bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiscale Hierarchical Patterning by Sacrificial Layer‐Assisted Creep Lithography
Authors: Jang Segeun , Choi Jiwoo , Shin Minho , Yeon Je Hyeon , Kim Sang Moon , Choi Mansoo
Published: July 2019

The capability to fabricate various multiscale structures without limitations of size, morphology, and number of hierarchies via a simple process is highly desired in modern research. This work reports a powerful multiscale‐patterning method called sacrificial layer‐assisted creep lithography (SCL). Multiscale structures are successfully obtained by introducing a sacrificial layer, which has low creep compliance and preferential solubility in a nonpolar solvent, on a Nafion film during an additional creep‐based imprinting process. Through this method, deformation or geometrical loss of preformed structures and complex multiscale structures could be prevented including three‐level structures that are successfully constructed with well‐preserved nano/microstructures thanks to the sacrificial layer. To assess the diverse applicability of the SCL, a multiscale poly(dimethylsiloxane) channel with vertically crossed two‐groove structures is fabricated, and the directional switching of droplet spreading depending on the direction of the applied strain is demonstrated with the structure. Further, using multiscale pyramid structures, the overlapped optical properties of nano‐ and microstructures, which enhance overall reflectance of the surface, are verified.
Vertically Aligned WS2 Layers for High‐Performing Memristors and Artificial Synapses
Authors: Kumar Mohit , Ban Dong‐Kyun , Kim Sang Moon , Kim Joondong , Wong Ching‐Ping
Published: July 2019

Inspired by the human brain, the quest for high‐performing neuromorphic architecture has recently gained more attention, which can be achieved by two‐terminal memristors. However, due to random and uncontrolled filament formation during a typical switching process, conventional memristors suffer from severe shortcomings such as temporal/spatial reproducibility as well as trivial sensitivity against applied spikes, however all these properties are crucial for accurate and quick information processing. Here, reproducible and robust two serially connected memristors comprised of ZnO and vertically grown WS2 layers are reported. The device demonstrates remarkable tunable dynamic range along with comprehensive synaptic functions, including short‐ to long‐term plasticity, paired‐pulse facilitation, and spike‐timing‐dependent plasticity. Vertically aligned WS2 layers confine the conduction along 1D channel and drastically enhance the performance. The dynamic processes of memorizing and forgetting are mimicked through a 3 × 3 memristive synapse array. A unique platform to design high‐performing and reproducible artificial synapses for neuromorphic computing is provided.
Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma
Authors: Li Tianjiao , Li Hao , Li Shuo , Xu Shuaishuai , Zhang Wuhu , Gao Heli , Xu Huaxiang , Wu Chuntao , Wang Wenquan , Yu Xianjun , Liu Liang
Published: July 2019

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR‐T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR‐T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR‐T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the “on‐target, off‐tumor” effect. Applying neoantigens of PDAC as targets for CAR‐T therapy, recognizing the CAR‐T subgroup with better antitumor effect, and designing a CAR‐T system targeting stroma of PDAC may contribute to develop a powerful CAR‐T therapy for PDAC in the future.
Broodmate aggression and life history variation in accipitrid birds of prey
Authors: Redondo Tomás , Romero José María , Díaz‐Delgado Ricardo , Nagy Jenő
Published: July 2019

Aggressive sibling competition for parental food resources is relatively infrequent in animals but highly prevalent and extreme among certain bird families, particularly accipitrid raptors (Accipitriformes). Intense broodmate aggression within this group is associated with a suite of traits including a large adult size, small broods, low provisioning rates, and slow development. In this study, we apply phylogenetic comparative analyses to assess the relative importance of several behavioral, morphological, life history, and ecological variables as predictors of the intensity of broodmate aggression in 65 species of accipitrid raptors. We show that intensity of aggression increases in species with lower parental effort (small clutch size and low provisioning rates), while size effects (adult body mass and length of nestling period) are unimportant. Intense aggression is more closely related to a slow life history pace (high adult survival coupled with a restrained parental effort), rather than a by‐product of allometry or food limitation. Consideration of several ecological variables affecting prey abundance and availability reveals that certain lifestyles (e.g., breeding in aseasonal habitats or hunting for more agile prey) may slow a species’ life history pace and favor the evolution of intense broodmate aggression.
Peripheral neurons: Master regulators of skin and mucosal immune response
Authors: Basso Lilian , Serhan Nadine , Tauber Marie , Gaudenzio Nicolas
Published: July 2019

The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro‐immune interactions.
Oligodendrocyte involvement in Gulf War Illness
Authors: Belgrad Jillian , Dutta Dipankar J. , Bromley‐Coolidge Samantha , Kelly Kimberly A. , Michalovicz Lindsay T. , Sullivan Kimberly A. , O'Callaghan James P. , Fields Richard. Douglas
Published: July 2019

