bluuebunny/crossref_metadata_2025 huggingface dataset:
Caspase-1 Activation of Interleukin-1β (IL-1β) and IL-18 Is Dispensable for Induction of Experimental Cerebral Malaria
Authors: Kordes Maximilian , Matuschewski Kai , Hafalla Julius Clemence R.
Published: June 2011

Malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be “clinically and diagnostically silent.” Merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. How the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. Likewise, how the initial liver stages may shape responses to blood-stage parasites is unknown. Here, using both sporozoite- and blood-stage-induced infections with the rodent malaria parasite
Plasmodium berghei
ANKA, we show that the MyD88 and Toll-like receptor 2/4 (TLR2/4) pathways play critical roles in the development of experimental cerebral malaria (ECM). Strikingly, an absolute dependence on MyD88 and TLR2/4 was observed when infections were initiated with sporozoites. In addition, we show that caspase-1 activation of interleukin-1β (IL-1β) and IL-18, which is associated with the inflammasome pathway, does not contribute to
P. berghei
ANKA-induced immunopathology. Consistent with these data, prophylactic cover with the IL-1β antagonist anakinra did not reduce the incidence of ECM. Therefore, we propose that protection against ECM due to loss of TLR signaling functions is caused by effector mechanisms other than IL-1β activation.
Alcohol-induced memory blackouts as an indicator of injury risk among college drinkers
Authors: Mundt Marlon P , Zakletskaia Larissa I , Brown David D , Fleming Michael F
Published: June 2011

Background

An alcohol-induced memory blackout represents an amnesia to recall events but does not involve a loss of consciousness. Memory blackouts are a common occurrence among college drinkers, but it is not clear if a history of memory blackouts is predictive of future alcohol-related injury above and beyond the risk associated with heavy drinking episodes.

Objective

To determine whether baseline memory blackouts can prospectively identify college students with alcohol-related injury in the next 24 months after controlling for heavy drinking days.

Methods

Data were analysed from the College Health Intervention Project Study (CHIPS), a randomised controlled trial of screening and brief physician intervention for problem alcohol use among 796 undergraduate and 158 graduate students at four university sites in the USA and one in Canada, conducted from 2004 to 2009. Multivariate analyses used generalised estimating equations with the logit link.

Results

The overall 24-month alcohol-related injury rate was 25.6%, with no significant difference between men and women (p=0.51). Alcohol-induced memory blackouts at baseline exhibited a significant dose–response on odds of alcohol-related injury during follow-up, increasing from 1.57 (95% CI 1.13 to 2.19) for subjects reporting 1–2 memory blackouts at baseline to 2.64 (95% CI 1.65 to 4.21) for students acknowledging 6+ memory blackouts at baseline. The link between memory blackouts and injury was mediated by younger age, prior alcohol-related injury, heavy drinking, and sensation-seeking disposition.

Conclusions

Memory blackouts are a significant predictor of future alcohol-related injury among college drinkers after adjusting for heavy drinking episodes.
SOME PHYSICAL PROPERTIES OFBaTiO3–CoFe2O4COMPOSITE
Authors: HEMEDA D. M. , TAWFIK A. , EL-SHAHAWY M. M.
Published: June 2011

[X]% BaTiO3[100-x]% CoFe2O4composites (x = 0, 20, 40, 60, 80, and 100) were prepared by the general ceramic method. X-ray diffraction patterns and IR spectra confirmed the presence of two phases beside identified phase in the composites with (x% = 40-80% BaTiO3).

The temperature variation of conductivity was mainly attributed to change of the drift mobility rather than to the variation of charge carrier concentration. All the composites showed p-type behaviors in the range of temperature 300–400 K. For T > 400 K all composites showed n-type behavior. At this high temperature, the conduction is mainly due to Fe3+→ Fe2+. Hence, there is a p–n transition.

The variation of dielectric constant as a function of temperature showed a peak value at the Curie temperature (around 390 K) of ferroelectric phase in composites. It is also noted that the phase transition temperature Tcvaried for different composites.

The relation between charge carrier mobility log (μd) versus (1/T) is nearly linear supporting the polaron hopping model for the conduction. The activation energies calculated from resistivity and that from mobility are in close agreement indicating localized model of charge carrier.

The initial permeability increased with increasing temperature which is due to the activation of hopping electrons between Fe3+and Fe2+giving rise to the magnetic moment of the composites.
INDUCING POLYGONS OF LINE ARRANGEMENTS
Authors: SCHARF LUDMILA , SCHERFENBERG MARC
Published: June 2011

We show that an arrangement [Formula: see text] of n lines in general position in the plane has an inducing polygon of size O(n). Additionally, we present a simple algorithm for finding an inducing n-path for [Formula: see text] in O(n log n) time and an algorithm that constructs an inducing n-gon for a special class of line arrangements within the same time bound.
Tectonic re-interpretation of the Banggai-Sula–Molucca Sea margin, Indonesia
Authors: Watkinson Ian M. , Hall Robert , Ferdian Farid
Published: June 2011

