bluuebunny/crossref_metadata_2025 huggingface dataset:
Active vibration control of a blade element with uncertainty modeling in PZT actuator force
Authors: Sivrioglu Selim , Bolat Fevzi Cakmak , Erturk Ercan
Published: August 2019

The aim of this research is to attenuate the vibrations of a blade structure with an attached piezoelectric actuator using robust multi-objective control. The force obtained from a piezoelectric patch loading has uncertainties due to the complicated shape (airfoil) of the blade element. A parameter-dependent model of the force equation is developed to understand the possible variation range of the actuation force. The modal analysis of the blade is performed to find vibration mode frequencies, and an aerodynamic load is generated experimentally to create steady-state vibration on the blade. A state-space model is obtained by considering certain vibration modes and the parameter-dependent part of the force in the input vector is taken outside of the plant model. The robust stability filter is modified with parameter dependency to have a cluster of the filter. Two different multi-objective controllers are designed with different design objectives. The designed controllers are implemented in experiments and performances of the controllers are compared using frequency and time domain responses. It is shown that the flexible blade vibrations are successfully suppressed with the proposed mixed norm robust controllers under the effect of steady-state aerodynamic disturbance with different air speeds. It is observed in experimental results that the performances of the [Formula: see text] controller are better than the [Formula: see text] controller.
Implementation and Outcomes of Lay Health Worker–Led Self-Management Interventions for Long-Term Conditions and Prevention: A Systematic Review
Authors: Punna Mari , Kettunen Tarja , Bagnall Anne-Marie , Kasila Kirsti
Published: August 2019

The aim of this study was to systematically review lay health worker (LHW)–led self-management interventions for adults with long-term conditions to see how the interventions have been implemented and to compose a synthesis of research findings, taking into consideration the intervention components that have been applied. We conducted systematic searches for articles published between January 2010 and December 2015 in five databases: Cochrane, MEDLINE, CINAHL, PsycINFO, and Web of Science. Forty original studies were found that met the inclusion criteria: self-management with diabetes ( n = 29), cardiovascular diseases ( n = 8), and those at risk of cardiovascular diseases ( n = 3). These consisted of 22 randomized controlled trials and 18 other trials, with durations of 1 day to 24 months. The findings showed that the training of LHWs and the implementation of interventions varied widely. A synthesis of the implementation methods covers the background of the LHWs and the interventions as well as the components applied in each. Eight interventions had effects on physical activity and eight on nutrition behavior. The review also includes preliminary findings on intervention components effective in improving physical activity and nutrition behavior, including self-monitoring as a behavior change technique and group meetings as an intervention format. The same components and behavior change techniques were applied in effective and noneffective interventions. The review found that LHW-led interventions have potential in promoting self-management in long-term condition. In the future, a qualified and evidence-based structure for LHW-led interventions is suggested in order to improve the systematization of interventions and their effects.
Implosive Multiculturalism: Staging of the Community in Bankstown, Sydney
Authors: Alian Sanaz , Wood Stephen
Published: August 2019

Drawing on interviews with 30 residents, users, and traders in Bankstown’s town center, this article examines how built form facilitates a certain staging of the community, underpinning simulated encounters with the other. The article describes how the interviewees celebrate “differences” and “diversity” in their community, even as they reveal a certain indifference; signs of “difference” are substituted for genuine, reciprocal exchanges with the other, to the extent that the latter primarily appears in simulated form. Drawing on Baudrillard’s concept of implosion, different ways in which otherness is simulated are discussed, ranging from programmed “cultural events” to staging of the other-as-victim.
Examination of diesel spray combustion in supercritical ambient fluid using large-eddy simulations
Authors: Chung Wai Tong , Ma Peter C , Ihme Matthias
Published: August 2019

High-pressure conditions in diesel engines can often surpass the thermodynamic critical limit of the working fluid. Consequently, the injection of fuel at these conditions can lead to complex behaviors that remain only incompletely understood. This study is concerned with investigating the application of a diffuse-interface method in conjunction with a finite-rate chemistry model in large-eddy simulations of diesel spray injection and ignition in a supercritical ambient environment. The presented numerical approach offers the capability of simulating these complex conditions without the need for parameter tuning that is commonly employed in spray-breakup models. Numerical simulations of inert and reacting n-dodecane sprays — under the Engine Combustion Network Spray A and Spray D configurations — are studied, and results are compared with experimental data for liquid/vapor penetration lengths and ignition timing. In addition, parametric studies are performed to identify flow sensitivities arising from the variation in nozzle diameters between both injectors, along with the impact of low-temperature oxidation on ignition in Spray D simulations. Spray A simulations are found to be insensitive to turbulence, and predictions for penetration length and ignition behavior are in good agreement with experiments. In contrast, Spray D predictions for penetration length and ignition delay demonstrated significant sensitivities to in-nozzle turbulence, introducing uncertainty to the predicted results and stipulating the need for quantitative measurements for model evaluation.
Understanding Ukrainian pedagogical sciences through textbook analysis of four ‘Pedagogy’ textbooks
Authors: Fim’yar Olena , Kushnir Iryna , Vitrukh Mariia
Published: August 2019

