bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstruction-Induced Pulmonary Vascular Remodeling
Authors: Chow Ming-Jay , Zou Yu , He Huamei , McGowan Francis X. , Zurakowski David , Zhang Yanhang
Published: October 2011

Pulmonary obstruction occurs in many common forms of congenital heart disease. In this study, pulmonary artery (PA) banding is used as a model for pulmonary stenosis. Significant remodeling of the vascular bed occurs as a result of a prolonged narrowing of the PAs, and here we quantify the biophysical and molecular changes proximal and distal to the obstruction. Main and branch PAs are harvested from banded and sham rabbits and their mechanical properties are assessed using a biaxial tensile tester. Measurements defined as initial and stiff slopes are taken, assuming a linear region at the start and end of the J-shaped stress-strain curves, along with a transitional knee point. Collagen, elastin assays, Movat’s pentachrome staining, and Doppler protocols are used to quantify biochemical, structural, and physiological differences. The banded main PAs have significantly greater initial slopes while banded branch PAs have lower initial slopes; however, this change in mechanical behavior cannot be explained by the assay results as the elastin content in both main and branch PAs is not significantly different. The stiff slopes of the banded main PAs are higher, which is attributed to the significantly greater amounts of insoluble collagen. Shifting of the knee points reveals a decreased toe region in the main PAs but an opposite trend in the branch PAs. The histology results show a loss of integrity of the media, increase in ground substance, and dispersion of collagen in the banded tissue samples. This indicates other structural changes could have led to the mechanical differences in banded and normal tissue.
Room temperature nanoimprinting using spin-coated hydrogen silsesquioxane with high boiling point solvent
Authors: Kang Yuji , Okada Makoto , Omoto Shinya , Haruyama Yuichi , Kanda Kazuhiro , Matsui Shinji
Published: October 2011

The authors have previously used two methods for nanoimprinting hydrogen silsesquioxane (HSQ) patterns. In the casting method, the HSQ pattern was replicated at a low imprinting pressure of less than 1 MPa, however, the imprinting produced an uneven residue. On the contrary, in the spin-coating method, an evenly distributed HSQ film was produced. However, the HSQ pattern required a high imprinting pressure of about 40 MPa. To achieve imprinting at a low pressure with the spin-coating method, we propose a new room temperature nanoimprinting method using spin-coated HSQ and a poly(dimethylsiloxane) mold. The authors used high boiling point solvent, with a boiling point of greater than 200 °C, in place of the previously used solvent that had a boiling point of 96 °C. This method produced an evenly coated film in the liquid-phase.
ANAT: A Tool for Constructing and Analyzing Functional Protein Networks
Authors: Yosef Nir , Zalckvar Einat , Rubinstein Assaf D. , Homilius Max , Atias Nir , Vardi Liram , Berman Igor , Zur Hadas , Kimchi Adi , Ruppin Eytan , Sharan Roded
Published: October 2011

Genome-scale screening studies are gradually accumulating a wealth of data on the putative involvement of hundreds of genes in various cellular responses or functions. A fundamental challenge is to chart the molecular pathways that underlie these systems. ANAT is an interactive software tool, implemented as a Cytoscape plug-in, for elucidating functional networks of proteins. It encompasses a number of network inference algorithms and provides access to networks of physical associations in several organisms. In contrast to existing software tools, ANAT can be used to infer subnetworks that connect hundreds of proteins to each other or to a given set of “anchor” proteins, a fundamental step in reconstructing cellular subnetworks. The interactive component of ANAT provides an array of tools for evaluating and exploring the resulting subnetwork models and for iteratively refining them. We demonstrate the utility of ANAT by studying the crosstalk between the autophagic and apoptotic cell death modules in humans, using a network of physical interactions. Relative to published software tools, ANAT is more accurate and provides more features for comprehensive network analysis. The latest version of the software is available at
http://www.cs.tau.ac.il/~bnet/ANAT_SI
.
Focus Issue: Recruiting Players for a Game of ERK
Authors: Gough Nancy R.
Published: October 2011

The latest research continues to add to the components and functions of the ERK mitogen-activated protein kinase signaling cascade.
Remembering About Cyclin E?
Authors: Adler Elizabeth M.
Published: October 2011

Cyclin E contributes to synaptic plasticity and memory independent of its role in the cell cycle.
Control and Cooperation
Authors: Ash Caroline
Published: October 2011

A beetle species synthesizes an antimicrobial peptide to constrain a bacterial symbiont in specialized organs.
Synergistic Effect of Thermal Energy on Bactericidal Action of Photolysis of H
2
O
2
in Relation to Acceleration of Hydroxyl Radical Generation
Authors: Shirato Midori , Ikai Hiroyo , Nakamura Keisuke , Hayashi Eisei , Kanno Taro , Sasaki Keiichi , Kohno Masahiro , Niwano Yoshimi
Published: October 2011

