bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor unit recruitment strategies and muscle properties determine the influence of synaptic noise on force steadiness
Authors: Dideriksen Jakob L. , Negro Francesco , Enoka Roger M. , Farina Dario
Published: March 2012

Motoneurons receive synaptic inputs from tens of thousands of connections that cause membrane potential to fluctuate continuously (synaptic noise), which introduces variability in discharge times of action potentials. We hypothesized that the influence of synaptic noise on force steadiness during voluntary contractions is limited to low muscle forces. The hypothesis was examined with an analytical description of transduction of motor unit spike trains into muscle force, a computational model of motor unit recruitment and rate coding, and experimental analysis of interspike interval variability during steady contractions with the abductor digiti minimi muscle. Simulations varied contraction force, level of synaptic noise, size of motor unit population, recruitment range, twitch contraction times, and level of motor unit short-term synchronization. Consistent with the analytical derivations, simulations and experimental data showed that force variability at target forces above a threshold was primarily due to low-frequency oscillations in neural drive, whereas the influence of synaptic noise was almost completely attenuated by two low-pass filters, one related to convolution of motoneuron spike trains with motor unit twitches (temporal summation) and the other attributable to summation of single motor unit forces (spatial summation). The threshold force above which synaptic noise ceased to influence force steadiness depended on recruitment range, size of motor unit population, and muscle contractile properties. This threshold was low (<10% of maximal force) for typical values of these parameters. Results indicate that motor unit recruitment and muscle properties of a typical muscle are tuned to limit the influence of synaptic noise on force steadiness to low forces and that the inability to produce a constant force during stronger contractions is mainly attributable to the common low-frequency oscillations in motoneuron discharge rates.
The relationship between voltage-sensitive dye imaging signals and spiking activity of neural populations in primate V1
Authors: Chen Yuzhi , Palmer Chris R. , Seidemann Eyal
Published: March 2012

Voltage-sensitive dye imaging (VSDI) is a powerful technique for measuring neural population responses from a large cortical region simultaneously with millisecond temporal resolution and columnar spatial resolution. However, the relationship between the average VSDI signal and the average spiking activity of neural populations is largely unknown. To better understand this relationship, we compared visual responses measured from V1 of behaving monkeys using VSDI and single-unit electrophysiology. We found large and systematic differences between position and orientation tuning properties obtained with these two techniques. We then determined that a simple computational model could explain these tuning differences. This model, together with our experimental results, allowed us to estimate the quantitative relationship between the average VSDI signal and local spiking activity. We found that this relationship is similar to the previously reported nonlinear relationship between average membrane potential and spike rate in single V1 neurons, suggesting that VSDI signals are dominated by subthreshold synaptic activity. This model, together with the VSDI measured maps for spatial position (retinotopy) and orientation, also allowed us to estimate the spatial integration area over which neural responses contribute to the VSDI signal at a given location. We found that the VSDI-integration area is consistent with a Gaussian envelope with a space constant of ∼230 μm. Finally, we show how this model and estimated parameters can be used to predict the pattern of population responses at the level of spiking activity from VSDI responses.
On the Dynamics of a Higher‐Order Difference Equation
Authors: El-Metwally H.
Published: March 2012

This paper deals with the investigation of the following more general rational difference equation: , n = 0,1, 2, …, where α, β, γ, p ∈ (0, ∞) with the initial conditions x0, x−1, …,x−2k, x−2k−1 ∈ (0, ∞). We investigate the existence of the equilibrium points of the considered equation and then study their local and global stability. Also, some results related to the oscillation and the permanence of the considered equation have been presented.
Directional Moving Target Indication: A Novel SAR Ambiguity Function for Traffic Monitoring
Authors: Marques Paulo
Published: March 2012

This paper presents and evaluates a novel SAR ambiguity function for traffic monitoring. The novelty consists in introducing the capability to discriminate targets moving in a predefined direction of interest, reducing the contribution of traffic moving in undesired directions. Experimental results show that the modified SAR ambiguity function provides better results than the traditional methodology and may, therefore, be useful for civil traffic monitoring using single‐channel synthetic aperture radar data.
Osteosarcoma Models: From Cell Lines to Zebrafish
Authors: Mohseny Alexander B. , Hogendoorn Pancras C. W. , Cleton-Jansen Anne-Marie
Published: March 2012

High-grade osteosarcoma is an aggressive tumor most commonly affecting adolescents. The early age of onset might suggest genetic predisposition; however, the vast majority of the tumors are sporadic. Early onset, most often lack of a predisposing condition or lesion, only infrequent (<2%) prevalence of inheritance, extensive genomic instability, and a wide histological heterogeneity are just few factors to mention that make osteosarcoma difficult to study. Therefore, it is sensible to design and use models representative of the human disease. Here we summarize multiple osteosarcoma models establishedin vitroandin vivo, comment on their utilities, and highlight newest achievements, such as the use of zebrafish embryos. We conclude that to gain a better understanding of osteosarcoma, simplification of this extremely complex tumor is needed. Therefore, we parse the osteosarcoma problem into parts and propose adequate models to study them each separately. A better understanding of osteosarcoma provides opportunities for discovering and assaying novel effective treatment strategies.
Ecological Adaptation and Speciation: The Evolutionary Significance of Habitat Avoidance as a Postzygotic Reproductive Barrier to Gene Flow
Authors: Feder Jeffrey L. , Egan Scott P. , Forbes Andrew A.
Published: March 2012

Habitat choice is an important component of most models of ecologically based speciation, especially when population divergence occurs in the face of gene flow. We examine how organisms choose habitats and ask whether avoidance behavior plays an important role in habitat choice, focusing on host-specific phytophagous insects as model systems. We contend that when a component of habitat choice involves avoidance, there can be repercussions that can have consequences for enhancing the potential for specialization and postzygotic reproductive isolation and, hence, for ecological speciation. We discuss theoretical and empirical reasons for why avoidance behavior has not been fully recognized as a key element in habitat choice and ecological speciation. We present current evidence for habitat avoidance, emphasizing phytophagous insects, and new results for parasitoid wasps consistent with the avoidance hypothesis. We conclude by discussing avenues for further study, including other potential roles for avoidance behavior in speciation related to sexual selection and reinforcement.
Capability of Tissue Stem Cells to Organize into Salivary Rudiments
Authors: Okumura Kenji , Shinohara Masanori , Endo Fumio
Published: March 2012

Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin andα6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues.
Nutrition and Sarcopenia: A Review of the Evidence and Implications for Preventive Strategies
Authors: Robinson Siân , Cooper Cyrus , Aihie Sayer Avan
Published: March 2012

Prevention of age-related losses in muscle mass and strength is key to protecting physical capability in older age and enabling independent living. To develop preventive strategies, a better understanding is needed of the lifestyle factors that influence sarcopenia and the mechanisms involved. Existing evidence indicates the potential importance of diets of adequate quality, to ensure sufficient intakes of protein, vitamin D, and antioxidant nutrients. Although much of this evidence is observational, the prevalence of low nutrient intakes and poor status among older adults make this a current concern. However, as muscle mass and strength in later life are a reflection of both the rate of muscle loss and the peak attained in early life, efforts to prevent sarcopenia also need to consider diet across the lifecourse and the potential effectiveness of early interventions. Optimising diet and nutrition throughout life may be key to preventing sarcopenia and promoting physical capability in older age.
Molecular Dynamics Simulations of Pressure-Driven Flows and Comparison with Acceleration-Driven Flows
Authors: To Quy Dong , Pham Thanh Tung , Lauriat Guy , Léonard Céline
Published: March 2012

We use molecular dynamics to simulate fluid flows between two parallel plates with constant wall temperature. Unlike the usual approach in molecular dynamics, instead of applying an external force on the molecules, the periodic boundary conditions are modified to create a pressure difference between the inlet and the outlet sections of the computational domain. The simulation results include velocity, pressure, density, and temperature profiles obtained by the new method. These results are compared with approximate solutions for nonisothermal Poiseuille flows. The method is also applied to simulate a flow in a rib-roughened channel.
Membrane Protein Stability Analyses by Means of Protein Energy Profiles in Case of Nephrogenic Diabetes Insipidus
Authors: Heinke Florian , Labudde Dirk
Published: March 2012

Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems.
Resident Corneal Cells Communicate with Neutrophils Leading to the Production of IP-10 during the Primary Inflammatory Response to HSV-1 Infection
Authors: Molesworth-Kenyon S. J. , Popham N. , Milam A. , Oakes J. E. , Lausch R. N.
Published: March 2012

In this study we show that murine and human neutrophils are capable of secreting IP-10 in response to communication from the HSV-1 infected cornea and that they do so in a time frame associated with the recruitment of CD8+T cells and CXCR3-expressing cells. Cellular markers were used to establish that neutrophil influx corresponded in time to peak IP-10 production, and cellular depletion confirmed neutrophils to be a significant source of IP-10 during HSV-1 corneal infection in mice. A novelex vivomodel for human corneal tissue infection with HSV-1 was used to confirm that cells resident in the cornea are also capable of stimulating neutrophils to secrete IP-10. Our results support the hypothesis that neutrophils play a key role in T-cell recruitment and control of viral replication during HSV-1 corneal infection through the production of the T-cell recruiting chemokine IP-10.
Facile Preparation and Photoinduced Superhydrophilicity of Highly Ordered Sodium-Free Titanate Nanotube Films by Electrophoretic Deposition
Authors: Zhou Minghua , Yu Huogen
Published: March 2012

Highly ordered sodium-free titanate nanotube films were one-step prepared on F-doped SnO2-coated (FTO) glass via an electrophoretic deposition method by using sodium titanate nanotubes as the precursor. It was found that the self-assembled formation of highly ordered sodium titanate nanotube films was accompanied with the effective removal of sodium ions in the nanotubes during the electrophoretic deposition process, resulting in the final formation of protonated titanate nanotube film. With increasing calcination temperature, the amorphous TiO2phase is formed by a dehydration process of the protonated titanate nanotubes at 300°C and further transforms into anatase TiO2when the calcination temperature is higher than 400°C. Compared with the as-prepared titanate nanotube film, the calcined titanate nanotube film (300–600°C) exhibits attractive photoinduced superhydrophilicity under UV-light irradiation. In particular, 500°C-calcined films show the best photoinduced superhydrophilicity, probably due to synergetic effects of enhanced crystallization, surface roughness, and ordered structures of the films.
A Note on Some Identities of Frobenius-Euler Numbers and Polynomials
Authors: Choi J. , Kim D. S. , Kim T. , Kim Y. H.
Published: March 2012

The purpose of this paper is to give some identities on the Frobenius-Euler numbers and polynomials by using the fermionicp-adicq-integral equation onℤp.
Multilayer Films Electrodes Consisted of Cashew Gum and Polyaniline Assembled by the Layer-by-Layer Technique: Electrochemical Characterization and Its Use for Dopamine Determination
Authors: Barros Sergio Bitencourt Araújo , Leite Cleide Maria da Silva , de Brito Ana Cristina Facundo , Dos Santos Júnior José Ribeiro , Zucolotto Valtencir , Eiras Carla
Published: March 2012

We take advantage of polyelectrolyte feature exhibited by natural cashew gum (Anacardium occidentaleL.) (CG), found in northeast Brazil, to employ it in the formation of electroactive nanocomposites prepared by layer-by-layer (LbL) technique. We used polyaniline unmodified (PANI) or modified with phosphonic acid (PA), PANI-PA as cationic polyelectrolyte. On the other hand, the CG or polyvinyl sulfonic (PVS) acids were used as anionic polyelectrolytes. The films were prepared with PANI or PANI-PA intercalated with CG or with PVS alternately resulting in four films with different sequences: PANI/CG PANI-PA/CG, PANI/PVS and PANI-PA/PVS, respectively. Analysis by cyclic voltammetry (CV) of the films showed that the presence of gum increases the stability of the films in acidic medium. The performance of the modified electrode of PANI-PA/CG was evaluated in electro analytical determination of dopamine (DA). The tests showed great sensitivity of the film for this analyte that was detected at 10−5 mol L−1.
Structural Heterogeneities in Southeast Tibet: Implications for Regional Flow in the Lower Crust and Upper Mantle
Authors: Wang Zhi , Wang Xuben , Huang Runqiu , Huang Wenli
Published: March 2012

Our seismic study together with the MT analysis reveal a “R-shape” flow existing in both the lower crust and uppermost mantle, which suggests the crustal deformation along the deep, large sutures (such as the Longmen Shan fault and the Anninghe Fault) under the southeastern Tibetan Plateau is maintained by dynamic pressure from the regional flow intermingled with the hot upwelling asthenosphere. The material in the lower crust and uppermost mantle flowing outward from the center of the plateau is buttressed by the old, strong lithosphere that underlies the Sichuan basin, pushing up on the crust above and maintaining steep orogenic belt through dynamic pressure. We therefore consider that the “R-shape” regional flow played a key role in the crustal deformation along the deep suture zones of the Bangong-Nujiang, the Longmen-Shan faults, and other local heavily faulted zones beneath the southeastern Tibetan Plateau.
Epidermal Growth Factor Receptor Variant III Contributes to Cancer Stem Cell Phenotypes in Invasive Breast Carcinoma
Authors: Del Vecchio Catherine A. , Jensen Kristin C. , Nitta Ryan T. , Shain A. Hunter , Giacomini Craig P. , Wong Albert J.
Published: March 2012

EGFRvIII is a tumor-specific variant of the epidermal growth factor receptor (EGFR). Although EGFRvIII is most commonly found in glioblastoma, its expression in other tumor types remains controversial. In this study, we investigated EGFRvIII expression and amplification in primary breast carcinoma. Our analyses confirmed the presence of EGFRvIII, but in the absence of amplification or rearrangement of the EGFR locus. Nested reverse transcriptase PCR and flow cytometry were used to detect a higher percentage of positive cases. EGFRvIII-positive cells showed increased expression of genes associated with self-renewal and epithelial–mesenchymal transition along with a higher percentage of stem-like cells. EGFRvIII also increased in vitro sphere formation and in vivo tumor formation. Mechanistically, EGFRvIII mediated its effects through the Wnt/β-catenin pathway, leading to increased β-catenin target gene expression. Inhibition of this pathway reversed the observed effects on cancer stem cell (CSC) phenotypes. Together, our findings show that EGFRvIII is expressed in primary breast tumors and contributes to CSC phenotypes in breast cancer cell lines through the Wnt pathway. These data suggest a novel function for EGFRvIII in breast tumorigenesis. Cancer Res; 72(10); 2657–71. ©2012 AACR.
Endoplasmic Reticulum Stress, the Unfolded Protein Response, Autophagy, and the Integrated Regulation of Breast Cancer Cell Fate
Authors: Clarke Robert , Cook Katherine L. , Hu Rong , Facey Caroline O.B. , Tavassoly Iman , Schwartz Jessica L. , Baumann William T. , Tyson John J. , Xuan Jianhua , Wang Yue , Wärri Anni , Shajahan Ayesha N.
Published: March 2012

How breast cancer cells respond to the stress of endocrine therapies determines whether they will acquire a resistant phenotype or execute a cell-death pathway. After a survival signal is successfully executed, a cell must decide whether it should replicate. How these cell-fate decisions are regulated is unclear, but evidence suggests that the signals that determine these outcomes are highly integrated. Central to the final cell-fate decision is signaling from the unfolded protein response, which can be activated following the sensing of stress within the endoplasmic reticulum. The duration of the response to stress is partly mediated by the duration of inositol-requiring enzyme-1 activation following its release from heat shock protein A5. The resulting signals appear to use several B-cell lymphoma-2 family members to both suppress apoptosis and activate autophagy. Changes in metabolism induced by cellular stress are key components of this regulatory system, and further adaptation of the metabolome is affected in response to stress. Here we describe the unfolded protein response, autophagy, and apoptosis, and how the regulation of these processes is integrated. Central topologic features of the signaling network that integrate cell-fate regulation and decision execution are discussed. Cancer Res; 72(6); 1321–31. ©2012 AACR.
Molecular Pathways: The Role of Primary Cilia in Cancer Progression and Therapeutics with a Focus on Hedgehog Signaling
Authors: Hassounah Nadia B. , Bunch Thomas A. , McDermott Kimberly M.
Published: March 2012

Abnormal Hedgehog (Hh) pathway activity has been reported in many cancers, including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas, glioblastomas, and breast and prostate cancers. For this reason, the Hh pathway is a flourishing area for development of anticancer drugs such as Hh ligand antagonists (e.g., 5E1 and robotnikinin), Smo inhibitors (e.g., GDC-0449 and IPI-926), and Gli transcriptional activity inhibitors (e.g., GANT58 and GANT61). It is now clear that primary cilia are required for activation of the Hh pathway in normal vertebrate cells. It is in the primary cilium that both positive and negative effectors of the Hh pathway are processed by posttranslational modifications. In many cancers, preliminary results suggest that primary cilia are lost. As drugs that inhibit different steps of the Hh pathway are developed, it will be important to consider how these drugs will function in the context of primary cilia in the tumor environment. Here, we discuss why some of the Hh inhibitors may be ineffective if primary cilia are lost on cancer cells. Understanding the relationships between clinical inhibitors of the Hh pathway and the presence or absence of primary cilia may turn out to be critical for targeting these therapeutics to the correct population of patients and improving their efficacy. Further work is needed in this area to maximize the potential of these exciting therapeutic targets. Clin Cancer Res; 18(9); 2429–35. ©2012 AACR.
PIK3CA/PTEN Mutations and Akt Activation As Markers of Sensitivity to Allosteric mTOR Inhibitors
Authors: Meric-Bernstam Funda , Akcakanat Argun , Chen Huiqin , Do Kim-Anh , Sangai Takafumi , Adkins Farrell , Gonzalez-Angulo Ana Maria , Rashid Asif , Crosby Katherine , Dong Mei , Phan Alexandria T. , Wolff Robert A. , Gupta Sanjay , Mills Gordon B. , Yao James
Published: March 2012

Purpose: We sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance.

Experimental Design: Cancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer cells and patients with neuroendocrine tumor (NET) were treated with rapalogs and Akt phosphorylation was assessed.

Results: Thirty-one cell lines were rapamycin sensitive (RS) and 12 were relatively rapamycin resistant (RR; IC50 > 100 nmol/L). Cells with PIK3CA and/or PTEN mutations were more likely to be RS (P = 0.0123). Akt phosphorylation (S473 and T308) was significantly higher in RS cells (P < 0.0001). Rapamycin led to a significantly greater pathway inhibition and greater increase in p-Akt T308 (P < 0.0001) and p-Akt S473 (P = 0.0009) in RS cells. Rapamycin and everolimus significantly increased Akt phosphorylation but inhibited growth in an in vivo NET model (BON). In patients with NETs treated with everolimus and octreotide, progression-free survival correlated with p-Akt T308 in pretreatment (R = 0.4762, P = 0.0533) and on-treatment tumor biopsies (R = 0.6041, P = 0.0102). Patients who had a documented partial response were more likely to have an increase in p-Akt T308 with treatment compared with nonresponders (P = 0.0146).

Conclusion: PIK3CA/PTEN genomic aberrations and high p-Akt levels are associated with rapamycin sensitivity in vitro. Rapamycin-mediated Akt activation is greater in RS cells, with a similar observation in patients with clinical responses on exploratory biomarker analysis; thus feedback loop activation of Akt is not a marker of resistance but rather may function as an indicator of rapamycin activity. Clin Cancer Res; 18(6); 1777–89. ©2012 AACR.
Increased Expression of Nox1 in Neointimal Smooth Muscle Cells Promotes Activation of Matrix Metalloproteinase-9
Authors: Xu Shaoping , Shriver Amy S. , Jagadeesha Dammanahalli K. , Chamseddine Ali H. , Szőcs Katalin , Weintraub Neal L. , Griendling Kathy K. , Bhalla Ramesh C. , Miller, Jr. Francis J.
Published: March 2012

Objective: Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). Methods and Results: Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. Conclusions: Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation.
Influence of Aldosterone and Salt or Ouabain in A10 Rat Aorta Smooth Muscle Cells
Authors: Schwerdt Gerald , Frisch Annett , Mildenberger Sigrid , Hilgenfeld Tim , Grossmann Claudia , Gekle Michael
Published: March 2012

Background/Aims: It is currently under debate whether aldosterone is able to induce fibrosis or whether it acts only as a cofactor under pathological conditions, e.g. as an elevated salt (NaCl) load. Methods: We tested the interaction of 10 nM aldosterone, 15 mM NaCl and 1 µM ouabain using rat aorta smooth muscle cells (A10) with respect to the following parameters: necrosis, apoptosis, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase activity, glutathione (GSH) content, collagen and fibronectin homeostasis and intracellular calcium distribution. Results: Necrosis rates were increased after 48 h of incubation with aldosterone, salt or ouabain and in the combination of aldosterone and salt or ouabain. Apoptosis rates were decreased. A reduced defense capacity against oxidative stress was mirrored in the decreased G6PD activity and GSH content. Collagen III or fibronectin synthesis rates were unchanged, but gelatinase activity was increased resulting in a decreased media collagen III and fibronectin content. Calcium stores were increased by aldosterone in combination with ouabain. Conclusion: Aldosterone and salt per se can lead to cell injury that is aggravated in combination or with cardiotonic steroids. In cooperation with other vascular cells, this can generate a permissive milieu enabling aldosterone or salt to promote more extensive vascular injury.
Pulmonary Arterial Dilatation in Pulmonary Hypertension: Prevalence and Prognostic Relevance
Authors: Badagliacca Roberto , Poscia Roberto , Pezzuto Beatrice , Papa Silvia , Nona Alfred , Mancone Massimo , Mezzapesa Mario , Nocioni Martina , Sciomer Susanna , Valli Gabriele , Cedrone Nadia , Fedele Francesco , Vizza Carmine Dario
Published: March 2012

Objectives: Pulmonary arterial dilatation is considered a consequence of chronic pulmonary hypertension (PH), but despite its relatively common detection, its prevalence and prognostic impact have not yet been systematically investigated. The aim of the study was to investigate these factors in a relatively large cohort of severe PH patients. Methods: One hundred and forty-one consecutive patients diagnosed with PH were monitored for a mean of 957 days. Data including functional class, exercise capacity, invasive hemodynamics and pulmonary artery (PA) echo/CT scan measurement were performed and outcomes prospectively collected. Results: PA dilatation is a common feature, present in the 76.6% of cases in this cohort of severe PH patients. Survival at 1, 2 and 3 years was 83, 71 and 58%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were related to pulmonary arterial hypertension associated with connective tissue disease (CDT-PAH), New York Heart Association (NYHA) functional class, 6-min walk test and right atrial pressure. On multivariate analysis only CDT-PAH and NYHA functional class remained independently associated with poor survival. Conclusions: PA dilatation is commonly detected in severe PH patients and is not associated with an increased risk of death.
Subjective and Objective Assessment of Edema during Adjuvant Chemotherapy for Breast Cancer Using Taxane-Containing Regimens in a Randomized Controlled Trial: The National Surgical Adjuvant Study of Breast Cancer 02
Authors: Ohsumi Shozo , Shimozuma Kojiro , Ohashi Yasuo , Takeuchi Ayano , Suemasu Kimito , Kuranami Masaru , Ohno Shinji , Watanabe Toru
Published: March 2012

Objective: To elucidate the time course of taxane-induced edema which may affect the patients’ quality of life (QOL). Patients and Methods: Our study included the first 300 Japanese patients assigned to 1 of 4 regimens using docetaxel (DTX) or paclitaxel (PTX) by 1:1:1:1 in a randomized controlled trial to evaluate the efficacy of adjuvant therapies for node-positive breast cancer. Patients’ QOL was prospectively assessed by the Functional Assessment of Cancer Therapy (FACT)-breast and -taxane (FACT-T) subscale. The scores of FACT items regarding edema and body weight were used as indicators of edema. Results: The scores for ‘anasarca’, ‘edema of the hands’ and ‘edema of the legs and feet’ of the FACT-T subscale worsened up to 1–2 months after chemotherapy, and body weights increased remarkably until cycle 8 in patients treated with DTX alone (75 mg/m2, 8 cycles, every 3 weeks). Edema-related symptoms and body weight were relatively stable in the other treatment groups. There were statistically significant differences in the scores of those items and in the changes of body weight both between the DTX-alone group and the other three groups combined, and between the groups using DTX and those using PTX. Conclusion: Many patients receiving DTX for >4 cycles suffered significantly from edema.
HER2/neu May Not Be an Interesting Target in Biliary Cancers: Results of an Early Phase II Study with Lapatinib
Authors: Peck Joshua , Wei Lai , Zalupski Mark , O’Neil Bert , Villalona Calero Miguel , Bekaii-Saab Tanios
Published: March 2012

Purpose: Biliary cancers (BCs) respond poorly to chemotherapy. Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, both implicated in cholangiocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in BC. Methods: A Fleming phase II design with a single stage of 25 patients was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/neu and EGFR.Results:Nine patients with BC enrolled in this study. The study was terminated early because of futility. The most common toxicities were nausea and fatigue (78%) and diarrhea (67%). No responses were observed. Of 8 evaluable patients, 4 (50%) had stable disease. Median progression-free survival was 2.6 months (95% CI 1.6–4.4) and median overall survival was 5.1 months (95% CI 2.0–16.5). No somatic mutations in EGFR (exons 18–21) or HER2/neu were found. We did not find evidence of HER2 overexpression. Conclusions:Lapatinib is well tolerated but failed to show activity as a single agent in treating patients with BC. Despite the small patient population, our study is consistent with previous findings, suggesting that targeting HER2/neu does not appear to be an effective therapy for BC.
Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study
Authors: Aoyagi Satoru , Hata Hiroo , Homma Erina , Shimizu Hiroshi
Published: March 2012

Objective: To determine the beneficial effect of maintenance therapy in stage II and III melanoma by sequential local injection of low-dose interferon-β. Methods: We reviewed 46 patients with stage II and III primary melanoma at our institution from 2004 through 2009. Twenty-one patients were treated with interferon-β maintenance therapy consisting of subcutaneous injection of natural interferon-β at a dose of 3 × 106 IU/day for 10 consecutive days, and 25 patients underwent observation alone. Results: Compared with all patients, overall survival and relapse-free survival were significantly worse in the observation group than in the interferon-β group (p = 0.024 and 0.029, respectively). In stage II, a significant difference in overall survival, but not in relapse-free survival, was seen between the two groups (p = 0.041). When the interferon-β group was stratified by subgroup, there was a statistical difference only between dosage and duration (p = 0.027 and p < 0.001, respectively). Conclusions: This study demonstrates that maintenance therapy by interferon-β is beneficial in the outcome of the disease without substantial toxic effects, especially in patients with stage II melanoma. Extension of the duration of treatment beyond 2 years could further improve the therapeutic efficacy of interferon-β.
Exercise Response in Hypertrophic Cardiomyopathy
Authors: Soullier Camille , Obert Philippe , Doucende Gregory , Nottin Stéphane , Cade Stéphane , Perez-Martin Antonia , Messner-Pellenc Patrick , Schuster Iris
Published: March 2012

Background—

Abnormal left ventricular (LV) deformational mechanics have been demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but there is a lack of information on their adaptation to exercise. The aim of this study was to assess the adaptability of LV strains and torsional mechanics during exercise in HCM patients.

Methods and Results—

Twenty nonobstructive HCM patients (age, 48.3±12.3 years; 14 men) and 20 control subjects underwent speckle-tracking echocardiographic measurement of longitudinal, radial, and circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at rest and submaximal exercise. HCM patients showed lower resting longitudinal (−15.7±5.0% versus −19.4±2.6%,
P
<0.001) and radial (38.1±11.3% versus 44.7±14.4%,
P
<0.05) strains but higher circumferential strain (−21.9±4.0% versus −18.8±2.3%,
P
<0.05) and twist (15.7±3.6° versus 9.3±2.6°,
P
<0.0001) than control subjects. Exercise induced an increase in all strains in control subjects but only a moderate increase in longitudinal strain (to −18.4±5.0%), without significant changes in radial and circumferential strains or twist in HCM patients. Exercise peak UTR was lower (−119.0±31.5°/s versus −137.3±41.1°/s) and occurred later (137±18% versus 125±11% systolic time,
P
<0.05) in HCM than in control subjects. A significant relationship between twist and UTR was obtained in control subjects (ß=−0.0807,
P
<0.001) but not in HCM patients (ß=−0.0051,
P
=0.68).

Conclusions—

HCM patients had severely limited strain adaptability and no LV twisting reserve at exercise. They had reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by twist-untwist mechanics.
Multiple Roles for Neutrophils in Atherosclerosis
Authors: Soehnlein Oliver
Published: March 2012

Because of their rare detection in atherosclerotic lesions, the involvement of neutrophils in the pathophysiology of atherosclerosis has been largely denied. However, over the past couple of years, studies have provided convincing evidence for the presence of neutrophils in atherosclerotic plaques and further revealed the causal contribution of neutrophils during various stages of atherosclerosis. This review describes mechanisms underlying hyperlipidemia-mediated neutrophilia and how neutrophils may enter atherosclerotic lesions. It also highlights possible mechanisms of neutrophil-driven atherogenesis and plaque destabilization. Knowledge of the contribution of neutrophils to atherosclerosis will allow for exploration of new avenues in the treatment of atherogenesis and atherothrombosis.
Lymphocytes and the Adventitial Immune Response in Atherosclerosis
Authors: Campbell Kirsti A. , Lipinski Michael J. , Doran Amanda C. , Skaflen Marcus D. , Fuster Valentin , McNamara Coleen A.
Published: March 2012

Although much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue. Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature.
P. V. Kane, Professor Kane's Contribution to Dharmaśāstra Literature
Authors: Lubin
Published: March 2012

No Abstract
Chenet, François: Psychogenèse et cosmogonie selon le Yoga-Vāsistha ``Le monde est dans l'âme''
Authors: Hanneder
Published: March 2012

No Abstract
Catherine Clémentin-Ojha, Le trident sur le palais: Une cabale anti-vishnouite dans un royaume hindou à l'époque coloniale
Authors: Horstmann
Published: March 2012

No Abstract
The Place of the Mālavikāgnimitra within Kālidāsa's oeuvre
Authors: Tieken
Published: March 2012

No Abstract
Pandanus '98: Flowers, Nature, Semiotics. Kāvya and Sangam. Edited by Jaroslav Vacek (and) Blanka Knotková-Čapková
Authors: Lienhard
Published: March 2012

No Abstract
Uddālaka's Teaching in Chāndogya Upanisad 6, 8–16
Authors: Bodewitz
Published: March 2012

No Abstract
Madhavi Bhaskar Kolhatkar, Surā: The Liquor and the Vedic Sacrifice
Authors: Steiner
Published: March 2012

No Abstract
Water and Salt (II): `Material' Causality and Hylozoic Thought in the Yājñavalkya-Maitreyī Dialogue?
Authors: Slaje
Published: March 2012

No Abstract
Nirmal Dass: Songs of the Saints from the Adi Granth
Authors: Boehm-Tettelbach
Published: March 2012

No Abstract
Pachow, W., A Comparative Study of the Prāatimoksasūtra on the Basis of Its Chinese, Tibetan, Sanskrit and Pāli Versions [Buddhist Tradition Series Volume 31]
Authors: v. Hinüber
Published: March 2012

No Abstract
H. Bechert, Der Buddhismus I. Der indische Buddhismus und seine Verzweigungen von Heinz Bechert, Johannes Bronkhorst, Jacob Ensink, Jens-Uwe Hartmann, Petra Kieffer-Pülz, Hans-Joachim Klimkeit, Siegfried Lienhard, Ian William Mabbett
Authors: v. Hinüber
Published: March 2012

No Abstract
Professor R.N. Dandekar March 17, 1909–December 11, 2001
Authors: Deshpande
Published: March 2012

No Abstract
Iris Colditz, Zur Sozialterminologie der iranischen Manichäer. Eine semantische Analyse im Vergleich zu den nichtmanichäischen iranischen Quellen
Authors: Degener
Published: March 2012

No Abstract
Bühnemann, Gudrun, The Iconography of Hindu Tantric Deities
Authors: Flood
Published: March 2012

No Abstract
On ``The Death of Sanskrit''
Authors: Hanneder
Published: March 2012

No Abstract
Grünendahl, Reinhold, South Indian Scripts in Sanskrit Manuscripts and Prints. Grantha Tamil – Malayalam – Telugu –Kannada – Nandinagari
Authors: v. Hinüber
Published: March 2012

No Abstract
Chojnacki, Christine; Jens-Uwe Hartmann und Volker M. Tschannerl (eds.), Vividharatnakarandaka. Festgabe für Adelheid Mette [Indica et Tibetica Band 37]
Authors: Skilling
Published: March 2012

No Abstract
N. Ramachandra Bhatt, La religion de S´iva d'après les sources sanskrites
Authors: Schreiner
Published: March 2012

No Abstract
Renate Syed, ``Ein Unglück ist die Tochter''. Zur Diskriminierung des Mädchens im alten und heutigen Indien
Authors: Waligora
Published: March 2012

No Abstract
Oskar v. Hinüber, Das ältere Mittelindisch im Überblick
Authors: Berger
Published: March 2012

No Abstract
Studies in Yama and Māra
Authors: Wayman Alex
Published: March 2012

Āryāsailga, or Asailga, has this passage in his Śravaka-bhümi as found in the photographic manuscript of the Bihar Research Society, and a translation follows immediately after the Sanskrit
Kant Et Le Mādhyamika a Propos D'un Livre Récent
Authors: May Jacques
Published: March 2012

Le système Mādhyamika n'avait pas fait jusqu'ici l'objet d'un vaste exposé d'ensemble. Les exposés de Stcherbatsky, La Vallée Poussin, Schayer restaient des introductions, quelque évidents que fussent leurs divers mérites: netteté des idées et vigueur polémique, minutie et soud du document, pénétration philosophique. Les Indledende Bemœrkninger de Poul Tuxen sont malheureusement écrites en une langue peu accessible.
Die Burušaski-Lehnwörter in Der Zigeunersprache
Authors: Berger Hermann
Published: March 2012

Wenn der äußerste Nordwesten Indiens zwar nicht, wie man früher annahm, als die ursprüngliche Heimat der Zigeuner, so doch wenigstens als ihre letzte Station vor dem Verlassen des indo-arischen Sprachbereichs gelten darf, so ist es nicht verwunderlich, wenn wir neben einigen Dardismen im Zig. auch Vokabeln aus dem Wortschatz des den dardischen Sprachen unmittelbar benachbarten Burušaski vorfinden. Die sicheren Beispiele sind zwar noch nicht sehr zahlreich, aber für die Sprachwissenschaft von ungleich größerem Interesse als die vielen Entlehnungen aus anderen nicht-indischen Sprachen (Persisch, Armenisch, Griechisch usw.), denn sie dienen im Gegensatz zu diesen nicht nur zur weiteren Aufhellung der Wanderwege der Zigeuner, sondern können ausnahmsweise auch neues Licht auf die Geschichte der gebenden Sprache werfen. Wenn wir nämlich, vorsichtig geschätzt, den Auszug der Zigeuner aus Nordwestindien in die Mitte des ersten nachchristlichen Jahrtausends verlegen, so können sie uns einen wenn auch nur bescheidenen Begriff von dem lautlichen Zustand des Bur. in einer Zeit geben, aus der sonst jedes Zeugnis fehlt. Die Veränderungen, die die betreffenden Bur.-Wörter durchgemacht haben, sind freilich in der Regel nicht sehr groß, was wiederum für den tröstlich sein wird, der angesichts des rapiden Lautverfalls mancher indogermanischer Sprachen dem von mir an anderer Stelle begonnenen Nachweis einer Verwandtschaft des Bur. mit dem Baskischen noch mit begreiflichem Mißtrauen gegenübersteht; sie müssen aber trotzdem mit Sorgfalt registriert werden, weil sie die mit Hilfe des Bask. gewonnenen Lautgesetze stützen oder die Entwicklung von Wörtern aufhellen, für die im Bask. keine Entsprechung mehr vorhanden ist.
Judeo-Persian Deverbatives in -ŠN and -ŠT*
Authors: Paper Herbert H.
Published: March 2012