High resolution multibeam bathymetric and seismic data from the area north of the Banggai-Sula Islands, Indonesia, provide a new insight into the geological history of the boundary between the East Sulawesi ophiolite, the Banggai-Sula microcontinent and the Molucca Sea collision zone. Major continuous faults such as the Sula Thrust and the North Sula–Sorong Fault, previously interpreted to bound and pass through the area are not seen. The south-verging Batui Thrust previously interpreted offshore to the east of Poh Head cannot be identified. In the areas where the thrust was interpreted there is a north-vergent thrust and fold zone overlain by almost undeformed sediments. Gently dipping strata of the Banggai-Sula microcontinent margin can be traced northwards beneath younger rocks. In the east, rocks of the Molucca Sea collision complex are deformed by multigenerational folds, thrusts and strike-slip faults. There is a series of small thrusts between the leading edge of the collision complex and the foot of the slope. In the west a zone of transpression close to the East Arm of Sulawesi is the termination of the dextral strike-slip Balantak Fault extending east from Poh Head.
Neogene climate history of the Makassar Straits, Indonesia
Authors: Morley Robert J. , Morley Harsanti P.
Published: June 2011

The Neogene climate history of the Makassar Straits has been assessed by combining palynological studies of two Late Quaternary cores from the ocean floor with analyses of petroleum exploration wells from the Makassar Straits, Indonesia, penetrating the Early Pleistocene to Middle Miocene.

The two Late Quaternary cores span 30 ka, located offshore the Mahakam Delta, east Kalimantan, and 95 ka, from offshore south Sulawesi. The first provides a record of the vegetation and climate history of the Mahakam catchment, and indicates rain forests through the last 30 ka, but with a cooler last glacial maximum, whereas the second provides a record of vegetation of the Java Sea region and south Sulawesi, and indicates extensive grasslands, suggesting a distinctly seasonal climate, during the last glacial maximum.

Based on a climate model constructed from the cores which link sea level change with changes of temperature and seasonality, the history of vegetation and climate for the Makassar Straits is then extrapolated back to the Middle Miocene using the record obtained from the two exploration wells. Results show that the equatorial climate has been everwet since the Middle Miocene, but at subequatorial latitudes seasonal climates became established from the Late Pliocene onward.
Oligocene palynological succession from the East Java Sea
Authors: Lelono Eko Budi , Morley Robert J.
Published: June 2011

Rich palynomorph assemblages have been obtained through a marine Oligocene succession from the East Java Sea (Indonesia) and provide the first instance of an independently dated Oligocene succession from SE Asia that has yielded a good quality palynological record. The succession has been independently dated by nannofossils and foraminifera.

The palynomorph succession suggests climatic control on Oligocene vegetation, on which basis a regionally applicable zonation is proposed. The Early Oligocene is characterized by common rain forest elements, suggesting an everwet, rain forest climate. The early part of the Late Oligocene contains much reduced rain forest elements with grass pollen, indicating a more seasonal climate, whereas for the latest Late Oligocene, rain forest elements return in abundance, suggesting a superwet rain forest climate. This palynological succession is similar to that from the Sunda Basin in the West Java Sea, allowing the Sunda Basin succession to be dated by correlation.

The study also extends the stratigraphic range of
Dacrydium
and
Casuarina
, two plant taxa previously thought to have dispersed from the Australian Plate into SE Asia at the time of the collision with Sunda, to well before the time of collision. A different means of dispersal for these taxa is proposed.
Pre-Cenozoic sedimentary section and structure as reflected in the JavaSPAN
TM
crustal-scale PSDM seismic survey, and its implications regarding the basement terranes in the East Java Sea
Authors: Granath J. W. , Christ J. M. , Emmet P. A. , Dinkelman M. G.
Published: June 2011

A new long-offset, long-record crustal-scale seismic survey of 9600 km called JavaSPAN was acquired in the Java Sea and Makassar Strait. The East Java Sea is underlain by continental basement with a prolonged multiphase history of deposition punctuated by extensional and compressional events. This East Java Terrane is a major component of SE Sundaland lying between the Meratus suture, the contemporary Java arc, and the west Sulawesi orogenic belt, but is poorly constrained on the north under the North Makassar Basin and in Kalimantan. A Precambrian to Permo-Triassic sedimentary section up to some 8.5 km in thickness overlies crystalline basement in a number of fault blocks and synformal structures below a strong angular unconformity. A thin overlap assemblage of Cretaceous to early Cenozoic sediments overlies that unconformity. Middle Eocene to Neogene clastic and carbonate rocks overlie another angular unconformity that marks the initiation of a well known history of Palaeogene extension, sag, and Neogene inversion. The East Java Terrane rifted from the Bonaparte-Arafura sector of northern Australia in the Jurassic and accreted onto a magmatic arc on the SW flank of what is now Kalimantan in the Cretaceous.
The Java convergent margin: structure, seismogenesis and subduction processes
Authors: Kopp Heidrun
Published: June 2011