The purpose of the present study is to evaluate the effect of thermal energy on the yield of and the bactericidal action of hydroxyl radical generated by photolysis of H
2
O
2
. Different concentrations of H
2
O
2
(250, 500, 750, and 1,000 mM) were irradiated with light-emitting diodes (LEDs) at a wavelength of 400 ± 20 nm at 25°C to generate hydroxyl radical. The 500 mM H
2
O
2
was irradiated with the LEDs at different temperatures (25, 35, 45, and 55°C). Electron spin resonance spin trapping analysis showed that the yield of hydroxyl radicals increased with the temperature, as well as the concentration of H
2
O
2
.
Streptococcus mutans
and
Enterococcus faecalis
were used in the bactericidal assay. The LED-light irradiation of the bacterial suspensions in 500 mM H
2
O
2
at 25°C could hardly kill the bacteria within 3 min, while the bactericidal effect was markedly enhanced with the temperature rise. For instance, a temperature increase to 55°C resulted in >99.999% reduction of viable counts of both bacterial species only within 1 min. The photolysis of 500 mM H
2
O
2
at 55°C could reduce the viable counts of bacteria more efficiently than did the photolysis of 1,000 mM H
2
O
2
at 25°C, although the yields of hydroxyl radical were almost the same under the both conditions. These findings suggest that the thermal energy accelerates the generation of hydroxyl radical by photolysis of H
2
O
2
, which in turn results in a synergistic bactericidal effect of hydroxyl radical and thermal energy.
Colistin-Resistant, Lipopolysaccharide-Deficient Acinetobacter baumannii Responds to Lipopolysaccharide Loss through Increased Expression of Genes Involved in the Synthesis and Transport of Lipoproteins, Phospholipids, and Poly-β-1,6-
N
-Acetylglucosamine
Authors: Henry Rebekah , Vithanage Nuwan , Harrison Paul , Seemann Torsten , Coutts Scott , Moffatt Jennifer H. , Nation Roger L. , Li Jian , Harper Marina , Adler Ben , Boyce John D.
Published: October 2011

We recently demonstrated that colistin resistance in
Acinetobacter baumannii
can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother.
54:
4971–4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how
A. baumannii
compensates for the lack of LPS, we compared the transcriptional profile of the
A. baumannii
type strain ATCC 19606 to that of an isogenic, LPS-deficient,
lpxA
mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-
N
-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the
A. baumannii
wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss,
A. baumannii
alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface.
Abrogation of Neuraminidase Reduces Biofilm Formation, Capsule Biosynthesis, and Virulence of Porphyromonas gingivalis
Authors: Li Chen , Kurniyati  , Hu Bo , Bian Jiang , Sun Jianlan , Zhang Weiyan , Liu Jun , Pan Yaping , Li Chunhao
Published: October 2011

The oral bacterium
Porphyromonas gingivalis
is a key etiological agent of human periodontitis, a prevalent chronic disease that affects up to 80% of the adult population worldwide.
P. gingivalis
exhibits neuraminidase activity. However, the enzyme responsible for this activity, its biochemical features, and its role in the physiology and virulence of
P. gingivalis
remain elusive. In this report, we found that
P. gingivalis
encodes a neuraminidase, PG0352 (Sia
Pg
). Transcriptional analysis showed that
PG0352
is monocistronic and is regulated by a sigma
70
-like promoter. Biochemical analyses demonstrated that Sia
Pg
is an exo-α-neuraminidase that cleaves glycosidic-linked sialic acids. Cryoelectron microscopy and tomography analyses revealed that the
PG0352
deletion mutant (ΔPG352) failed to produce an intact capsule layer. Compared to the wild type,
in vitro
studies showed that ΔPG352 formed less biofilm and was less resistant to killing by the host complement.
In vivo
studies showed that while the wild type caused a spreading type of infection that affected multiple organs and all infected mice were killed, ΔPG352 only caused localized infection and all animals survived. Taken together, these results demonstrate that Sia
Pg
is an important virulence factor that contributes to the biofilm formation, capsule biosynthesis, and pathogenicity of
P. gingivalis
, and it can potentially serve as a new target for developing therapeutic agents against
P. gingivalis
infection.
Perinuclear Localization of Internalized Outer Membrane Vesicles Carrying Active Cytolethal Distending Toxin from Aggregatibacter actinomycetemcomitans
Authors: Rompikuntal Pramod Kumar , Thay Bernard , Khan Muhammad Khanzeb , Alanko Jonna , Penttinen Anna-Maija , Asikainen Sirkka , Wai Sun Nyunt , Oscarsson Jan
Published: October 2011

