bluuebunny/crossref_metadata_2025 huggingface dataset:
IgM Antibodies to the Rescue!
Authors: Shum Anthony K.
Published: February 2012

One of our body’s natural defenses might help prevent organ transplant rejection.
Diverse Sequence Types of Klebsiella pneumoniae Contribute to the Dissemination of
bla
NDM-1
in India, Sweden, and the United Kingdom
Authors: Giske Christian G. , Fröding Inga , Hasan Chowdhury Mehedi , Turlej-Rogacka Agata , Toleman Mark , Livermore David , Woodford Neil , Walsh Timothy R.
Published: February 2012

Clinical isolates of
Klebsiella pneumoniae
producing NDM-1 carbapenemase from India (
n
= 22), the United Kingdom (
n
= 13), and Sweden (
n
= 4) were subjected to multilocus sequence typing (MLST), automated repetitive sequence-based PCR (rep-PCR), serotyping, virulence gene screening, and plasmid replicon typing. The most frequently detected MLST sequence types (STs) were ST14 (
n
= 13; all serotype K2), ST11, ST149, ST231, and ST147. The correlation between MLST and automated rep-PCR was excellent. IncA/C was the most frequently detected plasmid replicon type (
n
= 14). ST14, ST11, and other successful clones may be important for the dissemination of
bla
NDM-1
.
CpsY Influences Streptococcus iniae Cell Wall Adaptations Important for Neutrophil Intracellular Survival
Authors: Allen Jonathan P. , Neely Melody N.
Published: February 2012

The ability of a pathogen to evade neutrophil phagocytic killing mechanisms is critically important for dissemination and establishment of a systemic infection. Understanding how pathogens overcome these innate defenses is essential for the development of optimal therapeutic strategies for invasive infections. CpsY is a conserved transcriptional regulator previously identified as an important virulence determinant for systemic infection of
Streptococcus iniae
. While orthologs of CpsY have been associated with the regulation of methionine metabolism and uptake pathways, CpsY additionally functions in protection from neutrophil-mediated killing.
S. iniae
does not alter neutrophil phagosomal maturation but instead is able to adapt to the extreme bactericidal environment of a mature neutrophil phagosome, a property dependent upon CpsY. This CpsY-dependent adaptation appears to involve stabilization of the cell wall through peptidoglycan O-acetylation and repression of cellular autolysins. Furthermore,
S. iniae
continues to be a powerful model for investigation of bacterial adaptations during systemic streptococcal infection.
Escherichia coli Uropathogenesis
In Vitro
: Invasion, Cellular Escape, and Secondary Infection Analyzed in a Human Bladder Cell Infection Model
Authors: Andersen Thomas E. , Khandige Surabhi , Madelung Michelle , Brewer Jonathan , Kolmos Hans J. , Møller-Jensen Jakob
Published: February 2012

Uropathogenic
Escherichia coli
(UPEC) strains are capable of invading bladder epithelial cells (BECs) on the bladder luminal surface. Based primarily on studies in mouse models, invasion is proposed to trigger an intracellular uropathogenic cascade involving intracellular bacterial proliferation followed by escape of elongated, filamentous bacteria from colonized BECs. UPEC filaments on the mouse bladder epithelium are able to revert to rod-shaped bacteria, which are believed to invade neighboring cells to initiate new rounds of intracellular colonization. So far, however, these late-stage infection events have not been replicated
in vitro
. We have established an
in vitro
model of human bladder cell infection by the use of a flow chamber (FC)-based culture system, which allows investigation of steps subsequent to initial invasion. Short-term bacterial colonization on the FC-BEC layer led to intracellular colonization. Exposing invaded BECs to a flow of urine, i.e., establishing conditions similar to those faced by UPEC reemerging on the bladder luminal surface, led to outgrowth of filamentous bacteria similar to what has been reported to occur in mice. These filaments were capable of reverting to rods that could invade other BECs. Hence, under growth conditions established to resemble those present
in vivo
, the elements of the proposed uropathogenic cascade were inducible in a human BEC model system. Here, we describe the model and show how these characteristics are reproduced
in vitro
.
Increase in Campylobacter jejuni Invasion of Intestinal Epithelial Cells under Low-Oxygen Coculture Conditions That Reflect the
In Vivo
Environment
Authors: Mills Dominic C. , Gundogdu Ozan , Elmi Abdi , Bajaj-Elliott Mona , Taylor Peter W. , Wren Brendan W. , Dorrell Nick
Published: February 2012