Low level sarin nerve gas and other anti‐cholinesterase agents have been implicated in Gulf War illness (GWI), a chronic multi‐symptom disorder characterized by cognitive, pain and fatigue symptoms that continues to afflict roughly 32% of veterans from the 1990–1991 Gulf War. How disrupting cholinergic synaptic transmission could produce chronic illness is unclear, but recent research indicates that acetylcholine also mediates communication between axons and oligodendrocytes. Here we investigated the hypothesis that oligodendrocyte development is disrupted by Gulf War agents, by experiments using the sarin‐surrogate acetylcholinesterase inhibitor, diisopropyl fluorophosphate (DFP). The effects of corticosterone, which is used in some GWI animal models, were also investigated. The data show that DFP decreased both the number of mature and dividing oligodendrocytes in the rat prefrontal cortex (PFC), but differences were found between PFC and corpus callosum. The differences seen between the PFC and corpus callosum likely reflect the higher percentage of proliferating oligodendroglia in the adult PFC. In cell culture, DFP also decreased oligodendrocyte survival through a non‐cholinergic mechanism. Corticosterone promoted maturation of oligodendrocytes, and when used in combination with DFP it had protective effects by increasing the pool of mature oligodendrocytes and decreasing proliferation. Cell culture studies indicate direct effects of both DFP and corticosterone on OPCs, and by comparison with in vivo results, we conclude that in addition to direct effects, systemic effects and interruption of neuron–glia interactions contribute to the detrimental effects of GW agents on oligodendrocytes. Our results demonstrate that oligodendrocytes are an important component of the pathophysiology of GWI.
Cancer mortality in kidney transplant recipients: An Australian and New Zealand population‐based cohort study, 1980–2013
Authors: Rosales Brenda M. , De La Mata Nicole , Vajdic Claire M. , Kelly Patrick J. , Wyburn Kate , Webster Angela C.
Published: July 2019

Cancer burden is increasing in kidney transplant recipients, but differences in mortality compared to the general population remain unclear. We sought to compare cancer mortality in paediatric and adult kidney transplant recipients with the general population and describe any differences, by site, age and sex, country and over time. We included kidney transplant recipients from the Australian and New Zealand Dialysis and Transplantation Registry, 1980–2013. Date of death and underlying cause of death were ascertained by data‐linkage and classified using ICD10AM codes. Indirect standardisation was used to estimate standardised mortality ratios (SMR). There were 5,284 deaths in 17,628 kidney transplant recipients over 175,084 person‐years of observation, including 1,061 (20%) cancer deaths. Relative cancer mortality was higher than the general population for all‐site (SMR 2.9, 95% CI 2.7–3.1) cancer and highest for nonmelanoma skin cancer (SMR 50.9, 95% CI 43.5–59.6) and lymphoma (SMR 42.2, 95% CI 35.3–50.5). Relative cancer mortality decreased with increasing age in men (p < 0.001) and women (p = 0.001) but never reached parity with the general population. Relative mortality did not change with age for skin and lip, or colorectal cancers (p‐value >0.1). Only relative colorectal cancer mortality increased over time (p = 0.002). Our study shows cancer mortality in kidney transplant recipients was higher than expected in the general population. The magnitude of excess mortality varied by cancer site, age and sex. Further evidence is needed to identify whether this variation is due to differences at diagnosis or access and effectiveness of cancer treatments in this population.
Alignment control technology of liquid crystal molecules
Authors: Ishihara Shoichi , Mizusaki Masanobu
Published: July 2019

Liquid crystal displays are now indispensable in everyday life. The display characteristics considerably depend on the configuration of liquid crystal (LC) molecules and interactions between the LC molecules and an alignment film surface. In this paper, we introduce various methods to control parameters that dominate the LC alignment. These parameters include order parameters, the pretilt angle, the director direction, and surface anchoring strength. We also introduce their evaluation methods. In particular, recent alignment film‐free technology is explained in detail. In addition, details of how these parameters are related to the display characteristics, particularly wide viewing angles and fast response characteristics, are described primarily with reference to recent technologies.
Adaptive iterative regularization schemes for two‐dimensional integral‐algebraic systems
Authors: Farahani Mahdi S. , Hadizadeh Mahmoud , Bulatov Mikhail V. , Chistyakova Elena
Published: July 2019

