bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of Unilateral Inferior Oblique Recession
Authors: Singh Vinita , Agrawal Saurabh , Agrawal Siddharth
Published: November 2009

Purpose:

The aim of this study was to analyze the outcome of unilateral inferior oblique (IO) recession in patients with unilateral or asymmetrical IO overaction in terms of effectiveness, stability, and undesired effects.

Methods:

Fifteen patients with nonparalytic strabismus who underwent unilateral IO recession for unilateral or asymmetric IO overaction and horizontal muscle surgery were included in this study. Nine patients demonstrated asymmetric bilateral IO overaction, whereas 6 had unilateral overaction. All patients underwent IO recession to the Scheie Parks point in one eye, along with conventional horizontal muscle surgery. Clinical outcome assessment included changes in oblique muscle dysfunction in both eyes. Changes in horizontal deviation, V pattern, vertical deviation, and excyclotorsion were also studied.

Results:

Satisfactory outcome in terms of oblique muscle function, V pattern, vertical deviation, and cyclodeviation was achieved in all patients with unilateral IO overaction and 7 (77%) patients with bilateral IO over-action. Increased IO overaction in the other eye was noted in 2 patients. Satisfactory outcome in patients with bilateral overaction was related to degree of asymmetry in IO overaction between the 2 eyes.

Conclusion:

Unilateral IO recession is effective in patients with unilateral IO overaction and selected patients with largely asymmetrical bilateral IO overaction.

[J Pediatr Ophthalmol Strabismus 2009;46:350–357.]
Importance of the ‘Third Criterion’ for Retinopathy of Prematurity Screening in Developing Countries
Authors: Azad Rajvardhan , Chandra Parijat , Patwardhan Sourabh D. , Gupta Aparna
Published: November 2009

Purpose:

Developing countries often need a modification of the American screening guidelines for retinopathy of prematurity.

Methods:

A total of 1,302 eyes in 651 infants with retinopathy of prematurity were analyzed by the parameters of gestational age and birth weight suggested by the American guidelines.

Results:

With the use of current gestational age and birth weight guidelines, 86 of 1,302 eyes (6.6%) were missed, and 38 of these eyes (2.9%) had potentially treatable or more severe retinopathy of prematurity and were in need of treatment.

Conclusion:

Use of the “third criterion” (ie, neonatologist referral of sick infants who were believed to be at high risk for retinopathy of prematurity), enabled larger infants who were otherwise missed by the American guidelines to be included for screening. Even when the parameters were increased, a relatively small number of infants was still missed. Therefore, in view of the limited resources and manpower in developing countries, the American screening guidelines are appropriate.

[J Pediatr Ophthalmol Strabismus 2009;46:332–334.]
Prolonged Constant Eye Misalignment Leads to Failure to Develop Binocular Vision in Childhood Ocular Myasthenia Gravis
Authors: Emoto Yuko , Emoto Hirofumi , Fujie Waki , Wakakura Masato
Published: November 2009

Purpose:

Variable eye misalignment and blepharoptosis in childhood ocular myasthenia gravis can lead to permanent binocular visual loss. However, a standard ophthalmologic intervention for this condition has yet to be fully established. This study investigated the influence of variable eye misalignment and asymmetric blepharoptosis on the development of binocular vision in childhood ocular myasthenia gravis.

Methods:

The authors retrospectively reviewed clinical records of consecutive patients with childhood ocular myasthenia gravis whose age of onset was younger than 36 months and who had follow-up periods of more than 1 year. Five patients were enrolled and were treated medically with pyridostigmine or corticosteroids. Eye alignment, eye movements, and blepharoptosis were observed during the follow-up period. Stereoacuity was recorded before and at the end of follow-up using Titmus stereoscopic and major amblyoscopic tests.

Results:

None of the patients had amblyopia or anisometropia, but all had blepharoptosis that improved within 2 weeks after medication was administered. There was only one case in which stereoacutiy failed to develop, and this patient had a long period of constant exotropia lasting 48 months. In the remaining four cases, there was constant exotropia lasting less than 4 months or intermittent exotropia throughout the follow-up period. All of these patients regained or maintained binocular vision.

Conclusion:

Prolonged constant eye misalignment may be attributable to impaired binocular vision, and prompt eye alignment may be necessary in childhood ocular myasthenia gravis. Therefore, treatment based on precise assessment by a neuro-ophthalmologist or pediatric ophthalmologist that evaluates even slight eye misalignment is essential in ensuring normal development of binocular vision.