Campylobacter jejuni
infection often results in bloody, inflammatory diarrhea, indicating bacterial disruption and invasion of the intestinal epithelium. While
C. jejuni
infection can be reproduced
in vitro
using intestinal epithelial cell (IEC) lines, low numbers of bacteria invading IECs do not reflect these clinical symptoms. Performing
in vitro
assays under atmospheric oxygen conditions neither is optimal for microaerophilic
C. jejuni
nor reflects the low-oxygen environment of the intestinal lumen. A vertical diffusion chamber (VDC) model system creates microaerobic conditions at the apical surface and aerobic conditions at the basolateral surface of cultured IECs, producing an
in vitro
system that closely mimics
in vivo
conditions in the human intestine. Ninefold increases in interacting and 80-fold increases in intracellular
C. jejuni
11168H wild-type strain bacteria were observed after 24-h coculture with Caco-2 IECs in VDCs under microaerobic conditions at the apical surface, compared to results under aerobic conditions. Increased bacterial interaction was matched by an enhanced and directional host innate immune response, particularly an increased basolateral secretion of the proinflammatory chemokine interleukin-8 (IL-8). Analysis of the invasive ability of a nonmotile
C. jejuni
11168H
rpoN
mutant in the VDC model system indicates that motility is an important factor in the early stages of bacterial invasion. The first report of the use of a VDC model system for studying the interactions of an invasive bacterial pathogen with IECs demonstrates the importance of performing such experiments under conditions that represent the
in vivo
situation and will allow novel insights into
C. jejuni
pathogenic mechanisms.
Anaerobic Decomposition of Switchgrass by Tropical Soil-Derived Feedstock-Adapted Consortia
Authors: DeAngelis Kristen M. , Fortney Julian L. , Borglin Sharon , Silver Whendee L. , Simmons Blake A. , Hazen Terry C.
Published: February 2012

Tropical forest soils decompose litter rapidly with frequent episodes of anoxic conditions, making it likely that bacteria using alternate terminal electron acceptors (TEAs) play a large role in decomposition. This makes these soils useful templates for improving biofuel production. To investigate how TEAs affect decomposition, we cultivated feedstock-adapted consortia (FACs) derived from two tropical forest soils collected from the ends of a rainfall gradient: organic matter-rich tropical cloud forest (CF) soils, which experience sustained low redox, and iron-rich tropical rain forest (RF) soils, which experience rapidly fluctuating redox. Communities were anaerobically passed through three transfers of 10 weeks each with switchgrass as a sole carbon (C) source; FACs were then amended with nitrate, sulfate, or iron oxide. C mineralization and cellulase activities were higher in CF-FACs than in RF-FACs. Pyrosequencing of the small-subunit rRNA revealed members of theFirmicutes,Bacteroidetes, andAlphaproteobacteriaas dominant. RF- and CF-FAC communities were not different in microbial diversity or biomass. The RF-FACs, derived from fluctuating redox soils, were the most responsive to the addition of TEAs, while the CF-FACs were overall more efficient and productive, both on a per-gram switchgrass and a per-cell biomass basis. These results suggest that decomposing microbial communities in fluctuating redox environments are adapted to the presence of a diversity of TEAs and ready to take advantage of them. More importantly, these data highlight the role of local environmental conditions in shaping microbial community function that may be separate from phylogenetic structure.

IMPORTANCEAfter multiple transfers, we established microbial consortia derived from two tropical forest soils with different native redox conditions. Communities derived from the rapidly fluctuating redox environment maintained a capacity to use added terminal electron acceptors (TEAs) after multiple transfers, though they were not present during the enrichment. Communities derived from lower-redox soils were not responsive to TEA addition but were much more efficient at switchgrass decomposition. Though the communities were different, diversity was not, and both were dominated by many of the same species of clostridia. This reflects the inadequacy of rRNA for determining the function of microbial communities, in this case the retained ability to utilize TEAs that were not part of the selective growth conditions. More importantly, this suggests that microbial community function is shaped by life history, where environmental factors produce heritable traits through natural selection over time, creating variation in the community, a phenomenon not well documented for microbes.
SYMMETRIC HEAT CONDUCTION IN HARMONIC CHAIN WITH HARMONIC ON-SITE POTENTIAL AND MASS GRADIENT
Authors: HU TAO , HU KE , TANG YI
Published: February 2012

We investigate, using the exact Langevin equation, the properties of the heat conduction of an individual 1D harmonic chain with harmonic on-site potential. Each particle interacts with its own independent thermal reservoir. The results indicate that there is no rectification effect in this model even with mass gradient in the case of weak interparticle interaction. It may suggest that a system with harmonic on-site potential and asymmetric structure does not guarantee an asymmetric heat transport.
Policing the future
Authors: Greengard Samuel
Published: February 2012

Computer programs and new mathematical algorithms are helping law enforcement agencies better predict when and where crimes will occur.
The artificiality of natural user interfaces
Authors: Malizia Alessio , Bellucci Andrea
Published: February 2012

Toward user-defined gestural interfaces.
Commensal cuckoo
Authors: Sen Siddhartha , Freedman Michael J.
Published: February 2012

We present commensal cuckoo,* a secure group partitioning scheme for large-scale systems that maintains the correctness of many small groups, despite a Byzantine adversary that controls a constant (global) fraction of all nodes. In particular, the adversary is allowed to repeatedly rejoin faulty nodes to the system in an arbitrary adaptive manner, e.g., to collocate them in the same group. Commensal cuckoo addresses serious practical limitations of the state-ofthe- art scheme, the cuckoo rule of Awerbuch and Scheideler, tolerating 32x--41x more faulty nodes with groups as small as 64 nodes (as compared to the hundreds required by the cuckoo rule). Secure group partitioning is a key component of highly-scalable, reliable systems such as Byzantine faulttolerant distributed hash tables (DHTs).
Resonance-Enhanced Raman Spectroscopy on Explosives Vapor at Standoff Distances
Authors: Ehlerding Anneli , Johansson Ida , Wallin Sara , Östmark Henric
Published: February 2012

