegans, mouse, and human cells;
however, neither function nor application has been reported. Here,
we show for the first time that intron‐derived miRNAs are able to
induce RNA interference in not only human and mouse cells, but in
also zebrafish, chicken embryos, and adult mice, demonstrating the
evolutionary preservation of intron‐mediated gene silencing via
functional miRNA in cell and in vivo. These findings suggest an
intracellular miRNA‐mediated gene regulatory system, fine‐tuning
the degradation of protein‐coding messenger RNAs.
Essential Notes Regarding the Design of Functional siRNAs for Efficient Mammalian RNAi
Authors: Ui-Tei Kumiko , Naito Yuki , Saigo Kaoru
Published: August 2006

Short interfering RNAs (siRNAs) are widely used to bring about RNA
interference (RNAi) in mammalian cells. Numerous siRNAs may be
designed for any target gene though most of which would be
incapable of efficiently inducing mammalian RNAi. Certain highly
functional siRNAs designed for knockout of a particular gene may
render unrelated endogenous genes nonfunctional. These major
bottlenecks should be properly eliminated when RNAi technologies
are employed for any experiment in mammalian functional genomics.
This paper thus presents essential notes and findings regarding
the proper choice of siRNA‐sequence selection algorithms and
web‐based online software systems.
Fine-Tuning Reception in the Bone: PPARγand Company
Authors: Floyd Z. Elizabeth , Zvonic Sanjin , Nuttall Mark E. , Gimble Jeffrey M.
Published: August 2006

PPARγplays a central role in the formation of fat. Regulation of PPARγactivity depends on numerous factors ranging from dietary ligands to nuclear hormone coactivators and corepressors to oxygen-sensing mechanisms. In addition, the interplay of PPARγwith other nuclear hormone receptors has implications for the balance between adipogenesis and osteogenesis in mesenchymal stem cells of the bone marrow stroma. This review will explore a range of factors influencing PPARγactivity and how these interactions may affect osteogenesis.
Electroporation Therapy in Soft Tissue Sarcoma: A Potentially Effective Novel Treatment
Authors: de Bree Remco , Tijink Bernard M. , van Groeningen Cees J. , Leemans C. René
Published: August 2006

Purpose. Examination of the potential of electroporation therapy (EPT) in a patient with metastatic soft tissue sarcoma. Patient. A 24‐year‐old male who underwent extensive resection and postoperative radiotherapy for a malignant peripheral nerve sheath tumor in the right infratemporal fossa with intracranial extension and invasion of the maxillary sinus and mandible had a recurrence in the scar of his craniotomy for which he was initially treated with doxorubicin. After discontinuation of doxorubicin he developed a metastatic mass at the same site for which he was treated with electroporation therapy. Method. The subcutaneous metastasis was infiltrated with bleomycin and electroporated. Results. Gradually the tumor became increasingly necrotic and demarcated from surrounding tissue. After 10 weeks no tumor was seen anymore. The wound healed secondarily. Discussion. Intralesional bleomycin followed by EPT is potentially effective, well tolerated, and easy to perform in well accessible soft tissue sarcoma sites.
SPARC Represses E-Cadherin and Induces Mesenchymal Transition during Melanoma Development
Authors: Robert Guillaume , Gaggioli Cédric , Bailet Olivier , Chavey Carine , Abbe Patricia , Aberdam Edith , Sabatié Emilie , Cano Amparo , Garcia de Herreros Antonio , Ballotti Robert , Tartare-Deckert Sophie
Published: August 2006

