bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Butter Spoiling Yeasts and Their Inhibition by Some Spices
Authors: Sagdic Osman , Ozturk Ismet , Bayram Okan , Kesmen Zulal , Yilmaz Mustafa Tahsin
Published: November 2010

Abstract:  This study was designed to identify the yeasts in packaged and unpackaged butters and screen antiyeast activity of spices, including marjoram (Origanum majorana L.), summer savory (Satureja hortensis L.), and black cumin (Nigella sativa L.) against the most dominant yeast species in the packaged and unpackaged butters. Mean total yeast populations were 5.40 log CFU/g in unpackaged butter samples and 2.22 log CFU/g in packaged butter samples, indicating better hygienic quality of packaged samples. Forty‐nine yeast species were isolated and identified from butter samples with the most prevalent isolates belonging to genera Candida—C. kefyr, C. zeylanoides, and C. lambica—and with moderate number of isolates belonging to genera Cryptococcus, Rhodotorula, Saccharomyces, and Zygosaccharomyces. Black cumin exhibited the highest antiyeast activity against C. zeylanoides and C. lambica species, even inhibited these species, while summer savory inhibited C. kefyr. The results of this study revealed clear antimicrobial potential of black cumin against the yeast species isolated from butters. Marjoram, summer savory, and black cumin could be used as natural antimicrobial agents against spoilage yeasts in food preservation, especially in butter.

Practical Application:  Yeasts are known to play an important role in the dairy industry for several reasons. They play an essential role in the preparation of certain fermented products and in the ripening of certain cheeses. Yeasts also can be used to ferment dairy products. However, yeasts are also known to cause spoilage of dairy and other food products. Spices have generally been considered as nonnutritive substances and their possible benefit to human health has recently been considered. In addition, spices could perform different antimicrobial activities on pathogenic and food spoilage yeasts. For this purpose, this study was designed to cover the following items: (1) enumeration of the yeast populations in packaged and unpackaged butter samples; (2) isolation and identification of the yeast species to characterize the yeasts of the butter samples; (3) screening of antiyeast activity of these spices against the most dominant yeast species, Candida kefyr, C. zeylanoides, and C. lambica, in the packaged and unpackaged butter samples.
Lessons from the Salk Polio Vaccine: Methods for and Risks of Rapid Translation
Authors: Juskewitch, B.A. Justin E. , Tapia, B.A. Carmen J. , Windebank Anthony J.
Published: November 2010

The Salk inactivated poliovirus vaccine is one of the most rapid examples of bench‐to‐bedside translation in medicine. In the span of 6 years, the key basic lab discoveries facilitating the development of the vaccine were made, optimization and safety testing was completed in both animals and human volunteers, the largest clinical trial in history of 1.8 million children was conducted, and the results were released to an eagerly awaiting public. Such examples of rapid translation cannot only offer clues to what factors can successfully drive and accelerate the translational process but also what mistakes can occur (and thus should be avoided) during such a swift process. In this commentary, we explore the translational path of the Salk polio vaccine from the key basic science discoveries to the 1954 Field Trials and delve into the scientific and sociopolitical factors that aided in its rapid development. Moreover, we look at the Cutter and Wyeth incidents after the vaccine’s approval and the errors that led to them. Clin Trans Sci 2010; Volume 3: 182–185
Review Article: Phospholemman: A Novel Cardiac Stress Protein
Authors: Cheung Joseph Y. , Zhang Xue‐Qian , Song Jianliang , Gao Erhe , Rabinowitz Joseph E. , Chan Tung O. , Wang JuFang
Published: November 2010

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co‐localizes and co‐immunoprecipitates with Na+‐K+‐ATPase, Na+/Ca2+ exchanger, and L‐type Ca2+ channel. Functionally, when phosphorylated at serine68, PLM stimulates Na+‐K+‐ATPase but inhibits Na+/Ca2+ exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L‐type Ca2+ channel. Therefore, PLM occupies a key modulatory role in intracellular Na+ and Ca2+ homeostasis and is intimately involved in regulation of excitation–contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na+ overload and simultaneously preserves inotropy by inhibiting Na+/Ca2+ exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na+‐K+‐ATPase, Na+/Ca2+ exchanger, and potentially L‐type Ca2+ channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189–196
The preservation of fossil biomarkers during meteorite impact events: Experimental evidence from biomarker‐rich projectiles and target rocks
Authors: PARNELL John , BOWDEN Stephen , LINDGREN Paula , BURCHELL Mark , MILNER Daniel , PRICE Mark , BALDWIN Emily C. , CRAWFORD Ian A.
Published: November 2010

Abstract– A Devonian siltstone from Orkney, Scotland, shows survival of biomarkers in high‐velocity impact experiments. The biomarkers were detected in ejecta fragments from experiments involving normal incidence of steel projectiles at 5–6 km s−1, and in projectile fragments from impact experiments into sand and water at 2–5 km s−1. The associated peak shock pressures were calculated to be in the range of 110–147 GPa for impacts of the steel projectiles into the siltstone target, and hydrocode simulations are used to show the variation of peak pressure with depth in the target and throughout the finite volume projectiles. Thermally sensitive biomarker ratios, including ratios of hopanoids and steranes, and the methylphenanthrene ratio, showed an increase in thermal maturity in the ejecta, and especially the projectile, fragments. Measurement of absolute concentrations of selected biomarkers indicates that changes in biomarker ratios reflect synthesis of new material rather than selective destruction. Their presence in ejecta and projectile fragments suggests that fossil biomarkers may survive hypervelocity impacts, and that experiments using biomarker‐rich rock have high potential for testing survival of organic matter in a range of impact scenarios.
Anode Fuel and Steam Recycling for Internal Methane Reforming SOFCs: Analysis of Carbon Deposition
Authors: Eveloy Valérie
Published: November 2010