The starting point of this presentation of data is the modern Persian deverbative nominal abstract in -éš. These are freely formed in Persian from the present stems of verbs. A trustworthy standard source on the origin of this suffix is P. Horn, “Neupersische Schriftsprache”, Grundriss der Iranischen Philologie, I, 182
On the Meaning of SKR. (Pra)Bhinnāñjana
Authors: Vogel Claus
Published: March 2012

1. Among the many stereotyped similes occurring in Sanskrit literature, ornate and otherwise, those formed with (Pra)Bhinnāñjana require some elucidative comment inasmuch as neither the object nor the point of comparison are entirely clear in this case.
Avestisch Hizu.drājah- und Zānu.drājah
Authors: Schmitt Rüdiger
Published: March 2012

Bartholomae postuliert für avest. drājah- neben der ganz geläufigen und etymologisch gerechtfertigten Bedeutung “Strecke, Länge”, die als Simplex nur in dem Bereichsakkusativ drājō “an Länge”, ferner in mehr als einem Dutzend Zusammensetzungen vorkommt, einen Bedeutungsansatz “Strecken, Vorstrecken”, der sich nur in Zusammensetzungen nachweisen lasse. Damit können aber folgende adjektivische (Possessiv-) oder substantivische (Determinativ-) Komposita nicht gemeint sein: aēsö.drājah- (Bartholomae, Sp. 35) “ein aēša- lang”; aiiar.drājah- (Bartholomae, Sp. 158) “Dauer eines Tages”; čartu.drājah- (Bartholomae, Sp. 582) “Länge eines čartu-”; dānu.drājah- (Bartholomae, Sp. 734) “so lang wie ein Fluss”; baši.drājah- (Bartholomae, Sp. 952) “ein baši- lang”; biiär.drājah- (Bartholomae, Sp. 971) “Dauer von zwei Jahren”; frabāzu.dräjah- (Bartholomae, Sp. 985) “Länge eines Unterarms”; frabdö.drājah- (Bartholomae, Sp. 986) “Länge eines Vorderfusses”; frārāni.drājah- (Bartholomae, Sp. 1021) “Länge eines Elle”; yār.drājah- (Bartholomae, Sp. 1287) “Dauer eines Jahres”; vitasti.drājah- (Bartholomae, Sp. 1440) “Länge einer Spanne”; vībäbāzu.drājah- (Bartholomae, Sp. 1448) “Länge eines vībāzu-”. Hierzu tritt noch māz.- drājahiia-, ntr. (Bartholomae, Sp. 1170) “Dauer eines Monats”, das adjektivisches *māz.drājah- “einen Monat lang” voraussetzt. In all diesen Wörtern bezeichnet drājah- also zeitliche und räumliche Länge – ebenso übrigens bei der Verwendung des Simplex als accusativus limitationis -, wie das der zugrunde liegenden Wurzel (idg. *dlIgh-) von Hause aus zukam.
Considérations sur une technique du Rasāyana āyurvédique
Authors: Roşu Arion
Published: March 2012

Rejuvenation techniques, inspired by a common classical tradition, are described in Caraka (Cikitsā I, 1–4) and in Suśruta (Cikitsā XXVII–XXX), followed up by the Nāvanītaka (Bower Ms., sl.188–200) and by the Astāngahrdayasamhitā (Uttara XXXIX). Valuable mediaeval tīkā comment on the details of these techniques and indeed interesting modern examples of a treatment closely following the ancient medical texts are known.[Contrary to the cure taking place ‘in the open air and in the sun’ (vātātapika), the practice of rejuvenation characterized by the ku is applied indoors in premises called kutī or āgāra, built according to definite rules (site, architecture, etc.). The patient enters at a time astrologically auspicious, after performing certain rites and preparing his mind for a treatment which is as perilous as it is laborious.The rites of the operation and the unusual type of abode, difficult to interpret, permit, however, an examination of the textual data in a different light from that of the scholiasts themselves, who remain very guarded, and even obscure, on important points of detail. Here one must presume an initiation ceremony whose method was used for the legendary sages as well as patients of today. The technique which is called ‘retreat in a hut’ implies the idea of regressus ad uterum. Rejuvenation which constitutes, from the biological point of view, a regeneration of the body (kāyakalpa) must be considered on the symbolical plane as a ‘new birth’: the patient is assimilated to the embryo, and to the uterus correspond both the ‘hut’ described in the classical Āyurvedic treatises and the dark enclosed premises recommended by the modern kavirāj.