bluuebunny/crossref_metadata_2025 huggingface dataset:
ENTROPY FORM AND THE CONTACT GEOMETRY OF THE MATERIAL POINT MODEL
Authors: DOLFIN M. , FRANCAVIGLIA M. , PRESTON S. , RESTUCCIA L.
Published: February 2012

In this work we investigate a material point model (MP-model) and exploit the geometrical meaning of the "entropy form" introduced by Coleman and Owen. We show that a modification of the thermodynamical phase space (studied and exploited in numerous works) is an appropriate setting for the development of the MP-model in different physical situations. This approach allows to formulate the MP-model and the corresponding entropy form in terms similar to those of homogeneous thermodynamics. Closeness condition of the entropy form is reformulated as the requirement that admissible processes curves belong to the (extended) constitutive surfaces foliating the extended thermodynamical phase space [Formula: see text] of the model over the space X of basic variables. Extended constitutive surfaces ΣS,κ are described as the Legendre submanifolds ΣS of the space [Formula: see text]shifted by the flow of Reeb vector field. This shift is controlled by the entropy production function κ. We determine which contact Hamiltonian dynamical systems ξK are tangent to the surfaces ΣS,κ, introduce conformally Hamiltonian systems μξK where conformal factor μ characterizes the increase of entropy along the trajectories. These considerations are then illustrated by applying them to the Coleman–Owen model of thermoelastic point.
Hydrogen peroxide mediates oxidant-dependent stimulation of arterial smooth muscle L-type calcium channels
Authors: Chaplin Nathan L. , Amberg Gregory C.
Published: February 2012

Changes in calcium and redox homeostasis influence multiple cellular processes. Dysregulation of these signaling modalities is associated with pathology in cardiovascular, neuronal, endocrine, and other physiological systems. Calcium and oxidant signaling mechanisms are frequently inferred to be functionally related. To address and clarify this clinically relevant issue in the vasculature we tested the hypothesis that the ubiquitous reactive oxygen molecule hydrogen peroxide mediates oxidant-dependent stimulation of cerebral arterial smooth muscle L-type calcium channels. Using a combinatorial approach including intact arterial manipulations, electrophysiology, and total internal reflection fluorescence imaging, we found that application of physiological levels of hydrogen peroxide to isolated arterial smooth muscle cells increased localized calcium influx through L-type calcium channels. Similarly, oxidant-dependent stimulation of L-type calcium channels by the vasoconstrictor ANG II was abolished by intracellular application of catalase. Catalase also prevented ANG II from increasing localized subplasmalemmal sites of increased oxidation previously associated with colocalized calcium influx through L-type channels. Furthermore, catalase largely attenuated the contractile response of intact cerebral arterial segments to ANG II. In contrast, enhanced dismutation of superoxide to hydrogen peroxide with SOD had no effect on ANG II-dependent stimulation of L-type calcium channels. From these data we conclude that hydrogen peroxide is important for oxidant-dependent regulation of smooth muscle L-type calcium channels and arterial function. These data also support the emerging concept of hydrogen peroxide as a biologically relevant oxidant second messenger in multiple cell types with a diverse array of physiological functions.
Hormonal responses to extreme fasting in subantarctic fur seal (Arctocephalus tropicalis) pups
Authors: Verrier Delphine , Atkinson Shannon , Guinet Christophe , Groscolas René , Arnould John P. Y.
Published: February 2012

Surviving prolonged fasting implies closely regulated alterations in fuel provisioning to meet metabolic requirements, while preserving homeostasis. Little is known, however, of the endocrine regulations governing such metabolic adaptations in naturally fasting free-ranging animals. The hormonal responses to natural prolonged fasting and how they correlate to the metabolic adaptations observed, were investigated in subantarctic fur seal ( Arctocephalus tropicalis ) pups, which, because of the intermittent pattern of maternal attendance, repeatedly endure exceptionally long fasting episodes throughout their development (1–3 mo). Phase I fasting was characterized by a dramatic decrease in plasma insulin, glucagon, leptin, and total l-thyroxine (T4) associated with reductions in mass-specific resting metabolic rate (RMR), plasma triglycerides, glycerol, and urea-to-creatine ratio, while nonesterified fatty acids (NEFA) and β-OHB increased. In contrast, the metabolic steady-state of phase II fasting reached within 6 days was associated with minimal concentrations of insulin, glucagon, and leptin; unchanged cortisol and triiodothyronine (T3); and moderately increased T4. The early fall in insulin and leptin may mediate the shift to the strategy of energy conservation, protein sparing, and primary reliance on body lipids observed in response to the cessation of feeding. In contrast to the typical mammalian starvation response, nonelevated cortisol and minimal glucagon levels may contribute to body protein preservation and downregulation of catabolic pathways, in general. Furthermore, thyroid hormones may be involved in a process of energy conservation, independent of pups' nutritional state. These original hormonal settings might reflect an adaptation to the otariid repeated fasting pattern and emphasize the crucial importance of a tight physiological control over metabolism to survive extreme energetic constraints.
Cerebral perturbations during exercise in hypoxia
Authors: Verges Samuel , Rupp Thomas , Jubeau Marc , Wuyam Bernard , Esteve François , Levy Patrick , Perrey Stéphane , Millet Guillaume Y.
Published: February 2012

Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O2 delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole body exercise has been reported in hypoxia compared with normoxia, while changes in cerebral perfusion may depend on the brain region, the level of arterial oxygenation and hyperventilation induced alterations in arterial CO2. With the use of transcranial magnetic stimulation, inconsistent changes in cortical excitability have been reported in hypoxia, whereas a greater impairment in maximal voluntary activation following a fatiguing exercise has been suggested when arterial O2 content is reduced. Electromyographic recordings during exercise showed an accelerated rise in central motor drive in hypoxia, probably to compensate for greater muscle contractile fatigue. This accelerated development of muscle fatigue in moderate hypoxia may be responsible for increased inhibitory afferent signals to the central nervous system leading to impaired central drive. In severe hypoxia (arterial O2 saturation <70–75%), cerebral hypoxia per se may become an important contributor to impaired performance and reduced motor drive during prolonged exercise. This review examines the effects of acute and chronic reduction in arterial O2 (and CO2) on cerebral blood flow and cerebral oxygenation, neuronal function, and central drive to the muscles. Direct and indirect influences of arterial deoxygenation on central command are separated. Methodological concerns as well as future research avenues are also considered.
Glycerol uptake is by passive diffusion in the heart but by facilitated transport in RBCs at high glycerol levels in cold acclimated rainbow smelt (Osmerus mordax)
Authors: Clow Kathy A. , Driedzic William R.
Published: February 2012

Rainbow smelt ( Osmerus mordax ) is a small fish that accumulates glycerol at low winter seawater temperatures. In laboratory-held fish, glycerol concentration typically reaches 225 mM in plasma and in all cells. Glycerol uptake by the heart and red blood cells (RBCs) was assessed by tracking [14C(U)]glycerol into the acid-soluble pool. In fish acclimated to 9–10°C a decrease in perfusion/incubation temperature from 8 to 1°C resulted in a decrease in glycerol uptake with a Q10of 3.2 in heart and 2.4 in RBCs. Acclimation to ∼1.5°C did not result in an adaptive enhancement of glycerol uptake as rates were unchanged in heart and RBCs. Glycerol uptake at 1°C was by passive diffusion in heart as evidenced by a linear relationship between glycerol uptake and extracellular glycerol concentration and a lack of inhibition by phloretin. In contrast, in RBCs, glycerol uptake with respect to glycerol concentration showed two linear relationships with a transition point around 50 mM extracellular glycerol. The slope of the second phase was much steeper and eliminated with the inclusion of phloretin. In RBCs from Atlantic salmon ( Salmo salar), a related species that does not accumulate glycerol, glycerol uptake showed only a single linear curve and was not inhibited by phloretin. The data imply a strong facilitated component to glycerol uptake in rainbow smelt RBCs at high glycerol concentrations. We propose this is related to cyclic changes in RBC glycerol content involving a loss of glycerol at the gill and a reaccumulation during passage through the liver.
Receptive field dimensionality increases from the auditory midbrain to cortex
Authors: Atencio Craig A. , Sharpee Tatyana O. , Schreiner Christoph E.
Published: February 2012

In the primary auditory cortex, spectrotemporal receptive fields (STRFs) are composed of multiple independent components that capture the processing of disparate stimulus aspects by any given neuron. The origin of these multidimensional stimulus filters in the central auditory system is unknown. To determine whether multicomponent STRFs emerge prior to the forebrain, we recorded from single neurons in the main obligatory station of the auditory midbrain, the inferior colliculus. By comparing results of different spike-triggered techniques, we found that the neural responses in the inferior colliculus can be accounted for by a single stimulus filter. This was observed for all temporal response patterns, from strongly phasic to tonic. Our results reveal that spectrotemporal stimulus encoding undergoes a fundamental transformation along the auditory neuraxis, with the emergence of multidimensional receptive fields beyond the auditory midbrain.
Impact of Specifically Adsorbing Anions on the Electroless Growth of Gold Nanotubes
Authors: Muench Falk , Neetzel Cornelia , Lauterbach Stefan , Kleebe Hans-Joachim , Ensinger Wolfgang
Published: February 2012

Electroless metal deposition on nanochannel‐containing templates is a versatile route towards metal nanotubes and nanowires if the plating reaction can be sufficiently controlled. In this study, disulfitoaurate‐formaldehyde‐based gold plating baths were modified by the addition of halides, pseudohalides, and EDTA. The introduction of specifically adsorbing anions strongly affected the heterogeneously autocatalyzed plating reaction and allowed the regulation of the reaction rate and the product morphology. The new plating baths showed enhanced stability and allowed the synthesis of homogeneous nanotubes of high aspect ratios (>150) in 30 μm thick ion track‐etched polymer templates. Depending on the reaction conditions, solid and porous structures consisting of gold nanoparticles of differing size and shape were accessible. The presented strategy offers adapted gold thin films, nanotubes, and nanowires for applications in catalysis or sensing.
Design and Construction of a One‐Dimensional DNA Track for an Artificial Molecular Motor
Authors: Kovacic Suzana , Samii Laleh , Woolfson Derek N. , Curmi Paul M. G. , Linke Heiner , Forde Nancy R. , Blab Gerhard A.
Published: February 2012