Resonance-enhanced Raman spectroscopy has been used to perform standoff measurements on nitromethane (NM), 2,4-DNT, and 2,4,6-TNT in vapor phase. The Raman cross sections for NM, DNT, and TNT in vapor phase have been measured in the wavelength range 210–300 nm under laboratory conditions, in order to estimate how large resonance enhancement factors can be achieved for these explosives. The results show that the signal is enhanced up to 250,000 times for 2,4-DNT and up to 60,000 times for 2,4,6-TNT compared to the nonresonant signal at 532 nm. Realistic outdoor measurements on NM in vapor phase at 13 m distance were also performed, which indicate a potential for resonance Raman spectroscopy as a standoff technique for detection of vapor phase explosives. In addition, the Raman spectra of acetone, ethanol, and methanol were measured at the same wavelengths, and their influence on the spectrum from NM was investigated.
Low-Frequency Noise and Microplasma Analysis for c-Si Solar Cell Characterization
Authors: Vanek Jiří , Dolensky Jan , Chobola Zdenek , Luňák Mirek , Poruba Aleš
Published: February 2012

This paper brings the comparison of solar cell conversion efficiency and results from a noise spectroscopy and microplasma presence to evaluate the solar cell technology. Three sets of monocrystalline silicon solar cells (c-Si) varying in front side phosphorus doped emitters were produced by standard screen-printing technique. From the measurements it follows that the noise spectral density related to defects is of 1/ftype and its magnitude. It has been established that samples showing low noise feature high-conversion efficiency. The best results were reached for a group solar cells with selective emitter structure prepared by double-phosphorus diffusion process.
Significant Changes in the Levels of Secreted Cytokines in Brains of Experimental Antiphospholipid Syndrome Mice
Authors: Menachem Assaf , Chapman Joab , Katzav Aviva
Published: February 2012

Antiphospholipid syndrome (APS) is characterized by thromboses and neuropsychiatric manifestations possibly linked to brain inflammation. In order to examine the levels of proinflammatory and anti-inflammatory cytokines in experimental APS (eAPS) mice brains, we measured the levels of TNF-α, IFN-γ, and IL-10 in brain homogenates (cytosolic fractions) and in brain slices (secreted level) at 6, 15, and 24 weeks after immunization. We induced eAPS by immunization of Balb/c mice withβ2-glycoprotein I (β2GPI), the major autoantigen in the disease and controls with adjuvant alone. We found increased levels of secreted TNF-αin eAPS mice for the entire experiment period. Cytosolic and secreted IL-10 and IFN-γlevels in eAPS mice were lower at 6 and 15 weeks and higher at 24 weeks after immunization. The results suggest that brain disease in APS is associated with significant and complex changes in proinflammatory and anti-inflammatory cytokines.
Multimodel Inference for the Prediction of Disease Symptoms and Yield Loss of Potato in a Two-Year Crop Rotation Experiment
Authors: Van den Berg Wim , Vos Jan , Grasman Johan
Published: February 2012

The second order Akaike information criterion was used for the assessment of 139 regression models for three responses of potato test crops: (a) incidence ofSpongospora subterraneaon the harvested tubers, (b) percentage of haulms infected withVerticillium dahliae,and (c) tuber yield. Six variables that are likely related to the response variables were taken into consideration: soil infestations of the fungusVerticillium dahliaeand of three nematode species (Globodera pallida,Trichodoridae,andMeloidogynespp.) and, furthermore, soil pH and water soluble phosphor (P). Interactions betweenV. dahliaeand the three nematode species were included as well. Based on multimodelling, predictors are given a weight from which one may decide about the need to include them in a prediction of crop yield. The most important predictors were soil infestation levels ofV. dahliaeandG. pallidaand soil pH. The outcome also showed that tubers suffered more fromS. subterraneafor higher soil pH values. Finally, yield reduction from the presence ofV. dahliaewas enhanced by the presence of higher densities ofG. pallida.
Higuchi Fractal Properties of Onset Epilepsy Electroencephalogram
Authors: Khoa Truong Quang Dang , Ha Vo Quang , Toi Vo Van
Published: February 2012

Epilepsy is a medical term which indicates a common neurological disorder characterized by seizures, because of abnormal neuronal activity. This leads to unconsciousness or even a convulsion. The possible etiologies should be evaluated and treated. Therefore, it is necessary to concentrate not only on finding out efficient treatment methods, but also on developing algorithm to support diagnosis. Currently, there are a number of algorithms, especially nonlinear algorithms. However, those algorithms have some difficulties one of which is the impact of noise on the results. In this paper, in addition to the use of fractal dimension as a principal tool to diagnose epilepsy, the combination between ICA algorithm and averaging filter at the preprocessing step leads to some positive results. The combination which improved the fractal algorithm become robust with noise on EEG signals. As a result, we can see clearly fractal properties in preictal and ictal period so as to epileptic diagnosis.
Stereotactic Irradiation of GH-Secreting Pituitary Adenomas
Authors: Minniti G. , Scaringi C. , Amelio D. , Maurizi Enrici R.
Published: February 2012

Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques.
Hamster and Murine Models of Severe Destructive Lyme Arthritis
Authors: Munson Erik , Nardelli Dean T. , Du Chateau Brian K. , Callister Steven M. , Schell Ronald F.
Published: February 2012