Aggregatibacter actinomycetemcomitansis implicated in aggressive forms of periodontitis. Similarly to several other Gram-negative species, this organism produces and excretes a cytolethal distending toxin (CDT), a genotoxin associated with cell distention, G2cell cycle arrest, and/or apoptosis in many mammalian cell types. In this study, we have identifiedA. actinomycetemcomitansouter membrane vesicles (OMVs) as a vehicle for simultaneous delivery of multiple proteins, including CDT, into human cells. The OMV proteins were internalized in both HeLa cells and human gingival fibroblasts (HGF) via a mechanism of OMV fusion with lipid rafts in the plasma membrane. The active toxin unit, CdtB, was localized inside the nucleus of the intoxicated cells, whereas OmpA and proteins detected using an antibody specific to wholeA. actinomycetemcomitansserotype a cells had a perinuclear distribution. In accordance with a tight association of CdtB with OMVs, vesicles isolated fromA. actinomycetemcomitansstrain D7SS (serotype a), in contrast to OMVs from a D7SScdtABCmutant, induced a cytolethal distending effect on HeLa and HGF cells, indicating that OMV-associated CDT was biologically active. Association of CDT with OMVs was also observed inA. actinomycetemcomitansisolates belonging to serotypes b and c, indicating that OMV-mediated release of CDT may be conserved inA. actinomycetemcomitans. Although the role ofA. actinomycetemcomitansOMVs in periodontal disease has not yet been elucidated, our present data suggest that OMVs could deliver biologically active CDT and additional virulence factors into susceptible cells of the periodontium.
Unsystematic Risk Explanation to Momentum Profits in Taiwan
Authors: Wang Ching-Ping , Huang Hung-Hsi , Tu Kai-Jei
Published: October 2011

This study investigates the momentum profits and provides a systematic risk as well as time-varying unsystematic risk explanation, adopting the monthly returns in the Taiwan stock market during 2003–2008 periods. Through the regression models including and combining the CAPM, Fama–French three factor model, GARCH(1,1)-M and TGARCH(1,1)-M, the main results are as follows. First, most of the momentum strategies have not significant positive returns. Next, CAPM as well as Fama and French factors could roughly explain momentum returns. Additionally, it may make some profits likely if the time-varying unsystematic risk is further considered in an investment strategy. Moreover, the return volatility for the portfolio of winners is more sensitive to recent news than the losers. Conversely, the return volatility of the loser is more sensitive to distant news and has a larger response to bad news than the winner. Finally, TGARCH-M related models usually perform better than GARCH-M ones; this infers the presence of leverage effect in Taiwan stock market.
Asymmetric Information and Corporate Risk Management by Using Foreign Currency Derivatives
Authors: Lin Bingxuan , Lin Chen-Miao
Published: October 2011

We examine how information asymmetry affects a firm's incentive to hedge versus speculate by using foreign currency derivatives. We find a quadratic relation between asymmetric information and a firm's risk management activities. In particular, we find that the firms facing medium level of information asymmetry are more likely to hedge, while firms with very high and low levels of asymmetric information tend to speculate. Moreover, we find that our results hold primary for firms operating in highly competitive industries.
FORMAL INSTITUTIONAL CONTEXTS AS OWNERSHIP OF INTELLECTUAL PROPERTY RIGHTS AND THEIR IMPLICATIONS FOR THE ORGANIZATION OF COMMERCIALIZATION OF INNOVATIONS AT UNIVERSITIES — COMPARATIVE DATA FROM SWEDEN AND THE UNITED KINGDOM
Authors: LINDELÖF PETER
Published: October 2011

This paper identifies differences in institutional contexts (legislation) between Sweden and the UK and their effects on technology transfer policies. It then proceeds to examine how such activities are organized by universities. Empirical evidence from surveys conducted with technology transfer managers at eight Swedish universities and eleven UK universities gathered in Sweden and the UK during 2004 is analyzed. It is argued that the historical developments of these systems depend on different institutional contexts, which influence the modes of organization. The UK technology transfer system is based on similar legislation to that of the US, with IPRs being granted to the universities. The Swedish system, however, grants IPRs to the individual researchers, though with some new features — such as science parks and incubators — suggesting a change towards greater agent (university) involvement in encouraging technology transfer. This change indicates a breakthrough for the "entrepreneurial university" in Sweden.
Parallel circuit simulation with adaptively controlled projective integration
Authors: Dong Wei , Li Peng
Published: October 2011

In this article, a parallel transient circuit simulation approach based on an adaptively-controlled time-stepping scheme is proposed. Different from the widely-used implicit numerical integration techniques in most transient simulators, this work exploits the recently-developed explicit telescopic projective numerical integration method for efficient parallel circuit simulation. Because telescopic projective integration addresses the well-known stability issue of explicit numerical integrations by adopting combinations of inner integrators and outer integrators in a multilevel fashion, the simulation time-step is no longer limited by the smallest time constant in the circuit. With dynamic control of telescopic projective integration, the proposed projective integration framework not only leads to noticeable efficiency improvement in circuit simulation, it also lends itself to straightforward parallelization due to its explicit nature. The latter has led to encouraging runtime efficiencies, observed on shared-memory parallel platforms. In addition to solving standard initial-value problems (IVPs) of differential equations, the same telescopic integration framework is adopted for solving final-value problems (FVPs), where the system is integrated backwards in time. Through a new elegant formulation, we show how an IVP and FVP can be simultaneously solved to allow for a coarse-grained bidirectional parallel circuit simulation scheme. Such a bidirectional approach is demonstrated in the context of parallel shooting-Newton-based steady-state circuit analysis. The proposed bidirectional approach has unique and favorable properties: the solutions of the two ODE problems are completely data-independent with built-in automatic load balancing.
Clock Tree synthesis for TSV-based 3D IC designs
Authors: Kim Tak-Yung , Kim Taewhan
Published: October 2011