Anode fuel and steam recycling are explored as possible mitigation strategies against carbon deposition in an internal methane reforming solid oxide fuel cell (IR-SOFC) operated at steam-to-carbon ratios (S:Cs) of 0.5–1. Using a detailed computational fluid dynamics model, the cell behavior and spatial extent of carbon deposits within the anode are analyzed based on a thermodynamic analysis accounting for both the cracking and Boudouard reactions for fuel and steam recycling fractions of up to 90% (mass percent). At temperatures close to 1173 K, 50% fuel recycling is found to be an effective mitigation strategy against carbon deposition, with only a minor portion of the cell inlet affected by coking. Steam recycling reduces the extent of carbon deposits by a magnitude comparable to that obtained using fuel recycling, provided that recycling ratios on the order of 25% higher than that for fuel recycling are applied. Steam recycling could therefore be considered advantageous in terms of reduced overall mass flow. The mitigating effect of fuel recycling on the susceptibility to coking at the cell inlet is found to be through the direction of the cracking reaction, while steam recycling has a positive (but slightly less effective) impact on both the Boudouard and cracking reactions. The results suggest that partial anode gas recycling could help extend the operational range of IR-SOFCs to lower fuel humidification levels than typically considered, with reduced thermal stresses and risks of carbon deposits, while reducing system cost and complexity in terms of steam production.
Novel Approaches for the Integration of High Temperature PEM Fuel Cells Into Aircrafts
Authors: Novillo Eva , Pardo Mónica , García-Luis Alberto
Published: November 2010

Reduced greenhouse gas emissions via improved energy efficiency represent the ultimate challenge for the energy economy of the future. In this context, fuel cells for power generation aboard aircrafts have a promising potential to effectively contribute to the greening of air transportation. They can simplify today’s aircraft comprising electric, pneumatic, and hydraulic systems toward a more electric airplane. Although they are not considered in the short term as an alternative propulsion system for commercial aviation, many efforts are being devoted to their use as auxiliary power units and even aiming to build a distributed power network that might alleviate duties of the engine driven generators. In addition they allow new functions such as zero emission during taxiing on ground and/or increase safety by replacing the emergency ram-air turbine (RAT) by a fuel cell based emergency power generator. The present paper focuses on the effort that Compañía Española de Sistemas Aeronáuticos (CESA) is putting into the development of an aeronautical fuel cell system based on a high-temperature PEMFC covering all aspects from fundamental research in materials and processes to final integration concepts as a function of different architectures. A great deal of time and effort has been invested to overcome the challenges of PEM fuel cell operation at high temperatures. Among the advantages of these systems are the enhancement of electrochemical kinetics, the simplification of water management and cooling, the recovery of wasted heat, and the possibility of utilizing reformed hydrogen thanks to higher tolerance to impurities. However, new problems arise with the high-temperature concept that must be addressed such as structural and chemical degradation of materials at elevated temperatures. One of the aeronautical applications, where a fuel cell has an important role to play in the short term is the emergency power unit. Weight and mechanical complexity of traditional ram-air turbines could be drastically reduced by the introduction of a hydrogen fueled system. In addition, the output of the fuel cell is aircraft’s speed independent. This means additional power supply in case of emergency allowing a safer landing of the aircraft. However, a RAT replacement must overcome the specific difficulties concerning the very short start-up times allowed and the heating/cooling strategies to quickly raise the temperature to elevated levels and accurately maintaining the optimum operating range once in service.
Thermal Conductivity Measurement of Graphene Exfoliated on Silicon Dioxide
Authors: Seol Jae Hun , Moore Arden L. , Shi Li , Jo Insun , Yao Zhen
Published: November 2010

We have developed a nanofabricated resistance thermometer device to measure the thermal conductivity of graphene monolayers exfoliated onto silicon dioxide. The measurement results show that the thermal conductivity of the supported graphene is approximately 600 W/m K at room temperature. While this value is lower than the reported basal plane values for graphite and suspended graphene because of phonon leakage across the graphene-support interface, it is still considerably higher than the values for common thin film electronic materials. Here, we present a detailed discussion of the design and fabrication of the measurement device. Analytical and numerical heat transfer solutions are developed to evaluate the accuracy and uncertainty of this method for thermal conductivity measurement of high-thermal conductivity ultrathin films.
Impact of exposure doses on demolding process in UV nanoimprint lithography
Authors: Tanabe Toshiaki , Fujii Noriyoshi , Matsue Masato , Kawata Hiroaki , Hirai Yoshihiko
Published: November 2010

