bluuebunny/crossref_metadata_2025 huggingface dataset:
My Life in Sociology
Authors: Glazer Nathan
Published: June 2012

Following on an article in Bennett Berger (1990) , Authors of Their Own Lives, titled “From Socialism to Sociology,” in which I and other sociologists describe how we came to sociology, I continue with my academic and public career as a sociologist at the University of California–Berkeley (1963–1969) and at Harvard subsequently, in the Graduate School of Education and the Sociology Department. I describe my involvement in the formulation of urban policy in the Kennedy and Johnson administrations and beyond, and my attempt to understand the student revolt at Berkeley, which spread throughout the United States and indeed much of the world. I further discuss my long involvement in the issue of affirmative action, on which I in time changed my views, originally based on a distinctive conception of the course of ethnicity and ethnic and racial groups in the United States, from critical opposition to acceptance, and my similar involvement in the debates over social policy in the United States, in which a complex point of view has too often been summarized under the term neoconservatism.
Group Culture and the Interaction Order: Local Sociology on the Meso-Level
Authors: Fine Gary Alan
Published: June 2012

Although explicit attention to the role of small groups has waned in sociology, an empirical understanding of the interaction order is increasing. A focus on the group—the meso-level of analysis—enriches both structural and interactional approaches, stressing shared and ongoing meaning. Groups constitute social order, just as groups are themselves constituted by that order. The examination of local action reveals how interaction orders emerge and create meanings that spread throughout a wider network. Despite the limits of a meso-level analysis in examining both external webs of constraint and immediate negotiations, this approach addresses identity, social capital, collective action, group culture, networks, and civil society. By building on collective identity, shared history, common spaces, and ongoing social relations, groups provide mechanisms through which individuals fit into larger structures and through which social structures shape individuals.
CD24 can be used to isolate Lgr5+ putative colonic epithelial stem cells in mice
Authors: King Jeffrey B. , von Furstenberg Richard J. , Smith Brian J. , McNaughton Kirk K. , Galanko Joseph A. , Henning Susan J.
Published: June 2012

A growing body of evidence has implicated CD24, a cell-surface protein, as a marker of colorectal cancer stem cells and target for antitumor therapy, although its presence in normal colonic epithelium has not been fully characterized. Previously, our group showed that CD24-based cell sorting can be used to isolate a fraction of murine small intestinal epithelial cells enriched in actively cycling stem cells. Similarly, we hypothesized that CD24-based isolation of colonic epithelial cells would generate a fraction enriched in actively cycling colonic epithelial stem cells (CESCs). Immunohistochemistry performed on mouse colonic tissue showed CD24 expression in the bottom half of proximal colon crypts and the crypt base in the distal colon. This pattern of distribution was similar to enhanced green fluorescent protein (EGFP) expression in Lgr5-EGFP mice. Areas expressing CD24 contained actively proliferating cells as determined by ethynyl deoxyuridine (EdU) incorporation, with a distinct difference between the proximal colon, where EdU-labeled cells were most frequent in the midcrypt, and the distal colon, where they were primarily at the crypt base. Flow cytometric analyses of single epithelial cells, identified by epithelial cell adhesion molecule (EpCAM) positivity, from mouse colon revealed an actively cycling CD24+ fraction that contained the majority of Lgr5-EGFP+ putative CESCs. Transcript analysis by quantitative RT-PCR confirmed enrichment of active CESC markers [leucine-rich-repeat-containing G protein-coupled receptor 5 (Lgr5), ephrin type B receptor 2 (EphB2), and CD166] in the CD24+EpCAM+ fraction but also showed enrichment of quiescent CESC markers [leucine-rich repeats and immunoglobin domains (Lrig), doublecortin and calmodulin kinase-like 1 (DCAMKL-1), and murine telomerase reverse transcriptase (mTert)]. We conclude that CD24-based sorting in wild-type mice isolates a colonic epithelial fraction highly enriched in actively cycling and quiescent putative CESCs. Furthermore, the presence of CD24 expression in normal colonic epithelium may have important implications for the use of anti-CD24-based colorectal cancer therapies.
Mechanical and propelling efficiency in swimming derived from exercise using a laboratory-based whole-body swimming ergometer
Authors: Zamparo Paola , Swaine Ian L.
Published: June 2012

Determining the efficiency of a swimming stroke is difficult because different “efficiencies” can be computed based on the partitioning of mechanical power output (Ẇ) into its useful and nonuseful components, as well as because of the difficulties in measuring the forces that a swimmer can exert in water. In this paper, overall efficiency (ηO= ẆTOT/Ė, where ẆTOTis total mechanical power output, and Ė is overall metabolic power input) was calculated in 10 swimmers by means of a laboratory-based whole-body swimming ergometer, whereas propelling efficiency (ηP= ẆD/ẆTOT, where ẆDis the power to overcome drag) was estimated based on these values and on values of drag efficiency (ηD= ẆD/Ė): ηP= ηD/ηO. The values of ηDreported in the literature range from 0.03 to 0.09 (based on data for passive and active drag, respectively). ηOwas 0.28 ± 0.01, and ηPwas estimated to range from ∼0.10 (ηD= 0.03) to 0.35 (ηD= 0.09). Even if there are obvious limitations to exact simulation of the whole swimming stroke within the laboratory, these calculations suggest that the data reported in the literature for ηOare probably underestimated, because not all components of ẆTOTcan be measured accurately in this environment. Similarly, our estimations of ηPsuggest that the data reported in the literature are probably overestimated.
Exercise pressor reflex function in female rats fluctuates with the estrous cycle
Authors: Koba Satoshi , Yoshinaga Kenshi , Fujita Sayaka , Miyoshi Michio , Watanabe Tatsuo
Published: June 2012

In women, sympathoexcitation during static handgrip exercise is reduced during the follicular phase of the ovarian cycle compared with the menstrual phase. Previous animal studies have demonstrated that estrogen modulates the exercise pressor reflex, a sympathoexcitatory mechanism originating in contracting skeletal muscle. The present study was conducted in female rats to determine whether skeletal muscle contraction-evoked reflex sympathoexcitation fluctuates with the estrous cycle. The estrous cycle was judged by vaginal smear. Plasma concentrations of estrogen were significantly ( P < 0.05) higher in rats during the proestrus phase of the estrus cycle than those during the diestrus phase. In decerebrate rats, either electrically induced 30-s continuous static contraction of the hindlimb muscle or 30-s passive stretch of Achilles tendon (a maneuver that selectively stimulates mechanically sensitive muscle afferents) evoked less renal sympathoexcitatory and pressor responses in the proestrus animals than in the diestrus animals. Renal sympathoexcitatory response to 1-min intermittent (1- to 4-s stimulation to relaxation) bouts of static contraction was also significantly less in the proestrus rats than that in the diestrus rats. In ovariectomized female rats, 17β-estradiol applied into a well covering the dorsal surface of the lumbar spinal cord significantly reduced skeletal muscle contraction-evoked responses. These observations demonstrate that the exercise pressor reflex function and its mechanical component fluctuate with the estrous cycle in rats. Estrogen may cause these fluctuations through its attenuating effects on the spinal component of the reflex arc.
Dynamic interaction between the heart and its sympathetic innervation following T5 spinal cord transection
Authors: Lujan Heidi L. , Janbaih Hussein , DiCarlo Stephen E.
Published: June 2012

Midthoracic spinal cord injury (SCI) is associated with enhanced sympathetic support of heart rate as well as myocardial damage related to calcium overload. The myocardial damage may elicit an enhanced sympathetic support of contractility to maintain ventricular function. In contrast, the level of inotropic drive may be reduced to match the lower afterload that results from the injury-induced reduction in arterial pressure. Accordingly, the inotropic response to midthoracic SCI may be increased or decreased but has not been investigated and therefore remains unknown. Furthermore, the altered ventricular function may be associated with anatomical changes in cardiac sympathetic innervation. To determine the inotropic drive following midthoracic SCI, a telemetry device was used for repeated measurements of left ventricular (LV) function, with and without beta-adrenergic receptor blockade, in rats before and after midthoracic SCI or sham SCI. In addition, NGF content (ELISA) and dendritic arborization (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac-projecting sympathetic postganglionic neurons in the stellate ganglia were determined. Midthoracic SCI was associated with an enhanced sympathetic support of heart rate, dP/d t+, and dP/d t−. Importantly, cardiac function was lower following blockade of the sympathetic nervous system in rats with midthoracic SCI compared with sham-operated rats. Finally, these functional neuroplastic changes were associated with an increased NGF content and structural neuroplasticity within the stellate ganglia. Results document impaired LV function with codirectional changes in chronotropic and inotropic responses following midthoracic SCI. These functional changes were associated with a dynamic interaction between the heart and its sympathetic innervation.
Dopamine neurons in the ventral tegmental area fire faster in adolescent rats than in adults
Authors: McCutcheon James E. , Conrad Kelly L. , Carr Steven B. , Ford Kerstin A. , McGehee Daniel S. , Marinelli Michela
Published: June 2012

Adolescence may be a period of vulnerability to drug addiction. In rats, elevated firing activity of ventral tegmental area (VTA) dopamine neurons predicts enhanced addiction liability. Our aim was to determine if dopamine neurons are more active in adolescents than in adults and to examine mechanisms underlying any age-related difference. VTA dopamine neurons fired faster in adolescents than in adults as measured with in vivo extracellular recordings. Dopamine neuron firing can be divided into nonbursting (single spikes) and bursting activity (clusters of high-frequency spikes). Nonbursting activity was higher in adolescents compared with adults. Frequency of burst events did not differ between ages, but bursts were longer in adolescents than in adults. Elevated dopamine neuron firing in adolescent rats was also observed in cell-attached recordings in ex vivo brain slices. Using whole cell recordings, we found that passive and active membrane properties were similar across ages. Hyperpolarization-activated cation currents and small-conductance calcium-activated potassium channel currents were also comparable across ages. We found no difference in dopamine D2-class autoreceptor function across ages, although the high baseline firing in adolescents resulted in autoreceptor activation being less effective at silencing neurons. Finally, AMPA receptor-mediated spontaneous excitatory postsynaptic currents occurred at lower frequency in adolescents; GABAA receptor-mediated spontaneous inhibitory postsynaptic currents occurred at both lower frequency and smaller amplitude in adolescents. In conclusion, VTA dopamine neurons fire faster in adolescence, potentially because GABA tone increases as rats reach adulthood. This elevation of firing rate during adolescence is consistent with it representing a vulnerable period for developing drug addiction.
Efficient estimation of phase-response curves via compressive sensing
Authors: Hong Sungho , Robberechts Quinten , Schutter Erik De
Published: June 2012

The phase-response curve (PRC), relating the phase shift of an oscillator to external perturbation, is an important tool to study neurons and their population behavior. It can be experimentally estimated by measuring the phase changes caused by probe stimuli. These stimuli, usually short pulses or continuous noise, have a much wider frequency spectrum than that of neuronal dynamics. This makes the experimental data high dimensional while the number of data samples tends to be small. Current PRC estimation methods have not been optimized for efficiently discovering the relevant degrees of freedom from such data. We propose a systematic and efficient approach based on a recently developed signal processing theory called compressive sensing (CS). CS is a framework for recovering sparsely constructed signals from undersampled data and is suitable for extracting information about the PRC from finite but high-dimensional experimental measurements. We illustrate how the CS algorithm can be translated into an estimation scheme and demonstrate that our CS method can produce good estimates of the PRCs with simulated and experimental data, especially when the data size is so small that simple approaches such as naive averaging fail. The tradeoffs between degrees of freedom vs. goodness-of-fit were systematically analyzed, which help us to understand better what part of the data has the most predictive power. Our results illustrate that finite sizes of neuroscientific data in general compounded by large dimensionality can hamper studies of the neural code and suggest that CS is a good tool for overcoming this challenge.
In vivo dual intra- and extracellular recordings suggest bidirectional coupling between CA1 pyramidal neurons
Authors: Chorev Edith , Brecht Michael
Published: June 2012

Spikelets, small spikelike membrane potential deflections, are prominent in the activity of hippocampal pyramidal neurons in vivo. The origin of spikelets is still a source of much controversy. Somatically recorded spikelets have been postulated to originate from dendritic spikes, ectopic spikes, or spikes in an electrically coupled neuron. To differentiate between the different proposed mechanisms we used a dual recording approach in which we simultaneously recorded the intracellular activity of one CA1 pyramidal neuron and the extracellular activity in its vicinity, thus monitoring extracellularly the activity of both the intracellularly recorded cell as well as other units in its surroundings. Spikelets were observed in a quarter of our recordings ( n = 36). In eight of these nine recordings a second extracellular unit fired in correlation with spikelet occurrences. This observation is consistent with the idea that the spikelets reflect action potentials of electrically coupled nearby neurons. The extracellular spikes of these secondary units preceded the onset of spikelets. While the intracellular spikelet amplitude was voltage dependent, the simultaneously recorded extracellular unit remained unchanged. Spikelets often triggered action potentials in neurons, resulting in a characteristic 1- to 2-ms delay between spikelet onset and firing. Here we show that this relationship is bidirectional, with spikes being triggered by and also triggering spikelets. Secondary units, coupled to pyramidal neurons, showed discharge patterns similar to the recorded pyramidal neuron. These findings suggest that spikelets reflect spikes in an electrically coupled neighboring neuron, most likely of pyramidal cell type. Such coupling might contribute to the synchronization of pyramidal neurons with millisecond precision.
General Univalence Criterion Associated with the nth Derivative
Authors: Al-Refai Oqlah , Darus Maslina
Published: June 2012

For normalized analytic functions f(z)
with f(z) ≠ 0 for 0 < |z| < 1, we introduce a univalence
criterion defined by sharp inequality associated with the nth derivative of z/f(z), where n ∈ {3,4, 5, …}.
Flow and Heat Transfer of Cu‐Water Nanofluid between a Stretching Sheet and a Porous Surface in a Rotating System
Authors: Sheikholeslami M. , Ashorynejad H. R. , Domairry G. , Hashim I.
Published: June 2012

The aim of the present paper is to study the flow of nanofluid and heat transfer characteristics between two horizontal plates in a rotating system. The lower plate is a stretching sheet and the upper one is a solid porous plate. Copper (Cu) as nanoparticle and water as its base fluid have been considered. The governing partial differential equations with the corresponding boundary conditions are reduced to a set of ordinary differential equations with the appropriate boundary conditions using similarity transformation, which is then solved analytically using the homotopy analysis method (HAM). Comparison between HAM and numerical solutions results showed an excellent agreement. The results for the flow and heat transfer characteristics are obtained for various values of the nanoparticle volume fraction, suction/injection parameter, rotation parameter, and Reynolds number. It is shown that the inclusion of a nanoparticle into the base fluid of this problem is capable of causing change in the flow pattern. It is found that for both suction and injection, the heat transfer rate at the surface increases with increasing the nanoparticle volume fraction, Reynolds number, and injection/suction parameter and it decreases with power of rotation parameter.
Interference Cancellation Using Replica Signal for HTRCI‐MIMO/OFDM in Time‐Variant Large Delay Spread Longer Than Guard Interval
Authors: Ida Yuta , Ahn Chang-Jun , Kamio Takeshi , Fujisaka Hisato , Haeiwa Kazuhisa
Published: June 2012

Orthogonal frequency division multiplexing (OFDM) and multiple‐input multiple‐output (MIMO) are generally known as the effective techniques for high data rate services. In MIMO/OFDM systems, the channel estimation (CE) is very important to obtain an accurate channel state information (CSI). However, since the orthogonal pilot‐based CE requires the large number of pilot symbols, the total transmission rate is degraded. To mitigate this problem, a high time resolution carrier interferometry (HTRCI) for MIMO/OFDM has been proposed. In wireless communication systems, if the maximum delay spread is longer than the guard interval (GI), the system performance is significantly degraded due to the intersymbol interference (ISI) and intercarrier interference (ICI). However, the conventional HTRCI‐MIMO/OFDM does not consider the case with the time‐variant large delay spread longer than the GI. In this paper, we propose the ISI and ICI compensation methods for a HTRCI‐MIMO/OFDM in the time‐variant large delay spread longer than the GI.
Literature Retrieval and Mining in Bioinformatics: State of the Art and Challenges
Authors: Manconi Andrea , Vargiu Eloisa , Armano Giuliano , Milanesi Luciano
Published: June 2012

The world has widely changed in terms of communicating, acquiring, and storing information. Hundreds of millions of people are involved in information retrieval tasks on a daily basis, in particular while using a Web search engine or searching their e-mail, making such field the dominant form of information access, overtaking traditional database-style searching. How to handle this huge amount of information has now become a challenging issue. In this paper, after recalling the main topics concerning information retrieval, we present a survey on the main works on literature retrieval and mining in bioinformatics. While claiming that information retrieval approaches are useful in bioinformatics tasks, we discuss some challenges aimed at showing the effectiveness of these approaches applied therein.
Optimization of Concentric Ring Array Geometry for 3D Beam Scanning
Authors: Zhang Li , Jiao Yong-Chang , Chen Bo
Published: June 2012

Optimization of the element placement in a concentric ring array for three-dimensional (3D) beam scanning with minimum peak sidelobe levels (SLLs) is addressed in this paper. In order to achieve 3D beam scanning with the lowest peak SLL, both the radius and the element spacing of each ring are optimized. Moreover, the aperture size is a very important constraint for the array, since there is an upper limit for the aperture size of a given array in real-life environment. Hence, in our optimization design, the maximum radius of the concentric ring array is constrained. Through the optimization, the peak SLL of the optimal concentric ring array is about 6 dB lower than that of the uniform concentric ring array, but the directivity is reduced by only 0.3 dB.
Approaches to Low Fuel Regression Rate in Hybrid Rocket Engines
Authors: Pastrone Dario
Published: June 2012

Hybrid rocket engines are promising propulsion systems which present appealing features such as safety, low cost, and environmental friendliness. On the other hand, certain issues hamper the development hoped for. The present paper discusses approaches addressing improvements to one of the most important among these issues: low fuel regression rate. To highlight the consequence of such an issue and to better understand the concepts proposed, fundamentals are summarized. Two approaches are presented (multiport grain and high mixture ratio) which aim at reducing negative effects without enhancing regression rate. Furthermore, fuel material changes and nonconventional geometries of grain and/or injector are presented as methods to increase fuel regression rate. Although most of these approaches are still at the laboratory or concept scale, many of them are promising.
Explicit Iterative Method for Variational Inequalities on Hadamard Manifolds
Authors: Noor Muhammad Aslam , Noor Khalida Inayat
Published: June 2012

An explicit iterative method for solving the variational inequalities on Hadamard manifold is suggested and analyzed using the auxiliary principle technique. The convergence of this new method requires only the partially relaxed strongly monotonicity, which is a weaker condition than monotonicity. Results can be viewed as refinement and improvement of previously known results.
Ion-Exchange Membranes Based on Polynorbornenes with Fluorinated Imide Side Chain Groups
Authors: Santiago Arlette A. , Vargas Joel , Tlenkopatchev Mikhail A. , López-González Mar , Riande Evaristo
Published: June 2012

The electrochemical characteristics of cation-exchange membranes based on polynorbornenes with fluorinated and sulfonated dicarboximide side chain groups were reported. This study was extended to a block copolymer containing structural units with phenyl and 4-oxybenzenesulfonic acid, 2,3,5,6-tetrafluorophenyl moieties replacing the hydrogen atom of the dicarboximide group. A thorough study on the electrochemical characteristics of the membranes involving electromotive forces of concentration cells and proton conductivity is reported. The proton permselectivity of the membranes is also discussed.
The Corpus Callosum and the Visual Cortex: Plasticity Is a Game for Two
Authors: Pietrasanta Marta , Restani Laura , Caleo Matteo
Published: June 2012

Throughout life, experience shapes and selects the most appropriate brain functional connectivity to adapt to a changing environment. An ideal system to study experience-dependent plasticity is the visual cortex, because visual experience can be easily manipulated. In this paper, we focus on the role of interhemispheric, transcallosal projections in experience-dependent plasticity of the visual cortex. We review data showing that deprivation of sensory experience can modify the morphology of callosal fibres, thus altering the communication between the two hemispheres. More importantly, manipulation of callosal input activity during an early critical period alters developmental maturation of functional properties in visual cortex and modifies its ability to remodel in response to experience. We also discuss recent data in rat visual cortex, demonstrating that the corpus callosum plays a role in binocularity of cortical neurons and is involved in the plastic shift of eye preference that follows a period of monocular eyelid suture (monocular deprivation) in early age. Thus, experience can modify the fine connectivity of the corpus callosum, and callosal connections represent a major pathway through which experience can mediate functional maturation and plastic rearrangements in the visual cortex.
First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy
Authors: Sen Malabika , Thomas Sufi M. , Kim Seungwon , Yeh Joanne I. , Ferris Robert L. , Johnson Jonas T. , Duvvuri Umamaheswar , Lee Jessica , Sahu Nivedita , Joyce Sonali , Freilino Maria L. , Shi Haibin , Li Changyou , Ly Danith , Rapireddy Srinivas , Etter Jonathan P. , Li Pui-Kai , Wang Lin , Chiosea Simion , Seethala Raja R. , Gooding William E. , Chen Xiaomin , Kaminski Naftali , Pandit Kusum , Johnson Daniel E. , Grandis Jennifer R.
Published: June 2012

Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as “undruggable.” We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development.

Significance: This is the first study of a STAT3-selective inhibitor in humans and the first evidence that a transcription factor decoy can be modified to enable systemic delivery. These findings have therapeutic implications beyond STAT3 to other “undruggable” targets in human cancers. Cancer Discov; 2(8); 694–705. ©2012 AACR.

Read the Commentary on this article by Koppikar et al., p. 670.

This article is highlighted in the In This Issue feature, p. 653.
Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome
Authors: Bayles Richard , KN Harikrishnan , Lambert Elisabeth , Baker Emma K. , Agrotis Alex , Guo Ling , Jowett Jeremy B. M. , Esler Murray , Lambert Gavin , El-Osta Assam
Published: June 2012

Objective—

The postural tachycardia syndrome (POTS) has multiple symptoms, chief among which are tachycardia, weakness, and recurrent blackouts while standing. Previous research has implicated dysfunction of the norepinephrine transporter. A coding mutation in the norepinephrine transporter gene (
SLC6A2
) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the
SLC6A2
gene in POTS.

Methods and Results—

Sympathetic nervous system responses to head-up tilt were examined by combining norepinephrine plasma kinetics measurements and muscle sympathetic nerve activity recordings in patients with POTS compared with that in controls. The
SLC6A2
gene sequence was investigated in leukocytes from POTS patients and healthy controls using single nucleotide polymorphisms genotyping, bisulphite sequencing, and chromatin immunoprecipitation assays for histone modifications and binding of the transcriptional regulatory complex, methyl-CpG binding protein 2. The expression of norepinephrine transporter was lower in POTS patients compared with healthy volunteers. In the absence of altered
SLC6A2
gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications.

Conclusion—

We propose that chromatin-modifying events associated with
SLC6A2
gene suppression may constitute a mechanism of POTS.
Induction of Angiotensin-Converting Enzyme and Activation of the Renin–Angiotensin System Contribute to 20-Hydroxyeicosatetraenoic Acid–Mediated Endothelial Dysfunction
Authors: Cheng Jennifer , Garcia Victor , Ding Yan , Wu Cheng-Chia , Thakar Krutanjali , Falck John R. , Ramu Errabelli , Schwartzman Michal Laniado
Published: June 2012

Objective—

20-hydroxyeicosatetraenoic acid (20-HETE) promotes endothelial dysfunction by uncoupling endothelial NO synthase, stimulating O
2
−
production, and reducing NO bioavailability. Moreover, 20-HETE–dependent vascular dysfunction and hypertension are associated with upregulation of the renin–angiotensin system This study was undertaken to examine the contribution of renin–angiotensin system to 20-HETE actions in the vascular endothelium.

Methods and Results—

In endothelial cells, 20-HETE induced angiotensin-converting enzyme (ACE) mRNA levels and increased ACE protein and activity by 2- to 3-fold; these effects were negated with addition of the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20 HEDE). 20-HETE induced ACE expression was protein kinase C independent and epidermal growth factor receptor tyrosine kinase and IκB kinase β dependent. ACE short interfering RNA abolished 20-HETE–mediated inhibition of NO production and stimulation of O
2
−
generation, whereas angiotensin II type 1 receptor short interfering RNA attenuated these effects by 40%. 20-HETE–stimulated O
2
−
production was negated by 20-HEDE and was attenuated by lisinopril and losartan. Importantly, 20-HETE–mediated impairment of acetylcholine-induced relaxation in rat renal interlobar arteries was also attenuated by lisinopril and losartan.

Conclusion—

These results indicate that ACE and angiotensin II type 1 receptor activation contribute to 20-HETE–mediated endothelial cell and vascular dysfunction and further enforce the notion that excessive production of 20-HETE within the vasculature leads to hypertension via mechanisms that include the induction of endothelial ACE, thus, perpetuating an increase in vascular angiotensin which, together with 20-HETE, promotes vascular dysfunction.
Soluble Epoxide Hydrolase
Authors: Gupta Nandita C. , Davis Catherine M. , Nelson Jonathan W. , Young Jennifer M. , Alkayed Nabil J.
Published: June 2012

Objective—

Sex differences in cerebral ischemic injury are, in part, arrtibutable to the differences in cerebrovascular perfusion. We determined whether the brain microvascular endothelial cells (ECs) isolated from the female brain are more resistant to ischemic injury compared with male ECs, and whether the difference is attributable to lower expression of soluble epoxide hydrolase and higher levels of vasoprotective epoxyeicosatrienoic acids (EETs). We also determined whether protection by EETs is linked to the inhibition of rho-kinase (ROCK).

Methods and Results—

EC ischemic damage was measured after oxygen–glucose deprivation (OGD) using propidium iodide (PI) and cleaved caspase-3 labeling. Expression of soluble epoxide hydrolase was determined by quantitative polymerase chain reaction and immunocytochemistry, EETs levels by liquid chromatography-tandem mass spectrometry, and ROCK activity by ELISA. EC damage was higher in males compared with females, which correlated with higher soluble epoxide hydrolase mRNA, stronger immunoreactivity, and lower EETs compared with female ECs. Inhibition of soluble epoxide hydrolase abolished the sex difference in EC damage. ROCK activity was higher in male versus female ECs after OGD, and sex differences in EC damage and ROCK activity were abolished by 14,15-EET and ROCK inhibition.

Conclusion—

Sex differences in ischemic brain injury are, in part, attributable to differences in EET-mediated inhibition of EC ROCK activation after ischemia.
Combination Therapy With VELCADE and Tissue Plasminogen Activator Is Neuroprotective in Aged Rats After Stroke and Targets MicroRNA-146a and the Toll-Like Receptor Signaling Pathway
Authors: Zhang Li , Chopp Michael , Liu Xianshuang , Teng Hua , Tang Tao , Kassis Haifa , Zhang Zheng Gang
Published: June 2012

Objective—

Activation of the toll-like receptor (TLR) signaling pathway exacerbates ischemic brain damage. The present study tested the hypothesis that combination treatment with VELCADE and tissue plasminogen activator (tPA) modulates the TLR signaling pathway on cerebral vasculature, which leads to neuroprotection in aged rats after stroke.

Methods and Results—

Focal cerebral ischemia acutely increased TLR2, TLR4, and interleukin-1 receptor–activated kinases 1 immunoreactivity on fibrin/fibrinogen-positive vessels in aged rats. Monotherapy of tPA further amplified these signals. However, VELCADE in combination with tPA-blocked stroke- and tPA-potentiated vascular TLR signals, leading to robust reduction of infarct volume compared with respective monotherapies. Quantitative reverse transcription polymerase chain reaction analysis of cerebral endothelial cells isolated by laser capture microdissection revealed that the combination treatment increased miR-l46a levels, which was inversely associated with the reduction of vascular interleukin-1 receptor–activated kinases 1 immunoreactivity. In vitro, fibrin upregulated interleukin-1 receptor–activated kinases 1 and TLR4 expression and downregulated miR-146a on primary human cerebral endothelial cells. VELCADE elevated miR-146 levels and abolished fibrin-increased interleukin-1 receptor activated kinases 1 proteins.

Conclusion—

Stroke acutely activates the TLR signaling pathway on cerebral vasculature. Upregulation of miR-146a and inactivation of ischemia and tPA-potentiated TLR signaling pathway by VELCADE may play an important role in the neuroprotective effect of the combination therapy of VELCADE and tPA for acute stroke.
High-Resolution Association Mapping of Atherosclerosis Loci in Mice
Authors: Bennett Brian J. , Orozco Luz , Kostem Emrah , Erbilgin Ayca , Dallinga Marchien , Neuhaus Isaac , Guan Bo , Wang Xuping , Eskin Eleazar , Lusis Aldons J.
Published: June 2012

Objective—

The purpose of this study was to fine map previously identified quantitative trait loci affecting atherosclerosis in mice using association analysis.

Methods and Results—

We recently showed that high-resolution association analysis using common inbred strains of mice is feasible if corrected for population structure. To use this approach for atherosclerosis, which requires a sensitizing mutation, we bred human apolipoprotein B-100 transgenic mice with 22 different inbred strains to produce F1 heterozygotes. Mice carrying the dominant transgene were tested for association with high-density single nucleotide polymorphism maps. Here, we focus on high-resolution mapping of the previously described
atherosclerosis 30
locus on chromosome 1. Compared with the previous linkage analysis, association improved the resolution of the
atherosclerosis 30
locus by more than an order of magnitude. Using expression quantitative trait locus analysis, we identified one of the genes in the region, desmin, as a strong candidate.

Conclusion—

Our high-resolution mapping approach accurately identifies and fine maps known atherosclerosis quantitative trait loci. These results suggest that high-resolution genome-wide association analysis for atherosclerosis is feasible in mice.
Effect of Skeletal Muscle Na
+
Channel Delivered Via a Cell Platform on Cardiac Conduction and Arrhythmia Induction
Authors: Boink Gerard J.J. , Lu Jia , Driessen Helen E. , Duan Lian , Sosunov Eugene A. , Anyukhovsky Evgeny P. , Shlapakova Iryna N. , Lau David H. , Rosen Tove S. , Danilo Peter , Jia Zhiheng , Ozgen Nazira , Bobkov Yevgeniy , Guo Yuanjian , Brink Peter R. , Kryukova Yelena , Robinson Richard B. , Entcheva Emilia , Cohen Ira S. , Rosen Michael R.
Published: June 2012

Background—

In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na
+
channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1.

Methods and Results—

cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (
P
<0.05). During programmed electrical stimulation of epicardial border zones, QRS duration in cMSC/SkM1 was shorter than in cMSC and sham (
P
<0.05). Programmed electrical stimulation–induced ventricular tachycardia/ventricular fibrillation was equivalent in all groups (
P
>0.05).

Conclusion—

cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy.
Assessing Cell and Organ Senescence Biomarkers
Authors: de Jesus Bruno Bernardes , Blasco Maria A.
Published: June 2012

A major goal in cancer and aging research is to discriminate the biochemical modifications that happen locally that could account for the healthiness or malignancy of tissues. Senescence is one general antiproliferative cellular process that acts as a strong barrier for cancer progression, playing a crucial role in aging. Here, we focus on the current methods to assess cellular senescence, discriminating the advantages and disadvantages of several senescence biomarkers.
Stimulated Emission Depletion Live-Cell Super-Resolution Imaging Shows Proliferative Remodeling of T-Tubule Membrane Structures After Myocardial Infarction
Authors: Wagner Eva , Lauterbach Marcel A. , Kohl Tobias , Westphal Volker , Williams George S.B. , Steinbrecher Julia H. , Streich Jan-Hendrik , Korff Brigitte , Tuan Hoang-Trong M. , Hagen Brian , Luther Stefan , Hasenfuss Gerd , Parlitz Ulrich , Jafri M. Saleet , Hell Stefan W. , Lederer W. Jonathan , Lehnart Stephan E.
Published: June 2012

Rationale:

Transverse tubules (TTs) couple electric surface signals to remote intracellular Ca
2+
release units (CRUs). Diffraction-limited imaging studies have proposed loss of TT components as disease mechanism in heart failure (HF).

Objectives:

Objectives were to develop quantitative super-resolution strategies for live-cell imaging of TT membranes in intact cardiomyocytes and to show that TT structures are progressively remodeled during HF development, causing early CRU dysfunction.

Methods and Results:

Using stimulated emission depletion (STED) microscopy, we characterized individual TTs with nanometric resolution as direct readout of local membrane morphology 4 and 8 weeks after myocardial infarction (4pMI and 8pMI). Both individual and network TT properties were investigated by quantitative image analysis. The mean area of TT cross sections increased progressively from 4pMI to 8pMI. Unexpectedly, intact TT networks showed differential changes. Longitudinal and oblique TTs were significantly increased at 4pMI, whereas transversal components appeared decreased. Expression of TT-associated proteins junctophilin-2 and caveolin-3 was significantly changed, correlating with network component remodeling. Computational modeling of spatial changes in HF through heterogeneous TT reorganization and RyR2 orphaning (5000 of 20 000 CRUs) uncovered a local mechanism of delayed subcellular Ca
2+
release and action potential prolongation.

Conclusions:

This study introduces STED nanoscopy for live mapping of TT membrane structures. During early HF development, the local TT morphology and associated proteins were significantly altered, leading to differential network remodeling and Ca
2+
release dyssynchrony. Our data suggest that TT remodeling during HF development involves proliferative membrane changes, early excitation-contraction uncoupling, and network fracturing.
Vulnerability beyond Stereotypes: Context and Agency in Hurricane Risk Communication
Authors: Lazrus Heather , Morrow Betty H. , Morss Rebecca E. , Lazo Jeffrey K.
Published: June 2012

Risk communication may accentuate or alleviate the vulnerability of people who have particular difficulties responding to the threat of hazards such as hurricanes. The process of risk communication involves how hazard information is received, understood, and responded to by individuals and groups. Thus, risk communication and vulnerability interact through peoples' knowledge, attitudes, and practices. This study explores risk communication with several groups that may be at particular risk of hurricane impacts: older adults, newer residents, and persons with disabilities. Focus groups conducted in Miami, Florida, examined how members of these groups express their own vulnerability or agency in terms of receiving, interpreting, and responding to hurricane risk information. Findings indicate that people's interactions with risk information are deeply contextual and are facilitated by their individual agency to cope with their vulnerabilities.
Transformation of the US Healthcare System: Why is change so difficult?
Authors: Blank Robert H
Published: June 2012

The United States spends considerably more on medical care than any country in the world but is the only resource-rich country where a substantial portion of its residents lack health insurance coverage. Moreover, the US continues to rank low on most measures of health outcome compared to other developed countries. Therefore, there was considerable incredulity by those unfamiliar with the US as to why a revamping of this obviously broken system was not widely embraced by the American public when in 2009 a popularly elected president made healthcare reform his top priority. This commentary examines this phenomenon and discusses why a meaningful transformation of the US healthcare system has proven so elusive. Among the factors discussed here are political institutions and economic forces, a powerful medical establishment, the dominant private insurance industry, an extensive liability system and a public that is highly suspicious of any government involvement in healthcare.
Is decentralization good for your health? Transformations in the Italian NHS
Authors: Pavolini Emmanuele , Vicarelli Giovanna
Published: June 2012

Decentralization is a cornerstone of health policy reforms across Europe and beyond. This article analyses some of the effects of decentralization using the Italian National Health System (NHS) as a case study. The authors evaluate the risks of welfare state retrenchment and the rise of territorial inequalities in accessing healthcare, using document analysis, secondary sources and micro-data elaboration. The analysis does not confirm an overall welfare state retrenchment, but reveals an increase in territorial inequalities. The results highlight a paradox: if decentralization is to be implemented in a country with strong territorial socioeconomic divides and a critical financial situation, it needs a strong central government in order to support and control local authorities. Otherwise, decentralization may cause a zero-sum game where the gains for the better-off regions counterbalance the losses in performance of the weaker ones; a situation which could lead to the growth of social inequalities, including gender inequalities.
Living between languages: The politics of translation in Leila Aboulela’s Minaret and Xiaolu Guo’s A Concise Chinese-English Dictionary for Lovers
Authors: Gilmour Rachael
Published: June 2012

This essay examines the notion of “translational writing” – literary texts which bear the traces of multiple languages, foregrounding and dramatizing the processes of translation of which they are both product and representation – through detailed examination of two recent novels set in London: Leila Aboulela’s Minaret (2005), and Xiaolu Guo’s A Concise Chinese-English Dictionary for Lovers (2007). Both novels are narrated by their female protagonists, whose movement between linguistic planes defines a distinctively feminized, translingual identity. Each works to destabilize the assumed relationship between language and national belonging, in part by recasting London as a space of translation: a city of immigrants defined by its polyglossia, and a node in a deterritorialized transnational linguistic order. Yet, while both novels explore the possibilities, risks, and limitations of a life lived between languages, they also demonstrate that translational literature, like translation theory, offers no consensus on the practice of translation. Their divergent conclusions – about the relationship between languages, about the nature and purposes of translation, about the connections between language and truth – reveal much about the complexities of translational writing.
“Justice is on our side”? Animal’s People, generic hybridity, and eco-crime
Authors: Carrigan Anthony
Published: June 2012

This essay examines how a recent fictionalisation of post-disaster life in Bhopal, Indra Sinha’s novel Animal’s People (2007), opens up perspectives on eco-crime, disaster, and systemic injustice on the level of genre. It begins by showing how the novel evokes private eye, noir, and spy genres in ways that present similarly hybrid forms of detective agency and legal subjectivity as a means of responding to the disaster’s criminal dimensions. It then shows how this hybridity relates to the way Sinha plays off crime fiction’s genealogical relationship with revenge tragedy both to disrupt the disaster’s common real-world designation as ‘tragedy’ and to implicate readers in modes of active witnessing that probe legal-democratic failure. The essay concludes by discussing how these formal techniques shed light on the potential for interdisciplinary exchange between postcolonial ecocriticism and green criminology in relation to transnational crimes such as Bhopal.
Ngũgĩ wa Thiong’o and the African dictator novel
Authors: Spencer Robert
Published: June 2012

This article places the Kenyan intellectual Ngũgũ wa Thiong’o’s Wizard of the Crow (2006) in what has until now been seen as a predominantly Latin American tradition of dictator novels. Dictator novels unmask the intrinsic fallibility of power. The purported omnipotence of the dictator is undermined by dictation: that is, by his power’s reliance on the shifty and ambiguous medium of language, which these novels reveal to be a medium of democratic dialogue not of dictatorial control. Wizard of the Crow also performs power in the sense of staging power’s operations, dramatising its precariousness and exposing its crimes to censure. It also permits an understanding of the over-determined origins of dictatorship: in the legacies of colonialism, the lingering interference of Western states and corporations, and the failures of national leadership. The aims of the paper are, firstly, to demonstrate the longevity and efficacy of a decidedly topical literary tradition that has among its effects the illumination and explanation of enduring forms of colonial exploitation in Africa, and secondly to show how, especially through the reading strategies that it encourages, Ngũgũ’s novel resists this state of affairs and forecasts democratic alternatives to it.