In comparison to a vast literature on Soviet education little is known about Ukrainian pedagogical sciences apart from a mounting critique about the issues of academic dishonesty and plagiarism, which relates to all higher education disciplines, the absence of an empirical tradition in education research, a poor record of publication in peer-reviewed journals, and the dominance of a positivist approach, which seeks to discover ‘laws’ rather than reach ‘understanding’. This paper offers a thematic analysis of four ‘Pedagogy’ textbooks – three textbooks for under-graduate studies and one textbook for post-graduate study. The textbook analysis demonstrates that Ukrainian pedagogical sciences as a research tradition is deeply rooted in its own conceptual apparatus with no apparent relation to the current debates about teaching and learning in a wider Europe. The key proposition of the paper is that Ukrainian pedagogical sciences represent a mixture of Herbatianism and dialectical materialism, with more recent developments that emphasise ‘acme’ or ‘perfectionism’ that could be compared to debates on virtue ethics in education. Alongside these narratives the discourse of ‘Kozak pedagogy’ contributes to the nation-building narrative in education. The paper calls for a review of the content of ‘pedagogy’ textbooks currently used in higher education institutions in Ukraine and envisages that the newly established Ukrainian Educational Research Association can provide a platform for this important undertaking.
Looseness condition feature extraction of viscoelastic sandwich structure using dual-tree complex wavelet packet-based deep autoencoder network
Authors: Si Yue , Zhang Zhousuo , Kong Chuiqing , Li Shujuan , Yang Guigeng , Hu Bingbing
Published: August 2019

It is significant to perform looseness condition detection of viscoelastic sandwich structures to avoid serious accidents. Due to the multilayer characteristic of the viscoelastic sandwich structure, the vibration response signal of such structures is nonlinear and nonstationary. Furthermore, the looseness condition feature signal contained in the vibration response signal is very puny. Condition feature extraction has become a challenging task in the looseness condition detection of viscoelastic sandwich structures. Therefore, a novel method called dual-tree complex wavelet packet-based deep autoencoder network is proposed for this task. First, the vibration response signal of the viscoelastic sandwich structure is decomposed by dual-tree complex wavelet packet transform and the sub-band signals which contain rich energy are extracted. Then, the energies of the extracted sub-band signals are calculated to form a feature set. Finally, a deep autoencoder network is established to fuse the feature set, and the fused feature is viewed as the detection index to detect the looseness condition of the viscoelastic sandwich structure. The proposed method is applied to the connecting bolt looseness condition detection of the viscoelastic sandwich structure to validate its effectiveness. Compared with the detection method based on dual-tree complex wavelet packet transform and energy and the detection method based on dual-tree complex wavelet packet transform and permutation entropy, the results indicate that the effectiveness of the proposed method in this article is more superior to that of the other two methods.
When Participants Do Not Agree: Member Checking and Challenges to Epistemic Authority in Participatory Research
Authors: Caretta Martina Angela , Pérez María Alejandra
Published: August 2019

Transactional validity, a common approach in participatory research, is attained when preliminary analyses of research results are discussed with research participants and their feedback is incorporated in the analysis. Member checking is one way of achieving transactional validity, which has been heralded as a stronger version of validity reached through triangulation. Through member checking, we engaged with participants to ensure mutual agreement and understanding on the accounts and analysis to be published. Attaining methodological rigor and reliability is based on shared analytical understanding between researchers and research participants. However, this shared understanding does not always materialize. Participants do not always agree with researchers or with each other. As a result, efforts to increase validity created moments of conflict and challenged epistemic authority. This article provides detailed accounts of these conflicts and challenges and their eventual, even if problematic, resolution in the context of broader approaches in participatory research. The importance of a dialogical and recursive research process with participant communities, which cannot be assumed to be homogeneous, is underscored.
Electrospun nanofibers of poly (acrylonitrile-co-itaconic acid)/silver and polyacrylonitrile/silver: In situ preparation, characterization, and antimicrobial activity
Authors: Baskan Havva , Esentürk Imren , Dösler Sibel , Sarac A Sezai , Karakas Hale
Published: August 2019