During progression of melanoma, loss of the cell-cell adhesion molecule E-cadherin contributes to uncontrolled growth and invasive behavior of transformed melanocytes. Secreted protein acidic and rich in cysteine (SPARC) is a nonstructural matricellular protein that regulates cell-matrix interactions leading to alterations in cell adhesion and proliferation. Overexpression of SPARC has been associated with progression of various cancers, including melanoma; however, its role in primary tumor development is not well defined. We show that normal human melanocytes overexpressing SPARC adopt a fibroblast-like morphology, concomitant with loss of E-cadherin and P-cadherin expression, and increased expression of mesenchymal markers. Concurrent with these changes, SPARC expression stimulates melanocyte motility and melanoma cell invasion. Expression of SPARC results in transcriptional down-regulation of E-cadherin that correlates with induction of Snail, a repressor of E-cadherin. Conversely, SPARC depletion leads to up-regulation of E-cadherin and reduces Snail levels, and SPARC-null cells exhibit a marked change in their mesenchymal phenotype. Finally, analysis of SPARC, Snail, and E-cadherin levels in melanocytes and malignant melanoma cell lines further supports the functional relationship among these proteins during melanoma progression. Our findings provide evidence for the role of SPARC in early transformation of melanocytes and identify a novel mechanism, whereby tumor-derived SPARC promotes tumorigenesis by mediating Snail induction and E-cadherin suppression. (Cancer Res 2006; 66(15): 7516-23)
In vivoBiological Activity of the Histone Deacetylase Inhibitor LAQ824 Is detectable with 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography
Authors: Leyton Julius , Alao John P. , Da Costa Marco , Stavropoulou Alexandra V. , Latigo John R. , Perumal Meg , Pillai Radhakrishna , He Qimin , Atadja Peter , Lam Eric W.-F. , Workman Paul , Vigushin David M. , Aboagye Eric O.
Published: August 2006

Histone deacetylase inhibitors (HDACI) are emerging as growth inhibitory compounds that modulate gene expression and inhibit tumor cell proliferation. We assessed whether 3′-deoxy-3′-[18F]fluorothymidine–positron emission tomography ([18F]FLT-PET) could be used to noninvasively measure the biological activity of a novel HDACI LAQ824 in vivo. We initially showed that thymidine kinase 1 (TK1; EC2.7.1.21), the enzyme responsible for [18F]FLT retention in cells, was regulated by LAQ824 in a drug concentration–dependent manner in vitro. In HCT116 colon carcinoma xenograft–bearing mice, LAQ824 significantly decreased tumor [18F]FLT uptake in a dose-dependent manner. At day 4 of treatment, [18F]FLT tumor-to-heart ratios at 60 minutes (NUV60) were 2.16 ± 0.15, 1.86 ± 0.13, and 1.45 ± 0.20 in vehicle, and 5 and 25 mg/kg LAQ824 treatment groups, respectively (P ≤ 0.05). LAQ825 at 5 mg/kg also significantly reduced both TK1 levels and [18F]FLT uptake at day 10 but not at day 2 (P ≤ 0.05). [18F]FLT NUV60 correlated significantly with cellular proliferation (r = 0.68; P = 0.0019) and was associated with drug-induced histone H4 hyperacetylation. Of interest to [18F]FLT-PET imaging, both TK1 mRNA copy numbers and protein levels decreased in the order vehicle >5 mg/kg LAQ824 > 25 mg/kg LAQ824, providing a rationale for the use of [18F]FLT-PET in this setting. We also observed increases in Rb hypophosphorylation and p21 levels, factors that could have contributed to the alteration in TK1 transcription in vivo. In conclusion, we have shown the utility of [18F]FLT-PET for monitoring the biological activity of the HDACI, LAQ824. Drug-induced changes in tumor [18F]FLT uptake were due, at least in part, to reductions in TK1 transcription and translation. (Cancer Res 2006; 66(15): 7621-9)
Targeting the Heat Shock Factor 1 by RNA Interference: A Potent Tool to Enhance Hyperthermochemotherapy Efficacy in Cervical Cancer
Authors: Rossi Antonio , Ciafrè Stefania , Balsamo Mirna , Pierimarchi Pasquale , Santoro M. Gabriella
Published: August 2006

