bluuebunny/crossref_metadata_2025 huggingface dataset:
Solution of some Engineering Partial Differential Equations Governed by the Minimal of a Functional by Global Optimization Method
Authors: Cheng Y. M. , Li D. Z. , Li N. , Lee Y. Y , Au S. K.
Published: May 2013

Many engineering problems are governed by partial differential equations which can be solved by analytical as well as numerical methods, and examples include the plasticity problem of a geotechnical system, seepage problem and elasticity problem. Although the governing differential equations can be solved by either iterative finite difference method or finite element, there are however limitations to these methods in some special cases which will be discussed in the present paper. The solutions of these governing differential equations can all be viewed as the stationary value of a functional. Using an approximate solution as the initial solution, the stationary value of the functional can be obtained easily by modern global optimization method. Through the comparisons between analytical solutions and fine mesh finite element analysis, the use of global optimization method will be demonstrated to be equivalent to the solutions of the governing partial differential equations. The use of global optimization method can be an alternative to the finite difference/ finite element method in solving an engineering problem, and it is particularly attractive when an approximate solution is available or can be estimated easily.
Linear Analytical Study of Large Deflection of Piezoelectric Layered Plate Under Initial Tension
Authors: Chen C.-F. , Huang B.-C.
Published: May 2013

The linear problem of large deflection of a clamped and layered piezoelectric circular plate under initial tension due to lateral pressure is solved. Von Karman plate theory for large deflection is extended to a symmetrically laminated case including a piezoelectric layer. The thus derived nonlinear governing equations are simplified by neglecting the arising nonlinear terms, yielding a modified Bessel equation or a standard Bessel equation for the lateral slope. These equations are solved analytically by imposing boundary conditions for the clamped edge. For a 3-layered nearly monolithic plate with a low applied voltage upon the piezoelectric layer, the results are in a good agreement with those available in literature for a single-layered plate under pure mechanical loading, thus validates the present approach. Typical 3-layered piezoelectric plates are then implemented and the results show that, piezoelectric effect seems to be apparent only up to a moderate initial tension. For a relatively high pretension, the effect of initial tension appears to be dominant, yielding nearly the same results for the structural responses, regardless of the piezoelectric effect, i.e., the magnitude of voltage applied upon the piezo-electric layer.
Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin andIL-6in diet-induced obese rats
Authors: Luvizotto Renata de Azevedo Melo , Nascimento Andre F. , Imaizumi Erika , Pierine Damiana T. , Conde Sandro J. , Correa Camila R. , Yeum Kyung-Jin , Ferreira Ana Lucia A.
Published: May 2013

Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levelsin vivoin obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C,n6) or a hyperenergetic diet (DIO,n12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n6) and DIO supplemented with lycopene (DIO+L,n6). The animals received maize oil (C and DIO) or lycopene (DIO+L, 10 mg/kg body weight (BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1 (MCP-1),TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO+L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin andIL-6gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression ofMCP-1in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.
Dietary exposure biomarker-lead discovery based on metabolomics analysis of urine samples
Authors: Beckmann Manfred , Lloyd Amanda J. , Haldar Sumanto , Favé Gaëlle , Seal Chris J. , Brandt Kirsten , Mathers John C. , Draper John
Published: May 2013

Although robust associations between dietary intake and population health are evident from conventional observational epidemiology, the outcomes of large-scale intervention studies testing the causality of those links have often proved inconclusive or have failed to demonstrate causality. This apparent conflict may be due to the well-recognised difficulty in measuring habitual food intake which may lead to confounding in observational epidemiology. Urine biomarkers indicative of exposure to specific foods offer information supplementary to the reliance on dietary intake self-assessment tools, such as FFQ, which are subject to individual bias. Biomarker discovery strategies using non-targeted metabolomics have been used recently to analyse urine from either short-term food intervention studies or from cohort studies in which participants consumed a freely-chosen diet. In the latter, the analysis of diet diary or FFQ information allowed classification of individuals in terms of the frequency of consumption of specific diet constituents. We review these approaches for biomarker discovery and illustrate both with particular reference to two studies carried out by the authors using approaches combining metabolite fingerprinting by MS with supervised multivariate data analysis. In both approaches, urine signals responsible for distinguishing between specific foods were identified and could be related to the chemical composition of the original foods. When using dietary data, both food distinctiveness and consumption frequency influenced whether differential dietary exposure could be discriminated adequately. We conclude that metabolomics methods for fingerprinting or profiling of overnight void urine, in particular, provide a robust strategy for dietary exposure biomarker-lead discovery.
Reconsidering theAuctoritasof Augustus
Authors: Rowe Gregory
Published: May 2013