In this study, it was aimed to prepare silver nanoparticles by reduction of silver salt (AgNO3) in situ by means of only synthesized polyacrylonitrile (PAN) and poly(acrylonitrile-co-itaconic acid) (P(AN-co-IA)) polymers, and N,N dimethylformamide (DMF). Thereafter, PAN/Ag and P(AN-co-IA)/Ag nanofibers were prepared via electrospinning. Spectroscopic and morphologic characterizations, electrical and thermal features, and antimicrobial activities of the prepared nanofibers against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were carried out in detail. It was observed that P(AN-co-IA) was much more effective than PAN on the reduction of AgNO3 and formation of silver nanoparticles. Silver nanoparticles and also itaconic acid contributed to decrease the cyclization temperature of PAN by generating sharp exothermic peaks. In addition, electrical conductivity of the nanofibers increased dramatically from E−13 to E−4 related to the presence of silver nanoparticles. Furthermore, incorporation of silver nanoparticles to the nanofiber membranes let bactericidal/fungicidal activities, which started at 6–24 h and continued for up to 168 h, against S. aureus, E. coli, P. aeruginosa, and C. albicans. The prepared silver containing nanofibers can be regarded as good candidates for potential use in the biomedical and pharmaceutical applications.
Pilomatrixoma of the head and neck: Typical presentation of a rare lesion
Authors: Sirakaya Mert , Vydianath Sanjay
Published: August 2019

Pilomatrixomas are benign tumours of primitive hair follicles, usually presenting as painless lumps in the head and neck region in children. As they are uncommon, they are often misdiagnosed clinically. We discuss a case of a five-year-old boy presenting with a five-month history of a pre-auricular lump. The initial clinical differential diagnosis was of a dermoid or a branchial cleft cyst. However, on ultrasonography the lesion was typical of a pilomatrixoma. The imaging literature is reviewed to illustrate the sonographic appearances of pilomatrixomas.
Procedure for 2D fluid–structure interaction simulation
Authors: Zorn Joshua E , Davis Roger L
Published: August 2019

A numerical technique for the solution of the structural dynamics equations of motion is presented. The structural dynamics mass and momentum conservation equations are solved using a control volume technique which is second-order accurate in space along with a dual time-step scheme that is second order accurate in time. The momentum conservation equation is written in terms of the Piola–Kirchoff stresses and the displacement velocity components. The stress tensor is related to the Lagrangian strain and displacement tensors using the St. Venant–Kirchoff constitutive relationship. Source terms are included to account for surface pressure and body forces. Verification of the structural dynamics solution procedure is presented for a two-dimensional vibrating cantilever beam. In addition, the structural dynamics solution procedure has been implemented into a general purpose two dimensional conjugate heat transfer solution procedure that uses a similar dual time-step control volume technique to solve the fluid mass, energy, and Navier–Stokes equations as well as the structural energy heat conduction equation. The resulting overall solution procedure allows for solutions to fluid/structure, fluid/thermal, or fluid/thermal/structure interaction problems. Verification of the multidisciplinary procedure is performed using a cylinder with a flexible solid protruding downstream that mimics a cylinder-flag configuration. The approach is a proof of concept for compressible flow with continuum based solids. The methods are currently being extended to 3D flow fields and solids.
The influence of boot longitudinal flexural stiffness on external mechanical work and running economy during skate roller-skiing: A case study
Authors: Hladnik Jurij , Supej Matej , Vodičar Janez , Jerman Boris
Published: August 2019

