bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Detection of Nasopharyngeal Cocolonization by Multiple Pneumococcal Serotypes by Use of Latex Agglutination or Molecular Serotyping by Microarray
Authors: Turner Paul , Hinds Jason , Turner Claudia , Jankhot Auscharee , Gould Katherine , Bentley Stephen D. , Nosten François , Goldblatt David
Published: March 2011

Identification of
Streptococcus pneumoniae
in the nasopharynx is critical for an understanding of transmission, estimates of vaccine efficacy, and possible replacement disease. Conventional nasopharyngeal swab (NPS) culture and serotyping (the WHO protocol) is likely to underestimate multiple-serotype carriage. We compared the WHO protocol with methods aimed at improving cocolonization detection. One hundred twenty-five NPSs from an infant pneumococcal-carriage study, containing ≥1 serotype by WHO culture, were recultured in duplicate. A sweep of colonies from one plate culture was serotyped by latex agglutination. DNA extracted from the second plate was analyzed by
S. pneumoniae
molecular-serotyping microarray. Multiple serotypes were detected in 11.2% of the swabs by WHO culture, 43.2% by sweep serotyping, and 48.8% by microarray. Sweep and microarray were more likely to detect multiple serotypes than WHO culture (
P
< 0.0001). Cocolonization detection rates were similar between microarray and sweep, but the microarray identified the greatest number of serotypes. A common serogroup type was identified in 95.2% of swabs by all methods. WHO methodology significantly underestimates multiple-serotype carriage compared to these alternate methods. Sweep serotyping is cost-effective and field deployable but may fail to detect serotypes at low abundance, whereas microarray serotyping is more costly and technology dependent but may detect these additional minor carried serotypes.
Aptima Combo 2 Testing Detected Additional Cases of Neisseria gonorrhoeae Infection in Men and Women in Community Settings
Authors: Kapala Julius , Biers Kathy , Cox Michael , Kamionka Margaret , Sumner Jeff , Toor Ramandeep , Gilchrist Jodi , Jang Dan , Smieja Marek , Chernesky Max
Published: March 2011

Aptima Combo 2 (AC2)
Neisseria gonorrhoeae
testing of 81,405 patients who were tested by culture and 14,666 who were AC2 tested for
Chlamydia trachomatis
detected 142 extra infections and confirmed 106 culture-positive samples (the positivity rate increased from 0.13 in testing by culture to 0.26 in testing by AC2). Retrievable AC2 positive samples were confirmed (98.5%) by an alternate AGC test.
Comparison of the Xpert MTB/RIF Test with an IS
6110
-TaqMan Real-Time PCR Assay for Direct Detection of Mycobacterium tuberculosis in Respiratory and Nonrespiratory Specimens
Authors: Armand Sylvie , Vanhuls Pascale , Delcroix Guy , Courcol René , Lemaître Nadine
Published: March 2011

The sensitivities of the Xpert MTB/RIF test and an in-house IS
6110
-based real-time PCR using TaqMan probes (IS
6110
-TaqMan assay) for the detection of
Mycobacterium tuberculosis
complex (MTBC) DNA were compared by use of 117 clinical specimens (97 culture positive and 20 culture negative for MTBC) that were frozen in sediment. The 97 clinical specimens included 60 respiratory and 37 nonrespiratory specimens distributed into 36 smear-positive and 61 smear-negative specimens. Among the 97 culture-positive specimens, 4 had rifampin-resistant isolates. Both methods were highly specific and exhibited excellent sensitivity (100%) with smear-positive specimens. The sensitivity of the Xpert MTB/RIF test with the whole smear-negative specimens was more reduced than that of the IS
6110
-TaqMan assay (48
versus
69%,
P
= 0.005). Both methods exhibited similar sensitivities with smear-negative respiratory specimens, but the Xpert MTB/RIF test had lower sensitivity with smear-negative nonrespiratory specimens than the IS
6110
-TaqMan assay (37 versus 71%,
P
= 0.013). Finally, the sensitivities of the Xpert MTB/RIF test and the IS
6110
-TaqMan assay were 79% and 84%, respectively, with respiratory specimens and 53% and 78%, respectively (
P
= 0.013), with nonrespiratory specimens. The Xpert MTB/RIF test correctly detected the rifampin resistance in smear-positive specimens but not in the one smear-negative specimen. The Xpert MTB/RIF test is a simple rapid method well adapted to a routine laboratory that appeared to be as sensitive as the IS
6110
-TaqMan assay with respiratory specimens but less sensitive with paucibacillary specimens, such as smear-negative nonrespiratory specimens.
Herpes Simplex Virus Glycoproteins gB and gD Function in a Redundant Fashion To Promote Secondary Envelopment
Authors: Johnson David C. , Wisner Todd W. , Wright Catherine C.
Published: March 2011

