bluuebunny/crossref_metadata_2025 huggingface dataset:
Photocatalytic Activity and Characterization of Carbon-Modified Titania for Visible-Light-Active Photodegradation of Nitrogen Oxides
Authors: Huang Chun-Hung , Lin Yu-Ming , Wang I-Kai , Lu Chun-Mei
Published: February 2012

A variety of carbon-modified titania powders were prepared by impregnation method using a commercial available titania powder, Hombikat UV100, as matrix material while a range of alcohols from propanol to hexanol were used as precursors of carbon sources. Rising the carbon number of alcoholic precursor molecule, the modified titania showed increasing visible activities ofNOxphotodegradation. The catalyst modified with cyclohexanol exhibited the best activities of 62%, 62%, 59%, and 54% for the totalNOxremoval under UV, blue, green, and red light irradiation, respectively. The high activity with long wavelength irradiation suggested a good capability of photocatalysis in full visible light spectrum. Analysis of UV-visible spectrum indicated that carbon modification promoted visible light absorption and red shift in band gap. XPS spectroscopic analysis identified the existence of carbonate species (C=O), which increased with the increasing carbon number of precursor molecule. Photoluminescence spectra demonstrated that the carbonate species suppressed the recombination rate of electron-hole pair. As a result, a mechanism of visible-light-active photocatalyst was proposed according to the formation of carbonate species on carbon-modified TiO2.
Synthesis and Characterization of New Lead(II) and Organotin(IV) Complexes of Schiff Bases Derived from Histidine and Methionine
Authors: Singh Har Lal , Singh J. B.
Published: February 2012

New Schiff base (HL) ligand is prepared via condensation of isatins and amino acids in 1:1 molar ratio. Metal complexes are prepared and characterized by elemental analysis, molar conductance, electronic, infrared, and multinuclear magnetic resonance (1H NMR, 13C NMR, and 119Sn NMR). The analytical data showed that the ligand acts as bidentate toward metal ions via azomethine nitrogen and carboxylate oxygen by a stoichiometric reaction of metal : ligand (1 : 2) to from metal complexes (Pb(II)(L)2 and Bu2Sn(L)2, where L is the Schiff base ligands of histidine and methionine). The conductivity values between 15 and 25 Ω−1cm2 mol−1 in DMF imply the presence of nonelectrolyte species. On the basis of the above spectral studies, distorted octahedral and tetrahedral geometry have been proposed for the resulting organotin(IV) and lead(II) complexes.
Energy‐Efficient Multi‐Job Scheduling Model for Cloud Computing and Its Genetic Algorithm
Authors: Wang Xiaoli , Wang Yuping , Zhu Hai
Published: February 2012

For the problem that the energy efficiency of the cloud computing data center is low, from the point of view of the energy efficiency of the servers, we propose a new energy‐efficient multi‐job scheduling model based on Google’s massive data processing framework. To solve this model, we design a practical encoding and decoding method for the individuals and construct an overall energy efficiency function of the servers as the fitness value of each individual. Meanwhile, in order to accelerate the convergent speed of our algorithm and enhance its searching ability, a local search operator is introduced. Finally, the experiments show that the proposed algorithm is effective and efficient.
New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy
Authors: Soler María José , Riera Marta , Batlle Daniel
Published: February 2012

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.
Soret and Dufour Effects on Natural Convection Flow Past a Vertical Surface in a Porous Medium with Variable Viscosity
Authors: Moorthy M. B. K. , Senthilvadivu K.
Published: February 2012

The heat and mass transfer characteristics of natural convection about a vertical surface embedded in a saturated porous medium subject to variable viscosity are numerically analyzed, by taking into account the diffusion‐thermo (Dufour) and thermal‐diffusion (Soret) effects. The governing equations of continuity, momentum, energy, and concentrations are transformed into nonlinear ordinary differential equations, using similarity transformations, and then solved by using Runge‐Kutta‐Gill method along with shooting technique. The parameters of the problem are variable viscosity, buoyancy ratio, Lewis number, Prandtl number, Dufour effect, Soret effect, and Schmidt number. The velocity, temperature, and concentration distributions are presented graphically. The Nusselt number and Sherwood number are also derived and discussed numerically.
Isolation of Human Islets for Autologous Islet Transplantation in Children and Adolescents with Chronic Pancreatitis
Authors: Bottino Rita , Bertera Suzanne , Grupillo Maria , Melvin Patricia R. , Humar Abhinav , Mazariegos George , Moser A. James , Walsh R. Matthew , Fung John , Gelrud Andres , Slivka Adam , Soltys Kyle , Wijkstrom Martin , Trucco Massimo
Published: February 2012