The Java margin is characterized by a distinct variation in lower to upper plate material transfer and recurring catastrophic tsunamogenic earthquakes. Both processes are closely linked to the subduction of oceanic basement relief resulting in varying degrees of fore-arc deformation. Tomographic models of refraction seismic profiles and reflection seismic lines in combination with high-resolution multibeam bathymetric data reveal the variability in the deep structure and deformation of the Java fore-arc. Shallow subduction processes are governed by the sediment supply in the trench as well as by the nature and fabric of the oceanic lithosphere. The deep structure of the fore-arc reveals a shallow upper plate crust–mantle transition, present along the entire Java margin section. The serpentinized fore-arc mantle wedge governs the depth extent of the seismogenic zone here, which is narrower compared to its Sumatran analogue. In addition, offshore central Java, high relief oceanic basement features potentially act as asperities as well as barriers to seismic rupture, limiting the possible magnitude of subduction thrust earthquakes. However, the potential for geohazards, in particular tsunamis, is high along the entire margin. This results from tsunamogenic earthquakes, ubiquitous splay faults and potentially tsunamogenic landslides, which further increase the risk of future tsunamis.
Subducting slab structure below the eastern Sunda arc inferred from non-linear seismic tomographic imaging
Authors: Widiyantoro S. , Pesicek J. D. , Thurber C. H.
Published: June 2011

Detailed P-wave speed velocity structure beneath the Sunda arc has been successfully imaged by applying a non-linear approach to seismic tomography. Nearly one million compressional phases from events within the Indonesian region have been used. These include the surface-reflected depth phases pP and pwP in order to improve the sampling of the upper-mantle structure, particularly below the back-arc regions. We have combined a high-resolution regional inversion with a low-resolution global inversion to minimize the mapping of distant aspherical mantle structure into the study region. In this paper, we focus our discussion on the upper mantle structure beneath the eastern part of the Sunda arc. The tomographic images confirm previous observations of a hole in the subducted slab in the upper mantle beneath eastern Java. The images also suggest that a tear in the slab exists below the easternmost part of the Sunda arc, where the down-going slab is deflected in the mantle transition zone. In good agreement with previous studies, the properties of the deflected slab show a strong bulk-sound signature.
Reviewing peer review
Authors: Wing Jeannette M. , Chi Ed H.
Published: June 2011

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Jeannette M. Wing discusses peer review and its importance in terms of public trust. Ed H. Chi writes about alternatives, such as open peer commentary.
Values in design
Authors: Knobel Cory , Bowker Geoffrey C.
Published: June 2011

Focusing on socio-technical design with values as a critical component in the design process.
Non-myths about programming
Authors: Ben-Ari Mordechai (Moti)
Published: June 2011

Viewing computer science in a broader context to dispel common misperceptions about studying computer science.
Gabriel Graphs in Arbitrary Metric Space and their Cellular Automaton for Many Grids
Authors: Maignan Luidnel , Gruau Frédéric
Published: June 2011

Gabriel graphs are subgraphs of Delaunay graphs that are used in many domains such as sensor networks and computer graphics. Although very useful in their original form, their definition is bounded to applications involving Euclidean spaces only, but their principles seem to be applicable to a wider range of applications. In this article, we generalize this construct and define metric Gabriel graphs that transport the principles of Gabriel graphs on arbitrary metric space, allowing their use in domains like cellular automata and amorphous computing, or any other domains where a non-Euclidean metric is used. We study global/local properties of metric Gabriel graphs and use them to design a cellular automaton that draws the metric Gabriel graph of its input. This cellular automaton only uses seven states to achieve this goal and has been tested on hexagonal grids, 4-connected, and 8-connected square grids.
Macro Programming a Spatial Computer with Bayesian Networks
Authors: Mamei Marco
Published: June 2011

Macro programming a spatial computer is the ability to specify application tasks at a global level while relying on compiler-like software to translate the global tasks into the individual component activities. Bayesian networks can be regarded as a powerful tool for macro programming a spatial computer, such as a dense sensor network, in a variety of data analysis applications. In this article we present our architecture to program a spatial computer by means of a distributed Bayesian network and present some applications we developed over a sensor network testing both inference and anomaly-detection analysis.
Fast file existence checking in archiving systems
Authors: Tomazic Saso , Pavlovic Vesna , Milovanovic Jasna , Sodnik Jaka , Kos Anton , Stancin Sara , Milutinovic Veljko
Published: June 2011

This article presents a new Fast Hash-based File Existence Checking (FHFEC) method for archiving systems. During the archiving process, there are many submissions which are actually unchanged files that do not need to be re-archived. In this system, instead of comparing the entire files, only digests of the files are compared. Strong cryptographic hash functions with a low probability of collision can be used as digests. We propose a fast algorithm to check if a certain hash, that is, a corresponding file, is already stored in the system. The algorithm is based on dividing the whole domain of hashes into equally sized regions, and on the existence of a pointer array, which has exactly one pointer for each region. Each pointer points to the location of the first stored hash from the corresponding region and has a null value if no hash from that region exists. The entire structure can be stored in random access memory or, alternatively, on a dedicated hard disk. A statistical performance analysis has been performed that shows that in certain cases FHFEC performs nearly optimally. Extensive simulations have confirmed these analytical results. The performance of FHFEC has been compared to the performance of a binary search (BIS) and B+tree, which are commonly used in file systems and databases for table indices. The results show that FHFEC significantly outperforms both of them.
Hereditary Pancreatic and Hepatobiliary Cancers
Authors: Haddad Ashraf , Kowdley Gopal C. , Pawlik Timothy M. , Cunningham Steven C.
Published: June 2011

Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Screening for pancreatic cancer in high-risk individuals is typically performed by endoscopic ultrasound and should begin at least 10 years prior to the age of the youngest affected relative. Disease states known to be associated with increased risk of hepatocellular cancer include hereditary hemochromatosis, autoimmune hepatitis, porphyria, andα1-antitrypsin deficiency, with relative risks as high as 36-fold. Although much less is known about hereditary bile-duct cancers, Muir-Torre syndrome and bile salt export pump deficiency are diseases whose association with hereditary carcinogenesis is under investigation.
Wernicke's Encephalopathy in a Patient with Peptic Ulcer Disease
Authors: Uruha Akinori , Shimizu Toshio , Katoh Tomoji , Yamasaki Yasushi , Matsubara Shiro
Published: June 2011

We report a 74-year-old man with Wernicke's encephalopathy (WE) whose only prior illness was peptic ulcer disease. Upper gastrointestinal endoscopy demonstrated gastric ulcer scars accompanied by marked deformity, without pathologic evidence of malignancy. WE due to peptic ulcer disease in previous reports was substantially associated with thiamine deficiency due to recurrent vomiting or surgical procedures. In our case, however, there was no history of vomiting or gastrointestinal surgery. Besides, we thoroughly ruled out other known clinical settings related to WE. There is the possibility that peptic ulcer disease itself provoked thiamine deficiency due to malabsorption.
Isolation of Cellulose Nanofibers: Effect of Biotreatment on Hydrogen Bonding Network in Wood Fibers
Authors: Janardhnan Sreekumar , Sain Mohini
Published: June 2011

The use of cellulose nanofibres as high-strength reinforcement in nano-biocomposites is very enthusiastically being explored due to their biodegradability, renewability, and high specific strength properties. Cellulose, through a regular network of inter- and intramolecular hydrogen bonds, is organized into perfect stereoregular configuration called microfibrils which further aggregate to different levels to form the fibre. Intermolecular hydrogen bonding at various levels, especially at the elementary level, is the major binding force that one need to overcome to reverse engineer these fibres into their microfibrillar level. This paper briefly describes a novel enzymatic fibre pretreatment developed to facilitate the isolation of cellulose microfibrils and explores effectiveness of biotreatment on the intermolecular and intramolecular hydrogen bonding in the fiber. Bleached Kraft Softwood Pulp was treated with a fungus (OS1) isolated from elm tree infected with Dutch elm disease. Cellulose microfibrils were isolated from these treated fibers by high-shear refining. The % yield of nanofibres and their diameter distribution (<50 nm) isolated from the bio-treated fibers indicated a substantial increase compared to those isolated from untreated fibers. FT-IR spectral analysis indicated a reduction in the density of intermolecular and intramolecular hydrogen bonding within the fiber. X-ray spectrometry indicated a reduction in the crystallinity. Hydrogen bond-specific enzyme and its application in the isolation of new generation cellulose nano-fibers can be a huge leap forward in the field of nano-biocomposites.
Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study
Authors: Uranova Natalya A. , Vikhreva Olga V. , Rachmanova Valentina I. , Orlovskaya Diana D.
Published: June 2011

Schizophrenia is believed to result from altered neuronal connectivity and impaired myelination. However, there are few direct evidence for myelin abnormalities in schizophrenia. We performed electron microscopic study of myelinated fibers and oligodendrocytes and morphometric study of myelinated fibers in the prefrontal cortex in gray and white matters in schizophrenia and normal controls. Six types of abnormal fibers and ultrastructural alterations of oligodendrocytes were found in schizophrenia. No significant group differences in area density of myelinated fibers were found. Frequency of pathological fibers was increased significantly in gray matter in young and elderly schizophrenia patients and in patients with predominantly positive symptoms. In contrast, in white matter, frequency of altered fibers was increased significantly in elderly patients, in patients with predominantly negative symptoms, and correlated with illness duration. Progressive alterations of myelinated fibers in white matter might be followed by alterations of myelinated fibers in gray matter in schizophrenia.
Preparation of γ-Fe2O3/Ni2O3/FeCl3(FeCl2) Composite Nanoparticles by Hydrothermal Process Useful for Ferrofluids
Authors: Zhang Qingmei , Li Jian , Miao Hua , Fu Jun
Published: June 2011