Egress of herpes simplex virus (HSV) and other herpesviruses from cells involves extensive modification of cellular membranes and sequential envelopment and deenvelopment steps. HSV glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Capsids in the nucleus undergo primary envelopment at the inner nuclear membrane (INM), and then enveloped virus particles undergo deenvelopment by fusing with the outer nuclear membrane (ONM). Capsids delivered into the cytoplasm then undergo secondary envelopment, involving
trans
-Golgi network (TGN) membranes. The deenvelopment step involves HSV glycoproteins gB and gH/gL acting in a redundant fashion. This fusion has features common to the fusion that occurs between the virion envelope and cellular membranes when HSV enters cells, a process requiring gB, gD, and gH/gL. Whether HSV gD also participates (in a redundant fashion with gB or gH/gL) in deenvelopment has not been characterized. Secondary envelopment in the cytoplasm is known to involve HSV gD and gE/gI, also acting in a redundant fashion. Whether gB might also contribute to secondary envelopment, collaborating with gD and gE/gI, is also not clear. To address these questions, we constructed an HSV double mutant lacking gB and gD. The HSV gB
−
/gD
−
mutant exhibited no substantial defects in nuclear egress. In contrast, secondary envelopment was markedly reduced, and there were numerous unenveloped capsids that accumulated in the cytoplasm, as well as increased numbers of partially enveloped capsids and morphologically aberrant enveloped particles with thicker, oblong tegument layers. These defects were different from those observed with HSV gD
−
/gE
−
/gI
−
mutants, which accumulated capsids in large, aggregated masses in the cytoplasm. Our results suggest that HSV gB functions in secondary envelopment, apparently acting downstream of gE/gI.
Two Closely Related Env Antigens from the Same Patient Elicited Different Spectra of Neutralizing Antibodies against Heterologous HIV-1 Isolates
Authors: Vaine Michael , Duenas-Decamp Maria , Peters Paul , Liu Qin , Arthos James , Wang Shixia , Clapham Paul , Lu Shan
Published: March 2011

Identification of immunogens capable of eliciting broadly neutralizing antibody (NAb) responses against HIV-1 is a major goal toward the development of an AIDS vaccine. Despite significant progress in understanding the structural features of the HIV-1 envelope glycoprotein (Env) and the discovery of multiple broadly neutralizing monoclonal antibodies with defined antigenic structures, the design of optimal Env immunogens to elicit broad NAbs remains a major challenge. As the structural determinants of Env immunogenicity remain unclear, we assessed two closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features to identify what may result in a favorable immunogenic profile. One Env, B33, isolated from brain, was highly macrophage tropic with a high CD4 affinity, while the other, LN40, isolated from the lymph nodes, was poorly macrophage tropic with a low CD4 affinity. Using a DNA prime-protein boost approach, rabbits primed with LN40 Env antigen had a NAb response against heterologous primary isolates, while B33 Env antigens were capable of eliciting NAbs against only homologous and sensitive viral isolates. Further analysis revealed that the specificity of NAbs elicited by the LN40 antigen mapped to limited residues within or flanking the CD4 binding site. Certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs. This progress will facilitate the rational design of effective HIV-1 vaccine formulations with optimal Env antigens.
Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections
Authors: Johnson Philip L. F. , Kochin Beth F. , McAfee Megan S. , Stromnes Ingunn M. , Regoes Roland R. , Ahmed Rafi , Blattman Joseph N. , Antia Rustom
Published: March 2011

While T cell-based vaccines have the potential to provide protection against chronic virus infections, they also have the potential to generate immunopathology following subsequent virus infection. We develop a mathematical model to investigate the conditions under which T cells lead to protection versus adverse pathology. The model illustrates how the balance between virus clearance and immune exhaustion may be disrupted when vaccination generates intermediate numbers of specific CD8 T cells. Surprisingly, our model suggests that this adverse effect of vaccination is largely unaffected by the generation of mutant viruses that evade T cell recognition and cannot be avoided by simply increasing the quality (affinity) or diversity of the T cell response. These findings should be taken into account when developing vaccines against persistent infections.
The Polypyrimidine Tract-Binding Protein Affects Coronavirus RNA Accumulation Levels and Relocalizes Viral RNAs to Novel Cytoplasmic Domains Different from Replication-Transcription Sites
Authors: Sola Isabel , Galán Carmen , Mateos-Gómez Pedro A. , Palacio Lorena , Zúñiga Sonia , Cruz Jazmina L. , Almazán Fernando , Enjuanes Luis
Published: March 2011

The coronavirus (CoV) discontinuous transcription mechanism is driven by long-distance RNA-RNA interactions between transcription-regulating sequences (TRSs) located at the 5′ terminal leader (TRS-L) and also preceding each mRNA-coding sequence (TRS-B). The contribution of host cell proteins to CoV transcription needs additional information. Polypyrimidine tract-binding protein (PTB) was reproducibly identified in association with positive-sense RNAs of transmissible gastroenteritis coronavirus (TGEV) TRS-L and TRS-B by affinity chromatography and mass spectrometry. A temporal regulation of PTB cytoplasmic levels was observed during infection, with a significant increase from 7 to 16 h postinfection being inversely associated with a decrease in viral replication and transcription. Silencing the expression of PTB with small interfering RNA in two cell lines (Huh7 and HEK 293T) led to a significant increase of up to 4-fold in mRNA levels and virus titer, indicating a negative effect of PTB on CoV RNA accumulation. During CoV infection, PTB relocalized from the nucleus to novel cytoplasmic structures different from replication-transcription sites in which stress granule markers T-cell intracellular antigen-1 (TIA-1) and TIA-1-related protein (TIAR) colocalized. PTB was detected in these modified stress granules in TGEV-infected swine testis cells but not in stress granules induced by oxidative stress. Furthermore, viral genomic and subgenomic RNAs were detected in association with PTB and TIAR. These cytoplasmic ribonucleoprotein complexes might be involved in posttranscriptional regulation of virus gene expression.
The Naturally Attenuated Kunjin Strain of West Nile Virus Shows Enhanced Sensitivity to the Host Type I Interferon Response
Authors: Daffis Stephane , Lazear Helen M. , Liu Wen Jun , Audsley Michelle , Engle Michael , Khromykh Alexander A. , Diamond Michael S.
Published: March 2011