The impact of exposure doses on the demolding process in UV nanoimprint lithography (UV NIL) was studied. The PAK-01 resist was examined to investigate the dependence of the conversion ratio and elastic modulus on the adhesion force between the mold and the resist for various UV dosages. Also, adhesion forces between the resist and SiO2/Si mold were measured in various dosages. The results show that the adhesion force is unstable until the elastic modulus of the resist is enlarged enough even if the chemical conversion is completed by UV exposure. On the other hand, the demolding in the actual UV NIL experiment is not successful at lower dosages. Based on these evaluations, a suitable exposure dosage is suggested for successful demolding to realize a high throughput UV NIL process without demolding defects.
Three-dimensional microfluidic mixers using ion beam lithography and micromachining
Authors: Palacios E. , Ocola L. E. , Joshi-Imre A. , Bauerdick S. , Berse M. , Peto L.
Published: November 2010

In this article, the authors present microfluidic mixers containing three-dimensional (3D) geometries used to decrease mixing lengths in passive microfluidic systems. In order to create these 3D geometries, the authors use ion beam lithography and micromachining and address charging, redeposition, and stitching error effects that follow this type of fabrication. Prior to mixer fabrication, simulations were run and results were compared between a common straight mixer and two other mixers designed by the authors. The simulation results have shown that 3D geometries can generate lateral velocities and lower mixing lengths down to approximately 70 μm.
Evaluation of suicide awareness programmes delivered to veterinary undergraduates and academic staff
Authors: Mellanby R. J. , Hudson N. P. H. , Allister R. , Bell C. E. , Else R. W. , Gunn‐Moore D. A. , Byrne C. , Straiton S. , Rhind S. M.
Published: November 2010

In an effort to increase suicide awareness skills among veterinary undergraduates, a three‐hour suicide awareness workshop (safeTALK) was delivered to third‐year Royal (Dick) School of Veterinary Studies undergraduates as part of their professional development curriculum. Students were able to opt out of the session by contacting the course organisers. A total of 26 of 151 (17 per cent) third‐year students attended the workshop, and 17 completed a feedback questionnaire. The vast majority of the students reported that after completing the workshop they were more likely or much more likely to recognise the signs of a person at risk of suicide, approach a person at risk of suicide, ask a person about suicide, and connect a person at risk of suicide with help. Five veterinary academics attended a two‐day Applied Suicide Intervention Skills Training (ASIST) course, and all reported that the course was effective in improving suicide awareness and intervention skills.
Elimination of small ruminant lentivirus infection from sheep flocks and goat herds aided by health schemes in Great Britain
Authors: Synge B. A. , Ritchie C. M.
Published: November 2010

Over a period of 11 years, 33 sheep or goat holdings lost their maedi‐visna or caprine arthritis‐encephalitis accredited status (mean 2.8 per year [0.09 per cent] of the accredited holdings in Great Britain). Of these, 22 sheep flocks and two goat herds eradicated the infection and regained their accredited status. In addition, 10 sheep flocks and two goat herds managed to eradicate infection, having joined the scheme with infected animals. In flocks and herds with a high initial prevalence of infection, the adoption of an indirect ELISA, with greater sensitivity than the agar gel immunodiffusion test, improved success rates. A strategy was devised to interpret the ELISA results depending upon the prevalence of infection at the time. Eighteen of the 33 flocks/herds (54.5 per cent) that had introductions of infection also owned non‐accredited stock.
Nonempirical density-functional theory for van der Waals interactions
Authors: Becke Axel D. , Arabi Alya A. , Kannemann Felix O.
Published: November 2010

In previous work, Kannemann and Becke [ J. Chem. Theory Comput. 5, 719 (2009) and J. Chem. Theory Comput. 6, 1081 (2010) ] have demonstrated that the generalized gradient approximations (GGAs) of Perdew and Wang for exchange [Phys. Rev. B 33, 8800 (1986)] and Perdew, Burke, and Ernzerhof for correlation [Phys. Rev. Lett. 77, 3865 (1996)] , plus the dispersion density functional of Becke and Johnson [J. Chem. Phys. 127, 154108 (2007)] , comprise a nonempirical density-functional theory of high accuracy for thermochemistry and van der Waals complexes. The theory is nonempirical except for two universal cutoff parameters in the dispersion energy. Our calculations so far have been grid-based and have employed the local density approximation (LDA) for the orbitals. In this work, we employ orbitals from self-consistent GGA calculations using Gaussian basis sets. The results, on a benchmark set of 65 van der Waals complexes, are similar to our grid-based post-LDA results. This work sets the stage for van der Waals force computations and geometry optimizations.
On the nature of homo- and hetero-dinuclear metal–metal quadruple bonds — Analysis of the bonding situation and benchmarking DFT against wave function methods
Authors: Takagi Nozomi , Krapp Andreas , Frenking Gernot
Published: November 2010