Using a hydrothermal process in FeCl2 solution, γ-Fe2O3/Ni2O3/FeCl3(FeCl2) composite nanoparticles were obtained from the FeOOH/Ni(OH)2 precursor prepared by coprecipitation. The precursor and the as-prepared nanoparticles were investigated by vibrating sample magnetometer (VSM), X-ray diffraction (XRD), energy disperse X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). The experimental results showed that the paramagnetic amorphous precursor, in which Ni(OH)2 is formed outside FeOOH, is transformed to ferrimagnetic γ-Fe2O3/Ni2O3 composite when it is processed in FeCl2 solution (0.25, 0.50, 1.00 M) in an autoclave at 100°C for 1 hr. In addition, the dismutation reaction of FeCl2 produces FeCl3 and Fe. Some FeCl3 and little FeCl2 can be absorbed to form γ-Fe2O3/Ni2O3/FeCl3(FeCl2) composite nanoparticles in which Ni2O3 forms outside the γ-Fe2O3 core and the outermost layer is FeCl3 (FeCl2). The content of FeCl3 (FeCl2) in the particles increased, and the magnetization of the particles decreased with the concentration of FeCl2 solution increasing in the hydrothermal process. The FeCl3 (FeCl2) surface is chemically passive and nonmagnetic (paramagnetic). Accordingly, the composite nanoparticles are chemically stable, and their aggregation is prevented. The specific saturation magnetization of such composite nanoparticles can get to 57.4–62.2 emu/g and could be very suitable for synthesizing ferrofluids.
The Effect of Antivascular Endothelial Growth Factor on the Development of Adhesion Formation in Laparotomized Rats: Experimental Study
Authors: Basbug Murat , Bulbuller Nurullah , Camci Cemalettin , Ayten Refik , Aygen Erhan , Ozercan Ibrahim Hanifi , Arikanoglu Zulfu , Akbulut Sami
Published: June 2011

Aims.This study determined the effects of a single dose of bevacizumab, an antiangiogenic recombinant monoclonal antibody that specifically targets vascular endothelial growth factor (VEGF), on adhesion formation in the rat cecal abrasion model.Methodology.Thirty female Wistar albino rats (200–224 g) were divided into three groups. All rats underwent laparotomy at which time cecal wall abrasion and abdominal wall injuries were induced. Group I (control) underwent only the abrasion procedure; Groups II and III received saline or bevacizumab intraperitoneally, respectively, following the abrasion. The rats were killed on postoperative day 7, and the severity of adhesions was evaluated, together with histopathological fibrosis parameters and immunohistochemical staining to identify the VEGF receptor.Results.The mean adhesion severity score in Groups I–III was2.5±0.52,2.4±0.69, and0.7±0.82, respectively; the score in Group III was significantly lower than that in Groups I (P<0.001) and II (P<0.001). In the histopathological evaluation, the mean fibrosis score in Group III was significantly lower that the scores in Groups I (P<0.001) and II (P<0.001). VEGF staining of the adhesion areas in Group III was significantly lower than that in Groups I (P<0.001) and II (P<0.001).Conclusion. Bevacizumab decreases adhesion formation following laparotomy in rats by blocking VEGF receptor occupancy.
Minimally Invasive Approaches for the Management of “Difficult” Colonic Polyps
Authors: Cruz R. Alejandro , Ragupathi Madhu , Pedraza Rodrigo , Pickron T. Bartley , Le Anne T. , Haas Eric M.
Published: June 2011

Traditionally, patients with colonic polyps not amenable to endoscopic removal require open colectomy for management. We evaluated our experience with minimally invasive approaches including endoscopic mucosal resection (EMR), laparoscopic-assisted endoscopic polypectomy (LAEP), and laparoscopic-assisted colectomy (LAC). Patients referred for surgery for colonic polyps were selected for one of three minimally invasive modalities. A total of 123 patients were referred for resection of “difficult” polyps. Thirty underwent EMR, 25 underwent LAEP, and 68 underwent LAC. Of those selected to undergo EMR or LAEP, 76.4% were successfully managed without colon resection. The remaining 23.6% underwent LAC. Nine complications were encountered, including two requiring reoperative intervention. Of the 123 patients, three were found to have malignant disease on final pathology. Surgical resection can be avoided in a significant number of patients with “difficult” polyps referred for surgery by performing EMR and LAEP. In those who require surgery, minimally invasive resection can be achieved.
Activation of Nrf2-Regulated Glutathione Pathway Genes by Ischemic Preconditioning
Authors: Bell Karen F. S. , Fowler Jill H. , Al-Mubarak Bashayer , Horsburgh Karen , Hardingham Giles E.
Published: June 2011

Prophylactic pharmacological activation of astrocytic gene expression driven by the transcription factor Nrf2 boosts antioxidant defences and protects against neuronal loss in ischemia and other disease models. However, the role of Nrf2 in mediating endogenous neuroprotective responses is less clear. We recently showed that Nrf2 is activated by mild oxidative stress in both rodent and human astrocytes. Moreover, brief exposure to ischemic conditions was found to activate Nrf2 bothin vivoandin vitro, and this was found to contribute to neuroprotective ischemic preconditioning. Here we show that transient ischemic conditionsin vitroandin vivocause an increase in the expression of Nrf2 target genes associated with the glutathione pathway, including those involved in glutathione biosynthesis and cystine uptake. Taken together, these studies indicate that astrocytic Nrf2 may represent an important mediator of endogenous neuroprotective preconditioning pathways.
Postprocessing of Infrared Reflectography to Support the Study of a Painting: The Case of Vivarini's Polyptych
Authors: Fragasso Laura , Masini Nicola
Published: June 2011