Chronic pancreatitis is an inflammatory disease of the pancreas that causes permanent changes in the function and structure of the pancreas. It is most commonly a complication of cystic fibrosis or due to a genetic predisposition. Chronic pancreatitis generally presents symptomatically as recurrent abdominal pain, which becomes persistent over time. The pain eventually becomes disabling. Once specific medical treatments and endoscopic interventions are no longer efficacious, total pancreatectomy is the alternative of choice for helping the patient achieve pain control. While daily administrations of digestive enzymes cannot be avoided, insulin-dependent diabetes can be prevented by transplanting the isolated pancreatic islets back to the patient. The greater the number of islets infused, the greater the chance to prevent or at least control the effects of surgical diabetes. We present here a technical approach for the isolation and preservation of the islets proven to be efficient to obtain high numbers of islets, favoring the successful treatment of young patients.
Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model
Authors: Buller Kathryn M. , Wixey Julie A. , Reinebrant Hanna E.
Published: February 2012

Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia-ischemia, where in the brain they are damaged, and the mechanisms that produce neuronal losses are critical to determine the anatomical substrates responsible for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we describe our current work investigating how the serotonergic network in the brain is disrupted in a rodent model of preterm hypoxia-ischemia. One week after postnatal day 3 hypoxia-ischemia, losses of serotonergic raphé neurons, reductions in serotonin levels in the brain, and reduced serotonin transporter expression are evident. These changes can be prevented using two anti-inflammatory interventions; the postinsult administration of minocycline or ibuprofen. However, each drug has its own limitations and benefits for use in neonates to stem damage to the serotonergic network after hypoxia-ischemia. By understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced serotonergic damage we will hopefully move closer to developing a successful clinical intervention to treat neonatal brain injury.
Blood Pressure Reactivity to an Anger Provocation Interview Does Not Predict Incident Cardiovascular Disease Events: The Canadian Nova Scotia Health Survey (NSHS95) Prospective Population Study
Authors: Shaffer Jonathan A. , Wasson Lauren Taggart , Davidson Karina W. , Schwartz Joseph E. , Kirkland Susan , Shimbo Daichi
Published: February 2012

We examined the association between blood pressure (BP) reactivity to an anger provocation interview and 10-year incident CVD events in 1,470 adults from the population-based 1995 Nova Scotia Health Survey (NSHS95). In an unadjusted model, those in the highest decile of systolic BP reactivity were more than twice as likely to have an incident CVD event compared to those in the decile with no reactivity (HR = 2.33, 95% CI = 1.15 – 4.69,P= 0.02). However, after adjusting for age and sex, and then also for Framingham risk score, body mass index, and education, this relationship was attenuated and not statistically significant. Diastolic BP reactivity was not associated with CVD incidence in any model. Individual differences in BP reactivity to a laboratory-induced, structured anger provocation interview may not play a major role in clinical CVD endpoints.
Detection of Chromosome X;18 Breakpoints and Translocation of the Xq22.3;18q23 Regions Resulting in Variable Fertility Phenotypes
Authors: Szvetko Attila , Martin Nicole , Joy Chris , Hayward Andrea , Watson Bob , Cary Andrew , Withers Stephen
Published: February 2012

We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18)(q22.3;q23) genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X), t(X;18)(q22.3;q23). The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18)(q22.3;q23). Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility.
Fungal Rhinosinusitis: A Retrospective Microbiologic and Pathologic Review of 400 Patients at a Single University Medical Center
Authors: Montone Kathleen T. , Livolsi Virginia A. , Feldman Michael D. , Palmer James , Chiu Alexander G. , Lanza Donald C. , Kennedy David W. , Loevner Laurie A. , Nachamkin Irving
Published: February 2012

Fungal Rhinosinusitis (FRS) is a well known entity, but only in more recent times have the types of FRS been more fully defined. In this study, we evaluate the diagnosis of FRS in a single medical center. Cases were divided into 2 main categories, non-invasive and invasive. Non-invasive FRS included fungus ball (FB) and allergic fungal rhinosinusitis (AFRS). Invasive FRS included acute invasive fungal rhinosinusitis (AIFRS), chronic invasive fungal rhinosinusitis (CIFRS), and chronic invasive granulomatous fungal rhinosinusitis (CGFRS). Fungal culture data, if available was reviewed. 400 patients with FRS were identified. 87.25% were non-invasive (45% AFRS, 40% FB, and 2% combined AFRS and FB and 12.5% were invasive 11% AIFRS 1.2% CIFRS 0.5% CGFRS. One patient (0.25%) had combined FB/CGFRS.Aspergillus sp.or dematiaceous species were the most common fungi isolated in AFS whileAspergillus sp.was most common in FB and AIFRS. In our experience, most FRS is non-invasive. In our patient population, invasive FRS is rare with AIFRS representing >90% of cases. Culture data supports that a variety of fungal agents are responsible for FRS, butAspergillus sp.appears to be one of the most common organisms in patients with FRS.
Employing Photoassisted Ligand Exchange Technique in Layered Quantum Dot LEDs
Authors: Hu Wenjia , Gao Shuai , Prasad Paras N. , Wang Jingkang , Xu Jian
Published: February 2012

We presented in this paper a photoassisted ligand exchange approach whereby light will be introduced to facilitate the replacement of oleic acid (OA) ligand molecules over PbSe quantum dots (QDs). The ligand‐exchanged QDs were used to fabricate quantum dot light‐emitting‐diodes (QD‐LEDs), which outperform the devices comprising the QDs without ligand‐replacement.
Memantine as an Augmentation Therapy for Anxiety Disorders
Authors: Schwartz Thomas L. , Siddiqui Umar A. , Raza Shafi
Published: February 2012

Objective. Glutamate, an excitatory neurotransmitter in the central nervous system (CNS), may play a role in the development of anxiety. Memantine partially blocks N-methyl-D-aspartate (NMDA) receptors' glutamate channels located in the CNS. This paper evaluates memantine as an augmentation therapy for treatment of anxiety.Methods. 15 consecutive partially responding anxious patients were treated with adjunctive memantine for 10 weeks. Memantine was dosed 5–20 mg/day.Result. Memantine augmentation resulted in clinically relevant reduction in anxiety symptoms when compared to baseline. Forty percent of patients achieved remission (HAM-A ≥ 7). Memantine improved sleep quality. Mean dose was 14 mg/d (range 5–20 mg/d). Typical adverse events included nausea and headache.Conclusion. The NMDA receptor antagonist memantine may be an effective augmentation therapy in patients with treatment-resistant anxiety.
A New Anatomically Based Nomenclature for the Roots and Root Canals—Part 2: Mandibular Molars
Authors: Valerian Albuquerque Denzil , Kottoor Jojo , Velmurugan Natanasabapathy
Published: February 2012

Several terminologies have been employed in the dental literature to describe the roots and root canal systems of mandibular molars with no consensus being arrived at, thus far. The anatomical relation of roots and their root canals were identified and a naming system was formulated. The proposed nomenclature attempts to make certain essential modifications to the traditional approach to accommodate the naming of various aberrations presented in mandibular molars. A simple, yet extensive nomenclature system has been proposed that appropriately names the internal and external morphology of mandibular molars.
Neurogenic Bladder
Authors: Dorsher Peter T. , McIntosh Peter M.
Published: February 2012

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.
Photocatalytic Degradation of Using Ni-Containing TiO2
Authors: Tseng Yao-Hsuan , Huang Bo-Kai
Published: February 2012

The nickel-containing titania was synthesized and employed in the photomineralization of . A nickel-modified titania photocatalyst was prepared by photodeposition method with using Degussa-P25 TiO2particle and nickel chloride as raw materials, respectively. The physical analyses were carried out using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), transmittance electron microscope (TEM), and photoluminescence spectroscopy (PL), to observe changes in particles following nickel modification. The results showed that Ni does not enter into the crystal lattice and is dispersed onto the surface uniformly. Ni improved the intensity of PL spectra with an appropriate Ni content on the surface. The modified titanium dioxide with 0.1 mol% of nickel exhibited two times the -removal activity of bare under ultraviolet illumination. The nickel content in this photodeposition process plays an important role in affinity to molecules, recombination rate of electron-hole pair, and content of active site on the surface and therefore affects the optical and photocatalytic properties.
Design and Optimization of a Millimetre Wave Compact Folded Magic-T
Authors: Hua Guang , Zhang Jiefu , Wu Jiudong , Hong Wei
Published: February 2012

A millimetre wave-folded magic-T junction compensated with metal cone is designed using a particle swarm optimization (PSO) algorithm. An off-centred metallic frustum was used to enhance the bandwidth and a metallic post is used to compensate the mismatched E-arm. The geometrical parameters of the frustum and the post are optimized by PSO. The optimized magic-T for W-band application is designed and tested. The design features are simple in structure and easy to fabricate. The 2% bandwidth with centre frequency of 94 GHz and return loss less than −20 dB is achieved.
Changes in Body Mass Index across Age Groups in Iranian Women: Results from the National Health Survey
Authors: Bakhshi Enayatollah , Seifi Behjat , Biglarian Akbar , Mohammad Kazem
Published: February 2012

Background. To investigate the associations between some factors with weight gain across age groups in Iranian women.Methods. Proportional odds model was used to estimate the probability of BMI categorized as a function of education, economic index, workforce, smoking, marital status, and place of residence adjusted for age, using data from the “National Health Survey in Iran” database. It included 14176 women aged 20–69 years.Results. For all covariates, age was directly associated with overweight and obesity before 60 years of age. Among women aged 20–40 years, the rates of change in probabilities of overweight and obesity were highest. Among women, being inactive, with high economic index, married, being nonsmoker, in an urban residence, with lower educational attainment, all increased the probabilities of overweight and obesity.Conclusions. Women aged 20–40 years gained weight faster than other groups. They may need additional information and more support on how to reduce their risk for weight gain through positive health behaviors.
Spectral Distortion in Lossy Compression of Hyperspectral Data
Authors: Aiazzi Bruno , Alparone Luciano , Baronti Stefano , Lastri Cinzia , Selva Massimo
Published: February 2012

Distortion allocation varying with wavelength in lossy compression of hyperspectral imagery is investigated, with the aim of minimizing the spectral distortion between original and decompressed data. The absolute angular error, or spectral angle mapper (SAM), is used to quantify spectral distortion, while radiometric distortions are measured by maximum absolute deviation (MAD) for near‐lossless methods, for example, differential pulse code modulation (DPCM), or mean‐squared error (MSE) for lossy methods, for example, spectral decorrelation followed by JPEG 2000. Two strategies of interband distortion allocation are compared: given a target average bit rate, distortion may be set to be constant with wavelength. Otherwise, it may be allocated proportionally to the noise level of each band, according to the virtually lossless protocol. Comparisons with the uncompressed originals show that the average SAM of radiance spectra is minimized by constant distortion allocation to radiance data. However, variable distortion allocation according to the virtually lossless protocol yields significantly lower SAM in case of reflectance spectra obtained from compressed radiance data, if compared with the constant distortion allocation at the same compression ratio.
Factors That Influence HIV Risk among Hispanic Female Immigrants and Their Implications for HIV Prevention Interventions
Authors: Hernandez Amy M. , Zule William A. , Karg Rhonda S. , Browne Felicia A. , Wechsberg Wendee M.
Published: February 2012