Arthritis is a frequent complication of infection in humans withBorrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetentBorrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viableB. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology.
Determinants of Adherence to Antiretroviral Therapy among HIV-Infected Patients in Africa
Authors: Reda Ayalu A. , Biadgilign Sibhatu
Published: February 2012

Background. There are only a few comprehensive studies of adherence to ART and its challenges in Africa. This paper aims to assess the evidence on the challenges and prospects of ART adherence in sub-Saharan Africa.Methods. The authors reviewed original and review articles involving HIV-positive individuals that measured adherence to ART and its predictors in the past decade.Findings. Against expectations, sub-Saharan Africa patients have similar or higher adherence levels compared to those of developed countries. The challenges to ART adherence include factors related to patients and their families, socioeconomic factors, medication, and healthcare systems.Conclusion. Despite good adherence and program-related findings, antiretroviral treatment is challenged by a range of hierarchical and interrelated factors. There is substantial room for improvement of ART programs in sub-Sahara African countries.
Interactions between Serum Adipokines and Osteocalcin in Older Patients with Hip Fracture
Authors: Fisher Alexander , Srikusalanukul Wichat , Davis Michael , Smith Paul
Published: February 2012

Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated the hypothesis of a bidirectional link between adipokines and osteocalcin.Materials and Methods. In a cross-sectional study of 294 older patients with osteoporotic hip fracture, we estimated serum concentrations of leptin, adiponectin, resistin, osteocalcin, parameters of mineral metabolism, and renal function.Results. After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with resistin and positively with leptin, leptin/resistin ratio, and adiponectin/resistin ratio. In multivariate regression models, osteocalcin was an independent predictor of serum leptin, resistin, leptin/resistin, and adiponectin/resistin ratios.Conclusions. Our data support the bidirectional regulation between osteocalcin and adipokines, but contrary to the genetically modified animal models, in older subjects with osteoporotic hip fracture, serum osteocalcin is positively associated with leptin and inversely with resistin.
Integral and Variational Formulations for the Helmholtz Equation Inverse Source Problem
Authors: Rainha Marcelo L. , Roberty Nilson C.
Published: February 2012

The purpose of this paper is to explore the Hilbert space functional structure of the Helmholtz equation inverse source problem. An integral equation for the sources reconstruction based on the composition of the trace and Green′s function operators is introduced and compared with the reciprocity source reconstruction methodologies. An equivalence theorem comparing the integral inverse source equation with the variational weak reciprocity gap functional equation is then demonstrated. Some examples on applications to the unitary disk are presented.
An Extension of the Legendre‐Galerkin Method for Solving Sixth‐Order Differential Equations with Variable Polynomial Coefficients
Authors: Bhrawy A. H. , Alofi A. S. , El-Soubhy S. I.
Published: February 2012

We extend the application of Legendre‐Galerkin algorithms for sixth‐order
elliptic problems with constant coefficients to sixth‐order elliptic equations with variable polynomial
coefficients. The complexities of the algorithm are O(N) operations for a one‐dimensional domain with
(N − 5) unknowns. An efficient and accurate direct solution for algorithms based on the Legendre‐Galerkin
approximations developed for the two‐dimensional sixth‐order elliptic equations with variable coefficients
relies upon a tensor product process. The proposed Legendre‐Galerkin method for solving
variable coefficients problem is more efficient than pseudospectral method. Numerical examples are
considered aiming to demonstrate the validity and applicability of the proposed techniques.
Prevalence and Characteristics of Lung Involvement on High Resolution Computed Tomography in Patients with Ankylosing Spondylitis: A Systematic Review
Authors: El Maghraoui Abdellah , Dehhaoui Mohamed
Published: February 2012

To determine the prevalence of lung involvement and the spectrum of abnormalities revealed on HRCT in patients with AS, a systematic literature review was conducted in the Medline database up to May 2009 and in the abstracts of rheumatology scientific meetings (2006–2008). A hand search of references was also performed. Among the 264 selected articles, 10 articles (303 patients) allowed a calculation of the prevalence of lung abnormalities on thoracic HRCT in AS. A total of 185 patients (61%) had an abnormal thoracic HRCT: upper lobe fibrosis in 21 (6.9%), emphysema in 55 (18.1%), bronchiectasis in 33 (10.8%), and ground glass attenuation in 34 (11.2%). Non specific interstitial abnormalities were observed in 101 (33%) patients. The most common observed abnormalities were pleural thickening (52%), parenchymal bands (45%) and interlobular septal thickening (30%). Only the prevalence of upper lobe fibrosis increased significantly with disease duration (3 studies). Mild and non-specific interstitial abnormalities on thoracic HRCT are common in patients with AS, even in patients with early disease and without respiratory symptoms.
Reduced KCNQ4-Encoded Voltage-Dependent Potassium Channel Activity Underlies Impaired β-Adrenoceptor–Mediated Relaxation of Renal Arteries in Hypertension
Authors: Chadha Preet S. , Zunke Friederike , Zhu Hai-Lei , Davis Alison J. , Jepps Thomas A. , Olesen Søren P. , Cole William C. , Moffatt James D. , Greenwood Iain A.
Published: February 2012

