bluuebunny/crossref_metadata_2025 huggingface dataset:
A practical guide to the differential diagnosis of tremor
Authors: Alty Jane E , Kempster Peter A
Published: June 2011

Tremor is, by definition, a rhythmic oscillation of a body part. It is the most prevalent movement disorder in clinical medicine, so doctors working in many specialities and in general practice can expect to encounter it. Most tremors can be classified on the basis of four observable clinical characteristics: anatomical pattern; the relative prominence of the tremor at rest, on maintaining a posture, and with action; tremor frequency; and tremor amplitude. A resting tremor suggests Parkinson’s disease, and the diagnosis then depends on a judgement about whether the patient has other signs of parkinsonism. The most common causes of postural tremor are physiological tremor, essential tremor and drug-induced tremor. The differential diagnosis may also include dystonic tremor and psychogenic tremor, while metabolic tremor caused by thyrotoxicosis should be considered in any recent-onset postural tremor. Wilson’s disease and fragile X-associated tremor/ataxia syndrome are rarer conditions that may present with tremor and are very important to identify. There is a small but genuine diagnostic grey zone between Parkinson’s disease and more benign tremor disorders such as essential tremor and dystonic tremor, in which resting and postural tremor coexist with mild or equivocal non-tremor parkinsonian signs. The authors review clinical features and investigational techniques that may help to discriminate this group of hard-to-classify tremors.
ASYMPTOTICALLY VANISHING COSMOLOGICAL CONSTANT IN THE MULTIVERSE
Authors: KAWAI HIKARU , OKADA TAKASHI
Published: June 2011

We study the problem of the cosmological constant in the context of the multiverse in Lorentzian space–time, and show that the cosmological constant will vanish in the future. This sort of argument was started by Sidney Coleman in 1989, and he argued that the Euclidean wormholes make the multiverse partition function a superposition of various values of the cosmological constant Λ, which has a sharp peak at Λ = 0. However, the implication of the Euclidean analysis to our Lorentzian space–time is unclear. With this motivation, we analyze the quantum state of the multiverse in Lorentzian space–time by the WKB method, and calculate the density matrix of our universe by tracing out the other universes. Our result predicts vanishing cosmological constant. While Coleman obtained the enhancement at Λ = 0 through the action itself, in our Lorentzian analysis the similar enhancement arises from the front factor of eiS in the universe wave function, which is in the next leading order in the WKB approximation.
PREPARATIONS OF ZINC OXIDES AND CHARACTERIZATION OF THE PHOTOVOLTAIC BEHAVIOR USING A SCANNING KELVIN PROBE
Authors: HE Y. , ZHI W. , ZHOU B. O.
Published: June 2011

Surface photovoltage of semiconductors depend strongly on their electronic structures, in particular, their Fermi energy level. This offers a possibility to characterize photoelectronic behavior using the Kelvin probe structure by measurements of work function (WF). In this paper, ZnO films were prepared using the CVD method and their microstructures and morphology were characterized using the XRD and SEM. Furthermore, photovoltage evolution and WF of selected ZnO samples were measured using a scanning Kelvin probe (SKP) system. It is found that the surface photovoltage and its time-resolved evolution process as well as the energy level structure of ZnO films can be correlated to WF very well. The present study therefore provides a simple and practical methodology for the characterization of photovoltaic behavior of semiconductor films.
PREPARATION OF GRADATED NANO-TRANSIENT LAYER AT INTERFACE BETWEEN DEPOSITED FILM AND SUBSTRATE BY HIGH-INTENSITY PULSED ION BEAM IRRADIATION
Authors: LIANG JIACHANG , ZHANG LIPING , WANG ZHIPING , CHEN YIFEI , JI CHAOHUI , ZHANG YANYAN , ZHANG PENG , ZHANG XUEYANG , XU JIANXING , CHEN YUE , HU XUELAN , JIANG LIHUI , LE XIAOYUN , RONG CUIHUA , LEI MINGKAI , XIN JINGPING
Published: June 2011

We prepared gradated nano-transient layers at different interfaces between deposited film and substrates by high-intensity pulsed ion beam (HIPIB) irradiation. The deposited film was ( Al–Si ) alloy and substrates were Ni and Ti , respectively. The gradated nano-transient layers at different interfaces were measured by Rutherford backscattering, its spectra were solved by SIMNRA code and then the microstructures of the gradated nano-transient layers at the interfaces of these two irradiated samples were obtained. The experimental results were analyzed by STEIPIB code. The formation of the gradated distribution of element contents in nano-transient layer at the interface can eliminate the abrupt changes of thermal and elastic characteristics at the interface. And, it can greatly reduce the mismatch of thermal expansion coefficients and Young's modulus at the interface between deposited film and substrate. Thus, after the formation of the gradated nano-transient layer, the adhesion at the interface between different materials can be enhanced and the level of thermal stresses can also be reduced in the case of thermal loading.
MORPHOLOGICALLY CONTROLLED SYNTHESIS OF Au NANOCRYSTALS
Authors: SU FENFANG , PAN LIKUN , ZHENG YAN , SUN ZHUO
Published: June 2011