DNA is a versatile heteropolymer that shows great potential as a building block for a diverse array of nanostructures. We present here a solution to the problem of designing and synthesizing a DNA‐based nanostructure that will serve as the track along which an artificial molecular motor processes. This one‐dimensional DNA track exhibits periodically repeating elements that provide specific binding sites for the molecular motor. Besides these binding elements, additional sequences are necessary to label specific regions within the DNA track and to facilitate track construction. Designing an ideal DNA track sequence presents a particular challenge because of the many variable elements that greatly expand the number of potential sequences from which the ideal sequence must be chosen. In order to find a suitable DNA sequence, we have adapted a genetic algorithm which is well suited for a large but sparse search space. This algorithm readily identifies long DNA sequences that include all the necessary elements to both facilitate DNA track construction and to present appropriate binding sites for the molecular motor. We have successfully experimentally incorporated the sequence identified by the algorithm into a long DNA track meeting the criteria for observation of the molecular motor′s activity.
Study of Stability of Rotational Motion of Spacecraft with Canonical Variables
Authors: Reis Silva William , Zanardi Maria Cecília F. P. S. , Cabette Regina Elaine Santos , Formiga Jorge Kennety Silva
Published: February 2012

This work aims to analyze the stability of the rotational motion of artificial satellites in circular orbit with the influence of gravity gradient torque, using the Andoyer variables. The used method in this paper to analyze stability is the Kovalev‐Savchenko theorem. This method requires the reduction of the Hamiltonian in its normal form up to fourth order by means of canonical transformations around equilibrium points. The coefficients of the normal Hamiltonian are indispensable in the study of nonlinear stability of its equilibrium points according to the three established conditions in the theorem. Some physical and orbital data of real satellites were used in the numerical simulations. In comparison with previous work, the results show a greater number of equilibrium points and an optimization in the algorithm to determine the normal form and stability analysis. The results of this paper can directly contribute in maintaining the attitude of artificial satellites.
On the Computation of Blow‐up Solutions for Semilinear ODEs and Parabolic PDEs
Authors: Dlamini P. G. , Khumalo M.
Published: February 2012

We introduce an adaptive numerical method for computing blow‐up solutions for
ODEs and well‐known reaction‐diffusion equations. The method is based on the
implicit midpoint method and the implicit Euler method. We demonstrate that
the method produces superior results to the adaptive PECE‐implicit method
and the MATLAB solver of comparable order.
Probable Values of Current Solar Cycle Peak
Authors: Silbergleit V. M.
Published: February 2012

An analysis of multiple linear regression method applied to solar cycles 4 to 23 using lagged values of smoothed monthly mean sunspot numbers as independent variables is presented. According to that, the amplitude of current solar cycle 24 is estimated providing a quantitative prediction result. Our adjustment shows that the current cycle would have a sunspot peak less than the biggest one observed during the cycle 19 giving an additional support to the declination in solar activity which is currently happening.
Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis
Authors: Akin E. , Demirezer Bolat A. , Buyukasik S. , Algin O. , Selvi E. , Ersoy O.
Published: February 2012

Objective. The objective of this study was to assess the utility of magnetic resonance enterography (MRE) compared with capsule endoscopy (CE) for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP).Methods. Patients underwent MRE and CE. The polyps were classified according to size of polyp: <5 mm (small size), 5–10 mm (medium size), or >10 mm (large size). The location (jejunum or ileum) and the number of polyps (1–5, 6–20, >20) detected by CE were also assessed. MRE findings were compared with the results of CE.Results. Small-bowel polyps, were detected by CE in 4 of the 6 (66%) patients. Three patients had small-sized polyps and one patient had medium-sized polyps. CE detected polyps in four patients that, were not shown on MRE. Desmoid tumors were detected on anterior abdominal wall by MRE.Conclusion. In patients with FAP, CE can detect small-sized polyps in the small intestine not seen with MRE whereas MRE yields additional extraintestinal information.
Exploitative Competition and Risk of Parasitism in Two Host Ant Species: The Roles of Habitat Complexity, Body Size, and Behavioral Dominance
Authors: Wilkinson Elliot B. , Feener Donald H.
Published: February 2012

Habitat structural complexity can slow resource discovery by ants but can also lower the risk of parasitism during foraging. The relative importance of these two ecological facets of habitat complexity may differ in a species-specific manner and thus may be important in the outcome of exploitative competition over food resources. For the host ant speciesPheidole diversipilosaandP. bicarinata, we used in situ experimental manipulations to explore whether the effects of habitat complexity on exploitative competition depended on host body size and behavioral dominance, two characteristics likely to affect mobility and utilization of refuge from specialist Dipteran parasitoids (Apocephalus orthocladiusandA. pugilist, resp.). We found that habitat complexity affected the resource discovery and harvest components of exploitative competition in an opposing fashion for each species and discuss these results in light of the differences in body size and behavioral dominance between the two hosts.
Matricellular Proteins: A Sticky Affair with Cancers
Authors: Chong Han Chung , Tan Chek Kun , Huang Royston-Luke , Tan Nguan Soon
Published: February 2012