[J Pediatr Ophthalmol Strabismus 2009;46:358–361.]
OCT and In Vivo Confocal Microscopy of a Pigmented Corneal Tumor-like Lesion
Authors: Szaflik Jacek P. , Oldak Monika , Ulnska Magdalena , Tesla Piotr , Szaflik Jerzy
Published: November 2009

A 43-year-old woman presented with a pigmented flat tumor situated at the posterior surface of the cornea nasally in her left eye. Anterior-segment optical coherence tomography revealed that the lesion was similar to the iris leaf, was limited to the cornea, and did not communicate with the iridocorneal angle. In vivo scanning slit confocal microscopy imaged dense hyperreflective tissue behind the endothelium and bright spots dispersed on the adjacent endothelial surface. Multiple hyporeflective formations resembling cell nuclei were visualized within the hyperreflective mass and the cell borders were distinguished. The diagnosis of pigmented nevus or retrocorneal membrane was suspected. The authors conclude that anterior-segment optical coherence tomography and in vivo scanning slit confocal microscopy are useful in assessing the microstructure and penetration of pigmented corneal lesions.
[Ophthalmic Surg Lasers Imaging 2009;40:586–588.]
Studies on the behaviour of different spent fluidized-bed catalytic cracking catalysts on Portland cement
Authors: Payá J. , Borrachero M. V. , Monzó J. , Soriano L.
Published: November 2009

The fluidized-bed catalytic cracking catalyst (FCC) it is a residue from the industry of the petroleum that shows a high pozzolanic reactivity and, in cementing matrix, it significantly improves their mechanical behaviour as well as durability. In this research a comparative study on residues of catalyst from different sources has been carried out, in order to know if these residues can be used jointly in an indiscriminate way or, on the contrary, it is necessary to classify them according to their characteristics. Thus, a study on five different FCC residues, supplied from different companies, has been carried out, and their physical-chemical characteristics, pozzolanic reactivity by means of thermogravimetric analysis and the evolution of the mechanical strength of mortars were studied. After analyzing all the aspects, it can be concluded that no significant differences among the different tested catalysts were found.
Implementation of a Remote Session of Practical Work in Nuclear Physics on the Backscattering of ?-Particles
Authors: Fahli Ahmed , Taleb A. Aït , Moussetad M.
Published: November 2009

This work presents the implementation of a hardware and software package used to conduct a physical experiment via the web to create remotely a practical work laboratory. For this reason, we chose to put online a model of experiment concerning the backscattering ?-particles on a target material.
Low Cost Robots as Target System for Students Training Using Java
Authors: Samuelsen Dag Andreas Hals , Graven Olaf Hallan
Published: November 2009

The topic of this paper is a cost efficient programming environment designed with a focus on enhancing the studentsâ?? engagement and effort to complete the assignments. The environment is designed to give the students an approach that is similar to a professional work situation with respect to hardware-software interaction, documentation and complexity. The system presented is based on low-cost, off-the-shelf equipment for easy implementation on mass in an educational institution. As part of the system a low-cost positioning system for mobile robots in an indoor application is included, giving further opportunities for engaging task for the students.
Modulation of Allergenicity of Major House Dust Mite Allergens Der f 1 and Der p 1 by Interaction with an Endogenous Ligand
Authors: Takai Toshiro , Kato Takeshi , Hatanaka Hideki , Inui Kyoko , Nakazawa Takuya , Ichikawa Saori , Mitsuishi Kouichi , Ogawa Hideoki , Okumura Ko
Published: November 2009

Although many allergens bind endogenous molecules other than Abs in the human body, whether the interaction can modulate allergenicity has been unknown. Here, we investigated the effect of the interaction of recombinant major mite group 1 allergens (Der f 1 and Der p 1), which belong to the papain-like cysteine protease family, with an endogenous protease inhibitor, cystatin A, on their allergenicity. Cystatin A bound reduced forms of the allergens, in which the cysteine residue at the catalytic center of the protease activity was reduced by treatment with l-cysteine, but did not bind oxidized forms. Cystatin A partially inhibited the binding of IgE in mite-allergic volunteers’ sera to the reduced forms, but unexpectedly enhanced the basophil histamine-releasing activity. A catalytic site-mutant of Der f 1 behaved in terms of histamine release, similarly to the reduced form. Molecular modeling showed that cystatin A interacts with the allergens within a narrow area. The results indicate that interaction with cystatin A reduces the limited number of IgE epitopes of the allergens but enhances their biological activity to release histamine, suggesting a new concept, that interaction between allergens and their endogenous ligands modulates the allergenicity even toward enhancement in the effector phase. On the other hand, i.p. immunization without alum of mice with cystatin A-treated reduced Der f 1 induced less serum Der f 1-specific IgE than immunization with reduced Der f 1 alone, suggesting that endogenous protease inhibitors suppress the induction of allergen-specific IgE, which is dependent on the enzymatic activity of cysteine protease-allergens, in the sensitization process.
The Yellow Fever Virus Vaccine Induces a Broad and Polyfunctional Human Memory CD8+ T Cell Response
Authors: Akondy Rama S. , Monson Nathan D. , Miller Joseph D. , Edupuganti Srilatha , Teuwen Dirk , Wu Hong , Quyyumi Farah , Garg Seema , Altman John D. , Del Rio Carlos , Keyserling Harry L. , Ploss Alexander , Rice Charles M. , Orenstein Walter A. , Mulligan Mark J. , Ahmed Rafi
Published: November 2009

