bluuebunny/crossref_metadata_2025 huggingface dataset:
Norepinephrine protects against apoptosis of mesenchymal stem cells induced by high glucose
Authors: Kong Yanan , Cheng Liuhanghang , Ma Li , Li Haihong , Cheng Biao , Zhao Yu
Published: April 2019

In diabetes, the number of bone mesenchymal stem cells (MSCs) decreases and their differentiation is impaired. However, the exact mechanism is unclear. Patients with diabetes often experience sympathetic nerve injury. Norepinephrine (NE), a major mediator of the sympathetic nervous system, influences rat MSC migration in culture and in vivo. The present study aimed to investigate the effect of NE on MSCs under high glucose conditions; therefore MSCs were treated with high glucose and NE. High glucose‐induced MSCs apoptosis, which was reversed by NE. To verify the effect of NE, mice underwent sympathectomy and were used to establish a diabetic model. Diabetic mice with sympathectomy had a higher apoptosis rate and higher levels of reactive oxygen species in their bone marrow‐derived cells than diabetic mice without sympathectomy. High glucose inhibited p‐AKT production and B‐Cell CLL/Lymphoma 2 expression, and promoted BAX and caspase‐3 expression. NE reversed these effects of high glucose. An AKT inhibitor enhanced the effects of high glucose. Thus, NE had a protective effect on MSC apoptosis induced by high glucose, possibly via the AKT/BCL‐2 pathway.
Beam and dielectric materials impact on improvement of the performance of a novel capacitive shunt RF MEMS switch
Authors: Girija Sravani Kondavitee , Sudheer Babu Gopisetty , Ramesh Mamidichetti , Prudhvi Raj Viswanadhuni , Prathyusha Dinnipati , Srinivasa Rao Karumuri
Published: April 2019

This paper presents a novel radiofrequency micro‐electro‐mechanical systems (RF MEMS) shunt capacitive switch having high isolation and low insertion loss for microphone applications. The device optimization and various electromechanical analysis are performed using a finite element modeler (FEM) solver. The proposed switch results in a pull‐in voltage of 36.88 V to displace movable beam 2/3rd of its initial gap. By varying beam material, dielectric material, beam‐dielectric thickness, and air gap between movable beam and dielectric layer, various electromechanical and electromagnetic analyses are carried out. For better isolation, silicon nitride (Si3N4) is used for the dielectric layer than hafnium oxide (HfO2) and silicon carbide (SiC). To achieve maximum displacement of the beam, various materials such as aluminum, gold, nickel, and copper are chosen; among all, this gold shows high displacement because of its good conductivity. By implementing various meandering techniques along with perforations, pull‐in voltage and stiction problems are reduced. The switch exhibits good return loss of −28 dB and insertion loss of −0.017 dB during on‐state at 5 GHz and high isolation of −41.26 dB at 10.5 GHz during off‐state. The proposed switch is used at the subsystem/device level in the future microphone, aircraft navigation, and satellite applications.
Feeding Tube Insertion and Placement Confirmation Using Electromagnetic Guidance: A Team Review
Authors: McCutcheon Kevin P. , Whittet Wanda L. , Kirsten Julie L. , Fuchs John L.
Published: April 2019

Background

Challenges for bedside placement of small‐bore feeding tube (SBFT) include iatrogenic injury, multiple exposures to x‐rays, and prolonged placement times. In 2011, the study facility began a feeding tube placement team (FTPT) using the CORTRAK system (CS) in the adult intensive care unit (ICU) and medical‐surgical populations. In 2013, a protocol was implemented using the CS to determine final SBFT location.

Methods

Serial retrospective reviews were done of patients with SBFT placement by the FTPT during July 2011–December 2012 and 2015. Measures included pulmonary deviation, tube location, placement agreement beyond chance for CS tracing and confirmation radiography (CR), x‐ray frequency, and placement time intervals.

Results

A total of 6290 SBFT placements were completed for 4239 patients. First‐attempt SBFT locations were 12.78% gastric, 13.39% first through fourth portion of duodenum, and 73.83% ligament of Treitz/jejunum, with zero placements in esophagus or lung. In 2015, staff avoided 68 lung placements by recognizing proximal pulmonary deviation. X‐ray preprotocol vs protocol (mean [SD]: 1.02 [0.15] vs 0.26 [0.44]) resulted in 74% x‐ray reduction and cost avoidance of $346,000. Time intervals (mean [SD]; N = 6290) were 14.90 (12.74) minutes for insertion, 46.04 (13.80) minutes for placement event, and 3.85 (2.23) hours for consult conclusion. Agreement for n = 1692 placements was 85.28%, with k score of 0.622 (95% confidence limit: 0.582, 0.661; P = .0005).

