bluuebunny/crossref_metadata_2025 huggingface dataset:
2,3‐Dihydro‐1,2‐Diphenyl‐substituted 4H‐Pyridinone Derivatives as New Anti Flaviviridae Inhibitors
Authors: Peduto Antonella , Massa Antonio , Di Mola Antonia , de Caprariis Paolo , La Colla Paolo , Loddo Roberta , Altamura Sergio , Maga Giovanni , Filosa Rosanna
Published: March 2011

With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3‐dihydro‐4H‐pyridinone derivatives has been prepared and evaluated for antiviral activity. Compounds were evaluated in vitro in cell‐based assays for cytotoxicity and against a wide spectrum of viruses. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. The Pestiviruses (bovine viral diarrhoea virus) were inhibited by 4acis (CC50 > 100 μm; EC50 = 14 μm), compounds 4ccis and 6a showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC50 > 100 μm; EC50 = 18 μm, CC50 > 100 μm; EC50 = 10 μm). Among these, compound 6a displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC50 > 100 μm; EC50(1b) = 4 μm]. In vitro inhibitory activity against the HCV RNA‐dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound 6a can be selected as promising tool in novel anti‐flaviviruses development.
Antitubercular Activity of New Coumarins
Authors: Cardoso Silvia H. , Barreto Milena B. , Lourenço Maria C. S. , Henriques Maria das Graças M. de O. , Candéa André L. P. , Kaiser Carlos R. , de Souza Marcus V. N.
Published: March 2011

The present article describes a series of 21 N ′‐benzylidene‐2‐oxo‐2H‐chromene‐3‐carbohydrazides 4a–4v, which were synthesized and evaluated for their cell viabilities in non‐infected and Mycobacterium bovis Bacillus Calmette–Guerin‐infected macrophages. Subsequently, the non‐cytotoxic compounds 4c, 4g, 4h, 4j, 4l and 4t were assessed against Mycobacterium tuberculosis ATCC 27294 using the microplate Alamar Blue assay and the activity expressed as the minimum inhibitory concentration in μg/mL. These compounds exhibited a significant activity (50–100 μg/mL) when compared to the first‐line drugs, such as pyrazinamide (PZA >100 μg/mL). These results could be considered a good starting point for further studies to develop new lead compounds to treat multidrug‐resistant tuberculosis.
Blood Pressure Monitoring in the Assessment of Old Patients with Acute Stroke
Authors: Weiss Avraham , Beloosesky Yichayaou , Majadla Riad , Grossman Ehud
Published: March 2011

Background

Most patients have elevated blood pressure in the early phase of acute stroke that it often returns to normal within approximately seven-days. Most available data on the pattern of blood pressure in acute stroke are based on manual blood pressure measurements.

Aims

The aims of the present study were to assess with 24 h blood pressure monitoring the pattern of blood pressure in acute stroke, and the change in blood pressure during the first week of event in very old patients.

Methods

We studied 99 patients with acute stroke (58 males), mean age 83 ± 6 years (range 70–97). Casual blood pressure and 24 h blood pressure monitoring were recorded within 24 h of admission, and then after six- to seven-days.

Results

Casual blood pressure before beginning the 24 h blood pressure monitoring was 154 ± 23/80 ± 15 mmHg and the average 24 h blood pressure was 147 ± 20/74 ± 11 mmHg. One-week after stroke, casual blood pressure decreased by 15/7 mmHg, whereas 24 h blood pressure decreased by only 7/2 mmHg ( P<0·01). Blood pressure decreased remarkably only in those with admission elevated systolic blood pressure. The change in 24 h systolic blood pressure after one-week correlated to the 24 h admission systolic blood pressure ( R=0·47; P<0·01).

Conclusions

Casual blood pressure may overestimate blood pressure in stroke patients. Very old patients with stroke exhibit a mild increase in blood pressure during the acute phase, and blood pressure decreases spontaneously only in those with elevated blood pressure levels. Use of 24 h blood pressure monitoring may be helpful in elderly patients with acute stroke.
Total mercury in stranded marine mammals from the Oregon and southern Washington coasts
Authors: Wintle Nathan J. P. , Duffield Deborah A. , Barros (Deceased) Nélio B. , Jones Ronald D. , Rice James M.
Published: March 2011

Abstract

Muscle samples from 105 marine mammals stranded along the Oregon and Washington coasts (2002–2009) were tested for levels of total mercury (THg) by Cold Vapor Atomic Fluorescence Spectrometry. The THg present is in the form of the highly toxic methylmercury. After normalizing tissue to 75% water weight, Steller sea lions and northern elephant seals exhibited the highest mean concentrations of THg followed by harbor seals, harbor porpoises, and California sea lions, 0.34 ± 0.278, 0.34 ± 0.485, 0.21 ± 0.216, 0.17 ± 0.169, and 0.15 ± 0.126 mg/kg normalized wet weight (ww), respectively. The mean normalized values demonstrate limited muscle methylmercury accumulation in these species in the Pacific Northwest. However, actual ww concentrations in some of the stranded carcasses may pose a risk to scavengers. Normalizing muscle mercury concentrations eliminated the variability from desiccation, and allowed for a clearer indication of the amount of mercury the animal accumulated before stranding.
Excited‐State Double Proton Transfer of 7‐Azaindole Dimers in a Low‐Temperature Organic Glass
Authors: Lim Hyeongtaek , Park Sun‐Young , Jang Du‐Jeon
Published: March 2011