Carcinoma of the uterine cervix is one of the highest causes of mortality in female cancer patients worldwide, and improved treatment options for this type of malignancy are highly needed. Local hyperthermia has been successfully used in combination with systemic administration of cisplatin-based chemotherapy in phase I/II clinical studies. Heat-induced expression of cytoprotective and antiapoptotic heat shock proteins (HSP) is a known complication of hyperthermia, resulting in thermotolerance and chemoresistance and hindering the efficacy of the combination therapy. Heat shock transcription factor 1 (HSF1) is the master regulator of heat-induced HSP expression. In the present report, we used small interfering RNA (siRNA) to silence HSF1 and to examine the effect of HSF1 loss of function on the response to hyperthermia and cisplatin-based chemotherapy in HeLa cervical carcinoma. We have identified the 322-nucleotide to 340-nucleotide HSF1 sequence as an ideal target for siRNA-mediated HSF1 silencing, have created a pSUPER-HSF1 vector able to potently suppress the HSF1 gene, and have generated for the first time human cancer cell lines with stable loss of HSF1 function. We report that, although it surprisingly does not affect cancer cell sensitivity to cisplatin or elevated temperatures up to 43°C when administered separately, loss of HSF1 function causes a dramatic increase in sensitivity to hyperthermochemotherapy, leading to massive (>95%) apoptosis of cancer cells. These findings indicate that disruption of HSF1-induced cytoprotection during hyperthermochemotherapy may represent a powerful strategy to selectively amplify the damage in cancer cells and identify HSF1 as a promising therapeutic target in cervical carcinoma. (Cancer Res 2006; 66(15): 7678-85)
Vaccination Strategy Determines the Emergence and Dominance of CD8+ T-Cell Epitopes in a FVB/N Rat HER-2/neuMouse Model of Breast Cancer
Authors: Singh Reshma , Paterson Yvonne
Published: August 2006

The HER-2/neu oncogene has >25 HLA epitopes, yet only one FVB/N mouse CD8+ T-cell epitope has been mapped to date. This epitope has been termed the immunodominant epitope for the FVB/N mouse, but we propose that the vaccination strategy determines the dominance of epitopes. Using a series of overlapping peptides, we have mapped another CD8+ T-cell epitope that emerges in the FVB/N mouse following vaccination with Listeria monocytogenes–based vaccines that express fragments of HER-2/neu. Following the identification of this novel H-2Kq-restricted epitope, we sought to compare the T-cell response to this epitope with the previously identified PDSLRDLSVF epitope. This newly identified epitope and the previously identified epitope lie within fragments contained in different vaccines, the PDSLRDLSVF epitope in Lm-LLO-EC2 and the newly identified PYNYLSTEV epitope in Lm-LLO-EC1; thus, it has been possible to compare the responses of these epitopes independent of any competing response between the epitopes. CTL analysis of individual peptide-pulsed target cells and intracellular cytokine stain for IFN-γ produced by splenocytes from Lm-LLO-EC1 compared with Lm-LLO-EC2 vaccinated FVB/N mice shows that there is no difference between the responses generated to either of these epitopes. We also show that the avidity of the CD8+ T cells for either of these epitopes is similar based on the concentration of peptide necessary to mediate similar levels of lysis of target cells. In addition, HER-2/neu DNA vaccination followed by CTL analysis further showed that both of these peptides can emerge as epitopes. (Cancer Res 2006; 66(15): 7748-57)
Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer
Authors: Walser Tonya C. , Rifat Salah , Ma Xinrong , Kundu Namita , Ward Chris , Goloubeva Olga , Johnson Michael G. , Medina Julio C. , Collins Tassie L. , Fulton Amy M.
Published: August 2006

Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis. (Cancer Res 2006; 66(15): 7701-7)
Notch1-Induced Transformation of RKE-1 Cells Requires Up-regulation of Cyclin D1
Authors: Stahl Mark , Ge Changhui , Shi Shaolin , Pestell Richard G. , Stanley Pamela
Published: August 2006

RKE-1 cells induced to overexpress activated Notch1 (RKE-ER-Nic) exhibit increased cyclin D1 transcripts and become transformed. However, the oncogenic pathway of Notch1-induced transformation is not known. Here, we use mutational analysis to functionally identify the sole region of the cyclin D1 promoter that responds to activated Notch1. The same region responds to activated Notch4 as well as to physiologic Notch ligand-induced Notch receptor signaling. The cyclin D1 gene was subsequently found to be a physiologic target of Notch signaling in Pofut1−/− mouse embryos defective in canonical Notch signaling and in embryos with an inactivating mutation in Notch1. To determine if Notch1-induced cyclin D1 expression in RKE-ER-Nic cells plays a direct role in transformation, cyclin D1 up-regulation was inhibited using a cyclin D1 antisense cDNA. We report here that transformation of RKE-ER-Nic cells is dependent on increased expression of cyclin D1 protein, which represents a new mechanism of Notch1-induced transformation. (Cancer Res 2006; 66(15): 7562-70)
A Cascade of Modules of a Network Defines Cancer Progression
Authors: Thiagalingam Sam
Published: August 2006