For the cost-effective implementation of clock trees in through-silicon via (TSV)-based 3D IC designs, we propose core algorithms for 3D clock tree synthesis. For a given abstract tree topology, we propose DLE-3D (
d
eferred
l
ayer
e
mbedding for
3D
ICs), which optimally finds the embedding layers of tree nodes, so that the TSV cost required for a tree topology is minimized, and DME-3D (
d
eferred
m
erge
e
mbedding for
3D
ICs), which is an extended algorithm of the 2D merging segment, to minimize the total wirelength in 3D design space, with the consideration of the TSV effect on delay. In addition, when an abstract tree topology is not given, we propose NN-3D (
n
earest
n
eighbor selection for
3D
ICs), which constructs a (TSV and wirelength) cost-effective abstract tree topology for 3D ICs. Through experimentation, we have confirmed that the clock tree synthesis flow using the proposed algorithms is very effective, outperforming the existing 3D clock tree synthesis in terms of the number of TSVs, total wirelength, and clock power consumption.
Making information flow explicit in HiStar
Authors: Zeldovich Nickolai , Boyd-Wickizer Silas , Kohler Eddie , Mazières David
Published: October 2011

HiStar is a new operating system designed to minimize the amount of code that must be trusted. HiStar provides strict information flow control, which allows users to specify precise data security policies without unduly limiting the structure of applications. HiStar's security features make it possible to implement a Unix-like environment with acceptable performance almost entirely in an untrusted user-level library. The system has no notion of superuser and no fully trusted code other than the kernel. HiStar's features permit several novel applications, including privacy-preserving, untrusted virus scanners and a dynamic Web server with only a few thousand lines of trusted code.
Naive ray-tracing
Authors: Mora Benjamin
Published: October 2011

We present an efficient ray-tracing algorithm which, for the first time, does not store any data structures when performing spatial subdivisions, and directly computes intersections inside the scene. This new algorithm is often faster than comparable ray-tracing methods at rendering dynamic scenes, and has a similar level of performance when compared to static ray-tracers. Memory management is made minimal and deterministic, which simplifies ray-tracing engineering, as spatial subdivision data structures are no longer considered in the graphics pipeline. This is possible with a modification of Whitted's naive ray-tracing algorithm by using a divide-and-conquer approach, and by having a sufficient collection of rays in order to reduce the complexity of naive ray-tracing. In particular, the algorithm excels at spontaneously solving large Ray/Primitive intersection problems.
Reducing Repair Traffic in P2P Backup Systems
Authors: Huang Zhen , Biersack Ernst , Peng Yuxing
Published: October 2011

Peer to peer backup systems store data on “unreliable” peers that can leave the system at any moment. In this case, the only way to assure durability of the data is to add redundancy using either replication or erasure codes. Erasure codes are able to provide the same reliability as replication requiring much less storage space. Erasure coding breaks the data into blocks that are encoded and then stored on different nodes. However, when storage nodes permanently abandon the system, new redundant blocks must be created, which is referred to as repair. For “classical” erasure codes, generating a new block requires the transmission of k blocks over the network, resulting in a high repair traffic. Recently, two new classes of erasure codes, Regenerating Codes and Hierarchical Codes, have been proposed that significantly reduce the repair traffic. Regenerating Codes reduce the amount of data uploaded by each peer involved in the repair, while Hierarchical Codes reduce the number of nodes participating in the repair. In this article we propose to combine these two codes to devise a new class of erasure codes called ER-Hierarchical Codes that combine the advantages of both.
Thermal Stability and Tribological Performance of DLC-Si–O Films
Authors: Moolsradoo Nutthanun , Abe Shinya , Watanabe Shuichi
Published: October 2011