Conclusions

Team management of SBFT placement using the CS optimizes patient safety, standardizes practice, and decreases cost. Using the CS to determine final SBFT location is a safe alternative to CR.
Malnutrition Diagnosis in Critically Ill Patients Using 2012 Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition Standardized Diagnostic Characteristics Is Associated With Longer Hospital and Intensive Care Unit Length of Stay and Increased In‐Hospital Mortality
Authors: Hiura Grant , Lebwohl Benjamin , Seres David S.
Published: April 2019

Background

Standardized diagnostic criteria for malnutrition were developed by the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition (AND/ASPEN) in 2012. The criteria as a whole has had little validation, and the effect of underlying condition on the impact of malnutrition has not been well studied. We measured the association between severe malnutrition and hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality among critically ill inpatients.

Methods

We analyzed hospital records from 5606 patients whose admission included an ICU stay. Associations between severe malnutrition and LOS and mortality were examined by multivariable linear and logistic regression.

Results

Thirteen percent were diagnosed with severe malnutrition. These had significantly longer hospital LOS (18 [interquartile range 10–35] days vs 8 [5–14] days), total ICU LOS (7 [3–15] days vs 3 [1–6] days) and in‐hospital mortality (odds ratio [OR] 2.78, 95% confidence interval [CI] 2.33‐3.31), compared with those without severe malnutrition. After adjusting for demographics, we found significant interactions between severe malnutrition and ICU location. Patients with malnutrition in the cardiothoracic surgery ICU experienced the largest increases in hospital LOS (21.10 days, 95% CI 18.58‐23.61), ICU LOS (12.14 days, 95% CI 10.41‐13.87), and in‐hospital mortality (OR 8.78, 95% CI 5.11‐15.07).

Conclusion

Critically ill patients diagnosed with severe malnutrition based on the AND/ASPEN diagnostic characteristics experienced longer hospital and ICU LOS and increased mortality. The magnitude of effect of malnutrition was modified by ICU location, underscoring the need to identify the major comorbidities associated with malnutrition.
Landmark study finds education key factor to lifting economic burden of SMI
Authors: Canady Valerie A.
Published: April 2019

Observing that early diagnosis and intervention are key to getting people with serious mental illness (SMI) on a path to lifelong benefits, researchers of a national landmark study have found that improved education outcomes can greatly reduce the economic burden of serious mental illness.
Characterization of Crocetin‐Monoglucuronide as a Neuron‐Protective Metabolite of Crocin‐1
Authors: Zhu Anyun , Lao Chuyu , Wang Ze , Chen Yang , Bai Chuan
Published: April 2019

Scope

Crocins are important apocarotenoids in the extract of saffron (Crocus sativus L.) and fruits of gardenia (Gardenia jasminoides E.). Crocins have shown versatile biological activities and thus they have been considered to be promising therapeutics for neurodegenerative and heart diseases. Metabolism studies report that crocetin‐monoglucuronide (CM) is produced and detected in rat blood plasma after oral administration of crocins. However, due to the lack of standard compound of CM, its unambiguous identification, quantification, and bioactivity studies have been hindered.

Methods and results

CM is synthetized and its existence in blood plasma in Sprague–Dawley (SD) rats is quantified. The pharmacokinetic studies show that CM is produced in blood and brain after oral administration of crocin‐1. It is then discovered that CM possesses neuroprotective activity against beta‐amyloid (Aβ) toxicity in PC‐12 cells and drosophila models. The enzymatic assay shows that CM can effectively inhibit AChE and docking studies indicate that CM may bind in the gorge channel of AChE.

Conclusion

The work discovered that CM is a neuron‐protective metabolite of the orally administrated crocin‐1. It is demonstrated that AChE can be one of the targets of CM in its neuron‐protective activity.
Separation of water and fat signal in whole‐body gradient echo scans using convolutional neural networks
Authors: Andersson Jonathan , Ahlström Håkan , Kullberg Joel
Published: April 2019

Purpose

To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.

Methods

Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).

Results

The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.