Res Gestae34.3 (‘auctoritate omnibus praestiti’) is conventionally taken to reflect Augustus' conception of the fundamental nature of his rule, and a great deal of attention has consequently been given to the wordauctoritas. But no other source repeats this idea or gives weight toauctoritas. The passage is best understood as alluding to a specific event, probably Octavian's becomingprinceps senatusin 28b.c.
Cognitive Behaviour Therapy for Psychotic Symptoms: A Randomized Controlled Effectiveness Trial
Authors: Kråkvik Bodil , Gråwe Rolf W. , Hagen Roger , Stiles Tore C.
Published: May 2013

Background: Cognitive behavioural therapy for psychosis (CBTp) is currently a recommended form of psychosocial treatment for persons suffering from persistent psychotic symptoms. It has been argued that effect sizes from efficacy studies cannot be generalized to real clinical settings. Aims: Our aim was to evaluate whether the positive results from randomized controlled trials conducted by experts could be replicated in clinical setting with a heterogeneous sample of patients with psychotic disorder. Method: Patients referred to the study were either randomized to CBTp + TAU (the treatment group) or to a waiting-list group, only receiving TAU. The patients were assessed on different outcome measures such as the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Psychotic Symptom Rating Scales (PSYRATS), at pretreatment, at posttreatment (6 months), and at 12 months follow-up. In total, 45 patients participated in the study. Results: The results showed that 20 sessions of CBTp performed significantly better than the waiting list controls with respect to the global score on the BPRS, the delusional scale on the PSYRATS, and the GAF symptom score at posttreatment. At 12 months follow-up only the GAF symptom score remained significantly changed for the total sample. Conclusions: The study revealed that CBTp delivered by non-experts in routine clinical settings can produce improvements in positive psychotic symptoms, and also that some of these improvements can be maintained at one year follow-up.
Cs-Corrected Scanning Transmission Electron Microscopy Investigation of Dislocation Core Configurations at a SrTiO3/MgO Heterogeneous Interface
Authors: Zhu Yuanyuan , Song Chengyu , Minor Andrew M. , Wang Haiyan
Published: May 2013

Heterostructures and interfacial defects in a 40-nm-thick SrTiO3 (STO) film grown epitaxially on a single-crystal MgO (001) were investigated using aberration-corrected scanning transmission electron microscopy and geometric phase analysis. The interface of STO/MgO was found to be of the typical domain-matching epitaxy with a misfit dislocation network having a Burgers vector of ½ aSTO ⟨100⟩. Our studies also revealed that the misfit dislocation cores at the heterogeneous interface display various local cation arrangements in terms of the combination of the extra-half inserting plane and the initial film plane. The type of the inserting plane, either the SrO or the TiO2 plane, alters with actual interfacial conditions. Contrary to previous theoretical calculations, the starting film planes were found to be dominated by the SrO layer, i.e., a SrO/MgO interface. In certain regions, the starting film planes change to the TiO2/MgO interface because of atomic steps at the MgO substrate surface. In particular, four basic misfit dislocation core configurations of the STO/MgO system have been identified and discussed in relation to the substrate surface terraces and possible interdiffusion. The interface structure of the system in reverse—MgO/STO—is also studied and presented for comparison.
Pioneers in Optics: Louis de Broglie and Edwin Herbert Land
Authors: Davidson Michael W.
Published: May 2013

In the early twentieth century, the long standing argument about whether the character of light was particle-based or wavelike was finally coming to an end as the scientists of the day began to accept that light could assume a dual nature. The possibility that such a duality might apply to matter as well as light was first proposed by physicist Louis de Broglie. Born in Dieppe, France, de Broglie studied in Paris and was descended from members of the French nobility. In his youth, he considered a career as a diplomat but later turned to science and pursued the study of theoretical physics. His brother, Maurice, who had also decided to become a physicist and made many advances in the study of X rays, reportedly had a considerable influence on de Broglie and was the first to introduce him to the work of Albert Einstein and Max Planck.
Quantitative Analysis and High-Resolution X-ray Mapping with a Field Emission Electron Microprobe
Authors: Hombourger C. , Outrequin M.
Published: May 2013

The electron probe microanalyzer (EPMA) provides quantitative analysis for nearly all chemical elements with a spatial resolution of analysis about ~1 μm, which is relevant to microstructures in a wide variety of materials and mineral specimens. Recent implementation of the Schottky emitter field-emission gun (FEG) electron source in the EPMA has significantly improved the spatial resolution and detectability of the EPMA technique.
Riding in cars with boys: Elinor Ostrom's adventures with the police
Authors: BOETTKE PETER , PALAGASHVILI LIYA , LEMKE JAYME
Published: May 2013