The excited‐state double proton transfer of model DNA base pairs, 7‐azaindole (7AI) dimers, is explored in a low‐temperature organic glass of n‐dodecane using picosecond time‐resolved fluorescence spectroscopy. Reaction mechanisms are found to depend on the conformations of 7AI dimers at the moment of excitation; whereas planar conformers tautomerize rapidly (<10 ps), twisted conformers undergo double proton transfer to form tautomeric dimers on the time scale of 250 ps at 8 K. The proton transfer is found to consist of two orthogonal steps: precursor‐configurational optimization and intrinsic proton transfer via tunneling. The rate is almost isotope independent at cryogenic temperatures because configurational optimization is the rate‐determining step of the overall proton transfer. This optimization is assisted by lattice vibrations below 150 K or by librational motions above 150 K.
Thermogravimetric Analysis of Photodegraded Acrylic Coated Lime Wood
Authors: Popescu Carmen‐Mihaela , Tibirna Carmen Mihaela , Vasile Cornelia
Published: March 2011

A series of experiments were carried out to investigate the photodegradation of lime wood (Tilia cordata Mill.) coated with acrylic copolymer during artificial UV/Vis light irradiation for 600 h. Photodegradation of the Paraloid B72 films and Paraloid B72 treated lime wood samples was evaluated by thermogravimetry throughout the irradiation period of 100 h. The results obtained indicate a shifting of the DTG maxima to lower temperatures, which may be related to a decrease in the stability of the copolymer and wood during photodegradation. The decrease of weight loss with increasing time of exposure was observed, while the global kinetic parameters for the main peak increases when increasing exposure time of wood to the UV light. Even when the surface of the wood was covered with a thin layer of acrylic resin, some photodegradation reactions of the wood surface occurred. The modifications in the wood structure may be influenced by the newly formed structures from acrylic resin photodegradation.
Processes Versus Representations: Cognitive Control as Emergent, Yet Componential
Authors: Davelaar Eddy J.
Published: March 2011

In this commentary, I focus on the difference between processes and representations and how this distinction relates to the question of what is controlled. Despite some views that task switching is a prototypical control process, the analysis concludes that task switching depends on the task goal representation and that control processes are there to prevent goal representations from disintegrating. Over time, these processes become obsolete, leaving behind a representation that automatically controls task performance. The distinction between processes and representations relates to practice effects and automaticity and sheds light on what is meant by the phrase “automatic control.”
Fundamental Fraction Knowledge of Preservice Elementary Teachers: A Cross‐National Study in the United States and Taiwan
Authors: Luo Fenqjen , Lo Jane‐Jane , Leu Yuh‐Chyn
Published: March 2011

The purpose of this paper is to show the similarities as well as the differences of fundamental fraction knowledge owned by preservice elementary teachers from the United States (N= 89) and Taiwan (N= 85). To this end, we examined and compared their performance on an instrument including 15 multiple‐choice test items. The items were categorized into four different types of fundamental fraction constructs, including part–whole relationship, quotient, equivalence, and meanings of operations. Each item was embedded in the area, linear, or set model except for the items constructed out of the meaning of operations. Several items were featured with a pictorial illustration. Quantitative analysis showed that U.S. preservice teachers were significantly outperformed by their Taiwanese counterparts overall. The difference between the two groups was statistically significant on 12 of 15 items. Findings suggest that preservice elementary teachers from both countries need to be better prepared in their understanding of the meaning of fraction multiplication or division operations. Findings also suggest that U.S. preservice elementary teachers need to be more knowledgeable in dealing with fraction problems embedded in a linear model. Further research is suggested to study the issues raised from the findings.
CFD Prediction of Partload CO Emissions Using a Two-Timescale Combustion Model
Authors: Wegner Bernhard , Gruschka Uwe , Krebs Werner , Egorov Y. , Forkel H. , Ferreira J. , Aschmoneit Kai
Published: March 2011

Today’s and future electric power generation is characterized by a large diversification using all kind of sources, including renewables resulting in noncoherent fluctuations of power supply and power usage. In this context, gas turbines offer a high operational flexibility and a good turn down ratio. In order to guide the design and down select promising solutions for improving partload emissions, a new combustion model based on the assumption of two separate timescales for the fast premixed flame stabilization and the slow post flame burnout zone is developed within the commercial computational fluid dynamics (CFD) code ANSYS CFX. This model enables the prediction of CO emissions generally limiting the turn down ratio of gas turbines equipped with modern low NOx combustion systems. The model is explained and validated at lab scale conditions. Finally, the application of the model for a full scale analysis of a gas turbine combustion system is demonstrated.
Determining a Surrogate Contact Pair in a Hertzian Contact Problem
Authors: Sanders Anthony P. , Brannon Rebecca M.
Published: March 2011