Homo- and hetero-dimetallic (d–d)8 analogues of the formally quadruply bonded [Re2Cl8]2– system with the general formula [MM′Cl8]x (M, M′ = Tc, Re, Ru, Os, Rh, Ir and x = –2, –1, 0, +1, +2) have been calculated with the density functional theory (DFT) functionals SVWN, BLYP, BP86, PBE, OLYP, OPBE, HCTH, B3LYP, O3LYP, X3LYP, BH&HLYP, TPSS, VSXC, TPPSh, and ab initio methods (CASPT2, CCSD(T)) using basis sets of triple-ζ quality. The performance of the functionals for the description of the metal–metal bond distance and the bond dissociation energy as well as the singlet–triplet gap was evaluated with respect to ab initio data at the CASPT2 level. Generally, the generalized gradient approximation (GGA) functionals, BLYP, BP86, and PBE, show good performance in the description of the metal–metal bond distance and for the dissociation energy. Hybrid functionals are not to be used for compounds of the type discussed here as they lead to increasingly too short and too weak bonds with the amount of exact exchange included. All functionals underestimate the singlet–triplet gap, with the GGA functionals BLYP, BP86, PBE being the closest to the CASPT2 values. The bonding situations of the [MM′Cl8]x compounds were analyzed at the DFT level (BP86) using the natural bond orbital (NBO) method and the energy decomposition analysis. The M–M bond in homodimetallic compounds, [MMCl8]x, becomes weaker from group 7 to group 8 to group 9 metals and the bond is weaker for 4d metal systems than for 5d transition metal compounds. The M–M bonds have approximately 50% covalent and 50% electrostatic character and the covalent contribution is dominated by the π orbitals, whereas the δ orbitals do not contribute significantly to the covalent bonding. Heterodimetallic systems, [MM′Cl8]x, have significantly stronger metal–metal bonds than the homodimetallic compounds. This comes from weaker Pauli repulsion and stronger electrostatic attraction. The most stable heterodimetallic bonds are observed for 5d–5d metal pairs.
Configurations and conformations of glycosyl sulfoxides
Authors: Liang Hong , MacKay Micheline , Grindley T. Bruce , Robertson Katherine N. , Cameron T. Stanley
Published: November 2010

X-ray crystallographic studies of two axial glycosyl sulfoxides having RS configurations (derivatives of phenyl 2-azido-2-deoxy-1-thio-α-d-galactopyranoside S-oxide) show that they adopt anti conformations in the solid state, in contrast to previous observations and assumptions. Density functional theory (DFT) calculations at the B3lYP6–311G+(d,p)/6–31G(d) level confirm that anti conformations of both phenyl and methyl RS glycosyl sulfoxides of 2-azido-2-deoxy-α-d-pyranosides are more stable than exo-anomeric conformations in the gas phase. 1D NOE measurements indicate that the more polar exo-anomeric conformers are only populated to a slight extent in solution. The anti conformations are distorted so that the glycosyl substituents are closer to being eclipsed with H1. This distortion allows S n → σ* overlap if the sulfur lone pair is a p-type lone pair. Evidence for this overlap comes from short C1–S bond distances, as short as the comparable bond distances in the X-ray crystal structure and in the results from DFT calculations for the SS glycoside, which does adopt the expected exo-anomeric conformation, both in the solid state and in solution, and has normal n → σ* overlap. For 2-deoxy derivatives not bearing a 2-azido group, gas-phase DFT calculations at the same level indicate that the anti- and exo-anomeric conformers have comparable stabilities. Comparison of the results of the two series shows that electronegative substituents in equatorial orientations at C2 destabilize conformations with parallel S–O arrangements, the conformation favored by having an endocyclic C–O dipole antiparallel to the S–O dipole, by about 2.5 kcal mol–1 (1 cal = 4.184 J). An equatorial glycosyl sulfoxide, (SS) phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside S-oxide, also adopts an anti conformation in the solid state as shown by X-ray diffraction. It also adopts this conformation in solution, in contrast to studies of other equatorial glycosyl sulfoxides.
Non-Quasi-Static Modeling of Silicon Nanowire Metal–Oxide–Semiconductor Field-Effect Transistor and Its Model Verification up to 1 THz
Authors: Cho Seongjae , Kim Kyung Rok , Park Byung-Gook , Kang In Man
Published: November 2010

In this work, the radio-frequency (RF) performances of a silicon nanowire (SNW) metal–oxide–semiconductor field-effect transistor (MOSFET) were modeled by being grafted into the non-quasi-static (NQS) small-signal equivalent circuit for the first time. The parameters were analytically extracted from three-dimensional (3D) device simulations. The cutoff frequencies of an SNW MOSFET with a 30 nm channel length and a 5 nm radius were 504 and 545 GHz in the linear and saturation regions, respectively. The reliability of modeling results was verified by the simulations including realistic models. It was confirmed that the SNW MOSFET would be the promising candidate as a core component for RF systems aiming 1 THz operation.
Arsenic-Doped n-Type Diamond Grown by Microwave-Assisted Plasma Chemical Vapor Deposition
Authors: Kasu Makoto , Kubovic Michal
Published: November 2010

We grew n-type arsenic (As)-doped single-crystal diamond layers using tertiarybutylarsine as an As source. The n-type conduction of the As-doped layers was confirmed both in Hall measurements and from the current–voltage characteristics of the diodes. In the As-doped layers, electron concentration increased with As concentration in the layers. The ionization energy of the As donor decreased from 1.6 to 0.7 eV with As concentration from 1×1017 to 9×1019 cm-3. A diamond p–n junction diode with an n-type As-doped layer exhibited a rectification ratio of ∼1000 at ±10 V at room temperature.
Dietary cholesterol induces trafficking of intestinal Niemann-Pick Type C1 Like 1 from the brush border to endosomes
Authors: Skov Marianne , Tønnesen Carina K. , Hansen Gert H. , Danielsen E. Michael
Published: November 2010