Similar histologic subtypes of cancers often exhibit different spectrum of genetic and epigenetic alterations. The heterogeneity observed due to lack of consistent and defined alterations affecting a unique set of gene(s) or gene products in cancers derived from a specific tissue, or an organ, pose a challenge in unraveling the molecular basis of the disease. This dilemma also complicates diagnosis, prognosis, effective management, and treatment modalities. To streamline the available and emerging data into a coherent scheme of events, a multimodular molecular network (MMMN) cancer progression model is presented as a roadmap to dissect the complexity inherent to this disease. The fact that disruption/dysregulation of more than one alternate target gene could affect the functionality of each specific module of a cascade provides a molecular basis for genetic and epigenetic heterogeneity in any given cancer. Polymorphisms/mutations as well as the extracellular matrix and or the epigenetically/genetically conditioned surrounding stromal cells could also influence the rate of tumorigenesis and the properties of the tumor cells. The formulation of MMMN cancer progression models for specific cancers is likely to provide the blueprints for the markers and targets to aid diagnosis, prevention, and therapy of this deadly disease. (Cancer Res 2006; 66(15): 7379-85)
Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer
Authors: Wang Zhiwei , Sengupta Radha , Banerjee Sanjeev , Li Yiwei , Zhang Yuxiang , Rahman K.M. Wahidur , Aboukameel Amro , Mohammad Ramzi , Majumdar Adhip P.N. , Abbruzzese James L. , Sarkar Fazlul H.
Published: August 2006

The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy. EGFR-related protein (ERRP), a recently identified pan-erbB inhibitor, has been shown to inhibit growth and induce apoptosis of pancreatic cancer cells in vitro and tumor growth in a xenograft model. However, the precise molecular mechanism(s) by which ERRP exerts its antitumor activity remains unclear. The current investigation was undertaken to delineate the tumor growth inhibitory mechanism(s) of ERRP in pancreatic cancer cells. Using multiple molecular assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis, gene transfection, real-time reverse transcription-PCR, Western blotting, invasion, and electrophoretic mobility shift assay for measuring DNA-binding activity of nuclear factor-κB (NF-κB), we found that ERRP caused marked inhibition of pancreatic cancer cell growth. This was accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF-κB and down-regulation of NF-κB downstream genes, such as matrix metalloproteinase-9 and vascular endothelial growth factor, resulting in the inhibition of pancreatic cancer cell invasion through the Matrigel. We also found that down-regulation of Notch-1 by small interfering RNA before ERRP treatment resulted in enhanced cell growth inhibition and apoptosis. Our data suggest that the ERRP-mediated inactivation of EGFR, Notch-1, NF-κB, and its downstream target genes contributed to the inhibition of cell growth and invasion. We conclude that ERRP could be an effective agent for inhibiting tumor growth and invasion for the treatment of pancreatic cancer. (Cancer Res 2006; 66(15): 7653-60)
No Observable Relationship between the ACE Gene Insertion/Deletion Polymorphism and Psychometric IQ and Psychomotor Ability in Chinese Children
Authors: Gao Jianjun , Gao Xiaocai , Qin Wei , Dang Fangli , Zhang Fuchang , Qian Xueqing , Zeng Xiaoyang , Xing Qinghe , Zheng Zijian , Li Jun , Guo Tingwei , Chang Hongfen , Feng Guoyin , He Lin
Published: August 2006