The main idea of this paper is to utilize the adaptive iterative schemes based on regularization techniques for moderately ill‐posed problems that are obtained by a system of linear two‐dimensional Volterra integral equations with a singular matrix in the leading part. These problems may arise in the modeling of certain heat conduction processes as well as in the dynamic simulation packages such as compressible flow through a plant piping network. Owing to the ill‐posed nature of the first kind Volterra equation that appears in the system, we will focus on the two families of regularization algorithms, ie, the Landweber and Lavrentiev type methods, where we treat both the exact and perturbed data. Our aim is to work directly with the original Volterra equations without any kind of reduction. Two fast iterative algorithms with reasonable computational complexity are developed. Numerical experiments on a few test problems are used to illustrate the validity and efficiency of the proposed iterative methods in comparison with the classical regularization methods.
Chlorophyll Supplementation in Early Life Prevents Diet‐Induced Obesity and Modulates Gut Microbiota in Mice
Authors: Li Yuanyuan , Cui Yu , Hu Xiaosong , Liao Xiaojun , Zhang Yan
Published: July 2019

Scope

The high rates of overweight and obesity, currently occurring in children, underline the urgent need for preventive strategies in early life before excess weight is gained.

Methods and results

In this study, the alleviating obesity property of chlorophyll supplementation in early life is investigated using a 4‐week‐old C57BL/6J male mice model with obesity induced by high‐fat diet (HFD). The present study finds that chlorophyll supplementation in early life can effectively retard body weight gain, improve glucose tolerance, as well as reduce low‐grade inflammation in HFD‐fed mice. Consequently, high‐throughput sequencing of the 16S rRNA demonstrates that chlorophyll supplementation significantly reversed the HFD‐induced gut dysbiosis, as evidenced by the decreased Firmicutes‐to‐Bacteroidetes ratios as chlorophyll is introduced. Furthermore, in chlorophyll‐fed mice, the increased abundance of Blautia and norank_f_Bacteroidales_S24‐7_group, and the decreased abundance of Lactococcus and Lactobacillus, bring about the possibility that chlorophyll's alterations to the gut microbiota composition would be the main factors for dietary chlorophyll alleviating obesity‐related indexes.

Conclusion

Taken together, these results reveal that the intake of chlorophyll in early life may propel healthy weight management and produce beneficial effects against potential obesity in later life.
Stilbenoid‐Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor
Authors: Beetch Megan , Lubecka Katarzyna , Shen Kate , Flower Kirsty , Harandi‐Zadeh Sadaf , Suderman Matthew , Flanagan James M , Stefanska Barbara
Published: July 2019

Scope

Loci‐specific increase in DNA methylation occurs in cancer and may underlie gene silencing. It is investigated whether dietary stilbenoids, resveratrol, and pterostilbene exert time‐dependent effects on DNA methylation patterns and specifically methylation‐silenced tumor suppressor genes in breast cancer cells.

Methods and results

Following genome‐wide DNA methylation analysis with Illumina‐450K, changes characteristic of early and late response to stilbenoids are identified. Interestingly, often the same genes but at different CpG loci, the same gene families, or the same functional gene categories are affected. CpG loci that lose methylation in exposed cells correspond to genes functionally associated with cancer suppression. There is a group of genes, including SEMA3A, at which the magnitude of hypomethylation in response to stilbenoids rises with increasing invasive potential of cancer cells. Decreased DNA methylation at SEMA3A promoter and concomitant gene upregulation coincide with increased occupancy of active histone marks. Open chromatin upon exposure to stilbenoids may be linked to decreased DNMT3A binding followed by increased NF1C transcription factor occupancy. Sequestration of DNMT3A is possibly a result of stilbenoid‐mediated increase in SALL3 expression, which was previously shown to bind and inhibit DNMT3A activity.

Conclusions

The findings define mechanistic players in stilbenoid‐mediated epigenetic reactivation of genes suppressing cancer.
Application of Volatile Organic Compound Analysis in a Nutritional Intervention Study: Differential Responses during Five Hours Following Consumption of a High‐ and a Low‐Fat Dairy Drink
Authors: Hageman Jeske H. J. , Nieuwenhuizen Arie G. , van Ruth Saskia M. , Hageman Jos A. , Keijer Jaap
Published: July 2019

Scope

Exhaled volatile organic compounds (VOCs) are a possible relevant target for noninvasive assessment of metabolic responses. Using a breathomics approach, it is aimed to explore whether lipid intake influences VOC profiles in exhaled air, and to obtain insight in intra‐ and interindividual variations.

