bluuebunny/crossref_metadata_2025 huggingface dataset:
α
2A
-Adrenergic Receptor Polymorphism Potentiates Platelet Reactivity in Patients With Stable Coronary Artery Disease Carrying the Cytochrome P450 2C19*2 Genetic Variant
Authors: Peace Aaron J. , Mangiacapra Fabio , Bailleul Els , Delrue Leen , Dierickx Karen , Conte Micaela , Puymirat Etienne , Fraeymans Anne Lies , Meeus Pieter , Bartunek Jozef , Volpe Massimo , Barbato Emanuele
Published: April 2014

Objective—

Platelet α
2A
-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α
2A
-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α
2A
-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy).

Approach and Results—

Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (
P
<0.05) apart from 10 μmol/L (
P
=0.077). Percentage inhibition was lower (
P
=0.048) in 6.3-kb α
2A
-AR carriers. Percentage inhibition was lower (
P
=0.005) and P2Y12 reactivity units was higher (
P
=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (
P
=0.037) and lower percentage inhibition (
P
=0.009) were observed in carriers of both 6.3-kb α
2A
-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own.

Conclusions—

The 6.3-kb α
2A
-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.
Relative Localization of Auditory and Visual Events Presented in Peripheral Visual Field
Authors: Miyauchi Ryota , Kang Dea-Gee , Iwaya Yukio , Suzuki Yôiti
Published: April 2014

The brain apparently remaps the perceived locations of simultaneous auditory and visual events into a unified audio-visual space to integrate and/or compare multisensory inputs. However, there is little qualitative or quantitative data on how simultaneous auditory and visual events are located in the peripheral visual field (i.e., outside a few degrees of the fovea). We presented a sound burst and a flashing light simultaneously not only in the central visual field but also in the peripheral visual field and measured the relative perceived locations of the sound and flash. The results revealed that the sound and flash were perceptually located at the same location when the sound was presented at a 5° periphery of the flash, even when the participants’ eyes were fixed. Measurements of the unisensory locations of each sound and flash in a pointing task demonstrated that the perceived location of the sound shifted toward the front, while the perceived location of the flash shifted toward the periphery. As a result, the discrepancy between the perceptual location of the sound and the flash was around 4°. This suggests that the brain maps the unisensory locations of auditory and visual events into a unified audio-visual space, enabling it to generate unisensory spatial information about the events.
Incidence of PR3- and MPO-ANCA autoantibody specificity changes in ANCA-associated vasculitis
Authors: Holding Stephen , Fisher Victoria J , Abuzakouk Mohamed
Published: April 2014

Background

Monitoring of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in remission usually includes indirect immunofluorescence (IIF), proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA. Typically, PR3 and MPO-ANCA are both performed because patients sometimes switch specificity during follow up. Published data are limited to case reports and incidence of change is not reported. The aim of this study was to quantify the incidence of antibody switching.

Methods

Hull and East Yorkshire Hospitals National Health Service Trust serves a population of 720,000 for ANCA testing. We reviewed all ANCA results from January 2000 to August 2012 to quantify incidence of antibody switching. A total of 22,002 IIF screens (14,518 patients) were performed. A total of 9838 (45%) also had PR3- and MPO-ANCA (6439, 44% of patients). Patients that changed specificity from PR3- to MPO-ANCA and vice versa were identified and case notes reviewed.

Results

A total of 218 patients with confirmed AAV positive for PR3/MPO-ANCA were followed for a mean of 2.6 years (range <0.1 to 12.4 years; with 113 (52%) patients followed for >1 year). Five patients (2%) changed specificity during follow up (3 GPA, 1 MPA & 1 EGPA). In two patients this was associated with relapse. Incidence of specificity change was 1 per 82 years (including two reversions to presenting specificity) and one per 286 years for changes associated with relapse. Monitoring using only the initial antibody specificity would have resulted in missed relapse in one patient.

Conclusion

Antibody specificity changes in AAV are rare. Monitoring only the initial antibody specificity would have missed clinical events but rising C-reactive protein presaged relapse in these cases.
Intradermal Insulin Delivery
Authors: Hultström Michael , Roxhed Niclas , Nordquist Lina
Published: April 2014

The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines.
Medical Eponym Angst
Authors: Lawrence Abel Ernest
Published: April 2014

AbstractAn eponym is a person, real or fictitious, after whom something has been named. Eponyms have been an integral part of medical nomenclature and history for centuries, but their continued use, including their spelling, is contentious. This article reviews the history of the term, disagreements concerning its lexical legitimacy, and arguments pro and con about their place in modern medical nomenclature. Despite all the legitimate reasons for dropping them, eponyms are so deeply rooted in medicine that they are here to stay for the foreseeable future.
Naming Clues to the Layers of Transgression in El crimen del Padre Amaro
Authors: Marshall April D.
Published: April 2014

