bluuebunny/crossref_metadata_2025 huggingface dataset:
Can a smaller than expected crown–rump length reliably predict the occurrence of subsequent miscarriage in a viable first trimester pregnancy?
Authors: Abuelghar Wessam M. , Fathi Hisham M. , Ellaithy Mohamed I. , Anwar Mohammad A.
Published: July 2013

Aim

To elicit the diagnostic value of smaller than expected crown–rump length (CRL) to predict the occurrence of subsequent miscarriage in women with a viable first trimester pregnancy.

Methods

A cohort study was conducted in the fetal special care unit of a tertiary care maternity hospital. The recruited participants were young pregnant women at 6–13 weeks of gestation. Transvaginal ultrasonography was performed to determine pregnancy viability and measure the embryonic CRL. To compare the differences in CRL between those pregnancies that remained viable and those that subsequently miscarried, the deviation of observed and expected CRL was calculated and expressed in standard deviations (SD) as Z score. The primary outcome measure was the percentage of pregnancies with antecedent growth delay that miscarried by the end of the first trimester.

Results

Of the pregnancies that subsequently miscarried, 79.3% (42/53) had smaller than expected CRL, and in 56.6% (30/53) the CRL was 2 SD or less from that expected for gestational age (GA). The mean Z score for CRL was significantly lower in pregnancies that subsequently miscarried compared to pregnancies that remained viable (−2.9 ± 2.6 vs −0.8 ± 2.1, respectively, P < 0.001). A CRL of 2 SD or less from that expected for GA as a cut‐off point had a sensitivity of 56.6, specificity of 81.9, positive predictive value of 36.6, negative predictive value of 91.1, likelihood ratio positive of 3.1 and likelihood ratio negative of 0.5 in predicting subsequent miscarriage.

Conclusion

Viable first trimester pregnancies with small for GA CRL were associated with a higher probability of a subsequent miscarriage.
Genotypic prevalence of human papillomavirus infection during normal pregnancy: A cross‐sectional study
Authors: Kim Yun Hwan , Park Joong Shin , Norwitz Errol R. , Park Jeong Woo , Kim Sun Min , Lee Seung Mi , Park Chan‐Wook , Kim Byoung Jae , Koo Ja Nam , Oh Ig Hwan , Song Yong Sang
Published: July 2013

Aim

Genital human papillomavirus (HPV) infection is a necessary factor in most cases of cervical cancer, but malignant transformation requires the presence of additional cofactors such as pregnancy. Little is known about the effect of pregnancy on genital HPV carriage. We therefore analyzed the prevalence and genotypic patterns of genital HPV infections in normal pregnancies.

Methods

The prevalence of HPV infection was measured in 960 consecutive normal pregnant or post‐partum women by HPV‐DNA chip analysis of cervical swabs. Data were analyzed by trimester and adjusted for sociodemographic, reproductive and reported sexual history.

Results

The overall prevalence of HPV infection in the population was 24.3%. High‐risk HPV genotypes were detected in 68.2% of infected subjects, including HPV 16 (18.7%), 39 (16.4%), 53 (10.1%), and 56 (9.4%). High‐risk HPV genotypes were significantly more prevalent in the second trimester (23.8%) compared with the other periods (first trimester, 13.2%; third trimester, 17.4%; post‐partum, 15.1%; P = 0.010). However, the high‐risk HPV genotypes 16 or 18 were detected most frequently in the third trimester (7.2%) as compared to the other periods (first trimester, 2.9%; second trimester, 5.2%; post‐partum, 2.1%; P = 0.03). After adjusting for confounding variables, overall HPV infection (odds ratio = 1.84, 95% confidence interval = 1.24–2.75) and high‐risk HPV genotypes (odds ratio = 1.94, 95% confidence interval = 1.23–3.05) were significantly more common in the second trimester.

Conclusion

The second trimester may be the most vulnerable period in high‐risk HPV infections, which necessitates future investigations.
In vitro and in vivo characterization of porcine acellular dermal matrix for gingival augmentation procedures
Authors: Pabst A. M. , Happe A. , Callaway A. , Ziebart T. , Stratul S. I. , Ackermann M. , Konerding M. A. , Willershausen B. , Kasaj A.
Published: July 2013

Background and Objective

Recently, porcine acellular dermal matrix (PADM) has been proposed as a possible alternative to autogenous grafts in periodontal plastic surgery. The aim of the present study was to investigate the in vitro responses of four different oral cell lines cultured on a novel PADM. Furthermore, tissue reaction to PADM was evaluated histologically after subcutaneous implantation in mice.

Material and Methods

Human gingival fibroblasts (HGF), human osteoblast‐like cells, human umbilical vein endothelial cells and human oral keratinocytes (HOK) were cultured and transferred on to the PADM. A tissue culture polystyrene surface served as the control. The viability of all tested cell lines on PADM was measured by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide colorimetric assay and PrestoBlue® reagent. The ToxiLight® assay was performed to analyze the effect of PADM on adenylate kinase release. PADM was implanted into nude mice subcutaneously and subjected to histological analysis after 21 d.