This case study examines the impact of boot longitudinal flexural stiffness on the total external mechanical work of a skier’s centre of mass per distance travelled in the forward direction ([Formula: see text] EX (J/m)) and on running economy during skate roller-skiing under submaximal steady-state conditions. Moreover, it analyses time derivatives of total W EX, of W EX performed by the roller-skis and poles, respectively, and of the directly useful mechanical work (the sum of the work to overcome centre of mass’ gravity and rolling resistance) within a typical roller-skiing cycle. Multiple roller-skiing trials (G3 technique) were performed by one subject on an inclined treadmill with boots of soft, intermediate, and stiff flexural stiffness. The orientation and magnitude of the roller-ski and pole ground reaction forces, body kinematics, VO2, and lactic acid concentration were monitored. The stiff boots had 13.4% ( p < 0.01) lower [Formula: see text] EX compared to the intermediate boots, and 20.7% ( p < 0.001) lower [Formula: see text] EX compared to the soft boots. Regarding running economy, the soft boots had 2.2% ( p < 0.05) higher VO2 compared to the intermediate boots, but the same VO2 compared to the stiff boots. In conclusion, the soft boots had significantly higher [Formula: see text] EX and running economy, while stiff boots had significantly lower [Formula: see text] EX and intermediate boots significantly lower running economy. Moreover, [Formula: see text] EX appears to be a better indicator of the boot flexural stiffness impact on energy efficiency than running economy.
Dosage of Bioactive Molecules in the Nutricosmeceutical Helix aspersa Muller Mucus and Formulation of New Cosmetic Cream with Moisturizing Effect
Authors: Laneri Sonia , Lorenzo Ritamaria Di , Sacchi Antonia , Dini Irene
Published: August 2019

The present study was carried out to provide the allantoin and glycolic acid contents in the Helix aspersa Muller mucus of common Campania land (Italy) by using chromatographic method. The study continued with the formulation of a snail mucus cosmetic cream, whose ability to hydrate the skin was evaluated comparing the skin hydration and trans-epidermal water loss (TEWL) effects of a stable cosmetic preparation. The skin TEWL and skin hydration effects were measured by TEWAMETER and corneometer probe, respectively, at the beginning, after 1 hour, and 24 hours.
Practicing the Patience of God: A Response to Technologically Induced Impatience by Way of Ancient Holy Habit
Authors: Baker Samuel E.
Published: August 2019

This article addresses three interrelated concerns: the pervasive nature of technologically induced impatience, a theological understanding of divine patience, and, finally, a suitable response to techno-impatience by way of engagement with the art and practice of holy habit. As we have experienced faster flows of information, and larger amounts of information through which we must sort, we have become less patient people. This loss of patience continues to produce a new kind of personal and communal disquiet on an impressive scale. To address concerns with techno-impatience, arguments will be drawn from scriptural and theological concepts of divine patience. These concepts prompt us to rediscover, and reinvent, a richer understanding of patience as an individuated spiritual virtue. Accordingly, a corrective to the exacerbating effects of technologically induced impatience will be offered: namely, the explicit spiritual discipline of practicing holy patience.
A Sense of Mattering: A Group Intervention for African American Boys
Authors: Gibson Eva M. , Sandifer Mariama Cook , Bedford Winifred
Published: August 2019

African American boys have been disproportionately represented in school discipline data. School counselors are encouraged to integrate cultural considerations while developing interventions for African American boys. A middle school counselor (the first author) utilized discipline data to create a culturally responsive group intervention designed to affect behavior and develop social/emotional skills. Through the analysis of perception and outcome data, findings indicated improvement in behavior and social/emotional skills among participants. We discuss implications for school counselors, school counselor education programs, and school districts.
Social Relationship Quality Among Patients With Chronic Pain: A Population-Based Sample
Authors: Philpot Lindsey M , Schumann Matthew E , Ebbert Jon O
Published: August 2019

Objective:

Chronic daily pain is experienced by 11.2% of United States adults and psychosocial factors have significant impact on self-reported pain. Most research in this area has focused on pain-related conditions, not the general population. This study sought to understand the associations between clinically significant chronic pain and multiple dimensions of social relationship quality in a general population.

Methods:

A cross-sectional survey was deployed and adjusted logistic regression models were constructed for chronic pain against independent social support domains. The moderating effect of self-rated health on social support quality was explored.

Results:

Of all, 26.1% of surveys were completed (3920/15 000) and 18.8% reported clinically significant chronic pain. Patients with chronic pain had lower friendship quality (aOR = 0.78; 0.64-0.94) and higher perceived rejection (aOR = 1.26; 1.04-1.53) and perceived hostility (aOR = 1.26; 1.05-1.52). Within our moderation analysis, chronic pain patients with low self-rated health had higher odds of low friendship quality, high loneliness, and high perceived rejection.