The host determinants that contribute to attenuation of the naturally occurring nonpathogenic strain of West Nile virus (WNV), the Kunjin strain (WNV
KUN
), remain unknown. Here, we show that compared to a highly pathogenic North American strain, WNV
KUN
exhibited an enhanced sensitivity to the antiviral effects of type I interferon. Our studies establish that the virulence of WNV
KUN
can be restored in cells and mice deficient in specific interferon regulatory factors (IRFs) or the common type I interferon receptor. Thus, WNV
KUN
is attenuated primarily through its enhanced restriction by type I interferon- and IRF-3-dependent mechanisms.
The Capsid-Binding Nucleolar Helicase DDX56 Is Important for Infectivity of West Nile Virus
Authors: Xu Zaikun , Anderson Robert , Hobman Tom C.
Published: March 2011

Recent findings suggest that in addition to its role in packaging genomic RNA, the West Nile virus (WNV) capsid protein is an important pathogenic determinant, a scenario that requires interaction of this viral protein with host cell proteins. We performed an extensive multitissue yeast two-hybrid screen to identify capsid-binding proteins in human cells. Here we describe the interaction between WNV capsid and the nucleolar RNA helicase DDX56/NOH61. Coimmunoprecipitation confirmed that capsid protein binds to DDX56 in infected cells and that this interaction is not dependent upon intact RNA. Interestingly, WNV infection induced the relocalization of DDX56 from the nucleolus to a compartment in the cytoplasm that also contained capsid protein. This phenomenon was apparently specific for WNV, as DDX56 remained in the nucleoli of cells infected with rubella and dengue 2 viruses. Further analyses showed that DDX56 is not required for replication of WNV; however, virions secreted from DDX56-depleted cells contained less viral RNA and were 100 times less infectious. Together, these data suggest that DDX56 is required for assembly of infectious WNV particles.
The Influenza A Virus NS1 Protein Interacts with the Nucleoprotein of Viral Ribonucleoprotein Complexes
Authors: Robb Nicole C. , Chase Geoffrey , Bier Katja , Vreede Frank T. , Shaw Pang-Chui , Naffakh Nadia , Schwemmle Martin , Fodor Ervin
Published: March 2011

The influenza A virus genome consists of eight RNA segments that associate with the viral polymerase proteins (PB1, PB2, and PA) and nucleoprotein (NP) to form ribonucleoprotein complexes (RNPs). The viral NS1 protein was previously shown to associate with these complexes, although it was not clear which RNP component mediated the interaction. Using individual TAP (tandem affinity purification)-tagged PB1, PB2, PA, and NP, we demonstrated that the NS1 protein interacts specifically with NP and not the polymerase subunits. The region of NS1 that binds NP was mapped to the RNA-binding domain.
Reverse Genetic Analysis of Ourmiaviruses Reveals the Nucleolar Localization of the Coat Protein in Nicotiana benthamiana and Unusual Requirements for Virion Formation
Authors: Crivelli Giulia , Ciuffo Marina , Genre Andrea , Masenga Vera , Turina Massimo
Published: March 2011

Ourmia melon virus
(OuMV) is the type member of the genus
Ourmiavirus
. These viruses have a trisegmented genome, each part of which encodes a single protein. Ourmiaviruses share a distant similarity with other plant viruses only in their movement proteins (MP), whereas their RNA-dependent RNA polymerase (RdRP) shares features only with fungal viruses of the family
Narnaviridae
. Thus, ourmiaviruses are in a unique phylogenetic position among existing plant viruses. Here, we developed an agroinoculation system to launch infection in
Nicotiana benthamiana
plants. Using different combinations of the three segments, we demonstrated that RNA1 is necessary and sufficient for
cis
-acting replication in the agroinfiltrated area. RNA2 and RNA3, encoding the putative movement protein and the coat protein (CP), respectively, are both necessary for successful systemic infection of
N. benthamiana
. The CP is dispensable for long-distance transport of the virus through vascular tissues, but its absence prevents efficient systemic infection at the exit sites. Virion formation occurred only when the CP was translated from replication-derived RNA3. Transient expression of a green fluorescent protein-MP (GFP-MP) fusion via agroinfiltration showed that the MP is present in cytoplasmic connections across plant cell walls; in protoplasts the GFP-MP fusion stimulates the formation of tubular protrusions. Expression through agroinfiltration of a GFP-CP fusion displays most of the fluorescence inside the nucleus and within the nucleolus in particular. Nuclear localization of the CP was also confirmed through Western blot analysis of purified nuclei. The significance of several unusual properties of OuMV for replication, virion assembly, and movement is discussed in relation to other positive-strand RNA viruses.
Determination of glutathione and glutathione disulfide in human whole blood using HPLC with coulometric detection: A comparison with fluorescence detection
Authors: Kanďár Roman , Žáková Pavla , Marková Miroslava , Lotková Halka , Kučera Otto , Červinková Zuzana
Published: March 2011