The multistep process of metastasis is a major hallmark of cancer progression involving the cointeraction and coevolution of the tumor and its microenvironment. In the tumor microenvironment, tumor cells and the surrounding stromal cells aberrantly secrete matricellular proteins, which are a family of nonstructural proteins in the extracellular matrix (ECM) that exert regulatory roles via a variety of molecular mechanisms. Matricellular proteins provide signals that support tumorigenic activities characteristic of the metastastic cascade such as epithelial-to-mesenchymal (EMT) transition, angiogenesis, tumor cell motility, proliferation, invasion, evasion from immune surveillance, and survival of anoikis. Herein, we review the current understanding of the following matricellular proteins and highlight their pivotal and multifacted roles in metastatic progression: angiopoietin-like protein 4 (ANGPTL4), CCN family members cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) and CCN6, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC), tenascin C (TNC), and thrombospondin-1 and -2 (TSP1, TSP2). Insights into the signaling mechanisms resulting from the interaction of these matricellular proteins and their respective molecular partner(s), as well as their subsequent contribution to tumor metastasis, are discussed. In addition, emerging evidences of their promising potential as therapeutic options and/or targets in the treatment of cancer are also highlighted.
The Amyloid Precursor Protein Intracellular Domain-Fe65 Multiprotein Complexes: A Challenge to the Amyloid Hypothesis for Alzheimer's Disease?
Authors: Bórquez Daniel A. , González-Billault Christian
Published: February 2012

Since its proposal in 1994, the amyloid cascade hypothesis has prevailed as the mainstream research subject on the molecular mechanisms leading to the Alzheimer's disease (AD). Most of the field had been historically based on the role of the different forms of aggregation ofβ-amyloid peptide (Aβ). However, a soluble intracellular fragment termed amyloid precursor protein (APP) intracellular domain (AICD) is produced in conjunction with Aβfragments. This peptide had been shown to be highly toxic in both culture neurons and transgenic mice models. With the advent of this new toxic fragment, the centerpiece for the ethiology of the disease may be changed. This paper discusses the potential role of multiprotein complexes between the AICD and its adapter protein Fe65 and how this could be a potentially important new agent in the neurodegeneration observed in the AD.
Stem Cell Niche Dynamics: From Homeostasis to Carcinogenesis
Authors: Tieu Kevin S. , Tieu Ryan S. , Martinez-Agosto Julian A. , Sehl Mary E.
Published: February 2012

The stem cell microenvironment is involved in regulating the fate of the stem cell with respect to self-renewal, quiescence, and differentiation. Mathematical models are helpful in understanding how key pathways regulate the dynamics of stem cell maintenance and homeostasis. This tight regulation and maintenance of stem cell number is thought to break down during carcinogenesis. As a result, the stem cell niche has become a novel target of cancer therapeutics. Developing a quantitative understanding of the regulatory pathways that guide stem cell behavior will be vital to understanding how these systems change under conditions of stress, inflammation, and cancer initiation. Predictions from mathematical modeling can be used as a clinical tool to guide therapy design. We present a survey of mathematical models used to study stem cell population dynamics and stem cell niche regulation, both in the hematopoietic system and other tissues. Highlighting the quantitative aspects of stem cell biology, we describe compelling questions that can be addressed with modeling. Finally, we discuss experimental systems, most notablyDrosophila, that can best be used to validate mathematical predictions.
Social Behaviours under Anaerobic Conditions inPseudomonas aeruginosa
Authors: Toyofuku Masanori , Uchiyama Hiroo , Nomura Nobuhiko
Published: February 2012

Pseudomonas aeruginosais well adapted to grow in anaerobic environments in the presence of nitrogen oxides by generating energy through denitrification. Environmental cues, such as oxygen and nitrogen oxide concentrations, are important in regulating the gene expression involved in this process. Recent data indicate thatP. aeruginosaalso employs cell-to-cell communication signals to control the denitrifying activity. The regulation of denitrification by these signalling molecules may control nitric oxide production. Nitric oxide, in turn, functions as a signalling molecule by activating certain regulatory proteins. Moreover, under denitrifying conditions, drastic changes in cell physiology and cell morphology are induced that significantly impact group behaviours, such as biofilm formation.
An Energy Conservation Algorithm for Nonlinear Dynamic Equation
Authors: Pang Jian , Du Yu , Hu Ping , Li Weidong , Ma Z. D.
Published: February 2012

An energy conservation algorithm for numerically solving nonlinear multidegree‐of‐freedom (MDOF) dynamic equations is proposed. Firstly, by Taylor expansion and Duhamel integration, an integral iteration formula for numerically solving the nonlinear problems can be achieved. However, this formula still includes a parameter that is to be determined. Secondly, through some mathematical manipulations, the original dynamical equation can be further converted into an energy conservation equation which can then be used to determine the unknown parameter. Finally, an accurate numerical result for the nonlinear problem is achieved by substituting this parameter into the integral iteration formula. Several examples are used to compare the current method with the well‐known Runge‐Kutta method. They all show that the energy conservation algorithm introduced in this study can eliminate algorithm damping inherent in the Runge‐Kutta algorithm and also has better stability for large integral steps.
Dyskinesias and Treatment with Pramipexole in Patients with Parkinson's Disease
Authors: Piedad John C. P. , Cavanna Andrea E.
Published: February 2012