Laboratory testing of contact phenomena can be prohibitively expensive if the interacting bodies are geometrically complicated. This work demonstrates means to mitigate such problems by exploiting the established observation that two geometrically dissimilar contact pairs may exhibit the same contact mechanics. Specific formulas are derived that allow a complicated Hertzian contact pair to be replaced with an inexpensively manufactured and more easily fixtured surrogate pair, consisting of a plane and a spheroid, which has the same (to second-order accuracy) contact area and pressure distribution as the original complicated geometry. This observation is elucidated by using direct tensor notation to review a key assertion in Hertzian theory; namely, geometrically complicated contacting surfaces can be described to second-order accuracy as contacting ellipsoids. The surrogate spheroid geometry is found via spectral decomposition of the original pair’s combined Hessian tensor. Some numerical examples using free-form surfaces illustrate the theory, and a laboratory test validates the theory under a common scenario of normally compressed convex surfaces. This theory for a Hertzian contact substitution may be useful in simplifying the contact, wear, or impact testing of complicated components or of their constituent materials.
Microwave absorption properties of Mn- and Ni-doped zinc oxides
Authors: Wu Qi-Bai , Zhao Wei , Zeng Guo-Xun , Zhang Hai-Yan , Wei Ai-Xiang , Wang Jia
Published: March 2011

Microwave absorption properties of Mn- and Ni-doped zinc oxides were assessed in this study. Samples were prepared by the decomposition of acetate solid solutions. By changing the concentration of dopant ions in the reaction solutions, zinc oxides with different amounts of dopant were obtained. The morphologies, chemical compositions, and structures of the samples were investigated by scanning electron microscopy, energy dispersive x-ray spectroscopy, and x-ray powder diffraction. Electromagnetic characteristics of the doped samples were assessed by vector network analysis at a frequency range of 2–16 GHz. Both the real and imaginary parts of the complex permittivity decreased as Mn or Ni concentration increased. Results indicate that, compared with pure ZnO, Mn- and Ni-doped zinc oxides exhibit excellent microwave absorption properties. The highest level of microwave absorption observed was 80.7 dB at a frequency of 9.8 GHz, and the best frequency bandwidth was 8.6 GHz at reflection loss values below −10 dB.
Comment on “Does the Hydrated Electron Occupy a Cavity?”
Authors: Turi László , Madarász Ádám
Published: March 2011

Larsen
et al
. (Reports, 2 July 2010, p. 65) challenged the long-standing model of the solvent geometry surrounding a free electron in water using molecular dynamics simulations based on a newly derived electron-water pseudopotential. We illustrate that, in contrast to the model they used, the true electron-water interaction is repulsive in the region relevant to the reported extended electron distribution, consistent with the cavity model.
Response to Comments on “Does the Hydrated Electron Occupy a Cavity?”
Authors: Larsen Ross E. , Glover William J. , Schwartz Benjamin J.
Published: March 2011

Turi and Madarász and Jacobson and Herbert argue that the pseudopotential we derived for the hydrated electron contains inaccuracies that make it overly attractive. We show that our potential is derived correctly and argue that the criticisms presented are not relevant when evaluating a pseudopotential’s accuracy for condensed-phase simulation. Neither critique addresses our central result that the experimental properties of the hydrated electron are consistent with a noncavity picture.
Direct Observation of Continuous Electric Dipole Rotation in Flux-Closure Domains in Ferroelectric Pb(Zr,Ti)O
3
Authors: Jia Chun-Lin , Urban Knut W. , Alexe Marin , Hesse Dietrich , Vrejoiu Ionela
Published: March 2011

Domains can be stabilized in a thin ferroelectric material through the continuous rotation of the dipoles.
Independent and Parallel Recruitment of Preexisting Mechanisms Underlying C
4
Photosynthesis
Authors: Brown Naomi J. , Newell Christine A. , Stanley Susan , Chen Jit E. , Perrin Abigail J. , Kajala Kaisa , Hibberd Julian M.
Published: March 2011

Recurrent evolution of C
4
photosynthesis is due to conserved regulatory sequences that localize photosynthetic enzymes.
Precipitation Climatology on Titan
Authors: Tokano Tetsuya
Published: March 2011

Recent equatorial rainfall on Titan reveals the global-scale seasonal migration of its intertropical convergence zone.
A CRY to Rise
Authors: Hee Im Seol , Taghert Paul H.
Published: March 2011

Light-sensing CRYPTOCHROME activates the firing of neurons involved in circadian rhythms.
Waves of Destruction
Authors: Normile Dennis
Published: March 2011