The thermal stability and tribological performance of silicon- and oxygen-incorporated diamond-like carbon films were investigated. The DLC-Si-O films were deposited using plasma-based ion implantation (PBII) method. The deposited films were annealed at 400°C, 600°C, and 750°C for 1 hour in vacuum, in argon, and in air atmospheres. Film properties were investigated using the Fourier transforms infrared spectroscopy, Raman spectroscopy, energy dispersive X-ray spectroscopy, and a ball-on-disk friction tester. The structures of the DLC-Si-O films with a low Si content (25 at.%Si, 1 at.%O) and high Si content (25 at.%Si, 1 at.%O) were not affected by the thermal annealing in vacuum at 400°C and 600°C, respectively, while they were affected by thermal annealing in argon and in air at 400°C. Film with 34 at.%Si and 9 at.%O after annealing demonstrated almost constant atomic contents until annealing at 600°C in vacuum. The friction coefficient of DLC-Si–O films with 34 at.%Si and 9 at.%O was shown to be relatively stable, with a friction coefficient of 0.04 before annealing and 0.05 after annealing at 600°C in vacuum. Moreover, the low friction coefficient of film annealed at 600°C in vacuum with 34 at.%Si and 9 at.%O was corresponded with low wear rate of 1.85 10−7 mm3/Nm.
Techniques in Endovascular Aneurysm Repair
Authors: Phade Sachin V. , Garcia-Toca Manuel , Kibbe Melina R.
Published: October 2011

Endovascular repair of infrarenal abdominal aortic aneurysms (EVARs) has revolutionized the treatment of aortic aneurysms, with over half of elective abdominal aortic aneurysm repairs performed endoluminally each year. Since the first endografts were placed two decades ago, many changes have been made in graft design, operative technique, and management of complications. This paper summarizes modern endovascular grafts, considerations in preoperative planning, and EVAR techniques. Specific areas that are addressed include endograft selection, arterial access, sheath delivery, aortic branch management, graft deployment, intravascular ultrasonography, pressure sensors, management of endoleaks and compressed limbs, and exit strategies.
The Existence of Cone Critical Point and Common Fixed Point with Applications
Authors: Du Wei-Shih
Published: October 2011

We first establish some new critical point theorems for nonlinear dynamical
systems in cone metric spaces or usual metric spaces, and then we present some applications
to generalizations of Dancš‐Hegedüs‐Medvegyev′s principle and the existence theorem related with
Ekeland′s variational principle, Caristi′s common fixed point theorem for multivalued maps, Takahashi′s
nonconvex minimization theorem, and common fuzzy fixed point theorem. We also obtain
some fixed point theorems for weakly contractive maps in the setting of cone metric spaces and focus
our research on the equivalence between scalar versions and vectorial versions of some results of fixed
point and others.
Clinical Outcomes of Gamma Knife Radiosurgery in the Treatment of Patients with Trigeminal Neuralgia
Authors: Elaimy Ameer L. , Hanson Peter W. , Lamoreaux Wayne T. , Mackay Alexander R. , Demakas John J. , Fairbanks Robert K. , Cooke Barton S. , Thumma Sudheer R. , Lee Christopher M.
Published: October 2011

Since its introduction by Leksell, Gamma Knife radiosurgery (GKRS) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia (TN). For this reason, we performed a modern review of the literature analyzing the efficacy of GKRS in the treatment of patients who suffer from TN. For patients with medically refractory forms of the condition, GKRS has proven to be an effective initial and repeat treatment option. Cumulative research suggests that patients treated a single time with GKRS exhibit similar levels of facial pain control when compared to patients treated multiple times with GKRS. However, patients treated on multiple occasions with GKRS are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with GKRS. Although numerous articles have reported MVD to be superior to GKRS in achieving facial pain relief, the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and cannot be considered conclusive. Questions remain regarding optimal GKRS dosing and targeting strategies, which warrants further investigation into this controversial matter.
Brain-Selective Overexpression of Angiotensin-Converting Enzyme 2 Attenuates Sympathetic Nerve Activity and Enhances Baroreflex Function in Chronic Heart Failure
Authors: Xiao Liang , Gao Lie , Lazartigues Eric , Zucker Irving H.
Published: October 2011

Angiotensin-converting enzyme 2 (ACE2) has been suggested to be involved in the central regulation of autonomic function. During chronic heart failure (CHF), elevated central angiotensin II signaling contributes to the sustained increase of sympathetic outflow. This is accompanied by a downregulation of ACE2 in the brain. We hypothesized that central overexpression of ACE2 decreases sympathetic outflow and enhances baroreflex function in CHF. Transgenic mice overexpressing human ACE2 selectively in the brain (SYN-hACE2 [SA]) and wild-type littermates (WT) were used. CHF was induced by permanent coronary artery ligation. Four weeks after coronary artery ligation, both WT and SA mice exhibited a significant decrease in left ventricular ejection fraction (<40%). A slight decrease in mean arterial pressure was found only in SA mice. Compared with WT mice with CHF, brain-selective ACE2 overexpression attenuated left ventricular end-diastolic pressure; decreased urinary norepinephrine excretion; baseline renal sympathetic nerve activity (WT CHF: 71.6±7.6% max versus SA CHF: 49.3±6.1% max); and enhanced baroreflex sensitivity (maximum slope: WT sham: 1.61±0.16%/mm Hg versus SA CHF: 1.51±0.17%/mm Hg). Chronic subcutaneous blockade of mas receptor increased renal sympathetic nerve activity in SA mice with CHF (A779: 67.3±5.8% versus vehicle: 46.4±3.6% of max). An upregulation in angiotensin II type 1 receptor expression was detected in medullary nuclei in WT CHF mice, which was significantly attenuated in SA mice with CHF. These data suggest that central ACE2 overexpression exerts a potential protective effect in CHF through attenuating sympathetic outflow. The mechanism for this effect involves angiotensin (1-7) mas signaling, as well as a decrease in angiotensin II type 1 receptor signaling in the medulla.
Genetic Variants and Blood Pressure in a Population-Based Cohort
Authors: Oikonen Mervi , Tikkanen Emmi , Juhola Jonna , Tuovinen Tarja , Seppälä Ilkka , Juonala Markus , Taittonen Leena , Mikkilä Vera , Kähönen Mika , Ripatti Samuli , Viikari Jorma , Lehtimäki Terho , Havulinna Aki S. , Kee Frank , Newton-Cheh Christopher , Peltonen Leena , Schork Nicholas J. , Murray Sarah S. , Berenson Gerald S. , Chen Wei , Srinivasan Sathanur R. , Salomaa Veikko , Raitakari Olli T.
Published: October 2011