Results

Using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide colorimetric assays, all tested cell lines cultured on PADM demonstrated a significant increase of viability compared to the control group (each p < 0.001) with the exception of HGF and HOK after 3 d (each p > 0.05). According to the PrestoBlue® analysis, all cell lines demonstrated a significant increase of viability compared to the control group at the particular points of measurement after 18 h (HGF p < 0.01; human osteoblast‐like cells, human umbilical vein endothelial cells, HOK each p < 0.001). No significant cytotoxic effects of PADM on the tested cell lines could be observed, as assessed by changes in adenylate kinase release. Subcutaneous implantation of PADM into nude mice demonstrated good integration with surrounding tissues and significant revascularization of its collagen structure.

Conclusion

Overall, the results suggest that PADM is a promising substitute for autogenous soft tissue grafts in periodontal surgery.
Replication arrest is a major threat to growth at low temperature in Antarctic Pseudomonas syringae Lz4W
Authors: Sinha Anurag K. , Pavankumar Theetha L. , Kamisetty Srinivasulu , Mittal Pragya , Ray Malay K.
Published: July 2013

Chromosomal damage was detected previously in the recBCD mutants of the Antarctic bacterium Pseudomonas syringae Lz4W, which accumulated linear chromosomal DNA leading to cell death and growth inhibition at 4°C. RecBCD protein generally repairs DNA double‐strand breaks by RecA‐dependent homologous recombination pathway. Here we show that ΔrecA mutant of P. syringae is not cold‐sensitive. Significantly, inactivation of additional DNA repair genes ruvAB rescued the cold‐sensitive phenotype of ΔrecBCD mutant. The ΔrecA and ΔruvAB mutants were UV‐sensitive as expected. We propose that, at low temperature DNA replication encounters barriers leading to frequent replication fork (RF) arrest and fork reversal. RuvAB binds to the reversed RFs (RRFs) having Holliday junction‐like structures and resolves them upon association with RuvC nuclease to cause linearization of the chromosome, a threat to cell survival. RecBCD prevents this by degrading the RRFs, and facilitates replication re‐initiation. This model is consistent with our observation that low temperature‐induced DNA lesions do not evoke SOS response in P. syringae. Additional studies show that two other repair genes, radA (encoding a RecA paralogue) and recF are not involved in providing cold resistance to the Antarctic bacterium.
Moving forward: dispersal and species interactions determine biotic responses to climate change
Authors: Urban Mark C. , Zarnetske Phoebe L. , Skelly David K.
Published: July 2013

We need accurate predictions about how climate change will alter species distributions and abundances around the world. Most predictions assume simplistic dispersal scenarios and ignore biotic interactions. We argue for incorporating the complexities of dispersal and species interactions. Range expansions depend not just on mean dispersal, but also on the shape of the dispersal kernel and the population's growth rate. We show how models using species‐specific dispersal can produce more accurate predictions than models applying all‐or‐nothing dispersal scenarios. Models that additionally include species interactions can generate distinct outcomes. For example, species interactions can slow climate tracking and produce more extinctions than models assuming no interactions. We conclude that (1) just knowing mean dispersal is insufficient to predict biotic responses to climate change, and (2) considering interspecific dispersal variation and species interactions jointly will be necessary to anticipate future changes to biological diversity. We advocate for collecting key information on interspecific dispersal differences and strong biotic interactions so that we can build the more robust predictive models that will be necessary to inform conservation efforts as climates continue to change.
On their best behavior: how animal behavior can help determine the combined effects of species interactions and climate change
Authors: Harmon Jason P. , Barton Brandon T.
Published: July 2013

The increasingly appreciated link between climate change and species interactions has the potential to help us understand and predict how organisms respond to a changing environment. As this connection grows, it becomes even more important to appreciate the mechanisms that create and control the combined effect of these factors. However, we believe one such important set of mechanisms comes from species’ behavior and the subsequent trait‐mediated interactions, as opposed to the more often studied density‐mediated effects. Behavioral mechanisms are already well appreciated for mitigating the separate effects of the environment and species interactions. Thus, they could be at the forefront for understanding the combined effects. In this review, we (1) show some of the known behaviors that influence the individual and combined effects of climate change and species interactions; (2) conceptualize general ways behavior may mediate these combined effects; and (3) illustrate the potential importance of including behavior in our current tools for predicting climate change effects. In doing so, we hope to promote more research on behavior and other mechanistic factors that may increase our ability to accurately predict climate change effects.
‘The Chicken or the Egg?’ Interregional Contacts Viewed Through a Technological Lens at Late Bronze Age Tiryns, Greece
Authors: Brysbaert Ann
Published: July 2013