Most deaths and much of the destruction from last week's powerful earthquake in Japan were the handiwork of the tsunami: Many victims knew the waves were coming but could not escape or didn't try until it was too late.
Cold Almost-Stars May Herald Hordes of Unseen Lurkers
Authors: Bhattacharjee Yudhijit
Published: March 2011

Astrophysicists have discovered the coldest brown dwarfs ever seen, one with a temperature of 300 kelvin and the other 370 K, they report this week.
Quantum Mechanics Braces for the Ultimate Test
Authors: Merali Zeeya
Published: March 2011

Most accept that the quantum world is a bizarre place, but this has yet to be proved beyond all doubt. Quantum cryptography is now providing the incentive for reality's toughest test.
Embracing Invasives
Authors: Vince Gaia
Published: March 2011

The Galápagos, one of biodiversity's hot spots, has become a test case for a controversial approach to ecosystem management.
The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines
Authors: Thiem Vu Dinh , Lin Feng-Ying C. , Canh Do Gia , Son Nguyen Hong , Anh Dang Duc , Mao Nguyen Duc , Chu Chiayung , Hunt Steven W. , Robbins John B. , Schneerson Rachel , Szu Shousun C.
Published: March 2011

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) ofSalmonella entericaserovar Typhi (Vi) bound to recombinant exoprotein A ofPseudomonas aeruginosa(Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA orHaemophilus influenzaetype b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.
A Peptide-BasedPlasmodium falciparumCircumsporozoite Assay To Test for Serum Antibody Responses to Pre-Erythrocyte Malaria Vaccines
Authors: Kostense Stefan , Mommaas Bregje , Hendriks Jenny , Verhoeven Mariëlle , ter Haak Mariska , Tirion Felicia , Wiesken Edison , Pau Maria Grazia , Radošević Katarina , Goudsmit Jaap
Published: March 2011

Various pre-erythrocyte malaria vaccines are currently in clinical development, and among these is the adenovirus serotype 35-based circumsporozoite (CS) vaccine produced on PER.C6 cells. Although the immunological correlate of protection against malaria remains to be established, the CS antibody titer is a good marker for evaluation of candidate vaccines. Here we describe the validation of an anti-Plasmodium falciparumcircumsporozoite antibody enzyme-linked immunosorbent assay (ELISA) based on the binding of antibodies to a peptide antigen mimicking the CS repeat region. The interassay variability was determined to be below a coefficient of variation (CV) of 15%, and sensitivity was sufficient to detect low antibody titers in subjects from endemic regions. Antibody titers were in agreement with total antibody responses to the whole CS protein. Due to its simplicity and high performance, the ELISA is an easy and rapid method for assessment of pre-erythrocyte malaria vaccines based on CS.
Identification and Characterization of a Novel, 37-Kilodalton Leishmania donovani Antigen for Diagnosis of Indian Visceral Leishmaniasis
Authors: Kumar Subodh , Kumar Dinesh , Chakravarty Jaya , Sundar Shyam
Published: March 2011

The biggest challenge in the serological diagnosis of visceral leishmaniasis (VL) is to find a biomarker with a high specificity. This study was undertaken to identify novelLeishmania donovaniantigens to solve the existing problem. The solubleL. donovanipromastigote antigen was separated by SDS-PAGE, and a Western blot was probed with pooled sera of five subjects with confirmed VL before (n= 9 pools) and after (n= 9 pools) treatment and at the 6-month follow-up visit (n= 9 pools), healthy controls not from an area of endemicity (n= 9 pools), and healthy controls from an area of endemicity. The antibody response to the identified partially purified antigen was ascertained by an enzyme-linked immunosorbent assay (ELISA) with 70 sera from patients with parasitologically confirmed VL, 48 sera from healthy controls from an area where the disease is not endemic, 60 sera from healthy controls from an area of endemicity, and 42 sera from patients in different disease groups. The eluted protein was subjected to two-dimensional (2D) gel electrophoresis, Western blotted, and probed with sera from patients with confirmed VL and from healthy controls not from an area of endemicity. The antigenic protein was further characterized by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. The identified protein (BHUP2) corresponds to a cytochromec-like synthesis protein of 37 kDa. ELISA results were 94% sensitive, whereas specificities with sera from healthy controls from an area of endemicity, healthy controls not from an area of endemicity, and disease controls were 98%, 100%, and 97%, respectively. The antigen identified via a proteomics-based approach has a strong potential for further development as a diagnostic tool for VL.
Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolates in Korea
Authors: Kim Eu Suk , Lee Hye Jin , Chung Gyung-Tae , Lee Yeong-Seon , Shin Dong-Hyeon , Jung Sook-In , Song Kyoung-Ho , Park Wan-Beom , Kim Nam Joong , Park Kyoung Un , Kim Eui-Chong , Oh Myoung-don , Kim Hong Bin
Published: March 2011

We used several molecular typing methods to analyze 196 methicillin-resistant
Staphylococcus aureus
(MRSA) and 139 methicillin-susceptible
S. aureus
(MSSA) isolates collected between 1996 and 2005. The sequence type 72 MRSA has increased in frequency in the community in the Republic of Korea and in hospitals in recent years.
Methicillin-Resistant Staphylococcus aureus in Northeastern Scotland in 2003 to 2007: Evolving Strain Distribution and Resistance Patterns
Authors: Hunt A. C. , Edwards B. , Girvan E. K. , Cosgrove B. , Edwards G. F. S. , Gould I. M.
Published: March 2011

This study explored strain distribution and resistance patterns of methicillin-resistant
Staphylococcus aureus
(MRSA) over a 5-year period in northeastern Scotland. We noted a shift in the relative rates of epidemic strains and an increase in community-associated strains. Use of oral antibiotics to eradicate throat carriage may have contributed to trimethoprim resistance, which was observed to increase 10-fold.
Comparison of the Luminex xTAG Respiratory Viral Panel with xTAG Respiratory Viral Panel Fast for Diagnosis of Respiratory Virus Infections
Authors: Pabbaraju Kanti , Wong Sallene , Tokaryk Kara L. , Fonseca Kevin , Drews Steven J.
Published: March 2011

Nucleic acid tests are sensitive and specific and provide a rapid diagnosis, making them invaluable for patient and outbreak management. Multiplex PCR assays have additional advantages in providing an economical and comprehensive panel for many common respiratory viruses. Previous reports have shown the utility of the xTAG respiratory viral panel (RVP) assay manufactured by Luminex Molecular Diagnostics for this purpose. A newer generation of this kit, released in Canada in early 2010, is designed to simplify the procedure and reduce the turnaround time by about 24 h. The assay methodology and targets included in this version of the kit are different; consequently, the objective of this study was to compare the detection of a panel of respiratory viral targets using the older Luminex xTAG RVP (RVP Classic) assay with that using the newer xTAG RVP Fast assay. This study included 334 respiratory specimens that had been characterized for a variety of respiratory viral targets; all samples were tested by both versions of the RVP assay in parallel. Overall, the RVP Classic assay was more sensitive than the RVP Fast assay (88.6% and 77.5% sensitivities, respectively) for all the viral targets combined. Targets not detected by the RVP Fast assay included primarily influenza B virus, parainfluenza virus type 2, and human coronavirus 229E. A small number of samples positive for influenza A virus, respiratory syncytial virus B, human metapneumovirus, and parainfluenza virus type 1 were not detected by the RVP Classic assay and in general had low viral loads.
Modified Multiple-Locus Variable-Number Tandem-Repeat Analysis for Rapid Identification and Typing of Clostridium difficile during Institutional Outbreaks
Authors: Broukhanski George , Low Donald E. , Pillai Dylan R.
Published: March 2011

A modified multiple-locus variable-number tandem-repeat analysis (MMLVA) method was validated on
Clostridium difficile
-infected stool specimens from institutional outbreaks. The method allows simultaneous detection of toxin genes, deletions, and tandem repeats from cultured isolates or stool specimens. Results were used to aid institutional outbreak investigation by identifying clusters of NAP1/027.
Myocarditis Caused by Human Parainfluenza Virus in an Immunocompetent Child Initially Associated with 2009 Influenza A (H1N1) Virus
Authors: Romero-Gómez María P. , Guereta Luis , Pareja-Grande Julia , Martínez-Alarcón José , Casas Inmaculada , Ruiz-Carrascoso Guillermo , de Ory Fernando , Pozo Francisco
Published: March 2011

The association between respiratory viruses and myocarditis has hardly ever been described. We report a case of acute myocarditis in an immunocompetent child associated with the presence of parainfluenza virus type 3 infection, in a context of recent influenza illness, confirmed by molecular and serological studies.
Human Immunodeficiency Virus Type 1 Infection Is Associated with Increased NK Cell Polyfunctionality and Higher Levels of KIR3DL1+NK Cells in Ugandans Carrying the HLA-B Bw4 Motif
Authors: Eller Michael A. , Koehler Rebecca N. , Kijak Gustavo H. , Eller Leigh Anne , Guwatudde David , Marovich Mary A. , Michael Nelson L. , de Souza Mark S. , Wabwire-Mangen Fred , Robb Merlin L. , Currier Jeffrey R. , Sandberg Johan K.
Published: March 2011