Conclusions:

Chronic pain patients experience social relationships differently than those without, and self-rated health differentially impacts these perceptions.
Diverse ecologies: Mapping complexity in environmental governance
Authors: Fletcher Robert
Published: August 2019

This article outlines a novel framework for investigating complex intersections among divergent approaches to enacting environmental governance. I term this the study of “diverse ecologies.” The framework builds on J.K. Gibson-Graham’s influential “diverse economies” perspective but seeks to integrate this with research in political ecology that devotes greater attention to issues of structural power. In particular, the article draws on growing analysis of environmental governance as a form of “environmentality” building on Foucault’s influential governmentality analytic. While early literature in this area overlooked the multiple forms of environmentality that may intersect within a given context, more recent research emphasizes this diversity. Integrating multiple environmentalities and diverse economies perspectives thus provides the grounding for the “diverse ecologies” framework outlined herein. The framework’s application is illustrated through analysis of a popular payment for environmental services program in Costa Rica.
The multi-peak adaptive landscape of crocodylomorph body size evolution
Authors: Godoy Pedro L. , Benson Roger B. J. , Bronzati Mario , Butler Richard J.
Published: August 2019

Background

Little is known about the long-term patterns of body size evolution in Crocodylomorpha, the > 200-million-year-old group that includes living crocodylians and their extinct relatives. Extant crocodylians are mostly large-bodied (3–7 m) predators. However, extinct crocodylomorphs exhibit a wider range of phenotypes, and many of the earliest taxa were much smaller (< 1.2 m). This suggests a pattern of size increase through time that could be caused by multi-lineage evolutionary trends of size increase or by selective extinction of small-bodied species. Here, we characterise patterns of crocodylomorph body size evolution using a model fitting-approach (with cranial measurements serving as proxies). We also estimate body size disparity through time and quantitatively test hypotheses of biotic and abiotic factors as potential drivers of crocodylomorph body size evolution.

Results

Crocodylomorphs reached an early peak in body size disparity during the Late Jurassic, and underwent an essentially continual decline since then. A multi-peak Ornstein-Uhlenbeck model outperforms all other evolutionary models fitted to our data (including both uniform and non-uniform), indicating that the macroevolutionary dynamics of crocodylomorph body size are better described within the concept of an adaptive landscape, with most body size variation emerging after shifts to new macroevolutionary regimes (analogous to adaptive zones). We did not find support for a consistent evolutionary trend towards larger sizes among lineages (i.e., Cope’s rule), or strong correlations of body size with climate. Instead, the intermediate to large body sizes of some crocodylomorphs are better explained by group-specific adaptations. In particular, the evolution of a more aquatic lifestyle (especially marine) correlates with increases in average body size, though not without exceptions.

Conclusions

Shifts between macroevolutionary regimes provide a better explanation of crocodylomorph body size evolution on large phylogenetic and temporal scales, suggesting a central role for lineage-specific adaptations rather than climatic forcing. Shifts leading to larger body sizes occurred in most aquatic and semi-aquatic groups. This, combined with extinctions of groups occupying smaller body size regimes (particularly during the Late Cretaceous and Cenozoic), gave rise to the upward-shifted body size distribution of extant crocodylomorphs compared to their smaller-bodied terrestrial ancestors.
RETRACTED ARTICLE: Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathway
Authors: Qi Chen , Xiaofeng Chen , Dongen Li , Liang Yang , Liping Xu , Yue Hu , Jianshuai Jiang
Published: August 2019

Background

Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are dysregulated and correlate with the pathophysiological basis of malignant tumors. The objective of this research is to uncover the possible molecular mechanism of MACC1-AS1 regarding the regulation of pancreatic carcinoma (PC) metastasis.

Methods

lncRNA microarray and qRT-PCR were applied to identify differentially expressed lncRNA profile in PC. The function and role of MACC1-AS1 in PC were assessed via in vitro as well as in vivo assays. Luciferase analyses, RNA immunoprecipitation, and RNA pull-down were performed to determined the underlying MACC1-AS1 mechanisms.

Results

Numbers of differentially expressed lncRNAs in PC were identified via lncRNA microarrays, among which MACC1-AS1 was revealed as the most abundant lncRNA. The upregulation of MACC1-AS1 in PC was further confirmed in two expanded PC cohorts, which showed that MACC1-AS1 expression was upregulated in those PC patients with poor survival. Functionally, knockdown of MACC1-AS1 inhibited the proliferation as well as metastasis of PC cells. Meanwhile, MACC1-AS1 upregulated the expression of PAX8 protein, which promoted aerobic glycolysis and activated NOTCH1 signaling. Additionally, PAX8 was upregulated in PC tissues, which was correlated with the expression of MACC1-AS1 and the overall survival of PC patients.