We describe a relatively simple method for the determination of glutathione (GSH) and glutathione disulfide (GSSG) in human whole blood. We have used an HPLC with coulometric electrochemical detection for the simultaneous measurement of GSH and GSSG. Diluted and filtered trichloroacetic acid extracts were injected directly into the HPLC system and were eluted isocratically on a Polaris 5u C18-A, 250 × 4.6 mm analytical column. Glutathione in samples extracted with trichloroacetic acid and diluted with 1.0 mMhydrochloric acid was stable at 4 °C for at least 8 h. The analytical performance of this method is satisfactory: the intra-assay and inter-assay coefficients of variation were below 10%. Quantitative recoveries from spiked whole blood samples were at intervals 91.6–97.6% for GSH and 85.0–104.4% for GSSG. The linear range is 5.0–2000.0 μmol/l, with a detection limit of 2.1 μmol/l (signal-to-noise ratio = 3) for GSH and 2.0–250.0 μmol/l, with a detection limit of 0.9 μmol/l for GSSG.
Adsorption of thiourea and its methyl derivatives from chlorate(VII) with varied water activity
Authors: Nosal-Wiercińska Agnieszka , Grochowski Mariusz
Published: March 2011

The comparison of thiourea, methylthiourea, dimethylthiourea and tetramethylthiourea adsorption at mercury|sodium chlorate(VII) interface was done. For the sake of due to the specific interactions between sulfur and mercury all the compounds examined are pointed with their negative end towards mercury, even at the negative values of an electrode charge. However the change of an electrode charge is connected with the change of an adsorbate reorientation. It was found that with the increase of the methyl group amount in a molecule of thiourea methyl derivatives: (i) the range of adsorption potentials is expanded, (ii) the values of zero charge potentials and surface tension decrease, (iii) the surface excesses increase. Whereas the considerable changes of adsorption energy values were not fund. The lack of symmetry results in a molecule, while the methylthiourea interaction constants are much more higher than the interaction constants of the other compounds examined. The changes of adsorption parameters as a function of the supporting electrolyte concentration are analogous for all the adsorbates examined. They point to the competitive adsorption of thiourea methyl derivatives and ClO4–.
Pd-catalyzed allylic substitution of purin-8-yl(allyl) acetate: Route to (E)-alkenylpurines
Authors: Tobrmanová Miroslava , Tobrman Tomáš , Dvořák Dalimil
Published: March 2011

C8-Alkenylpurines were synthesized starting from purin-8-yl(allyl) acetates using Pd-catalyzed allylic substitution. The described protocol allows, by reaction of purin-8-yl(allyl) acetates with stabilized nucleophiles, an access to novel (E)-8-alkenylpurine derivatives under Pd2dba3·CHCl3 catalysis in dry THF in yields ranging from 31 to 76%. A wide range of nucleophiles showed exclusive E-alkene formation, however, ethyl nitroacetate gave mixture of E/Z-alkenes. On contrary, purin-2-yl(allyl) acetates reacted smoothly only with dimethyl malonate.
THE RELATIVE WEAK ASYMPTOTIC HOMOMORPHISM PROPERTY FOR INCLUSIONS OF FINITE VON NEUMANN ALGEBRAS
Authors: FANG JUNSHENG , GAO MINGCHU , SMITH ROGER R.
Published: March 2011

A triple of finite von Neumann algebras B ⊆ N ⊆ M is said to have the relative weak asymptotic homomorphism property if there exists a net of unitary operators {uλ}λ∈Λin B such that [Formula: see text] for all x,y ∈ M. We prove that a triple of finite von Neumann algebras B ⊆ N ⊆ M has the relative weak asymptotic homomorphism property if and only if N contains the set of all x ∈ M such that [Formula: see text] for a finite number of elements x1, …, xnin M. Such an x is called a one-sided quasi-normalizer of B, and the von Neumann algebra generated by all one-sided quasi-normalizers of B is called the one-sided quasi-normalizer algebra of B. We characterize one-sided quasi-normalizer algebras for inclusions of group von Neumann algebras and use this to show that one-sided quasi-normalizer algebras and quasi-normalizer algebras are not equal in general. We also give some applications to inclusions L(H) ⊆ L(G) arising from containments of groups. For example, when L(H) is a masa we determine the unitary normalizer algebra as the von Neumann algebra generated by the normalizers of H in G.
COLLECTIVE BEHAVIOR OF BIOPHYSICAL SYSTEMS WITH THERMODYNAMIC FEEDBACK LOOPS: A CASE STUDY FOR A NONLINEAR MARKOV MODEL — THE TAKATSUJI SYSTEM
Authors: FRANK T. D.
Published: March 2011

We study order–disorder transitions and the emergence of collective behavior using a particular mean field model: the dynamic Takatsuji system. This model satisfies linear non-equilibrium thermodynamics and can be described in terms of a nonlinear Markov process defined by a nonlinear Fokker–Planck equation, that is, an evolution equation that is nonlinear with respect to its probability density. We discuss quantitatively the impact of a feedback loop that involves a macroscopic, thermodynamic variable. We demonstrate by means of semi-analytical methods and numerical simulations that the feedback loop increases the magnitude of order, increases the gap between the free energy of the ordered and disordered states, and increases the maximal rate of entropy production that can be observed during the order–disorder transition.
THE EINSTEIN–BRILLOUIN–KELLER ACTION QUANTIZATION FOR DIRAC FERMIONS
Authors: ONORATO P.
Published: March 2011

The Einstein–Brillouin–Keller semiclassical quantization and the topological Maslov index are used to compute the electronic structure of carbon based nanostructures with or without transverse magnetic field. The calculation is based on the Dirac Fermions approach in the limit of strong coupling for the pseudospin.

The electronic bandstructure for carbon nanotubes and graphene nanoribbons are discussed, focusing on the role of the chirality and of the unbonded edges configuration respectively. The effects of a transverse uniform magnetic field are analyzed, the different kinds of classical trajectories are discussed and related to the corresponding energies.