AbstractMexican director, Carlos Carrera, employs names in El crimen del Padre Amaro (2002) to illuminate the complex internal struggles of key characters as well as the power struggles between them. Names in the film also expose contemporary moral and religious dilemmas in Mexican society. The film is based on a nineteenth-century Portuguese novel of the same name. This investigation discusses the way in which nomenclature in the modern cinematic work reveals clues about individual transgressions as well as larger societal and institutional corruption that determine the fate of the characters and the parish where the story takes place.
“Kankakee”: An Old Etymological Puzzle
Authors: McCafferty Michael
Published: April 2014

AbstractA clean linguistic analysis of a place name as important in history and geography as “Kankakee” is presented here. The original place name, from the Miami-Illinois language, while faithfully recorded in the early 1680s by the explorer René de La Salle, was distorted by the French in the years that followed. This article explains the original form of this place name and its development into the form “Kankakee.” It even shows how aspects of the original Indian and French pronunciation of the name are still with us in the English pronunciation of this name.
One siRNA pool targeting the λ constant region stops λ light-chain production and causes terminal endoplasmic reticulum stress
Authors: Zhou Ping , Ma Xun , Iyer Lakshmanan , Chaulagain Chakra , Comenzo Raymond L.
Published: April 2014

Key Points

Immunoglobulin light-chain and antibody production by plasma cells is significantly reduced by siRNA for the light-chain constant region. In plasma cells making intact antibodies, knockdown of light chains can cause terminal ER stress because of unpaired heavy chains.
A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR-ABL+ leukemias
Authors: Dubrovsky Leonid , Pankov Dmitry , Brea Elliott Joseph , Dao Tao , Scott Andrew , Yan Su , O’Reilly Richard J , Liu Cheng , Scheinberg David A.
Published: April 2014

Key Points

This study shows the effective anticancer activity of a T-cell receptor mimic antibody targeting WT1 in resistant human Ph+ ALL. In combination with tyrosine kinase inhibitors, ESKM can result in cure of Ph+ ALL in murine models.
No correlation between minimal electrical charge at the tip of the stimulating catheter and the efficacy of the peripheral nerve block catheter for brachial plexus block: a prospective blinded cohort study
Authors: Schoenmakers Karin PW , Heesterbeek Petra JC , Jack Nigel TM , Stienstra Rudolf
Published: April 2014

Background

Stimulating catheters offer the possibility of delivering an electrical charge via the tip of the catheter. This may be advantageous as it allows verifying if the catheter tip is in close proximity to the target nerve, thereby increasing catheter performance. This prospective blinded cohort study was designed to investigate whether there is a correlation between the minimal electrical charge at the tip of the stimulating catheter, and the efficacy of the peripheral nerve block (PNB) catheter as determined by 24 h postoperative morphine consumption.

Methods

Forty adult patients with ASA physical health classification I-III scheduled for upper extremity surgery under combined continuous interscalene block and general anesthesia were studied. Six patients were excluded from analysis.

After inserting a stimulating catheter as if it were a non-stimulating catheter for 2–5 cm through the needle, the minimal electrical charge necessary to obtain an appropriate motor response was determined. A loading dose of 20 mL ropivacaine 0.75% ropivacaine was then administered, and postoperative analgesia was provided by a continuous infusion of ropivacaine 0.2% 8 mL.h-1 via the brachial plexus catheter, and an intravenous morphine patient-controlled analgesia (PCA) device.

Main outcome measures include the minimal electrical charge (MEC) at the tip of the stimulating catheter necessary to elicit an appropriate motor response, and the efficacy of the PNB catheter as determined by 24 h postoperative PCA morphine consumption.

Results

Mean (SD) [range] MEC at the tip of the stimulating catheter was 589 (1414) [30 – 5000] nC. Mean (SD) [range] 24 h morphine consumption was 8.9 (9.9) [0–29] mg. The correlation between the MEC and 24 h postoperative morphine consumption was Spearman’s Rho rs = -0.26, 95% CI -0.56 to 0.09.

Conclusion

We conclude that there is no proportional relation between MEC at the tip of the blindly inserted stimulating catheter and 24 h postoperative morphine consumption.

Trial registration

Trialregister.nl identifier: NTR2328
Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies
Authors: Wan You-Dong , Sun Tong-Wen , Kan Quan-Cheng , Guan Fang-Xia , Zhang Shu-Guang
Published: April 2014

Introduction

Observational data have suggested that statin therapy may reduce mortality in patients with infection and sepsis; however, results from randomized studies are contradictory and do not support the use of statins in this context. Here, we performed a meta-analysis to investigate the effects of statin therapy on mortality from infection and sepsis.