The primary aim of this study was to investigate the impact of the angiotensin I-converting enzyme gene (ACE) on general cognitive ability, specific cognitive ability and psychomotor function in Chinese children. In total, 450 children completed both C-WISC tests and ACE I/D genotyping. Of these, 320 children were examined using psychomotor tests. The quantitative traits of psychometric IQ and psychomotor abilities were calculated to determine whether there were any significant differences related to their ACE genotypes on the basis of an analysis of variance. F test results showed no significant differences with regard to any aspect of intelligence or psychomotor performance relative to the various ACE I/D genotypes (all p > 0.05). Our study suggests that ACE I/D do not have a measurable impact on any aspects of IQ or psychomotor ability and that psychomotor ability correlates well with IQ in Chinese children.
Personality, Dopamine Receptor D4 Exon III Polymorphisms, and Academic Achievement in Medical Students
Authors: Ham Byung-Joo , Lee Young-Mee , Kim Meyoung-Kon , Lee Juneyoung , Ahn Duck-Sun , Choi Myoung-Jin , Lyoo In Kyoon , Choi Ihn-Geun , Lee Min-Soo
Published: August 2006

This study investigated the relationships between genetic polymorphisms, personality traits, and academic achievement in medical school students. Study subjects were 220 1st-year medical students at Korea University Medical School during two consecutive academic years (2003–2004). Grade-point averages (GPA) during the second semester of the 1st year of the medical school were obtained as a measure of academic achievement. In addition, all participants completed the Temperament and Character Inventory and questionnaires on depression and anxiety. The polymorphisms in exon III of the dopamine D4 receptor (DRD4) were determined using the polymerase chain reaction. Our results revealed that both male and female subjects with a higher GPA may be characterized as having higher persistence and lower novelty seeking traits. In addition, male subjects with high GPA had higher scores in self directedness and female subjects with a higher GPA may be characterized as having higher scores in harm avoidance. Male students with 4-repeat alleles had a significantly lower GPA than male students without 4-repeat alleles.This relationship also remained after controlling for the personality variables, none of which showed a relationship with the polymorphism after Bonferroni correction. For females, however, no associations could be found between GPA and the polymorphism. Thus, the present study demonstrated for the first time a possible influence of the DRD4 48 bp variable number of tandem repeats polymorphism on academic achievement and proved that this was not mediated by performance-associated personality traits.
Are Public Subsidies to Higher Education Regressive?
Authors: Johnson William R.
Published: August 2006

This article estimates the dollar amount of public higher education subsidies received by U.S. youth and examines the distribution of subsidies and the taxes that finance them across parental and student income levels. Although youths from high-income families obtain more benefit from higher education subsidies, highincome households pay sufficiently more in taxes that the net effect of the spending and associated taxation is distributionally neutral or mildly progressive. These results are robust to alternative assumptions and are consistent with Hansen and Weisbrod's earlier celebrated findings for California, although not with the conclusions often drawn from those findings.
National Board Teachers Are More Effective, But Are They in the Classrooms Where They're Needed the Most?
Authors: Goldhaber Dan
Published: August 2006

This brief summarizes findings from several research articles that focus on the National Board for Professional Teaching Standards (NBPTS). This work focuses on three key questions: Who applies for and becomes National Board certified? Where do National Board Certified Teachers (NBCTs) teach? Are they more effective than other teachers? The findings suggest that: (1) teachers are less likely to become certified if teaching disadvantaged students; (2) NBCTs are more effective than noncertified NBPTS-applicants and nonapplicants; and (3) the mobility patterns of NBCTs decrease the chances that low-performing students will be taught by a teacher with this credential.
Ekphrasis, Lorenzo Lotto's Annunciation, and the Hermeneutics of Suspicion
Authors: Padgett Jacqueline Olson
Published: August 2006

Lorenzo Lotto's Recanati Annunciation develops the second of the traditional pericopes in St. Luke's narrative of the Annunciation, presenting to the spectator the Virgin's startled reaction to the arrival of the angel Gabriel and suggesting that we might employ a hermeneutics of suspicion in reading the Gospel text. Recent literary responses to Lotto's painting and to the Lukan text engage in a similar hermeneutics to offer an understanding of personal and cultural responses to the Annunciation narrative and to present at times a counter-narrative.
On a Mysterious Term in the Āzarī Verses of Maghrebi Tebrizi
Authors: Ale-Osfur Seyyed Mohammad
Published: August 2006

The article is an attempt to interpret a mystical term, n'd (nād), in the writings of the 14th century Āzarī poet Shams ad-din Muhammad Maghrebi Tabrizi.
Abkhaz Loans in Megrelian
Authors: Chirikba Vyacheslav
Published: August 2006