Infrared (IR) reflectography is an imaging diagnostic technique widely used to study and evaluate the assessment of paintings' conservation state. The study case analyzed in this paper is related to a polyptych panel attributed to Vivarini's workshop conserved in the “Sigismondo Castromediano” Museum in Lecce. The painting's IR reflectography has been acquired through a CCD camera with spectral sensitivity ranging 400–1150 nm and manual positioning system. In order to offset the technological limits of the CCD camera, reflectograms have been processed through Principal Component Analysis and spectral indices. Postprocessing provided information related to the different pictorial drafting and restoration works, as well as emphasized graphic details and shadings, useful to improve the knowledge of the painting techniques.
Melamine Nitrate: A Novel and Efficient Reagent for Regioselective Nitration of Phenols
Authors: Chen Yong-qiang , Jiang Hong
Published: June 2011

Melamine nitrate (MN) as a novel nitration reagent was easily prepared. Regioselective nitration of phenols to their corresponding o-nitrophenols occurred using MN with p-toluenesulfonic acid as catalyst in good to excellent yields. A distinct advantage of this method is the easy separation of products by simple filtration.
Determination of Trace Silver in Water Samples by Online Column Preconcentration Flame Atomic Absorption Spectrometry Using Termite Digestion Product
Authors: Bianchin Joyce Nunes , Martendal Edmar , Carasek Eduardo
Published: June 2011

A new method for Ag determination in water samples using solid phase extraction (SPE) coupled to a flow injection system and flame atomic absorption spectrometry was developed. The sorbent used for Ag preconcentration and extraction was the termite digestion product. Flow and chemical variables of the system were optimized through a multivariate procedure. The factors selected were adsorbent mass, buffer type and concentration, sample pH, and sample flow rate. The detection limit and precision were 3.4 μg L−1and 3.8% (n=6, 15 μg L−1), respectively. The enrichment factor and the linear working range were, respectively, 21 and 10–50 μg L−1. Results for recovery tests using different water samples were between 96 and 107%. The proposed methodology was applied with success for the determination of Ag in water used to wash clothes impregnated with silver nanoparticles, supplied by a factory located in Santa Catarina, Brazil.
Cross-Talk between Apolipoprotein E and Cytokines
Authors: Zhang Hongliang , Wu Li-Min , Wu Jiang
Published: June 2011

Apolipoprotein E (apoE) is a multifunctional glycosylated protein characterized by its wide tissue distribution. Despite its importance in lipid transport and atherosclerosis pathogenesis, apoE is associated with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson disease, and autoimmune disorders such as multiple sclerosis and psoriasis. Among others, the role of apoE in modulating inflammation and oxidation is crucial in elucidating the risk factors of the above diseases since the function of apoE is closely linked with both proinflammatory and antiinflammatory cytokines. Moreover, apoE modulates inflammatory and immune responses in an isoform-dependent manner. Correspondingly, inflammatory cytokines can either upregulate or downregulate the production of apoE in various tissue types. However, studies on the interactions between apoE and cytokines occasionally yield conflicting results, highlighting the complex roles of apoE and cytokines in various disorders. The present paper summarizes the current knowledge about the cross-talk between apoE and cytokines, with emphasis on the effects of apoE on the Th1/Th2 balance.
Profound Coordinated Alterations of Intratumoral NK Cell Phenotype and Function in Lung Carcinoma
Authors: Platonova Sophia , Cherfils-Vicini Julien , Damotte Diane , Crozet Lucile , Vieillard Vincent , Validire Pierre , André Pascale , Dieu-Nosjean Marie-Caroline , Alifano Marco , Régnard Jean-François , Fridman Wolf-Herman , Sautès-Fridman Catherine , Cremer Isabelle
Published: June 2011

Both the innate and adaptive immune systems contribute to tumor immunosurveillance in mice and humans; however, there is a paucity of direct evidence of a role for natural killer (NK) cells in this important process. In this study, we investigated the intratumoral phenotypic profile and functions of NK cells in primary human tumor specimens of non–small cell lung carcinoma (NSCLC). We used in situ methods to quantify and localize NK cells using the NKp46 marker and we characterized their phenotype in blood, tumoral, and nontumoral samples of NSCLC patients. Intratumoral NK cells displayed a profound and coordinated alteration of their phenotype, with a drastic reduction of NK cell receptor expression specifically detected in the tumoral region. According to their altered phenotype, intratumoral NK cells exhibited profound defects in the ability to activate degranulation and IFN-γ production. We found that the presence of NK cells did not impact the clinical outcome of patients with NSCLC. Finally, we showed that tumor cells heterogeneously express ligands for both activating and inhibitory NK receptors. Taken together, our results suggest that the NSCLC tumor microenvironment locally impairs NK cells, rendering them less tumorcidal and thereby supportive to cancer progression. Cancer Res; 71(16); 5412–22. ©2011 AACR.
Olmesartan Induces Renoprotective Effects by Stimulating Angiotensin Type 2 Receptors and Reducing Oxidative Stress in Diabetic Nephropathy
Authors: Jo Fusakazu , Morimoto Satoshi , Nakahigashi Mitsutaka , Kusabe Makiko , Someya Kazunori , Morita Tatsuyori , Jo Hiromi , Imada Takanobu , Kosaki Atsushi , Toyoda Nagaoki , Nishikawa Mitsushige , Iwasaka Toshiji
Published: June 2011