Methods

We searched electronic databases (PubMed and Embase) for articles published before November 2013. Randomized or observational studies reporting the effects of statin therapy on mortality in patients with infection or sepsis were eligible. Randomized and observational studies were separately pooled with relative risks (RRs) and random-effects models.

Results

We examined 5 randomized controlled trials with 867 patients and 27 observational studies with 337,648 patients. Among the randomized controlled trials, statins did not significantly decrease in-hospital mortality (RR, 0.98; 95% confidence interval (CI), 0.73 to 1.33) or 28-day mortality (RR, 0.93; 95% CI, 0.46 to 1.89). However, observational studies indicated that statins were associated with a significant decrease in mortality with adjusted data (RR, 0.65; 95% CI, 0.57 to 0.75) or unadjusted data (RR, 0.74; 95% CI, 0.59 to 0.94).

Conclusions

Limited evidence suggests that statins may not be associated with a significant reduction in mortality from infection and sepsis. Although meta-analysis from observational studies showed that the use of statins was associated with a survival advantage, these outcomes were limited by high heterogeneity and possible bias in the data. Therefore, we should be cautious about the use of statins in infection and sepsis.
Book Reviews
Authors: Courtois Cédric , Given Jock , Picard Robert G.
Published: April 2014

The Social Use of Media, Helena Bilandzic, Geoffroy Patriarche and Paul Traudt (eds) (2012) Bristol/Chicago: Intellect, 202 pp., ISBN: 9781841505121, p/bk, £25

Shut-Off: the Canadian Digital Television Transition, Gregory Taylor (2013) Montreal: McGill-Queen’s University Press, 232 pp., ISBN: 9780773540491, p/bk, $29.95

Private Television in Western Europe: Content, Markets, Policies, Karen Donders, Caroline Pauwels and Jan Loisen (eds) (2013) Basingstoke: Palgrave Macmillan, 296 pp., ISBN: 9782248027543, h/bk, £55
Treatment of basal cell carcinoma using a combination of pulsed dye laser and imiquimod – Case report and review
Authors: Gaitanis Georgios , Ikiades Aris , Bassukas Ioannis D.
Published: April 2014

Objective:

To evaluate the feasibility and efficacy of a pulsed dye laser (PDL) during a 5-week course of 5% topical imiquimod application in a patient with a nodular basal cell carcinoma (BCC) and to review the literature for data on PDL treatment of BCC.

Methods:

A 74-year-old patient with a 7-mm biopsy-proven BCC on his nose was treated with topical daily imiquimod for 2 weeks. Subsequently a laser session was performed with a flash lamp-pumped dye laser at 595 nm (Dermobeam 2000; Deka M.E.L.A., Florence, Italy) employing one pass with the following parameters: fluence 15 J/cm

Results:

Topical imiquimod was continued for a further 3 weeks after the PDL session with a minimal increase in irritation. The tumor cleared and there has been no recurrence for 12 months. The literature search revealed a total of 7 small studies that included 120 tumors, the majority treated with a 595-nm device (104/120). Overall 81/120 (67.5%) treated tumors have been assessed as complete responders. No differences were recorded in relapse rates in association with the localization of the tumor, the histology (superficial vs. non-superficial), the wavelength of the device employed (595 vs. 585 nm), or the application of dynamic cooling. From the treatment parameters, only the use of multiple vs. single PDL sessions affected the outcome favorably (

Conclusion:

The combination of PDL with imiquimod could be a promising approach for the treatment of BCC and should be further evaluated in future studies.
An energy-based equivalent inclusion for the determination of nanocomposite behavior
Authors: Maalej Yamen , Dormieux Luc , Lemarchand Eric
Published: April 2014

Achieving remarkable mechanical properties for very low levels of reinforcement, nanocomposites are nowadays a new class of materials with high potential. Thanks to the stiffening aspect of the interface region between the matrix and the inclusions, nanocomposites often exhibit improved mechanical and physical properties compared to the conventional composites reinforced with micron-sized particles. This paper presents a strategy based on the introduction of an equivalent inclusion phase that allows managing the ellipsoidal morphology of inhomogeneous inclusion nanophase in the determination of estimates for the homogenized elastic moduli. Application to clay-polymer nanocomposites is presented in the framework of the dilute scheme. The latter gives theoretical estimates in good agreement with experimental results reported in the literature.
Materials, Measurement, and Error: Comparative Class Data and Scientific Argumentation via a Cloud-based Application
Authors: Sinex Scott A. , Chambers Theodore L. , Halpern Joshua B.
Published: April 2014

The Next Generation Science Standards make scientific discourse a vital part of the classroom and arguing with evidence needs to become a common practice for students. Analysis and interpretation of data are an integral part as well. We present an approach using 21st-century technology combined with collection of laboratory data that is suitable for middle school through college. In an experiment using common nuts and bolts first semester chemistry students form six groups and determine a bolt mass indirectly. They collect mass data; then enter the data into an online form that compiles the data into a spreadsheet in Google Drive, a free cloud-based application. Once all the groups have submitted their data, they access the spreadsheet online and start an emulated online discussion in the laboratory as if the groups were globally dispersed using the chat feature available in Google Drive. Each group is identified by a group number having a unique group email address so there is a semi-anonymous sense among the members that allows for a fairly free discussion among students.
The NANOLAB Project: Educational Nanoscience at High School
Authors: Lisotti Annamaria , De Renzi Valentina , Goldoni Guido
Published: April 2014

The growing role of the nano-perspective in contemporary technologies naturally calls for the inclusion of Nanoscience in high school curricula. Reasons range from-the need to educate future responsible citizens to more exquisitely didactical ones. Nanosciences are-in fact a natural playground to introduce modern Physics in a hands-on interdisciplinary way, therefore opening the possibility to expose intrinsically quantum phenomena even in school laboratories. In some cases in fact the unusual properties of nanomaterials can be probed by simple experiments, including systematic data collection, in contrast to spectacular but qualitative-only demonstrations. In this paper-we will present NANOLAB, an open project by FIM Department of Modena and Reggio E. University in Italy, which aims at including nano-inspired hands-on activities in high schools. It consists of simple, cheap, robust and safe experimental protocols, currently covering four areas of nanoscience: smart metals, nanoparticles, conductive polymers, nanostructured surfaces, each linked to one of Nanoscience “big ideas”. The experimental activities range from manual to digital data collection and elaboration, including use of pupils’ own mobile devices (cell and smart phones, tablets) which turn out to be powerful, low-cost, sensitive multi-purpose lab tools, with an added impact on students’ motivation and active involvement in what we could rightly call a high-tech hands-on approach. All accompanying materials are published under Creative Commons license. In such a picture teachers’ role is crucial. To give them adequate support and provide solid background knowledge a coaching program has been running since 2011.
Fabrication of a Large-area-patterned Monolayer of Polytetrafluoroethylene Nanoparticles by Surface Charge Induced Colloidal deposition
Authors: Du Chuan , Wang Jiadao , Chen Darong
Published: April 2014

A facile and novel method of fabricating large-area-patterned monolayer of polytetrafluoroethylene(PTFE) nanoparticles was achieved using surface charge induced colloidal deposition. Chemical processes of amination and hydroxylation were used to make the silicon substrates positively and negatively charged, respectively, while the PTFE colloidal nanoparticles were anisotropic and negatively charged. After colloidal deposition, an ordered monolayer with microholes was formed on the amination surface, while an island-like monolayer was achieved on the hydroxylation surface. Both of the two kinds of monolayers were as large as 1.5 square centimeters. It is worth pointing out that these large-area-patterned monolayers were fabricated without any templates and the whole process only took several hours. The formation mechanism of the different structures can be generally attributed to the cooperation and competition of three-body, two-body and particle-wall interactions. It is believed that the interesting patterned monolayer formation mechanism, high production efficiency, good adaptability and quality will make this novel method attractive.
The Role of Radiation Therapy for Resectable Adenocarcinoma of the Gastroesophageal Junction
Authors: Al-Batran Salah-Eddin
Published: April 2014

Adenocarcinoma of the gastroesophageal junction has become a very important subentity, for which multidisciplinary care is the widely accepted treatment approach; however, the role of radiation therapy for adenocarcinoma of gastroesophageal junction remains unclear.
Canary Wharf Crossrail station cofferdam, London, UK: design, construction and performance
Authors: Travers Ronan , Yeow Hoe-Chian
Published: April 2014

The construction of the first Crossrail station at Canary Wharf in London, UK reached a significant milestone in March 2012 when the station box was formally handed over to Crossrail for the preparation of the tunnel eyes to receive and re-launch the tunnel-boring machine. The station box is constructed in the North Dock at Canary Wharf in around 9 m of dock water. Excavation of the 265 m long, 25–30 m wide and 18 m deep station box was completed in about 12 months. This paper provides useful guidance for practising engineers on the design and construction of cofferdams' retaining walls in a dock environment. It describes the performance of the retaining structures constructed using the innovative Japanese Giken tubular pile system. Some details are also included of the site-wide dewatering undertaken to lower the groundwater in the Chalk and control it, allowing excavation into the Upnor Formation and Thanet Sand. The effects of unexploded ordnance probing on the performance of the retaining wall are described. Together with details of the laboratory tests undertaken to inform the ship impact berm design and the monitoring system used to verify the retaining wall design and comparison of the predicted and measured wall movements during excavation.
Homogenity of oil and sugar components of flour amaranth investigated by GC-MS
Authors: Psodorov Djordje , Acanski Marijana , Vujic Djura , Brkljaca Jovana , Psodorov Dragan
Published: April 2014

