bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of an efficient Bayesian discretization method to biomedical data
Authors: Lustgarten Jonathan L , Visweswaran Shyam , Gopalakrishnan Vanathi , Cooper Gregory F
Published: July 2011

Background

Several data mining methods require data that are discrete, and other methods often perform better with discrete data. We introduce an efficient Bayesian discretization (EBD) method for optimal discretization of variables that runs efficiently on high-dimensional biomedical datasets. The EBD method consists of two components, namely, a Bayesian score to evaluate discretizations and a dynamic programming search procedure to efficiently search the space of possible discretizations. We compared the performance of EBD to Fayyad and Irani's (FI) discretization method, which is commonly used for discretization.

Results

On 24 biomedical datasets obtained from high-throughput transcriptomic and proteomic studies, the classification performances of the C4.5 classifier and the naïve Bayes classifier were statistically significantly better when the predictor variables were discretized using EBD over FI. EBD was statistically significantly more stable to the variability of the datasets than FI. However, EBD was less robust, though not statistically significantly so, than FI and produced slightly more complex discretizations than FI.

Conclusions

On a range of biomedical datasets, a Bayesian discretization method (EBD) yielded better classification performance and stability but was less robust than the widely used FI discretization method. The EBD discretization method is easy to implement, permits the incorporation of prior knowledge and belief, and is sufficiently fast for application to high-dimensional data.
Rigorous assessment and integration of the sequence and structure based features to predict hot spots
Authors: Chen Ruoying , Chen Wenjing , Yang Sixiao , Wu Di , Wang Yong , Tian Yingjie , Shi Yong
Published: July 2011

Background

Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need.

Results

In this study, we first comprehensively collect the features to discriminate hot spots and non-hot spots and analyze their distributions. We find that hot spots have lower relASA and larger relative change in ASA, suggesting hot spots tend to be protected from bulk solvent. In addition, hot spots have more contacts including hydrogen bonds, salt bridges, and atomic contacts, which favor complexes formation. Interestingly, we find that conservation score and sequence entropy are not significantly different between hot spots and non-hot spots in Ab+ dataset (all complexes). While in Ab- dataset (antigen-antibody complexes are excluded), there are significant differences in two features between hot pots and non-hot spots. Secondly, we explore the predictive ability for each feature and the combinations of features by support vector machines (SVMs). The results indicate that sequence-based feature outperforms other combinations of features with reasonable accuracy, with a precision of 0.69, a recall of 0.68, an F1 score of 0.68, and an AUC of 0.68 on independent test set. Compared with other machine learning methods and two energy-based approaches, our approach achieves the best performance. Moreover, we demonstrate the applicability of our method to predict hot spots of two protein complexes.

Conclusion

Experimental results show that support vector machine classifiers are quite effective in predicting hot spots based on sequence features. Hot spots cannot be fully predicted through simple analysis based on physicochemical characteristics, but there is reason to believe that integration of features and machine learning methods can remarkably improve the predictive performance for hot spots.
Genome evolution in the fish family salmonidae: generation of a brook charr genetic map and comparisons among charrs (Arctic charr and brook charr) with rainbow trout
Authors: Timusk Evan R , Ferguson Moira M , Moghadam Hooman K , Norman Joseph D , Wilson Chris C , Danzmann Roy G
Published: July 2011

Background

Salmonids are regarded as 4R derivative species, having experienced 4 whole genome duplication events in their ancestry. Many duplicated chromosome regions still share extensive homology with one another which is maintained primarily through male-based homeologous chromosome pairings during meiosis. The formation of quadrivalents during meiosis leads to pseudolinkage. This phenomenon is more prevalent within 5 of the 12 ancestral teleost linkage groups in salmonids.

Results

We constructed a genetic linkage map for brook charr and used this in combination with the genetic map from Arctic charr, to make comparisons with the genetic map of rainbow trout. Although not all chromosome arms are currently mapped, some homologous chromosome rearrangements were evident between Arctic charr and brook charr. Notably, 10 chromosome arms in brook charr representing 5 metacentric chromosomes in Arctic charr have undergone rearrangements. Three metacentrics have one arm translocated and fused with another chromosome arm in brook charr to a make a new metacentrics while two metacentrics are represented by 4 acrocentric pairs in brook charr. In two cases (i.e., BC-4 and BC-16), an apparent polymorphism was observed with the identification of both a putative metacentric structure (similar to metacentric AC-4 = BC-4 and a joining of acrocentric AC-16 + one arm of AC-28 = BC-16), as well as two separate acrocentric linkage groups evident in the mapping parents. Forty-six of the expected 50 karyotypic arms could be inter-generically assigned. SEX in brook charr (BC-4) was localized to the same homologous linkage group region as in Arctic charr (AC-4). The homeologous affinities detected in the two charr species facilitated the identification of 20 (expected number = 25) shared syntenic regions with rainbow trout, although it is likely that some of these regions were partial or overlapping arm regions.

Conclusions

Inter-generic comparisons among 2 species of charr (genus Salvelinus) and a trout (genus Oncorhynchus) have identified that linkage group arm arrangements are largely retained among these species. Previous studies have revealed that up to 7 regions of high duplicate marker retention occur between Salmo species (i.e., Atlantic salmon and brown trout) and rainbow trout, with 5 of these regions exhibiting higher levels of pseudolinkage. Pseudolinkage was detected in the charr species (i.e., BC-1/21, AC-12/27, AC-6/23, = RT-2p/29q, RT-12p/16p, and RT-27p/31p, respectively) consistent with three of the five 'salmonid-specific' pseudolinkage regions. Chromosome arms with the highest number of duplicated markers in rainbow trout are the linkage group arms with the highest retention of duplicated markers in both charr species.
Addressing challenges in the production and analysis of illumina sequencing data
Authors: Kircher Martin , Heyn Patricia , Kelso Janet
Published: July 2011

Advances in DNA sequencing technologies have made it possible to generate large amounts of sequence data very rapidly and at substantially lower cost than capillary sequencing. These new technologies have specific characteristics and limitations that require either consideration during project design, or which must be addressed during data analysis. Specialist skills, both at the laboratory and the computational stages of project design and analysis, are crucial to the generation of high quality data from these new platforms. The Illumina sequencers (including the Genome Analyzers I/II/IIe/IIx and the new HiScan and HiSeq) represent a widely used platform providing parallel readout of several hundred million immobilized sequences using fluorescent-dye reversible-terminator chemistry. Sequencing library quality, sample handling, instrument settings and sequencing chemistry have a strong impact on sequencing run quality. The presence of adapter chimeras and adapter sequences at the end of short-insert molecules, as well as increased error rates and short read lengths complicate many computational analyses. We discuss here some of the factors that influence the frequency and severity of these problems and provide solutions for circumventing these. Further, we present a set of general principles for good analysis practice that enable problems with sequencing runs to be identified and dealt with.
Patterns, trends and sex differences in HIV/AIDS reported mortality in Latin American countries: 1996-2007
Authors: Alonso Gonzalez Monica , Martin Luise , Munoz Sergio , Jacobson Jerry O
Published: July 2011

Background

International cohort studies have shown that antiretroviral treatment (ART) has improved survival of HIV-infected individuals. National population based studies of HIV mortality exist in industrialized settings but few have been presented from developing countries. Our objective was to investigate on a population basis, the regional situation regarding HIV mortality and trends in Latin America (LA) in the context of adoption of public ART policies and gender differences.

Methods

Cause of death data from vital statistics registries from 1996 to 2007 with "good" or "average" quality of mortality data were examined. Standardized mortality rates and Poisson regression models by country were developed and differences among countries assessed to identify patterns of HIV mortality over time occurring in Latin America.

Results

Standardized HIV mortality following the adoption of public ART policies was highest in Panama and El Salvador and lowest in Chile. During the study period, three overall patterns were identified in HIV mortality trends- following the adoption of the free ART public policies; a remarkable decrement, a remarkable increment and a slight increment. HIV mortality was consistently higher in males compared to females. Mean age of death attributable to HIV increased in the majority of countries over the study period.

Conclusions

Vital statistics registries provide valuable information on HIV mortality in LA. While the introduction of national policies for free ART provision has coincided with declines in population-level HIV mortality and increasing age of death in some countries, in others HIV mortality has increased. Barriers to effective ART implementation and uptake in the context of free ART public provision policies should be further investigated.
Core indicators evaluation of effectiveness of HIV-AIDS preventive-control programmes carried out by nongovernmental organizations. A mixed method study
Authors: Berenguera Anna , Pujol-Ribera Enriqueta , Violan Concepció , Romaguera Amparo , Mansilla Rosa , Giménez Albert , Ascaso Carlos , Almeda Jesús
Published: July 2011

Background

The number of nongovernmental organizations working on AIDS has grown. There is great diversity in the type of activities and population groups that have been targeted. The purposes of this study are: to describe and analyze the objectives and HIV-AIDS preventive activities that are carried out by the AIDS-NGOs that work with AIDS in Catalonia and that receive subsidies from the Department of Health; and to develop a comprehensive proposal for measurable and agreed upon core quality evaluation indicators to monitor and assess those objectives and activities that can have an impact on the fight against inequalities and stigmatization, and incorporate the perspectives of the service providers and users.

Methods

A mixed method study has been carried out with professionals from the 36 NGOs that work with HIV/AIDS in Catalonia, as well as their users. This study achieved the completeness model using the following phases:

1. A systematic review of AIDS-NGOs annual reports and preparation of a catalogue of activities grouped by objectives, level of prevention and AIDS-NGOs target population; 2. A transversal study through an ad-hoc questionnaire administered to the AIDS-NGOs representatives; 3. A qualitative study with a phenomenological approach through focus groups, individual interviews and observations; 4. Consensus meetings between AIDS-NGOs professionals and the research team using Haddon matrices in order to establish a proposal of evaluation indicators.

Results

The information was classified according to level of prevention and level of intervention. A total of 248 objectives and 258 prevention activities were identified. 1564 evaluation indicators, addressed to 7 target population groups, were produced. Thirty core activities were selected. The evaluation indicators proposed for these activities were: 76 indicators for 15 primary prevention activities, 43 for 5 secondary prevention activities and 68 for 10 tertiary prevention activities.

Conclusions

The results could help to homogeneously assess the preventive-control activities carried out of AIDS-NGOs. The proposed indicators could help the professionals to improve the evaluation of the preventive-control AIDS-NGOs activities. Furthermore, the Haddon matrix enables us to identify deficiencies of activities at intervention levels and strategies to bear in mind in order to enhance the future AIDS prevention programs.
Non-cysteine linked MUC1 cytoplasmic dimers are required for Src recruitment and ICAM-1 binding induced cell invasion
Authors: Bernier Ashlyn J , Zhang Jing , Lillehoj Erik , Shaw Andrew RE , Gunasekara Nirosha , Hugh Judith C
Published: July 2011

Background

The mucin MUC1, a type I transmembrane glycoprotein, is overexpressed in breast cancer and has been correlated with increased metastasis. We were the first to report binding between MUC1 and Intercellular adhesion molecule-1 (ICAM-1), which is expressed on stromal and endothelial cells throughout the migratory tract of a metastasizing breast cancer cell. Subsequently, we found that MUC1/ICAM-1 binding results in pro-migratory calcium oscillations, cytoskeletal reorganization, and simulated transendothelial migration. These events were found to involve Src kinase, a non-receptor tyrosine kinase also implicated in breast cancer initiation and progression. Here, we further investigated the mechanism of MUC1/ICAM-1 signalling, focusing on the role of MUC1 dimerization in Src recruitment and pro-metastatic signalling.

Methods

To assay MUC1 dimerization, we used a chemical crosslinker which allowed for the detection of dimers on SDS-PAGE. We then generated MUC1 constructs containing an engineered domain which allowed for manipulation of dimerization status through the addition of ligands to the engineered domain. Following manipulation of dimerization, we immunoprecipitated MUC1 to investigate recruitment of Src, or assayed for our previously observed ICAM-1 binding induced events. To investigate the nature of MUC1 dimers, we used both non-reducing SDS-PAGE and generated a mutant construct lacking cysteine residues.

Results

We first demonstrate that the previously observed MUC1/ICAM-1signalling events are dependent on the activity of Src kinase. We then report that MUC1 forms constitutive cytoplasmic domain dimers which are necessary for Src recruitment, ICAM-1 induced calcium oscillations and simulated transendothelial migration. The dimers are not covalently linked constitutively or following ICAM-1 binding. In contrast to previously published reports, we found that membrane proximal cysteine residues were not involved in dimerization or ICAM-1 induced signalling.

Conclusions

Our data implicates non-cysteine linked MUC1 dimerization in cell signalling pathways required for cancer cell migration.
The relationship between self-reported substance use and psychiatric symptoms in low-threshold methadone maintenance treatment clients
Authors: Fulton Heather G , Barrett Sean P , MacIsaac Cindy , Stewart Sherry H
Published: July 2011

Background

Ongoing psychiatric symptoms and substance use are common difficulties experienced by clients enrolled in methadone maintenance treatment (MMT). However, little research to date has evaluated if specific types of current substance use are related to specific types of current psychiatric symptoms. The present study investigated these relationships with a sample of clients enrolled in a low-threshold MMT program (i.e., clients are not expelled if they continue to use substances). Some clients enrolled in low-threshold programs may never achieve complete abstinence from all substances. Thus, understanding the possibly perpetuating relationships between concurrent substance use and psychiatric symptoms is important. Understanding such relationships may aid in developing possible target areas of treatment to reduce substance use and/or related harms in this population.

Methods

Seventy-seven individuals were interviewed regarding methadone usage and current and past substance use. Current psychiatric symptoms were assessed using a modified version of the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Relationships between types of substances used in the past 30 days and the types and number of psychiatric symptoms experienced in the same timeframe were examined.

Results

The majority of participants (87.0%) reported using alcohol, illicit substances, non-prescribed prescription opioids, or non-prescribed benzodiazepines in the past 30 days and 77.9% of participants reported currently experiencing psychiatric symptoms at levels that would likely warrant diagnosis. Current non-prescribed benzodiazepine use was a predictor for increased severity (i.e., symptom count) of almost all anxiety and mood disorders assessed. Conversely, number and presence of generalized anxiety symptoms and presence of social phobia symptoms predicted current non-prescribed benzodiazepine and alcohol use, respectively.

Conclusions

Individuals enrolled in the present low-threshold MMT program experience a wide variety of psychiatric symptoms and continue to use a variety of substances, including opioids. There was a particularly consistent pattern of associations between non-prescribed benzodiazepine use and a variety of psychiatric symptoms (particularly anxiety) suggesting that addressing concurrent illicit benzodiazepine use and anxiety symptoms in MMT clients warrants further clinical attention and research.
Molecular evolution of Azagny virus, a newfound hantavirus harbored by the West African pygmy shrew (Crocidura obscurior) in Côte d'Ivoire
Authors: Kang Hae Ji , Kadjo Blaise , Dubey Sylvain , Jacquet François , Yanagihara Richard
Published: July 2011

Background

Tanganya virus (TGNV), the only shrew-associated hantavirus reported to date from sub-Saharan Africa, is harbored by the Therese's shrew (Crocidura theresae), and is phylogenetically distinct from Thottapalayam virus (TPMV) in the Asian house shrew (Suncus murinus) and Imjin virus (MJNV) in the Ussuri white-toothed shrew (Crocidura lasiura). The existence of myriad soricid-borne hantaviruses in Eurasia and North America would predict the presence of additional hantaviruses in sub-Saharan Africa, where multiple shrew lineages have evolved and diversified.

Methods

Lung tissues, collected in RNAlater®, from 39 Buettikofer's shrews (Crocidura buettikoferi), 5 Jouvenet's shrews (Crocidura jouvenetae), 9 West African pygmy shrews (Crocidura obscurior) and 21 African giant shrews (Crocidura olivieri) captured in Côte d'Ivoire during 2009, were systematically examined for hantavirus RNA by RT-PCR.

Results

A genetically distinct hantavirus, designated Azagny virus (AZGV), was detected in the West African pygmy shrew. Phylogenetic analysis of the S, M and L segments, using maximum-likelihood and Bayesian methods, under the GTR+I+Γ model of evolution, showed that AZGV shared a common ancestry with TGNV and was more closely related to hantaviruses harbored by soricine shrews than to TPMV and MJNV. That is, AZGV in the West African pygmy shrew, like TGNV in the Therese's shrew, did not form a monophyletic group with TPMV and MJNV, which were deeply divergent and basal to other rodent- and soricomorph-borne hantaviruses. Ancestral distributions of each hantavirus lineage, reconstructed using Mesquite 2.74, suggested that the common ancestor of all hantaviruses was most likely of Eurasian, not African, origin.

Conclusions

Genome-wide analysis of many more hantaviruses from sub-Saharan Africa are required to better understand how the biogeographic origin and radiation of African shrews might have contributed to, or have resulted from, the evolution of hantaviruses.
Classification and treatment of proximal humerus fractures: inter-observer reliability and agreement across imaging modalities and experience
Authors: Foroohar Abtin , Tosti Rick , Richmond John M , Gaughan John P , Ilyas Asif M
Published: July 2011

Proximal humerus fractures (PHF) are common injuries, but previous studies have documented poor inter-observer reliability in fracture classification. This disparity has been attributed to multiple variables including poor imaging studies and inadequate surgeon experience. The purpose of this study is to evaluate whether inter-observer agreement can be improved with the application of multiple imaging modalities including X-ray, CT, and 3D CT reconstructions, stratified by physician experience, for both classification and treatment of PHFs.

Methods

Inter-observer agreement was measured for classification and treatment of PHFs. A total of sixteen fractures were imaged by plain X-ray (scapular AP and lateral), CT scan, and 3D CT reconstruction, yielding 48 randomized image sets. The observers consisted of 16 orthopaedic surgeons (4 upper extremity specialists, 4 general orthopedists, 4 senior residents, 4 junior residents), who were asked to classify each image set using the Neer system, and recommend treatment from four pre-selected choices. The results were evaluated by kappa reliability coefficients for inter-observer agreement between all imaging modalities and sub-divided by: fracture type and observer experience.

Results

All kappa values ranged from "slight" to "moderate" (k = .03 to .57) agreement. For overall classification and treatment, no advanced imaging modality had significantly higher scores than X-ray. However, when sub-divided by experience, 3D reconstruction and CT scan both had significantly higher agreement on classification than X-ray, among upper extremity specialists. Agreement on treatment among upper extremity specialists was best with CT scan. No other experience sub-division had significantly different kappa scores. When sub-divided by fracture type, CT scan and 3D reconstruction had higher scores than X-ray for classification only in 4-part fractures. Agreement on treatment of 4 part fractures was best with CT scan. No other fracture type sub-division had significantly different kappa scores.

Conclusions

Although 3D reconstruction showed a slight improvement in the inter-observer agreement for fracture classification among specialized upper extremity surgeons compared to all imaging modalities, fracture types, and surgeon experience; overall all imaging modalities continue to yield low inter-observer agreement for both classification and treatment regardless of physician experience.
DNA vaccines delivered by human papillomavirus pseudovirions as a promising approach for generating antigen-specific CD8+ T cell immunity
Authors: Peng Shiwen , Ma Barbara , Chen Shu-Hsia , Hung Chien-Fu , Wu TC
Published: July 2011

Background

Human papillomavirus (HPV) pseudovirions have recently been shown to deliver DNA efficiently in vivo, resulting in the priming of antigen-specific CD8+ T cells in vaccinated mice. In the current study, we compare the different preparation methods for the generation of HPV pseudovirions for their ability to efficiently infect cells. We also compare the antigen-specific CD8+ T cell immune responses generated by different DNA delivery methods and several commonly used forms of vaccination with that of HPV pseudovirions.

Results

We found that the preparation method of pseudovirions is important for the efficient delivery of encapsidated DNA. We have shown that vaccination with DNA encoding model antigen ovalbumin (OVA) delivered by HPV-16 pseudovirions was capable of generating therapeutic antitumor effects against OVA-expressing tumor. In addition, vaccination with DNA encoding OVA delivered by HPV-16 pseudovirions generated the highest number of OVA-specific CD8+ T cells in mice in our system compared to DNA delivered by other delivery methods. We also found that vaccination with OVA DNA delivered by HPV-16 pseudovirions generated the highest number of OVA-specific CD8+ T cells in mice compared to other forms of antigen-specific vaccines. Furthermore, HPV-16 pseudovirions were capable of carrying DNA vaccine encoding clinically relevant antigen, telomerase reverse transcriptase, to generate antigen-specific CD8+ T cell immune responses.

Conclusions

Our data suggest that DNA vaccines delivered by HPV-16 pseudovirions may be advantageous compared to other delivery methods and other forms of antigen-specific vaccines for application to antigen-specific immunotherapy.
Extensive characterization of NF-κB binding uncovers non-canonical motifs and advances the interpretation of genetic functional traits
Authors: Wong Daniel , Teixeira Ana , Oikonomopoulos Spyros , Humburg Peter , Lone Imtiaz Nisar , Saliba David , Siggers Trevor , Bulyk Martha , Angelov Dimitar , Dimitrov Stefan , Udalova Irina A , Ragoussis Jiannis
Published: July 2011

Background

Genetic studies have provided ample evidence of the influence of non-coding DNA polymorphisms on trait variance, particularly those occurring within transcription factor binding sites. Protein binding microarrays and other platforms that can map these sites with great precision have enhanced our understanding of how a single nucleotide polymorphism can alter binding potential within an in vitro setting, allowing for greater predictive capability of its effect on a transcription factor binding site.

Results

We have used protein binding microarrays and electrophoretic mobility shift assay-sequencing (EMSA-Seq), a deep sequencing based method we developed to analyze nine distinct human NF-κB dimers. This family of transcription factors is one of the most extensively studied, but our understanding of its DNA binding preferences has been limited to the originally described consensus motif, GGRRNNYYCC. We highlight differences between NF-κB family members and also put under the spotlight non-canonical motifs that have so far received little attention. We utilize our data to interpret the binding of transcription factors between individuals across 1,405 genomic regions laden with single nucleotide polymorphisms. We also associated binding correlations made using our data with risk alleles of disease and demonstrate its utility as a tool for functional studies of single nucleotide polymorphisms in regulatory regions.

Conclusions

NF-κB dimers bind specifically to non-canonical motifs and these can be found within genomic regions in which a canonical motif is not evident. Binding affinity data generated with these different motifs can be used in conjunction with data from chromatin immunoprecipitation-sequencing (ChIP-Seq) to enable allele-specific analyses of expression and transcription factor-DNA interactions on a genome-wide scale.
Predictive genetic testing for the identification of high-risk groups: a simulation study on the impact of predictive ability
Authors: Mihaescu Raluca , Moonesinghe Ramal , Khoury Muin J , Janssens A Cecile JW
Published: July 2011

Background

Genetic risk models could potentially be useful in identifying high-risk groups for the prevention of complex diseases. We investigated the performance of this risk stratification strategy by examining epidemiological parameters that impact the predictive ability of risk models.

Methods

We assessed sensitivity, specificity, and positive and negative predictive value for all possible risk thresholds that can define high-risk groups and investigated how these measures depend on the frequency of disease in the population, the frequency of the high-risk group, and the discriminative accuracy of the risk model, as assessed by the area under the receiver-operating characteristic curve (AUC). In a simulation study, we modeled genetic risk scores of 50 genes with equal odds ratios and genotype frequencies, and varied the odds ratios and the disease frequency across scenarios. We also performed a simulation of age-related macular degeneration risk prediction based on published odds ratios and frequencies for six genetic risk variants.

Results

We show that when the frequency of the high-risk group was lower than the disease frequency, positive predictive value increased with the AUC but sensitivity remained low. When the frequency of the high-risk group was higher than the disease frequency, sensitivity was high but positive predictive value remained low. When both frequencies were equal, both positive predictive value and sensitivity increased with increasing AUC, but higher AUC was needed to maximize both measures.

Conclusions

The performance of risk stratification is strongly determined by the frequency of the high-risk group relative to the frequency of disease in the population. The identification of high-risk groups with appreciable combinations of sensitivity and positive predictive value requires higher AUC.
Cholesterol in pregnancy: a review of knowns and unknowns
Authors: Bartels Änne , O'Donoghue Keelin
Published: July 2011

Cholesterol forms part of every cell in the human body, and also helps make and metabolize hormones, bile acids and vitamin D. Human plasma cholesterol levels are determined by production in the liver and by dietary intake. Lipoproteins carry cholesterol around the body, and facilitate it crossing the placenta. Cholesterol is carefully monitored in the non-pregnant adult population, where its association with atherosclerosis and cardiovascular disease is well understood. Although it is known that cholesterol rises in pregnancy, at present it is not routinely measured or treated. The effects of maternal high cholesterol on pregnancy and on fetal development are not yet fully understood. However, a growing body of evidence from animal and human studies suggests adverse consequences of high cholesterol levels in pregnancy.
A conserved RNA pseudoknot in a putative molecular switch domain of the 3′-untranslated region of coronaviruses is only marginally stable
Authors: Stammler Suzanne N. , Cao Song , Chen Shi-Jie , Giedroc David P.
Published: July 2011

The 3′-untranslated region (UTR) of the group 2 coronavirus mouse hepatitis virus (MHV) genome contains a predicted bulged stem–loop (designated P0ab), a conserved cis-acting pseudoknot (PK), and a more distal stem–loop (designated P2). Base-pairing to create the pseudoknot-forming stem (P1pk) is mutually exclusive with formation of stem P0a at the base of the bulged stem–loop; as a result, the two structures cannot be present simultaneously. Herein, we use thermodynamic methods to evaluate the ability of individual subdomains of the 3′ UTR to adopt a pseudoknotted conformation. We find that an RNA capable of forming only the predicted PK (58 nt; 3′ nucleotides 241–185) adopts the P2 stem–loop with little evidence for P1pk pairing in 0.1 M KCl and the absence of Mg2+; as Mg2+ or 1 M KCl is added, a new thermal unfolding transition is induced and assignable to P1pk pairing. The P1pk helix is only marginally stable, ΔG25 ≈ 1.2 ± 0.3 kcal/mol (5.0 mM Mg2+, 100 mM K+), and unfolded at 37°C. Similar findings characterize an RNA 5′ extended through the P0b helix only (89 nt; 294–185). In contrast, an RNA capable of forming either the P0a helix or the pseudoknot (97 nt; 301–185) forms no P1pk helix. Thermal unfolding simulations are fully consistent with these experimental findings. These data reveal that the PK forms weakly and only when the competing double-hairpin structure cannot form; in the UTR RNA, the double hairpin is the predominant conformer under all solution conditions.
Characterization of Transparent Soil for Unsaturated Applications
Authors: Peters S. B. , Siemens G. , Take W. A.
Published: July 2011

Experimental characterization of unsaturated soils is of primary importance to further understanding of fundamental behavior, as well as allow for accurate modeling and predictions, of constitutive and field behavior. In the laboratory, the most common research methodology used to investigate the hydraulic behavior of unsaturated soils involves placing the unsaturated soil in a column apparatus with measurements of pore pressure and moisture content being made at discrete locations distributed along the elevation of column. These types of tests have provided many valuable insights into unsaturated flow phenomena; however, there are some limitations with this methodology including the discrete nature of the measurement points. In this paper, an alternative method is proposed which aims to combine the use of digital image analysis with a transparent soil to avoid the ambiguity of traditional boundary image measurements of moisture content in column experiments. At 100% saturation, the transparent soil particles appear invisible and allows for the ability to see through the soil mass. Any air bubbles will be visible within the soil voids and as a result, at varying degrees of saturation less than 100%, the soil will become progressively non-transparent. The relationship between pixel intensity of the unsaturated soil and degree of saturation is defined and validated. This relationship allows definition of the degree of saturation throughout the column profile thus giving the opportunity to verify and further develop constitutive models for unsaturated hydraulic behavior.
Strength and Small-Strain Stiffness Characteristics of Unsaturated Sand
Authors: Nyunt T. T. , Leong E. C. , Rahardjo H.
Published: July 2011

Experiments were performed to investigate the effects of initial matric suction and net confining pressure on the small-strain stiffness and shear strength of reconstituted unsaturated sand. A series of constant water content tests was carried out using a modified triaxial apparatus equipped with local displacement transducers and bender elements. Reconstituted sand specimens were allowed to equalize at the required matric suction under net confining pressure using the axis- translation technique before shearing. After reaching matric suction equilibrium, shear wave velocities were measured prior to shearing. Multi-stage shearing tests were performed in order to investigate the effect of initial matric suction using the same specimen. The experimental results showed that at each net confining pressure, small-strain stiffness and peak shear strength showed a nonlinear relationship with matric suction with the change point near the air-entry value of the soil-water characteristic curve. Relationship between small-strain stiffness and net confining pressure was observed to be similar for saturated and unsaturated sands.
A Flexible Wall Permeameter for the Determination of the Water Permeability Function in Unsaturated Soils
Authors: Moncada M. P. H. , de Campos T. M. P. , Steger G.
Published: July 2011

This paper describes the development of a suction controlled flexible wall permeameter for the direct determination of the water permeability function in unsaturated soils. The new permeameter works with applied constant head or constant rate of flow, i.e., the common steady-state techniques. Total volume change of soil specimens during the test are monitored using a high resolution electronic scale. Numerical simulations were performed to evaluate the influence of factors such as flow velocity and matric suction distribution within the specimen and effects of sample height on such factors. Analyses of tests conducted on two tropical soil samples are used to evaluate conventional proposals for the determination of the water permeability function. It is shown that such proposals do not apply in the case of the materials tested and solutions to that are put forwards.
A Stress-controlled Erosion Apparatus for Studying Internal Erosion in Soils
Authors: Chang D. S. , Zhang L. M.
Published: July 2011

Suffusion in soil involves selective erosion of fine particles within the matrix of coarse soil particles under seepage flow. Such loss of fine particles affects the hydraulic and mechanical behavior of the soil. In this study, a stress-controlled erosion apparatus was developed to investigate the initiation and development of suffusion under complex stress states and to study the effect of suffusion on soil stress-strain behavior. The apparatus allows independent control of hydraulic gradient and stress state. The hydraulic gradient is controlled using a water-head control method. The eroded soil and the outflow rate are measured using a soil collection system and a water collection system, respectively. The measurements can be used to study the erosion rate and variations in soil permeability during the erosion process. A series of erosion tests was conducted on a gap-graded soil under the same confining stress but different deviatoric stresses. The results show that the maximum erosion rate, the variations in soil permeability, and the total deformation of the soil specimen increase with the increase of deviatoric stress. After the loss of a significant amount of fine particles in the soil, the stress-strain behavior of the test soil changes from dilative behavior to contractive behavior.
Deflection Lag, Load Lag, and Time Lag of Buried Flexible Pipe
Authors: Howard Amster
Published: July 2011

The Iowa formula was published by Professor M. G. Spangler of Iowa State Univ. in 1941 to predict the deflection of buried flexible pipe. In the equation, he used the term “deflection lag” to describe the increase in flexible pipe defection after the maximum load was reached over the pipe. Unfortunately, the term is currently improperly used in ASTM, AWWA, and ASCE manuals and standards to reflect the increase in deflection starting the day the backfill is completed over the pipe, rather than when the maximum load occurs. The maximum load on a pipe is generally not attained until after 3–12 months after construction. The history of the deflection lag term and the use of the term “load lag” by Professor Spangler are explored. For the increase in pipe deflection following construction completion, the use of the term “time lag” should be used. A table of time lag values for use in estimating deflection is presented. The table is based on empirical data from field measurements.
Effects of Austenitizing Temperatures on Primary Structure Transformation in Cast High-Speed Steel of M2 Type Inoculated with Powder Additions of W and TiB2
Authors: Chaus Alexander S. , Boháčik Michal , Úradník Peter , Porubský Ján
Published: July 2011

The influence of heat treatment on the microstructure of AISI M2 type high-speed steels modified with powder additions of W and TiB2 was studied. The primary focus was on the effects of austenitizing temperatures on the prior austenite grain size and size distribution, volume fraction, and morphology of the eutectic carbides M2C, M6C, and MC, as well as the character of the secondary precipitation of carbides in the high-speed steels studied. It was shown that austenitizing significantly affects the changes in the chemical composition, morphology, size, and character of distribution of the eutectic carbides in the high-speed steels studied, as well as the volume fraction of retained austenite in the matrix and the prior austenite grain size. These changes in carbides seemed to be induced by a diffusion-induced redistribution of alloying elements between the steel matrix and the carbide phases due to their mutual interaction at high temperatures, which is accompanied by carbide decomposition, coagulation and dissolution and, as a consequence, saturation of the solid solution by alloying elements.
Detector Tube Method for Ammonia Compared to Ion Selective Electrode for Selected Class C and Class F Fly Ash
Authors: Butler Steven Roy
Published: July 2011

An investigation into the field tests used to test for ammonia in fly ash was conducted for comparison to the ASTM C311-07 ammonia determination by the ion selective electrode (ISE) test method. “Ammonia tube result” (ATR) refers to a Gastec tube reading on trapped gas over a slurried fly ash mixture that is correlated to the ISE results by linear regression. This paper contains the following: A comparison of the actual ammonia measurement in the lab by ISE and EPA Method 350.1. Testing was performed on the same samples and in duplicate as a confirmation. The statistical correlation of ASTM C-618–08a, class C fly ash by the ATR to the ASTM C311-07 test method is demonstrated which is comparable to the correlation with the EPA method. A discussion of the differences between the ATR and referenced analytical methods on both ASTM C 618 - 08a class C and class F fly ashes is presented. The effect of sodium hydroxide addition as a catalyst for the ammonia release was significant for both ASTM C-618–08a class C and class F fly ash but differences were noted and are presented.
Serum vaspin levels in hypothyroid patients
Authors: Çinar Neşe , Gülçelik Neşe Ersöz , Aydín Kadriye , Akín Şafak , Usman Aydan , Gürlek Alper
Published: July 2011

Objective

To elucidate the link between TSH and obesity, the relationship between TSH and adipocytokines were previously studied. Animal studies demonstrated a possible relationship between vaspin levels and thyroid functions. In this study, we aimed to investigate vaspin levels in hypothyroid states and its relationship with insulin resistance parameters in humans.

Design

Prospective observational study.

Methods

We enrolled 27 overt hypothyroid, 33 subclinical hypothyroid and 41 euthyroid patients. We measured the body mass index (BMI), fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), lipid profile, TSH, free triiodothyronine, free thyroxine and vaspin levels. The change in vaspin levels in 12 overt hypothyroid patients after establishment of euthyroidism was analysed.

Results

All groups were age-matched. Overt hypothyroid group had higher BMI values (P<0.05) than other groups. No significant difference was observed in insulin levels and HOMA-IR among the groups (P>0.05). Adjusted vaspin levels for BMI and age were similar among the groups. Mean vaspin levels in overt, subclinical and euthyroid patients were 1.20±1.17, 1.48±0.93 and 0.95±0.75 ng/ml respectively (P>0.05). There was no significant association between vaspin levels and BMI, fasting glucose, insulin and HOMA-IR (P>0.05). Establishing euthyroidism in hypothyroid patients did not result in a significant change in vaspin levels (before and after treatment, 1.35±1.06 and 1.25±0.68 ng/ml, respectively; P>0.05).

Conclusion

We herein present novel data indicating vaspin levels are neither altered in overt and subclinical hypothyroidism nor have a relationship with features of insulin resistance in hypothyroid patients.
Circulating glucagon is associated with inflammatory mediators in metabolically compromised subjects
Authors: Ortega Francisco J , Moreno-Navarrete José M , Sabater Mónica , Ricart Wifredo , Frühbeck Gema , Fernández-Real José M
Published: July 2011

Background

Acute phase mediators promote metabolic changes by modifying circulating hormones. However, there is virtually no data about the link between glucagon and inflammatory parameters in obesity-related chronic low-grade inflammation.

Study design

We performed both cross-sectional and longitudinal (diet-induced weight loss) studies.

Methods

Circulating glucagon concentrations (ELISA), parameters of glucose and lipid metabolism, interleukin 6 (IL6), and complement factor B (CFB) were analyzed in 316 subjects (250 men and 66 women). The effects of weight loss were investigated in an independent cohort of 20 subjects.

Results

Circulating glucagon significantly correlated with glucose (r=0.407,P<0.0001), HbAlc (r=0.426,P<0.0001), fasting triglycerides (r=0.356,P=0.001), and parameters of innate immune response system such as IL6 (r=0.342,P=0.050) and CFB (r=0.404,P=0.002) in obese subjects with altered glucose tolerance, but not in individuals with normal glucose tolerance (NGT). In obese and NGT subjects, glucagon was associated with fasting triglycerides (r=0.475,P=0.003) and CFB (r=0.624,P=0.001). In obese subjects, glucagon (P=0.019) and CFB (P=0.002) independently contributed to 26% of fasting triglyceride variance (P<0.0001) after controlling for the effects of age and fasting serum glucose concentration in multiple lineal regression models. Moreover, concomitant with fat mass, fasting triglycerides, and CFB, weight loss led to significantly decreased circulating glucagon (−23.1%,P=0.004).

Conclusions

According to the current results, acute phase reactants such as IL6 and CFB are associated with fasting glucagon in metabolically compromised subjects. This suggests that glucagon may be behind the association between inflammatory and metabolic parameters in obesity-associated chronic low-grade inflammation.
Skeletal muscle mitochondrial function in polycystic ovarian syndrome
Authors: Rabøl Rasmus , Svendsen Pernille F , Skovbro Mette , Boushel Robert , Schjerling Peter , Nilas Lisbeth , Madsbad Sten , Dela Flemming
Published: July 2011

Objective

Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry.

Methods

Hyperinsulinemic–euglycemic clamps (40 mU/min per m2) and muscle biopsies were performed on 23 women with PCOS (nine lean (body mass index (BMI) <25 kg/m2) and 14 obese (BMI >25 kg/m2)) and 17 age- and weight-matched controls (six lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function.

Results

Insulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mitochondrial DNA/genomic DNA. We found no correlation between mitochondrial function and indices of insulin sensitivity.

Conclusions

In contrast to previous reports, we found no evidence that skeletal muscle mitochondrial respiration is reduced in skeletal muscle of women with PCOS compared with control subjects. Furthermore, mitochondrial content did not differ between our control and PCOS groups. These results question the causal relationship between reduced mitochondrial function and skeletal muscle IR in PCOS.