Hispanics are the fastest growing minority group in North Carolina with increasing incidence of HIV infection. Gender roles, cultural expectations, and acculturation of women may explain some of Hispanic women’s risks. The perspectives of Hispanic female immigrants and community-based providers were sought to identify services they offer, understand HIV risk factors, and support the adaptation of a best-evidence HIV behavioural intervention for Hispanic women. Two sets of focus groups were conducted to explicate risks and the opportunities to reach women or couples and the feasibility to conduct HIV prevention in an acceptable manner. Salient findings were that Hispanic female immigrants lacked accurate HIV/AIDS and STI knowledge and that traditional gender roles shaped issues surrounding sexual behaviour and HIV risks, as well as condom use, partner communication, and multiple sexual partnerships. Intervention implications are discussed such as developing and adapting culturally appropriate HIV prevention interventions for Hispanics that address gender roles and partner communication.
Approximation Analysis of Learning Algorithms for Support Vector Regression and Quantile Regression
Authors: Xiang Dao-Hong , Hu Ting , Zhou Ding-Xuan
Published: February 2012

We study learning algorithms generated by regularization schemes in reproducing
kernel Hilbert spaces associated with an ϵ‐insensitive pinball loss. This loss
function is motivated by the ϵ‐insensitive loss for support vector regression and the
pinball loss for quantile regression. Approximation analysis is conducted for these
algorithms by means of a variance‐expectation bound when a noise condition is
satisfied for the underlying probability measure. The rates are explicitly derived
under a priori conditions on approximation and capacity of the reproducing kernel
Hilbert space. As an application, we get approximation orders for the support
vector regression and the quantile regularized regression.
Arterial Microcalcifications in the Breast Mimicking Malignancy
Authors: Janzen Katrin , Janzen Jan
Published: February 2012

Microcalcifications in the breast are highly suggestive of malignancy; they can occur in many pathological conditions. A 36-years-old nondiabetic woman came to the gynaecologist with a suspect palpable mass in the upper outer quadrant of the right breast. Histopathological examination confirmed a calcification of a small artery (diameter: 0.45 mm). Arterial calcifications can mimic a malignant lesion in the breast.
Antiallodynic Effect of Herbal Medicine Yokukansan on Peripheral Neuropathy in Rats with Chronic Constriction Injury
Authors: Suzuki Yasuyuki , Mitsuhata Hiromasa , Yuzurihara Mitsutoshi , Kase Yoshio
Published: February 2012

Yokukansan, one of the traditional Japanese herbal medicines, ameliorated neuropathic pain symptoms in patients. In this study, we investigated the effects of yokukansan on neuropathic pain in chronic constriction injury (CCI) model. Oral administration of yokukansan significantly inhibited mechanical and cold allodynia in the von Frey hair or acetone test, respectively. In comparison, amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not significant, antiallodynic effects in the mechanical and cold tests. Yokukansan significantly inhibited the cerebrospinal fluid dialysate level of glutamate that had increased by the stimulation of brush or acetone. Glutamate transporter inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that yokukansan was confirmed to have antiallodynic effects in CCI rats, which are related to a blockade of glutamatergic neurotransmission via activation of glutamate transporters in the spinal cord.
Tailoring the Composition and Properties of Sprayed CuSbS2Thin Films by Using Polymeric Additives
Authors: Popovici Ionut , Duta Anca
Published: February 2012

CuSbS2thin films were obtained by spray pyrolysis deposition, using polymeric additives for controlling the surface properties and film’s composition. Ternary crystalline chalcostibite compounds have been obtained without any postdeposition treatments. XRD spectra and IR spectroscopy were used to characterize films composition and interactions between components. Films morphology and surface energy were investigated using AFM microscopy and contact angle measurements. Hydrophobic and hydrophilic polymers strongly influence the composition and film morphology.
Engineering Airway Epithelium
Authors: Soleas John P. , Paz Ana , Marcus Paula , McGuigan Alison , Waddell Thomas K.
Published: February 2012

Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.
Glioblastoma Stem–like Cell Lines with Either Maintenance or Loss of High-Level EGFR Amplification, Generated via Modulation of Ligand Concentration
Authors: Schulte Alexander , Günther Hauke S. , Martens Tobias , Zapf Svenja , Riethdorf Sabine , Wülfing Clemens , Stoupiec Malgorzata , Westphal Manfred , Lamszus Katrin
Published: February 2012

Purpose: Despite the high incidence of epidermal growth factor receptor (EGFR) gene amplification and rearrangement in glioblastomas, no suitable cell line exists that preserves these alterations in vitro and is tumorigenic in immunocompromised mice. On the basis of previous observations that glioblastoma cells cultured with serum lose the EGFR amplification rapidly and that EGF can inhibit the growth of EGFR-amplified tumor cells, we hypothesized that serum-free and EGF-free culture conditions could promote maintenance of the EGFR amplification.

Experimental Design: Cells from EGFR-amplified glioblastomas were taken into culture using neural stem cell conditions with modifications, including varying oxygen concentrations and omission of routine EGF supplementation.

Results: High-level EGFR amplification was rapidly lost in 5 glioblastoma cultures supplemented with EGF, whereas it was preserved in cultures from the same tumors established without EGF. Cultures from 2 glioblastomas developed into pairs of cell lines, with either stable maintenance or irreversible loss of high-level EGFR amplification in the majority of cells. One EGFR-amplified cell line preserved expression of the receptor variant EGFRvIII. Cell lines with high-level EGFR amplification/EGFRvIII expression formed highly aggressive tumors in nude mice, whereas nonamplified cell lines were either nontumorigenic or grew significantly more slowly. In contrast, nonamplified cell lines proliferated faster in vitro. All cell lines responded to erlotinib, with inhibition of receptor activation and proliferation but partly different effects on downstream signaling and migration.

Conclusions: Isogenic glioblastoma cell lines maintaining stable differences in EGFR/EGFRvIII status can be derived by varying exposure to EGF ligand and reflect the intratumoral genetic heterogeneity. Clin Cancer Res; 18(7); 1901–13. ©2012 AACR.
NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies
Authors: Valsasina Barbara , Beria Italo , Alli Cristina , Alzani Rachele , Avanzi Nilla , Ballinari Dario , Cappella Paolo , Caruso Michele , Casolaro Alessia , Ciavolella Antonella , Cucchi Ulisse , De Ponti Anna , Felder Eduard , Fiorentini Francesco , Galvani Arturo , Gianellini Laura M. , Giorgini Maria L. , Isacchi Antonella , Lansen Jaqueline , Pesenti Enrico , Rizzi Simona , Rocchetti Maurizio , Sola Francesco , Moll Jürgen
Published: February 2012

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings. Mol Cancer Ther; 11(4); 1006–16. ©2012 AACR.
Body Mass Index and the Risk for Developing Invasive Breast Cancer among High-Risk Women in NSABP P-1 and STAR Breast Cancer Prevention Trials
Authors: Cecchini Reena S. , Costantino Joseph P. , Cauley Jane A. , Cronin Walter M. , Wickerham D. Lawrence , Land Stephanie R. , Weissfeld Joel L. , Wolmark Norman
Published: February 2012

High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women. Cancer Prev Res; 5(4); 583–92. ©2012 AACR.
MC4R Dimerization in the Paraventricular Nucleus and GHSR/MC3R Heterodimerization in the Arcuate Nucleus: Is There Relevance for Body Weight Regulation?
Authors: Rediger Anne , Piechowski Carolin Leonie , Habegger Kirk , Grüters Annette , Krude Heiko , Tschöp Matthias H. , Kleinau Gunnar , Biebermann Heike
Published: February 2012

The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization.
Topical Imiquimod 5% Cream for Pediatric Plaque Morphea: A Prospective, Multiple-Baseline, Open-Label Pilot Study
Authors: Pope Elena , Doria Andrea S. , Theriault Marc , Mohanta Arun , Laxer Ronald M.
Published: February 2012