Methods and results

Three human interventions are performed. In the first, 12 males consume a high‐fat drink on three study days. In the second, 12 males receive a high‐ and a low‐fat drink on 6 days. In the third, three volunteers consume the high‐fat drink again for tentative compound identification. Participants are asked to exhale, for 5 h postprandial with 15–20 min intervals, into a proton‐transfer‐reaction mass spectrometer, and VOCs in exhaled air are measured. Consumption of a drink alters the VOC profile, with considerable interindividual variation and quantitative intraindividual differences between days. Consumption of two different drinks results in a distinct VOC profile, caused by several specific m/z values. Most of these compounds are identified as being related to ketone body formation and lipid oxidation, showing an increase in high‐ versus low‐fat drink.

Conclusion

Exhaled VOCs have the potential to assess differences in metabolic responses induced by nutrition, especially when day‐to‐day variation can be minimized.
Industrial Trans Fatty Acids Stimulate SREBP2‐Mediated Cholesterogenesis and Promote Non‐Alcoholic Fatty Liver Disease
Authors: Oteng Antwi‐Boasiako , Loregger Anke , van Weeghel Michel , Zelcer Noam , Kersten Sander
Published: July 2019

Scope

The mechanisms underlying the deleterious effects of trans fatty acids on plasma cholesterol and non‐alcoholic fatty liver disease (NAFLD) are unclear. Here, the aim is to investigate the molecular mechanisms of action of industrial trans fatty acids.

Methods and results

Hepa1‐6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans‐unsaturated, cis‐unsaturated, or saturated fatty acids. Transcriptomics analysis of Hepa1‐6 cells shows that elaidate but not oleate or palmitate induces expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate is mediated by increased sterol regulatory element‐binding protein 2 (SREBP2) activity and is dependent on SREBP cleavage–activating protein (SCAP), yet independent of liver‐X receptor and ubiquitin regulatory X domain‐containing protein 8. Elaidate decreases intracellular free cholesterol levels and represses the anticholesterogenic effect of exogenous cholesterol. In mice, the trans‐unsaturated diet increases the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, alanine aminotransferase activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis‐unsaturated and saturated diets.

Conclusion

Elaidate induces cholesterogenesis in vitro by activating the SCAP–SREBP2 axis, likely by lowering intracellular free cholesterol and attenuating cholesterol‐dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Projection‐based improvement of 3D reconstructions from motion‐impaired dental cone beam CT data
Authors: Niebler Stefan , Schömer Elmar , Tjaden Henning , Schwanecke Ulrich , Schulze Ralf
Published: July 2019

Purpose

Computed tomography (CT) and, in particular, cone beam CT (CBCT) have been increasingly used as a diagnostic tool in recent years. Patient motion during acquisition is common in CBCT due to long scan times. This results in degraded image quality and may potentially increase the number of retakes. Our aim was to develop a marker‐free iterative motion correction algorithm that works on the projection images and is suitable for local tomography.

Methods

We present an iterative motion correction algorithm that allows the patient's motion to be detected and taken into account during reconstruction. The core of our method is a fast GPU‐accelerated three‐dimensional reconstruction algorithm. Assuming rigid motion, motion correction is performed by minimizing a pixel‐wise cost function between all captured x‐ray images and parameterized projections of the reconstructed volume.

Results

Our method is marker‐free and requires only projection images. Furthermore, it can deal with local tomography data. We demonstrate the effectiveness of our approach on both simulated and real motion‐beset patient images. The results show that our new motion correction algorithm leads to accurate reconstructions with sharper edges, better contrasts and more detail.

Conclusions

The presented method allows for correction of patient motion with observable improvements in image quality compared to uncorrected reconstructions. Potentially, this may reduce the number of retakes caused by corrupted reconstructions due to patient movements.
Reduced effectiveness of repellents in a pyrethroid‐resistant strain of Aedes aegypti (Diptera: culicidae) and its correlation with olfactory sensitivity
Authors: Yang Liu , Norris Edmund J , Jiang Shiyao , Bernier Ulrich R , Linthicum Kenneth J , Bloomquist Jeffrey R
Published: July 2019

BACKGROUND

The mosquito, Aedes aegypti (Diptera: Culicidae), is a vector of dengue fever, zika, chikungunya, and yellow fever viruses, and in many areas possesses significant levels of resistance to pyrethroids. Behavioral performance was assessed in 15, 30, and 60 min exposures in a high throughput vapor phase spatial repellency assay to three contact repellent standards: N,N‐diethyl‐3‐methylbenzamide (DEET), ethyl 3‐[acetyl(butyl)amino] propanoate (IR3535), and 2‐undecanone, as well as pyrethrum extract, transfluthrin, and metofluthrin in susceptible (Orlando) and a pyrethroid‐resistant Puerto Rico strain of Aedes aegypti. Additionally, electroantennographic studies were used to investigate the antennal sensitivities to these compounds in both strains.

