bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial Na+ sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei
Authors: Teruyama Ryoichi , Sakuraba Mayumi , Wilson Lori L. , Wandrey Narine E. J. , Armstrong William E.
Published: November 2011

The epithelial Na+ channels (ENaCs) are present in kidney and contribute to Na+ and water homeostasis. All three ENaC subunits (α, β, and γ) were demonstrated in the cardiovascular regulatory centers of the rat brain, including the magnocellular neurons (MNCs) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). However, the functional significance of ENaCs in vasopressin (VP) and oxytocin (OT) synthesizing MNCs is completely unknown. In this study, we show with immunocytochemical double-labeling that the α-ENaC is colocalized with either VP or OT in MNCs in the SON and PVN. In addition, parvocellular neurons in the dorsal, ventrolateral, and posterior subregions of the PVN (not immunoreactive to VP or OT) are also immunoreactive for α-ENaC. In contrast, immunoreactivity to β- and γ-ENaC is colocalized with VP alone within the MNCs. Furthermore, immunoreactivity for a known target for ENaC expression, the mineralcorticoid receptor (MR), is colocalized with both VP and OT in MNCs. Using single-cell RT-PCR, we detected mRNA for all three ENaC subunits and MR in cDNA libraries derived from single MNCs. In whole cell voltage clamp recordings, application of the ENaC blocker benzamil reversibly reduced a steady-state inward current and decreased cell membrane conductance approximately twofold. Finally, benzamil caused membrane hyperpolarization in a majority of VP and about one-half of OT neurons in both spontaneously firing and quiet cells. These results strongly suggest the presence of functional ENaCs that may affect the firing patterns of MNCs, which ultimately control the secretion of VP and OT.
Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women
Authors: González Frank , Nair K. Sreekumaran , Daniels Janice K. , Basal Eati , Schimke Jill M.
Published: November 2011

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo ( n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-κB, p65 and p105 NF-κB subunit RNA, TNFα and IL-1β mRNA, and NF-κB p65 and inhibitory-κB (IκB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-κB, p65, p105, TNFα, and IL-1β RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IκB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-κB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population.
The Influences of Thickness on the Optical and Electrical Properties of Dual-Ion-Beam Sputtering-Deposited Molybdenum-Doped Zinc Oxide Layer
Authors: Kuo Chin-Chiuan , Liu Chi-Chang , He Shao-Chih , Chang Jing-Tang , He Ju-Liang
Published: November 2011

The thickness of transparent conductive oxide (TCO) layer significantly affects not only the optical and electrical properties, but also its mechanical durability. To evaluate these influences on the molybdenum-doped zinc oxide layer deposited on a flexible polyethersulfone (PES) substrate by using a dual-ion-beam sputtering system, films with various thicknesses were prepared at a same condition and their optical and electrical performances have been compared. The results show that all the deposited films present a crystalline wurtzite structure, but the preferred orientation changes from (002) to (100) with increasing the film thickness. Thicker layer contains a relative higher carrier concentration, but the consequently accumulated higher internal stress might crack the film and retard the carrier mobility. The competition of these two opposite trends for carrier concentration and carrier mobility results in that the electrical resistivity of molybdenum-doped zinc oxide first decreases with the thickness but suddenly rises when a critical thickness is reached.
Responses of Airway Epithelium to Environmental Injury: Role in the Induction Phase of Childhood Asthma
Authors: Kumar Rakesh K. , Siegle Jessica S. , Kaiko Gerard E. , Herbert Cristan , Mattes Joerg E. , Foster Paul S.
Published: November 2011

The pathogenesis of allergic asthma in childhood remains poorly understood. Environmental factors which appear to contribute to allergic sensitisation, with development of a Th2-biased immunological response in genetically predisposed individuals, include wheezing lower respiratory viral infections in early life and exposure to airborne environmental pollutants. These may activate pattern recognition receptors and/or cause oxidant injury to airway epithelial cells (AECs). In turn, this may promote Th2 polarisation via a “final common pathway” involving interaction between AEC, dendritic cells, and CD4+ T lymphocytes. Potentially important cytokines produced by AEC include thymic stromal lymphopoietin and interleukin-25. Their role is supported by in vitro studies using human AEC, as well as by experiments in animal models. To date, however, few investigations have employed models of the induction phase of childhood asthma. Further research may help to identify interventions that could reduce the risk of allergic asthma.
The Synthesis of Highly Aligned Cupric Oxide Nanowires by Heating Copper Foil
Authors: Liang Jianbo , Kishi Naoki , Soga Tetsuo , Jimbo Takashi
Published: November 2011