Dopamine agonists such as pramipexole (PPX) have first been proposed as adjunctive treatment to levodopa (L-DOPA) for patients with Parkinson’s disease (PD) and then as a monotherapy alternative to alleviate dyskinesia. Treatment with PPX has overall been associated with improvement in parkinsonian symptoms. Although the majority of placebo-controlled studies demonstrated that dyskinesia was more prevalent in the PPX compared to the placebo groups, some studies did not detect any dyskinesia as a side effect of this medication. PPX was consistently associated with lower risk for developing dyskinesia compared to L-DOPA. Moreover, the presence of these symptoms in the placebo groups suggests involvement of non-PPX-related factors for developing dyskinesia. It is suggested that future research should aim at ascertaining whether cotherapy with L-DOPA, PPX dosage, and other patient characteristics are contributory factors for the development of PPX-related dyskinesia in patients with PD.
Toxin-Based Targeted Therapy for Malignant Brain Tumors
Authors: Chandramohan Vidyalakshmi , Sampson John H. , Pastan Ira , Bigner Darell D.
Published: February 2012

Despite advances in conventional treatment modalities for malignant brain tumors—surgery, radiotherapy, and chemotherapy—the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages.
The Self-Potential Anomaly Produced by a Subsurface Flow at the Contact of Two Horizontal Layers and Its Quantitative Interpretation
Authors: Skianis Georgios Aim.
Published: February 2012

In the present paper the problem of a polarized cylinder with a small cross-section, which is located at the contact of two horizontal layers with different resistivities, is studied. Such a polarization geometry simulates the self-potential (SP) field produced by a horizontal flow at the contact between the two layers. First, the expression of the self potential at the space domain is derived, applying the image technique. Then, the expression for the Fourier transform of the SP anomaly is found and the behavior of the amplitude spectrum is studied. Based on this study, a direct interpretation method at the spatial frequency domain is proposed, in order to calculate the depth of the flow and the reflection coefficient of the stratified medium. Experimentation with a synthetic model shows that the method works well (small deviations between true and calculated values). When the SP curve contains noise, deviations between calculated and true depths are smaller than those between calculated and true reflection coefficients. The proposed method, which is also applied on SP data from a geothermal system (Mauri et al., 2010), may be useful in detecting underground water or heat flows.
Outcomes of Disconnective Surgery in Intractable Pediatric Hemispheric and Subhemispheric Epilepsy
Authors: Thomas Santhosh George , Chacko Ari George , Thomas Maya Mary , Babu K. Srinivasa , Russell Paul Swamidhas Sudhakar , Daniel Roy Thomas
Published: February 2012

Objectives: To study the outcome of disconnective epilepsy surgery for intractable hemispheric and sub-hemispheric pediatric epilepsy.Methods: A retrospective analysis of the epilepsy surgery database was done in all children (age <18 years) who underwent a peri-insular hemispherotomy (PIH) or a peri-insular posterior quadrantectomy (PIPQ) from April 2000 to March 2011. All patients underwent a detailed pre surgical evaluation. Seizure outcome was assessed by the Engel’s classification and cognitive skills by appropriate measures of intelligence that were repeated annually.Results: There were 34 patients in all. Epilepsy was due to Rasmussen’s encephalitis (RE), Infantile hemiplegia seizure syndrome (IHSS), Hemimegalencephaly (HM), Sturge Weber syndrome (SWS) and due to post encephalitic sequelae (PES). Twenty seven (79.4%) patients underwent PIH and seven (20.6%) underwent PIPQ. The mean follow up was 30.5 months. At the last follow up, 31 (91.1%) were seizure free. The age of seizure onset and etiology of the disease causing epilepsy were predictors of a Class I seizure outcome.Conclusions: There is an excellent seizure outcome following disconnective epilepsy surgery for intractable hemispheric and subhemispheric pediatric epilepsy. An older age of seizure onset, RE, SWS and PES were good predictors of a Class I seizure outcome.
Total Laparoscopic Hysterectomy: Evaluation of an Evidence-Based Educational Strategy Using a Novel Simulated Suture and Knot-Tying Challenge, the “Holiotomy”
Authors: O'Hanlan Katherine A. , Beingesser Kelli R. , Dibble Suzanne L.
Published: February 2012