Conclusions

Together, our findings indicate a critical role of MACC1-AS1/PAX8/NOTCH1 signaling, which may be an alternative treatment target in PC therapy.
The progression rate of peripheral arterial disease in patients with intermittent claudication: a systematic review
Authors: Mizzi A. , Cassar K. , Bowen C. , Formosa C.
Published: August 2019

Background

Intermittent claudication (IC) is the most common symptom of peripheral arterial disease and is generally treated conservatively due to limited prognostic evidence to support early revascularisation in the individual patient. This approach may lead to the possible loss of opportunity of early revascularisation in patients who are more likely to deteriorate to critical limb ischaemia. The aim of this review is to evaluate the available literature related to the progression rate of symptomatic peripheral arterial disease.

Methods

We conducted a systematic review of the literature in PubMed and MEDLINE, Cochrane library, Elsevier, Web of Science, CINAHL and Opengrey using relevant search terms to identify the progression rate of peripheral arterial disease in patients with claudication. Outcomes of interest were progression rate in terms of haemodynamic measurement and time to development of adverse outcomes. Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. Quality of evidence was evaluated using the Cochrane recommendations for assessing risk of bias and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines.

Results

Seven prospective cohort studies and one retrospective cohort study were identified and included in this review with the number of participants in each study ranging from 38 to 1244. Progression rate reports varied from a yearly decrease of 0.01 in ankle‐brachial pressure index (ABPI) to a yearly decrease ABPI of 0.014 in 21% of participants. Quality of evidence ranged from low to moderate mostly due to limited allocation concealment at recruitment and survival selection bias.

Conclusions

Progression of PAD in IC patients is probably underestimated in the literature due to study design issues. Predicting which patients with claudication are likely to deteriorate to critical limb ischaemia is difficult since there is a lack of evidence related to lower limb prognosis. Further research is required to enable early identification of patients at high risk of progressing to critical ischaemia and appropriate early revascularisation to reduce lower limb morbidity.
Stratigraphic architecture and petrophysical characterization of formations for deep disposal in the Fort Worth Basin, Texas
Authors: Smye Katie M. , Lemons Casee R. , Eastwood Ray , McDaid Guinevere , Hennings Peter H.
Published: August 2019

Disposal of hydraulic fracturing flowback and produced water into Ordovician and Cambrian formations of the Fort Worth Basin (FWB), coupled with an increase in observed seismicity in the Dallas-Fort Worth area, necessitates an understanding of the geologic character of these disposal targets. More than 2 billion barrels (Bbbls) of wastewater have been disposed into the Ordovician Ellenburger Group of the FWB over the past 35 years. Since the implementation of the TexNet Earthquake Catalog (1 January 2017), more than 20 earthquakes of local magnitude ML2.0 or greater have been detected in the area, with depths ranging from 2 to 10 km (approximately 6500–33,000 ft). The cited mechanism for inducement of these earthquakes is reactivation of basement faults due to pore pressure changes, either directly related to proximal disposal or due to disposal volume buildup over time. Here, we present a stratigraphic and petrophysical analysis of FWB disposal targets and their relation to basement rocks. The Ellenburger consists of alternating layers of limestone and dolomite, with minor siliciclastics above the basement toward the Llano Uplift. Matrix porosity averages <5 porosity units (p.u.), with higher porosity in dolomitic layers than in limestone. Dolomite dominates at the top of the Ellenburger, which was exposed at the end of both the Lower and Upper Ordovician. Where crystalline basement rocks are penetrated, the composition ranges from granitic to chlorite-bearing metamorphosed lithology. The basement-sediment interface is frequently marked by increased porosity. An updated map of structure on top of basement indicates elevations ranging from outcrop at the Llano Uplift to more than [Formula: see text] ([Formula: see text]) subsea toward the northeast. The disposal zone pore volume is estimated from thickness and porosity maps and ranges from [Formula: see text] to [Formula: see text] billion barrels per square mile ([Formula: see text]).
Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse
Authors: León Silvia , Fergani Chrysanthi , Talbi Rajae , Simavli Serap , Maguire Caroline A , Gerutshang Achi , Navarro Víctor M
Published: August 2019

The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.
PKCδ Mediates Mineralocorticoid Receptor Activation by Angiotensin II to Modulate Smooth Muscle Cell Function
Authors: Lu Qing , Davel Ana P , McGraw Adam P , Rao Sitara P , Newfell Brenna G , Jaffe Iris Z
Published: August 2019