Gas chromatography with mass spectrometry (GC-MS) was used for performing a
qualitative analysis of liposoluble and hydrosoluble flour extracts of three
genotypes of Amaranthus sp. All three samples were first defatted with
hexane. Hexane extracts were used for the analysis of fatty acids of lipid
components. TMSH (Trimethylsulfonium hydroxide, 0.2M in methanol) was used as
the transesterification reagent. With transesterification reaction, fatty
acids were esterified from acilglycerol to methyl-esters. Defatted flour
samples were dried in the air and then extracted with ethanol. Ethanol
extracts were used for the analysis of soluble carbohydrates. TMSI
(trimethylsilylimidazole) was used as a reagent for the derivatization of
carbohydrates into trimethylsilylethers. The results show that the dominant
methyl-esters of fatty acids are very similar in all the three samples. Such
a similarity was not detected in the analysis of soluble sugars. The
following test cluster analysis was used for the comparison of liposoluble
and hydrosoluble flour extracts of three genotypes of Amaranthus sp.
The vortex flow caused by sound in a bubbly liquid
Authors: Perelomova Anna , Wojda Pawel
Published: April 2014

Generation of vorticity in the field of intense sound in a bubbly liquid in the free half-space is considered. The reasons for generation of vorticity are nonlinearity, diffraction, and dispersion. Acoustic streaming differs from that in a Newtonian fluid. Under some conditions, the vortex flow changes its direction. Conclusions concern streaming induced by a harmonic or an impulse Gaussian beam.
Electrovac universes with a cosmological constant
Authors: Posada-Aguirre Nelson , Batic Davide
Published: April 2014

We present the extension of the Einstein-Maxwell system called electrovac universes by introducing a cosmological constant Λ. In the absence of the Λ term, the crucial equation in solving the Einstein-Maxwell system is the Laplace equation. The cosmological constant modifies this equation to become in a nonlinear partial differential equation which takes the form ΔU =2ΛU 3. We offer special solutions of this equation.
Cramér–Rao Lower-Bound Optimization of Flush Atmospheric Data System Sensor Placement
Authors: Dutta Soumyo , Braun Robert D.
Published: April 2014

Flush atmospheric data systems take measurements of the pressure distribution on the forebodies of vehicles and improve the estimate of freestream parameters during reconstruction. These systems have been present on many past entry vehicles, but design of the pressure transducer suites and the placement of the sensors on the vehicle forebody have largely relied on engineering judgment and heuristic techniques. This paper develops a flush atmospheric data system design methodology using Cramér–Rao lower-bound optimization to define the smallest theoretical variance possible from the estimation process. Application of this methodology yields Pareto frontiers of possible optimal configurations and identifies the number of ports that serve as the point of diminishing returns. The methodology is tested with a simulated Mars entry, descent, and landing trajectory.
The Women of Bataille D’Alger
Authors: Sawers Catherine
Published: April 2014

This article explores the gendered subtext of film criticism that both praises and vilifies Gillo Pontecorvo’s Bataille d’Alger. The female characters play a prominent role in the film’s action, and, in particular, the women’s roles underscore the film’s ideological emphasis on anti-colonialism, as well as the need for personal and political independence. In analyzing film critique from the last forty-five years, from the original release in France to contemporary screenings, this article demonstrates how the critics’ views of female characters as participants in irregular war are central to their overall reactions to the film. Whether they love or hate the film, it is the critics’ views of the female characters that judge the film as a complete artistic piece.
Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage
Authors: Zhang Xiang-Sheng , Zhang Xin , Zhou Meng-Liang , Zhou Xiao-Ming , Li Ning , Li Wei , Cong Zi-Xiang , Sun Qing , Zhuang Zong , Wang Chun-Xi , Shi Ji-Xin
Published: April 2014

Object

Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property.

Methods

Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation.

Results

It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH.

Conclusions

These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.
Intradural tumor recurrence after resection of extradural metastasis: a rare but potential complication of intraoperative durotomy
Authors: Kasliwal Manish K. , Tan Lee A. , O'Toole John E.
Published: April 2014

Spinal metastases are the most common of spinal neoplasms and occur predominantly in an extradural location. Their appearance in an intradural location is uncommon and is associated with a poor prognosis. Cerebrospinal fluid dissemination accounts for a significant number of intradural spinal metastases mostly manifesting as leptomeningeal carcinomatoses or drop metastases from intracranial tumors. The occurrence of local tumor dissemination intradurally following surgery for an extradural spinal metastasis has not been reported previously. The authors describe 2 cases in which local intradural and intramedullary tumor recurrences occurred following resection of extradural metastases that were complicated by unintended durotomy. To heighten clinical awareness of this unusual form of local tumor recurrence, the authors discuss the possible etiology and clinical consequences of this entity.
Considerations When Deploying Canopy Temperature to Select High Yielding Wheat Breeding Lines under Drought and Heat Stress
Authors: Mason R. , Singh Ravi
Published: April 2014

Developing cultivars with improved adaptation to drought and heat stressed environments is a priority for plant breeders. Canopy temperature (CT) is a useful tool for phenotypic selection of tolerant genotypes, as it integrates many physiological responses into a single low-cost measurement. The objective of this study was to determine the ability of CT to predict grain yield within the flow of a wheat breeding program and assess its utility as a tool for indirect selection. CT was measured in both heat and drought stressed field experiments in northwest Mexico on 18 breeding trials totaling 504 spring wheat lines from the International Maize and Wheat Improvement Center (CIMMYT) Irrigated Bread Wheat program. In the heat treatment, CT was significantly correlated with yield (r = −0.26) across all trials, with a maximum coefficient of determination within the individual trials of R2 = 0.36. In the drought treatment, a significant correlation across all trials was only observed when days to heading or plant height was used as a covariate. However, the coefficient of determination within individual trials had a maximum of R2 = 0.54, indicating that genetic background may impact the ability of CT to predict yield. Overall a negative slope in the heat treatment indicated that a cooler canopy provided a yield benefit under stress, and implementing selection strategies for CT may have potential for breeding tolerant genotypes.
L'indemnité viagère de départ dans l'Allier et ses incidences sur les structures agraires
Authors: Chevrier S.
Published: April 2014

Résumé

L'attribution de l'indemnité viagère de départ (qui est un supplément de retraite pour les cultivateurs âgés laissant leur domaine dans des conditions qui permettent la « restructuration » d'autres exploitations) a eu dans le département de l'Allier des répercussions inégales selon les régions agricoles et originales par rapport aux résultats enregistrés pour l'ensemble de la France. Agrandissement des exploitations moyennes, disparition de celles trop petites, le but visé par la loi semble atteint ; mais pratiquement, le fils reprenant souvent l'exploitation du père, la cohabitation de plusieurs générations subsiste, atténuant ainsi sensiblement la portée de la loi.
Pays en voie de développement et tourisme
Authors: Burnet L.
Published: April 2014

Les pays en vote de développement bénéficient, en général, d'une nature et d'une vie humaine originales. Cependant, bien souvent, les moments où ils peuvent être fréquentés ne correspondent pas aux périodes de loisirs dans les pays évolués. Ces derniers, d'ailleurs, disposent encore d'un énorme potentiel touristique non exploité.

Il faut aussi ajouter que les pays en voie de développement manquent d'une infrastructure solide, de capitaux et de personnel spécialisé. Ils sont exposés plus que les autres à la spéculation qui hypothèque leurs possibilités d'avenir.

Si l'on peut être optimiste, c'est uniquement en espérant qu'une législation draconienne sauvegardera leur patrimoine.
Phénomènes périglaciaires en Sibérie orientale. Définition d'une nouvelle province périglaciaire actuelle.
Authors: Journaux André , Dresch Jean
Published: April 2014

Résumé.

La Yakoutie Centrale, traversée par la Lena, présente des exemples morphogénétiques particuliers, grâce à son climat très rude en hiver et très chaud en été. Sous une taiga de mélèzes, le permafrost atteint 1.450 m d'épaisseur. Fentes de gel, coins de glace et soil veins y présentent toutes sortes de variétés : leur origine et leur évolution en sont discutées. Mais ce sont les effets localisés de la thermokarstie (notamment les dépressions ou alass, les cirques d'érosion thermique), et les effets généralisés de la thermokarstie (largeur des vallées sibériennes et abaissement général du niveau des plaines) qui caractérisent le mieux une nouvelle province périglaciaire actuelle.
Un exemple de développement volontariste dans la région de Korhogo (Côte-d'Ivoire)
Authors: Coulibaly Sinali
Published: April 2014

Résumé. - Le pays Senoufo, dans le Nord de la Côte-d'Ivoire, est réputé pour son isolement, son exceptionnelle densité de population, son archaïsme social et économique. Dans le cadre de sa lutte contre les disparités régionales, l'Etat y conduit une politique d'investissements qui a connu jusqu'ici deux étapes. La première a eu pour objectif le développement de la riziculture irriguée dans la zone dense de Korhogo puis dans les vallées périphériques : aménagement des bas-fonds et barrages permettent désormais de compléter les ressources de la polyculture pluviale traditionnelle par le produit de rizières donnant deux récoltes annuelles. La modernisation du milieu rural est recherchée aussi dans la diffusion de la culture attelée. La seconde étape de la politique d'intervention gouvernementale dans la région est constituée par la création, aux environs de Ferkessédougou, d'un périmètre de culture irriguée de la canne à sucre, assorti d'installations industrielles, capable de produire plus que la consommation nationale. Ainsi le pays senoufo est-il le théâtre de transformations profondes qui traduisent la politique volontariste de l'Etat ivoirien dans le domaine de l'aménagement du territoire.
The Social Identities of Japanese Backpackers
Authors: Bui Huong T. , Wilkins Hugh C. , Lee Young-Sook
Published: April 2014

This research adopted a qualitative approach with data collected through in-depth interviews, informal conversations, and participant observation to identify the social identities of Japanese young travelers in relation to their group dynamic. The findings indicate that the diversity
of out-group interactions with travelers from different countries enhances cross-cultural understanding and language learning, while in-group interactions with other Japanese offer a pseudohome while traveling. The issue of identity ambivalence is important as the spheres of familiarity and
diversity in travel group interactions are dynamic and complementary. The current research furthers our understanding of the interrelation between culture, communication, and the action of travel among independent travelers.
Experience-Driven Development: Effector/Memory-Like αE+Foxp3+ Regulatory T Cells Originate from Both Naive T Cells and Naturally Occurring Naive-Like Regulatory T Cells
Authors: Siewert Christiane , Lauer Uta , Cording Sascha , Bopp Tobias , Schmitt Edgar , Hamann Alf , Huehn Jochen
Published: April 2014

Naturally occurring Foxp3+CD25+CD4+ regulatory T cells (Treg) have initially been described as anergic cells; however, more recent in vivo studies suggest that Tregs vigorously proliferate under both homeostatic as well as inflammatory conditions. We have previously identified a subset of murine CD4+ Tregs, which is characterized by expression of the integrin αEβ7 and which displays an effector/memory-like phenotype indicative of Ag-specific expansion and differentiation. In the present study, the αE+ Treg subset was found to contain a large fraction of cycling cells under homeostatic conditions in healthy mice. Using an adoptive transfer system of Ag-specific T cells, we could demonstrate that the vast majority of transferred natural, naive-like CD25+CD4+ Tregs acquired expression of the integrin αEβ7 upon tolerogenic application of Ag via the oral route. In addition, using the same system, Foxp3+ Tregs could be de novo induced from conventional naive CD25−CD4+ T cells, and this conversion was associated with concomitant expression of αE. These findings suggest that Tregs expressing the integrin αE are effector/memory Tregs with a high turnover rate that can develop in the periphery upon Ag contact under tolerogenic conditions, both from thymic-derived CD25+CD4+ Tregs with a naive-like phenotype as well as from conventional naive T cells.
Early Effector T Cells Producing Significant IFN-γ Develop into Memory
Authors: Bell J. Jeremiah , Ellis Jason S. , Guloglu F. Betul , Tartar Danielle M. , Lee Hyun-Hee , Divekar Rohit D. , Jain Renu , Yu Ping , Hoeman Christine M. , Zaghouani Habib
Published: April 2014

Currently, transition of T cells from effector to memory is believed to occur as a consequence of exposure to residual suboptimal Ag found in lymphoid tissues at the waning end of the effector phase and microbial clearance. This led to the interpretation that memory arises from slightly activated late effectors producing reduced amounts of IFN-γ. In this study, we show that CD4 T cells from the early stage of the effector phase in which both the Ag and activation are optimal also transit to memory. Moreover, early effector T cells that have undergone four divisions expressed significant IL-7R, produced IFN-γ, and yielded rapid and robust memory responses. Cells that divided three times that had marginal IL-7R expression and no IFN-γ raised base level homeostatic memory, whereas those that have undergone only two divisions and produced IFN-γ yielded conditioned memory despite low IL-7R expression. Thus, highly activated early effectors generated under short exposure to optimal Ag in vivo develop into memory, and such transition is dependent on a significant production of the cell’s signature cytokine, IFN-γ.
Increased Antigen Presentation Efficiency by Coupling Antigens to MHC Class I Trafficking Signals
Authors: Kreiter Sebastian , Selmi Abderraouf , Diken Mustafa , Sebastian Martin , Osterloh Phillip , Schild Hansjörg , Huber Christoph , Türeci Özlem , Sahin Ugur
Published: April 2014

Genetic modification of vaccines by linking the Ag to lysosomal or endosomal targeting signals has been used to route Ags into MHC class II processing compartments for improvement of CD4+ T cell responses. We report in this study that combining an N-terminal leader peptide with an MHC class I trafficking signal (MITD) attached to the C terminus of the Ag strongly improves the presentation of MHC class I and class II epitopes in human and murine dendritic cells (DCs). Such chimeric fusion proteins display a maturation state-dependent subcellular distribution pattern in immature and mature DCs, mimicking the dynamic trafficking properties of MHC molecules. T cell response analysis in vitro and in mice immunized with DCs transfected with Ag-encoding RNA showed that MITD fusion proteins have a profoundly higher stimulatory capacity than wild-type controls. This results in efficient expansion of Ag-specific CD8+ and CD4+ T cells and improved effector functions. We used CMVpp65 and NY-ESO-1 Ags to study preformed immune responses in CMV-seropositive individuals and cancer patients. We show that linking these Ags to the MITD trafficking signal allows simultaneous, polyepitopic expansion of CD8+ and CD4+ T cells, resulting in distinct CD8+ T cell specificities and a surprisingly broad and variable Ag-specific CD4+ repertoire in different individuals.
Cutting Edge: Requirement for TRAF6 in the Induction of T Cell Anergy
Authors: King Carolyn G. , Buckler Jodi L. , Kobayashi Takashi , Hannah Jeffrey R. , Bassett Garrett , Kim Taesoo , Pearce Erika L. , Kim Gregory G. , Turka Laurence A. , Choi Yongwon
Published: April 2014

TRAF6, TNFR-associated factor 6, is a key adaptor downstream from the TNF receptor and TLR superfamily members. T cell-specific deletion of TRAF6 (TRAF6-ΔT) was recently shown to result in the development of multiorgan inflammatory disease and the resistance of responder T cells to suppression by CD4+CD25+ regulatory T cells. In this study we examined the role of TRAF6 in an additional mechanism of peripheral tolerance, anergy. We have determined that the loss of TRAF6 restores the ability of CD28−/− T cells to proliferate and produce IL-2. Consistent with this, TRAF6-ΔT T cells were resistant to anergizing signals both in vitro and in vivo. Resistance to anergy was correlated with decreased expression of Cbl-b. These findings reveal that in addition to its role in rendering T cells susceptible to control by CD4+CD25+ regulatory T cells, TRAF6 is essential for the induction of T cell anergy, implicating TRAF6 as a critical mediator of peripheral tolerance.
HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D
Authors: Chentoufi Aziz Alami , Zhang Xiuli , Lamberth Kasper , Dasgupta Gargi , Bettahi Ilham , Nguyen Alex , Wu Michelle , Zhu Xiaoming , Mohebbi Amir , Buus Søren , Wechsler Steven L. , Nesburn Anthony B. , BenMohamed Lbachir
Published: April 2014

Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10 amino acids in length, exhibited high-affinity binding in vitro to purified human HLA-A*0201 molecules. Three of these four peptide epitopes, gD53–61, gD70–78, and gD278–286, significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-γ ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53–61, gD70–78, and gD278–286 epitopes. In addition, CD8+ T cell lines generated by gD53–61, gD70–78, and gD278–286 peptides recognized infected target cells expressing native gD. Lastly, CD8+ T cell responses specific to gD53–61, gD70–78, and gD278–286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.
NF-κB Signaling, Elastase Localization, and Phagocytosis Differ in HIV-1 Permissive and Nonpermissive U937 Clones
Authors: Bristow Cynthia L. , Wolkowicz Roland , Trucy Maylis , Franklin Aaron , Di Meo Fernando , Kozlowski Mark T. , Winston Ronald , Arnold Roland R.
Published: April 2014

To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte elastase (HLE) in a granule-like compartment (HLEG) that was never detected at the cell surface (HLECS). In contrast to the minus clone, the plus clone expressed HLE on the cell surface and was adherent to coverslips coated with the HLECS ligands α1proteinase inhibitor (α1PI, α1antitrypsin) and the HIV-1 fusion peptide. The phosphorylation status of several important signaling proteins was studied at the single cell level. Tumor suppressor p53, NF-κB p65, and Akt were constitutively phosphorylated in the plus clone, but not in the minus clone. Surprisingly, both α1PI and LPS induced phosphorylation of NF-κB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in the plus clone only. HIV-1 permissivity was conferred to the minus clone in a manner that required stimulation by both α1PI and LPS and was coincident to NF-κB p65 phosphorylation/dephosphorylation events as well as translocation of HLE to the cell surface. Even when stimulated, the minus clone exhibited greater reverse transcriptase activity, but less p24, than the plus clone. Results presented suggest that HIV-1 uptake and production efficiency are influenced by signaling profiles, receptor distribution, and the phagocytic capacity specific to the stage of differentiation of the CD4+ target cell.