The live yellow fever vaccine (YF-17D) offers a unique opportunity to study memory CD8+ T cell differentiation in humans following an acute viral infection. We have performed a comprehensive analysis of the virus-specific CD8+ T cell response using overlapping peptides spanning the entire viral genome. Our results showed that the YF-17D vaccine induces a broad CD8+ T cell response targeting several epitopes within each viral protein. We identified a dominant HLA-A2-restricted epitope in the NS4B protein and used tetramers specific for this epitope to track the CD8+ T cell response over a 2 year period. This longitudinal analysis showed the following. 1) Memory CD8+ T cells appear to pass through an effector phase and then gradually down-regulate expression of activation markers and effector molecules. 2) This effector phase was characterized by down-regulation of CD127, Bcl-2, CCR7, and CD45RA and was followed by a substantial contraction resulting in a pool of memory T cells that re-expressed CD127, Bcl-2, and CD45RA. 3) These memory cells were polyfunctional in terms of degranulation and production of the cytokines IFN-γ, TNF-α, IL-2, and MIP-1β. 4) The YF-17D-specific memory CD8+ T cells had a phenotype (CCR7−CD45RA+) that is typically associated with terminally differentiated cells with limited proliferative capacity (TEMRA). However, these cells exhibited robust proliferative potential showing that expression of CD45RA may not always associate with terminal differentiation and, in fact, may be an indicator of highly functional memory CD8+ T cells generated after acute viral infections.
Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani
Authors: Sharma Ankur , Madhubala Rentala
Published: November 2009

Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.
The IL-27 p28 Subunit Binds Cytokine-Like Factor 1 to Form a Cytokine Regulating NK and T Cell Activities Requiring IL-6R for Signaling
Authors: Crabé Sandrine , Guay-Giroux Angélique , Tormo Aurélie Jeanne , Duluc Dorothée , Lissilaa Rami , Guilhot Florence , Mavoungou-Bigouagou Ulrick , Lefouili Fouad , Cognet Isabelle , Ferlin Walter , Elson Greg , Jeannin Pascale , Gauchat Jean-François
Published: November 2009

IL-27 is formed by the association of a cytokine subunit, p28, with the soluble cytokine receptor EBV-induced gene 3 (EBI3). The IL-27R comprises gp130 and WSX-1. The marked difference between EBI3−/− and WSX-1−/− mice suggests that p28 has functions independent of EBI3. We have identified an alternative secreted complex formed by p28 and the soluble cytokine receptor cytokine-like factor 1 (CLF). Like IL-27, p28/CLF is produced by dendritic cells and is biologically active on human NK cells, increasing IL-12- and IL-2-induced IFN-γ production and activation marker expression. Experiments with Ba/F3 transfectants indicate that p28/CLF activates cells expressing IL-6Rα in addition to the IL-27R subunits. When tested on CD4 and CD8 T cells, p28/CLF induces IL-6Rα-dependent STAT1 and STAT3 phosphorylation. Furthermore, p28/CLF inhibits CD4 T cell proliferation and induces IL-17 and IL-10 secretion. These results indicate that p28/CLF may participate in the regulation of NK and T cell functions by dendritic cells. The p28/CLF complex engages IL-6R and may therefore be useful for therapeutic applications targeting cells expressing this receptor. Blocking IL-6R using humanized mAbs such as tocilizumab has been shown to be beneficial in pathologies like rheumatoid arthritis and juvenile idiopathic arthritis. The identification of a new IL-6R ligand is therefore important for a complete understanding of the mechanism of action of this emerging class of immunosuppressors.
TLR2 Engagement on Dendritic Cells Promotes High Frequency Effector and Memory CD4 T Cell Responses
Authors: Chandran Smita S. , Verhoeven David , Teijaro John R. , Fenton Matthew J. , Farber Donna L.
Published: November 2009

Ligation of TLR by distinct pathogen components provides essential signals for T cell priming, although how individual TLR engagement affects primary and memory T cell responses is not well defined. In this study, we demonstrate distinct effects of TLR2 vs TLR4 engagement on primary and memory CD4 T cell responses due to differential effects on APC. Priming of influenza hemagglutinin (HA)-specific naive CD4 T cells with HA peptide and the TLR2 agonist Pam3CysK in vivo resulted in a high frequency of activated HA-specific CD4 T cells that predominantly produced IL-2 and IL-17, whereas priming with HA peptide and the TLR4 agonist LPS yielded a lower frequency of HA-specific CD4 T cells and predominant IFN-γ producers. TLR2 agonist priming depended on TLR2 expression by APC, as wild-type CD4 T cells did not expand in response to peptide and Pam3CysK in TLR2-deficient hosts. TLR2-mediated priming also led to an increased frequency of Ag-specific memory CD4 T cells compared with TLR4 priming and mediated enhanced secondary responses to influenza challenge. Our results show that TLR engagement on APC influences both primary and secondary CD4 T cell responses, and suggest that long-term functional capacities of T cells are set by innate signals during early phases of an infection.
Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells
Authors: Sekine Yuichi , Ikeda Osamu , Tsuji Satoshi , Yamamoto Chikako , Muromoto Ryuta , Nanbo Asuka , Oritani Kenji , Yoshimura Akihiko , Matsuda Tadashi
Published: November 2009