Objective. The purpose of this study was to evaluate perceptions of skills and practice patterns of gynecologists attending a course on total laparoscopic hysterectomy (TLH). This course employed extensive use of pelvic trainer boxes to accomplish the Holiotomy Challenge. The “Holiotomy Challenge” entailed suturing two plastic pieces with six figure-of-N sutures tied with four square knots each.Methods. A survey was administered before the course and 3 months later. Data were analyzed by pairedt-tests, McNemar’s Chi Squares, and ANCOVAs with significance setP<.05.Results. At baseline, 216 surgeons and at 3 months 102 surgeons returned the survey. Surgeons’ self-perceptions of their skills significantly increased from 6.24 to 7.28. Their reports of their surgical practice at home revealed significantly increased rates of minimally invasive procedures, from 42% to 54%. Significantly more surgeons reported having the ability to close the vagina, or a small cystotomy or enterotomy. Participation in the cadaver lab and presence of their practice partner did not impact these rates.Conclusions. A comprehensive course employing laparoscopic surgical simulation focused on basic surgical skills essential to TLH has a positive impact on attendees' self-rated skill level and rate of laparoscopic approaches. Many had begun performing TLH after the course.
An Innovative High-Tech Acupuncture Product: SXDZ-100 Nerve Muscle Stimulator, Its Theoretical Basis, Design, and Application
Authors: Gao Xinyan , Rong Peijing , Li Liang , He Wei , Ben Hui , Zhu Bing
Published: February 2012

We introduce the theoretical basis, design, and application of a patented innovative high-tech product, SXDZ-100 nerve and muscle stimulator. This product is featured with a built-in chip containing transcoding information from different acupuncture manipulation collected from the wide dynamic neurons (WDR) in the spinal dorsal horn in animal experiments, which is bioinformation feedback therapy. The discharges of WDR neurons excited by different manipulations are analyzed using chaos theory in this study. It combines the advantages of manual acupuncture (MA) like no receptor adaptation and treatment individualization and that of electroacupuncture (EA) such as relatively low stimulation intensity and good quantification and thus makes it more effective than common stimulators in acupuncture clinic.
Total Parathyroidectomy with Presternal Intramuscular Autotransplantation in Renal Patients: A Prospective Study of 66 Patients
Authors: Santos R. O. , Ohe M. N , Carvalho A. B. , Neves M. C. , Kunii I. , Lazaretti-Castro M. , Abrahão M. , Cervantes O. , Vieira J. G. H.
Published: February 2012

Surgical treatment of secondary (SHPT) and tertiary hyperparathyroidism (THPT) may involve various surgical approaches. The aim of this paper was to evaluate presternal intramuscular autotransplantation of parathyroid tissue as a surgical option in SHPT and THPT treatment. 66 patients with renal chronic disease underwent surgery from April 2000 to April 2005 at Universidade Federal São Paulo, Brazil. There were 38 SHPT patients (24 women/14 men), mean age of 39.yrs (range: 14–58), and 28 THPT patients (14 women/14 men), mean age of 43.4 yrs (range: 24–62). Postoperative average followup was 42.9 months (range: 12–96). Postoperative intact PTH increased throughout followup from 73.5 pg/mL to 133 pg/mL on average from 1st to the 5th year, respectively, in SHPT and from 54.9 pg/mL to 94.7 pg/mL on average from 1st to 5th year, respectively, in THPT group. Definitive hypoparathyroidism was observed in 4 (6.06%) patients and graft-dependent recurrence in 6 (9.09%). Presternal intramuscular autotransplantation of parathyroid tissue is a feasible and safe surgical option in SHPT and THPT treatment.
Tailoring of Magnetocaloric Effect in Ni45.5Mn43.0In11.5 Metamagnetic Shape Memory Alloy
Authors: Rosa W. O. , González L. , García J. , Sánchez T. , Vega V. , Escoda Ll. , Suñol J. J. , Santos J. D. , Alves M. J. P. , Sommer R. L. , Prida V. M. , Hernando B.
Published: February 2012

We investigate the direct and inverse magnetocaloric effect in Ni45.5Mn43.0In11.5 Heusler alloy ribbons comparing the results obtained for the as-quenched sample with the ones after different annealing procedures. An enhancement and shift of the entropy maximum to near room temperature is observed in all annealed samples. A remarkable magnetocaloric effect is observed in samples with short-time treatment (10 minutes) and at the lowest annealing temperature. We show that the suppressing of uncompensated martensitic transition and thermal hysteresis are both influenced by the heat treatment. Also, an improvement on Curie’s temperature is observed and, at low magnetic field, it has been risen up to 310 K. Our results demonstrate that the martensitic transformation is highly sensitive to the applied magnetic field and also to the annealing treatment, which means that the magnetocaloric effect can be tuned showing different behaviors for each sample.
One-Pot Template-Free Hydrothermal Synthesis of Monoclinic Hollow Microspheres and Their Enhanced Visible-Light Photocatalytic Activity
Authors: Cheng Bei , Wang Wenguang , Shi Lei , Zhang Jun , Ran Jingrun , Yu Huogen
Published: February 2012