We have investigated the effects of grain size and orientation of copper substrates for the growth of cupric oxide nanowires by thermal oxidation method. Long, less-roughness, high-density, and aligned cupric oxide nanowires have been synthesized by heating (200) oriented copper foils with small grain size in air gas. Long and aligned nanowires of diameter around 80 nm can only be formed within a short temperature range from 400 to 700°C. On the other hand, uniform, smooth-surface, and aligned nanowires were not formed in the case of larger crystallite size of copper foils with (111) and (200) orientation. Smaller grain size of copper foil with (200) orientation is favorable for the growth of highly aligned, smooth surface, and larger-diameter nanowires by thermal oxidation method.
The Sheared Central Venous Catheter?
Authors: Hegde Harihar V. , Yaliwal Vijay G. , Joshi Shyamsundar K. , Rao P. Raghavendra
Published: November 2011

A fractured central venous catheter (CVC) with embolization of the distal fragment may lead to life-threatening complications. We had inserted a right subclavian CVC in a 68-year-old female which upon a follow-up chest X-ray appeared to have been sheared. A guidewire was inserted through the CVC until the J-tip was just beyond the tip of the CVC which were then withdrawn as a single assembly. We suspected that the tip of the guidewire might have been entrapped in the opening of the middle port, which upon withdrawal of the guidewire could have led to CVC folding upon itself and shearing.
Scattering of a Plane Wave by an Anisotropic Plasma-Coated Conducting Sphere
Authors: Geng You-Lin
Published: November 2011

The electromagnetic field in homogeneous plasma anisotropic medium can be expressed as the addition of the first and second spherical vector wave functions in plasma anisotropic medium. The tangential electromagnetic fields are continued in the boundary between the homogeneous plasma anisotropic medium and free space, and the tangential electrical field is zero in the surface of conducting sphere. The coefficients of electromagnetic fields in plasma anisotropic medium expanded in terms of spherical vector wave functions in plasma anisotropic medium are derived, and then the coefficients of scattering fields in terms of spherical vector functions in free space can be obtained. Numerical results between this paper and hybrid finite element-boundary integral-multilevel fast multipole algorithm (FE-BI-MLFMA) are given, and they are in agreement very well. Some new numerical results of a plane wave scattering by an anisotropic plasma-coated conducting sphere are obtained.
Generalized Projective Synchronization for Different Hyperchaotic Dynamical Systems
Authors: El-Dessoky M. M. , Saleh E.
Published: November 2011

Projective synchronization and generalized projective synchronization have recently been observed in the coupled hyperchaotic systems. In this paper a generalized projective synchronization technique is applied in the hyperchaotic Lorenz system and the hyperchaotic Lü. The sufficient conditions for achieving projective synchronization of two different hyperchaotic systems are derived. Numerical simulations are used to verify the effectiveness of the proposed synchronization techniques.
The Noise Performance of a Multiple-Input-Port and Multiple-Output-Port Low-Noise Amplifier Connected to an Array of Coupled Antennas
Authors: Broydé Frédéric , Clavelier Evelyne
Published: November 2011

We address the noise characterization of a multiple-input-port and multiple-output-port (MIPMOP) device receiving signals from an array of antennas. A definition of the noise figures and natural noise figures of a MIPMOP device is provided, and the resulting properties are detailed in the impedance and admittance representations. We compute the natural noise figures of a low-noise MIPMOP amplifier comprising a MIMO series-series feedback amplifier (MIMO-SSFA), designed for a wireless receiver front-end.
Aqueous Synthesis and Characterization of CdSe/ZnO Core-Shell Nanoparticles
Authors: Rakgalakane B. P. , Moloto M. J.
Published: November 2011

Core-shell nanomaterials based on CdSe as the core and ZnO as the shell were prepared using an aqueous route involving the use of Cd salt and NaBH4in reaction with Se to generate CdSe in the presence of thioglycerol (TG) as a stabilizer. ZnO has been prepared at pH 12 using stronger base such as NaOH at lower concentration and by varying amounts of Zn2+ions ranging from 2.5, 5, 25 mL, and 50 mL to prepare core-shell nanomaterials. The absorption and emission spectral features are dominated by CdSe nanoparticles with typical shift in the emission maxima red-shifted in relation to the band edges. There is an observable change in the band edge from the core as the amount of ZnO is increased. The TEM features showed the formation of the core-shell from the volume of 5 mL which is indicated by the thin layer of shell on the surface of the CdSe core.
Stability of Optimal Controls for the Stationary Boussinesq Equations
Authors: Alekseev Gennady , Tereshko Dmitry
Published: November 2011

The stationary Boussinesq equations describing the heat transfer in the viscous heat‐conducting fluid under inhomogeneous Dirichlet boundary conditions for velocity and mixed boundary
conditions for temperature are considered. The optimal control problems for these equations
with tracking‐type functionals are formulated. A local stability of the concrete control problem
solutions with respect to some disturbances of both cost functionals and state equation is proved.
Regulation of Suppressors of Cytokine Signaling as a Therapeutic Approach in Autoimmune Diseases, with an Emphasis on Multiple Sclerosis
Authors: Ramgolam Vinod S. , Markovic-Plese Silva
Published: November 2011