The development is concise, transparent, and involves only elementary integral calculus and provides a conceptual and intuitive introduction to the quantum nature of carbon nanostructures.
LOSCHMIDT ECHO OF A CENTRAL SPIN COUPLED TO AN XY SPIN CHAIN WITH DZYALOSHINSKY–MORIYA INTERACTION
Authors: LIAN HAN LI , TIAN DONG PING
Published: March 2011

By introducing the Dzyaloshinsky–Moriya (DM) interaction, the Loschmidt Echo (LE) of a quantum system consisting of a central spin and its surrounding environment characterized by an XY spin chain was investigated. The analytical expression of the LE was obtained. The effects of magnetic field, DM interaction, spin chain size, and anisotropy parameter on the evolution behavior of the LE were discussed numerically. At the critical points of magnetic field, the LE presents an obvious decay following with local oscillation. The decaying and oscillation behavior of the LE can be tuned by the intensity of the DM interaction. With increasing the spin chain size, the decaying amplitude is increased and the following oscillation behavior vanishes for the spin chain with larger size. The effect of the anisotropy parameter on the LE presents different properties at both sides of the knee point. The effect of the DM interaction on the decay of the LE is also related to the value of anisotropy parameter.
PROBING SINGLE AND BILAYER GRAPHENE FIELD EFFECT TRANSISTORS BY RAMAN SPECTROSCOPY
Authors: DAS A. , CHAKRABORTY B. , SOOD A. K.
Published: March 2011

This article is a review of our work related to Raman studies of single layer and bilayer graphenes as a function Fermi level shift achieved by electrochemically top gating a field effect transistor. Combining the transport and in situ Raman studies of the field effect devices, a quantitative understanding is obtained of the phonon renormalization due to doping of graphene. Results are discussed in the light of time dependent perturbation theory, with electron phonon coupling parameter as an input from the density functional theory. It is seen that phonons near Γ and K points of the Brillouin zone are renormalized very differently by doping. Further, Γ-phonon renormalization is different in bilayer graphene as compared to single layer, originating from their different electronic band structures near the zone boundary K-point. Thus Raman spectroscopy is not only a powerful probe to characterize the number of layers and their quality in a graphene sample, but also to quantitatively evaluate electron phonon coupling required to understand the performance of graphene devices.
Gold corroles
Authors: Alemayehu Abraham B. , Ghosh Abhik
Published: March 2011

Although a variety of conditions proved unsuccessful for gold insertion into β-unsubstituted meso-triarylcorroles, refluxing free-base β-octabromo-meso-triarylcorrole ligands, H3[Br8T (p- X-P)C] ( X = MeO , n- Bu , CH3 , H , and CF3 ), with chloroauric acid in dichloromethane containing a small amount of triethylamine for 30 min led to 54–65% yields of the corresponding gold complexes.
SysML to UML model transformation for test generation purpose
Authors: Lasalle Jonathan , Bouquet Fabrice , Legeard Bruno , Peureux Fabien
Published: March 2011

The work introduced in this paper is in line with an original Model-Based Testing approach by taking as input a SysML specification of a system under test and automatically translating it into an equivalent behavioural UML model. This generated UML model is finally used to derive test cases and executable test scripts. This test generation process is supported by an existing UML/OCL Model-Based Test generation tool. This paper focuses on the definition of the subset of SysML notation supported by this Model-Based Testing approach, and proposes rewriting rules to derive UML test model from SysML model
Formal verification of UML state diagrams
Authors: Choppy Christine , Klai Kais , Zidani Hacene
Published: March 2011

In spite of its informal semantics and of some ambiguities, UML is a widespread modelling language used in both industry and academia. On the other hand, Petri nets are a mathematical modelling language with a formal semantics and are well suited for formal verification. However, altough there is a growing interest in model checking techniques from industry, the software engineers continue to be unfamiliar with such a formalism. For that reason, it is convenient to supply formal verification techniques of UML diagrams that are completely automatic and transparent to the designer. This is the issue discussed in this paper. We propose to translate UML state diagrams into Coloured Petri nets on which verification of some desired properties can be checked automatically. We show on our example that, when expected properties are not checked, this is an opportunity to revise the model into a more adequate one
Machine Translation Errors
Authors: Condon S. , Parvaz D. , Aberdeen J. , Doran C. , Freeman A. , Awad M.
Published: March 2011

Errors in machine translations of English-Iraqi Arabic dialogues were analyzed using the methods developed for the Human Translation Error Rate measure (HTER). Human annotations were used to refine the Translation Error Rate (TER) annotations. The analyses were performed on approximately 100 translations into each language from four translation systems. Results include high frequencies of pronoun errors and errors involving the copula in translations to English. High frequencies of errors in subject/person inflection and closed-word classes characterized translations to Iraqi Arabic. There were similar frequencies of word order errors in both translation directions and low frequencies of polarity errors. The problems associated with many errors can be predicted from structural differences between the two languages. Also problematic is the need to insert lexemes not present in the source or vice versa. Some problems associated with deictic elements like pronouns will require knowledge of the discourse context to resolve.
Automatic Detection of Arabic Non-Anaphoric Pronouns for Improving Anaphora Resolution
Authors: Abdul-Mageed Muhammad
Published: March 2011