RESULTS

Resistance was found to all tested insect repellents in the Puerto Rico strain of Ae. aegypti. Resistance ratios at the different time points were about 2 for DEET, 3 for 2‐undecanone, and 12 for IR3535. Resistance was also observed to pyrethrum extract (∼9‐fold), transfluthrin (∼5‐fold), and metofluthrin (∼48‐fold) in repellent behavioral response. Electrophysiological analysis found decreased antennal sensitivity to all repellents tested, consistent with their behavioral effects.

CONCLUSION

The reduced sensitivity to these repellents may represent a fitness cost arising from the kdr mutation present in Puerto Rico Aedes aegypti. This work highlights the need for understanding collateral effects from the evolution of pesticide resistance in mosquitoes, and the importance of finding alternative strategies to control resistance development. © 2019 Society of Chemical Industry
A Bayesian structural equation model in general pedigree data analysis
Authors: Akbarzadeh Mahdi , Moghimbeigi Abbas , Morris Nathan , Daneshpour Maryam S. , Mahjub Hossein , Soltanian Ali Reza
Published: July 2019

Structural equation modeling (SEM) is a powerful, comprehensive, and flexible multivariate statistical method for modeling relationships between observed and latent variables. However, in genetic association analysis, frequentist approaches to fitting SEMs do not always lead to convergence and admissible solutions for complex models, categorical variables, complicated data structures such as pedigree data and small sample sizes. Accordingly, to conduct a SEM pedigree data analysis, Stan platform as a probabilistic programming language was applied in our study to propose a new version of the Bayesian approach that adopts Hamiltonian Monte Carlo (HMC) and data augmentation techniques. At first, a comprehensive simulation study was conducted to compare the precision of each parameter of the suggested method with that of the classic technique in terms of bias, alpha error rate, and coverage probability. After that, the method was applied to real data with a conceptual model including ordinal indicators in order to conduct genetic association analysis of two well‐known genetic markers with metabolic syndrome trait. The simulation findings revealed the proposed Bayesian method was a more efficient technique than MLE approach. Moreover, Bayesian approach yielded a better statistical performance in solving the problems than did classic approach.
A mobilities perspective on migration in the context of environmental change
Authors: Wiegel Hanne , Boas Ingrid , Warner Jeroen
Published: July 2019

Academic, political, and policy debates about the connection between environmental change and human migration have long focused on migration drivers and outcomes, resulting in a limited discussion between the discourses of “desolate climate refugees” and “environmental migrants as agents of adaptation.” These perspectives remain dominant, particularly in policy and media circles, despite academic critique and the recent emergence of more diverse approaches. In this intervention, we contribute to the recent turn in environmental migration research by seeking to better ground and pluralize our understanding of how environmental change and human mobility relate. We do so by offering a mobilities perspective that centers on the practices, motives, and experiences of mobility and immobility in the context of environmental change: When and why do people decide to move—or not to move—in response to environmental changes? How do they cope with migration pressures? Where do they move, under what conditions, and who can or must stay behind? This approach attends to the diverse aspirations and differential capabilities that underlie particular practices of movement or nonmovement, reflecting both individual characteristics as well as interconnections with uneven power relations across local, regional, and global scales. A mobilities approach offers a starting point for an expanded research agenda on environmental im/mobilities. This enables academic analysis and policy discussion of the human (im)mobility‐environmental change nexus to become better attuned to the actual practice and heterogeneous needs of those affected.

This article is categorized under:

Climate and Development > Social Justice and the Politics of Development

Vulnerability and Adaptation to Climate Change > Values‐Based Approach to Vulnerability and Adaptation
Elements and (first) principles in chemistry
Authors: Hendry Robin Findlay
Published: July 2019

The first principle of chemical composition is that elements are actually present in their compounds. It is a golden thread running through the history of compositional thinking in chemistry since before the chemical revolution. Opposed to this principle, which I call Actually Present Elements (APE), is the idea that elements are merely potentially present in their compounds: although not actually present, it is possible to recover them. In this paper I follow that golden thread, and then discuss the status of APE itself: is it true? What arguments were there for it, and when? I argue that APE is a metaphysical principle, albeit at a lower level of generality and abstraction than the term ‘metaphysical’ usually suggests. I critically examine a range of different views on how metaphysical principles might be involved in research programmes in empirical science, and conclude by endorsing Elie Zahar’s view that metaphysical principles such as APE are to be found at the very heart of science. Moreover, they can be recipients of empirical support just like other parts of scientific theory.
Spironolactone May be a Cause of Hormonally Associated Vestibulodynia and Female Sexual Arousal Disorder
Authors: Mitchell Leia , Govind Vaishnavi , Barela Karissa , Goldstein Andrew T.
Published: July 2019

Background

Although spironolactone is an effective treatment for androgen-mediated cutaneous disorders, the potential sexual side-effects are poorly documented in current literature.

Aim

The purpose of this study was to provide clinical evidence that spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder.

Methods

A database search of a vulvar disorders clinic revealed 7 cases in which spironolactone may have caused or contributed to dyspareunia and decreased arousal. In all cases, the patients stopped taking spironolactone and used a compounded estradiol 0.01%/testosterone 0.1% gel to the vestibule twice daily. 2 cases are discussed to further illustrate these previously unreported side effects.

Outcomes

Improvement in sexual function was determined after treatment.

Results

Examination of women taking spironolactone who presented with the complaints of introital dyspareunia revealed vulvar vestibular atrophy and tenderness, especially at the glandular ostia. After stopping spironolactone and applying a topical estrogen/testosterone gel to the vestibule, all women had significant improvement in their vulvar atrophy, resolution of their dyspareunia, and improved sexual arousal.

Clinical Implications

Use of spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder.

Strengths and Limitations

The influence of spironolactone on vulvar health and sexual function is poorly documented in the medical literature. The strength of this paper is that it examines the potential deleterious side effects of this medication on female sexual function. However, the most significant limitation of this case series is that it was not a prospective, controlled study.

Conclusions

Although treatment of androgen-mediated cutaneous disorders is warranted, medical providers should be aware of the potential sexual side effects of this anti-androgenic medication.
Research on the process of fabricating a multi-layer metal micro-structure based on UV-LIGA overlay technology
Authors: Ma Yali , Liu Wenkai , Liu Chong
Published: July 2019

In this paper, we report the study of the process of fabricating a multi-layer metal micro-structure using UV-LIGA overlay technology, including mask fabrication, substrate treatment, and UV-LIGA overlay processes. To solve the process problems in the masking procedure, the swelling problem of the first layer of SU-8 thick photoresist was studied experimentally. The 5 µm line-width compensation and closed 20 µm and 30 µm isolation strips were designed and fabricated around the micro-structure pattern. The pore problem in the Ni micro-electroforming layer was analyzed and the electroforming parameters were improved. The pH value of the electroforming solution should be controlled between 3.8 and 4.4 and the current density should be below 3 A/dm2. To solve the problems of high inner stress and incomplete development of the micro-cylinder hole array with a diameter of 30 µm, the lithography process was optimized. The pre-baking temperature was increased via gradient heating and rose every 5 °C from 65 °C to 85 °C and then remained at 85 °C for 50 min – 1 h. In addition, the full contact exposure was used. Finally, a multi-layer metal micro-structure with high precision and good quality of micro-electroforming layer was fabricated using UV-LIGA overlay technology.
Comparative genomics of casein genes
Authors: Madende Moses , Osthoff Gernot
Published: July 2019

This research paper addresses the hypothesis that comparative genomics can give a new insight into the functionality of casein genes with respect to the casein micelle. Comparative genomics is a rapidly emerging field in computational biology whereby two or more genomes are compared in order to obtain a global view on genomes as well as assigning previously unknown functions for genes. Casein genes are among the most rapidly evolving mammalian genes, with the gene products mainly grouped into four types (αs1-, αs2-, β- and κ-casein). Functionally, casein genes are central to the casein micelle, the exact structure of which is still a subject of intense debate. Moreover, and adding to this complexity, some mammals lack some of the casein genes, although casein micelles have been observed in their milk. This observation has prompted an investigation into the distribution of casein genes across a host of mammalian species. It was apparent from this study that casein gene sequences are very diverse from each other and we confirmed that many mammalian species lack one or more of the casein genes. The genes encoding β- and κ-caseins are present in most mammals whereas α-casein encoding genes are less represented. This suggests different mechanisms for casein micelle formation in different species as well as the functions that are assigned to each individual casein.
Four reasons why early detection centers for psychosis should be renamed and their treatment targets reconsidered: we should not catastrophize a future we can neither reliably predict nor change
Authors: Moritz Steffen , Gawęda Łukasz , Heinz Andreas , Gallinat Jürgen
Published: July 2019