This paper reviews the environmental circumstances of the ostrich and its eggs, in order to provide a geographical overview of past human usage and modification of ostrich eggshells in the Aegean and, more specifically, at Tiryns, while placing this craft in its contemporary context in the Late Bronze Age Mediterranean basin. This ostrich shell evidence from Tiryns is contextualized and analysed through the approach of the chaîne opératoire in order to understand the material in the framework of Tiryns' Late Bronze Age craft activities, and within the Late Bronze Age Aegean network of contacts that brought this material to Tiryns in the first place.
Investigating Dietary Variation With Burial Ritual in Iron Age Hampshire: An Isotopic Comparison of Suddern Farm Cemetery and Danebury Hillfort Pit Burials
Authors: Stevens Rhiannon E. , Lightfoot Emma , Hamilton Julie , Cunliffe Barry , Hedges Robert E.M.
Published: July 2013

The formal Iron Age cemetery at Suddern Farm, located near Danebury hillfort, provides a unique opportunity to investigate whether differences in burial tradition and ritual behaviour seen at the two sites are linked to access to food resources during life. We measured the carbon and nitrogen isotopic ratios of 40 humans from Suddern Farm and compared this information to previously published faunal data from the site and human isotopic data from Danebury. Despite substantial variation in the faunal isotope signatures, the adult humans have notably homogeneous isotopic results, which are very similar to those at Danebury. This indicates that they had similar access to dietary resources, and supports other evidence for the interdependence of sites with regard to their farming practices. Any social practices that define groups within Hampshire Iron Age society at these sites do not seem to have had any detectable influence on diet.
Luminescent Hybrid Ionogels Functionalized with rare Earth fluoride Up‐conversion Nanocrystals Dispersing in Ionic Liquid
Authors: Yan Zhi‐Yuan , Yan Bing
Published: July 2013

Rare earth doped fluorides (BaMgF4, aYF4 and BaYF5/BaLuF5) have been synthesized and dispersed in an ionic liquid compound, (3‐triethoxysilyl) propyl‐3‐methylimidazolium chloride (denoted as IM+Cl−). Through the cohydrolysis and copolycondensatoin reaction between the alkoxy group (3‐triethoxysilyl) of IM+ and tetraethoxysilane in the presence of carboxylic acids (formic acid) as catalyst and water source, luminescent hybrid ionogels form subsequently. 1H NMR spectroscopy, X‐ray diffraction, transmission electron microscopy, scanning electron microscopy and especially up‐conversion (UC) luminescence spectroscopy are used to characterize the precursors and the resulted hybrid ionogels. These hybrid ionogels exhibit the UC luminescence properties of immobilized rare earth fluoride nanocrystals (BaMgF4, NaYF4 and BaYF5/BaLuF5) doped Er3+/Tm3+, Yb3+.
A sun holiday is a sunburn holiday
Authors: Petersen Bibi , Thieden Elisabeth , Philipsen Peter Alshede , Heydenreich Jakob , Young Antony Richard , Wulf Hans Christian
Published: July 2013

Many people take holidays in sunny locations with the express aim of sunbathing. This may result in sunburn, which is a risk factor for skin cancer. We investigated 25 Danish sun seekers during a week's holiday in the Canary Islands. The percentage of body surface area with sunburn was determined by daily skin examinations by the same observer. Erythemally effective ultraviolet radiation (UVR) exposure was assessed with time‐stamped personal dosimeters worn on the wrist. Volunteers reported their clothing cover and sunscreen use in diaries, and this information was used to determine body site‐specific UVR doses after adjustment for sun protection factor. Remarkably, we found that all volunteers sunburned at some point. The risk of sunburn correlated significantly with the adjusted body site‐specific UVR dose. Furthermore, there was also a significant relationship between the daily UVR dose and percentage of body surface area with sunburn. Our study shows that holiday UVR exposure results in a high risk of sunburn, which potentially increases the risk of skin cancer. Possible protection by melanogenesis is insufficient to protect against sunburn during a 1‐week sun holiday. Finally, our data clearly support a substantial skin cancer risk from sun holidays.
Smoking‐related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung
Authors: Antoniou Katerina M. , Walsh Simon L. , Hansell David M. , Rubens Michael R. , Marten Katharina , Tennant Rachel , Hansel Trevor , Desai Sujal R. , Siafakas Nikolaos M. , du Bois Roland M , Wells Athol U.
Published: July 2013

Background and objective

A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis‐interstitial lung disease (RA‐ILD)), and to compare the morphological features of lung fibrosis between smokers and non‐smokers.

Methods

Using high‐resolution computed tomography, the prevalence of emphysema and the pack‐year smoking histories associated with emphysema were compared between current/ex‐smokers with IPF (n = 186) or RA‐ILD (n = 46), and non‐chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non‐smokers.

Results

Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA‐ILD, was associated with lower pack‐year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack‐year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02–1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non‐smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA‐ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non‐smokers.