Clinical relevance of a genetic predisposition to elevated blood pressure was quantified during the transition from childhood to adulthood in a population-based Finnish cohort (N=2357). Blood pressure was measured at baseline in 1980 (age 3–18 years) and in follow-ups in 1983, 1986, 2001, and 2007. Thirteen single nucleotide polymorphisms associated with blood pressure were genotyped, and 3 genetic risk scores associated with systolic and diastolic blood pressures and their combination were derived for all of the participants. Effects of the genetic risk score were 0.47 mm Hg for systolic and 0.53 mm Hg for diastolic blood pressures (both
P
<0.01). The combination genetic risk score was associated with diastolic blood pressure from age 9 years onward (β=0.68 mm Hg;
P
=0.015). Replications in 1194 participants of the Bogalusa Heart Study showed essentially similar results. The participants in the highest quintile of the combination genetic risk score had a 1.82-fold risk of hypertension in adulthood (
P
<0.0001) compared with the lowest quintile, independent of a family history of premature hypertension. These findings show that genetic variants are associated with preclinical blood pressure traits in childhood; individuals with several susceptibility alleles have, on average, a 0.5-mm Hg higher blood pressure, and this trajectory continues from childhood to adulthood.
Insulin Resistance, Low Cardiorespiratory Fitness, and Increased Exercise Blood Pressure
Authors: Huot Maxime , Arsenault Benoit J. , Gaudreault Valérie , Poirier Paul , Pérusse Louis , Tremblay Angelo , Bouchard Claude , Després Jean-Pierre , Rhéaume Caroline
Published: October 2011

Individuals with insulin resistance and low cardiorespiratory fitness are frequently found to have an increased waist circumference and high exercise blood pressure. We tested the hypothesis that the relationships among insulin resistance, low cardiorespiratory fitness, and increased exercise blood pressure may be mediated by an elevated waist circumference. This study included 317 apparently healthy men and women (mean age: 34.8±12.8 years; mean body mass index: 26.1±5.2 kg/m
2
). Exercise blood pressure values were measured using a submaximal ergometer test evaluating physical working capacity. Plasma insulin and glucose levels were measured during a 3-hour oral glucose tolerance test. Multivariate regression analyses showed that waist circumference accounted for 32.8% (
P
<0.0001) and 45.1% (
P
<0.0001) of the variance in exercise systolic blood pressure in men and women, respectively. Participants were classified into tertiles according to either insulin response, measured during the oral glucose tolerance test, or fitness levels and then further subdivided into 2 subgroups using sex-specific waist circumference thresholds. Individuals with an increased waist circumference (≥94 cm and ≥80 cm for men and women, respectively) had higher exercise systolic blood pressure compared with individuals with low waist circumference, irrespective of their level of insulin resistance (10.6 versus 6.8, 12.2 versus 7.7, and 13.2 versus 8.7 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles;
P
<0.05) or fitness levels (13.1 versus 8.2, 12.0 versus 7.9, and 10.6 versus 7.1 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles;
P
<0.05). Individuals with a higher waist circumference have elevated exercise systolic blood pressure, regardless of their insulin sensitivity or level of cardiorespiratory fitness.
Residential Segregation from the Sixteenth to the Nineteenth Century: Evidence from the Netherlands
Authors: Lesger Clé , Van Leeuwen Marco H. D.
Published: October 2011

A case study of three early modern Dutch cities (Alkmaar, Delft, and Amsterdam) using geographical information systems and confronting earlier historical, sociological, and geographical models finds clear patterns of segregation below the level of the city block, thus necessitating block-face mapping. The remarkable continuity in patterns of residential segregation is best explained by the workings of the real-estate market, allowing the well-to-do and middle classes to realize their preferences. In Amsterdam, the merchant elites were able to use their political dominance to plan a scenic and expansive residential environment free from noisy and odorous activities.
Biblio-MetReS: A bibliometric network reconstruction application and server
Authors: Usié Anabel , Karathia Hiren , Teixidó Ivan , Valls Joan , Faus Xavier , Alves Rui , Solsona Francesc
Published: October 2011