Conclusion

It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.
Land‐sharing/‐sparing connectivity landscapes for ecosystem services and biodiversity conservation
Authors: Grass Ingo , Loos Jacqueline , Baensch Svenja , Batáry Péter , Librán‐Embid Felipe , Ficiciyan Anoush , Klaus Felix , Riechers Maraja , Rosa Julia , Tiede Julia , Udy Kristy , Westphal Catrin , Wurz Annemarie , Tscharntke Teja
Published: April 2019

The land‐sharing versus land‐sparing debate recently stagnated, lacking an integrating perspective in agricultural landscapes as well as consideration of ecosystem services. Here, we argue that land‐sharing (i.e. wildlife‐friendly farming systems) and land‐sparing (i.e. separation of high‐yielding agriculture and natural habitats) are not mutually exclusive, as both are needed to balance management needs for the multifunctionality of agricultural landscapes.

Land‐sharing promotes ecosystem services in agricultural settings, thereby allowing for environmentally friendly production. Land set aside in protected areas by land‐sparing is crucial for conservation of those species that are incompatible with agriculture.

Importantly, as species move throughout the landscape and exploit different habitats, increased connectivity between environmentally friendly managed and protected areas is needed to (a) promote spillover of ecosystem service providers from land‐sharing/‐sparing measures to agricultural production and rescue service‐providing species from extinction in hostile areas, (b) to facilitate immigration and counteract possible extinctions in spared habitats and (c) to conserve response diversity of species communities for ensuring resilience of ecosystem services in changing environments.

In conclusion, the successful management of multifunctional landscapes requires the combination of context‐specific land‐sharing and land‐sparing measures within spatially well‐connected landscape mosaics, resulting in land‐sharing/‐sparing connectivity landscapes.

A plain language summary is available for this article.
An upfront immunomodulatory therapy protocol for pediatric opsoclonus‐myoclonus syndrome
Authors: Wilbur Colin , Yea Carmen , Licht Christoph , Irwin Meredith S. , Yeh E. Ann
Published: April 2019

Background

Treatment of opsoclonus‐myoclonus syndrome (OMS) has historically involved corticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6‐12 months or longer. This study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab reduces the duration of OMS therapy without adversely affecting OMS outcomes.

Procedure

Retrospective chart review was performed for consecutive children diagnosed with OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada). Children treated within 3 months of diagnosis with a treatment protocol involving pulse methylprednisolone (3‐5 days, followed by an oral steroid taper), IVIG and/or plasma exchange, and rituximab (protocol group, n = 7) were compared to a historical group treated primarily with prednisone and IVIG (n = 8).

Results

The duration of corticosteroid treatment was shorter in the protocol (median 4.5 [range 3‐12] months) compared to that in the historical group (median 21.5 [range 6‐70] months, P = .005), and subjects in the protocol group received fewer cycles of IVIG (median 1 [range 0‐7] cycle vs 7 [range 1‐70] cycles, P = .01). The proportion of children with OMS relapse was similar between the protocol and historic groups (2/6 vs 5/8, P = .59). OMS symptom rating scales at 12‐month follow‐up were similar in the protocol group (median 2.5, range 0‐3) compared to that in the historical group (median 1, range 0‐7; P = .66).

Conclusions

An upfront immunomodulatory therapy protocol with rituximab permits reduction in the duration of corticosteroid and IVIG therapy without a detrimental effect on OMS outcomes. Future studies with longer follow‐up will have to determine whether neurocognitive and psychosocial outcomes are improved by this approach.
Inkjet Printed Nanopatterned Aptamer‐Based Sensors for Improved Optical Detection of Foodborne Pathogens
Authors: Díaz‐Amaya Susana , Zhao Min , Lin Li‐Kai , Ostos Carlos , Allebach Jan P. , Chiu George T.‐C. , Deering Amanda J. , Stanciu Lia A.
Published: April 2019