Natural killer (NK) cells are important innate effector cells controlled by an array of activating and inhibitory receptors. Some alleles of the inhibitory killer-cell immunoglobulin-like receptor KIR3DL1 in combination with its HLA class I ligand Bw4 have been genetically associated with slower HIV-1 disease progression. Here, we observed that the presence of HLA-B Bw4 was associated with elevated frequencies of KIR3DL1+CD56dimNK cells in chronically HIV-1-infected individuals from the rural district of Kayunga, Uganda. In contrast, levels of KIR2DL1+CD56dimNK cells were decreased, and levels of KIR2DL3+CD56dimNK cells were unchanged in infected subjects carrying their respective HLA-C ligands. Furthermore, the size of the KIR3DL1+NK cell subset correlated directly with viral load, and this effect occurred only in HLA-B Bw4+patients, suggesting that these cells expand in response to viral replication but may have relatively poor antiviral capacity. In contrast, no association with viral load was present for KIR2DL1+and KIR2DL3+NK cells. Interestingly, chronic HIV-1 infection was associated with an increased polyfunctional response in the NK cell compartment, and, upon further investigation, KIR3DL1+CD56dimNK cells exhibited a significantly increased functional response in the patients carrying HLA-B Bw4. These results indicate that chronic HIV-1 infection is associated with increased NK cell polyfunctionality and elevated levels of KIR3DL1+NK cells in Ugandans carrying the HLA-B Bw4 motif.
Immune Evasion of Porcine Reproductive and Respiratory Syndrome Virus through Glycan Shielding Involves both Glycoprotein 5 as Well as Glycoprotein 3
Authors: Vu Hiep L. X. , Kwon Byungjoon , Yoon Kyoung-Jin , Laegreid William W. , Pattnaik Asit K. , Osorio Fernando A.
Published: March 2011

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response
in vivo
. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, in two of its envelope glycoproteins, one in GP3 (position 131) and the other in GP5 (position 51). To determine the influence of these missing N-glycosylation sites on the distinct neutralization phenotype of PRRSV-01, a chimeric virus (FL01) was generated by replacing the structural genes of type II PRRSV strain FL12 cDNA infectious clone with those from PRRSV-01. N-glycosylation sites were reintroduced into GP3 and GP5 of FL01, separately or in combination, by site-directed mutagenesis. Reintroduction of the N-glycosylation site in either GP3 or GP5 allowed recovery of
in vivo
and
in vitro
glycan shielding capacity, with an additive effect when these sites were reintroduced into both glycoproteins simultaneously. Although the loss of these glycosylation sites has seemingly occurred naturally (presumably by passage through cell cultures), PRRSV-01 virus quickly regains these glycosylation sites through replication
in vivo
, suggesting that a strong selective pressure is exerted at these sites. Collectively, our data demonstrate the involvement of an N-glycan moiety located in GP3 in glycan shield interference.
Identification of a Novel Apoptosis Suppressor Gene from the Baculovirus Lymantria dispar Multicapsid Nucleopolyhedrovirus
Authors: Yamada Hayato , Shibuya Miyuki , Kobayashi Michihiro , Ikeda Motoko
Published: March 2011

Ld652Y cells from
Lymantria dispar
readily undergo apoptosis upon infection with a variety of nucleopolyhedroviruses (NPVs), while
L. dispar
multicapsid NPV (LdMNPV) infection of Ld652Y cells results in the production of a high titer of progeny viruses. Here, we identify a novel LdMNPV apoptosis suppressor gene,
apsup
, which functions to suppress apoptosis induced in Ld652Y cells by infection with vAcΔp35, a
p35
-defective recombinant
Autographa californica
MNPV.
apsup
also suppresses apoptosis of Ld652Y cells induced by actinomycin D and UV exposure. Apsup is expressed in LdMNPV-infected Ld652Y cells late in infection, and RNA interference-mediated
apsup
ablation induces apoptosis of LdMNPV-infected Ld652Y cells.
The Mouse Cytomegalovirus Glycoprotein m155 Inhibits CD40 Expression and Restricts CD4 T Cell Responses
Authors: Loewendorf Andrea I. , Steinbrueck Lars , Peter Christoph , Busche Andreas , Benedict Chris A. , Kay-Jackson Penelope C.
Published: March 2011

Cytomegaloviruses (CMV) utilize a variety of immunomodulatory strategies to facilitate the establishment of lifelong persistence in their infected hosts. We show that the mouse CMV (MCMV) m155 open reading frame (ORF) is required for the posttranscriptional inhibition of CD40 expression in infected antigen-presenting cells. Consistent with the known importance of CD40-mediated costimulation of T cells, a m155-deficient virus induces enhanced MCMV epitope-specific CD4 T cell responses.
Activities of ICP0 Involved in the Reversal of Silencing of Quiescent Herpes Simplex Virus 1
Authors: Ferenczy Michael W. , Ranayhossaini Daniel J. , DeLuca Neal A.
Published: March 2011