KCNQ4-encoded voltage-dependent potassium (Kv7.4) channels are important regulators of vascular tone that are severely compromised in models of hypertension. However, there is no information as to the role of these channels in responses to endogenous vasodilators. We used a molecular knockdown strategy, as well as pharmacological tools, to examine the hypothesis that Kv7.4 channels contribute to β-adrenoceptor–mediated vasodilation in the renal vasculature and underlie the vascular deficit in spontaneously hypertensive rats. Quantitative PCR and immunohistochemistry confirmed gene and protein expression of KCNQ1, KCNQ3, KCNQ4, KCNQ5, and Kv7.1, Kv7.4, and Kv7.5 in rat renal artery. Isoproterenol produced concentration-dependent relaxation of precontracted renal arteries and increased Kv7 channel currents in isolated smooth muscle cells. Application of the Kv7 blocker linopirdine attenuated isoproterenol-induced relaxation and current. Isoproterenol-induced relaxations were also reduced in arteries incubated with small interference RNAs targeted to KCNQ4 that produced a ≈60% decrease in Kv7.4 protein level. Relaxation to isoproterenol and the Kv7 activator S-1 were abolished in arteries from spontaneously hypertensive rats, which was associated with ≈60% decrease in Kv7.4 abundance. This study provides the first evidence that Kv7 channels contribute to β-adrenoceptor–mediated vasodilation in the renal vasculature and that abrogation of Kv7.4 channels is strongly implicated in the impaired β-adrenoceptor pathway in spontaneously hypertensive rats. These findings may provide a novel pathogenic link between arterial dysfunction and hypertension.
Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models
Authors: Ammirati Enrico , Cianflone Domenico , Vecchio Viviana , Banfi Michela , Vermi Anna C. , De Metrio Monica , Grigore Liliana , Pellegatta Fabio , Pirillo Angela , Garlaschelli Katia , Manfredi Angelo A. , Catapano Alberico L. , Maseri Attilio , Palini Alessio G. , Norata Giuseppe D.
Published: February 2012

Background

Adaptive T‐cell response is promoted during atherogenesis and results in the differentiation of naïve CD4
+
T cells to effector and/or memory cells of specialized T‐cell subsets. Aim of this work was to investigate the relationship between circulating CD4
+
T‐cell subsets and atherosclerosis.

Methods and Results

We analyzed 57 subsets of circulating CD4
+
T cells by 10‐parameter/8‐color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA‐DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free‐living population (
n
=183), effector memory T cells (T
EM
: CD3
+
CD4
+
CD45RA
−
CD45RO
+
CCR7
−
cells) were strongly related with intima‐media thickness of the common carotid artery, even after adjustment for age (
r
=0.27;
P
<0.001). Of note, a significant correlation between T
EM
and low‐density lipoproteins was observed. In the second cohort (
n
=130), T
EM
levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA‐DR
+
T
EM
were the T
EM
subpopulation with the strongest association with the atherosclerotic process (
r
=0.37;
P
<0.01). Finally, in animal models of atherosclerosis, T
EM
(identified as CD4
+
CD44
+
CD62L
−
) were significantly increased in low‐density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (
r
=0.56;
P
<0.01).

Conclusions

Circulating T
EM
cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4
+
T‐cell subset related to the atherosclerotic process.

(
J Am Heart Assoc
2012;1:27‐41.)
Dicer1 deletion in myeloid-committed progenitors causes neutrophil dysplasia and blocks macrophage/dendritic cell development in mice
Authors: Alemdehy Mir Farshid , van Boxtel Nicole G. J. A. , de Looper Hans W. J. , van den Berge Iris J. , Sanders Mathijs A. , Cupedo Tom , Touw Ivo P. , Erkeland Stefan J.
Published: February 2012

MicroRNAs (miRNAs) have the potential to regulate cellular differentiation programs; however, miRNA deficiency in primary hematopoietic stem cells (HSCs) results in HSC depletion in mice, leaving the question of whether miRNAs play a role in early-lineage decisions un-answered. To address this issue, we deleted Dicer1, which encodes an essential RNase III enzyme for miRNA biogenesis, in murine CCAAT/enhancer-binding protein α (C/EBPA)–positive myeloid-committed progenitors in vivo. In contrast to the results in HSCs, we found that miRNA depletion affected neither the number of myeloid progenitors nor the percentage of C/EBPA–positive progenitor cells. Analysis of gene-expression profiles from wild-type and Dicer1-deficient granulocyte-macrophage progenitors (GMPs) revealed that 20 miRNA families were active in GMPs. Of the derepressed miRNA targets in Dicer1-null GMPs, 27% are normally exclusively expressed in HSCs or are specific for multipotent progenitors and erythropoiesis, indicating an altered gene-expression landscape. Dicer1-deficient GMPs were defective in myeloid development in vitro and exhibited an increased replating capacity, indicating the regained self-renewal potential of these cells. In mice, Dicer1 deletion blocked monocytic differentiation, depleted macrophages, and caused myeloid dysplasia with morphologic features of Pelger-Huët anomaly. These results provide evidence for a miRNA-controlled switch for a cellular program of self-renewal and expansion toward myeloid differentiation in GMPs.
miRTrail - a comprehensive webserver for analyzing gene and miRNA patterns to enhance the understanding of regulatory mechanisms in diseases
Authors: Laczny Cedric , Leidinger Petra , Haas Jan , Ludwig Nicole , Backes Christina , Gerasch Andreas , Kaufmann Michael , Vogel Britta , Katus Hugo A , Meder Benjamin , Stähler Cord , Meese Eckart , Lenhof Hans-Peter , Keller Andreas
Published: February 2012

Background

Expression profiling provides new insights into regulatory and metabolic processes and in particular into pathogenic mechanisms associated with diseases. Besides genes, non-coding transcripts as microRNAs (miRNAs) gained increasing relevance in the last decade. To understand the regulatory processes of miRNAs on genes, integrative computer-aided approaches are essential, especially in the light of complex human diseases as cancer.