Background/Aims: Therapeutic options for the treatment of plaque morphea are limited. We explored the efficacy and safety of imiquimod cream in children with plaque morphea. Methods: Prospective, open-label, double-baseline study, using imiquimod 5% cream topically for 9 months. The primary outcome measure was improvement in the thickening of morphea plaques using a visual analog scale (VAS) and the DIET score (dyspigmentation/induration/erythema/telangiectasia). Secondary outcome measures were clinicoradiographic correlations and frequency of adverse events. Results: Nine patients, 89% females, with a mean age of 11.33 years (SD = 3.52) were enrolled. At 36 weeks, the mean VAS had decreased from 48.08 (SD = 18.85) to 22.7 (SD = 12.9) (p < 0.0001), and the mean DIET score from 4.38 (SD = 1.2) to 3.06 (SD = 1.39) (p = 0.23). There was very good interrater reliability between DIET score assessments (intraclass correlation coefficient, ICC = 0.75) and VAS (ICC = 0.59) and moderate agreement between parent and investigator VAS (ICC = 0.5). Ultrasonographically measured dermis thickness changed from 1.05 (SD = 0.34) to 0.95 (SD = 0.19) (p = 0.001). One patient experienced ulceration that required temporary discontinuation of intervention. Conclusions: This proof of concept study revealed that imiquimod 5% cream is effective in decreasing the thickening of plaque morphea and safe for pediatric use. Further prospective studies are warranted.
Systolic Heart Function, Kidney Filtration and the Number of Coronary Atherosclerotic Plaques in Lean and Overweight Patients
Authors: Ferreira-Filho Sebastião Rodrigues , Rosa César Augusto Saldanha , Reis Samir Seme Arab , Botelho Roberto Vieira , Pereira Vilmar José , Pellaza Bruno Bordin
Published: February 2012

The objective of this study was to quantify the number of vessels with stenotic points in the coronary circulation of lean and overweight individuals submitted to coronary angiography and ventriculography to verify the possible associations with glomerular filtration and the systolic ventricular function. Eighty-six patients with a previous history of myocardial ischemia were studied. Two groups were formed: non-elderly (G1), n = 38, 52.8 ± 1.2 years old, and elderly (G2), n = 48, 70.1 ± 1.2 years old. Both groups were divided into 2 subgroups according to the estimated glomerular filtration rate (eGFR): ≥60 and <60 ml/min/m2. The results showed that G1 had 0.36 ± 0.11 versus 1.25 ± 0.45 stenoses/patient (≥60 vs. <60 ml/min/m2; p < 0.05, respectively) and G2 had 0.91 ± 0.28 versus 1.83 ± 0.33 stenoses/patient (≥60 vs. <60 ml/min/m2, respectively). The other variables, such as central and brachial arterial blood pressures, did not manifest significant differences in relation to the eGFR. The following significant correlations were observed: between the quantity of coronary stenotic points and the eGFR (R2 = 11.2%; r = -0.33; p < 0.001), and between eGFR and the ventricular ejection fraction (R2 = 5.1%; r = 0.57; p < 0.0001). The ejection fraction correlated significantly with the number of vessels with stenoses in the coronary bed (R2 = 13.4%; r = -0.36; p < 0.008). In conclusion, although the correlations are considered weak, interrelationships between heart and kidney were demonstrated in this study.
Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation
Authors: Gallego Pilar , Roldán Vanessa , Torregrosa José Miguel , Gálvez Josefa , Valdés Mariano , Vicente Vicente , Marín Francisco , Lip Gregory Y.H.
Published: February 2012

Background—

Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF.

Methods and Results—

We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0–3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0–6; 29% with a score ≥3 [ie, high risk]). Median follow-up was 861 days (range, 718–1016 days). Independent predictors for major bleeding were age ≥75 years (hazard ratio [HR], 1.74; 95% CI, 1.05–2.87;
P
=0.030), male sex (HR, 1.70; 95% CI, 1.03–2.80;
P
=0.036), renal impairment (HR, 2.12; 95% CI, 1.20–3.73;
P
=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73–9.67;
P
<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03–5.06;
P
=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13–4.18;
P
=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40–3.46;
P
=0.001), heart failure (HR, 1.78; 95% CI, 1.20–2.86;
P
=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20–2.86;
P
<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68–2.49;
P
<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27–1.81;
P
<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all-cause mortality (HR, 1.68; 95% CI, 1.40–2.01;
P
<0.001).