In this work, a convenient and efficient procedure to control the morphologies of Au nanocrystals has been reported. The Au nanospheres are generated in polyvinyl-pyrrolidone/ethanol glycol system through a thermal chemical method. However, by adding a small amount of K2CO3 which influences the growth rate of various facets during the crystal growth, Au nanoplates with broad surface plasmon resonance band in 500–800 nm can be obtained.
EVALUATING COUPLING OF ADSORBED MOLECULES TO THEIR ENVIRONMENT IN SCANNING TUNNELING MICROSCOPY
Authors: GRADO-CAFFARO M. A. , GRADO-CAFFARO M.
Published: June 2011

We present a new theoretical approach to determine the interaction energy due to the coupling of adsorbed molecules to their environment in scanning tunneling microscopy. In fact, the above coupling energy is estimated by assuming the involved adsorbed molecules as Morse oscillators and their environment (electrodes, leads) as external reservoir.
BURGERS EQUATION AND KOLMOGOROV–PETROVSKY–PISKUNOV EQUATION ON MANIFOLDS
Authors: MATSKEVICH S. E.
Published: June 2011

In this paper the analogue of the Hopf–Cole transformation is introduced for manifolds. It has been shown that under certain conditions this transformation connects the Burgers equation and Kolmogorov–Petrovsky–Piskunov equation on pseudo-Riemannian manifolds.
HARNACK INEQUALITIES AND APPLICATIONS FOR MULTIVALUED STOCHASTIC EVOLUTION EQUATIONS
Authors: OUYANG SHUN-XIANG
Published: June 2011

By the method of coupling and Girsanov transformation, Harnack inequalities (F.-Y. Wang, 1997) and strong Feller property are proved for the transition semigroup associated with the multivalued stochastic evolution equation on a Gelfand triple. The concentration property of the invariant measure for the semigroup is investigated. As applications of Harnack inequalities, explicit upper bounds of the Lp-norm of the density, contractivity, compactness and entropy-cost inequality for the semigroup are also presented.
GROUND STATE OF THE YUKAWA MODEL WITH CUTOFFS
Authors: TAKAESU TOSHIMITSU
Published: June 2011

The ground state of the Yukawa model is considered. The Yukawa model describes the system of a Dirac field interacting with a Klein–Gordon field. By introducing ultraviolet cutoffs and spatial cutoffs, the total Hamiltonian is defined as a self-adjoint operator on a boson–fermion Fock space. It is shown that the total Hamiltonian has a positive spectral gap for all values of coupling constants. In particular, the existence of the ground state is proven.
ON STOCHASTIC GENERALIZED FUNCTIONS
Authors: CATUOGNO PEDRO , OLIVERA CHRISTIAN
Published: June 2011

In this work we introduce a new algebra of stochastic generalized functions. The regular Hida distributions in [Formula: see text] are embedded in this algebra via their chaos expansions. As an application, we prove the existence and uniqueness of the solution of a stochastic Cauchy problem involving singularities.
ANALYTIC INVESTIGATIONS OF THE WALSH FUNCTIONS COMBINED WITH THE SUMUDU TRANSFORM AND APPLICATIONS TO THE TRANSPORT EQUATION
Authors: Abdelouahab Kadem
Published: June 2011

We develop spectral approximation for solving the three-dimensional transport equation with isotropic scattering in a bounded domain. The method can be extended easily to general linear transport problem in a unbounded domain or semi infinite domain. The technique used involves the reduction of the three-dimensional equation to a system of one-dimensional equations. The idea of using the spectral method for searching solutions to the multi-dimensional transport problems, leads us to a solution for all values of the independent variables.
THE BANACH-LIE *-ALGEBRA OF MULTIPLICATION OPERATORS ON A W*-ALGEBRA
Authors: Alqurashi Maysaa , Altwaijry Najla A. , Edwards C. Martin , Hoskin Christopher S.
Published: June 2011