Multiple sclerosis (MS) is an inflammatory demyelinating, presumably autoimmune disease of the central nervous system (CNS). Among the available MS therapies, interferon (IFN)βand the recently introduced statins have been reported to exert their immunomodulatory effects through the induction of SOCS1 and SOCS3 in various inflammatory cell subsets. The SOCS proteins negatively regulate cytokine and Toll-like receptors- (TLR-) induced signaling in the inflammatory cells. SOCS1 and SOCS3 have been reported to play an important role in the regulation of Th17-cell differentiation through their effects on the cells of the innate and adaptive immune systems. IFNβand statins inhibit Th17-cell differentiationdirectlyandindirectlyvia induction of SOCS1 and SOCS3 expression in monocytes, dendritic cells (DCs), and B-cells. Due to their rapid induction and degradation, and SOCS-mediated regulation of multiple cytokine-signaling pathways, they represent an attractive therapeutic target in the autoimmune diseases, and particularly relapsing remitting (RR) MS.
Role of Nasal Endoscopy in Chronic Osteomyelitis of Maxilla and Zygoma: A Case Report
Authors: Arunkumar J. S. , Naik Ashok S. , Prasad K. C. , Santhosh S. G.
Published: November 2011

Osteomyelitis of the jaws was relatively common before the era of antibiotic therapy and preventive and restorative dentistry. Osteomyelitis is an acute or chronic inflammatory process that can involve cortical and trabecular aspects of bone or bone marrow. Cranial bones are infrequently involved, but spreading of inflammation with involvement of surrounding structures represents important risk, such as cerebral abscess, encephalitis, or meningitis. The mandible is more commonly involved than the maxilla. Dentogenic infections cause 38% of mandibular and 25% of maxillary involvement. Involvement of zygoma is very rare. Factors like viral fevers, malnutrition, malaria, anemia,tobacco chewing, immunodeficiency, osteopetrosis, Paget’s disease of bone, and florid cemento-osseous dysplasia (FCOD) result in decreased vascularity of the affected bone, predisposing to the development of osteomyelitis. We present a case of osteomyelitis of left maxilla and zygoma with oroantral fistula in an immunocompetent adult male caused by dentogenic infection. The complete resolution of infection was gained with surgical treatment using nasal endoscope and antibiotic therapy. The aims of this paper are to illustrate diagnostic patterns, to report radiographic findings and surgical treatment using nasal endoscope in a case of osteomyelitis of maxilla and zygoma. The prognosis and cosmetic results are discussed.
Potential for Modulation of the Fas Apoptotic Pathway by Epidermal Growth Factor in Sarcomas
Authors: Joyner David E. , Jones Kevin B. , Lessnick Stephen L. , Schiffman Joshua D. , Randall R. Lor
Published: November 2011

One important mechanism by which cancer cells parasitize their host is by escaping apoptosis. Thus, selectively facilitating apoptosis is a therapeutic mechanism by which oncotherapy may prove highly advantageous. One major apoptotic pathway is mediated by Fas ligand (FasL). The death-inducing signaling Ccmplex (DISC) and subsequent death-domain aggregations are created when FasL is bound by its receptor thereby enabling programmed cell death. Conceptually, if a better understanding of the Fas pathway can be garnered, an oncoselective prodeath therapeutic approach can be tailored. Herein, we propose that EGF and CTGF play essential roles in the regulation of the Fas apoptotic pathway in sarcomas. Tumor andin vitrodata suggest viable cells counter the prodeath signal induced by FasL by activating EGF, which in turn induces prosurvival CTGF. The prosurvival attributes of CTGF ultimately predominate over the death-inducing FasL. Cells destined for elimination inhibit this prosurvival response via a presently undefined pathway. This scenario represents a novel role for EGF and CTGF as regulators of the Fas pathway in sarcomas.
Characterization of Periodic, Quasiperiodic, and Chaotic States in Nonpremixed Biodiesel/Air Jet Flames
Authors: Xu Jianxin , Wang Hua , Fang Hui
Published: November 2011

Characterization for nonpremixed biodiesel/air jet flames instability is investigated by the 0‐1 test for chaos and recurrence plots. Test conditions involve biodiesel from Jatropha curcas. L‐fueled flames have inlet oil pressure of 0.2–0.6 MPa, fuel flow rates (Q1) of 15–30 kg/h, and combustion air flow rate (Q2) of 150–750 m3/h. This method is based on image analysis and nonlinear dynamics. Structures of flame are analyzed using an image analysis technique to extract position series which are representative of the relative change in temperature of combustion chamber. Compared with the method of maximum Lyapunov exponent, the 0‐1
test succeeds in detecting the presence of regular and chaotic components in flame position series. Periodic
and quasiperiodic characteristics are obtained by the Poincaré sections. A common characteristic of regular
nonpremixed flame tip position series is detected by recurrence plots. Experimental results show that these
flame oscillations follow a route to chaos via periodic and quasiperiodic states.
VLSI Implementation of a Distributed Algorithm for Fault-Tolerant Clock Generation
Authors: Fuchs Gottfried , Steininger Andreas
Published: November 2011