Background: Angiotensin receptor blockers reduce the progression of diabetic nephropathy primarily by inhibiting angiotensin type 1 (AT1) receptors. In the present study, we investigated the role of angiotensin type 2 (AT2) receptors on the renoprotective effects of olmesartan in diabetic nephropathy. Methods: Six-week-old mice were treated with streptozotocin and divided into four groups: the OLM group (mice treated with olmesartan), the OLM+Ang II group (mice treated with olmesartan and angiotensin II), the OLM+PD group (mice treated with olmesartan and the AT2 antagonist PD 123319), and the vehicle group. Nondiabetic mice were used as controls. We measured blood glucose levels and urinary excretions of albumin and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which is a marker for oxidative stress. Results: Although urinary albumin excretion in the OLM and OLM+Ang II groups showed a tendency to be reduced compared to the vehicle group, it was significantly lower compared to the OLM+PD group. Urinary excretion of 8-OHdG was also significantly lower in the OLM and OLM+Ang II groups compared to the OLM+PD group. Conclusions: In diabetic nephropathy, the renoprotective effects of olmesartan are due not only to the blockade of AT1 receptors, but also to a reduction in oxidative stress via stimulation of AT2 receptors.
Possible Sites of Therapeutic Action in Restless Legs Syndrome: Focus on Dopamine and α2δ Ligands
Authors: Thorpe Andrew J. , Clair Andrew , Hochman Shawn , Clemens Stefan
Published: June 2011

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by abnormal sensations that occur primarily at rest or during sleep, which are alleviated by movement of the affected limb. The pathophysiology of RLS remains unclear, although roles for dopamine dysfunction and brain iron deficiency have been proposed. The hypothalamic A11 dopaminergic circuit is used to explain the dopamine dysfunction in RLS and the potential therapeutic actions of dopamine D2 agonists. Modulation of central and peripher- al neuronal circuits may also explain the potential therapeutic sites of action of opioids, adenosine receptor ligands, and voltage-gated calcium channel α2δ ligands in RLS. The known and possible therapeutic benefits of these agents and their relationship to dopaminergic dysfunction in RLS are discussed in this review.
Intravenous Recombinant Tissue Plasminogen Activator Therapy for Stroke Patients Receiving Maintenance Hemodialysis: The Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement (SAMURAI) rt-PA Registry
Authors: Naganuma Masaki , Mori Mayumi , Nezu Tomohisa , Makihara Noriko , Koga Masatoshi , Okada Yasushi , Minematsu Kazuo , Toyoda Kazunori ,   on behalf of the Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement (SAMURAI) Study Investigators
Published: June 2011

Background: To examine the therapeutic effect of intravenous recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients receiving maintenance hemodialysis (HD). Methods: Of 600 stroke patients receiving intravenous rt-PA using 0.6 mg/kg alteplase who were enrolled in a multicenter observational study in Japan, 4 patients (3 men, 64–77 years old) on maintenance HD were studied. Results: The primary kidney disease requiring HD was glomerulonephritis in 2 patients, diabetic nephropathy in 1, and undetermined in 1. The duration of HD ranged between 1.2 and 28 years. Three patients developed stroke on the day of HD, including 1 during HD and another just after HD. All patients had stroke in the carotid arterial territory. Pretreatment NIH Stroke Scale scores ranged between 4 and 20, and decreased by 2–5 points at 7 days. One patient needed intravenous antihypertensive therapy before rt-PA; he developed an ectopic cortical hematoma and intraventricular hemorrhage after rt-PA. The other 3 did not develop hemorrhagic complications. The modified Rankin Scale score at 3 months was 0 in 1 patient, 2 in 2 patients, and 4 in 1 patient. Conclusions: rt-PA therapy for stroke patients receiving maintenance HD might improve the stroke outcome. Ectopic hematoma was a unique complication in our case series.
Saphenous Vein Grafts With Multiple Versus Single Distal Targets in Patients Undergoing Coronary Artery Bypass Surgery
Authors: Mehta Rajendra H. , Ferguson T. Bruce , Lopes Renato D. , Hafley Gail E. , Mack Michael J. , Kouchoukos Nicholas T. , Gibson C. Michael , Harrington Robert A. , Califf Robert M. , Peterson Eric D. , Alexander John H.
Published: June 2011

Background—

Limited information exists on the intermediate-term graft patency and 5-year clinical outcomes of patients receiving saphenous vein grafts with multiple (m-SVG) versus single distal targets (s-SVG) during coronary artery bypass graft (CABG) surgery in the current era.