Since the 1990s, facilities for individuals at putative risk for psychosis have mushroomed and within a very short time have become part of the standard psychiatric infrastructure in many countries. The idea of preventing a severe mental disorder before its exacerbation is laudable, and early data indeed strongly suggested that the sooner the intervention, the better the outcome. In this paper, the authors provide four reasons why they think that early detection or prodromal facilities should be renamed and their treatment targets reconsidered. First, the association between the duration of untreated psychosis and outcome is empirically established but has become increasingly weak over the years. Moreover, its applicability to those who are considered at risk remains elusive. Second, instruments designed to identify future psychosis are prone to many biases that are not yet sufficiently controlled. None of these instruments allows an even remotely precise prognosis. Third, the rate of transition to psychosis in at-risk patients is likely lower than initially thought, and evidence for the success of early intervention in preventing future psychosis is promising but still equivocal. Perhaps most importantly, the treatment is not hope-oriented. Patients are more or less told that schizophrenia is looming over them, which may stigmatize individuals who will never, in fact, develop psychosis. In addition self-stigma has been associated with suicidality and depression. The authors recommend that treatment of help-seeking individuals with mental problems but no established diagnosis should be need-based, and the risk of psychosis should be de-emphasized as it is only one of many possible outcomes, including full remission. Prodromal clinics should not be abolished but should be renamed and restructured. Such clinics exist, but the transformation process needs to be facilitated.
Algorithm Spots Climate-Altering Ship Tracks in Satellite Data
Authors: Kornei Katherine
Published: July 2019

Tens of thousands of ship tracks—cloud structures created when ships’ exhaust plumes interact with the atmosphere—are pinpointed automatically, furthering study of these climate-altering features.
Autophagy flux in critical illness, a translational approach
Authors: Tardif Nicolas , Polia Franck , Tjäder Inga , Gustafsson Thomas , Rooyackers Olav
Published: July 2019

Recent clinical trials suggest that early nutritional support might block the induction of autophagy in critically ill patients leading to the development of organ failure. However, the regulation of autophagy, especially by nutrients, in critical illness is largely unclear. The autophagy flux (AF) in relation to critical illness and nutrition was investigated by using an in vitro model of human primary myotubes incubated with serum from critically ill patients (ICU). AF was calculated as the difference of p62 expression in the presence and absence of chloroquine (50 µM, 6 h), in primary myotubes incubated for 24 h with serum from healthy volunteers (n = 10) and ICU patients (n = 93). We observed 3 different phenotypes in AF, non-altered (ICU non-responder group), increased (ICU inducer group) or blocked (ICU blocker group). This block was not associate with a change in amino acids serum levels and was located at the accumulation of autophagosomes. The increase in the AF was associated with lower serum levels of non-essential amino acids. Thus, early nutrition during critical illness might not block autophagy but could attenuate the beneficial effect of starvation on reactivation of the autophagy process. This could be of clinical importance in the individual patients in whom this process is inhibited by the critical illness insult.
Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to 68Ga-PSMA PET-CT
Authors: Meißner Sebastian , Janssen Jan-Carlo , Prasad Vikas , Diederichs Gerd , Hamm Bernd , Brenner Winfried , Makowski Marcus R.
Published: July 2019

The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1–88.9%), 98.6% (CI 97.6–99.2%), 73.5% (CI 52.1–87.6%) and 99.5% (CI 98.8–99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.
The effect of asymmetric reproductive ability on the evolution of cooperation on interdependent networks
Authors: Du Chunpeng , Geng Yini , Yin Xiaoxiao , Ma Yongjuan , Li Xiaogang , Shi Lei
Published: July 2019

In this paper, we consider an asymmetric reproductive ability on interdependent networks and investigate how this setting affects the evolution of cooperation. In detail, players decide to update their strategies at each step on main network (network B), while for sub network (network A), players update their strategies with a fixed probability p. Obviously, the system restores the traditional case when p = 1, where cooperation can survive by interdependent network reciprocity. And our asymmetric set-up comes into play when p < 1. Numerical simulation results show that our asymmetric coupling will hinder the overall cooperation level for small p. In detail, the introduction of asymmetric reproductive ability urges the formation of symmetry breaking and further weakens the positive impact by location synchronous effect. And the root cause is entirely distinct situation of utility differences on two networks. These observations further demonstrate a class of phenomena on interdependent networks that it would have catastrophic consequences on one network even if a unrelated change only occurs seemingly on another network.
Molecular complexity of the major urinary protein system of the Norway rat, Rattus norvegicus
Authors: Gómez-Baena Guadalupe , Armstrong Stuart D. , Halstead Josiah O. , Prescott Mark , Roberts Sarah A. , McLean Lynn , Mudge Jonathan M. , Hurst Jane L. , Beynon Robert J.
Published: July 2019

Major urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.
Evaluation of reference genes for real-time quantitative PCR analysis in southern corn rootworm, Diabrotica undecimpunctata howardi (Barber)
Authors: Basu Saumik , Pereira Adriano E. , Pinheiro Daniele H. , Wang Haichuan , Valencia-Jiménez Arnubio , Siegfried Blair D. , Louis Joe , Zhou Xuguo ‘Joe’ , Vélez Ana Maria
Published: July 2019