The hermitian part [Formula: see text] of the Banach-Lie *-algebra [Formula: see text] of multiplication operators on the W *-algebra A is a unital GM-space, the base of the dual cone in the dual GL-space [Formula: see text] of which is affine isomorphic and weak*-homeomorphic to the state space of [Formula: see text]. It is shown that there exists a Lie *-isomorphism ϕ from the quotient (A ⊕∞ Aop)/K of an enveloping W *-algebra A ⊕∞ Aop of A by a weak*-closed Lie *-ideal K onto [Formula: see text], the restriction to the hermitian part ((A ⊕∞ Aop)/K)h of which is a bi-positive real linear isometry, thereby giving a characterization of the state space of [Formula: see text]. In the special case in which A is a W *-factor this leads to a further identification of the state space of [Formula: see text] in terms of the state space of A. For any W *-algebra A, the Banach-Lie *-algebra [Formula: see text] coincides with the set of generalized derivations of A, and, as an application, a formula is obtained for the norm of an element of [Formula: see text] in terms of a centre-valued 'norm' on A, which is similar to that previously obtained by non-order-theoretic methods.
THE COMPUTATIONAL EFFICIENCY OF WALSH APPROXIMATION FOR TWO-DIMENSIONAL VOLTERRA INTEGRAL EQUATIONS
Authors: Anderyance S. , Hadizadeh M.
Published: June 2011

In this research, we give details of a new numerical method for the approximate solution of a general two-dimensional Volterra integral equation, using the discontinuous wavelet packets e.g. Walsh functions. The double Walsh approximation we have adopted utilizes a simple robust numerical scheme for approximate solution of the equations. The two-dimensional operational matrix of integration for each subinterval [Formula: see text] is explicitly constructed, where m is a power of 2. Finally the reliability and efficiency of the proposed scheme are demonstrated by some numerical results.
WEAK CONVERGENCE OF AN IMPLICIT ITERATIVE PROCESS WITH ERRORS FOR AN ASYMPTOTICALLY QUASI I-NONEXPANSIVE MAPPING IN BANACH SPACES
Authors: Mukhamedov Farrukh , Saburov Mansoor
Published: June 2011

In this paper we prove the weak convergence of the implicit iterative process with errors to a common fixed point of an asymptotically quasi I-nonexpansive mapping T and an asymptotically quasi-nonexpansive mapping I in Banach spaces.
GLOBAL STABILITY OF AN HIV/AIDS MODEL WITH STOCHASTIC PERTURBATION
Authors: Yang Junyuan , Wang Xiaoyan , Li Xuezhi
Published: June 2011

In this paper, we investigate the dynamic behavior of an HIV model with stochastic perturbation. Firstly, in ODE model, the disease-free equilibrium E0 is globally asymptotically stable if the basic reproductive number R0 < 1. When R0 > 1, the endemic equilibrium E* is globally asymptotically stable. Secondly, the criterion for robustness of the system is established under stochastic perturbations. The conditions of stochastic stability of the endemic equilibrium E* are obtained. Finally, we simulate our analytical results.
SEMILATTICES OF SUBDIMONOIDS
Authors: Zhuchok Anatolii V.
Published: June 2011

We present some congruence on the dimonoid with an idempotent operation and use it to obtain semilattice decompositions of an idempotent dimonoid. Also we give necessary and sufficient conditions under which an arbitrary dimonoid is a semilattice of archimedean subdimonoids.
DESIGN AND VALIDATION OF A MODEL FOR A HUMAN'S FUNCTIONAL STATE AND PERFORMANCE
Authors: BOSSE TIBOR , BOTH FIEMKE , HOOGENDOORN MARK , JAFFRY S. WAQAR , LAMBALGEN RIANNE VAN , OORBURG ROGIER , SHARPANSKYKH ALEXEI , TREUR JAN , DE VOS MICHAEL
Published: June 2011

This paper presents a computational model of the dynamics of a human's functional state in relation to task performance and environment. It can be used in intelligent systems that support humans in demanding circumstances. The model takes task demand and situational aspects as input and calculates internal factors related to human functioning, such as the experienced pressure, exhaustion, and motivation, and how they affect performance. Simulation experiments under different parameter settings pointed out that the model is able to produce realistic behavior of humans with different types of personalities. Moreover, by a mathematical analysis the equilibria of the model have been determined, and by automated checking a number of expected properties of the model have been confirmed. In addition to this "internal" validation of the model, an experiment has been designed for the purpose of external validation, addressing the estimation of aspects of the human process that are relevant for its practical application. Output from the experiment, like information about personality characteristics and performance quality, has been used to perform estimation of the parameters of the model. By the parameter estimation, a set of parameter values has been identified by which an adequate representation of a person's functional state when performing a task is achieved.
On optimal multidimensional mechanism design
Authors: Cai Yang , Daskalakis Constantinos , Weinberg S. Matthew
Published: June 2011

We solve the
optimal multi-dimensional mechanism design problem
when either the number of bidders is a constant or the number of items is a constant. In the first setting, we need that the values of each bidder for the items are i.i.d., but allow different distributions for each bidder. In the second setting, we allow the values of each bidder for the items to be arbitrarily correlated, but assume that the bidders are i.i.d. For all ε > 0, we obtain an efficient additive ε-approximation, when the value distributions are bounded, or a multiplicative (1--ε)-approximation when the value distributions are unbounded, but satisfy the Monotone Hazard Rate condition. When there is a single bidder, we generalize these results to independent but not necessarily identically distributed value distributions, and to independent regular distributions.
Online algorithms with stochastic input
Authors: Devanur Nikhil R.
Published: June 2011

The design and analysis of
online
algorithms, where the input to the algorithm is revealed over time and the algorithm has to make decisions immediately without knowing the future input, has received a revived interest in the last few years primarily due to their application to online advertising. The canonical problem is the
Adwords
problem, which is motivated by the problem of optimally allocating ad slots on search queries to budget constrained advertisers. It involves simplifications that ignore certain aspects of the actual way this allocation is done. For instance, it assumes a "first-price" pay-per-impression scheme, ignoring the game theoretic aspects, and considers only one slot per query. To be precise, the Adwords problem is as follows.
Review: 'A New Culture of Learning' by Douglas Thomas and John Seely Brown
Authors: Silvers Aaron
Published: June 2011

Many organizations are focused on creating a world that Douglas Thomas and John Seely Brown describe in "A New Culture of Learning," a world that is constantly changing. It's worth it to you to have a picture in your mind's eye of what will be mainstream learning over the next 30 years.
Learning Solutions Conference 2011
Authors: Parish Tracy
Published: June 2011

The 2011 Learning Solutions Conference brought out more than 1000 attendees and engaged countless others, who were unable to attend, thanks to social media. Using the hashtag #ls2011, users populated the Twitter backchannel with live updates from the conference. Thus providing access to sessions dedicated to all things learning.
Nelson Croom's e-Learning Crusade
Authors: Little Bob
Published: June 2011

We seem to be entering a new era in e-learning content creation. Immediacy and expediency, not instructional design fidelity, are the new watchwords. Elearning today is really only about addressing "remembering and understanding."
Role of SPECT and SPECT/CT in the Surgical Treatment of Primary Hyperparathyroidism
Authors: Taubman Michele L. , Goldfarb Melanie , Lew John I.
Published: June 2011

Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient population. This condition is usually the result of a single hyperfunctioning parathyroid gland. Targeted parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) through a small cervical incision has replaced traditional bilateral neck exploration (BNE) as the initial approach in the surgical treatment of primary hyperparathyroidism at many medical centers worldwide. Preoperative sestamibi-technetium 99m scintigraphy serves as an important prerequisite for successful targeted parathyroidectomy. Single-photon emission computed tomography (SPECT) and CT fusion, however, is a recent imaging technique that provides a three-dimensional functional image with advanced contrast resolution to greatly improve preoperative localization of parathyroid tumors.
Metastasis Update: Human Prostate Carcinoma Invasion via Tubulogenesis
Authors: Nagle Raymond B. , Cress Anne E.
Published: June 2011

This paper proposes that human prostate carcinoma primarily invades as a cohesive cell collective through a mechanism similar to embryonic tubulogenesis, instead of the popular epithelial-mesenchymal transformation (EMT) model. Evidence supporting a tubulogenesis model is presented, along with suggestions for additional research. Additionally, observations documenting cell adhesion molecule changes in tissue and stromal components are reviewed, allowing for comparisons between the current branching morphogenesis models and the tubulogenesis model. Finally, the implications of this model on prevailing views of therapeutic and diagnostic strategies for aggressive prostatic disease are considered.
Herpes Simplex Virus Type‐1 (HSV‐1) Entry into Human Mesenchymal Stem Cells Is Heavily Dependent on Heparan Sulfate
Authors: Choudhary Samiksha , Marquez Maribel , Alencastro Frances , Spors Frank , Zhao Yuanxiang , Tiwari Vaibhav
Published: June 2011

Hematopoietic stem cells recipients remain susceptible to opportunistic viral infections including herpes simplex virus type‐1 (HSV‐1). The purpose of this investigation was to analyze susceptibility of human mesenchymal stem cells (hMSCs) to HSV‐1 infection and identify the major entry receptor. Productive virus infection in hMSCs was confirmed by replication and plaque formation assays using a syncytial HSV‐1 KOS (804) virus. To examine the significance of entry receptors, RT‐PCR and antibody‐blocking assays were performed. RT‐PCR data showed the expression of gD receptors: nectin‐1, 3‐O sulfotransferase‐3 (3‐OST‐3), and HVEM. Antibody‐blocking assay together with heparinase treatment suggested an important role for HS and 3‐O‐sulfated heparan sulfate (3‐OS HS), but not nectin‐1 or HVEM, in mediating HSV‐1 entry and spread in hMSCs. Taken together, our results provide strong evidence demonstrating that HSV‐1 is capable of infecting hMSCs and HS and 3‐OS HS serve as its entry receptors during this process.
Tuberculosis: New Aspects of an Old Disease
Authors: Jordao Luisa , Vieira Otilia V.
Published: June 2011

Tuberculosis is an ancient infectious disease that remains a threat for public health around the world. Although the etiological agent as well as tuberculosis pathogenesis is well known, the molecular mechanisms underlying the host defense to the bacilli remain elusive. In this paper we focus on the innate immunity of this disease reviewing well-established and consensual mechanisms likeMycobacterium tuberculosisinterference with phagosome maturation, less consensual mechanism like nitric oxide production, and new mechanisms, such as mycobacteria translocation to the cytosol, autophagy, and apoptosis/necrosis proposed mainly during the last decade.
Solutions of a Class of Deviated‐Advanced Nonlocal Problems for the Differential Inclusion x1(t) ∈ F(t, x(t))
Authors: El-Sayed A. M. A. , Hamdallah E. M. , Elkadeky Kh. W.
Published: June 2011

We study the existence of solutions for deviated‐advanced nonlocal and integral condition problems for the differential inclusion x1(t) ∈ F(t, x(t)).
Neighborhood Urban Environmental Quality Conditions Are Likely to Drive Malaria and Diarrhea Mortality in Accra, Ghana
Authors: Fobil Julius N. , Kraemer Alexander , Meyer Christian G. , May Juergen
Published: June 2011

Background. Urbanization is a process which alters the structure and function of urban environments. The alteration in the quality of urban environmental conditions has significant implications for health. This applies both to the ecology of insect vectors that may transmit diseases and the burden of disease.Study Objectives. To investigate the relationship between malaria and infectious diarrhea mortality and spatially varied neighborhood environmental quality conditions in a low-income economy.Design. A one time point spatial analysis of cluster-level environmental conditions and mortality data using principal component analysis (PCA), one-way analysis of variance (ANOVA) and generalized linear models (GLMs).Methods. Environmental variables were extracted from the Ghana Census 2000 database while mortality data were obtained from the Ghana Births and Deaths Registry in Accra over the period 1998–2002.Results. Whereas there was a strong evidence of a difference in relative mortality of malaria across urban environmental zones of differing neighborhood environmental conditions, no such evidence of mortality differentials was observed for diarrhea. In addition, whereas bivariate analyses showed a weak to strong evidence of association between the environmental variables and malaria mortality, no evidence of association was found between diarrhea mortality and environmental variables.Conclusion. We conclude that environmental management initiatives intended for infectious disease control might substantially reduce the risk of urban malaria mortality and to a less extent that for urban diarrhea mortality in rapidly urbanizing areas in a low-income setting.
Spin Polarized Transport in an AC-Driven Quantum Curved Nanowire
Authors: Zein Walid A. , Ibrahim Nabil A. , Phillips Adel H.
Published: June 2011

Using the effective-mass approximation method, and Floquet theory, we study the spin transport characteristics through a curved quantum nanowire. The spin polarization, P, and the tunneling magnetoresistance, TMR, are deduced under the effect of microwave and infrared radiations of wide range of frequencies. The results show an oscillatory behavior of both the spin polarization and the tunneling magnetoresistance. This is due to Fano-type resonance and the interplay between the strength of spin-orbit coupling and the photons in the subbands of the one-dimensional nanowire. The present results show that this investigation is very important, and the present device might be used to be a sensor for small strain in semiconductor nanostructures and photodetector.
Boundary‐Value Problems for Weakly Nonlinear Delay Differential Systems
Authors: Boichuk A. , Diblík J. , Khusainov D. , Růžičková M.
Published: June 2011

Conditions are derived of the existence of solutions of nonlinear boundary‐value problems for systems of n ordinary differential equations with constant coefficients and single delay (in the linear part) and with a finite number of measurable delays of argument in nonlinearity: , assuming that these solutions satisfy the initial and boundary conditions z(s): = ψ(s) if s∉[a, b], ℓz(·) = α ∈ ℝm. The use of a delayed matrix exponential and a method of pseudoinverse by Moore‐Penrose matrices led to an explicit and analytical form of sufficient conditions for the existence of solutions in a given space and, moreover, to the construction of an iterative process for finding the solutions of such problems in a general case when the number of boundary conditions (defined by a linear vector functional ℓ) does not coincide with the number of unknowns in the differential system with a single delay.
Necrotizing Periodontal Diseases in a Semirural District of South Africa
Authors: Wood Neil Hamilton , Blignaut Elaine , Lemmer Johan , Meyerov Robin , Feller Liviu
Published: June 2011

Objectives. The aim of this study was to characterize the lesions of necrotizing gingivitis (NG) and necrotizing periodontitis (NP) with regard to extent and severity, and to correlate these parameters with the host HIV serostatus, CD4+ T-cell count, neutrophil count, age, and gender.Methods. Eighty-four consecutive patients, 39 black females and 45 black males aged 20–46 years, diagnosed with NG/NP were recruited to the study over a period of two years.Results. For both HIV-seropositive and -seronegative patients, the mandibular anterior gingiva was most frequently affected; 74% had NG/NP affecting ≥5 gingival tooth sites. Ninety percent of all patients had a mean severity of ≤4 mm. There was no statistically significant association between either extent or severity of NG/NP and HIV serostatus, CD4+ T-cell count, neutrophil count, age, or gender. The difference between the number of HIV-seropositive patients with NG/NP who had CD4+ T-cell counts ≤200 cells/mm3and those who had CD4+ T cell counts of 201–499 cells/mm3was not statistically significant.Conclusion. The clinical signs of NG/NP are similar in HIV-seropositive and -seronegative patients, and are not related to CD4+ T-cell count, to neutrophil count, to gender, or to age.
Triple-Negative Breast Cancer: Adjuvant Therapeutic Options
Authors: Gucalp Ayca , Traina Tiffany A.
Published: June 2011

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.
Differential Subordinations for Certain Meromorphically Multivalent Functions Defined by Dziok‐Srivastava Operator
Authors: Yang Ying , Tao Yu-Qin , Liu Jin-Lin
Published: June 2011

By making use of the Dziok‐Srivastava operator, we introduce a new class of meromorphically multivalent functions. Some inclusion properties of functions belonging to this class are derived.
Intermittent High Glucose Enhances Apoptosis in INS-1 Cells
Authors: Shi Xiao-li , Ren Yue-zhong , Wu Jing
Published: June 2011

To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducingβ-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5 mmol/L), SHG (33.3 mmol/L), and IHG (5.5 mmol/L and 33.3 mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious toβ-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.
Comparison of Cell Proliferation, Protein, and Glucose Metabolism in Musculoskeletal Tumors in a PET Study
Authors: Tian Mei , Zhang Hong , Endo Keigo
Published: June 2011

11C‐choline and 18F‐FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of 11C‐Choline and 18F‐FAMT PET in diagnosis of musculoskeletal tumors in thirty‐six patients in comparison of 18F‐FDG PET. 11C‐Choline and 18F‐FDG PET were positive in all the malignant tumors (n=13), whereas 18F‐FAMT was positive in 11 tumors. The mean SUVs for malignant tumors were significantly higher than those for benign lesions in all three tracers imaging. A moderate correlation was found between 11C‐Choline and 18F‐FDG (r=0.540, P < .05), or 18F‐FAMT and FDG (r=0.596, P < .05). The diagnostic sensitivity and specificity for malignancy were 91.7% and 71.4%, respectively, using 11C‐choline with a SUV cut‐off of 2.69. The sensitivity and specificity of 18F‐FAMT for malignancy were 66.7% and 85.7%, respectively, using a SUV cut‐off of 1.26. For 18F‐FDG, using a SUV cut‐off of 2.77, the sensitivity and specificity were 83.3% and 71.4%, respectively. According to ROC analysis, the ROC curves for 11C‐Choline, 18F‐FAMT, and 18F‐FDG were 0.855, 0.734, and 0.847, respectively. 11C‐Choline PET is superior in the visualization of musculoskeletal tumors with high contrast imaging, whereas the combination of 18F‐FAMT and 18F‐FDG PET provides valuable information for the preoperative planning in patients with musculoskeletal tumors.
Social Capital and International Migration from Latin America
Authors: Massey Douglas S. , Aysa-Lastra María
Published: June 2011

We combine data from the Latin American Migration Project and the Mexican Migration Project to estimate models predicting the likelihood of taking of first and later trips to the United States from five nations: Mexico, the Dominican Republic, Costa Rica, Nicaragua, and Peru. The models test specific hypotheses about the effects of social capital on international migration and how these effects vary with respect to contextual factors. Our findings confirm the ubiquity of migrant networks and the universality of social capital effects throughout Latin America. They also reveal how the sizes of these effects are not uniform across settings. Social capital operates more powerfully on first as opposed to later trips and interacts with the cost of migration. In addition, effects are somewhat different when considering individual social capital (measuring strong ties) and community social capital (measuring weak ties). On first trips, the effect of strong ties in promoting migration increases with distance whereas the effect of weak ties decreases with distance. On later trips, the direction of effects for both individual and community social capital is negative for long distances but positive for short distances.
Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases
Authors: Bartoli M. L. , Novelli F. , Costa F. , Malagrinò L. , Melosini L. , Bacci E. , Cianchetti S. , Dente F. L. , Di Franco A. , Vagaggini B. , Paggiaro P. L.
Published: June 2011

Background. Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary oxidative stress biomarkers such as malondialdehyde (MDA).Subjects and Methods. We measured MDA levels in EBC in a large number of patients (N=194) with respiratory diseases: asthma (N=64), bronchiectasis (BE,N=19), chronic obstructive pulmonary disease (COPD,N=73), idiopathic pulmonary fibrosis (IPF,N=38). Fourteen healthy nonsmoking subjects were included as controls.Results. Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV1% (rho: −0.24,P<.05).Conclusions. EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV1reduction.
Targeting Nuclear Hormone Receptors: PPARαAgonists as Potential Disease-Modifying Drugs for Rheumatoid Arthritis
Authors: Shirinsky Ivan V. , Shirinsky Valery S.
Published: June 2011

In recent years, peroxisome proliferator-activated receptors (PPARs) have received growing interest due to the broad spectrum of their biological activities. PPARα, an isoform of PPAR, plays an important role in lipid homeostasis and inflammation, which makes it a potential target for the treatment of chronic inflammatory disorders, including RA. This paper reviews studies on the properties of PPARαagonists which may be pertinent to the treatment of RA. These properties include effects on lipid metabolism, inflammation, and angiogenesis, as well as interference with glucocorticoid effects, and a potential role in gender dimorphism of autoimmune disorders. However, current clinical experience with this class of drugs in RA is limited. New studies are needed to elucidate whether PPARαagonism may be an effective treatment strategy for RA patients.
PM02734 (Elisidepsin) Induces Caspase-Independent Cell Death Associated with Features of Autophagy, Inhibition of the Akt/mTOR Signaling Pathway, and Activation of Death-Associated Protein Kinase
Authors: Ling Yi-He , Aracil Miguel , Zou Yiyu , Yuan Ziqiang , Lu Bo , Jimeno José , Cuervo Ana Maria , Perez-Soler Roman
Published: June 2011

Purpose: PM02734 (elisidepsin) is a synthetic marine-derived cyclic peptide of the kahalalide family currently in phase II clinical development. The mechanisms of cell death induced by PM02734 remain unknown.

Experimental Design: Human non–small-cell lung cancer (NSCLC) cell lines H322 and A549 were used to evaluate PM02734-induced cytotoxicity, apoptosis, and autophagy, as well as effects on cell death–related signaling pathways.

Results: PM02734 at clinically achievable concentrations (0.5–1 μmol/L) was cytotoxic to H322 and A549 cells but did not cause nuclear fragmentation, PARP cleavage, or caspase activation, suggesting that classical apoptosis is not its main mechanism of cell death. In contrast, PM02734-induced cell death was associated with several characteristics of autophagy, including an increase in acidic vesicular organelle content, levels of GFP-LC3–positive puncta, elevation of the levels of Atg-5/12 and LC3-II, and an associated compromise of the autophagic flux resulting in increased number of autophagosomes and/or autolysosomes. Cotreatment with 3-methyladenine (3-MA) and downregulation of Atg-5 gene expression by siRNA partially inhibited PM02734-induced cell death. PM02734 caused inhibition of Akt/mTOR signaling pathways and cotreatment with the Akt inhibitor wortmannin or with the mTOR inhibitor rapamycin led to a significant increase in PM02734-induced cell death. Furthermore, PM02734 caused the activation of death-associated protein kinase (DAPK) by dephosphorylation at Ser308, and downregulation of DAPK expression with siRNA caused also a partial but significant reduction of PM02734-induced cell death. In vivo, PM02734 significantly inhibited subcutaneous A549 tumor growth in nude mice (P < 0.05) in association with induction of autophagy.

Conclusions: Our data indicate that PM02734 causes cell death by a complex mechanism that involves increased autophagosome content, due for the most part to impairment of autophagic flux, inhibition of the Akt/mTOR pathway, and activation of DAPK. This unique mechanism of action justifies the continued development of this agent for the treatment of NSCLC. Clin Cancer Res; 17(16); 5353–66. ©2011 AACR.
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study
Authors: DuBois Steven G. , Shusterman Suzanne , Ingle Ashish M. , Ahern Charlotte H. , Reid Joel M. , Wu Bing , Baruchel Sylvain , Glade-Bender Julia , Ivy Percy , Grier Holcombe E. , Adamson Peter C. , Blaney Susan M.
Published: June 2011

Purpose: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population.

Experimental Design: Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m2/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle.

Results: Twenty-three patients were treated (median age 13.9 years; range, 3.9–20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m2/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles.

Conclusions: Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m2/d for 28 days followed by a 14-day break. Clin Cancer Res; 17(15); 5113–22. ©2011 AACR.
Combinatorial Effects of Lapatinib and Rapamycin in Triple-Negative Breast Cancer Cells
Authors: Liu Tongrui , Yacoub Rami , Taliaferro-Smith LaTonia D. , Sun Shi-Yong , Graham Tisheeka R. , Dolan Ryan , Lobo Christine , Tighiouart Mourad , Yang Lily , Adams Amy , O'Regan Ruth M.
Published: June 2011

Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation. Mol Cancer Ther; 10(8); 1460–9. ©2011 AACR.
Dynamically Shaped Magnetic Fields
Authors: Gang Eli S. , Nguyen Bich Lien , Shachar Yehoshua , Farkas Leslie , Farkas Laszlo , Marx Bruce , Johnson David , Fishbein Michael C. , Gaudio Carlo , Kim Steven J.
Published: June 2011

Background—

To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed that provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described.

Methods and Results—

A real-time, high-speed, closed-loop, magnetic RNS system (Catheter Guidance Control and Imaging) comprises 8 electromagnets that create unique dynamically shaped (“lobed”) magnetic fields around the subject's torso. The real-time reshaping of these magnetic fields produces the appropriate 3D motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX 3D electroanatomic mapping system (St Jude Medical) and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm-tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by Catheter Guidance Control and Imaging. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 seconds to reach targets). At postmortem examination, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness.

Conclusions—

A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target radiofrequency ablation points within the pig left atrium. Validation of the system in clinical settings is under way.
Signature microRNA Expression Profile of Essential Hypertension and Its Novel Link to Human Cytomegalovirus Infection
Authors: Li Shuqiang , Zhu Jianguo , Zhang Weili , Chen Youren , Zhang Ke , Popescu Laurentiu M. , Ma Xinliang , Bond Lau Wayne , Rong Rong , Yu Xueqing , Wang Bingbing , Li Yafeng , Xiao Chuanshi , Zhang Mingming , Wang Shuyan , Yu Liping , Chen Alex F. , Yang Xinchun , Cai Jun
Published: June 2011

Background—

Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension.

Methods and Results—

Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296–5p, let-7e, and a human cytomegalovirus [HCMV]–encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296–5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all
P
<0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112. Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%,
P
=0.0005; 1870 versus 54 copies per 1 mL plasma,
P
<0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15;
P
=0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46;
P
<0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27;
P
<0.0001, respectively).

Conclusions—

We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00420784.
Heme Oxygenase 1 Is Differentially Involved in Blood Flow–Dependent Arterial Remodeling
Authors: Freidja Mohamed Lamine , Toutain Bertrand , Caillon Antoine , Desquiret Valérie , Lambert Diane , Loufrani Laurent , Procaccio Vincent , Henrion Daniel
Published: June 2011

Heme oxygenase 1 is induced by hemodynamic forces in vascular smooth muscle and endothelial cells. We investigated the involvement of heme oxygenase 1 in flow (shear stress)-dependent remodeling. Two or 14 days after ligation of mesenteric resistance arteries, vessels were isolated. In rats, at 14 days, diameter increased by 23% in high-flow arteries and decreased by 22% in low-flow arteries compared with normal flow vessels. Heme oxygenase activity inhibition using Tin-protoporphyrin abolished diameter enlargement in high-flow arteries and accentuated arterial narrowing in low-flow arteries (32% diameter decrease versus 22% in control). Two days after ligation, heme oxygenase 1 expression increased in high-flow and low-flow vessels, in association with a reduced mitochondrial aconitase activity (marker of oxidative stress) in high-flow arteries only. Inhibition of macrophage infiltration (clodronate) decreased heme oxygenase 1 induction in low-flow but not in high-flow arteries. Similarly, inhibition of NADPH oxidase activity (apocynin) decreased heme oxygenase 1 induction in low-flow but not high-flow arteries. However, dihydroethidium staining was higher in high-flow and low-flow compared with normal flow arteries. In arteries cannulated in an arteriograph, heme oxygenase 1 mRNA increased in a flow-dependent manner and was abolished by
N
G
-nitro-
l
-arginine methyl ester, catalase, or mitochondrial electron transport chain inhibition. Furthermore, heme oxygenase 1 induction using cobalt-protoporphyrin restored altered high-flow remodeling in endothelial NO synthase knockout mice. Thus, in high-flow remodeling, heme oxygenase 1 induction depends on shear stress–generated NO and mitochondria-derived hydrogen peroxide. In low-flow remodeling, heme oxygenase 1 induction requires macrophage infiltration and is mediated by NADPH oxidase–derived superoxide.