Monoclinic-phase BiVO4hollow microspheres with diameters of about 2–4 μm have been successfully fabricated in high yield by a one-pot template-free hydrothermal route. The reaction duration and urea concentration are shown to play important roles in the formation of the BiVO4hollow microspheres. X-ray diffraction, scanning electron microscopy, nitrogen adsorption-desorption isotherms, fourier transform infrared spectrometry, and UV-visible diffuse reflectance spectroscopy are used to characterize the products. The results show that all the as-prepared BiVO4samples have monoclinic phase structure and exhibit good crystallinity. A formation mechanism for the BiVO4hollow spherical structure via a localized Ostwald ripening is proposed based on the experimental observations. In addition, studies of the photocatalytic properties by exposure to visible light irradiation demonstrate that the as-obtained BiVO4hollow spheres show potential photocatalytic application. Hydroxyl radicals (•OH) are not detected on the surface of visible-light-illuminated BiVO4by the photoluminescence technique, suggesting that•OH is not the dominant photooxidant and photogenerated hole could directly take part in photocatalytic reaction. The prepared BiVO4hollow spheres are also of great interest in pigment, catalysis, separation technology, biomedical engineering, and nanotechnology.
Micellar Liquid Chromatographic Determination of Carbaryl and 1-Naphthol in Water, Soil, and Vegetables
Authors: Chin-Chen Mei-Liang , Rambla-Alegre Maria , Durgbanshi Abhilasha , Bose Devasish , Mourya Sandeep K. , Esteve-Romero Josep , Carda-Broch Samuel
Published: February 2012

A liquid chromatographic procedure has been developed for the determination of carbaryl, a phenyl-N-methylcarbamate, and its main metabolite 1-naphthol, using a C18 column (250’mm’ × ’4.6’mm) with a micellar mobile phase and fluorescence detection at maximum excitation/emission wavelengths of 225/333’nm, respectively. In the optimization step, surfactants sodium dodecyl sulphate (SDS), Brij-35 andN-cetylpyridinium chloride monohydrate, and organic solvents propanol, butanol, and pentanol were considered. The selected mobile phase was 0.15’M SDS-6% (v/v)-pentanol-0.01’M NaH2PO4buffered at pH 3. Validation studies, according to the ICH Tripartite Guideline, included linearity (r>0.999), limit of detection (5 and 18’ng mL-1, for carbaryl and 1-naphthol, resp.), and limit of quantification (15 and 50’ng mL-1, for carbaryl and 1-naphthol, resp.), with intra- and interday precisions below 1%, and robustness parameters below 3%. The results show that the procedure was adequate for the routine analysis of these two compounds in water, soil, and vegetables samples.
Imaging Diagnosis of Interstitial Pneumonia with Emphysema (Combined Pulmonary Fibrosis and Emphysema)
Authors: Sakai Fumikazu , Tominaga Junya , Kaga Akiko , Usui Yutaka , Kanazawa Minoru , Ogura Takashi , Yanagawa Noriyo , Takemura Tamiko
Published: February 2012

Based on clinical and radiological findings, Cottin defined combined pulmonary fibrosis and emphysema (CPFE) as pulmonary emphysema in the upper lungs and interstitial pneumonia in the lower lungs with various radiological patterns. Pathologic findings of CPFE probably corresponded with diffuse interstitial pneumonia with pulmonary emphysema, emphysema with fibrosis, and the combination of both. We described reported radiological findings of CPFE.
Intracellular Tumor-Associated Antigens Represent Effective Targets for Passive Immunotherapy
Authors: Noguchi Takuro , Kato Takuma , Wang Linan , Maeda Yuka , Ikeda Hiroaki , Sato Eiichi , Knuth Alexander , Gnjatic Sacha , Ritter Gerd , Sakaguchi Shimon , Old Lloyd J. , Shiku Hiroshi , Nishikawa Hiroyoshi
Published: February 2012

Monoclonal antibody (mAb) therapy against tumor antigens expressed on the tumor surface is associated with clinical benefit. However, many tumor antigens are intracellular molecules that generally would not be considered suitable targets for mAb therapy. In this study, we provide evidence challenging this view through an investigation of the efficacy of mAb directed against NY-ESO-1, a widely expressed immunogen in human tumors that is expressed intracellularly rather than on the surface of cells. On their own, NY-ESO-1 mAb could neither augment antigen-specific CD8+ T-cell induction nor cause tumor eradication. To facilitate mAb access to intracellular target molecules, we combined anti-NY-ESO-1 mAb with anticancer drugs to accentuate the release of intracellular NY-ESO-1 from dying tumor cells. Strikingly, combination therapy induced a strong antitumor effect that was accompanied by the development of NY-ESO-1–specific effector/memory CD8+ T cells that were not elicited by single treatments alone. The combinatorial effect was also associated with upregulation of maturation markers on dendritic cells, consistent with the organization of an effective antitumor T-cell response. Administration of Fc-depleted F(ab) mAb or combination treatment in Fcγ receptor–deficient host mice abolished the therapeutic effect. Together, our findings show that intracellular tumor antigens can be captured by mAbs and engaged in an efficient induction of CD8+ T-cell responses, greatly expanding the possible use of mAb for passive cancer immunotherapy. Cancer Res; 72(7); 1672–82. ©2012 AACR.
Met Kinase Inhibitor E7050 Reverses Three Different Mechanisms of Hepatocyte Growth Factor–Induced Tyrosine Kinase Inhibitor Resistance in EGFR Mutant Lung Cancer
Authors: Wang Wei , Li Qi , Takeuchi Shinji , Yamada Tadaaki , Koizumi Hitomi , Nakamura Takahiro , Matsumoto Kunio , Mukaida Naofumi , Nishioka Yasuhiko , Sone Saburo , Nakagawa Takayuki , Uenaka Toshimitsu , Yano Seiji
Published: February 2012

Purpose: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer cells by activating Met and the downstream phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, continuous exposure to HGF accelerates the emergence of EGFR-TKI–resistant clones. We assayed whether a new Met kinase inhibitor, E7050, which is currently being evaluated in clinical trials, could overcome these three mechanisms of resistance to EGFR-TKIs.