ICP0 is a transcriptional activating protein required for the efficient replication and reactivation of latent herpes simplex virus 1 (HSV-1). Multiple regions of ICP0 contribute its activity, the most prominent of which appears to be the RING finger, which confers E3 ubiquitin ligase activity. A region in the C terminus of ICP0 has also been implicated in several activities, including the disruption of a cellular repressor complex, REST/CoREST/HDAC1/2/LSD1. We used quiescent infection of MRC-5 cells with a virus that does not express immediate-early proteins, followed by superinfection with various viral mutants to quantify the ability of ICP0 variants to reactivate gene expression and alter chromatin structure. Superinfection with wild-type virus resulted in a 400-fold increase in expression from the previously quiescent d109 genome, the removal of heterochromatin and histones from the viral genome, and an increase in histone marks associated with activated transcription. RING finger mutants were unable to reactivate transcription or remove heterochromatin from d109, while mutants that are unable to bind CoREST activate gene expression from quiescent d109, albeit to a lesser degree than the wild-type virus. One such mutant, R8507, resulted in the partial removal of heterochromatin. Infection with R8507 did not result in the hyperacetylation of H3 and H4. The results demonstrate that (i) consistent with previous findings, the RING finger domain of ICP0 is required for the activation of quiescent genomes, (ii) the RF domain is also crucial for the ultimate removal of repressive chromatin, (iii) activities or interactions specified by the carboxy-terminal region of ICP0 significantly contribute to activation, and (iv) while the effects of the R8507 on chromatin are consistent with a role for REST/CoREST/HDAC1/2/LSD1 in the repression of quiescent genomes, the mutation may also affect other activities involved in derepression.
A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses
Authors: Wu Kailang , Chen Lang , Peng Guiqing , Zhou Wenbo , Pennell Christopher A. , Mansky Louis M. , Geraghty Robert J. , Li Fang
Published: March 2011

How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.
A Role for the Small GTPase Rab6 in Assembly of Human Cytomegalovirus
Authors: Indran Sabarish V. , Britt William J.
Published: March 2011

In human-cytomegalovirus (HCMV)-infected cells, the localization of the viral protein pp150 to the virus assembly compartment (AC) is dependent on its direct interaction with the cellular protein Bicaudal D1 through a dynein- and microtubule-dependent mechanism. We found that the small GTPase Rab6 also interacts indirectly with pp150 through its interaction with Bicaudal D1. Inhibition of Rab6 activity in HCMV-infected cells interrupted the intracellular trafficking of pp150, significantly reducing infectious virus production without affecting the formation of the AC, arguing for an important function for this cellular GTPase in the intracellular localization of pp150 during virus assembly.
Transgenic Expression of Polyomavirus Middle T Antigen in the Mouse Prostate Gives Rise to Carcinoma
Authors: Lee Sang Hyun , Jia Shidong , Zhu Yanni , Utermark Tamara , Signoretti Sabina , Loda Massimo , Schaffhausen Brian , Roberts Thomas M.
Published: March 2011

The middle T (MT) antigen of polyomavirus has provided fundamental insights into the regulation of mammalian cell growthin vitroand important animal models for the analysis of tumor induction. The mouse mammary tumor virus (MMTV)-MT model of breast cancer has been important for probing the cellular signaling pathways in mammary tumorigenesis. MT itself has no intrinsic enzymatic activity but, rather, transforms by binding to and activating key intracellular signaling molecules, phosphatidylinositol 3-kinase (PI3-kinase) being the best studied of these. Thus, MT mimics a constitutively activated receptor tyrosine kinase (RTK). Our recent work suggests that MT signaling, like that of RTKs, is often quite dependent on cellular contextin vitro. Here, we examine contextual effects on signaling in animal models as well. In this study, we generated transgenic mice in which MT is expressed in the mouse prostate under the control of an (ARR)2-Probasin promoter. All male transgenic mice displayed mouse prostatic intraepithelial neoplasia (mPIN) in the ventral and dorsal/lateral prostate as early as 8 weeks of age. Notably, during the course of tumor development over time, invasive cancer, reactive stroma, and infiltration of inflammatory cells were seen. Transcriptional profiling analyses show regulation of multiple pathways, with marked upregulation of both the NF-κB and inflammatory pathways. Comparison of expression profiles of our MT prostate model with those from an MMTV-MT breast model (23) shows both tissue-specific and tissue-independent MT effects. The signature of genes regulated by MT in a tissue-independent manner may have prognostic value.
Optimum
Authors: Mraidha Chokri , Tucci-Piergiovanni Sara , Gerard Sebastien
Published: March 2011

The construction of a design model is a critical phase in RTS development as the choices made have a direct impact on timing aspects. In traditional model-based approaches, the design relies largely on the designer experience. Once the design model is constructed, a convenient schedulability test has to be found in order to ensure that the design allows the respect of the timing constraints. This late analysis does not guarantee the existence of a test for the given design and does not allow early detection of unfeasible designs. In order to enhance reliability of RTS, this paper proposes a two step methodology for schedulability-aware real-time software design models construction. Having a high-level functional model as entry, the first methodology step consists in the workload model specification. The workload model represents the system end-to-end workload of critical scenarios triggered by an external stimulus and subject to hard-real time constraints. The second step is the refinement of the workload model towards a Schedulability Analysis Model defining an appropriate and analyzable threading strategy model. The threading strategy defines the set of units of execution taken into account by the scheduler of the system and their scheduling parameters. Different threading strategies can be then evaluated from a schedulability point of view in order to guide the designer towards the choice of the most appropriate one
Embedding domain-specific modelling languages in maude specifications
Authors: Rusu Vlad
Published: March 2011