Results

Here, we present miRTrail, an integrative tool that allows for performing comprehensive analyses of interactions of genes and miRNAs based on expression profiles. The integrated analysis of mRNA and miRNA data should generate more robust and reliable results on deregulated pathogenic processes and may also offer novel insights into the regulatory interactions between miRNAs and genes. Our web-server excels in carrying out gene sets analysis, analysis of miRNA sets as well as the combination of both in a systems biology approach. To this end, miRTrail integrates information on 20.000 genes, almost 1.000 miRNAs, and roughly 280.000 putative interactions, for Homo sapiens and accordingly for Mus musculus and Danio rerio. The well-established, classical Chi-squared test is one of the central techniques of our tool for the joint consideration of miRNAs and their targets. For interactively visualizing obtained results, it relies on the network analyzers and viewers BiNA or Cytoscape-web, also enabling direct access to relevant literature. We demonstrated the potential of miRTrail by applying our tool to mRNA and miRNA data of malignant melanoma. MiRTrail identified several deregulated miRNAs that target deregulated mRNAs including miRNAs hsa-miR-23b and hsa-miR-223, which target the highest numbers of deregulated mRNAs and regulate the pathway "basal cell carcinoma". In addition, both miRNAs target genes like PTCH1 and RASA1 that are involved in many oncogenic processes.

Conclusions

The application on melanoma samples demonstrates that the miRTrail platform may open avenues for investigating the regulatory interactions between genes and miRNAs for a wide range of human diseases. Moreover, miRTrail cannot only be applied to microarray based expression profiles, but also to NGS-based transcriptomic data. The program is freely available as web-server at mirtrail.bioinf.uni-sb.de.
Transmission capacity for dual-hop relaying in wireless ad hoc networks
Authors: Lee Jaeyoung , Shin Hyundong , Tae Kim Joon , Heo Jun
Published: February 2012

To account for randomly distributed nodes in a wireless ad hoc network, the transmission capacity is defined as the number of successful transmissions taking place in the network per unit area under an outage constraint. In this paper, we analyze the transmission capacity for dual-hop relaying in a wireless ad hoc network in the presence of both cochannel interference and thermal noise, where interferers are spatially distributed following a Poisson distribution. Specifically, we first present the exact outage probability for amplify-and-forward and decode-and-forward protocols in a Poisson field of interferers without neglecting noise at all nodes. We then derive the transmission capacity of such networks, which determines the maximum allowable density of transmitting nodes for each relay strategy at a specified outage probability and data rate. Numerical results demonstrate that the dual-hop relaying is still beneficial in terms of the transmission capacity in wireless ad hoc Poisson networks.
An efficient joint estimation of wideband polynomial-phase signal parameters and direction-of-arrival in sensor array
Authors: Djurović Igor , Djukanović Slobodan , Simeunović Marko , Raković Predrag , Barkat Braham
Published: February 2012

We consider the joint estimation of the direction-of-arrival (DOA) and parameters of wideband polynomial-phase signals (PPSs) in sensor array. Unlike concurrent methods that require multidimensional searches, the proposed method requires 1D searches for all the parameters of interest. In this way, we can efficiently estimate the considered parameters in applications where large antenna arrays, containing tens or hundreds of sensors, are used. As special cases, we consider in detail the estimation of the second- and third-order PPSs. The former are estimated using the high-order ambiguity function (HAF), while the latter are estimated using the cubic phase function (CPF), known to outperform the HAF in terms of both accuracy and signal-to-noise ratio (SNR) threshold. In both cases, the estimation of the highest order parameter reaches the Cramér-Rao lower bound (CRLB), while the DOA estimation is above the CRLB for around 1 dB (second-order PPS) and around 6 dB (third-order PPS).
Post-radiation increase in VEGF enhances glioma cell motility in vitro
Authors: Kil Whoon Jong , Tofilon Philip J , Camphausen Kevin
Published: February 2012

Background

Glioblastoma multiforme (GBM) is among the most lethal of all human tumors, with frequent local recurrences after radiation therapy (RT). The mechanism accounting for such a recurrence pattern is unclear. It has classically been attributed to local recurrence of treatment-resistant cells. However, accumulating evidence suggests that additional mechanisms exist that involve the migration of tumor or tumor stem cells from other brain regions to tumor bed. VEGFs are well-known mitogens and can be up-regulated after RT. Here, we examine the effect of irradiation-induced VEGF on glioma cell motility.

Materials and methods

U251 and LN18 cell lines were used to generate irradiated-conditioned medium (IR-CM). At 72 h after irradiation, the supernatants were harvested. VEGF level in IR-CM was quantified by ELISA, and expression levels for VEGF mRNA were detected by RT-PCR. In vitro cancer cell motility was measured in chambers coated with/without Matrigel and IR-CM as a cell motility enhancer and a VEGF antibody as a neutralizer of VEGF bioactivity. Immunoblots were performed to evaluate the activity of cell motility-related kinases. Proliferation of GBM cells after treatment was measured by flow cytometry.

Results

Irradiation increased the level of VEGF mRNA that was mitigated by pre-RT exposure to Actinomycin D. U251 glioma cell motility (migration and invasion) was enhanced by adding IR-CM to un-irradiated cells (174.9 ± 11.4% and 334.2 ± 46% of control, respectively). When we added VEGF antibody to IR-CM, this enhanced cell motility was negated (110.3 ± 12.0% and 105.7 ± 14.0% of control, respectively). Immunoblot analysis revealed that IR-CM increased phosphorylation of VEGF receptor-2 (VEGFR2) secondary to an increase in VEGF, with a concomitant increase of phosphorylation of the downstream targets (Src and FAK). Increased phosphorylation was mitigated by adding VEGF antibody to IR-CM. There was no difference in the mitotic index of GBM cells treated with and without IR-CM and VEGF.

Conclusions

These results indicate that cell motility can be enhanced by conditioned medium from irradiated cells in vitro through stimulation of VEGFR2 signaling pathways and suggest that this effect involves the secretion of radiation-induced VEGF, leading to an increase in glioma cell motility.
Identification of the Receptors for Prolactin-Releasing Peptide (PrRP) and Carassius RFamide Peptide (C-RFa) in Chickens
Authors: Wang Yajun , Wang Crystal Ying , Wu Yuting , Huang Guian , Li Juan , Leung Frederick C.
Published: February 2012

Prolactin-releasing peptide (PrRP) and its structurally related peptide, Carassius Arg-Phe-amide peptide (C-RFa), have been reported to play similar roles in regulating food intake and pituitary functions in vertebrates. However, the identity, functionality, and expression of the receptor(s) for PrRP and C-RFa remain largely unknown in nonmammalian vertebrates, including birds. In this study, three receptors homologous to mammalian PrRP receptor (PrRPR), named cPrRPR1, cPrRPR2, and cC-RFaR, respectively, were cloned from chicken brain by RT-PCR. Using a pGL3-NFAT-RE-luciferase reporter system, we demonstrated that cPrRPR1 and cPrRPR2 expressed in Chinese hamster ovarian cells could be activated by cPrRP20 and cC-RFa20 potently, whereas cC-RFaR could only be activated effectively by cC-RFa20 (EC50, 0.11 nm), indicating that cPrRPR1 and cPrRPR2 can function as common receptors for PrRP and C-RFa, whereas cC-RFaR is a receptor specific to C-RFa. Using a pGL3-CRE-luciferase reporter system, cPrRPR1, cPrRPR2, and cC-RFaR expressed in Chinese hamster ovarian cells were also shown to activate intracellular protein kinase A signaling pathway upon cC-RFa20 treatment (100 nm). Moreover, RT-PCR assay revealed that cPrRPR1, cPrRPR2, and cC-RFaR were widely expressed in most adult chicken tissues examined, including various regions of brain. These findings, together with evidence of PrRP and C-RFa encoded by separate genes in chicken, Xenopus, and zebrafish, and the differential expression of PrRP and C-RFa genes in chicken tissues, strongly suggest that PrRP and C-RFa may play similar yet distinctive roles in nonmammalian vertebrates, including chicken, and their actions are mediated by common receptor(s) or a specific C-RFa receptor.
Induction of membrane circular dorsal ruffles requires co-signalling of integrin–ILK-complex and EGF receptor
Authors: Azimifar S. Babak , Böttcher Ralph T. , Zanivan Sara , Grashoff Carsten , Krüger Marcus , Legate Kyle R. , Mann Matthias , Fässler Reinhard
Published: February 2012

Integrin and receptor tyrosine kinase signalling networks cooperate to regulate various biological functions. The molecular details underlying the integration of both signalling networks remain largely uncharacterized. Here we identify a signalling module composed of a fibronectin–α5β1-integrin–integrin-linked-kinase (ILK) complex that, in concert with epidermal growth factor (EGF) cues, cooperatively controls the formation of transient actin-based circular dorsal ruffles (DRs) in fibroblasts. DR formation depends on the precise spatial activation of Src at focal adhesions by integrin and EGF receptor signals, in an ILK-dependent manner. In a SILAC-based phosphoproteomics screen we identified the tumour-suppressor Cyld as being required for DR formation induced by α5β1 integrin and EGF receptor co-signalling. Furthermore, EGF-induced Cyld tyrosine phosphorylation is controlled by integrin–ILK and Src as a prerequisite for DR formation. This study provides evidence for a novel function of integrin–ILK and EGF signalling crosstalk in mediating Cyld tyrosine phosphorylation and fast actin-based cytoskeletal rearrangements.
Inquiry-Based Science Instruction and Performance Literacy for Students Who Are Deaf or Hard of Hearing
Authors: Wang Ye
Published: February 2012