More than 40 years ago, Elinor Ostrom began her adventures with the police. In order to combat the conventional view that ‘bigger means better’, Ostrom pioneered a fieldwork-based framework for measuring police services that utilized consumer surveys and thereby created a community-centered model of analysis for public services. In this paper, we contend that although Ostrom's career demonstrated the importance of employing multiple methods, her most enduring contributions and legacy came from on-the-ground research. Her case studies and fieldwork proved to be necessary for examining complex systems beyond the state–market dichotomy, and these methods of analysis should be defended as critical for inquiry into the variety of institutional arrangements.
Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke
Authors: Ruscher Karsten , Kuric Enida , Liu Yawei , Walter Helene L , Issazadeh-Navikas Shohreh , Englund Elisabet , Wieloch Tadeusz
Published: May 2013

After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3 +) and CD3 + /CD4 + T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.
Teachers' Perceptions of Adolescent Females With Voice Disorders
Authors: Zacharias Stephanie R. C. , Kelchner Lisa N. , Creaghead Nancy
Published: May 2013

Purpose

The purpose of this study was to explore teachers' attitudes toward, and perceptions of personality traits of, female adolescents who presented with voice disorders.

Method

For this comparative study consisting of a 25-item web-based semantic differential survey, teachers rated voice recordings of 4 female adolescents (considered normophonic, mildly, moderately, and severely dysphonic, respectively) on 18 personality traits and 6 teacher attitude parameters. A flyer with a link to the survey was distributed via e-mail to teachers at 8 middle and high schools in Ohio.

Results

Thirty-two teachers completed the survey. Results revealed differences in teachers' perceptions of female adolescents with a normal voice compared to those with voice disorders.

Conclusion

Adolescent female students with voice disorders may be at risk for academic, social, and vocational difficulties. These results highlight and support the need to inform teachers, speech-language pathologists, students, and families about the potential for subtle biases and negative perceptions of students with voice disorders by teachers. Furthermore, teaching self-advocacy to students who have voice disorders may help them obtain an optimal education experience.
Severe Speech Sound Disorders: An Integrated Multimodal Intervention
Authors: King Amie M. , Hengst Julie A. , DeThorne Laura S.
Published: May 2013

Purpose

: This study introduces an integrated multimodal intervention (IMI) and examines its effectiveness for the treatment of persistent and severe speech sound disorders (SSD) in young children. The IMI is an activity-based intervention that focuses simultaneously on increasing the
quantity
of a child's meaningful productions of target words and providing supports to shape the
quality
of natural speech productions of target sounds by systematically incorporating the full range of each child's communicative repertoire, including augmentative and alternative communication (AAC) systems and natural speech and language.

Method

: A multiple-probe single-subject research design was used to assess the effectiveness of the IMI for 3 boys (ages 4 to 8) with moderate to severe SSD, all of whom used speech-generating AAC.

Results

: All 3 participants demonstrated an increase in the amount of speech they produced (i.e., quantity) and an increase in the production accuracy of their target speech sounds (i.e., quality).

Conclusion

This study demonstrated that simultaneously targeting natural speech and AAC speech using an integrated multimodal approach was effective in producing positive changes in both communication and speech production goals. These findings strongly suggest that integrating multimodal speech-generating AAC with traditional speech intervention was effective at supporting natural speech production for these children.
Morphological Awareness Intervention With Kindergartners and First- and Second-Grade Students From Low Socioeconomic Status Homes: A Feasibility Study
Authors: Apel Kenn , Brimo Danielle , Diehm Emily , Apel Lynda
Published: May 2013

Purpose

The effect of a morphological awareness intervention on the morphological awareness and literacy skills of students from low socioeconomic status homes was investigated.

Method

A 9-week intervention designed to increase awareness of affixes and the relations between base words and their inflected and derived forms was conducted with students in kindergarten (
n
 =  19), 1st grade (
n
 =  21), and 2nd grade (
n
 =  21). Groups of 4–5 students were provided with instruction 4 times a week for 25 min a day.

Results

Results showed medium to very large clinically significant gains in morphological awareness and literacy abilities (
d
s  =  0.29–2.96) across all participants.

Conclusion

The results of this feasibility study suggest that morphological awareness instruction that requires students to analyze, recognize, orally produce, and determine the spelling patterns of multimorphemic words leads to therapeutic effects within a population of young students who are at risk for future reading difficulties. Initial clinical implications, limitations of the study, and research suggestions are discussed.
Orbital Floor Reconstruction with Free Flaps after Maxillectomy
Authors: Sampathirao Leela Mohan C. S. R. , Thankappan Krishnakumar , Duraisamy Sriprakash , Hedne Naveen , Sharma Mohit , Mathew Jimmy , Iyer Subramania
Published: May 2013

Background

The purpose of this study is to evaluate the outcome of orbital floor reconstruction with free flaps after maxillectomy.

Methods

This was a retrospective analysis of 34 consecutive patients who underwent maxillectomy with orbital floor removal for malignancies, reconstructed with free flaps. A cross-sectional survey to assess the functional and esthetic outcome was done in 28 patients who were alive and disease-free, with a minimum of 6 months of follow-up.

Results

Twenty-six patients had bony reconstruction, and eight had soft tissue reconstruction. Free fibula flap was the commonest flap used ( n = 14). Visual acuity was normal in 86%. Eye movements were normal in 92%. Abnormal globe position resulted in nine patients. Esthetic satisfaction was good in 19 patients (68%). Though there was no statistically significant difference in outcome of visual acuity, eye movement, and patient esthetic satisfaction between patients with bony and soft tissue reconstruction, more patients without bony reconstruction had abnormal globe position ( p = 0.040).

Conclusion

Free tissue transfer has improved the results of orbital floor reconstruction after total maxillectomy, preserving the eye. Good functional and esthetic outcome was achieved. Though our study favors a bony orbital reconstruction, a larger study with adequate power and equal distribution of patients among the groups would be needed to determine this. Free fibula flap remains the commonest choice when a bony reconstruction is contemplated.
Finite Element Analysis Comparison of Plate Designs in Managing Fractures Involving the Mental Foramen
Authors: Mahathi Neralla , Azariah Emmanuel , Ravindran C.
Published: May 2013

Introduction

The aim of the study was to propose an ideal plating design for fractures running through the mental foramen.

Methods

The study compared three plating designs—two four-hole miniplates, 2 × 2-hole three-dimensional (3D) plate, and modified 2 × 2-hole 3D plate (posterior strut removed)—using finite element analysis. Von Mises stresses generated around the plates and bone were measured, as well as the mobility that is generated between the fracture fragments by applying muscle forces to generate bite force in one test and applying a force of 500 N over the premolars and first molar region in the second test.

Results

Von Mises stress in bone with miniplates measured 9.24 MPa in test 1 and 131.99 MPa in test 2. The stress with unmodified 3D plates measured 34.9 MPa in test 1 and150.03 MPa in test 2. The stress with modified 3D plates measured 24.98 MPa in test 1 and 150.59 MPa in test 2. Von Mises stress on the plates and screws measured 28.23 MPa, 95.97 MPa, 72.93 MPa in test 1 and 458.63 MPa, 779.01 MPa, 742.39 MPa in test 2 on miniplates, unmodified 3D plates, and modified 3D plates, respectively. The fracture mobility generated in the model with miniplates measured 0.001 mm in test 1 and 0.01 mm in test 2 and 0.007 mm and 0.02 mm in the model with unmodified 3D plates in test 1 and in test 2, respectively. In the model with modified 3D plates, the value was 0.001 mm and 0.01 mm in tests 1 and 2, respectively.

Conclusion

The ideal plate design is the two-plate technique with minimal stress generation on the bone and the hardware. The modified 3D plate has adequate strength to be used in the region but needs to be studied in detail.
Chaos at fifty
Authors: Motter Adilson E. , Campbell David K.
Published: May 2013

In 1963 an MIT meteorologist revealed deterministic predictability to be an illusion and gave birth to a field that still thrives.
Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa
Authors: Fujihara Yoshitaka , Tokuhiro Keizo , Muro Yuko , Kondoh Gen , Araki Yoshihiko , Ikawa Masahito , Okabe Masaru
Published: May 2013

Formation of spermatozoa of normal shape, number, and motility is insufficient for the male siring of pups. The spermatozoa must be accompanied by sound fertilizing ability. We found that males with disrupted testis-expressed gene 101 (
Tex101
) produce normal-looking but fertilization-incompetent spermatozoa, which were accompanied by a deficiency of a disintegrin and metallopeptidase domain 3 (ADAM3) on sperm plasma membrane. It was also found that the existence of TEX101 on spermatozoa was regulated by angiotensin-converting enzyme (ACE). The removal of GPI-anchored protein TEX101 by ACE was essential to produce fertile spermatozoa, and the function of ACE was not depending on its well-known peptidase activity. The finding of TEX101 as a unique specific substrate for ACE may provide a potential target for the production of an awaited contraceptive medicine for men.
Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factorMYBL1
Authors: Ramkissoon Lori A. , Horowitz Peleg M. , Craig Justin M. , Ramkissoon Shakti H. , Rich Benjamin E. , Schumacher Steven E. , McKenna Aaron , Lawrence Michael S. , Bergthold Guillaume , Brastianos Priscilla K. , Tabak Barbara , Ducar Matthew D. , Van Hummelen Paul , MacConaill Laura E. , Pouissant-Young Tina , Cho Yoon-Jae , Taha Hala , Mahmoud Madeha , Bowers Daniel C. , Margraf Linda , Tabori Uri , Hawkins Cynthia , Packer Roger J. , Hill D. Ashley , Pomeroy Scott L. , Eberhart Charles G. , Dunn Ian F. , Goumnerova Liliana , Getz Gad , Chan Jennifer A. , Santagata Sandro , Hahn William C. , Stiles Charles D. , Ligon Azra H. , Kieran Mark W. , Beroukhim Rameen , Ligon Keith L.
Published: May 2013

Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart fromBRAFkinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factorMYBL1with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related genev-myb avian myeloblastosis viral oncogene homolog(MYB) on 6q23.3. Whole-genome sequencing of aMYBL1-rearranged diffuse astrocytoma grade II demonstratedMYBL1tandem duplication and few other events. TruncatedMYBL1transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors withMYBL1partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas.
Surface display of a massively variable lipoprotein by a
Legionella
diversity-generating retroelement
Authors: Arambula Diego , Wong Wenge , Medhekar Bob A. , Guo Huatao , Gingery Mari , Czornyj Elizabeth , Liu Minghsun , Dey Sanghamitra , Ghosh Partho , Miller Jeff F.
Published: May 2013

Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by facilitating localized DNA sequence evolution through a specialized error-prone reverse transcription process. We characterized a DGR in
Legionella pneumophila
, an opportunistic human pathogen that causes Legionnaires disease. The
L. pneumophila
DGR is found within a horizontally acquired genomic island, and it can theoretically generate 10
26
unique nucleotide sequences in its target gene, legionella determinent target A (
ldtA
), creating a repertoire of 10
19
distinct proteins. Expression of the
L. pneumophila
DGR resulted in transfer of DNA sequence information from a template repeat to a variable repeat (VR) accompanied by adenine-specific mutagenesis of progeny VRs at the 3′end of
ldtA
.
ldtA
encodes a twin-arginine translocated lipoprotein that is anchored in the outer leaflet of the outer membrane, with its C-terminal variable region surface exposed. Related DGRs were identified in
L. pneumophila
clinical isolates that encode unique target proteins with homologous VRs, demonstrating the adaptability of DGR components. This work characterizes a DGR that diversifies a bacterial protein and confirms the hypothesis that DGR-mediated mutagenic homing occurs through a conserved mechanism. Comparative bioinformatics predicts that surface display of massively variable proteins is a defining feature of a subset of bacterial DGRs.
A new member of the 4-methylideneimidazole-5-one–containing aminomutase family from the enediyne kedarcidin biosynthetic pathway
Authors: Huang Sheng-Xiong , Lohman Jeremy R. , Huang Tingting , Shen Ben
Published: May 2013

4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of
l
-α-amino acids to β-amino acids with either an (
R
) or an (
S
) configuration.
l
-Phenylalanine and
l
-tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an (
R
)-2-aza-3-chloro-β-tyrosine moiety reminiscent of the (
S
)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, the biosynthesis of which uncovered the first known MIO-containing aminomutase, SgcC4. Comparative analysis of the KED and C-1027 biosynthetic gene clusters inspired the proposal for (
R
)-2-aza-3-chloro-β-tyrosine biosynthesis starting from 2-aza-
l
-tyrosine, featuring KedY4 as a putative MIO-containing aminomutase. Here we report the biochemical characterization of KedY4, confirming its proposed role in KED biosynthesis. KedY4 is an MIO-containing aminomutase that stereospecifically catalyzes the conversion of 2-aza-
l
-tyrosine to (
R
)-2-aza-β-tyrosine, exhibiting no detectable activity toward 2-aza-
l
-phenylalanine or
l
-tyrosine as an alternative substrate. In contrast, SgcC4, which stereospecifically catalyzes the conversion of
l
-tyrosine to (
S
)-β-tyrosine in C-1027 biosynthesis, exhibits minimal activity with 2-aza-
l
-tyrosine as an alternative substrate but generating (
S
)-2-aza-β-tyrosine, a product with the opposite stereochemistry of KedY4. This report of KedY4 broadens the scope of known substrates for the MIO-containing aminomutase family, and comparative studies of KedY4 and SgcC4 provide an outstanding opportunity to examine how MIO-containing aminomutases control substrate specificity and product enantioselectivity.
Targeted resequencing implicates the familial Mediterranean fever gene
MEFV
and the toll-like receptor 4 gene
TLR4
in Behçet disease
Authors: Kirino Yohei , Zhou Qing , Ishigatsubo Yoshiaki , Mizuki Nobuhisa , Tugal-Tutkun Ilknur , Seyahi Emire , Özyazgan Yilmaz , Ugurlu Serdal , Erer Burak , Abaci Neslihan , Ustek Duran , Meguro Akira , Ueda Atsuhisa , Takeno Mitsuhiro , Inoko Hidetoshi , Ombrello Michael J. , Satorius Colleen L. , Maskeri Baishali , Mullikin James C. , Sun Hong-Wei , Gutierrez-Cruz Gustavo , Kim Yoonhee , Wilson Alexander F. , Kastner Daniel L. , Gül Ahmet , Remmers Elaine F.
Published: May 2013

Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (
IL10, IL23R
,
CCR1
,
STAT4
,
KLRK1
,
KLRC1, KLRC2, KLRC3, KLRC4
, and
ERAP1
) and 11 genes selected for their role in innate immunity
(IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4
) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene,
IL23R
(
P
= 6.9 × 10
−5
), and one gene involved in innate immunity,
TLR4
(
P
= 8.0 × 10
−4
), were associated with BD. In addition, damaging or rare damaging
NOD2
variants were nominally significant across all three burden tests applied (
P
= 0.0063–0.045). Furthermore, carriage of the familial Mediterranean fever gene (
MEFV
) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65;
P
= 1.8 × 10
−12
). The disease-associated NSVs in
MEFV
and
TLR4
implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.
Iraqi sociology and Al Wardi’s contributions
Authors: Al Hashimi Hamied G. M.
Published: May 2013

This paper offers an appraisal of the contribution of Dr Ali Al Wardi – one of the Middle East’s pioneers in sociology – to the foundation of Iraqi sociology. It opens with an introduction to sociology in Iraq past and present, followed by an assessment of the sociological approach of Al Wardi, his hypotheses including his theories on the ‘ambivalent personality’ exemplified in Iraq, which was later generalized to the Arab personality more broadly, and his sociological critiques. It was in these areas that Al Wardi became one of the leading liberal thinkers in the Arab world and his books continue to be bestsellers to this day. The paper will also posit the direct reasons for the success of his scientific contribution and the popularity of his premises and arguments. To achieve these objectives, it examines the most lasting aspects of his research, Al Wardi’s own published works and those written about his contribution, including books, papers and articles which either glorify or criticize, to help form a better understanding of Al Wardi’s contributions to Iraqi sociology.
Pointwise confidence intervals for a survival distribution with small samples or heavy censoring
Authors: Fay Michael P. , Brittain Erica H. , Proschan Michael A.
Published: May 2013

We propose a beta product confidence procedure (BPCP) that is a non-parametric confidence procedure for the survival curve at a fixed time for right-censored data assuming independent censoring. In such situations, the Kaplan–Meier estimator is typically used with an asymptotic confidence interval (CI) that can have coverage problems when the number of observed failures is not large, and/or when testing the latter parts of the curve where there are few remaining subjects at risk. The BPCP guarantees central coverage (i.e. ensures that both one-sided error rates are no more than half of the total nominal rate) when there is no censoring (in which case it reduces to the Clopper–Pearson interval) or when there is progressive type II censoring (i.e. when censoring only occurs immediately after failures on fixed proportions of the remaining individuals). For general independent censoring, simulations show that the BPCP maintains central coverage in many situations where competing methods can have very substantial error rate inflation for the lower limit. The BPCP gives asymptotically correct coverage and is asymptotically equivalent to the CI on the Kaplan–Meier estimator using Greenwood’s variance. The BPCP may be inverted to create confidence procedures for a quantile of the underlying survival distribution. Because the BPCP is easy to implement, offers protection in settings when other methods fail, and essentially matches other methods when they succeed, it should be the method of choice.
Future Cereal Starch Bioengineering: Cereal Ancestors Encounter Gene Technology and Designer Enzymes
Authors: Blennow Andreas , Jensen Susanne L. , Shaik Shahnoor S. , Skryhan Katsiaryna , Carciofi Massimiliano , Holm Preben B. , Hebelstrup Kim H. , Tanackovic Vanja
Published: May 2013

The importance of cereal starch production worldwide cannot be overrated. However, the qualities and resulting values of existing raw and processed starch do not fully meet future demands for environmentally friendly production of renewable, advanced biomaterials, functional foods, and biomedical additives. New approaches for starch bioengineering are needed. In this review, we discuss cereal starch from a combined universal bioresource point of view. The combination of new biotechniques and clean technology methods can be implemented to replace, for example, chemical modification. The recently released cereal genomes and the exploding advancement in whole genome sequencing now pave the road for identifying new genes to be exploited to generate a multitude of completely new starch functionalities directly in the cereal grain, converting cereal crops to production plants. Newly released genome data from cereal ancestors can potentially allow for the reintroduction of cereal traits including, for example, health‐promoting carbohydrates that may have been lost during domestication. Raw materials produced in this manner can be processed by clean enzyme‐assisted techniques or thermal treatment in combination to further functionalize or stabilize the starch polymers. Importantly, such products can be multifunctional in the sense of combined food/material or food/pharma purposes, for example, edible plastics, shape memory materials, and cycloamylose carriers and stabilizers for diverse bioactives.
Characterization of the LOV1-Mediated, Victorin-Induced, Cell-Death Response with Virus-Induced Gene Silencing
Authors: Gilbert Brian M. , Wolpert Thomas J.
Published: May 2013

Accepted 11 April 2013.

Victoria blight, caused by Cochliobolus victoriae, is a disease originally described on oat and recapitulated on Arabidopsis. C. victoriae pathogenesis depends upon production of the toxin victorin. In oat, victorin sensitivity is conferred by the Vb gene, which is genetically inseparable from the Pc2 resistance gene. Concurrently, in Arabidopsis, sensitivity is conferred by the LOCUS ORCHESTRATING VICTORIN EFFECTS1 (LOV1) gene. LOV1 encodes a nucleotide-binding site leucine-rich repeat protein, a type of protein commonly associated with disease resistance, and LOV1 “guards” the defense thioredoxin, TRX-h5. Expression of LOV1 and TRX-h5 in Nicotiana benthamiana is sufficient to confer victorin sensitivity. Virus-induced gene silencing was used to characterize victorin-induced cell death in N. benthamiana. We determined that SGT1 is required for sensitivity and involved in LOV1 protein accumulation. We screened a normalized cDNA library and identified six genes that, when silenced, suppressed LOV1-mediated, victorin-induced cell death and cell death induced by expression of the closely related RPP8 resistance gene: a mitochondrial phosphate transporter, glycolate oxidase, glutamine synthetase, glyceraldehyde 3-phosphate dehydrogenase, and the P- and T-protein of the glycine decarboxylase complex. Silencing the latter four also inhibited cell death and disease resistance mediated by the PTO resistance gene. Together, these results provide evidence that the victorin response mediated by LOV1 is a defense response.
Rice yellow stunt rhabdovirus Protein 6 Suppresses Systemic RNA Silencing by Blocking RDR6-Mediated Secondary siRNA Synthesis
Authors: Guo Hongyan , Song Xiaoguang , Xie Chuanmiao , Huo Yan , Zhang Fujie , Chen Xiaoying , Geng Yunfeng , Fang Rongxiang
Published: May 2013

The P6 protein of Rice yellow stunt rhabdovirus (RYSV) is a virion structural protein that can be phosphorylated in vitro. However its exact function remains elusive. We found that P6 enhanced the virulence of Potato virus X (PVX) in Nicotiana benthamiana and N. tabacum plants, suggesting that it might function as a suppressor of RNA silencing. We examined the mechanism of P6-mediated silencing suppression by transiently expressing P6 in both N. benthamiana leaves and rice protoplasts. Our results showed that P6 could repress the production of secondary siRNAs and inhibit systemic green fluorescent protein RNA silencing but did not interfere with local RNA silencing in N. benthamiana plants or in rice protoplasts. Intriguingly, P6 and RDR6 had overlapping subcellular localization and P6 bound both rice and Arabidopsis RDR6 in vivo. Furthermore, transgenic rice plants expressing P6 showed enhanced susceptibility to infection by Rice stripe virus. Hence, we propose that P6 is part of the RYSV's counter-defense machinery against the plant RNA silencing system and plays a role mainly in affecting RDR6-mediated secondary siRNA synthesis. Our work provides a new perspective on how a plant-infecting nucleorhabdovirus may counteract host RNA silencing-mediated antiviral defense.
Guard Cell Purification and RNA Isolation Suitable for High-Throughput Transcriptional Analysis of Cell-Type Responses to Biotic Stresses
Authors: Obulareddy Nisita , Panchal Shweta , Melotto Maeli
Published: May 2013

Stomata, micro-pores on the leaf surface, are formed by a pair of guard cells. In addition to controlling water loss and gas exchange between the plant and the environment, these cells act as immunity gates to prevent pathogen invasion of the plant apoplast. Here, we report a brief procedure to obtain highly pure guard cell preparations using conditions that preserve the guard cell transcriptome as much as possible for a robust high-throughput RNA sequence analysis. The advantages of this procedure included i) substantial shortening of the time required for obtaining high yield of >97% pure guard cell protoplasts (GCP), ii) extraction of enough high quality RNA for direct sequencing, and iii) limited RNA decay during sample manipulation. Gene expression analysis by reverse transcription quantitative polymerase chain reaction revealed that wound-related genes were not induced during release of guard cells from leaves. To validate our approach, we performed a high-throughput deep-sequencing of guard cell transcriptome (RNA-seq). A total of 18,994 nuclear-encoded transcripts were detected, which expanded the transcriptome by 70%. The optimized GCP isolation and RNA extraction protocols are simple, reproducible, and fast, allowing the discovery of genes and regulatory networks inherent to the guard cells under various stresses.
Predictors of Survival from Perioperative Cardiopulmonary Arrests
Authors: Ramachandran Satya Krishna , Mhyre Jill , Kheterpal Sachin , Christensen Robert E. , Tallman Kristen , Morris Michelle , Chan Paul S.
Published: May 2013

Background:

Perioperative cardiopulmonary arrests are uncommon and little is known about rates and predictors of in-hospital survival.

Methods:

Using the Get With The Guidelines®-Resuscitation national in-hospital resuscitation registry, we identified all patients aged 18 yr or older who experienced an index, pulseless cardiac arrest in the operating room or within 24 h postoperatively. The primary outcome was survival to hospital discharge, and the secondary outcome was neurologically intact recovery among survivors. Multivariable logistic regression models using generalized estimating equation models were used to identify independent predictors of survival and neurologically intact survival.

Results:

A total of 2,524 perioperative cardiopulmonary arrests were identified from 234 hospitals. The overall rate of survival to discharge was 31.7% (799/2,524), including 41.8% (254/608) for ventricular tachycardia and ventricular fibrillation, 30.5% (296/972) for asystole, and 26.4% (249/944) for pulseless electrical activity. Ventricular fibrillation and pulseless ventricular tachycardia were independently associated with improved survival. Asystolic arrests occurring in the operating room and postanesthesia care unit were associated with improved survival when compared to other perioperative locations. Among patients with neurological status assessment at discharge, the rate of neurologically intact survival was 64.0% (473/739). Prearrest neurological status at admission, patient age, inadequate natural airway, prearrest ventilatory support, duration of event, and event location were significant predictors of neurological status at discharge.

Conclusion:

Among patients with a perioperative cardiac arrest, one in three survived to hospital discharge, and good neurological outcome was noted in two of three survivors.
Interleukin‐17 Immunity in Pediatric Crohn Disease and Ulcerative Colitis
Authors: Hölttä Veera , Klemetti Paula , Salo Harri M. , Koivusalo Antti , Pakarinen Mikko , Westerholm‐Ormio Mia , Kolho Kaija‐Leena , Vaarala Outi
Published: May 2013

Objective:

The present understanding of inflammatory bowel disease pathogenesis mainly relies on studies of adult patients. Therefore, we studied the balance between T‐effector and regulatory cells in pediatric inflammatory bowel disease.

Methods:

Quantitative polymerase chain reaction and immunohistochemistry served to quantify the expression of immunological markers in mucosal biopsies and flow cytometry analysis was used in peripheral blood mononuclear cells.

Results:

Colonic interleukin (IL)‐17, IL‐22, and IL‐6 mRNA upregulation and increase in the number of colonic IL‐17+ cells were demonstrated in both Crohn disease (CD) and ulcerative colitis (UC). Likewise, colonic forkhead box P3 (FOXP3) mRNA expression and the number of colonic FOXP3+ cells were increased both in CD and in UC and were accompanied in CD also with increased numbers of FOXP3+CD25highCD4 cells in peripheral blood. Ileal relation of IL‐17+/CD4+ cells was increased only in CD.

Conclusions:

We showed activation of colonic IL‐17/IL‐22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics. Upregulation of IL‐17 was restricted to colon in UC, but existed in the ileum and in the colon in active CD.
Effect of Infant and Follow‐on Formulas Containing B lactis and Galacto‐ and Fructo‐oligosaccharides on Infection in Healthy Term Infants
Authors: Bocquet Alain , Lachambre Emmanuelle , Kempf Christian , Beck Laurence
Published: May 2013

Objective:

The aim of the present study was to compare the effect of Bifidobacterium animalis subspecies lactis (B lactis) alone or with 90% galacto‐oligosaccharide (GOS) and 10% fructo‐oligosaccharide (FOS) on infections in infants.

Methods:

In a multicenter trial, healthy, term, newborn infants ages 42 days or younger whose mothers had decided not to breast‐feed beyond this age received infant and follow‐on formulas containing B lactis (107 colony‐forming units/g) + GOS/FOS (0.4 g/100 mL, intention‐to‐treat, n = 261) or B lactis alone (107 colony‐forming units/g, intention‐to‐treat, n = 267). Investigators accessed computer‐generated randomization sequences via a remote server. Infants were exclusively fed formulas until 4 to 6 months of age and along with complementary feeding thereafter up to 12 months. The primary outcome was the mean number of annual infections reported by the investigators. Secondary outcomes were mean gains in anthropometric measurements, frequency of antibiotic use, and occurrence of adverse events based on investigators' records at each visit and gastrointestinal tolerance (daily stool frequency and consistency) and volume of formula intake recorded in 6‐day diaries by parents.

Results:

Mean ± standard deviation infection rates in infants followed up to 12 months (full analysis set) were 4.9 ± 3.2 per infant per year in the B lactis + GOS/FOS group (n = 219) and 4.5 ± 3.0 per infant per year in the B lactis group (n = 220; analysis of variance, P = 0.18). Mean daily weight gain was slightly lower in the B lactis + GOS/FOS than the B lactis group (16.1 ± 2.9 vs 16.6 ± 2.6 g/day, P = 0.046), but was not clinically significant. Other outcomes were not significantly different between groups.

Conclusions:

Formulas containing B lactis + GOS/FOS did not reduce infection rates beyond those containing only B lactis.