Quantitative reverse transcription PCR (RT-qPCR) is one of the most efficient, reliable and widely used techniques to quantify gene expression. In this study, we evaluated the performance of six southern corn rootworm, Diabrotica undecimpunctata howardi (Barber), housekeeping genes (HKG), β-actin (Actin), β-tubulin (Tubulin), elongation factor 1 alpha (EF1α), glyceraldehyde-3 phosphate dehydrogenase (GAPDH), 40 S ribosomal protein S9 (RpS9) and ubiquitin-conjugating protein (Ubi), under different experimental conditions such as developmental stage, exposure of neonate and adults to dsRNA, exposure of adults to different temperatures, different 3rd instar larva tissues, and neonate starvation. The HKGs were analyzed with four algorithms, including geNorm, NormFinder, BestKeeper, and delta-CT. Although the six HKGs showed a relatively stable expression pattern among different treatments, some variability was observed. Among the six genes, EF1α exhibited the lowest Ct values for all treatments while Ubi exhibited the highest. Among life stages and across treatments, Ubi exhibited the least stable expression pattern. GAPDH, Actin, and EF1α were among the most stable HKGs in the majority of the treatments. This research provides HKG for accurate normalization of RT-qPCR data in the southern corn rootworm. Furthermore, this information can contribute to future genomic and functional genomic research in Diabrotica species.
Optimization of Molecules via Deep Reinforcement Learning
Authors: Zhou Zhenpeng , Kearnes Steven , Li Li , Zare Richard N. , Riley Patrick
Published: July 2019

We present a framework, which we call Molecule Deep Q-Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (double Q-learning and randomized value functions). We directly define modifications on molecules, thereby ensuring 100% chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. MolDQN achieves comparable or better performance against several other recently published algorithms for benchmark molecular optimization tasks. However, we also argue that many of these tasks are not representative of real optimization problems in drug discovery. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works.
Modeling the Amplification of Immunoglobulins through Machine Learning on Sequence-Specific Features
Authors: Döring Matthias , Kreer Christoph , Lehnen Nathalie , Klein Florian , Pfeifer Nico
Published: July 2019

Successful primer design for polymerase chain reaction (PCR) hinges on the ability to identify primers that efficiently amplify template sequences. Here, we generated a novel Taq PCR data set that reports the amplification status for pairs of primers and templates from a reference set of 47 immunoglobulin heavy chain variable sequences and 20 primers. Using logistic regression, we developed TMM, a model for predicting whether a primer amplifies a template given their nucleotide sequences. The model suggests that the free energy of annealing, ΔG, is the key driver of amplification (p = 7.35e-12) and that 3′ mismatches should be considered in dependence on ΔG and the mismatch closest to the 3′ terminus (p = 1.67e-05). We validated TMM by comparing its estimates with those from the thermodynamic model of DECIPHER (DE) and a model based solely on the free energy of annealing (FE). TMM outperformed the other approaches in terms of the area under the receiver operating characteristic curve (TMM: 0.953, FE: 0.941, DE: 0.896). TMM can improve primer design and is freely available via openPrimeR (http://openPrimeR.mpi-inf.mpg.de).
Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells
Authors: Kengelbach-Weigand Annika , Tasbihi Kereshmeh , Strissel Pamela L. , Schmid Rafael , Marques Jasmin Monteiro , Beier Justus P. , Beckmann Matthias W. , Strick Reiner , Horch Raymund E. , Boos Anja M.
Published: July 2019

Due to the increasing clinical application of adipose-derived stem cells (ADSC), e.g. lipotransfer for breast reconstruction, this study aimed to gain novel insights regarding ADSC influence on breast tissue remodeling and determine patient-dependent factors affecting lipotransfer as well as begin to address its oncological risks. The ADSC secretome was analyzed from five normal breast reduction patients and contained elevated levels of growth factors, cytokines and proteins mediating invasion. ADSC/ADSC secretomes were tested for their influence on the function of primary mammary epithelial cells, and tumor epithelial cells using cell culture assays. ADSC/ADSC secretomes significantly stimulated proliferation, transmigration and 3D-invasion of primary normal and tumor epithelial cells. IL-6 significantly induced an EMT and invasion. The ADSC secretome significantly upregulated normal epithelial cell gene expression including MMPs and ECM receptors. Our study supports that ADSC and its secretome promote favorable conditions for normal breast tissue remodeling by changing the microenvironment. and may also be important regarding residual breast cancer cells following surgery.