We present a novel approach for the on-chip generation of a fault-tolerant clock. Our method is based on the hardware implementation of a tick synchronization algorithm from the distributed systems community. We discuss the selection of an appropriate algorithm, present the refinement steps necessary to facilitate its efficient mapping to hardware, and elaborate on the key challenges we had to overcome in our actual ASIC implementation. Our measurement results confirm that the approach is indeed capable of creating a globally synchronized clock in a distributed fashion that is tolerant to a (configurable) number of arbitrary faults. This property facilitates eliminating the clock as a single point of failure. Our solution is based on purely asynchronous design, obviating the need for crystal oscillators. It is capable of adapting to parameter variations as well as changes in temperature and power supply–properties that are considered highly desirable for future technology nodes.
Robust Interval-Based Localization Algorithms for Mobile Sensor Networks
Authors: Mourad Farah , Snoussi Hichem , Kieffer Michel , Richard Cédric
Published: November 2011

This paper considers the localization problem in mobile sensor networks. Such a problem is a challenging task, especially when measurements exchanged between sensors may contain outliers, that is, data not matching the observation model. This paper proposes two algorithms robust to outliers. These algorithms perform a set-membership estimation, where only the maximal number of outliers is required to be known. Using these algorithms, estimates consist of sets of boxes whose union surely contains the correct location of the sensor, provided that the considered hypotheses are satisfied. This paper proposes as well a technique for evaluating the number of outliers to be robust to. In order to corroborate the efficiency of both algorithms, a comparison of their performances is performed in simulations using Matlab.
Invasive Mold Infections: Virulence and Pathogenesis ofMucorales
Authors: Morace Giulia , Borghi Elisa
Published: November 2011

Mucoraleshave been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the orderMucoralesare responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to theMucoraceaefamily.Mucoralesare able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses.
Core‐Shell Structure of a Silicon Nanorod/Carbon Nanotube Field Emission Cathode
Authors: Huang Bohr-Ran , Yang Ying-Kan , Lin Tzu-Ching , Yang Wen-Luh
Published: November 2011

A novel core‐shell structure of silicon nanorods/carbon nanotubes (SiNRs/CNTs) is developed for use in field emission cathodes. The CNTs were synthesized on SiNRs, using the Ag‐assisted electroless etching technique to form the SiNRs/CNT core‐shell structure. This resulting SiNRs/CNT field emission cathode demonstrated improved field emission properties including a lower turn‐on electric field Eon (1.3 V/μm, 1 μA/cm2), a lower threshold electric field Eth (1.8 V/μm, 1 mA/cm2), and a higher enhancement factor β (2347). These superior properties indicate that this core‐shell structure of SiNRs/CNTs has good potential in field emission cathode applications.
UPR-Mediated Membrane Biogenesis in B Cells
Authors: Brewer Joseph W. , Jackowski Suzanne
Published: November 2011

The unfolded protein response (UPR) can coordinate the regulation of gene transcription and protein translation to balance the load of client proteins with the protein folding and degradative capacities of the ER. Increasing evidence also implicates the UPR in the regulation of lipid synthesis and membrane biogenesis. The differentiation of B lymphocytes into antibody-secreting cells is marked by significant expansion of the ER, the site for antibody synthesis and assembly. In activated B cells, the demand for membrane protein and lipid components leads to activation of the UPR transcriptional activator XBP1(S) which, in turn, initiates a cascade of biochemical events that enhance supplies of phospholipid precursors and build machinery for the synthesis, maturation, and transport of secretory proteins. The alterations in lipid metabolism that occur during this developmental transition and the impact of membrane phospholipid restriction on B cell secretory characteristics are discussed in this paper.
Epitaxial Growth of Germanium on Silicon for Light Emitters
Authors: Chen Chengzhao , Li Cheng , Huang Shihao , Zheng Yuanyu , Lai Hongkai , Chen Songyan
Published: November 2011

This paper describes the role of Ge as an enabler for light emitters on a Si platform. In spite of the large lattice mismatch of ~4.2% between Ge and Si, high-quality Ge layers can be epitaxially grown on Si by ultrahigh-vacuum chemical vapor deposition. Applications of the Ge layers to near-infrared light emitters with various structures are reviewed, including the tensile-strained Ge epilayer, the Ge epilayer with a delta-doping SiGe layer, and the Ge/SiGe multiple quantum wells on Si. The fundamentals of photoluminescence physics in the different Ge structures are discussed briefly.
Cardiac Autonomic Imbalance in Newly Diagnosed and Established Diabetes Is Associated with Markers of Adipose Tissue Inflammation
Authors: Lieb David C. , Parson Henri K. , Mamikunian Gregg , Vinik Aaron I.
Published: November 2011

Introduction. Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes.Materials and Methods. Non-diabetics, newly diagnosed diabetics, and established diabetics were included. Anthropomorphic and biochemical measurements were obtained, and insulin resistance was approximated. Cardiac autonomic function was assessed using conventional measures and with power spectral analysis of heart rate.Results and Discussion. Heart rate variability was reduced in all diabetics. Interleukin-6 was higher in diabetics, as was the high molecular weight adiponectin-to-leptin ratio. Interleukin-6 correlated negatively with measures of autonomic balance. Ratios of adiponectin to leptin correlated positively with measures of autonomic balance. Cardiac autonomic imbalance and inflammation occur early in diabetes and are interrelated.Conclusions. Cardiac autonomic imbalance correlates with the adipose tissue-derived inflammation seen early in type 2 diabetes.
Vasoprotection by Dietary Supplements and Exercise: Role of TNFαSignaling
Authors: Zhang Hanrui , Zhang Cuihua
Published: November 2011

Vascular dysfunction contributes to the pathogenesis of various cardiovascular diseases. Dietary supplements, including fish oil, dietary fibers, and various natural products, and exercise training exert vasoprotective effects. However, the mechanisms underlying the vasoprotective benefits of dietary supplements and physical activity demand extensive investigation. Accumulating evidence suggests that inflammatory cytokine tumor necrosis factor-alpha (TNFα) plays a pivotal role in the dysregulation of macrovascular and microvascular function. TNFαinduces vascular inflammation, monocyte adhesion to endothelial cells, vascular oxidative stress, apoptosis, and atherogenic response and participates in the regulation of thrombosis and coagulation through multiple signaling pathways involving NFκB, Sp1, activator protein 1, JNK, p38, STAT3, and so forth. Dietary supplements and exercise training decrease TNFαproduction and ameliorate TNFα-mediated pathological changes in vasculature. Thus, the inhibitory effects of dietary supplements and physical exercise on TNFαproduction and TNFαsignaling may contribute to their vasoprotective properties.
MicroRNA-494 Downregulates KIT and Inhibits Gastrointestinal Stromal Tumor Cell Proliferation
Authors: Kim Won Kyu , Park Misun , Kim Young-Kook , Tae You Kwon , Yang Han-Kwang , Lee Jae Myun , Kim Hoguen
Published: November 2011

Purpose: Gain-of-function mutations and KIT overexpression are well-known tumorigenesis mechanisms in gastrointestinal stromal tumors (GIST). This study aimed to discover microRNAs (miRNA) that target KIT and reveal the relationship between the discovered miRNAs and KIT expression in GISTs.

Experimental Design: Fresh-frozen GISTs from 31 patients were used to confirm the relationship between miR-494 and KIT expression using quantitative reverse transcription-PCR to assess miR-494 expression levels and Western blotting to assess KIT protein expression levels. A luciferase assay was conducted for the target evaluation. The functional effects of miR-494 on GIST882 cells (GIST cell line with activating KIT mutation) were validated by a cell proliferation assay and fluoresce-activated cell sorting analysis.

Results: An inverse relationship was found between the expression levels of miR-494 and KIT in GISTs (r = −0.490, P = 0.005). The direct targeting of KIT by miR-494 was shown by the reduction in KIT expression after miR-494 overexpression and the increase in KIT expression after inhibiting endogenous miR-494 expression. We showed that miR-494 regulates KIT by binding two different seed match sites. Induced miR-494 overexpression in GIST882 reduced the expression of downstream molecules in KIT signaling transduction pathways, including phospho-AKT and phospho-STAT3. Finally, miR-494 overexpression provoked apoptosis and inhibited GIST cell growth, which were accompanied by changes in G1 and S phase content.

Conclusion: Our findings indicate that miR-494 is a negative regulator of KIT in GISTs and overexpressing miR-494 in GISTs may be a promising approach to GIST treatment. Clin Cancer Res; 17(24); 7584–94. ©2011 AACR.
Integrating Pain Metrics into Oncology Clinical Trials
Authors: Cleeland Charles S. , O'Mara Ann , Zagari Martin , Baas Carole
Published: November 2011

Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. Clin Cancer Res; 17(21); 6646–50. ©2011 AACR.
Aortopulmonary Window with Atrial Septal Defect: Prenatal Diagnosis, Management and Outcome
Authors: Alvarez Rosa , García-Díaz Lutgardo , Coserria Félix , Hosseinpour Reza , Antiñolo Guillermo
Published: November 2011

A case of prenatally diagnosed aortopulmonary window is reported. The mother was referred for fetal echocardiography at 26 weeks’ gestation because of suspected congenital heart disease. Prenatal echocardiography showed an aortopulmonary septum defect close to the pulmonary artery bifurcation and a left-to-right shunt flow in systole and early diastole detected by color flow Doppler. Postnatal echocardiography confirmed prenatal diagnosis, the aortopulmonary window was a 9-mm type III aortopulmonary window. An atrial septal defect with shunt flow left to right was also found. Surgical repair was performed 4 weeks after birth, the postsurgical period was uneventful and the newborn was discharged without complications 7 days after surgery.
Induction of Antibodies Binding to the Membrane Proximal External Region of gp36 of HIV-2
Authors: Behrendt R. , Fiebig U. , Kurth R. , Denner J.
Published: November 2011

Objective: The ability to induce neutralizing antibodies may be the most important feature of an antiretroviral vaccine, preventing infection of target cells and subsequent integration of the virus into the cellular genome where the virus may persist. Broadly neutralizing antibodies directed against conserved epitopes in the membrane proximal external region (MPER) of the transmembrane envelope (TM) protein gp41 of HIV-1 such as the monoclonal antibodies (mAb) 2F5 and mAb 4E10 have been found in infected individuals; however, all attempts to induce such antibodies failed. In individuals infected with HIV-2 such antibodies were not yet reported. Methods: Two recombinant proteins corresponding to the ectodomain of the TM protein gp36 of HIV-2 were produced, rats were immunized and sera were analyzed for binding and neutralizing antibodies. Results: Although binding antibodies were induced, none of the sera neutralized HIV-2. Most interestingly, epitope mapping showed specific binding of the antibodies to the MPER of gp36, to a region homologous to the binding site of the mAb 4E10 in gp41 of HIV-1. Conclusions: Although MPER-specific antibodies were induced by vaccination with gp36, these antibodies did not neutralize HIV-2. This is similar to the situation with HIV-1, but in contrast to that with gammaretroviruses.
Mode of Delivery Influences the Regression of Abnormal Cervical Cytology
Authors: Chung Sue Min , Son Ga Hyun , Nam Eun Ji , Kim Young Han , Kim Young Tae , Park Yong Won , Kwon Ja Young
Published: November 2011

Aims: The purpose was to investigate the influence of delivery mode on the postpartum regression of abnormal cervical cytology. Methods: A retrospective review was conducted of 64 pregnant women with abnormal cervical cytology at Yonsei University Health System in Korea between 2001 and 2008. A Papanicolaou smear and pathological data were categorized into three groups by cervical intraepithelial neoplasia classification. Postpartum evaluation was taken 3–6 months after delivery. The regression rates of cervical cytologic findings were compared between the vaginal delivery group and Cesarean section group. p < 0.05 was considered significant. Results: Of the 64 women, 45 (70.3%) were delivered vaginally and 19 (29.7%) by cesarean section. No significant difference was found between the two groups with respect to age, gestational age, parity, smoking, and HPV (human papilloma virus) screening. Postpartum regression was shown in 39 (92.9%) women who delivered vaginally and in 12 (63.2%) women who underwent cesarean section (p = 0.016). In the cesarean section group, 1 patient had progressed from CIN2 to microinvasive cancer and 2 patients from carcinoma in situ to invasive cancer. Conclusion: The rate of spontaneous regression of antepartum abnormal cervical cytology was higher after vaginal delivery.
Use of a Segmental Thermoexpandable Metal Alloy Stent in the Management of Malignant Ureteric Obstruction: A Single Centre Experience in the UK
Authors: Zaman F. , Poullis C. , Bach C. , Moraitis K. , Junaid I. , Buchholz N. , Masood J.
Published: November 2011

Introduction: The Memokath 051™ is a semipermanent inert metal alloy ureteric stent which can bridge strictures and, compared to double J stents, causes less bladder irritation and pain, is more resistant to external compression forces and may be more effective in patients with malignant ureteric obstruction. We present our experience with this novel stent in such cases. Methods: All suitable patients referred to us with malignancy-associated ureteric strictures over a 4-year period had ureteric Memokath 051™ stents inserted. Data on aetiology and position of the strictures as well as length of the Memokath stents used and their efficacy and complications were recorded prospectively. Results: 42 ureteric Memokath 051™ stents were inserted in 37 patients (mean age 64 years). 40.5% of strictures were related to gynaecological cancer, 21% to bowel cancer, 14% were post radiation, 14% occurred in prostate cancer patients and 9.5% were found in other cancers. The mean follow-up was 22 months (range 5–60 months). The main complications were stent migrations in 5, urinary tract infections in 3 and blockage of stent due to progressive transitional cell carcinoma of the ureter in 2 cases. Conclusion: Memokath 051™ ureteric stents are safe, effective and durable in the long-term treatment of malignant strictures.
Improvement in Antenatal Diagnosis of Critical Congenital Heart Disease Implications for Postnatal Care and Screening
Authors: Israel Stephanie W. , Roofe Lindsay R. , Saville Benjamin R. , Walsh William F.
Published: November 2011

Objective: This observational study was performed to examine the current timing and mode of diagnosis of critical congenital heart disease (CCHD), since early detection of cardiac lesions can significantly improve morbidity and mortality. Method: Ninety cases of CCHD in infants born in Middle Tennessee in 2009 were identified by weekly review of admissions to a single cardiac referral center. CCHD is defined as lesions requiring admission or re-admission for surgical or medical intervention within 1 month of life. Results: Overall, the observed antenatal detection rate of 49% is significantly greater than published values of 25%. Hypoplastic left heart syndrome was detected in 11/11, but only 5/16 coarctations were detected. Conclusion: Compared to earlier reports, our study showed a doubling of the antenatal detection rate. Perhaps efforts to improve early diagnosis of CCHD could focus on antenatal ultrasound screening techniques for lesions that are missed most often as well as on postnatal screening.
FOXG1-Related Disorders: From Clinical Description to Molecular Genetics
Authors: Florian C. , Bahi-Buisson N. , Bienvenu T.
Published: November 2011

Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mutations in loci other than MECP2 have also been found in individuals that have been labeled as atypical RTT. Among them, a mutation in the gene forkhead box G1 (FOXG1) has been involved in the molecular aetiology of the congenital variant of RTT. The FOXG1 gene encodes a winged-helix transcriptional repressor essential for the development of the ventral telencephalon in embryonic forebrain. Later, FOXG1 continues to be expressed in neurogenetic zones of the postnatal brain. Although RTT affects quasi-exclusively girls, FOXG1 mutations have also been identified in male patients. As far as we know, about 12 point mutations and 13 cases with FOXG1 molecular abnormalities (including translocation, duplication and large deletion on the chromosome 14q12) have been described in the literature. Affected individuals with FOXG1 mutations have shown dysmorphic features and Rett-like clinical course, including normal perinatal period, postnatal microcephaly, seizures and severe mental retardation. Interestingly, the existing animal models of FOXG1 deficiency showed similar phenotype, suggesting that animal models may be a fascinating model to understand this human disease. Here, we describe the impacts of FOXG1 mutations and their associated phenotypes in human and mouse models.
Influenza Virus Hemagglutinin: A Model for Protein N-Glycosylation in Recombinant Escherichia coli
Authors: Farahmand Behrokh , Khodabandeh Mahvash , Mahboudi Fereidoun , Fotouhi Fatemeh , Saleh Maryam , Barkhordari Farzaneh , Tabatabaian Mansoureh , Nasab Farnoush Parsaie , Kheiri Masoumeh Tavassoti
Published: November 2011

Background: The hemagglutinin molecule of influenza virus is considered as an ideal model to study biological processes as well as the effect of glycosylation on the function of glycoproteins. Objectives: The large subunit of the influenza virus A/New Caledonia/20/99 (H1N1) hemagglutinin (HA1) was expressed in recombinant Escherichia coli containing the glycosylation system of Campylobacter jejuni. This viral glycoprotein contains glycosylation motifs recognized by prokaryotic and eukaryotic oligosaccharyltransferases. Methods: In order to express the hemagglutinin large subunit gene, the gene was amplified using reverse transcription polymerase chain reaction (RT-PCR), and it was cloned in pET22b for periplasmic expression. Results: Western blotting and lectin blotting bands confirmed glycosylation of the HA1 in recombinant E. coli. Conclusion: Such a successful accomplishment of hemagglutinin expression in recombinant E. coli can be used to construct carbohydrates in hemagglutinin molecules of different strains in order to produce effective antigens for vaccine and rapid diagnostic kits against new emerging viruses.
Survival Impact of Adjuvant Paclitaxel and Carboplatin for Early-Stage Ovarian Clear-Cell Carcinoma with Complete Surgical Staging
Authors: Kajiyama Hiroaki , Shibata Kiyosumi , Suzuki Shiro , Ino Kazuhiko , Kawai Michiyasu , Nagasaka Tetsuro , Nawa Akihiro , Kikkawa Fumitaka
Published: November 2011

Objectives: The aim of this study was to estimate the survival impact of adjuvant paclitaxel and carboplatin (TC) compared to cisplatin (CDDP)-based chemotherapies for early-stage ovarian clear-cell carcinoma (CCC). Methods: Clinicopathologic information on 99 stage I–II CCC patients was obtained between 1987 and 2005. All patients underwent complete surgical staging including systemic lymphadenectomy, followed by TC or various CDDP-based regimens. In the present study, only CCC patients with no residual tumor were enrolled. Results: The median age was 53 years and ranged from 30 to 69 years. Fifty-three (53.5%) patients received TC and 46 (46.5%) patients underwent various CDDP-based chemotherapies after initial surgery. Five-year progression-free survival (PFS) rates of TC and various CDDP groups were 66.5 and 75.8%, respectively (n.s., p = 0.933). In addition, 5-year overall survival (OS) rates of TC and various CDDP groups were 82.4 and 82.3%, respectively (n.s., p = 0.583). In multivariate analyses of OS and PFS, the regimen of chemotherapywas not a significant prognostic factor (OS, p = 0.502; PFS, p = 0.977. Conclusions: In our current examination of the long-term survival of early-stage CCC patients, we did not identify a superiority of TC over various CDDP-based regimens as frontline adjuvant chemotherapy.
Diagnosis of Immediate Hypersensitivity to β-Lactam Antibiotics Can Be Made Safely with Current Approaches
Authors: Celik Gulfem E. , Aydin Ömür , Dogu Figen , Çipe Funda , Boyvat Ayşe , Ikinciogullari Aydan , Akyol Aynur , Demirel Yavuz S.
Published: November 2011