Deaf and hard of hearing students, who cannot successfully access and utilize information in print, experience various difficulties in conventional science instruction, which heavily relies on lectures and textbooks. The purpose of the present review is threefold. First, an overview of inquiry-based science instruction reform, including the sociohistorical forces behind the movement, is presented. Then, the author examines the empirical research on science education for students who are deaf or hard of hearing from the 1970s to the present and identifies and rates inquiry-based practice. After discussing the difficulty of using science texts with deaf and hard of hearing students, the author introduces a conceptual framework that integrates inquiry-based instruction and the construct of performance literacy. She suggests that this integration should enable students who are deaf or hard of hearing to access the general education curriculum.
Nabokov’s Memory War against Freud
Authors: Kwon Teckyoung
Published: February 2012

Nabokov rejects systematic thinkers who engage in social and ideological generalizations. Reading Nabokov and Freud side by side, the author examines the origin of the Russian writer’s antipathy toward the psychoanalyst in three steps. First, she surveys the criticism addressing Nabokov’s views on Freud to determine if anything has been overlooked. Next, she compares Freud’s concept of screen memories to Nabokov’s childhood memories. Finally, she juxtaposes Nabokov’s art of memory, which is reflected in Lolita , and Freud’s system of remembering informing his analysis of the Wolf Man. Throughout, the author suggests how the delight Nabokov finds in both butterfly hunting and fiction writing leads him to engage in generalizations in his own way. This poet, who was also a scientist, engaged in a playful, even joyful, negation of Freud, a scientist who was also a poet. Freud, as a scientist, was compelled to generalize a theory, while Nabokov, as a poet, was ultimately unable to avoid generalizing the deceptive magic of the human psyche, art, and nature. Moreover, without the memory system to which Freud devoted his life, it would have been impossible for Nabokov to produce fiction based on a recollection of the past.
On dispersion of small energy solutions of the nonlinear Klein Gordon equation with a potential
Authors: Bambusi Dario , Cuccagna Scipio
Published: February 2012

In this paper we study small amplitude solutions of nonlinear Klein Gordon equations
with a potential. Under suitable smoothness and decay assumptions on the potential and
a genericity assumption on the nonlinearity, we prove that all small energy solutions
are asymptotically free. In cases where the linear system has at most one bound state
the result was already proved by Soffer and Weinstein: we obtain here a result valid in
the case of an arbitrary number of possibly degenerate bound states. The proof is based
on a combination of Birkhoff normal form techniques and dispersive estimates.
Canonical singular hermitian metrics on relative canonical bundles
Authors: Tsuji Hajime
Published: February 2012

We introduce a new class of canonical analytic Zariski decompositions (AZD's in short) called the
supercanonical AZD's on the canonical bundles of smooth projective varieties with pseudoeffective
canonical classes.\ We study the variation of the supercanonical AZD $\hat{h}_{{\rm can}}$ under
projective deformations and give a new proof of the invariance of plurigenera.
Rectifiable and flat G chains in a metric space
Authors: De Pauw Thierry , Hardt Robert
Published: February 2012

Chains, in a complete metric space, which have coefficients in a normed
abelian group $G$ are studied. An $m$ dimensional rectifiable chain is the
Lipschitz push-forward of a region in ${\Bbb R}^m$ equipped with a
measurable $G$-valued density. Flat chains are obtained by completion using
a certain flat norm on polyhedral or Lipschitz chain approximations.
Numerous basic results of geometric measure theory for these chains are
derived including the rectifiability of finite mass flat chains provided
that $G$ contains no nonconstant Lipschitz curves. The work here
generalizes, and uses many ideas from, the 1999 paper of B. White on at $G$
chains in ${\Bbb R}^n$ and the 2000 paper of L. Ambrosio and B. Kirchheim on
currents in a metric space. The use of flat and rectifiable chains in
geometric variational problems or in defining geometric homology theories
may reveal geometric properties of spaces.
“What, for me, constitutes life in a sound?”: Electronic Sounds as Lively and Differentiated Individuals
Authors: Rodgers Tara
Published: February 2012

The common metaphor of electronic sounds as lively and differentiated individuals emerged alongside developments in scientific modernism and industrial capitalism. Through widespread applications of graphical methods by scientists in the nineteenth century, sounds and living bodies became similarly legible through waveform representations: characterized by extensions into space, fluctuations over time, part-whole relations, and associated aesthetic variations. This knowledge was advanced by the German scientist Hermann von Helmholtz, whose work was central to the emerging fields of acoustics and electronic music in the United States by the early twentieth century. During a period of American history in which industrialization and urbanization engendered new patterns of encounter, audio-technical practitioners learned to distinguish individual sounds by aesthetic signifiers, like purity and deviation, that marked such social differences as race, class, and gender. I frame this history with a feminist theory of technological worlding, proposing that the “worlds of sound” made in audio-technical discourse are spaces of encounter and contestable realms of cultural politics.
Strange Bedfellows: Politics, Miscegenation, and Translatio in Two Lays of Lanval
Authors: McLoone Katherine
Published: February 2012

This article compares Marie de France's 'Lanval' and Thomas Chestre's Sir Launfal to explore the relationship between colonialism and translatio , arguing that both authors offer pessimistic readings of the colonial threats relevant to their eras yet counterbalance that threat with an optimistic reading of the possibilities of translatio , not from the classical past but from the literature of languages spoken at the time of writing.