Background

Reconstruction of genes and/or protein networks from automated analysis of the literature is one of the current targets of text mining in biomedical research. Some user-friendly tools already perform this analysis on precompiled databases of abstracts of scientific papers. Other tools allow expert users to elaborate and analyze the full content of a corpus of scientific documents. However, to our knowledge, no user friendly tool that simultaneously analyzes the latest set of scientific documents available on line and reconstructs the set of genes referenced in those documents is available.

Results

This article presents such a tool, Biblio-MetReS, and compares its functioning and results to those of other user-friendly applications (iHOP, STRING) that are widely used. Under similar conditions, Biblio-MetReS creates networks that are comparable to those of other user friendly tools. Furthermore, analysis of full text documents provides more complete reconstructions than those that result from using only the abstract of the document.

Conclusions

Literature-based automated network reconstruction is still far from providing complete reconstructions of molecular networks. However, its value as an auxiliary tool is high and it will increase as standards for reporting biological entities and relationships become more widely accepted and enforced. Biblio-MetReS is an application that can be downloaded from http://metres.udl.cat/. It provides an easy to use environment for researchers to reconstruct their networks of interest from an always up to date set of scientific documents.
Differential regulation of two closely related integrative and conjugative elements from Streptococcus thermophilus
Authors: Carraro Nicolas , Libante Virginie , Morel Catherine , Decaris Bernard , Charron-Bourgoin Florence , Leblond Pierre , Guédon Gérard
Published: October 2011

Background

Two closely related ICEs, ICESt1 and ICESt3, have been identified in the lactic acid bacterium Streptococcus thermophilus. While their conjugation and recombination modules are almost identical (95% nucleotide identity) and their regulation modules related, previous work has demonstrated that transconjugants carrying ICESt3 were generated at rate exceeding by a 1000 factor that of ICESt1.

Results

The functional regulation of ICESt1 and ICESt3 transcription, excision and replication were investigated under different conditions (exponential growth or stationary phase, DNA damage by exposition to mitomycin C). Analysis revealed an identical transcriptional organization of their recombination and conjugation modules (long unique transcript) whereas the transcriptional organization of their regulation modules were found to be different (two operons in ICESt1 but only one in ICESt3) and to depend on the conditions (promoter specific of stationary phase in ICESt3). For both elements, stationary phase and DNA damage lead to the rise of transcript levels of the conjugation-recombination and regulation modules. Whatever the growth culture conditions, excision of ICESt1 was found to be lower than that of ICESt3, which is consistent with weaker transfer frequencies. Furthermore, for both elements, excision increases in stationary phase (8.9-fold for ICESt1 and 1.31-fold for ICESt3) and is strongly enhanced by DNA damage (38-fold for ICESt1 and 18-fold for ICESt3). Although ICEs are generally not described as replicative elements, the copy number of ICESt3 exhibited a sharp increase (9.6-fold) after mitomycin C exposure of its harboring strain CNRZ385. This result was not observed when ICESt3 was introduced in a strain deriving ICESt1 host strain CNRZ368, deleted for this element. This finding suggests an impact of the host cell on ICE behavior.

Conclusions

All together, these results suggest a novel mechanism of regulation shared by ICESt1, ICESt3 and closely related ICEs, which we identified by analysis of recently sequenced genomes of firmicutes. This is the first report of a partial shutdown of the activity of an ICE executed by a strain belonging to its primary host species. The sharp increase of ICESt3 copy number suggests an induction of replication; such conditional intracellular replication may be common among ICEs.
Identification and characterization of the Non-race specific Disease Resistance 1 (NDR1) orthologous protein in coffee
Authors: Cacas Jean-Luc , Petitot Anne-Sophie , Bernier Louis , Estevan Joan , Conejero Geneviève , Mongrand Sébastien , Fernandez Diana
Published: October 2011

Background

Leaf rust, which is caused by the fungus Hemileia vastatrix (Pucciniales), is a devastating disease that affects coffee plants (Coffea arabica L.). Disadvantages that are associated with currently developed phytoprotection approaches have recently led to the search for alternative strategies. These include genetic manipulations that constitutively activate disease resistance signaling pathways. However, molecular actors of such pathways still remain unknown in C. arabica. In this study, we have isolated and characterized the coffee NDR1 gene, whose Arabidopsis ortholog is a well-known master regulator of the hypersensitive response that is dependent on coiled-coil type R-proteins.