Angiotensin II (AngII) and the mineralocorticoid receptor (MR) ligand aldosterone both contribute to cardiovascular disorders, including hypertension and adverse vascular remodeling. We previously demonstrated that AngII activates MR-mediated gene transcription in human vascular smooth muscle cells (SMCs), yet the mechanism and the impact on SMC function are unknown. Using an MR-responsive element-driven transcriptional reporter assay, we confirm that AngII induces MR transcriptional activity in vascular SMCs and endothelial cells, but not in Cos1 or human embryonic kidney-293 cells. AngII activation of MR was blocked by the MR antagonist spironolactone or eplerenone and the protein kinase C-δ (PKCδ) inhibitor rottlerin, implicating both in the mechanism. Similarly, small interfering RNA knockdown of PKCδ in SMCs prevented AngII-mediated MR activation, whereas knocking down of MR blocked both aldosterone- and AngII-induced MR function. Coimmunoprecipitation studies reveal that endogenous MR and PKCδ form a complex in SMCs that is enhanced by AngII treatment in association with increased serine phosphorylation of the MR N terminus. AngII increased mRNA expression of the SMC-MR target gene, FKBP51, via an MR-responsive element in intron 5 of the FKBP51 gene. The impact of AngII on FKBP51 reporter activity and gene expression in SMCs was inhibited by spironolactone and rottlerin. Finally, the AngII-induced increase in SMC number was also blocked by the MR antagonist spironolactone and the PKCδ inhibitor rottlerin. These data demonstrate that AngII activates MR transcriptional regulatory activity, target gene regulation, and SMC proliferation in a PKCδ-dependent manner. This new mechanism may contribute to synergy between MR and AngII in driving SMC dysfunction and to the cardiovascular benefits of MR and AngII receptor blockade in humans.
Imaging and Manipulating Pituitary Function in the Awake Mouse
Authors: Hoa Ombeline , Lafont Chrystel , Fontanaud Pierre , Guillou Anne , Kemkem Yasmine , Kineman Rhonda D , Luque Raul M , Fiordelisio Coll Tatiana , Le Tissier Paul , Mollard Patrice
Published: August 2019

Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. These methodologies are now readily applicable for longitudinal studies of short-lived events (e.g., calcium signals controlling hormone exocytosis) and slowly evolving processes such as tissue remodeling in health and disease over a period of days to weeks.
Acute Deletion of METTL14 in β-Cells of Adult Mice Results in Glucose Intolerance
Authors: Men Lili , Sun Juan , Luo Guanzheng , Ren Decheng
Published: August 2019

N6-Methyladenosine (m6A) is the most common and abundant mRNA modification that involves regulating the RNA metabolism. However, the role of m6A in regulating the β-cell function is unclear. Methyltransferase-like 14 (METTL14) is a key component of the m6A methyltransferase complex. To define the role of m6A in regulating the β-cell function, we generated β-cell METTL14-specific knockout (βKO) mice by tamoxifen administration. Acute deletion of Mettl14 in β-cells results in glucose intolerance as a result of a reduction in insulin secretion in β-cells even though β-cell mass is increased, which is related to increased β-cell proliferation. To define the molecular mechanism, we performed RNA sequencing to detect the gene expression in βKO islets. The genes responsible for endoplasmic reticulum stress, such as Ire1α, were among the top upregulated genes. Both mRNA and protein levels of IRE1α and spliced X-box protein binding 1 (sXBP-1) were increased in βKO islets. The protein levels of proinsulin and insulin were decreased in βKO islets. These results suggest that acute METTL14 deficiency in β-cells induces glucose intolerance by increasing the IRE1α/sXBP-1 pathway.
Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond
Authors: Cabanillas Maria E , Ryder Mabel , Jimenez Camilo
Published: August 2019

The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.
Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency
Authors: Bacila Irina , Adaway Jo , Hawley James , Mahdi Sundus , Krone Ruth , Patel Leena , Alvi Sabah , Randell Tabitha , Gevers Evelien , Dattani Mehul , Cheetham Timothy , Kyriakou Andreas , Schiffer Lina , Ryan Fiona , Crowne Elizabeth , Davies Justin H , Ahmed Syed Faisal , Keevil Brian , Krone Nils
Published: August 2019

Background

Monitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH.

Objective

To establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy.

Design

This prospective cross-sectional study recruited patients between 2015 and 2018.

Setting

Multicenter study including 13 tertiary centers in the United Kingdom.

Participants

Seventy-eight children with CAH and 62 matched healthy controls.

Methods

Using liquid chromatography–tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice.

Results

Strong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT.

Conclusions

The current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH.
Exercise Mitigates Bone Loss in Women With Severe Obesity After Roux-en-Y Gastric Bypass: A Randomized Controlled Trial
Authors: Murai Igor H , Roschel Hamilton , Dantas Wagner S , Gil Saulo , Merege-Filho Carlos , de Cleva Roberto , de Sá-Pinto Ana L , Lima Fernanda , Santo Marco A , Benatti Fabiana B , Kirwan John P , Pereira Rosa M , Gualano Bruno
Published: August 2019

Context

Bone loss after bariatric surgery potentially could be mitigated by exercise.