The transmembrane protein Niemann-Pick C1 Like 1 (NPC1L1) belongs to the Niemann-Pick C1 (NPC1) family of cholesterol transporters and is mainly expressed in the liver and the small intestine. NPC1L1 is believed to be the main transporter responsible for the absorption of dietary cholesterol. Like NPC1, NPC1L1 contains a sterol sensing domain, suggesting that it might be sensitive to dietary cholesterol. To test this hypothesis, mucosal explants were cultured in the presence or absence of cholesterol. In the absence of cholesterol NPC1L1 was localized mainly in the brush border of the enterocyte, colocalizing with the brush border enzyme aminopeptidase N (APN), and only a minor part was present in intracellular compartments. In contrast, following culture in the presence of cholesterol a major part of NPC1L1 was found in intracellular compartments positive for the early endosomal marker early endosome antigen 1, whereas only a minor fraction was left in the brush border. Neither APN, lactase, nor sucrase-isomaltase was endocytosed in parallel, demonstrating that this is a selective cholesterol-induced endocytosis of NPC1L1. Conceivably either the induced internalization could be due to NPC1L1 acting as an endocytic cholesterol receptor or it could be a mechanism to reduce the cholesterol uptake. The fluorescent cholesterol analog NBD-cholesterol readily labeled the cytoplasm also under conditions nonpermissible for endocytosis, arguing against a receptor-mediated uptake. We therefore propose that cholesterol is absorbed by NPC1L1 acting as a membrane transporter and that NPC1L1 is internalized to an endosomal compartment to reduce the absorption of cholesterol.
Multidetector Row Computed Tomography to Assess Changes in Airways Linked to Asthma Control
Authors: Brillet Pierre-Y. , Attali Valérie , Nachbaur Gaëlle , Capderou André , Becquemin Marie-H. , Beigelman-Aubry Catherine , Fetita Catalin I. , Similowski Thomas , Zelter Marc , Grenier Philippe A.
Published: November 2010

Background: In asthma, multidetector row computed tomography (MDCT) detects abnormalities that are related to disease severity, including increased bronchial wall thickness. However, whether these abnormalities could be related to asthma control has not been investigated yet. Objective: Our goal was to determine which changes in airways could be linked to disease control. Methods: Twelve patients with poor asthma control were included and received a salmeterol/fluticasone propionate combination daily for 12 weeks. Patients underwent clinical, functional, and MDCT examinations before and after the treatment period. MDCT examinations were performed using a low-dose protocol at a controlled lung volume (65% TLC). Bronchial lumen (LA) and wall areas (WA) were evaluated at a segmental and subsegmental level using BronCare software. Lung density was measured at the base of the lung. Baseline and end-of-treatment data were compared using the Wilcoxon signed-rank test. Results: After the 12-week treatment period, asthma control was achieved. Airflow obstruction and air trapping decreased as assessed by the changes in FEV1 (p < 0.01) and expiratory reserve volume (p < 0.01). Conversely, LA and WA did not vary significantly. However, a median decrease in LA of >10% was observed in half of the patients with a wide intra- and intersubject response heterogeneity. This was concomitant with a decrease in lung density (p < 0.02 in the anteroinferior areas). Conclusions: MDCT is insensitive for demonstrating any decrease in bronchial wall thickness. This is mainly due to changes in bronchial caliber which may be linked to modifications of the elastic properties of the bronchopulmonary system under treatment.
Epidemiological and Clinical Features of 308 Hospitalized Patients with Novel 2009 Influenza A (H1N1) Virus Infection in China during the First Pandemic Wave
Authors: Zhang Guoliang , Xia Zhang , Liu Yingxia , Li Xiuhui , Tan Xinghua , Tian Yimei , Liang Lianchun , Nie Guang , Zhou Boping
Published: November 2010

Objectives: To investigate the epidemiological and clinical features of 308 hospitalized patients suffering from infection with novel H1N1 influenza virus in China from May to August 2009, and to examine the effects of oseltamivir treatment for mild cases. Methods: Information on H1N1 influenza patients confirmed by real-time RT-PCR assay was gathered and analyzed from an influenza surveillance system, including demographic features, clinical symptoms and signs, therapeutic regimen, and duration of fever and virus shedding. Results: The clinical course of infected individuals appeared mild. Mainly young adults were affected. Most cases had low or mid-level fever, cough, headache, rhinorrhoea, and sore throat. Few patients had vomiting (1.3%) and diarrhea (3.9%). Oseltamivir treatment did not shorten the duration of fever. Furthermore, early oseltamivir treatment as well as early conventional supportive treatment without antiviral drugs contributed to a reduction in the duration of virus shedding. Conclusions: In the first pandemic wave, novel H1N1 virus caused disease primarily in adults, causing mild febrile illness. Mildly ill patients cleared the virus rapidly even in the absence of oseltamivir treatment.
Postnatal Docosahexaenoic Acid Deficiency Is an Inevitable Consequence of Current Recommendations and Practice in Preterm Infants
Authors: Lapillonne Alexandre , Eleni dit Trolli Sergio , Kermorvant-Duchemin Elsa
Published: November 2010