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a YXXQ motif in its C-terminal region. Our previous studies revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1α (SDF-1α)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1α-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1α-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling.
β-Defensins 2 and 3 Together Promote Resistance toPseudomonas aeruginosaKeratitis
Authors: Wu Minhao , McClellan Sharon A. , Barrett Ronald P. , Zhang Yunfan , Hazlett Linda D.
Published: November 2009

Defensins play an important role in both innate and adaptive immunity due to their antimicrobial, regulatory, and chemotactic effects. Nonetheless, the role of murine β-defensins (mBD) 3 and 4, the murine homologs of human β-defensins (hBD) 2 and 3, remains unknown in Pseudomonas aeruginosa keratitis. This study explored their role in corneal infection and potential synergy with mBD2, a defensin associated with better outcome in this disease. Immunostaining and real-time RT-PCR data demonstrated that mBD3 and mBD4 expression was inducible and differentially regulated in the infected cornea of resistant BALB/c vs susceptible C57BL/6 (B6) mice. Knockdown studies using small interfering RNA treatment indicated that mBD3, but not mBD4, is required in ocular defense. Moreover, in vivo studies demonstrated individual and combined effects of mBD2 and mBD3 that modulate bacterial load, polymorphonuclear neutrophil (PMN) infiltration, and production of IFN-γ, MIP-2, IL-1β, TNF-α, inducible NO synthase (iNOS), TLR2, TLR4, MyD88, and NF-κB. Most notably, bacterial load was increased at 5 days postinfection by silencing either mBD2 or mBD3, but it was elevated at both 1 and 5 days postinfection when silencing both defensins. PMN infiltration was increased at 1 day postinfection by silencing both defensins or mBD3, but not mBD2 alone. iNOS expression was elevated by silencing mBD2, but it was reduced after silencing mBD3 or both defensins. Additionally, cell sources of mBD2 (macrophages, PMN and fibroblasts) and mBD3 (PMN) in corneal stroma were identified by dual label immunostaining after infection. Collectively, the data provide evidence that mBD2 and mBD3 together promote resistance against corneal infection.
Accumulation of CD11b+ Lung Dendritic Cells in Response to Fungal Infection Results from the CCR2-Mediated Recruitment and Differentiation of Ly-6Chigh Monocytes
Authors: Osterholzer John J. , Chen Gwo-Hsiao , Olszewski Michal A. , Curtis Jeffrey L. , Huffnagle Gary B. , Toews Galen B.
Published: November 2009

Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans is associated with the CCR2-mediated accumulation of lung dendritic cells (DC) and the development of a T1 adaptive immune response. The objective of this study was to identify the circulating DC precursor(s) responsible for this large increase in lung DC numbers. An established murine model was used to evaluate putative DC precursors in the blood, bone marrow, and lungs of CCR2+/+ mice and CCR2−/− mice throughout a time course following infection with C. neoformans. Results demonstrate that numbers of Ly-6Chigh monocytes increased in parallel in the peripheral blood and lungs of CCR+/+ mice, whereas CD11c+ MHC class II+ pre-DC were 10-fold less prevalent in the peripheral blood and did not differ between the two strains. Accumulation of Ly-6Chigh monocytes correlated with a substantial increase in the numbers of CD11b+ DC in the lungs of infected CCR2+/+ mice. Comparative phenotypic analysis of lung cells recovered in vivo suggests that Ly-6Chigh monocytes differentiate into CD11b+ DC in the lung; differentiation is associated with up-regulation of costimulatory molecules and decreased Ly-6C expression. Furthermore, in vitro experiments confirmed that Ly-6Chigh monocytes differentiate into CD11b+ DC. Accumulation of Ly-6Chigh monocytes and CD11b+ DC was not attributable to their proliferation in situ. We conclude that the CCR2-mediated accumulation of CD11b+ DC in the lungs of Cryptococcus-infected mice is primarily attributable to the continuous recruitment and differentiation of Ly-6Chigh monocytes.
Nature as creation from an eco-hermeneutical perspective: From a ‘natural theology’ to a ‘theology of nature’
Authors: Buitendag Johan
Published: November 2009

For researchers who are interested in the relationship between theology and the natural sciences, 2009 is of special importance. It is now 500 years since Calvin was born and 450 years since his Institution of the Christian Religion was finally published. It is also 200 years since Darwin’s birth and 150 years since his On the Origin of Species appeared in print for the first time. Calvin and Darwin are representative of two separate lines which converge in a particular ‘transversal space’. Such insights are regenerating light on our search for scientific truth today. Neither the absolutisation of transcendent revelation, nor that of immanent knowledge of nature, provides an accountable understanding of reality. Against this background, the challenge for Systematic Theology today is to conceive of a ‘theology of nature’, which can be offered as a dialectical third option. An ‘ecohermeneutics’ offers a possibility of establishing such an option for theology. However, such an option will, on the one hand, have to deconstruct the reformed criticism of a natural theology and will, on the other hand, have to make serious work of an evolutionary epistemology.
Role of p53 in transcriptional regulation of proteases in mammals.
Authors: Katara Rahul , Singh N
Published: November 2009

p53, besides being a tumor suppressor protein, is a transcription factor with a powerful activation domain. Mutation(s) in this gene is a frequent event in human carcinogenesis. Several of these mutations lead to loss of its function as transcription factor. Proteases are thought to play an important role in tumor invasion and metastasis by degradation of extra cellular matrices and basement membranes. The function of protein-coding genes is carried out by the protein product, it is important to study p53-dependent expression at the protein level. There are many factors which regulate the expression of proteases in the cell, however here in this review we have focused on the p53 gene and its regulatory effect on the expression of proteases.
Congenital leukemia - A diagnostic dilemma
Authors: Prakash KP , Rau ATK , Bhat ST , Rau AR
Published: November 2009

A 6 day old newborn presented with fever, lethargy, poor suck and mild hepatosplenomegaly, features suggestive of sepsis. Septic work up was negative. Peripheral smear revealed hyperleukocytosis, thrombocytopenia and presence of atypical cells. Bone marrow examination revealed increased myeloblasts. Other causes of leukemoid reaction were ruled out and a final diagnosis of congenital leukaemia was made.
Stress‐Dependent Elastic Properties of Porous Microcracked Ceramics
Authors: Pozdnyakova Irina , Bruno Giovanni , Efremov Alexander M. , Clausen Bjørn , Hughes Darren
Published: November 2009

Although ceramics are considered linear elastic materials, we have observed a non‐linear pseudo‐elastic behavior in porous cellular microcracked ceramics such as β‐eucryptite. This is attributed to the evolution of microstructure in these materials. This behavior is particularly different from that of non‐microcracked ceramics such as silicon carbide. It is shown that in microcracked materials two processes, namely stiffening and softening, always compete when a compressive external load is applied. The first regime is attributed to microcrack closure, and the second to microcracks opening, i.e. to a damage introduced by the applied stress. On the other hand rather a continuous damage is observed in the non‐microcracked case. A comparison has been done between the microscopic (as measured by neutron diffraction) and the macroscopic stress‐strain response. Also, it has been found that at constant load a significant strain relaxation occurs, which has two timescales, possibly driven by the two phenomena quoted above. Indeed, no such relaxation is observed for non‐microcracked SiC. Implications of these findings are discussed.
Formation and Stability of Near Convoluted Structure Obtained in the Ti–46Al–8Ta Alloy Via Air Quenching and Ageing
Authors: Imayev Valery , Gaisin Ramil , Wunderlich Rainer , Valiev Ruslan , Fecht Hans‐Jörg
Published: November 2009

Microstructure evolution after air quenching and variable ageing treatment has been investigated in small‐sized ingot bars of the Ti–46Al–8Ta alloy. It was found that air quenching and subsequent ageing at 1200–1260 °C led to the formation of a homogeneous refined near convoluted microstructure. To increase the stability of the near convoluted structure, very slow cooling after high‐temperature ageing and final long‐term ageing at around 900 °C can be recommended.
Recent Advances in White Organic Light‐Emitting Materials and Devices (WOLEDs)
Authors: Kamtekar Kiran T. , Monkman Andrew P. , Bryce Martin R.
Published: November 2009

WOLEDs offer new design opportunities in practical solid‐state lighting and could play a significant role in reducing global energy consumption. Obtaining white light from organic LEDs is a considerable challenge. Alongside the development of new materials with improved color stability and balanced charge transport properties, major issues involve the fabrication of large‐area devices and the development of low‐cost manufacturing technology. This Review will describe the types of materials (small molecules and polymers) that have been used to fabricate WOLEDs. A range of device architectures are presented and appraised.
Selective Hydrogenation of 5‐Ethoxymethylfurfural over Alumina‐Supported Heterogeneous Catalysts
Authors: Ras Erik‐Jan , Maisuls Sergio , Haesakkers Paul , Gruter Gert‐Jan , Rothenberg Gadi
Published: November 2009

We report here the synthesis and testing of a set of 48 alumina‐supported catalysts for hydrogenation of 5‐ethoxymethylfurfural. This catalytic reaction is very important in the context of converting biomass to biofuels. The catalysts are composed of one main metal (gold, copper, iridium, nickel, palladium, platinum, rhodium, ruthenium) and one promoter metal (bismuth, chromium, iron, sodium, tin, tungsten). Using a 16‐parallel trickle‐flow reactor, we tested all 48 catalyst combinations under a variety of conditions. The results show that both substrate conversion and product selectivity are sensitive towards temperature changes and solvent effects. The best results of >99% yield to the desired product, 5‐ethoxymethylfurfuryl alcohol, are obtained using an iridium/chromium (Ir/Cr) catalyst. The mechanistic implications of different possible reaction pathways in this complex hydrogenation system are discussed.
Silver Acetate/TF‐BiphamPhos‐Catalyzed endo‐Selective Enantioselective 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Vinyl Phenyl Sulfone
Authors: Liang Gang , Tong Min‐Chao , Wang Chun‐Jiang
Published: November 2009

The first catalytic endo‐selective 1,3‐dipolar cycloaddition of azomethine ylides and vinyl phenyl sulfone has been developed successfully. The highly efficient silver acetate (AgOAc)/TF‐BiphamPhos catalytic system exhibited high reactivity, excellent diastereoselectivity (>98:2), good enantioselectivity (67–92% ee) and broad substrate scope under mild conditions.
A Spirocyclic Chiral Borate for Catalytic Enantioselective Nozaki‐Hiyama Allylation of Ketones
Authors: Huang Xin‐Ren , Chen Chinpiao , Lee Gene‐Hsian , Peng Shie‐Ming
Published: November 2009

A new class of chiral spirocyclic borate ligands 5a–d with a rigid borocycle has been developed. The catalyst formed from chromium(II)‐5a promotes the highly efficient enantioselective Nozaki–Hiyama allylation of alkyl and aryl ketones using allyl bromide. The scope of the present method is shown to be wide, and it affords an efficient access to chiral tertiary homoallylic alcohols.
Cancer mortality among French nuclear contract workers
Authors: Guérin Sylvie , Richard Gaël , Biau Alain , Lebre Sophie , Crescini Danièle , Haddy Nadia , Guldner Laurence , Paoletti Catherine , Hill Catherine , de Vathaire Florent
Published: November 2009

Background

Nuclear workers from French contracting companies have received higher doses than workers from Electricité de France (EDF) or Commissariat à l'Energie Atomique (CEA).

Methods

A cohort study of 9,815 workers in 11 contracting companies, monitored for exposure to ionizing radiation between 1967 and 2000 were followed up for a median duration of 12.5 years. Standardized mortality ratios (SMRs) were computed.

Results

Between 1968 and 2002, 250 deaths occurred. Our study demonstrated a clear healthy worker effect (HWE) with mortality attaining half that expected from national mortality statistics (SMR = 0.54, 95% CI = [0.47–0.61]). The HWE was lower for all cancers (SMR = 0.65) than for non‐cancer deaths (SMR = 0.46). The analysis by cancer site showed no excess compared with the general population. Significant trends were observed according to the level of exposure to ionizing radiation for deaths from cancer, deaths from digestive cancer and deaths from respiratory cancer.

Conclusions

The mortality of nuclear workers from contracting companies is very low compared to French national mortality. Am. J. Ind. Med. 52:916–925, 2009. © 2009 Wiley‐Liss, Inc.
Absence of Lamin A/C gene mutations in four Wiedemann–Rautenstrauch syndrome patients
Authors: Morales Luis C. , Arboleda Gonzalo , Rodríguez Yeldy , Forero Diego A. , Ramírez Nelson , Yunis Juan J. , Arboleda Humberto
Published: November 2009

The Wiedemann–Rautenstrauch syndrome (WRS, OMIM: 264090) characterizes a premature aging syndrome in which several features of aging are apparent at birth. We did not find mutations in Lamin A/C (LMNA) gene in four WRS patients, and in particular, we did not find the G608G mutation (GGC > GGT transition) which is associated with most cases with Hutchinson–Gilford progeria (OMIM 176670). These findings suggest that WRS represents a distinct progeroid entity that may be caused by recessive mutations of a different gene. © 2009 Wiley‐Liss, Inc.
Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome
Authors: Yatsenko Svetlana A. , del Valle Torrado Maria , Fernandes Priscilla H. , Wiszniewska Joanna , Gallego Marta , Herrera Jorge , Bacino Carlos A.
Published: November 2009

The etiology of Noonan syndrome (NS) has been greatly elucidated with the discovery of the disease causative genes PTPN11, KRAS, SOS1, and RAF1, all involved in the RAS/MAPK‐signaling cascade. Given that overall mutations are identified in about 70% of patients, identification of other NS associated genes remains a high priority to fully understand the etiopathogenesis of the condition. We report two affected siblings with an apparently balanced rearrangement of chromosome 12 ins(12)(q12p11.2p12.3) which segregates with the Noonan phenotype. The rearrangement was inherited from the phenotypically normal mother who had mosaicism for the derivative chromosome 12. There were no mutations of PTPN11, KRAS, SOS1, or RAF1 genes detected in the probands. Using fluorescence in situ hybridization analysis we identified the three breakpoints involved at 12p12.3, 12p11.2, and 12q12. By microarray analysis, there were no gains or losses near the breakpoints. Neither, the PTPN11 or KRAS region on chromosome 12 was involved in the rearrangement. We hypothesize that other NS candidate gene(s) may be located in the breakpoint regions of chromosome 12 causing the Noonan phenotype in both of these children. © 2009 Wiley‐Liss, Inc.
Goldenhar phenotype in a child with distal 22q11.2 deletion and intracranial atypical teratoid rhabdoid tumor
Authors: Lafay‐Cousin Lucie , Payne Eric , Strother Douglas , Chernos Judy , Chan Michael , Bernier Francois P.
Published: November 2009

Chromosome‐specific low copy repeats (LCRs) are implicated in several clinically significant microdeletion and microduplication syndromes. The well‐recognized phenotype of DiGeorge/velocardiofacial syndrome (DG/VCF) results from deletions of the long arm of chromosome 22 (22q11.2) mediated by the proximal LCRs in this region. More recent evidence suggests that the distal LCRs within 22q11.2 are also implicated in microdeletions and microduplications with less characterized phenotypes. Here we report on an infant diagnosed with Goldenhar syndrome (GS) phenotype who developed an atypical teratoid rhabdoid tumor (AT/RT) of the brain due to a distal deletion of the chromosome 22q11.2 region encompassing theINI1/SMARCB1tumor suppressor. We also discuss the phenotype of patients with germline deletions of this region and the possible implication of the 22q11.2 region in the GS. © 2009 Wiley‐Liss, Inc.
Altered transmission of HOX and apoptotic SNPs identify a potential common pathway for clubfoot
Authors: Ester Audrey R. , Weymouth Katelyn S. , Burt Amber , Wise Carol A. , Scott Allison , Gurnett Christina A. , Dobbs Matthew B. , Blanton Susan H. , Hecht Jacqueline T.
Published: November 2009

Clubfoot is a common birth defect that affects 135,000 newborns each year worldwide. It is characterized by equinus deformity of one or both feet and hypoplastic calf muscles. Despite numerous study approaches, the cause(s) remains poorly understood although a multifactorial etiology is generally accepted. We considered the HOXA and HOXD gene clusters and insulin‐like growth factor binding protein 3 (IGFBP3) as candidate genes because of their important roles in limb and muscle morphogenesis. Twenty SNPs from the HOXA and HOXD gene clusters and 12 SNPs in IGFBP3 were genotyped in a sample composed of non‐Hispanic white and Hispanic multiplex and simplex families (discovery samples) and a second sample of non‐Hispanic white simplex trios (validation sample). Four SNPs (rs6668, rs2428431, rs3801776, and rs3779456) in the HOXA cluster demonstrated altered transmission in the discovery sample, but only rs3801776, located in the HOXA basal promoter region, showed altered transmission in both the discovery and validation samples (P = 0.004 and 0.028). Interestingly, HOXA9 is expressed in muscle during development. An SNP in IGFBP3, rs13223993, also showed altered transmission (P = 0.003) in the discovery sample. Gene–gene interactions were identified between variants in HOXA, HOXD, and IGFBP3 and with previously associated SNPs in mitochondrial‐mediated apoptotic genes. The most significant interactions were found between CASP3 SNPS and variants in HOXA, HOXD, and IGFBP3. These results suggest a biologic model for clubfoot in which perturbation of HOX and apoptotic genes together affect muscle and limb development, which may cause the downstream failure of limb rotation into a plantar grade position. © 2009 Wiley‐Liss, Inc.
Familial occurrence of an association of multiple intestinal atresia and choanal atresia: A new syndrome?
Authors: Ferrarini Alessandra , Osterheld Maria‐Chiara , Vial Yvan , de Viragh Pierre A. , Cotting Jacques , Martinet Danielle , Beckmann Jacques S. , Fellmann Florence
Published: November 2009

We report on two familial cases from a non‐consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post‐mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high‐resolution array CGH revealed no visible anomalies. © 2009 Wiley‐Liss, Inc.
Molecular analysis of cell lines from patients with mucolipidosis II and mucolipidosis III
Authors: Zarghooni Maryam , Dittakavi Sarma S.R.
Published: November 2009

Mucolipidosis II and III are autosomal recessive disorders due to mutations in the GNPTAB and GNPTG genes encoding the αβ‐ and γ‐subunits of the GlcNAc‐1‐phosphotransferase, respectively. This protein has a subunit structure of α2β2γ2 and initiates the first step of tagging lysosomal enzymes with mannose‐6‐phosphate (M6P). In the present study, we screened four MLII and three MLIII cell lines for mutations in GNPTAB and GNPTG. Nine novel mutations in GNPTAB and two previously reported mutations in GNPTAB and GNPTG were identified. By using anti‐peptide antibodies against the α‐ and β‐subunits, we show that mutations in the γ‐subunit affected the assembly and intracellular distribution of the α‐ and β‐subunits. Furthermore, the biochemical phenotypes of MLII and MLIII fibroblasts can be corrected by transfection with wild‐type cDNA expression constructs encoding the α/β‐ and γ‐subunits of GlcNAc‐1‐phosphotransferase, respectively. © 2009 Wiley‐Liss, Inc.
Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study
Authors: Ehlers Cindy L. , Gizer Ian R. , Vieten Cassandra , Wilhelmsen Kirk C.
Published: November 2009

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis‐related phenotypes of “craving” and “withdrawal” using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM‐IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome‐wide significance for linkage (LOD > 3.0) was not found for the DSM‐IV cannabis dependence diagnosis; however, linkage analyses of cannabis “craving” and the cannabis withdrawal symptom of “nervous, tense, restless, or irritable” revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes. © 2009 Wiley‐Liss, Inc.
The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches
Authors: Kitson Russell R. A. , Millemaggi Alessia , Taylor Richard J. K.
Published: November 2009

The amount of research activity concerning α‐methylene‐γ‐butyrolactones and α‐alkylidene‐γ‐butyrolactones has increased dramatically in recent years. This Review summarizes the structural types, biological activities, and biosynthesis of these compounds, concentrating on publications from the past 10 years. Traditional approaches to α‐methylene‐γ‐butyrolactones and α‐alkylidene‐γ‐butyrolactones are then reviewed together with novel approaches, including those from our own research group, reported more recently.
Human Sperm Anatomy: Ultrastructural Localization of the Cannabinoid1 Receptor and a Potential Role of Anandamide in Sperm Survival and Acrosome Reaction
Authors: Aquila Saveria , Guido Carmela , Santoro Antonietta , Perrotta Ida , Laezza Chiara , Bifulco Maurizio , Sebastiano Andò
Published: November 2009

Recently, the endocannabinoid (EC) system and the presence of CB1 receptor (CB1‐R), have been identified in human sperm. However, the effects of EC receptor ligands such as anandamide (N‐arachidonoylethanolamine) and the role of EC system in male fertility is still largely unexplored. In the present study, we investigated the ultrastructural compartmentalization of CB1‐R and analyzed the effects of its stimulation by using a stable analog of anandamide, 2‐methylarachidonyl‐2′‐fluoro‐ethylamide (MET‐F‐AEA). We focused particularly on sperm survival and acrosin activity. The study of human sperm anatomy by transmission electron microscopy with immunogold analysis revealed the location of the CB1‐R prevalently in the sperm membranes of the head and interestingly on the mitochondria. The effect of different concentrations of MET‐F‐AEA from 100 nM to 1 μM evidenced a significant decrease of sperm survival. Interestingly, we analyzed this negative effect at molecular level, testing the EC action on different known sperm survival targets. MET‐F‐AEA‐treatment decreased both pBCL2 and pAkt, two prosurvival proteins, and increased pPTEN expression which is the main regulator of the PI3K/Akt pathway. Moreover, a biphasic effect was observed with increasing MET‐F‐AEA concentrations on the acrosin activity. The blockage of the CB1‐R by using its selective antagonist SR141716 (rimonabant) induced an opposite action on sperm survival supporting a role for this receptor in the biology of the male gamete. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.
A Sensitivity Analysis for Shared‐Parameter Models for Incomplete Longitudinal Outcomes
Authors: Creemers An , Hens Niel , Aerts Marc , Molenberghs Geert , Verbeke Geert , Kenward Michael G.
Published: November 2009

All models for incomplete data either explicitly make assumptions about aspects of the distribution of the unobserved outcomes, given the observed ones, or at least implicitly imply such. One consequence is that there routinely exist a whole class of models, coinciding in their description of the observed portion of the data but differing with respect to their “predictions” of what is unobserved. Within such a class, there always is a single model corresponding to so‐called random missingness, in the sense that the mechanism governing missingness depends on covariates and observed outcomes, but given these not further on unobserved outcomes. We employ these results in the context of so‐called shared‐parameter models where outcome and missingness models are connected by means of common latent variables or random effects, to devise a sensitivity analysis framework. Precisely, the impact of varying unverifiable assumptions about unobserved measurements on parameters of interest is studied. Apart from analytic considerations, the proposed methodology is applied to assess treatment effect in data from a clinical trial in toenail dermatophyte onychomycosis. While our focus is on longitudinal outcomes with incomplete outcome data, the ideas developed in this paper are of use whenever a shared‐parameter model could be considered.
Score Tests for Exploring Complex Models: Application to HIV Dynamics Models
Authors: Drylewicz Julia , Commenges Daniel , Thiébaut Rodolphe
Published: November 2009

In biostatistics, more and more complex models are being developed. This is particularly the case in system biology. Fitting complex models can be very time‐consuming, since many models often have to be explored. Among the possibilities are the introduction of explanatory variables and the determination of random effects. The particularity of this use of the score test is that the null hypothesis is not itself very simple; typically, some random effects may be present under the null hypothesis. Moreover, the information matrix cannot be computed, but only an approximation based on the score. This article examines this situation with the specific example of HIV dynamics models. We examine the score test statistics for testing the effect of explanatory variables and the variance of random effect in this complex situation. We study type I errors and the statistical powers of this score test statistics and we apply the score test approach to a real data set of HIV‐infected patients.