Conclusions—

The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events.
Is There a Clinically Significant Interaction Between Calcium Channel Antagonists and Clopidogrel?
Authors: Good Christopher W. , Steinhubl Steven R. , Brennan Danielle M. , Lincoff A. Michael , Topol Eric J. , Berger Peter B.
Published: February 2012

Background—

Clopidogrel is an inactive prodrug; it is converted to its active metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel blockers (CCBs). Several studies have reported that CCBs reduce the ability of clopidogrel to inhibit platelet aggregability; one suggested that CCBs reduce the efficacy of clopidogrel.

Methods and Results—

We performed a post hoc analysis of the Clopidogrel for the Reduction of Events During Observation (CREDO) study to compare the treatment effect of clopidogrel in patients on CCBs versus not on CCBs. In CREDO, 2116 patients were randomly assigned to pretreatment with 300 mg clopidogrel 3–24 hours before a planned percutaneous coronary intervention followed by 1 year of 75 mg/d clopidogrel, versus 75 mg clopidogrel at the time of the procedure and continued for 28 days only. The primary end points were a combined end point of death, myocardial infarction, and stroke at 28 days and 1 year. Among the 580 patients (27%) on CCBs at enrollment, at 28 days, the combined end point was reached in 17 patients (6%) on clopidogrel versus 28 (9%) on placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.39–1.29). At 1 year, the combined end point was reached in 27 patients (10%) on clopidogrel versus 46 (15%) on placebo (HR, 0.68; 95% CI, 0.42–1.09). The treatment effect of clopidogrel was similar in patients not on CCBs at 1 year (HR, 0.78; 95% CI, 0.56–1.09). After adjustment for differences between patients on and not on CCB, there was still no evidence of an interaction between clopidogrel treatment and CCB (HR for patients not on CCBs, 0.87; 95% CI, 0.62–1.23; HR for patients on CCBs, 0.74; 95% CI, 0.45–1.21).

Conclusions—

In CREDO, there was no evidence that CCBs decrease the efficacy of clopidogrel.
When Collateral Supply is Accounted For Epicardial Stenosis Does Not Increase Microvascular Resistance
Authors: Layland Jamie , MacIsaac Andrew I. , Burns Andrew T. , Somaratne Jithendra B. , Leitl George , Whitbourn Robert J. , Wilson Andrew M.
Published: February 2012

Background—

The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis.

Methods and Results—

Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89,
P
=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06,
P
<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89,
P
=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78,
P
=0.42).

Conclusions—

When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.
Vascular Tissue Reaction to Acute Malapposition in Human Coronary Arteries
Authors: Gutiérrez-Chico Juan Luis , Wykrzykowska Joanna , Nüesch Eveline , van Geuns Robert Jan , Koch Karel T. , Koolen Jacques J. , di Mario Carlo , Windecker Stephan , van Es Gerrit-Anne , Gobbens Pierre , Jüni Peter , Regar Evelyn , Serruys Patrick W.
Published: February 2012

Background—

The vascular tissue reaction to acute incomplete stent apposition (ISA) is not well known. The aim of this study was to characterize the vascular response to acute ISA in vivo and to look for predictors of incomplete healing.

Methods and Results—

Optical coherence tomography studies of 66 stents of different designs, implanted in 43 patients enrolled in 3 randomized trials, were analyzed sequentially after implantation and at 6 to 13 months. Seventy-eight segments with acute ISA were identified in 36 of the patients and matched with the follow-up study by use of fiduciary landmarks. The morphological pattern of healing in the ISA segments was categorized as homogeneous, layered, crenellated, bridged, partially bridged, or bare, depending on the persistence of ISA and on the coverage. After 6 months, acute ISA volume decreased significantly, and 71.5% of the ISA segments were completely integrated into the vessel wall. Segments with acute ISA had higher risk of delayed coverage than well-apposed segments (relative risk 2.37, 95% confidence interval 2.01–2.78). Acute ISA size (estimated as ISA volume or maximum ISA distance per strut) was an independent predictor of ISA persistence and of delayed healing at follow-up.

Conclusions—

Neointimal healing tends to reduce ISA, with the malapposed stent struts often integrated completely into the vessel wall, resulting in characteristic morphological patterns. Coverage of ISA segments is delayed with respect to well-apposed segments. The larger the acute ISA, the greater the likelihood of persistent malapposition at follow-up and delayed healing.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00617084 and NCT00934752.