Results

Two highly homologous cDNAs coding for putative NDR1 proteins were identified and cloned from leaves of coffee plants. One of the candidate coding sequences was then expressed in the Arabidopsis knock-out null mutant ndr1-1. Upon a challenge with a specific strain of the bacterium Pseudomonas syringae (DC3000::AvrRpt2), analysis of both macroscopic symptoms and in planta microbial growth showed that the coffee cDNA was able to restore the resistance phenotype in the mutant genetic background. Thus, the cDNA was dubbed CaNDR1a (standing for Coffea arabica Non-race specific Disease Resistance 1a). Finally, biochemical and microscopy data were obtained that strongly suggest the mechanistic conservation of the NDR1-driven function within coffee and Arabidopsis plants. Using a transient expression system, it was indeed shown that the CaNDR1a protein, like its Arabidopsis counterpart, is localized to the plasma membrane, where it is possibly tethered by means of a GPI anchor.

Conclusions

Our data provide molecular and genetic evidence for the identification of a novel functional NDR1 homolog in plants. As a key regulator initiating hypersensitive signalling pathways, CaNDR1 gene(s) might be target(s) of choice for manipulating the coffee innate immune system and achieving broad spectrum resistance to pathogens. Given the potential conservation of NDR1-dependent defense mechanisms between Arabidopsis and coffee plants, our work also suggests new ways to isolate the as-yet-unidentified R-gene(s) responsible for resistance to H. vastatrix.
In-hospital informal caregivers' needs as perceived by themselves and by the nursing staff in Northern Greece: A descriptive study
Authors: Lavdaniti Maria , Raftopoulos Vasilios , Sgantzos Markos , Psychogiou Maria , Areti Tsaloglidou , Georgiadou Charikleia , Serpanou Ismini , Sapountzi-Krepia Despina
Published: October 2011

Background

Informal care is common in many countries, especially in Greece, where families provide care in hospitals. Health education and informational needs are important factors for family members which are often underestimated by nursing staff. The aim of this study was to compare the perceptions of the nurses and the in-hospital informal caregivers about the in-hospital informal caregivers' knowledge and informational needs, as well as the factors that influence these perceptions.

Methods

This was a non-experimental descriptive study conducted in three general hospitals in Greece. The sample consisted of 320 nurses and 370 in-hospital informal caregivers who completed questionnaires. Descriptive statistics were analyzed using t-tests; group comparisons were conducted using ANOVA.

Results

The score of the questionnaire for health education and informational needs was significantly greater for informal caregivers (57.1 ± 6.9 and 26.6 ± 2.8) than for nurses (53.4 ± 5.7 and 22.4 ± 3.1) (p < 0.001). For the nursing staff, the factors that influence the informational needs of patients' caregivers were level of education and working experience, while for the caregivers the level of education was independently associated with the score for the health education needs. Finally, age, marital status, and level of education of informal caregivers' were independently associated with informational needs.

Conclusions

The in-hospital informal caregivers perceived that they have more educational and informational needs than the nurses did. The findings of this study also show that the nursing staff has to identify the needs of in-hospital informal caregivers in order to be able to meet these needs.
Congenital hyperinsulinism: current trends in diagnosis and therapy
Authors: Arnoux Jean-Baptiste , Verkarre Virginie , Saint-Martin Cécile , Montravers Françoise , Brassier Anaïs , Valayannopoulos Vassili , Brunelle Francis , Fournet Jean-Christophe , Robert Jean-Jacques , Aigrain Yves , Bellanné-Chantelot Christine , de Lonlay Pascale
Published: October 2011

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.
Robust Control of PEP Formation Rate in the Carbon Fixation Pathway of C4 Plants by a Bi-functional Enzyme
Authors: Hart Yuval , Mayo Avraham E , Milo Ron , Alon Uri
Published: October 2011

Background

C4 plants such as corn and sugarcane assimilate atmospheric CO2 into biomass by means of the C4 carbon fixation pathway. We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a precise rate, regulated by light, despite fluctuations in substrate and enzyme levels constituting and regulating this process.

Results

We present a putative mechanism for robustness in C4 carbon fixation, involving a key enzyme in the pathway, pyruvate orthophosphate dikinase (PPDK), which is regulated by a bifunctional enzyme, Regulatory Protein (RP). The robust mechanism is based on avidity of the bifunctional enzyme RP to its multimeric substrate PPDK, and on a product-inhibition feedback loop that couples the system output to the activity of the bifunctional regulator. The model provides an explanation for several unusual biochemical characteristics of the system and predicts that the system's output, phosphoenolpyruvate (PEP) formation rate, is insensitive to fluctuations in enzyme levels (PPDK and RP), substrate levels (ATP and pyruvate) and the catalytic rate of PPDK, while remaining sensitive to the system's input (light levels).

Conclusions

The presented PPDK mechanism is a new way to achieve robustness using product inhibition as a feedback loop on a bifunctional regulatory enzyme. This mechanism exhibits robustness to protein and metabolite levels as well as to catalytic rate changes. At the same time, the output of the system remains tuned to input levels.