Anaphora resolution is one of the most difficult tasks in NLP. The ability to identify non-referential pronouns before attempting an anaphora resolution task would be significant, since the system would not have to attempt resolving such pronouns and hence end up with fewer errors. In addition, the number of non-referential pronouns has been found to be non-trivial in many domains. The task of detecting non-referential pronouns could also be incorporated into a part-of-speech tagger or a parser, or treated as an initial step in semantic interpretation. In this article, I describe a machine learning method for identifying non-referential pronouns in an annotated subsegment of the Penn Arabic Treebank using three different feature settings. I achieve an accuracy of 97.22% with 52 different features extracted from a small window size of -5/+5 tokens surrounding each potentially non-referential pronoun.
Regulation of V-ATPase recycling via a RhoA- and ROCKII-dependent pathway in epididymal clear cells
Authors: Shum Winnie Waichi , Da Silva Nicolas , Belleannée Clémence , McKee Mary , Brown Dennis , Breton Sylvie
Published: March 2011

Luminal acidification in the epididymis is critical for sperm maturation and storage. Clear cells express the vacuolar H+-ATPase (V-ATPase) in their apical membrane and are major contributors to proton secretion. We showed that this process is regulated via recycling of V-ATPase-containing vesicles. We now report that RhoA and its effector ROCKII are enriched in rat epididymal clear cells. In addition, cortical F-actin was detected beneath the apical membrane and along the lateral membrane of “resting” clear cells using a pan-actin antibody or phalloidin-TRITC. In vivo luminal perfusion of the cauda epididymal tubule with the ROCK inhibitors Y27632 (10–30 μM) and HA1077 (30 μM) or with the cell-permeable Rho inhibitor Clostridium botulinum C3 transferase (3.75 μg/ml) induced the apical membrane accumulation of V-ATPase and extension of V-ATPase-labeled microvilli in clear cells. However, these newly formed microvilli were devoid of ROCKII. In addition, Y27632 (30 μM) or HA1077 (30 μM) decreased the ratio of F-actin to G-actin detected by Western blot analysis in epididymal epithelial cells, and Y27632 also decreased the ratio of F-actin to G-actin in clear cells isolated by fluorescence activated cell sorting from B1-enhanced green fluorescence protein (EGFP) transgenic mice. These results provide evidence that depolymerization of the cortical actin cytoskeleton via inhibition of RhoA or its effector ROCKII favors the recruitment of V-ATPase from the cytosolic compartment into the apical membrane in clear cells. In addition, our data suggest that the RhoA-ROCKII pathway is not locally involved in the elongation of apical microvilli. We propose that inhibition of RhoA-ROCKII might be part of the intracellular signaling cascade that is triggered upon agonist-induced apical membrane V-ATPase accumulation.
Food reward, hyperphagia, and obesity
Authors: Berthoud Hans-Rudolf , Lenard Natalie R. , Shin Andrew C.
Published: March 2011

Given the unabated obesity problem, there is increasing appreciation of expressions like “my eyes are bigger than my stomach,” and recent studies in rodents and humans suggest that dysregulated brain reward pathways may be contributing not only to drug addiction but also to increased intake of palatable foods and ultimately obesity. After describing recent progress in revealing the neural pathways and mechanisms underlying food reward and the attribution of incentive salience by internal state signals, we analyze the potentially circular relationship between palatable food intake, hyperphagia, and obesity. Are there preexisting individual differences in reward functions at an early age, and could they be responsible for development of obesity later in life? Does repeated exposure to palatable foods set off a cascade of sensitization as in drug and alcohol addiction? Are reward functions altered by secondary effects of the obese state, such as increased signaling through inflammatory, oxidative, and mitochondrial stress pathways? Answering these questions will significantly impact prevention and treatment of obesity and its ensuing comorbidities as well as eating disorders and drug and alcohol addiction.
The interactive effects of hypoxemia, hyperoxia, and temperature on the gill morphology of goldfish (Carassius auratus)
Authors: Tzaneva Velislava , Bailey Shawn , Perry Steve F.
Published: March 2011

Acclimation of crucian carp and goldfish to temperatures below 15°C causes covering of the gill lamellae by a mass of cells termed the interlamellar cell mass (ILCM). Here we explore the cues underlying gill remodeling (removal or growth of an ILCM) and specifically test the hypotheses that 1) depletion of internal O2stores in the absence of any change in external O2status can trigger the removal of the ILCM in goldfish acclimated to 7°C, 2) exposing fish acclimated to 25°C to an abundance of O2(hyperoxia) can reverse the gill remodeling (i.e., cause the covering of lamellae by an expansion of the ILCM), and 3) neuroepithelial cells (NECs) are involved in signaling the shedding of the ILCM. Hypoxemia induced by phenylhydrazine (anemia) or 5% CO caused a decrease in the ILCM from 80% to 23% and 35%, respectively. Hyperoxia exposure at 25°C caused an increase to 67% of total ILCM and a smaller decrease in the size of the ILCM when fish were transferred from 7 to 25°C. Daily sodium cyanide injections were used to stimulate NECs; this treatment led to a significant decrease in the ILCM. Thus, the three major conclusions of this study are 1) that gill remodeling can occur during periods of internal hypoxemia, 2) that O2supply and demand may be a significant driving force shaping gill remodeling in goldfish, and 3) the NECs may play a role in triggering the shedding of the ILCM during hypoxia.
Modulation of respiratory responses to chemoreflex activation by l-glutamate and ATP in the rostral ventrolateral medulla of awake rats
Authors: Moraes Davi J. A. , Bonagamba Leni G. H. , Zoccal Daniel B. , Machado Benedito H.
Published: March 2011