Methods and Results—

We studied the association of the use of m-SVG versus s-SVG conduits with 1-year SVG failure (defined as ≥75% angiographic stenosis) and 5-year clinical events (death; death or myocardial infarction [MI]; and death, MI, or revascularization) in 3014 patients undergoing their first CABG surgery enrolled in the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV. Of 3014 patients enrolled in PREVENT IV, 1045 (34.7%) had ≥1 m-SVGs during CABG. Vein graft failure at 1-year was higher for m-SVG compared with s-SVG (adjusted odds ratio 1.24, 95% confidence interval 1.03 to 1.48). At 5 years, the adjusted composite of death, MI (including perioperative MI), or revascularization (hazard ratio 1.15, 95% confidence interval 1.00 to 1.31) and death or MI (hazard ratio 1.21, 95% confidence interval 1.03 to 1.43) were significantly higher in patients receiving m-SVGs.

Conclusions—

In patients undergoing first CABG surgery, the use of m-SVG was associated with a higher 1-year vein graft failure rate and trends toward worse clinical outcomes. Additional studies are needed to better understand the most appropriate conduit to improve long-term graft patency and clinical outcomes of patients undergoing CABG surgery. In the meantime, these data should encourage the use of s-SVG over m-SVG when feasible.
Ticagrelor Compared With Clopidogrel by Geographic Region in the Platelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Mahaffey Kenneth W. , Wojdyla Daniel M. , Carroll Kevin , Becker Richard C. , Storey Robert F. , Angiolillo Dominick J. , Held Claes , Cannon Christopher P. , James Stefan , Pieper Karen S. , Horrow Jay , Harrington Robert A. , Wallentin Lars
Published: June 2011

Background—

In the Platelet Inhibition and Patient Outcomes (PLATO) trial, a prespecified subgroup analysis showed a significant interaction between treatment and region (
P
=0.045), with less effect of ticagrelor in North America than in the rest of the world.

Methods and Results—

Reasons for the interaction were explored independently by 2 statistical groups. Systematic errors in trial conduct were investigated. Statistical approaches evaluated the likelihood of play of chance. Cox regression analyses were performed to quantify how much of the regional interaction could be explained by patient characteristics and concomitant treatments, including aspirin maintenance therapy. Landmark Cox regressions at 8 time points evaluated the association of selected factors, including aspirin dose, with outcomes by treatment. Systematic errors in trial conduct were ruled out. Given the large number of subgroup analyses performed and that a result numerically favoring clopidogrel in at least 1 of the 4 prespecified regions could occur with 32% probability, chance alone cannot be ruled out. More patients in the United States (53.6%) than in the rest of the world (1.7%) took a median aspirin dose ≥300 mg/d. Of 37 baseline and postrandomization factors explored, only aspirin dose explained a substantial fraction of the regional interaction. In adjusted analyses, both Cox regression with median maintenance dose and landmark techniques showed that, in patients taking low-dose maintenance aspirin, ticagrelor was associated with better outcomes compared with clopidogrel, with statistical superiority in the rest of the world and similar outcomes in the US cohort.

Conclusions—

The regional interaction could arise from chance alone. Results of 2 independently performed analyses identified an underlying statistical interaction with aspirin maintenance dose as a possible explanation for the regional difference. The lowest risk of cardiovascular death, myocardial infarction, or stroke with ticagrelor compared with clopidogrel is associated with a low maintenance dose of concomitant aspirin.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872.
Aerobic Exercise Training–Induced Left Ventricular Hypertrophy Involves Regulatory MicroRNAs, Decreased Angiotensin-Converting Enzyme-Angiotensin II, and Synergistic Regulation of Angiotensin-Converting Enzyme 2-Angiotensin (1-7)
Authors: Fernandes Tiago , Hashimoto Nara Y. , Magalhães Flávio C. , Fernandes Fernanda B. , Casarini Dulce E. , Carmona Adriana K. , Krieger José E. , Phillips M. Ian , Oliveira Edilamar M.
Published: June 2011

Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart.
Dopamine Receptor Type 5 in the Primary Cilia Has Dual Chemo- and Mechano-Sensory Roles
Authors: Abdul-Majeed Shakila , Nauli Surya M.
Published: June 2011

Polycystic kidney disease is characterized by cardiovascular irregularities, including hypertension. Dopamine, a circulating hormone, is implicated in essential hypertension in humans and animal models. Vascular endothelial primary cilia are known to function as mechano-sensory organelles. Although both primary cilia and dopamine receptors play important roles in vascular hypertension, their relationship has never been explored. To determine the roles of the dopaminergic system and mechano-sensory cilia, we studied the effects of dopamine on ciliary length and function in wild-type and mechano-insensitive polycystic mutant cells (

Pkd1
−/

−

and

Tg737
orpk/orpk

). We show for the first time that mouse vascular endothelia exhibit dopamine receptor-type 5 (DR5), which colocalizes to primary cilia in cultured cells and mouse arteries in vivo. DR5 activation increases cilia length in arteries and endothelial cells through cofilin and actin polymerization. DR5 activation also restores cilia function in the mutant cells. In addition, silencing DR5 completely abolishes mechano-ciliary function in WT cells. We found that DR5 plays very important roles in ciliary length and function. Furthermore, the chemo-sensory function of cilia can alter the mechano-sensory function through changes in sensitivity to fluid-shear stress. We propose that ciliary DR5 has functional chemo- and mechano-sensory roles in endothelial cells.