Background: Diagnosing immediate hypersensitivity to β-lactam antibiotics is still a significant problem. Recently, a new penicillin testing reagent was introduced to the market. In this study, the recommendations of the European Network of Drug Allergy (ENDA) for the diagnosis of immediate reactions to β-lactams were followed, and the negative predictive value of this approach with currently available reagents was assessed. Methods: Eighty patients (age range: 6–74 years) with a history of immediate reactions to β-lactams were included. All cases underwent skin testing with benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM), followed by the culprit drug if necessary. If this step was negative, a drug provocation test was offered. If this step also yielded a negative result, then the patients were recommended to use β-lactam antibiotics in future whenever their use was indicated. Results: Overall, 29 patients (36.2%) were diagnosed as β-lactam allergic. The majority of the cases (72.4%) were diagnosed by positive skin tests to either PPL or MDM, whereas 10.3% were diagnosed by skin testing with culprit drugs and 17.2% with drug provocation tests. Regarding the use of the tested drug in the long term, almost half of the contacted patients had had an indication to use the tested drug and the majority had taken the whole course without problems. Conclusions: Although currently available new penicillin tests provide sufficient allergy data, all the steps recommended by ENDA should be followed in the diagnosis of immediate reactions to β-lactams. If these steps are negative, the patients usually tolerate β-lactams and only a few develop mild, non-life-threatening reactions in the long term.
Medical versus Surgical Abortion Methods for Pregnancy in China: A Cost-Minimization Analysis
Authors: Xia Wei , She Shouzhang , Lam Tai Hing
Published: November 2011

Background: Both medical and surgical abortions are popular in developing countries. However, the monetary costs of these two methods have not been compared. Methods: 430 women seeking abortions were recruited in 2008. Either a medical or surgical method was used for the abortion. We adopted the perspective of a third-party payer. Cost-minimization analysis was used based on all charges for the overall procedures in an out-patient clinic in Guangzhou, China. Results: 219 subjects (51%) chose a medical method (mifepristone and misoprostol), whereas 211 subjects (49%) chose a surgical method. The efficacy in the surgical group was significantly higher than in the medical group (100 vs. 90%, p < 0.001). Surgical abortion incurred much more costs than medical abortion on average after initial treatment. When the subsequent costs were accumulated within the 2-week follow-up, the mean total cost in the medical group increased significantly due to failure of abortion and persistent bleeding. Patients undergoing medical abortion eventually incurred equivalent expenses compared to patients undergoing surgical abortion (p = 0.42). Conclusions: There was no difference in the mean final costs between the two abortion methods. Complications of persistent bleeding and failure to abort (requiring surgical intervention) in the medical treatment group increased the final mean total cost substantially.
Molecular and Clinical Aspects of Angelman Syndrome
Authors: Dagli A. , Buiting K. , Williams C.A.
Published: November 2011

The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2–q13 genomic region identifies 75–80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5–10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity.
Müller Glial Cells in Retinal Disease
Authors: Bringmann Andreas , Wiedemann Peter
Published: November 2011

Virtually all pathogenic stimuli activate Müller cells. Reactive Müller cells exert protective and toxic effects on photoreceptors and neurons. They contribute to oxidative stress and glutamate toxicity due to malfunctions of glutamate uptake and glutathione synthesis. Downregulation of potassium conductance disrupts transcellular potassium and water transport, resulting in neuronal hyperexcitability and edema. Protective effects of reactive Müller cells include upregulation of adenosine 5′-triphosphate (ATP)-degrading ectoenzymes, which enhances the extracellular availability of the neuroprotectant adenosine, abrogation of the osmotic release of ATP, which might protect retinal ganglion cells from apoptosis, and the release of antioxidants and neurotrophic factors. The dedifferentiation of reactive Müller cells to progenitor-like cells might have an impact on future therapeutic approaches. A better understanding of the gliotic mechanisms will be helpful in developing efficient therapeutic strategies aiming at increased protective and regenerative properties and decreased toxicity of reactive Müller cells.
Fertility Preservation in Heterotopic Cervical Pregnancy: What Is the Best Procedure?
Authors: Sánchez-Ferrer María Luisa , Machado-Linde Francisco , Pertegal-Ruiz Miriam , García-Sánchez Francisco , Pérez-Carrión Antonio , Capel-Aleman Antonio , Parilla-Paricio Juan José , Abad-Martínez Lorenzo
Published: November 2011

We describe a patient who underwent assisted reproduction techniques and was diagnosed with heterotopic cervical pregnancy, and then discuss the management of this entity, which is rare and has no standard protocols. Treatment consisted of intra-arterial methotrexate (50 mg/m2 body surface area) and simultaneous selective embolization of uterine arteries. The literature is also reviewed to identify other approaches and outcomes.