Presympathetic neurons in the different anteroposterior aspects of rostral ventrolateral medulla (RVLM) are colocalized with expiratory [Bötzinger complex (BötC)] and inspiratory [pre-Bötzinger complex (pre-BötC)] neurons of ventral respiratory column (VRC), suggesting that this region integrates the cardiovascular and respiratory chemoreflex responses. In the present study, we evaluated in different anteroposterior aspects of RVLM of awake rats the role of ionotropic glutamate and purinergic receptors on cardiorespiratory responses to chemoreflex activation. The bilateral ionotropic glutamate receptors antagonism with kynurenic acid (KYN) (8 nmol/50 nl) in the rostral aspect of RVLM (RVLM/BötC) enhanced the tachypneic (120 ± 9 vs. 180 ± 9 cpm; P < 0.01) and attenuated the pressor response (55 ± 2 vs. 15 ± 1 mmHg; P < 0.001) to chemoreflex activation ( n = 7). On the other hand, bilateral microinjection of KYN into the caudal aspect of RVLM (RVLM/pre-BötC) caused a respiratory arrest in four awake rats used in the present study. Bilateral P2X receptors antagonism with PPADS (0.25 nmol/50 nl) in the RVLM/BötC reduced chemoreflex tachypneic response (127 ± 6 vs. 70 ± 5 cpm; P < 0.001; n = 6), but did not change the chemoreflex pressor response. In addition, PPADS into the RVLM/BötC attenuated the enhancement of the tachypneic response to chemoreflex activation elicited by previous microinjections of KYN into the same subregion (188 ± 2 vs. 157 ± 3 cpm; P < 0.05; n = 5). Our findings indicate that: 1) l-glutamate, but not ATP, in the RVLM/BötC is required for pressor response to peripheral chemoreflex and 2) both transmitters in the RVLM/BötC are required for the processing of the ventilatory response to peripheral chemoreflex activation in awake rats.
A design-based method for estimating glomerular number in the developing kidney
Authors: Cullen-McEwen Luise A. , Armitage James A. , Nyengaard Jens R. , Moritz Karen M. , Bertram John F.
Published: March 2011

Low glomerular (nephron) endowment has been associated with an increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 wk of gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was due in part to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here, we describe a method that uses lectin histochemistry to identify developing glomeruli and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number ( Nglom). We have characterized Nglom throughout development in kidneys from 76 rats and model this development with a 5-parameter logistic equation to predict Nglom from embryonic day 17.25 to adulthood ( r2 = 0.98). This approach represents the first design-based method with which to estimate Nglom in the developing kidney.
High-fat feeding inhibits exercise-induced increase in mitochondrial respiratory flux in skeletal muscle
Authors: Skovbro Mette , Boushel Robert , Hansen Christina Neigaard , Helge Jørn Wulff , Dela Flemming
Published: March 2011

Twenty one healthy untrained male subjects were randomized to follow a high-fat diet (HFD; 55–60E% fat, 25–30E% carbohydrate, and 15E% protein) or a normal diet (ND; 25–35E% fat, 55–60E% carbohydrate, and 10–15E% protein) for 21/2 wk. Diets were isocaloric and tailored individually to match energy expenditure. At 21/2 wk of diet, one 60-min bout of bicycle exercise (70% of maximal oxygen uptake) was performed. Muscle biopsies were obtained before and after the diet, immediately after exercise, and after 3-h recovery. Insulin sensitivity (hyperinsulinemic-euglycemic clamp) and intramyocellular triacylglycerol content did not change with the intervention in either group. Indexes of mitochondrial density were similar across the groups and intervention. Mitochondrial respiratory rates, measured in permeabilized muscle fibers, showed a 31 ± 11 and 26 ± 9% exercise-induced increase ( P < 0.05) in state 3 (glycolytic substrates) and uncoupled respiration, respectively. However, in HFD this increase was abolished. At recovery, no change from resting respiration was seen in either group. With a lipid substrate (octanoyl-carnitine with or without ADP), similar exercise-induced increases (31–62%) were seen in HFD and ND, but only in HFD was an elevated ( P < 0.05) respiratory rate seen at recovery. With HFD complex I and IV protein expression decreased ( P < 0.05 and P = 0.06, respectively). A fat-rich diet induces marked changes in the mitochondrial electron transport system protein content and in exercise-induced mitochondrial substrate oxidation rates, with the effects being present hours after the exercise. The effect of HFD is present even without effects on insulin sensitivity and intramyocellular lipid accumulation. An isocaloric high-fat diet does not cause insulin resistance.
Correlation of neural response properties with auditory thalamus subdivisions in the awake marmoset
Authors: Bartlett Edward L. , Wang Xiaoqin
Published: March 2011

As the information bottleneck of nearly all auditory input that reaches the cortex, the auditory thalamus serves as the basis for establishing auditory cortical processing streams. The functional organization of the primary and nonprimary subdivisions of the auditory thalamus is not well characterized, particularly in awake primates. We have recorded from neurons in the auditory thalamus of awake marmoset monkeys and tested their responses to tones, band-pass noise, and temporally modulated stimuli. We analyzed the spectral and temporal response properties of recorded neurons and correlated those properties with their locations in the auditory thalamus, thereby forming the basis for parallel output channels. Three medial geniculate body (MGB) subdivisions were identified and studied physiologically and anatomically, although other medial subdivisions were also identified anatomically. Neurons in the ventral subdivision (MGV) were sharply tuned for frequency, preferred narrowband stimuli, and were able to synchronize to rapid temporal modulations. Anterodorsal subdivision (MGAD) neurons appeared well suited for temporal processing, responding similarly to tone or noise stimuli but able to synchronize to the highest modulation frequencies and with the highest temporal precision among MGB subdivisions. Posterodorsal subdivision (MGPD) neurons differed substantially from the other two subdivisions, with many neurons preferring broadband stimuli and signaling changes in modulation frequency with nonsynchronized changes in firing rate. Most neurons in all subdivisions responded to increases in tone sound level with nonmonotonic changes in firing rate. MGV and MGAD neurons exhibited responses consistent with provision of thalamocortical input to core regions, whereas MGPD neurons were consistent with provision of input to belt regions.
EphA activation overrides the presynaptic actions of BDNF
Authors: Bi Caixia , Yue Xin , Zhou Renping , Plummer Mark R.
Published: March 2011