We propose an approach for embedding Domain-Specific Modelling Languages (DSML) into Maude, based on representing models and metamodels as Maude specifications, and on representing operational semantics and model transformations as computable functions/relations between such specifications. This provides us, on the one hand, with abstract definitions of essential concepts of domain-specific modelling languages: model-to-metamodel conformance, operational semantics, and (operational-semanticspreserving) model transformations; and, on the other hand, with equivalent executable definitions for those concepts, which can be directly used in Maude for formal verification purposes
Exploiting Separation of Closed-Class Categories for Arabic Tokenization and Part-of-Speech Tagging
Authors: Kulick Seth
Published: March 2011

Research on the problem of morphological disambiguation of Arabic has noted that techniques developed for lexical disambiguation in English do not easily transfer over, since the affixation present in Arabic creates a very different tag set than for English, encoding both inflectional morphology and more complex tokenization sequences. This work takes a new approach to this problem based on a distinction between the open-class and closed-class categories of tokens, which differ both in their frequencies and in their possible morphological affixations. This separation simplifies the morphological analysis problem considerably, making it possible to use a Conditional Random Field model for joint tokenization and “core” part-of-speech tagging of the open-class items, while the closed-class items are handled by regular expressions. This work is therefore situated between data-driven approaches and those that use a morphological analyzer. For the tasks of tokenization and core part-of-speech tagging, the resulting system outperforms, on the given test set, a system that incorporates a morphological analyzer. We also evaluate the effects of the differences on parser performance when the tagger output is used for parser input.
Instant anonymization
Authors: Nergiz Mehmet Ercan , Tamersoy Acar , Saygin Yucel
Published: March 2011

Anonymization-based privacy protection ensures that data cannot be traced back to individuals. Researchers working in this area have proposed a wide variety of anonymization algorithms, many of which require a considerable number of database accesses. This is a problem of efficiency, especially when the released data is subject to visualization or when the algorithm needs to be run many times to get an acceptable ratio of privacy/utility. In this paper, we present two instant anonymization algorithms for the privacy metricsk-anonymity and ℓ-diversity. Proposed algorithms minimize the number of data accesses by utilizing the summary structure already maintained by the database management system for query selectivity. Experiments on real data sets show that in most cases our algorithm produces an optimal anonymization, and it requires a single scan of data as opposed to hundreds of scans required by the state-of-the-art algorithms.
Generating sound workflow views for correct provenance analysis
Authors: Liu Ziyang , Davidson Susan B. , Chen Yi
Published: March 2011

Workflow views abstract groups of tasks in a workflow into high level composite tasks, in order to reuse subworkflows and facilitate provenance analysis. However, unless a view is carefully designed, it may not preserve the dataflow between tasks in the workflow, that is, it may not be
sound
. Unsound views can be misleading and cause incorrect provenance analysis.

This article studies the problem of efficiently identifying and correcting unsound workflow views with minimal changes, and constructing minimal sound and elucidative workflow views with a set of user-specified relevant tasks. In particular, two related problems are investigated. First, given a workflow view, we wish to split each unsound composite task into the minimal number of tasks, such that the resulting view is sound. Second, given a workflow and a set of user specified relevant tasks, we generate a sound view, such that each composite task contains at most one relevant task, and the total number of tasks is minimized. We prove that both problems are NP-hard by reduction from independent set. We then propose two local optimality conditions (weak and strong) for each problem, and design polynomial time algorithms for both problems to meet these conditions. Experiments show that our proposed algorithms are reasonably effective and efficient. The proposed techniques are useful for view analysis/construction for not only workflows, but general networks as well.
Amniotic membrane inhibits squamous metaplasia of human conjunctival epithelium
Authors: Tan Yehui , Qiu Fangfang , Qu Yang-Luowa , Li Cheng , Shao Yi , Xiao Qiguo , Liu Zuguo , Li Wei
Published: March 2011

Squamous metaplasia is a common pathological process that occurs in the ocular surface epithelium. At present, there is no effective treatment for this abnormality. In the current study, we established an ex vivo conjunctival squamous metaplasia model by culturing human conjunctival tissues at an air-liquid interface for durations of up to 12 days. We then investigated the effects of amniotic membrane (AM) on squamous metaplasia through coculture of conjunctival tissues with AM or AM extract. We found that metaplasia features such as hyperproliferation and abnormal epidermal differentiation of conjunctival epithelium could be inhibited by AM or its extract. In addition, existing squamous metaplasia of conjunctival epithelium could be reversed to a nearly normal phenotype by AM. The mechanism by which AM prevents squamous metaplasia may involve downregulation of p38 mitogen-activated protein kinase and Wnt signaling pathways, which were activated in conjunctival explants cultured with an airlift technique. In conclusion, AM can inhibit and reverse squamous metaplasia of conjunctival epithelium. This finding may shed new light on prevention and treatment of diseases that involve epithelial squamous metaplasia.