Conclusions

In IPF and RA‐ILD, a high prevalence of concurrent emphysema, in association with low pack‐year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases.
The Differential Effects of Noneconomic Damage Cap Levels on Medical Malpractice Insurers
Authors: Born Patricia , Neale Faith Roberts
Published: July 2013

This study examines the effect of tort reform on medical malpractice insurers with an emphasis on the effect of cap levels on noneconomic damages. While previous research finds that caps on noneconomic damages have a beneficial effect on insurer performance, these studies do not evaluate the effects of caps of varying size. Examining insurer data from 1997 to 2007, we test whether cap levels matter. We find that insurer performance generally improves when the cap is set at $250,000, but caps exceeding $250,000 are not associated with improved performance, as they are possibly not binding on award amounts.
Market Implications of Public Policy Interventions: The Case of Florida's Property Insurance Market
Authors: Medders Lorilee A. , Nyce Charles M. , Bradley Karl J.
Published: July 2013

This article asserts that the market for property insurance, particularly homeowners insurance, in the State of Florida is experiencing failures, and that a combination of market problems, externalities, and interventions unique to Florida led to these failures. The authors provide evidence of market failures in the form of undesirable market outcomes, both over time and in comparison to other coastal states. Also, they provide a narrative description of the market events, problems, and policies preceding these adverse market developments and link the narrative to the evidence. Recommendations for a return to risk‐based pricing and incentives for appropriate property mitigation are made.
The Right to Know? State Politics of Fracking Disclosure
Authors: Fisk Jonathan M.
Published: July 2013

U.S. energy firms are increasingly expanding their production of natural gas oftentimes by relying on a controversial extraction technique known as hydraulic fracturing. While proponents cite a litany of benefits including economic development and reduced carbon emissions, opponents articulate concerns typically centering on environmental quality. Caught between these opposing points of view, states are turning to disclosure requirements. Yet all disclosure statutes are not created equally. In order to better understand this variation, I utilize Abel, Stephan, and Kraft's (ASK) 2007 performance model, which evaluates the effectiveness of information‐based disclosure rules for industry. The model here, however, is applied in an attempt to understand why disclosure regulations emerge and vary across states. Results generally validate the ASK approach but with one caveat. I find that in the context of differing disclosure regulations, the ASK model's pollution severity/risk measure may be refined by including risk perception.
The third paradigm in labour pain preparation and management: the childbearing woman's paradigm
Authors: Karlsdottir Sigfridur Inga , Halldorsdottir Sigridur , Lundgren Ingela
Published: July 2013

The study's rationale

Women's experiences regarding labour pain preparation and management have been largely neglected.

Aims and objectives

Explore women's experiences regarding labour pain preparation and management in normal childbirth.

Methodological design and justification

The Vancouver School of doing phenomenology was the methodological approach of the study since it provides inside information about the lived experience.

Research methods

Data were collected through in‐depth interviews with 14 participants; seven primiparous and seven multiparous women.

Results

The women described a challenging journey of no return through labour pain, with different landmarks on the journey. They described how they prepared for the pain; the context of the pain experience; how they experienced and managed the pain with different strategies and how they saw the pain at the journey's end. The quality of the midwife's presence and professionalism was of great importance to them. The ‘good midwives’ they described created a special atmosphere which was warm and secure and was conducive to their managing the pain. The women also described how important it was for them to have a supportive partner, with whom they had a mutual understanding, in order to manage the pain.

Conclusions

In this paper, we are presenting a study within the third paradigm in labour pain preparation and management: the childbearing woman's paradigm – the first and second being the midwifery and the medical paradigm, respectively. Midwives can play a major role in working with women in their preparation and management of labour pain. In the future, more research has to be done to illuminate this essential part of the childbearing woman's paradigm.
Isolating the Network Effect of Immigrants on Trade
Authors: Aleksynska Mariya , Peri Giovanni
Published: July 2013

Within the migration–trade nexus literature, this paper proposes a more carefully defined measure of migration business networks and quantifies its impact on bilateral trade. Using cross‐sectional data and controlling for the overall bilateral stock of migrants, the share of migrants employed in managerial/business‐related occupations has a strong additional effect on trade. Those immigrants should be the ones directly involved in the diffusion and transmission of information relevant for companies trading with other countries. Their presence is found to increase the volume of trade, especially of imports, beyond the already known effect of immigrants or highly educated immigrants. When we control for the presence of highly educated immigrants, the share of immigrants in business network occupations shows a particularly large effect on trade in differentiated goods. We also find that highly educated individuals in business‐related occupations are those contributing to stimulate import and export by the largest margin. Business network effects seem particularly important in stimulating exports to culturally different countries, such as those with different language and legal origin.
Assessment of predictive molecular variables in feline oral squamous cell carcinoma treated with stereotactic radiation therapy
Authors: Yoshikawa H. , Ehrhart E. J. , Charles J. B. , Custis J. T. , LaRue S. M.
Published: July 2013

This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression‐free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO2). MedianSTandPFIwere 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higherMVDor more keratinizedSCChad significantly shorterSTorPFIthan patients with lowerMVDor less keratinizedSCC(P= 0.041 and 0.049, respectively). Females had significantly longerPFIandSTthan males (P≤ 0.016). Acute toxicities were minimal. However, treatment‐related complications such as fractured mandible impacted quality of life. In conclusion,SRTalone should be considered as a palliative treatment.MVDand degree of keratinization may be useful prognostic markers.
Bacterial culture of apheresis platelets: a mathematical model of the residual rate of contamination based on unconfirmed positive results
Authors: Benjamin R. J. , Dy B. , Perez J. , Eder A. F. , Wagner S. J.
Published: July 2013

Background

Platelet septic reactions result from low concentrations of bacteria that escape detection by quality‐control BacT/ALERT™ culture testing. We estimate the contamination rate with these bacteria at the time of testing using a mathematical model.

Methods

Culture results and reported septic reactions are described for platelets collected between January 2007 and December 2011. Initial positive results with negative confirmatory cultures were reclassified assuming some of the ‘unconfirmed positive results’ represent collections contaminated with low‐concentration, dormant bacteria. A mathematical model based on the probability of the detection of bacteria describes the upper limit of the residual rate of contamination.

Results

The rate of confirmed or unconfirmed positive apheresis platelet donations was 188 per million (1:5317) and 110 per million (1:9124), respectively. The rate of post‐transfusion sepsis and reported fatalities per distributed component was 1:106 931 and 1:1 015 843, respectively. A linear decrease in unconfirmed positive Bacillus spp. cultures most likely reflected diminishing environmental contamination over time. The remaining unconfirmed positive results identified similar bacteria species as those associated with septic reactions. Assuming that these represent contamination of the collection with low‐concentration, dormant bacteria, the model identified a residual contamination of 3524–204 per million (1:284–1:4902) for collections contaminated with 1–20 bacteria, respectively.

Discussion

Greater than 99·5% of collections contain no viable, aerobic bacteria in solution at the time of early culture testing. For every confirmed positive contaminated collection detected, there are at most 19 collections with low concentrations of dormant bacteria that are not readily detected by early BacT/ALERT™ culture.
Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans
Authors: Stephens Francis B. , Wall Benjamin T. , Marimuthu Kanagaraj , Shannon Chris E. , Constantin‐Teodosiu Dumitru , Macdonald Ian A. , Greenhaff Paul L.
Published: July 2013

Key points

Carnitine is a substrate for the carnitine palmitoyltransferase 1 enzyme, a rate‐limiting step in fatty acid oxidation within skeletal muscle.

Insulin stimulates carnitine transport into skeletal muscle.

A 20% increase in muscle carnitine content, achieved via 12 weeks of twice daily supplementation of a beverage containing 1.36 g of l‐carnitine and 80 g of carbohydrate (in order to stimulate insulin‐mediated muscle carnitine transport), prevented an 18% increase in body fat mass associated with carbohydrate supplementation alone in healthy young men.

A novel finding of the present study was that this prevention of fat gain was associated with a greater energy expenditure and fat oxidation during low‐intensity physical activity, and an adaptive increase in expression of gene networks involved in muscle insulin signalling and fatty acid metabolism.

Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during exercise.

Abstract  Twelve weeks of daily l‐carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of l‐carnitine and carbohydrate feeding on energy metabolism, body fat mass and muscle expression of fuel metabolism genes. Twelve males exercised at 50% maximal oxygen consumption for 30 min once before and once after 12 weeks of twice daily feeding of 80 g carbohydrate (Control, n= 6) or 1.36 g l‐carnitine + 80 g carbohydrate (Carnitine, n= 6). Maximal carnitine palmitolytransferase 1 (CPT1) activity remained similar in both groups over 12 weeks. However, whereas muscle total carnitine, long‐chain acyl‐CoA and whole‐body energy expenditure did not change over 12 weeks in Control, they increased in Carnitine by 20%, 200% and 6%, respectively (P < 0.05). Moreover, body mass and whole‐body fat mass (dual‐energy X‐ray absorptiometry) increased over 12 weeks in Control by 1.9 and 1.8 kg, respectively (P < 0.05), but did not change in Carnitine. Seventy‐three of 187 genes relating to fuel metabolism were upregulated in Carnitine vs. Control after 12 weeks, with ‘insulin signalling’, ‘peroxisome proliferator‐activated receptor signalling’ and ‘fatty acid metabolism’ as the three most enriched pathways in gene functional analysis. In conclusion, increasing muscle total carnitine in healthy humans can modulate muscle metabolism, energy expenditure and body composition over a prolonged period, which is entirely consistent with a carnitine‐mediated increase in muscle long‐chain acyl‐group translocation via CPT1. Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during low‐intensity exercise.
An Improved Closed-Loop Heat Extraction Method From Geothermal Resources
Authors: Dahi Taleghani Arash
Published: July 2013

Disposal of produced water and induced earthquakes are two major issues that have endangered development of the geothermal energy as a renewable source of energy. To avoid these problems, circulation of a low-boiling working fluid in a closed loop has been proposed; however; since the major mechanism in this method for heat extraction is conduction rather than convection and additionally the heat conduction is limited to the wellbore surface. To overcome this shortcoming, the formation can be fractured with high conductivity material (for instance, silicon carbide ceramic proppants or cements with silane and silica fume as admixtures) to artificially increase the contact area between the “working fluid” and the reservoir. Our calculations show that fracturing increases the contact area by thousand times, additionally, the fracturing materials reinforce and stressed the formation, which reduce the risk of seismic activity due to temperature or pressure changes of the system during the production.
The Effect of Microstructure, Thickness Variation, and Crack on the Natural Frequency of Solar Silicon Wafers
Authors: Saffar S. , Gouttebroze S. , Zhang Z. L.
Published: July 2013

Vibration is one of the most common loading modes during handling and transport of solar silicon wafers and has a great influence on the breakage rate. In order to control the breakage rate during handling and facilitate the optimization of the processing steps, it is important to understand the factors which influence the natural frequency of thin silicon wafers. In this study, we applied nonlinear finite element method to investigate the correlation of natural frequency of thin solar silicon wafer with material microstructures (grain size and grain orientation), thickness variation and crack geometry (position and size). It has been found that the natural frequency for anisotropic single crystal silicon wafer is a strong function of material orientation. Less than 10% thickness variation will have a negligible effect on natural frequency. It is also found out that cracks smaller than 20 mm have no dominant effect on the first five natural frequency modes anywhere in the silicon wafer.
Uncertainty Analysis and Characterization of the SOFAST Mirror Facet
Characterization System
Authors: Finch Nolan S. , Andraka Charles E.
Published: July 2013

Sandia Optical Fringe Analysis Slope Tool (SOFAST) is a mirror facet characterization system based on fringe reflection technology that has been applied to dish and heliostat mirror facet development at Sandia National Laboratories and development partner sites. The tool provides a detailed map of mirror facet surface normals as compared to design and fitted surfaces. In addition, the surface fitting process provides insights into systematic facet slope characterization, such as focal lengths, tilts, and twist of the facet. In this paper, an analysis of the sensitivities of the facet characterization outputs to variations of SOFAST input parameters is presented. The results of the sensitivity analysis provided the basis for a linear uncertainty analysis, which is also included here. Input parameters included hardware parameters and SOFAST setup variables. Output parameters included the fitted shape parameters (focal lengths and twist) and the residuals (typically called slope error). The study utilized empirical propagation of input parameter errors through facet characterization calculations to the output parameters, based on the measurement of an Advanced Dish Development System (ADDS) structural gore point-focus facet. Thus, this study is limited to the characterization of sensitivities of the SOFAST embodiment intended for dish facet characterization, using an LCD screen as a target panel. With reasonably careful setup, SOFAST is demonstrated to provide facet focal length characterization within 0.5% of actual. Facet twist is accurate within ±0.03 mrad/m. The local slope deviation measurement is accurate within ±0.05 mrad, while the global slope residual is accurate within ±0.005 mrad. All uncertainties are quoted with 95% confidence.
Optimal Design of Solenoid Actuators Driving Butterfly Valves
Authors: Mousavi Peiman N. , Nataraj C.
Published: July 2013

Smart valves are used in cooling applications and are responsible for regulating and supplying the coolant, which is critical for safe and effective operation of many components on naval and commercial ships. In order to be operated under local power (for various mission-critical reasons) they need to consume as little energy as possible in order to ensure continued operability. This paper focuses on optimized design of a typical system using high fidelity nonlinear dynamic models for all the subsystems with full consideration of stability constraints. A simulated annealing algorithm is applied to explore optimal design using two sets of design variables. The results indicate that substantial amount of energy can be saved by an intelligent design that helps select parameters carefully, but also uses hydrodynamic loads to augment the closing effort.
Design of Crashworthy Structures With Controlled Energy Absorption in the Hybrid Cellular Automaton Framework
Authors: Bandi Punit , Schmiedeler James P. , Tovar Andrés
Published: July 2013

This work presents a novel method for designing crashworthy structures with controlled energy absorption based on the use of compliant mechanisms. This method helps in introducing flexibility at desired locations within the structure, which in turn reduces the peak force at the expense of a reasonable increase in intrusion. For this purpose, the given design domain is divided into two subdomains: flexible (FSD) and stiff (SSD) subdomains. The design in the flexible subdomain is governed by the compliant mechanism synthesis approach for which output ports are defined at the interface between the two subdomains. These output ports aid in defining potential load paths and help the user make better use of a given design space. The design in the stiff subdomain is governed by the principle of a fully stressed design for which material is distributed to achieve uniform energy distribution within the design space. Together, FSD and SSD provide for a combination of flexibility and stiffness in the structure, which is desirable for most crash applications.
Reliability Based Design Optimization Modeling Future Redesign With Different Epistemic Uncertainty Treatments
Authors: Matsumura Taiki , Haftka Raphael T.
Published: July 2013

Design under uncertainty needs to account for aleatory uncertainty, such as variability in material properties, and epistemic uncertainty including errors due to imperfect analysis tools. While there is a consensus that aleatory uncertainty be described by probability distributions, for epistemic uncertainty there is a tendency to be more conservative by taking worst case scenarios or 95th percentiles. This conservativeness may result in substantial performance penalties. Epistemic uncertainty, however, is usually reduced by additional knowledge typically provided by tests. Then, redesign may take place if tests show that the design is not acceptable. This paper proposes a reliability based design optimization (RBDO) method that takes into account the effects of future tests possibly followed by redesign. We consider each realization of epistemic uncertainty to correspond to a different design outcome. Then, the future scenario, i.e., test and redesign, of each possible design outcome is simulated. For an integrated thermal protection system (ITPS) design, we show that the proposed method reduces the mass penalty associated with a 95th percentile of the epistemic uncertainty from 2.7% to 1.2% compared to standard RBDO, which does not account for the future. We also show that the proposed approach allows trading off mass against development costs as measured by probability of needing redesign. Finally, we demonstrate that the tradeoff can be achieved even with the traditional safety factor based design.
The Basis for the Distinct Biological Activities of Vascular Endothelial Growth Factor Receptor–1 Ligands
Authors: Anisimov Andrey , Leppänen Veli-Matti , Tvorogov Denis , Zarkada Georgia , Jeltsch Michael , Holopainen Tanja , Kaijalainen Seppo , Alitalo Kari
Published: July 2013

Differences in how two ligands interact with VEGFR-1 explain why only one ligand is strongly angiogenic.
Science Signaling
Podcast: 2 July 2013
Authors: Alitalo Kari , VanHook Annalisa M.
Published: July 2013

Domain swapping experiments reveal how two related VEGF ligands trigger distinct biological outcomes by binding to the same receptor.
R-Spondin Co-Receptors
Authors: VanHook Annalisa M.
Published: July 2013

Crystal structures reveal how R-spondin binds to two transmembrane proteins to promote Wnt signaling.
Halting Mitochondria at Axonal Branch Points
Authors: Gough Nancy R.
Published: July 2013

A pathway involving the kinases LKB1 and NUAK1 signals mitochondria to stop at the sites of axon branching.
Tomato Tubers
Authors: VanHook Annalisa M.
Published: July 2013

Ectopic expression of a cytokinin biosynthesis enzyme activates the tuber formation program in tomato.
Resistance of Human Cytomegalovirus to Cyclopropavir Maps to a Base Pair Deletion in the Open Reading Frame of
UL97
Authors: Gentry Brian G. , Vollmer Laura E. , Hall Ellie D. , Borysko Katherine Z. , Zemlicka Jiri , Kamil Jeremy P. , Drach John C.
Published: July 2013

Human cytomegalovirus (HCMV) is a widespread pathogen in the human population, affecting many immunologically immature and immunocompromised patients, and can result in severe complications, such as interstitial pneumonia and mental retardation. Current chemotherapies for the treatment of HCMV infections include ganciclovir (GCV), foscarnet, and cidofovir. However, the high incidences of adverse effects (neutropenia and nephrotoxicity) limit the use of these drugs. Cyclopropavir (CPV), a guanosine nucleoside analog, is 10-fold more active against HCMV than GCV (50% effective concentrations [EC
50
s] = 0.46 and 4.1 μM, respectively). We hypothesize that the mechanism of action of CPV is similar to that of GCV: phosphorylation to a monophosphate by viral pUL97 protein kinase with further phosphorylation to a triphosphate by endogenous kinases, resulting in inhibition of viral DNA synthesis. To test this hypothesis, we isolated a CPV-resistant virus, sequenced its genome, and discovered that bp 498 of
UL97
was deleted. This mutation caused a frameshift in
UL97
resulting in a truncated protein that lacks a kinase domain. To determine if this base pair deletion was responsible for drug resistance, the mutation was engineered into the wild-type viral genome, which was then exposed to increasing concentrations of CPV. The results demonstrate that the engineered virus was approximately 72-fold more resistant to CPV (EC
50
= 25.8 ± 3.1 μM) than the wild-type virus (EC
50
= 0.36 ± 0.11 μM). We conclude, therefore, that this mutation is sufficient for drug resistance and that pUL97 is involved in the mechanism of action of CPV.
Identification of an Aminothiazole with Antifungal Activity against Intracellular Histoplasma capsulatum
Authors: Edwards Jessica A. , Kemski Megan M. , Rappleye Chad A.
Published: July 2013

As eukaryotes, fungi possess relatively few molecules sufficiently unique from mammalian cell components to be used as drug targets. Consequently, most current antifungals have significant host cell toxicity. Primary fungal pathogens (e.g.,
Histoplasma
) are of particular concern, as few antifungals are effective in treating them. To identify additional antifungal candidates for the treatment of histoplasmosis, we developed a high-throughput platform for monitoring
Histoplasma
growth and employed it in a phenotypic screen of 3,600 commercially available compounds. Seven hit compounds that inhibited
Histoplasma
yeast growth were identified. Compound 41F5 has fungistatic activity against
Histoplasma
yeast at micromolar concentrations, with a 50% inhibitory concentration (IC
50
) of 0.87 μM, and has the greatest selectivity for yeast (at least 62-fold) relative to host cells. Structurally, 41F5 consists of an aminothiazole core with an alicyclic substituent at the 2-position and an aromatic substituent at the 5-position. 41F5 inhibits
Histoplasma
growth in liquid culture and similarly inhibits yeast cells within macrophages, the actual host environment of this fungal pathogen during infection. Importantly, 41F5 protects infected host cells from
Histoplasma
-induced macrophage death, making this aminothiazole hit compound an excellent candidate for development as an antifungal for
Histoplasma
infections.
The BpeEF-OprC Efflux Pump Is Responsible for Widespread Trimethoprim Resistance in Clinical and Environmental Burkholderia pseudomallei Isolates
Authors: Podnecky Nicole L. , Wuthiekanun Vanaporn , Peacock Sharon J. , Schweizer Herbert P.
Published: July 2013

Trimethoprim-sulfamethoxazole (co-trimoxazole) is the primary drug used for oral eradication therapy of
Burkholderia pseudomallei
infections (melioidosis). Here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast Thailand and northern Australia. This resistance was shown to be due to BpeEF-OprC efflux pump expression. No dihydrofolate reductase target mutations were involved, although frequent insertion of IS
Bma
2 was noted within the putative
folA
transcriptional terminator. All isolates tested remained susceptible to trimethoprim-sulfamethoxazole, suggesting that resistance to trimethoprim alone in these strains probably does not affect the efficacy of co-trimoxazole therapy.
Effect of Prednisone on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir
Authors: Song Ivy H. , Borland Julie , Chen Shuguang , Savina Paul , Peppercorn Amanda F. , Piscitelli Stephen
Published: July 2013

Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed to determine whether prednisone coadministration affected the pharmacokinetics of dolutegravir (DTG). In this open-label, repeat-dose study, 12 healthy subjects were administered DTG at 50 mg daily alone for 5 days and then with concomitant prednisone for 10 days (prednisone at 60 mg daily for 5 days, followed by a 5-day taper). Serial blood sampling and safety assessments were performed during the trial. Pharmacokinetic parameters were determined using noncompartmental methods and geometric least-square mean ratios, and 90% confidence intervals were generated. Coadministration of DTG and 5-day high-dose prednisone with a 5-day taper had a modest effect on DTG exposure. The area under the DTG plasma concentration-time curve, maximum observed DTG concentration, and 24-hour postdose DTG concentration were increased by 11%, 6%, and 17%, respectively, on day 10 of the combination. Similar results were observed after 5 days of DTG and prednisone. Dolutegravir and prednisone coadministration was well tolerated. The changes in plasma exposures of DTG in healthy individuals as a result of prednisone dosing were not clinically significant. No dose adjustment is required for DTG coadministered with prednisone. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01425099.)
Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations
Authors: Bangert Mathieu , Wright Adam K. , Rylance Jamie , Kelly Matthew J. , Wright Angela D. , Carlone George M. , Sampson Jacquelyn S. , Rajam Gowrisankar , Ades Edwin W. , Kadioglu Aras , Gordon Stephen B.
Published: July 2013

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of
Streptococcus pneumoniae
ex vivo
. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on
ex vivo
-derived human lung cells.
Relationship between Trough Plasma and Epithelial Lining Fluid Concentrations of Voriconazole in Lung Transplant Recipients
Authors: Heng Siow-Chin , Snell Gregory I. , Levvey Bronwyn , Keating Dominic , Westall Glen P. , Williams Trevor J. , Whitford Helen , Nation Roger L. , Slavin Monica A. , Morrissey Orla , Kong David C. M.
Published: July 2013

Trough (predose) voriconazole concentrations in plasma and pulmonary epithelial lining fluid (ELF) of lung transplant recipients receiving oral voriconazole preemptive treatment were determined. The mean (± standard deviation [SD]) ELF/plasma ratio was 12.5 ± 6.3. A strong positive linear relationship was noted between trough plasma and ELF voriconazole concentrations (
r
2
= 0.87), suggesting the feasibility of using trough plasma voriconazole concentration as a surrogate to estimate the corresponding concentration in ELF of lung transplant recipients.
Rapid Emergence of Echinocandin Resistance in Candida glabrata Resulting in Clinical and Microbiologic Failure
Authors: Lewis James S. , Wiederhold Nathan P. , Wickes Brian L. , Patterson Thomas F. , Jorgensen James H.
Published: July 2013

We report a case of
Candida glabrata
candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. Pre- and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within
FKS2
.