Background: Very preterm infants are particularly susceptible to nutrient deficiencies. Although a lot of attention has been focused on the early nutrient supply, they are at high risk of long-chain polyunsaturated fatty acid deficiency. Objectives: To estimate docosahexaenoic acid (DHA) intake, the metabolizable (i.e. absorbed) DHA, the DHA available for accretion and to quantify the DHA deficit, if any, during the first month of life of preterm infants born ≤28 weeks of gestation. Methods: Monocentric study. Nutritional data for the first 28 days of life were collected in 40 preterm infants born with a gestational age ≤28 weeks. Results: The metabolizable DHA intake (i.e. parenteral DHA + absorbed DHA) during the 1st, 2nd, 3rd and 4th weeks of life increased significantly over time (p < 0.0001), but corresponded to 7, 21, 30 and 39% of the fetal DHA accretion rate, respectively. Assuming endogenous synthesis, all infants exhibited a severe DHA deficit which reached on average 661 ± 100 mg/kg, which represents at least half of the DHA that should have been accumulated. The DHA deficit was highly correlated with birth weight, demonstrating that the smaller the infant, the larger the DHA deficit. Conclusions: The current nutritional management of preterm infants is likely to lead to an early and severe DHA deficit which may represent, at 1 month of age, about half of the fetal DHA accumulation.
Retinal Nerve Fiber Layer Thinning in CADASIL: An Optical Coherence Tomography and MRI Study
Authors: Rufa Alessandra , Pretegiani Elena , Frezzotti Paolo , De Stefano Nicola , Cevenini Gabriele , Dotti Maria Teresa , Federico Antonio
Published: November 2010

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a genetic form of small-vessel disease causing subcortical dementia. A relevant role of axonal injury was recently proposed to explain disability and cognitive decline in this disease. The retinal nerve fiber layer (RNFL) is the only part of the brain where unmyelinated axons can be visualized and quantified in vivo. Their assessment may be an easily reproducible marker of neurodegenerative processes. The aim of this study was to investigate axonal degeneration in CADASIL by measuring RNFL thickness and correlating it with MRI measures of global and regional cerebral atrophy. Methods: RNFL thickness was measured using optical coherence tomography in 17 CADASIL patients. Average values per quadrant (temporal, superior, nasal, inferior) and overall values were compared with those of normal sex- and age-matched subjects. Data of 13 patients were analyzed for correlations with MRI-based global and regional brain volumes normalized for head size. Results: RNFL thickness was significantly reduced in CADASIL patients with respect to controls (p < 0.05). No significant correlations were found between RNFL thinning and brain atrophy. Conclusions: RNFL thinning suggests that retinal axonal loss occurs in CADASIL, even in the absence of subjective visual deficit.
Quantitative expression analysis and study of the novel human kallikrein-related peptidase 14 gene (KLK14) in malignant and benign breast tissues
Authors: Papachristopoulou Georgia , Avgeris Margaritis , Charlaftis Antonios , Scorilas Andreas
Published: November 2010

Human kallikrein-related peptidase 14 gene (KLK14) is regulated by androgens and progestins. This gene is expressed in the central nervous system and endocrine tissues such as the breast, prostate and ovary. The differential KLK14 mRNA expression levels are related to several human neoplasias, among them breast cancer. The aim of this study was to analyse the KLK14 expression in breast tissues and to investigate its differential diagnostic and prognostic value in the mammary carcinomas. For this purpose, we isolated total RNA from 70 malignant and 33 benign specimens. After testing RNA quality, we synthesised cDNA by reverse transcription and applied a highly sensitive quantitative real-time PCR (qRT-PCR) method for KLK14 mRNA quantification using the SYBR Green® chemistry. HPRT1 was used as a reference gene and the BT20 breast cancer cell line as a calibrator. Relative quantification analysis was performed using the comparative CT method 2−ΔΔCT. KLK14 expression was detected in both types of breast tumours. However, a statistically significant increase of the KLK14 mRNA level was observed in the malignant, compared to the benign tumour samples (p<0.001), highlighting its value in discriminating these breast lesions. Elevated KLK14 expression profiles were associated with higher tumour grade (p=0.043) and size (p=0.007) in cancerous samples. Furthermore, KLK14 mRNA expression showed negative correlation in a statistically significant manner with estrogen receptor status (p=0.024). In accordance with logistic regression models (p=0.012) and receiver-operating-characteristics analysis (p<0.001), KLK14 gene expression could be evaluated as a putative independent diagnostic biomarker in breast tumour biopsies.
ADAMTS13 activity is decreased in a septic porcine model
Authors: Bockmeyer Clemens , Reuken Philipp , Simon Tim , Budde Ulrich , Lösche Wolfgang , Bauer Michael , Birschmann Ingvild , Becker Jan , Marx Gernot , Claus Ralf
Published: November 2010

During sepsis, the balance between abundantly secreted von Wille-brand factor (VWF) and the activity of its size regulating protease ADAMTS13 is assumed to be involved in coagulation abnormalities. We aimed to establish a porcine model with haemorrhagic shock with consecutive sepsis and hypothesised that a decreased ADAMTS13-activity as well as an altered VWF multimer pattern is associated with renal failure. Animals (n=21) were subjected to haemorrhagic shock. After volume replacement, intraperitoneal Escherichia coli sepsis was induced. Blood samples were drawn at baseline, after haemorrhage and sepsis induction. Directly postmortem we examined renal tissue by JONES-silver, CD61, VWF and fibrin staining for characterisation of thrombi. Renal failure was analysed by scoring PAS-stained sections for acute tubular damage. Glomerular microthrombi were observed in six of 21 septic animals. Porcine ADAMTS13 activity declined significantly during sepsis, accompanied by a drop-off in platelet count. At 12 hours after sepsis induction, ADAMTS13 activity was significantly diminished compared to sham controls, and an elevated acute tubular damage score was associated with an increased proportion of high-molecular-weight VWF multimers. Compared to baseline the proportion of high-molecular-weight VWF multimers increased significantly in septic animals. Similar to human sepsis, diminished ADAMTS13 activity was observed in a septic porcine model associated with a shift to rather thrombogenic VWF multimers and deposition of microthrombi. Therefore, this porcine model seems to be appropriate for performing functional and therapeutic studies in sepsis-associated ADAMTS13 deficiency.
Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis
Authors: Salomon Ophira , Steinberg David , Zucker Michal , Varon David , Zivelin Ariella , Seligsohn Uri
Published: November 2010

Factor XI (FXI) plays a dual role in haemostasis and thrombosis. It contributes to thrombin generation and promotes inhibition of fibrinolysis. Severe FXI deficiency was shown to confer protection against arterial and venous thrombosis in animal models without compromising haemostasis. We have previously shown that patients with severe FXI deficiency have a low incidence of ischaemic stroke, but display the usual incidence of myocardial infarction. In the present study, we compared the incidence of deep-vein thrombosis (DVT) in 219 unrelated patients with severe FXI deficiency aged 20–94 to the incidence in a large population-based study. No cases of DVT were observed in the FXI-deficient cohort, a result that is significantly lower than the expected number (4.68) computed from the population-based study. The low incidence remains statistically significant when compared to three other population-based studies. These data suggest that severe FXI deficiency provides protection against DVT.
Perturbation of Cullin Deneddylation via Conditional Csn8 Ablation Impairs the Ubiquitin–Proteasome System and Causes Cardiomyocyte Necrosis and Dilated Cardiomyopathy in Mice
Authors: Su Huabo , Li Jie , Menon Suchithra , Liu Jinbao , Kumarapeli Asangi R. , Wei Ning , Wang Xuejun
Published: November 2010

Rationale:

Ubiquitin–proteasome system (UPS) dysfunction has been implicated in cardiac pathogenesis. Understanding how cardiac UPS function is regulated will facilitate delineating the pathophysiological significance of UPS dysfunction and developing new therapeutic strategies. The COP9 (constitutive photomorphogenesis mutant 9) signalosome (CSN) may regulate the UPS, but this has not been tested in a critical vertebrate organ. Moreover, the role of CSN in a postmitotic organ and the impact of cardiomyocyte-restricted UPS dysfunction on the heart have not been reported.

Objective:

We sought to determine the role of CSN-mediated deneddylation in UPS function and postnatal cardiac development and function.

Methods and Results:

Cardiomyocyte-restricted Csn8 gene knockout (CR-Csn8KO) in mice was achieved using a Cre-LoxP system. CR-Csn8KO impaired CSN holocomplex formation and cullin deneddylation and resulted in decreases in F-box proteins. Probing with a surrogate misfolded protein revealed severe impairment of UPS function in CR-Csn8KO hearts. Consequently, CR-Csn8KO mice developed cardiac hypertrophy, which rapidly progressed to heart failure and premature death. Massive cardiomyocyte necrosis rather than apoptosis appears to be the primary cause of the heart failure. This is because (1) massive necrotic cell death and increased infiltration of leukocytes were observed before increased apoptosis; (2) increased apoptosis was not detectable until overt heart failure was observed; and (3) cardiac overexpression of Bcl2 failed to ameliorate CR-Csn8KO mouse premature death.

Conclusions:

Csn8/CSN plays an essential role in cullin deneddylation, UPS-mediated degradation of a subset of proteins, and the survival of cardiomyocytes and, therefore, is indispensable in postnatal development and function of the heart. Cardiomyocyte-restricted UPS malfunction can cause heart failure.
Modulation of Fate Determinants Olig2 and Pax6 in Resident Glia Evokes Spiking Neuroblasts in a Model of Mild Brain Ischemia
Authors: Kronenberg Golo , Gertz Karen , Cheung Giselle , Buffo Annalisa , Kettenmann Helmut , Götz Magdalena , Endres Matthias
Published: November 2010

Background and Purpose—

Although in vitro studies suggest that non-neurogenic regions of the adult central nervous system potentially contain multipotent parenchymal progenitors, neurons are clearly not replaced in most brain regions after injury. Here, in a well-established model of mild transient brain ischemia, we explored Olig2 antagonism and Pax6 overexpression as potential avenues to redirect endogenous progenitors proliferating in situ toward a neuronal fate.

Methods—

Retroviral vectors containing either Pax6 or a strong activator form of the repressor Olig2 (Olig2VP16), ie, a functionally dominant negative form of Olig2, were stereotaxically injected into the lateral striatum at 48 hours after 30 minutes middle cerebral artery occlusion (MCAo)/reperfusion.