Objective

To investigate the role of exercise training (ET) in attenuating bariatric surgery–induced bone loss.

Design

Randomized, controlled trial.

Setting

Referral center for bariatric surgery.

Patients

Seventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB).

Intervention

Supervised, 6-month, ET program after RYGB vs. standard of care (RYGB only).

Outcomes

Areal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes.

Results

Surgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), −2.91%; P = 0.007;], total hip (EMD, −2.26%; P = 0.009), distal radius (EMD, −1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, −2.09%; P = 0.024). Exercise also attenuated CTX (EMD, −0.20 ng/mL; P = 0.002), P1NP (EMD, −17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, −610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium).

Conclusion

Exercise mitigated bariatric surgery–induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass.
Continuous Free Cortisol Profiles—Circadian Rhythms in Healthy Men
Authors: Bhake R C , Kluckner V , Stassen H , Russell G M , Leendertz J , Stevens K , Linthorst A C E , Lightman S L
Published: August 2019

Context

The pituitary–adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device has provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings.

Methods

Two separate experiments were conducted in healthy male volunteers. The total and subcutaneous (SC) free cortisol levels were measured at 10-minute intervals for a 24-hour period in one experiment, and the SC free cortisol levels were measured at 20-minute interval for 72 consecutive hours in free-living individuals in the second experiment.

Results

The characteristic circadian rhythm was evident in both serum total and SC free cortisol, with the lowest levels achieved and maintained in the hours surrounding sleep onset and the peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across the 72-hour period, despite a wide range of activities. All the participants also showed increased cortisol after the consumption of lunch. The lowest levels during all 24-hour periods were observed during the hours after lights off, at the onset of sleep.

Conclusions

To the best of our knowledge, the present study is the first to report up to three consecutive 24-hour measurements of SC free cortisol in healthy individuals. We believe our study is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously for a period of 72 hours in free-living individuals performing their day-to-day activities whether healthy or with diseases involving the hypothalamic–pituitary–adrenal axis.
Mutations in MAGEL2 and L1CAM Are Associated With Congenital Hypopituitarism and Arthrogryposis
Authors: Gregory Louise C , Shah Pratik , Sanner Juliane R F , Arancibia Monica , Hurst Jane , Jones Wendy D , Spoudeas Helen , Le Quesne Stabej Polona , Williams Hywel J , Ocaka Louise A , Loureiro Carolina , Martinez-Aguayo Alejandro , Dattani Mehul T
Published: August 2019

Context

Congenital hypopituitarism (CH) is rarely observed in combination with severe joint contractures (arthrogryposis). Schaaf-Yang syndrome (SHFYNG) phenotypically overlaps with Prader-Willi syndrome, with patients also manifesting arthrogryposis. L1 syndrome, a group of X-linked disorders that include hydrocephalus and lower limb spasticity, also rarely presents with arthrogryposis.

Objective

We investigated the molecular basis underlying the combination of CH and arthrogryposis in five patients.

Patients

The heterozygous p.Q666fs*47 mutation in the maternally imprinted MAGEL2 gene, previously described in multiple patients with SHFYNG, was identified in patients 1 to 4, all of whom manifested growth hormone deficiency and variable SHFYNG features, including dysmorphism, developmental delay, sleep apnea, and visual problems. Nonidentical twins (patients 2 and 3) had diabetes insipidus and macrocephaly, and patient 4 presented with ACTH insufficiency. The hemizygous L1CAM variant p.G452R, previously implicated in patients with L1 syndrome, was identified in patient 5, who presented with antenatal hydrocephalus.

Results

Human embryonic expression analysis revealed MAGEL2 transcripts in the developing hypothalamus and ventral diencephalon at Carnegie stages (CSs) 19, 20, and 23 and in the Rathke pouch at CS20 and CS23. L1CAM was expressed in the developing hypothalamus, ventral diencephalon, and hindbrain (CS19, CS20, CS23), but not in the Rathke pouch.

Conclusion

We report MAGEL2 and L1CAM mutations in four pedigrees with variable CH and arthrogryposis. Patients presenting early in life with this combined phenotype should be examined for features of SHFYNG and/or L1 syndrome. This study highlights the association of hypothalamo-pituitary disease with MAGEL2 and L1CAM mutations.