Experimental Design: The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion and H1975 with an T790M secondary mutation. PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into severe combined immunodeficient mice, and the therapeutic effects of E7050 plus gefitinib were assayed.

Results: E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells.

Conclusions: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF-induced resistance to gefitinib and next-generation EGFR-TKIs. Clin Cancer Res; 18(6); 1663–71. ©2012 AACR.
Statistical Issues and Recommendations for Noninferiority Trials in Oncology: A Systematic Review
Authors: Tanaka Shiro , Kinjo Yousuke , Kataoka Yoshiki , Yoshimura Kenichi , Teramukai Satoshi
Published: February 2012

To provide an overview of noninferiority trials in oncology with a special emphasis on methodologic issues, we conducted a systematic review of randomized trials assessing noninferiority of antineoplastic treatments. We identified 72 articles, of which 65 were randomized phase III trials with a single control arm, 3 were factorial phase III trials, and 4 were randomized phase II trials. Forty-six were trials in lung, colorectal, or breast cancer. The quality of reporting was improved chronologically (P < 0.01); the major deficiencies were claims of noninferiority when the results did not meet statistical criteria for noninferiority (7 articles) or when the noninferiority margin was not prespecified (5 articles). Four trials (6%) presented plans for switching from superiority to noninferiority. The analysis populations were intent to treat (ITT) in 52, per-protocol set (PPS) in 6, and both ITT and PPS in 11 trials. Noninferiority margins were set in 68 trials (94%); 1 trial used both of the conventional and effect retention methods, 17 trials used the conventional method, 5 trials used the effect retention method, and in 45 trials, the method was not specified. Some trials used margins that possibly were larger than the assured effects of the active controls. No trials explicitly took into consideration uncertainty in historical data. Two trials (3%) specified 2 values of margins. Our findings highlight critical deficiencies in design and reporting of noninferiority trials. Seven practical recommendations are presented. Clin Cancer Res; 18(7); 1837–47. ©2012 AACR.
Rationale Behind Targeting Fibroblast Activation Protein–Expressing Carcinoma-Associated Fibroblasts as a Novel Chemotherapeutic Strategy
Authors: Brennen W. Nathaniel , Isaacs John T. , Denmeade Samuel R.
Published: February 2012

The tumor microenvironment has emerged as a novel chemotherapeutic strategy in the treatment of cancer. This is most clearly exemplified by the antiangiogenesis class of compounds. Therapeutic strategies that target fibroblasts within the tumor stroma offer another treatment option. However, despite promising data obtained in preclinical models, such strategies have not been widely used in the clinical setting, largely due to a lack of effective treatments that specifically target this population of cells. The identification of fibroblast activation protein α (FAP) as a target selectively expressed on fibroblasts within the tumor stroma or on carcinoma-associated fibroblasts led to intensive efforts to exploit this novel cellular target for clinical benefit. FAP is a membrane-bound serine protease of the prolyl oligopeptidase family with unique post-prolyl endopeptidase activity. Until recently, the majority of FAP-based therapeutic approaches focused on the development of small-molecule inhibitors of enzymatic activity. Evidence suggests, however, that FAP's pathophysiological role in carcinogenesis may be highly contextual, depending on both the exact nature of the tumor microenvironment present and the cancer type in question to determine its tumor-promoting or tumor-suppressing phenotype. As an alternative strategy, we are taking advantage of FAP's restricted expression and unique substrate preferences to develop a FAP-activated prodrug to target the activation of a cytotoxic compound within the tumor stroma. Of note, this strategy would be effective independently of FAP's role in tumor progression because its therapeutic benefit would rely on FAP's localization and activity within the tumor microenvironment rather than strictly on inhibition of its function. Mol Cancer Ther; 11(2); 257–66. ©2012 AACR.
β-arrestin-1 participates in thrombosis and regulates integrin αIIbβ3 signalling without affecting P2Y receptors desensitisation and function
Authors: Schaff Mathieu , Receveur Nicolas , Bourdon Catherine , Ohlmann Philippe , Lanza François , Gachet Christian , Mangin Pierre
Published: February 2012

β-arrestin-1 (β-arr1) and β-arrestin-2 (β-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of β-arr1 or β-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in β-arr1−/− and β-arr2−/− platelets. In addition, deficiency in β-arr1 or β-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between β-arr1 and β-arr2 may explain these unchanged platelet responses. Interestingly, β-arr1−/− but not β-arr2−/− mice were protected against laser- and FeCl3-induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in β-arr1−/− and β-arr2−/− mice, suggesting no defect in haemostasis. β-arr1−/− platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 ± 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin αIIbβ3. β-arr1 appeared to be located downstream of Src family kinases and to regulate αIIbβ3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for β-arr1 in promoting thrombus formation, in part through its participation in αIIbβ3 signalling, and no role of β-arr1 and β-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation.