bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EQUIVALENCE PRINCIPLE IN KALUZA–KLEIN GRAVITY
Authors: PONCE DE LEON J.
Published: April 2009

In four-dimensional general relativity the space–time outside of an isolated spherical star is described by a unique line element, which is the Schwarzschild metric. As a consequence, the "gravitational" mass and the "inertial" mass of a star are equal to each other. However, theories that envision our world as being embedded in a larger universe, with more than four dimensions, permit a number of possible non-Schwarzschild 4D exteriors, which typically lead to different masses, violating the weak equivalence principle of ordinary general relativity. Therefore, the question arises as to whether the violation of this principle, i.e. the equality of gravitational and inertial mass, is a necessary consequence of the existence of extra dimensions. In this paper, in the context of Kaluza–Klein gravity in 5D, we show that the answer to this question is negative. We find a one-parameter family of asymptotically flat non-Schwarzschild static exteriors for which the inertial and gravitational masses are equal to each other, and equal to the Deser–Soldate mass. This family is consistent with the Newtonian weak field limit as well as with the general-relativistic Schwarzschild limit. Thus, we conclude that the existence of an extra dimension, and the corresponding non-Schwarzschild exterior, does not necessarily require different masses. However, to an observer in 4D, it does affect the motion of test particles in 4D, which is a consequence of the departure from the usual (4D) law of geodesic motion.
MODELS FOR OPTIMIZATION OF PRODUCTION ENVIRONMENTAL STRESS TESTING ON ELECTRONIC CIRCUIT PACKS
Authors: JOYCE TOBY , HONARI BAHMAN , WILSON SIMON , DONOVAN JOHN , GAFFNEY OONAGH
Published: April 2009

The problem of optimizing accelerated production testing is a pressing one in most electronic manufacturing facilities. Yet, practical models are scarce in the literature, especially for testing high volumes of electronic circuit packs in failure-accelerating environments. In this paper, we develop both a log-linear and linear model, based initially on the Weibull distribution. The models developed are suitable for modeling accelerated production testing data from a temperature-cycled environment. The model is "piecewise" in that the failures in each discrete "piece" of the temperature cycle are modeled as if the testing was in parallel rather than sequential mode. An extra covariate is introduced to indicate age at the start of each piece. The failures in a piece then depend on the stress in the piece itself and the time elapsed to the start of the piece. This last dependence captures the influence of reliability growth and has the result of providing an alternative linear model to the log-linear one. The paper demonstrates a simpler use of Poisson regression. An application, using actual production data, is described. Uses of the Loglogistic, Logistic, Lognormal and Normal distributions are also illustrated.
THE EXACT RUN LENGTH DISTRIBUTION AND DESIGN OF THE S2 CHART WHEN THE IN-CONTROL VARIANCE IS ESTIMATED
Authors: CASTAGLIOLA PHILIPPE , CELANO GIOVANNI , CHEN GEMAI
Published: April 2009

When monitoring the process variability, it is a common practice that a Phase I data set is used to estimate the unknown in-control process standard deviation σ0 or variance [Formula: see text] to set up the control limits, then monitoring proceeds. Once the process is considered to be in-control, the estimated control limits are assumed as fixed. This practice ignores the effect of estimating the unknown in-control process variance [Formula: see text]. In this paper, we derive the exact run length distribution of the S2 control chart when the in-control process variance [Formula: see text] is estimated and find that m = 200 or more Phase I samples are needed to neglect the effect of using estimated control limits. New control limits when m is small are also derived.
A PROBABILISTIC SELF-ORGANIZING MAP FOR BINARY DATA TOPOGRAPHIC CLUSTERING
Authors: LEBBAH MUSTAPHA , BENNANI YOUNÈS , ROGOVSCHI NICOLETA
Published: April 2009

This paper introduces a probabilistic self-organizing map for topographic clustering, analysis and visualization of multivariate binary data or categorical data using binary coding. We propose a probabilistic formalism dedicated to binary data in which cells are represented by a Bernoulli distribution. Each cell is characterized by a prototype with the same binary coding as used in the data space and the probability of being different from this prototype. The learning algorithm, Bernoulli on self-organizing map, that we propose is an application of the EM standard algorithm. We illustrate the power of this method with six data sets taken from a public data set repository. The results show a good quality of the topological ordering and homogenous clustering.
ITERATION-FREE FRACTAL CODING FOR IMAGE COMPRESSION USING GENETIC ALGORITHM
Authors: KAMAL A. R. NADIRA BANU , SELVI S. THAMARAI , SELVARAJ HENRY
Published: April 2009

An iteration-free fractal coding for image compression is proposed using genetic algorithm (GA) with elitist model. The proposed methodology reduces the coding process time by minimizing intensive computations. The proposed technique utilizes the GA, which greatly decreases the search space for finding the self-similarities in the given image. The performance of the proposed method is compared with the iteration-free fractal-based image coding using vector quantization method for both single block and Quad tree partition on benchmark images for parameters such as image quality and coding time. It is observed that the proposed method achieves excellent performance in image quality with reduction in computing time.
Sedimentation and subsidence in the South Caspian Basin, Azerbaijan
Authors: Green Tim , Abdullayev Nazim , Hossack Jake , Riley Greg , Roberts Alan M.
Published: April 2009

The South Caspian Basin is believed to contain more than 20 km of Mesozoic and Tertiary sediments deposited on oceanic or thinned continental crust. Mesozoic, Palaeogene and Oligo-Miocene sediments have not been penetrated within the South Caspian Basin itself but are exposed onshore in the basin margins. The Pliocene–Recent sequence has been mapped on a regionally extensive grid of two-dimensional (2D) seismic data and penetrated by recently drilled exploration wells, and is over 7 km thick. Most of this sequence (6 km) is formed of fluvial–lacustrine deltaic sediments of the Pliocene Productive Series that are deposited unconformably above a marine Miocene shale sequence and form the principal hydrocarbon reservoirs in the basin. The Productive Series is overlain by about 1 km of Late Pliocene–Recent marine sediments

The thickness of the Pliocene sedimentary sequence implies that relatively rapid, late Tertiary subsidence occurred in the South Caspian Basin; however, there is no geological evidence of a tectonic event capable of generating a major thermal subsidence event at this time. Modelling presented in this paper suggests that it is possible to account for the observed pattern of subsidence and sedimentation in the South Caspian Basin by a process of sediment loading and compaction on a thermally subsiding, late Mesozoic crust without the need for additional Tertiary subsidence mechanisms. Crucially, this model interprets the Pliocene Productive Series to have been deposited in a topographic depression, isolated from the global oceanic system, in which base level was controlled by local factors rather than by global sea level.
The drift history of Iran from the Ordovician to the Triassic
Authors: Muttoni Giovanni , Mattei Massimo , Balini Marco , Zanchi Andrea , Gaetani Maurizio , Berra Fabrizio
Published: April 2009

New Late Ordovician and Triassic palaeomagnetic data from Iran are presented. These data, in conjunction with data from the literature, provide insights on the drift history of Iran as part of Cimmeria during the Ordovician–Triassic. A robust agreement of palaeomagnetic poles of Iran and West Gondwana is observed for the Late Ordovician–earliest Carboniferous, indicating that Iran was part of Gondwana during that time. Data for the Late Permian–early Early Triassic indicate that Iran resided on subequatorial palaeolatitudes, clearly disengaged from the parental Gondwanan margin in the southern hemisphere. Since the late Early Triassic, Iran has been located in the northern hemisphere close to the Eurasian margin. This northward drift brought Iran to cover much of the Palaeotethys in approximately 35 Ma, at an average plate speed of
c
. 7–8 cm year
−1
, and was in part coeval to the transformation of Pangaea from an Irvingian B to a Wegenerian A-type configuration.
The Eo-Cimmerian (Late? Triassic) orogeny in North Iran
Authors: Zanchi Andrea , Zanchetta Stefano , Berra Fabrizio , Mattei Massimo , Garzanti Eduardo , Molyneux Stewart , Nawab Amir , Sabouri Jafar
Published: April 2009

The Eo-Cimmerian orogen results from the Late Triassic collision of Iran, a microplate of Gondwanan affinity, with the southern margin of Eurasia. The orogen is discontinuously exposed along the northern side of the Alborz Mountains of North Iran below the siliciclastic deposits of the Shemshak Group (Late Triassic–Jurassic). A preserved section of the external part of the belt crops out in the Neka Valley (eastern Alborz) south of Gorgan. Here the Mesozoic successions (Shemshak Group–Upper Cretaceous limestones) overlay a pre-Jurassic Eo-Cimmerian thrust stack with a sharp unconformity. The stack includes the Gorgan Schists, an Upper Ordovician–Lower Silurian low-grade metamorphic complex, overthrusted southward above a strongly deformed Late Palaeozoic–Middle Triassic succession belonging to north Iran. In the Talesh Mountains (western Alborz), the Shanderman Complex, previously interpreted as an ophiolitic remnant isolated along the Eo-Cimmerian suture, is considered an allochthonous nappe of deeply subducted continental crust. The new evidence for this is the occurrence of previously unknown eclogites dating to the Carboniferous, and probably related to the Variscan history of Transcaucasia. South of the Shanderman Complex, Upper Palaeozoic slates and carbonates occurring below the Lower Jurassic Shemshak Group also record the occurrence of an Eo-Cimmerian metamorphic event. Based on our new data, the Eo-Cimmerian structures exposed in the Alborz appear to be remnants of a collisional orogen consisting mainly of deformed continental crust where no ophiolites are preserved.
Collagen Structure and Stability
Authors: Shoulders Matthew D. , Raines Ronald T.
Published: April 2009

Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New evidence demonstrates that stereoelectronic effects and preorganization play a key role in that stability. The fibrillar structure of type I collagen—the prototypical collagen fibril—has been revealed in detail. Artificial collagen fibrils that display some properties of natural collagen fibrils are now accessible using chemical synthesis and self-assembly. A rapidly emerging understanding of the mechanical and structural properties of native collagen fibrils will guide further development of artificial collagenous materials for biomedicine and nanotechnology.
Endogenous cardiac natriuretic peptides protect the heart in a mouse model of dilated cardiomyopathy and sudden death
Authors: Yasuno Shinji , Usami Satoru , Kuwahara Koichiro , Nakanishi Michio , Arai Yuji , Kinoshita Hideyuki , Nakagawa Yasuaki , Fujiwara Masataka , Murakami Masao , Ueshima Kenji , Harada Masaki , Nakao Kazuwa
Published: April 2009

Ventricular myocytes are known to show increased expression of the cardiac hormones atrial and brain natriuretic peptide (ANP and BNP, respectively) in response to pathological stress on the heart, but their function during the progression of nonischemic dilated cardiomyopathy remains unclear. In this study, we crossed a mouse model of dilated cardiomyopathy and sudden death, which we generated by cardioselectively overexpressing a dominant-negative form of the transcriptional repressor neuron-restrictive silencer factor (dnNRSF Tg mice), with mice lacking guanylyl cyclase-A (GC-A), a common receptor for ANP and BNP, to assess the effects of endogenously expressed natriuretic peptides during progression of the cardiomyopathy seen in dnNRSF Tg mice. We found that dnNRSF Tg;GC-A−/− mice were born normally, but then most died within 4 wk. The survival rates among dnNRSF Tg;GC-A+/− and dnNRSF Tg mice were comparable, but dnNRSF Tg;GC-A+/− mice showed greater systolic dysfunction and a more severe cardiomyopathic phenotype than dnNRSF Tg mice. Collectively, our findings suggest that endogenous ANP/BNP protects the heart against the death and progression of pathological remodeling in a mouse model of dilated cardiomyopathy and sudden death.
Use of a three-dimensional cell culture model to study airway smooth muscle-mast cell interactions in airway remodeling
Authors: Ceresa Claudia C. , Knox Alan J. , Johnson Simon R.
Published: April 2009

Increased airway smooth muscle (ASM) mass and infiltration by mast cells are key features of airway remodeling in asthma. We describe a model to investigate the relationship between ASM, the extracellular matrix, mast cells, and airway remodeling. ASM cells were cultured in a three-dimensional (3-D) collagen I gel (3-D culture) alone or with mast cells. Immunocytochemistry and Western blotting of ASM in 3-D cultures revealed a spindle-shaped morphology and significantly lower α-smooth muscle actin and vimentin expression than in ASM cultured in monolayers on collagen type I or plastic (2-D culture). In 3-D cultures, basal ASM proliferation, examined by Ki67 immunocytochemistry, was reduced to 33 ± 7% ( P < 0.05) of that in 2-D cultures. The presence of mast cells in cocultures increased ASM proliferation by 1.8-fold ( P < 0.05). Gelatin zymography revealed more active matrix metalloproteinase (MMP)-2 in 3-D than in 2-D culture supernatants over 7 days. Functional MMP activity was examined by gel contraction. The spontaneous gel contraction over 7 days was significantly inhibited by the MMP inhibitor ilomastat. Mast cell coculture enhanced ASM gel contraction by 22 ± 16% (not significant). Our model shows that ASM has different morphology, with lower contractile protein expression and basal proliferation in 3-D culture. Compared with standard techniques, ASM synthetic function, as shown by MMP production and activity, is sustained over longer periods. The presence of mast cells in the 3-D model enhanced ASM proliferation and MMP production. Airway remodeling in asthma may be more accurately modeled by our system than by standard culture systems.
Influence of repeated sprint training on pulmonary O2 uptake and muscle deoxygenation kinetics in humans
Authors: Bailey Stephen J. , Wilkerson Daryl P. , DiMenna Fred J. , Jones Andrew M.
Published: April 2009

We hypothesized that a short-term training program involving repeated all-out sprint training (RST) would be more effective than work-matched, low-intensity endurance training (ET) in enhancing the kinetics of oxygen uptake (V̇o2) and muscle deoxygenation {deoxyhemoglobin concentration ([HHb])} following the onset of exercise. Twenty-four recreationally active subjects (15 men, mean ± SD: age 21 ± 4 yr, height 173 ± 9 cm, body mass 71 ± 11 kg) were allocated to one of three groups: RST, which completed six sessions of four to seven 30-s RSTs; ET, which completed six sessions of work-matched, moderate-intensity cycling; and a control group (CON). All subjects completed moderate-intensity and severe-intensity “step” exercise transitions before (Pre) and after the 2-wk intervention period (Post). Following RST, [HHb] kinetics were speeded, and the amplitude of the [HHb] response was increased during both moderate and severe exercise ( P < 0.05); the phase II V̇o2 kinetics were accelerated for both moderate (Pre: 28 ± 8, Post: 21 ± 8 s; P < 0.01) and severe (Pre: 29 ± 5, Post: 23 ± 5 s; P < 0.05) exercise; the amplitude of the V̇o2 slow component was reduced (Pre: 0.52 ± 0.19, Post: 0.40 ± 0.17 l/min; P < 0.01); and exercise tolerance during severe exercise was improved by 53% (Pre: 700 ± 234, Post: 1,074 ± 431 s; P < 0.01). None of these parameters was significantly altered in the ET and CON groups. Six sessions of RST, but not ET, resulted in changes in [HHb] kinetics consistent with enhanced fractional muscle O2 extraction, faster V̇o2 kinetics, and an increased tolerance to high-intensity exercise.
Response of the respiratory muscles to rehabilitation in COPD
Authors: Decramer Marc
Published: April 2009

Respiratory rehabilitation is known to improve outcomes in patients with chronic obstructive pulmonary disease (COPD). The question addressed in the present review is whether these beneficial effects are related to improvements in inspiratory muscle function. Respiratory muscle fatigue often did not occur during exercise in patients with COPD, since exercise limitation usually occurred when significant force reserve in the inspiratory muscles was still present. Notwithstanding, a number of observations may provide indirect evidence that respiratory muscle fatigue may occur during exercise. Some evidence is present that, in normal humans, whole body exercise training improved inspiratory muscle endurance, but no studies are available in patients with COPD. Animal studies invariably demonstrated that exercise training increased the number of oxidative fibers and oxidative enzyme activity in inspiratory muscles. These effects, however, were considerably smaller than the effects found on peripheral muscles with similar fiber composition. Clear evidence indicated that inspiratory muscle training (IMT) improved inspiratory muscle function. Two large meta-analyses indicated that, if the training load was properly controlled, IMT alone or combined with general exercise reconditioning improved inspiratory muscle strength and endurance and dyspnea. The combination did not result in greater improvements in functional exercise capacity. Animal studies and one patient study confirmed the occurrence of structural remodeling of the inspiratory muscles in response to IMT. The final question is whether improvements in inspiratory muscle function produced by IMT lead to improved outcomes in COPD. In all five studies in which training load was adequately controlled, a significant reduction of dyspnea during activities of daily living was found. Eight randomized studies examined the effects of the combination. Greater improvements in exercise capacity were only found in three studies, and none showed a greater reduction in dyspnea.
A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse
Authors: Caron Annabelle Z. , Drouin Geneviève , Desrosiers Justine , Trensz Frédéric , Grenier Guillaume
Published: April 2009

Skeletal muscle atrophy is a serious concern for patients afflicted by limb restriction due to surgery (e.g., arthrodesis), several articular pathologies (e.g., arthralgia), or simply following cast immobilization. To study the molecular events involved in this immobilization-induced debilitating condition, a convenient mouse model for atrophy is lacking. Here we provide a new immobilization procedure exploiting the normal flexion of the mouse hindlimb using a surgical staple to fix the ventral part of the foot to the distal part of the calf. Histological analysis revealed that our approach induced significant skeletal muscle atrophy by reducing the myofiber size of the tibialis anterior (TA) muscle by 36% compared with the untreated contralateral TA within a few days postimmobilization. Two molecular markers for atrophy, atrogin-1/muscle atrophy F-box (atrogin-1/MAFbx) and muscle ring finger 1 (MuRF-1) mRNAs, were significantly upregulated by 1.9- and 5.9-fold, respectively. Interestingly, our model also revealed the presence of an early inflammatory process during atrophy, characterized by the mRNA upregulation of TNF-α, IL-1, and IL-6 (1.9-, 2.4-, and 3.4-fold, respectively) simultaneously with the upregulation of the common leukocyte marker CD45 (6.1-fold). Moreover, muscle rapidly recovered on remobilization, an event associated with significantly increased levels of uncoupling protein-3 and peroxisome proliferator-activated receptor γ coactivator-1α mRNA, key components of prooxidative muscle metabolism. This model offers unexpected new insights into the molecular events involved in immobilization atrophy.
Frailty Syndrome: A Transitional State in a Dynamic Process
Authors: Lang Pierre-Olivier , Michel Jean-Pierre , Zekry Dina
Published: April 2009

Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.
Caloric Restriction and Exercise Increase Plasma ANGPTL4 Levels in Humans via Elevated Free Fatty Acids
Authors: Kersten Sander , Lichtenstein Laeticia , Steenbergen Emma , Mudde Karin , Hendriks Henk F.J. , Hesselink Matthijs K. , Schrauwen Patrick , Müller Michael
Published: April 2009

Objective—

Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human. Here we set out to identify physiological determinants of plasma ANGPTL4 levels in humans, focusing on the effect of energy restriction and plasma FFAs.

Methods and Results—

We developed an ELISA for quantitative measurement of ANGPTL4 in human plasma. Using this assay we found major variations in baseline plasma ANGPTL4 levels between individuals. Within an individual, plasma ANGPTL4 levels remain stable throughout the day but increase significantly in response to long-term fasting, chronic caloric restriction, and endurance exercise. Intralipid injection as well as treatment with a β-adrenergic agonist, both of which lead to elevated plasma FFA levels, increased plasma ANGPTL4 levels compared to control treatment. Fatty acids markedly induced ANGPTL4 gene expression in rat hepatoma FAO cells, human primary myocytes, and mouse intestinal MSIE cells.

Conclusion—

In conclusion, our results show that plasma ANGPTL4 levels are increased by fasting, caloric restriction, and exercise, which is likely mediated by elevated plasma FFAs.
Late Outgrowth Endothelial Cells Derived From Wharton Jelly in Human Umbilical Cord Reduce Neointimal Formation After Vascular Injury
Authors: Wang Shu-Huei , Lin Shing-Jong , Chen Yung-Hsiang , Lin Fen-Yen , Shih Jin-Chung , Wu Chau-Chung , Wu Hua-Lin , Chen Yuh-Lien
Published: April 2009

Objectives—

The number of endothelial progenitor cells (EPCs) that can be obtained from adult bone marrow and peripheral blood to treat cardiovascular diseases is limited. The goal was to examine the endothelial potential of Wharton jelly in human umbilical cord (WJC)-derived stem cells and evaluate their potential to affect neointimal formation after vascular injury.

Methods and Results—

Mesenchymal cells (MCs) were isolated from WJC and cultured in endothelial growth medium. Differentiation into late outgrowth endothelial cells (WJC-OECs) was demonstrated by incorporation of acetylated low-density lipoprotein and expression of the endothelial-specific markers. Transplantation of these cells into wire-injured femoral arteries in mice led to rapid reendothelialization. At 4 weeks after injury, the neointima/media area ratio was reduced and strong expression of pigment epithelium-derived factor (PEDF) compared to saline-or MC- or cord blood-OEC-treated mice. WJC-OECs-conditioned medium has an extremely strong capacity to inhibit the migration and proliferation of smooth muscle cells. The effects were inhibited by neutralizing antibody for PEDF and by siRNA silencing of PEDF.

Conclusions—

We firstly demonstrated the presence of a cell population within WJC that has the potential to differentiate into OECs. Transplantation of WJC-OECs may play a crucial role in reestablishing endothelial integrity in injured vessels, thereby inhibiting neointimal hyperplasia. These findings have implications for a novel and practical cell-based therapy for vascular diseases.
Amplification of Coronary Arteriogenic Capacity of Multipotent Stromal Cells by Epidermal Growth Factor
Authors: Belmadani Souad , Matrougui Khalid , Kolz Chris , Pung Yuh Fen , Palen Desiree , Prockop Darwin J. , Chilian William M.
Published: April 2009

Objective—

We determined whether increasing adherence of multipotent stromal cells (MSCs) would amplify their effects on coronary collateral growth (CCG).

Methods and Results—

Adhesion was established in cultured coronary endothelials cells (CECs) or MSCs treated with epidermal growth factor (EGF). EGF increased MSCs adhesion to CECs, and increased intercellular adhesion molecule (ICAM-1) or vascular cell adhesion molecule (VCAM-1) expression. Increased adherence was blocked by EGF receptor antagonism or antibodies to the adhesion molecules. To determine whether adherent MSCs, treated with EGF, would augment CCG, repetitive episodes of myocardial ischemia (RI) were introduced and CCG was measured from the ratio of collateral-dependent (CZ) and normal zone (NZ) flows. CZ/NZ was increased by MSCs without treatment versus RI-control and was further increased by EGF-treated MSCs. EGF-treated MSCs significantly improved myocardial function versus RI or RI+MSCs demonstrating that the increase in collateral flow was functionally significant. Engraftment of MSCs into myocardium was also increased by EGF treatment.

Conclusions—

These results reveal the importance of EGF in MSCs adhesion to endothelium and suggest that MSCs may be effective therapies for the stimulation of coronary collateral growth when interventions are used to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium.
The SWI/SNF Chromatin Remodeling Complex Regulates Myocardin-Induced Smooth Muscle–Specific Gene Expression
Authors: Zhou Jiliang , Zhang Min , Fang Hong , El-Mounayri Omar , Rodenberg Jennifer M. , Imbalzano Anthony N. , Herring B. Paul
Published: April 2009

Objective—

Regulatory complexes comprising myocardin and serum response factor (SRF) are critical for the transcriptional regulation of many smooth muscle–specific genes. However, little is known about the epigenetic mechanisms that regulate the activity of these complexes. In the current study, we investigated the role of SWI/SNF ATP-dependent chromatin remodeling enzymes in regulating the myogenic activity of myocardin.

Methods and Results—

We found that both Brg1 and Brm are required for maintaining expression of several smooth muscle–specific genes in primary cultures of aortic smooth muscle cells. Furthermore, the ability of myocardin to induce expression of smooth muscle–specific genes is abrogated in cells expressing dominant negative Brg1. In SW13 cells, which lack endogenous Brg1 and Brm1, myocardin is unable to induce expression of smooth muscle–specific genes. Whereas, reconstitution of wild-type, or bromodomain mutant forms Brg1 or Brm1, into SW13 cells restored their responsiveness to myocardin. SWI/SNF complexes were found to be required for myocardin to increase SRF binding to the promoters of smooth muscle–specific genes. Brg1 and Brm directly bind to the N terminus of myocardin, in vitro, through their ATPase domains and Brg1 forms a complex with SRF and myocardin in vivo in smooth muscle cells.

Conclusion—

These data demonstrate that the ability of myocardin to induce smooth muscle–specific gene expression is dependent on its interaction with SWI/SNF ATP-dependent chromatin remodeling complexes.
Ion Channel Transcript Expression at the Rabbit Atrioventricular Conduction Axis
Authors: Greener Ian D. , Tellez James O. , Dobrzynski Halina , Yamamoto Mitsuru , Graham Gillian M. , Billeter Rudi , Boyett Mark R.
Published: April 2009

Background—

Little is known about the distribution of gap junctions and ion channels in the atrioventricular node, even though the physiology and pathology of the atrioventricular node is ultimately dependent on them.

Methods and Results—

The abundance of 30 transcripts for markers, gap junctions, ion channels, and Ca
2+
-handling proteins in different regions of the rabbit atrioventricular node (nodal extension and proximal and distal penetrating bundle of His as well as atrial and ventricular muscle) was measured using a novel quantitative polymerase chain reaction technique and in situ hybridization. The expression profile of the nodal extension (slow pathway into penetrating bundle) was similar to that of the sinoatrial node. For example, in the nodal extension, in contrast to the atrial muscle and as expected for a slowly conducting tissue with pacemaker activity, there was no or reduced expression of Cx43, Na
v
1.5, Ca
v
1.2, K
v
1.4, KChIP2, and RYR3 and high expression of Ca
v
1.3 and HCN4. The expression profile of the penetrating bundle was less specialized. In situ hybridization revealed a transitional zone with reduced expression of Cx43, Na
v
1.5, and KChIP2 that may form the fast pathway into the penetrating bundle.

Conclusions—

At the atrioventricular node, the expression of gap junctions and ion channels in the nodal extension (slow pathway) and a transitional zone (putative fast pathway) as well as the penetrating bundle (output pathway) is specialized and heterogeneous and roughly matches the electrophysiology of the different regions.
Contribution of Insulin and Akt1 Signaling to Endothelial Nitric Oxide Synthase in the Regulation of Endothelial Function and Blood Pressure
Authors: Symons J. David , McMillin Shawna L. , Riehle Christian , Tanner Jason , Palionyte Milda , Hillas Elaine , Jones Deborah , Cooksey Robert C. , Birnbaum Morris J. , McClain Donald A. , Zhang Quan-Jiang , Gale Derrick , Wilson Lloyd J. , Abel E. Dale
Published: April 2009

Impaired insulin signaling via phosphatidylinositol 3-kinase/Akt to endothelial nitric oxide synthase (eNOS) in the vasculature has been postulated to lead to arterial dysfunction and hypertension in obesity and other insulin resistant states. To investigate this, we compared insulin signaling in the vasculature, endothelial function, and systemic blood pressure in mice fed a high-fat (HF) diet to mice with genetic ablation of insulin receptors in all vascular tissues (TTr-IR−/−) or mice with genetic ablation of Akt1 (Akt1−/−). HF mice developed obesity, impaired glucose tolerance, and elevated free fatty acids that was associated with endothelial dysfunction and hypertension. Basal and insulin-mediated phosphorylation of extracellular signal-regulated kinase 1/2 and Akt in the vasculature was preserved, but basal and insulin-stimulated eNOS phosphorylation was abolished in vessels from HF versus lean mice. In contrast, basal vascular eNOS phosphorylation, endothelial function, and blood pressure were normal despite absent insulin-mediated eNOS phosphorylation inTTr-IR−/−mice and absent insulin-mediated eNOS phosphorylation via Akt1 in Akt1−/− mice. In cultured endothelial cells, 6 hours of incubation with palmitate attenuated basal and insulin-stimulated eNOS phosphorylation and NO production despite normal activation of extracellular signal-regulated kinase 1/2 and Akt. Moreover, incubation of isolated arteries with palmitate impaired endothelium-dependent but not vascular smooth muscle function. Collectively, these results indicate that lower arterial eNOS phosphorylation, hypertension, and vascular dysfunction following HF feeding do not result from defective upstream signaling via Akt, but from free fatty acid-mediated impairment of eNOS phosphorylation.
Structural and Molecular Mechanisms of Gap Junction Remodeling in Epicardial Border Zone Myocytes following Myocardial Infarction
Authors: Kieken Fabien , Mutsaers Nancy , Dolmatova Elena , Virgil Kelly , Wit Andrew L. , Kellezi Admir , Hirst-Jensen Bethany J. , Duffy Heather S. , Sorgen Paul L.
Published: April 2009

Lateralization of the ventricular gap junction protein connexin 43 (Cx43) occurs in epicardial border zone myocytes following myocardial infarction (MI) and is arrhythmogenic. Alterations in Cx43 protein partners have been hypothesized to play a role in lateralization although mechanisms by which this occurs are unknown. To examine potential mechanisms we did nuclear magnetic resonance, yeast 2-hybrid, and surface plasmon resonance studies and found that the SH3 domain of the tyrosine kinase c-Src binds to the Cx43 scaffolding protein zonula occludens-1 (ZO-1) with a higher affinity than does Cx43. This suggests c-Src outcompetes Cx43 for binding to ZO-1, thus acting as a chaperone for ZO-1 and causing unhooking from Cx43. To determine whether c-Src/ZO-1 interactions affect Cx43 lateralization within the epicardial border zone, we performed Western blot, immunoprecipitation, and immunolocalization for active c-Src (p-cSrc) post-MI using a canine model of coronary occlusion. We found that post-MI p-cSrc interacts with ZO-1 as Cx43 begins to decrease its interaction with ZO-1 and undergo initial loss of intercalated disk localization. This indicates that the molecular mechanisms by which Cx43 is lost from the intercalated disk following MI includes an interaction of p-cSrc with ZO-1 and subsequent loss of scaffolding of Cx43 leaving Cx43 free to diffuse in myocyte membranes from areas of high Cx43, as at the intercalated disk, to regions of lower Cx43 content, the lateral myocyte membrane. Therefore shifts in Cx43 protein partners may underlie, in part, arrhythmogenesis in the post-MI heart.
Trends for Blood Pressure and Its Contribution to Stroke Incidence in the Middle-Aged Japanese Population
Authors: Imano Hironori , Kitamura Akihiko , Sato Shinichi , Kiyama Masahiko , Ohira Tetsuya , Yamagishi Kazumasa , Noda Hiroyuki , Tanigawa Takeshi , Iso Hiroyasu , Shimamoto Takashi
Published: April 2009

Background and Purpose—

Hypertension is a major risk factor for stroke. However, a substantial decrease in blood pressure levels in Japanese during the past 3 decades may have reduced contributions of hypertension to risk of stroke. The population attributable fraction, the percentage of outcomes attributable to exposure, of blood pressure for the incidence of stroke was investigated during 3 survey periods between 1963 and 1994 by means of a population-based cohort study.

Methods—

We explored 3 cohort data of residents aged 40 to 69 years in 4 Japanese communities in 1963 to 1971 (n=5439), 1975 to 1984 (n=9945), and 1985 to 1994 (n=11 788) baseline surveys. Mean follow-up period for each cohort was 10 years.

Results—

Higher blood pressure levels were associated with higher risk of stroke. Positive associations were also observed even within nonhypertension levels. From the first to the third cohorts, the blood pressure category with a majority of stroke incidence shifted from severe or moderate hypertension to mild hypertension. The population attributable fraction of the severe hypertension category in the first, second, and third cohorts were 20%, 14%, and 9%, respectively, and those of the moderate hypertension category were 19%, 24%, and 11%, respectively, whereas those of the mild hypertension category were 17%, 26%, and 23%, respectively. The results were similar when participants on antihypertensive medication were excluded.

Conclusions—

The higher risk of stroke incidence with higher blood pressure levels even in nonhypertension categories and the shift of stroke burden from severe/moderate hypertension to mild hypertension support the early management of hypertension and primary prevention of high blood pressures for the prevention of stroke.
The Psychoanalytic Assumption of the Primary Process: Extrapsychoanalytic Evidence and Findings
Authors: Brakel Linda A. W.
Published: April 2009

No evidence for an assumption of a theory can be gained by data derived from methods dependent on that theory. Three experiments, using methods independent of psychoanalysis, test the psychoanalytic posit that primary process exists as a formal mental mode distinct from secondary process. The three experiments, using a nonpsychoanalytic index for primary process, test for a preponderance of primary process organization in three areas in which Freud observed primary process: (1) in unconscious mental states and during implicit tasks; (2) in the mental productions of preschool children; and (3) in anxiety states, as these are typically associated with unconscious conflict. All three experiments show significant results in favor of the primary process. Further, the three experiments taken together, because they account for seemingly disparate data, lend further credence to the original assumption. These positive results suggest that primary process may be more important than even Freud suspected. Perhaps it is the basic mental organization in many nonhuman mammals and some birds. Primary process organization may also underlie aspects of such basic psychological operations as generalizations in conditioning and assessments-in-action, as opposed to judgments proper, about how one would act. Finally, primary process may play a key role in drive activity. Three types of experiments are proposed to test these far-reaching applications of the primary process concept.
The Death of the Analyst: Patients Whose Previous Analyst Died While They Were in Treatment
Authors: Galatzer-Levy Robert M.
Published: April 2009

A few heroic analysts have described their work in the face of life-threatening illness. However, there are only limited descriptions of these illnesses and deaths from the patient's point of view. Experiences of less heroic colleagues are almost unavailable. Clinical experience with ten patients whose previous analyst died while they were in treatment, two whose analyst died shortly after termination, and two terminally ill colleagues who sought consultation suggests that the analysts' understandable denial of the severity of their illness and the patients' collusion in this denial often affects patients negatively. Extensive difficulties commonly arose during the illness and after the analyst's death. These often involved significant boundary crossings and violations. The analytic community does not seem to handle these situations well. Recommendations are offered that might spare patients unnecessary pain and harm.
Change After Long-Term Psychoanalytic Psychotherapy
Authors: Barber Jacques P. , Gustavsson J. Petter , Åsberg Marie , Weinryb Robert M. , Wilczek Alexander
Published: April 2009