The adult pattern of neural connectivity is shaped by repulsive and attractive factors, many of which are modulated by activity. Although much is known about the actions of these factors when studied in isolation, little is known about how they interact. To address this question, we examined the effects of sequential or coapplication of brain-derived neurotrophic factor (BDNF) and Fc-conjugated ephrin-A5 or EphA5 in cultured embryonic hippocampal neurons. BDNF promotes neurite outgrowth and synapse formation, and when applied acutely, it elicits an increase in ongoing synaptic activity. Members of the ephrin family of ligands and receptors can be repulsive and prevent formation of synaptic contacts. Acute exposure to either ephrin-A5-Fc or EphA5-Fc transiently enhanced synaptic activity when applied alone, but when applied prior to BDNF, they dramatically reduced the electrophysiological effects of the neurotrophin. Conversely, BDNF had no effect on subsequently applied ephrin-A5-Fc or EphA5-Fc. Consistent with this, ephrin-A5-Fc also prevented BDNF-induced activation of p42/44 MAPK. The effect of ephrin-A5-Fc appears to be presynaptic, as it prevented the BDNF-induced increase in spontaneous miniature postsynaptic current frequency, whereas EphA5-Fc did not. These results suggest that these factors can be categorized differently, with the contact-mediated activation of EphA receptors by ephrin-A5 overriding the diffusion-mediated effect of BDNF.
Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina
Authors: Chan Leanne L. H. , Lee Eun-Jin , Humayun Mark S. , Weiland James D.
Published: March 2011

Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal and S334ter line 3 (RD) rats (ages 84–782 days). We stimulated the retina in anesthetized animals and recorded evoked responses in the superior colliculus. Current pulses were delivered with a platinum-iridium (Pt-Ir) electrode of 75-μm diameter positioned on the epiretinal surface. In the same animals used for electrophysiology, SMI-32 immunolabeling of the retina enabled ganglion cell counting. An increase in threshold currents positively correlated with age of RD rats. SMI-32-labeled retinal ganglion cell density negatively correlated with age of RD rats. ANOVA shows that RD postnatal day (P)100 and P300 rats have threshold and density similar to normal rats, but RD P500 and P700 rats have threshold and density statistically different from normal rats ( P < 0.05). Threshold charge densities were within the safety limits of Pt for all groups and pulse configurations, except at RD P600 and RD P700, where pulses were only safe up to 1- and 0.2-ms duration, respectively. Preservation of ganglion cells may enhance the efficiency and safety of electronic retinal implants.
Statistical characterization of social interactions and collective behavior in medicinal leeches
Authors: Bisson Giacomo , Torre Vincent
Published: March 2011

In the present study we analyzed the behavior and interactions among leeches in the same observation tank. Colored beads were glued onto their skin so that their behavior could be followed and quantified. When two or three leeches were present in the observation tank, they searched around for a maximum of 2 h and their motion and behavior were independent from those of their conspecifics. When the number of leeches in the tank was increased to 10, leeches were attracted to each other and exhibited episodes of highly correlated behavior. Solitary leeches injected with serotonin or dopamine increased the portion of time spent pseudoswimming and crawling, respectively. The behavior of three to five leeches injected with serotonin was not statistically independent, and leeches were attracted to their conspecifics and exhibited episodes of correlated behavior. Therefore, serotonin not only induces pseudoswimming in leeches but also promotes social interactions, characterized by a mutual attraction and by episodes of correlated/collective behavior.
A Counterexample to "An Extension of Gregus Fixed Point Theorem"
Authors: Moradi Sirous
Published: March 2011

In the paper by Olaleru and Akewe (2007), the authors tried to generalize Gregus fixed point theorem. In this paper we give a counterexample on their main statement.
Multiscale Time‐Splitting Strategy for Multiscale Multiphysics Processes of Two‐Phase Flow in Fractured Media
Authors: Kou Jisheng , Sun Shuyu , Yu Bo
Published: March 2011

The temporal discretization scheme is one important ingredient of efficient simulator for two‐phase flow in the fractured porous media. The application of single‐scale temporal scheme is restricted by the rapid changes of the pressure and saturation in the fractured system with capillarity. In this paper, we propose a multi‐scale time splitting strategy to simulate multi‐scale multi‐physics processes of two‐phase flow in fractured porous media. We use the multi‐scale time schemes for both the pressure and saturation equations; that is, a large time‐step size is employed for the matrix domain, along with a small time‐step size being applied in the fractures. The total time interval is partitioned into four temporal levels: the first level is used for the pressure in the entire domain, the second level matching rapid changes of the pressure in the fractures, the third level treating the response gap between the pressure and the saturation, and the fourth level applied for the saturation in the fractures. This method can reduce the computational cost arisen from the implicit solution of the pressure equation. Numerical examples are provided to demonstrate the efficiency of the proposed method.