Results—

Retroviral modulation of fate determinants resulted in a significant number of infected cells differentiating into Doublecortin (DCX)-expressing immature neurons that were not observed after injection of a control virus. Whole-cell patch-clamp recordings in acute brain slices showed that the percentage of virus-infected cells with Na
+
currents was increased by inhibition of the repressor function of Olig2 and by overexpression of Pax6. Furthermore, on retroviral transduction of fate determinants, we detected newly generated cells within the ischemic lesion that were capable of generating single action potentials and that received synaptic input.

Conclusions—

Taken together, these data show that resident glia in the striatum can be reprogrammed toward functional neuronal differentiation following brain injury.
Low Cerebral Blood Volume Is Predictive of Diffusion Restriction Only in Hyperacute Stroke
Authors: Knash Michael , Tsang Adrian , Hameed Bilal , Saini Monica , Jeerakathil Thomas , Beaulieu Christian , Emery Derek , Butcher Kenneth
Published: November 2010

Background and Purpose—

Diffusion-weighted MRI (DWI) demonstrates ischemic tissue with high sensitivity. Although low cerebral blood volume (CBV) is also used as a marker for infarction, the quantitative relationship between diffusion abnormalities and CBV is unknown. We tested the hypothesis that CBV would decrease proportionally to the apparent diffusion coefficient in patients with acute stroke and thus could be used as a surrogate parameter for diffusion restriction.

Methods—

Perfusion-weighted imaging and DWI was performed in 54 patients within 28 hours of symptom onset. Mean apparent diffusion coefficient, cerebral blood flow, and CBV were measured within DWI lesions and contralateral regions.

Results—

Within DWI lesions, CBV (3.3±1.9 mL/100 g) was significantly decreased relative to contralateral regions (4.1±2.1 mL/100 g,
P
<0.001). Relative CBV was not decreased in patients with evidence of early reperfusion (1.2±0.5) or mild stroke (National Institutes of Health Stroke Scale <4, 1.1±0.6). Linear regression indicated that relative CBV was predictive of relative apparent diffusion coefficient only in patients imaged within 9 hours of symptom onset (
R
=0.50,
P
=0.02). Ischemic tissue volumes generated using a CBV threshold of the 50th percentile of normal tissue were correlated with DWI lesion volumes (
R
=0.73,
P
<0.001). The mean difference between the CBV threshold of the 50th percentile of normal tissue and DWI lesion volumes was 6.3 mL (95% limits of agreement, 0.1 to 12.6 mL).

Conclusions—

Decreases in relative CBV are predictive of diffusion abnormalities in ischemic stroke. The pattern of CBV changes varies with clinical severity and symptom duration. Ischemic tissue volumes comparable to DWI lesions can be generated using CBV thresholds, but the use of this method is limited in patients with minor stroke.
Urban Insurgency, 'Drug War' and International Humanitarian Law: The Case of Rio de Janeiro
Authors: Peterke Sven
Published: November 2010

In Rio de Janeiro so-called drug factions hold control over most of the shanty towns. The State has reacted by 'militarising' its police operations. The result is a humanitarian tragedy that has already cost the lives of thousands of Brazilian citizens. Many of those affected by the violence are of the opinion that the city has become the battlefield of a 'war'. This article addresses the issue of whether the legal concept of armed conflict could and should be applied to such situations.
Austral Spring Stratospheric and Tropospheric Circulation Interannual Variability
Authors: Agosta Eduardo Andrés , Canziani Pablo Osvaldo
Published: November 2010

The relationship between the October (spring) total ozone column (TOC) midlatitude zonal asymmetry over the Southern Hemisphere (SH) and the stratospheric quasi-stationary wave 1 (QSW1) interannual phase variability is analyzed. Once contributions to the TOC from known global predictors, estimated with a multiregression model, are removed, the residual TOC interannual variability is observed to be dynamically coupled to the stratospheric QSW1 phase behavior. The stratospheric QSW1 interannual phase variability, when classified according to specifically designed indices, yields different circulation patterns in the troposphere and stratosphere. High (upper quartile) index values correspond to a westward rotation of the midlatitude ozone trough and the stratospheric QSW1 phase, while low (lower quartile) index values represent their eastward-rotated state. These values can be associated with statistically different tropospheric circulation patterns: a predominantly single poleward tropospheric jet structure for high index values and a predominantly double-jet structure for low index values. For the latter, there is a higher daily probability of double-jet occurrence in the troposphere and a stronger stratospheric jet. These jet structures and their daily behavior are supported by significant synoptic-scale activity anomalies over SH mid- to high latitudes as well as changes in tropospheric quasi-stationary waves 1–3. The wave activity flux (W flux) diagnosis shows the contribution of active quasi-stationary waves in the observed tropospheric anomalies associated with high and low index values. With low index values, the quasi-stationary waves lead to a self-sustaining state of the stratospheric–tropospheric coupled system. With high index values, the overall mid- to high latitude circulation is associated with wave energy propagation from the tropical central Pacific into higher latitudes. Thus, during the austral spring, there are interactions between the troposphere and stratosphere, leading to the locally well-defined upward and downward propagation of wave anomalies, that is, significant upper troposphere (UT)–lower stratosphere (LS) interactions can occur within a spring month itself.