Psychoanalytic psychotherapy in clinical practice is traditionally a long-term treatment conducted by well-trained psychotherapists. However, very few studies have been published that evaluate the effects of such treatment. To redress this lack of studies, 55 individuals selected for long-term psychoanalytic psychotherapy (average, 3 years) were invited to participate in a naturalistic study. The psychotherapists had a mean of 15 years of professional experience. The 36 patients who completed psychotherapy manifested a substantial reduction in symptomatic suffering and decreased levels of character pathology, as measured by the Karolinska Psychodynamic Profile (KAPP) and the Karolinska Scales of Personality. Generally, such changes were not found in the individuals who did not engage in treatment. In the therapy group, improvements were found on eight KAPP subscales defining different aspects of character: Intimacy and Reciprocity, Frustration Tolerance, Regression in the Service of the Ego, Coping with Aggressive Affects, Conceptions of Bodily Appearance and their Significance for Self-esteem, Sexual Function, Sexual Satisfaction, and Personality Organization. The results indicate that individuals who engaged in psychotherapy improved their capacity to handle crucial aspects of life and reduced their symptomatic suffering.
Writing About Patients: Iv. Patients' Reactions To Reading About Themselves
Authors: Kantrowitz Judy L.
Published: April 2009

When analysands read about themselves in reports, their reactions range from anger, disappointment, or condemnation to a sense of appreciation or even idealization of the analyst. The eleven interviews reported here reflect only conscious responses; the unconscious layers were not probed for. It should be kept in mind also that the analysts of these patients might report very different stories. Other limitations are the small sample size and the representation only of patients who volunteered. Nonetheless, the information they provide may help analysts consider how and when writing about patients may influence their representation of themselves, the analyst, and analysis itself.
Translating Child Analysis From the Playroom To the Classroom: Opportunities and Choices
Authors: Rosenblitt Donald L.
Published: April 2009

Over the years, psychoanalysts and educators have made efforts to meld a psychoanalytic orientation with the education of young children. The resulting programs have variously been called psychoanalytic nurseries, therapeutic nurseries, therapeutic preschools, or psychoanalytic early childhood programs. The methodology of the application or integration of psychoanalysis with the education of young children has received relatively little attention. After a brief historical review of the application of psychoanalysis to helping children in group educational settings, a number of features common to programs integrating psychoanalysis and early childhood education are described. A specimen program is next presented in which an application of psychoanalysis is used to assist children whose development is proceeding in a psychopathological direction. Also demonstrated are various ways in which psychoanalysis may be adapted to early childhood programs, some options involved in this modification, and the capacity, realized and potential, for work within a therapeutic nursery to expand the field of inquiry and the therapeutic action of child analysis as conducted within a traditional framework.
Early Developmental Issues Reconsidered: Commentary On Pine's iDeas On Symbiosis
Authors: Silverman Doris
Published: April 2009

The concept of symbiosis is a powerful one expressing a significant emotional experience for many individuals. However, the concept needs to be differentiated from infant-stage symbiosis, Margaret Mahler's second stage of normal development. The latter idea, according to Pine (2004), was of “central” importance to Mahler. Although Pine acknowledges the influence of research findings and some critical challenges to this idea, he maintains nonetheless that it “remains quite valuable” and reports what he suggests are manifestations of symbiotic experiences in the infant-mother relationship. His recognition of infant observational data has led him to feature the idea of “moments” of merger between mother and infant. Empirical data, however, challenge both the idea of a more broadly defined stage of infantile symbiosis and the more narrowly conceived “moments.” A different understanding of development in the presence of early-stage symbiosis is provided.
Affects, Agency, and Self-Regulation: Complexity Theory in the Treatment of Children With Anxiety and Disruptive Behavior Disorders
Authors: Tyson Phyllis
Published: April 2009

In an increasingly unsettled and violent world, with swelling numbers of children who are abused, abandoned, or neglected, emotionally if not physically, and an increasing population of aggressive preschool children with anxiety and disruptive behavior disorders who cannot be contained in ordinary settings, psychoanalysts can make a contribution. Early intervention is essential. In very early childhood, new procedural memories for interacting with others and for regulating affects can be formed more easily than they can ever be again. Intervention should aim toward helping the child develop a sense of agency, establish moral standards, assume self-responsibility, and attain the capacity for emotional regulation. The principles of complex dynamic systems can inform psychoanalytic treatment strategies, as demonstrated with five children whose cases are presented.
Is There a Special Psychoanalytic Love?
Authors: Friedman Lawrence
Published: April 2009

Although the analyst's role mandates a degree of detachment, analysts have often said that they offer patients a special kind of love. They have tended to equate that love with understanding, thus neutralizing the paradox but also diluting the love. When something more resembling a loving affect is sought, the suggestions include the love a scholar feels for his subject, the love that accompanies immersion in great literature, and love that is self-generated by deliberate efforts to move toward the patient or to generate empathy in oneself. But a form of love may also arise from the analyst's unique and relatively pure acquaintance with a person's “appeal,” by which is meant the patient's effort to elicit responses from the analyst. Although the awareness of transference most obviously tends to immunize him, it also gives him a poignant “insider's” feel of the patient's appeal, since he is the target of that appeal while being unencumbered by the myriad considerations that would color his perception were he to regard himself as a proper object.