The paper presents a thorough investigation of the Abkhaz borrowings in Megrelian, including structural loans, grammatical elements, adjectives, adverbs, numerals, and appellativa (anatomical and medical terms, household items, terms related to husbandry and pasture, floristic and zoological names, religious terms, landscape, food, etc.). The author examines also the cases of the Abkhaz influence on Megrelian onomasticon.
Estimating Soil Wetness from the GOES Sounder
Authors: Rabin Robert M. , Schmit Timothy J.
Published: August 2006

In this note, the relationship between the observed daytime rise in surface radiative temperature, derived from the Geostationary Operational Environmental Satellites (GOES) sounder clear-sky data, and modeled soil moisture is explored over the continental United States. The motivation is to provide an infrared (IR) satellite–based index for soil moisture, which has a higher resolution than possible with the microwave satellite data. The daytime temperature rise is negatively correlated with soil moisture in most areas. Anomalies in soil moisture and daytime temperature rise are also negatively correlated on monthly time scales. However, a number of exceptions to this correlation exist, particularly in the western states. In addition to soil moisture, the capacity of vegetation to generate evapotranspiration influences the amount of daytime temperature rise as sensed by the satellite. In general, regions of fair to poor vegetation health correspond to the relatively high temperature rise from the satellite. Regions of favorable vegetation match locations of lower-than-average temperature rise.
A Quality Control Concept for Radar Reflectivity, Polarimetric Parameters, and Doppler Velocity
Authors: Friedrich Katja , Hagen Martin , Einfalt Thomas
Published: August 2006

Over the last few years the use of weather radar data has become a fundamental part of various applications like rain-rate estimation, nowcasting of severe weather events, and assimilation into numerical weather prediction models. The increasing demand for radar data necessitates an automated, flexible, and modular quality control. In this paper a quality control procedure is developed for radar reflectivity factors, polarimetric parameters, and Doppler velocity. It consists of several modules that can be extended, modified, and omitted depending on the user requirement, weather situation, and radar characteristics. Data quality is quantified on a pixel-by-pixel basis and encoded into a quality-index field that can be easily interpreted by a nontrained end user or an automated scheme that generates radar products. The quality-index algorithms detect and quantify the influence of beam broadening, the height of the first radar echo, ground clutter contamination, return from non-weather-related objects, and attenuation of electromagnetic energy by hydrometeors on the quality of the radar measurement. The quality-index field is transferred together with the radar data to the end user who chooses the amount of data and the level of quality used for further processing. The calculation of quality-index fields is based on data measured by the polarimetric C-band Doppler radar (POLDIRAD) located in the Alpine foreland in southern Germany.
Robust Confidence Interval for a Ratio of Standard Deviations
Authors: Bonett Douglas G.
Published: August 2006

Comparing variability of test scores across alternate forms, test conditions, or subpopulations is a fundamental problem in psychometrics. A confidence interval for a ratio of standard deviations is proposed that performs as well as the classic method with normal distributions and performs dramatically better with nonnormal distributions. A simple and accurate sample size planning formula is proposed for estimating a ratio of standard deviations with desired confidence and precision.
Item Diffficulty Modeling of Paragraph Comprehension Items
Authors: Gorin Joanna S. , Embretson Susan E.
Published: August 2006

Recent assessment research joining cognitive psychology and psychometric theory has introduced a new technology, item generation. In algorithmic item generation, items are systematically created based on specific combinations of features that underlie the processing required to correctly solve a problem. Reading comprehension items have been more difficult to model than other item types due to the complexities of quantifying text. However, recent developments in artificial intelligence for text analysis permit quantitative indices to represent cognitive sources of difficulty. The current study attempts to identify generative components for the Graduate Record Examination paragraph comprehension items through the cognitive decomposition of item difficulty. Text comprehension and decision processes accounted for a significant amount of the variance in item difficulties. The decision model variables contributed significantly to variance in item difficulties, whereas the text representation variables did not. Implications for score interpretation and future possibilities for item generation are discussed. Index terms: difficulty modeling, construct validity, comprehension tests, item generation