The increasing incidence of infectious outbreaks from contaminated food and water supply continues imposing a global burden for food safety, creating a market demand for on‐site, disposable, easy‐to‐use, and cost‐efficient devices. Despite of the rapid growth of biosensors field and the generation of breakthrough technologies, more than 80% of the platforms developed at lab‐scale never will get to meet the market. This work aims to provide a cost‐efficient, reliable, and repeatable approach for the detection of foodborne pathogens in real samples. For the first time an optimized inkjet printing platform is proposed taking advantage of a carefully controlled nanopatterning of novel carboxyl‐functionalized aptameric ink on a nitrocellulose substrate for the highly efficient detection of E. coli O157:H7 (25 colony forming units (CFU) mL−1 in pure culture and 233 CFU mL−1 in ground beef) demonstrating the ability to control the variation within ±1 SD for at least 75% of the data collected even at very low concentrations. From the best of the knowledge this work reports the lowest limit of detection of the state of the art for paper‐based optical detection of E. coli O157:H7, with enough evidence (p > 0.05) to prove its high specificity at genus, species, strain, and serotype level.
3D Bioprinting: from Benches to Translational Applications
Authors: Heinrich Marcel Alexander , Liu Wanjun , Jimenez Andrea , Yang Jingzhou , Akpek Ali , Liu Xiao , Pi Qingmeng , Mu Xuan , Hu Ning , Schiffelers Raymond Michel , Prakash Jai , Xie Jingwei , Zhang Yu Shrike
Published: April 2019

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high‐resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.
Mesoporous Silica‐Based Materials with Bactericidal Properties
Authors: Bernardos Andrea , Piacenza Elena , Sancenón Félix , Hamidi Mehrdad , Maleki Aziz , Turner Raymond J. , Martínez‐Máñez Ramón
Published: April 2019

Bacterial infections are the main cause of chronic infections and even mortality. In fact, due to extensive use of antibiotics and, then, emergence of antibiotic resistance, treatment of such infections by conventional antibiotics has become a major concern worldwide. One of the promising strategies to treat infection diseases is the use of nanomaterials. Among them, mesoporous silica materials (MSMs) have attracted burgeoning attention due to high surface area, tunable pore/particle size, and easy surface functionalization. This review discusses how one can exploit capacities of MSMs to design and fabricate multifunctional/controllable drug delivery systems (DDSs) to combat bacterial infections. At first, the emergency of bacterial and biofilm resistance toward conventional antimicrobials is described and then how nanoparticles exert their toxic effects upon pathogenic cells is discussed. Next, the main aspects of MSMs (e.g., physicochemical properties, multifunctionality, and biosafety) which one should consider in the design of MSM‐based DDSs against bacterial infections are introduced. Finally, a comprehensive analysis of all the papers published dealing with the use of MSMs for delivery of antibacterial chemicals (antimicrobial agents functionalized/adsorbed on mesoporous silica (MS), MS‐loaded with antimicrobial agents, gated MS‐loaded with antimicrobial agents, MS with metal‐based nanoparticles, and MS‐loaded with metal ions) is provided.
Ultrastable CsPbBr3 Perovskite Quantum Dot and Their Enhanced Amplified Spontaneous Emission by Surface Ligand Modification
Authors: Yan Dongdong , Shi Tongchao , Zang Zhigang , Zhou Tingwei , Liu Zhengzheng , Zhang Zeyu , Du Juan , Leng Yuxin , Tang Xiaosheng
Published: April 2019

The poor stability and aggregation problem of CsPbBr3 quantum dots (QDs) in air are great challenges for their future practical application. Herein, a simple and effective ligand‐modification strategy is proposed by introducing 2‐hexyldecanoic acid (DA) with two short branched chains to replace oleic acid (OA) with long chains during the synthesis process. These two short branched chains not only maintain their colloidal stability but also contribute to efficient radiative recombination. The calculations show that CsPbBr3 QDs with DA modification (CsPbBr3‐DA QDs) have larger binding energy than CsPbBr3 QDs with OA (CsPbBr3‐OA QDs), resulting in significantly enhanced stability. Due to the strong binding energy between DA ligands and QDs, CsPbBr3‐DA QDs exhibit no aggregation phenomenon even after stored in air for more than 70 d, and CsPbBr3‐DA QDs films can maintain 94.3% of initial PL intensity after 28 d, while in CsPbBr3‐OA QDs films occurs a rapid degradation of PL intensity. Besides, the enhanced amplified spontaneous emission (ASE) performance of CsPbBr3‐DA QDs films has been demonstrated under both one‐ and two‐photon laser excitation. The ASE threshold of CsPbBr3‐DA QDs films is reduced by more than 50% and their ASE photostability is also improved, in comparison to CsPbBr3‐OA QDs films.
Social relations: Building on Ludwig von Bertalanffy
Authors: Hofkirchner Wolfgang
Published: April 2019

Ludwig von Bertalanffy did not leave us a legacy of a social systems theory. Nonetheless, reconstructing his general approach to systems provides us with several ideas on how to build a theory of social systems. The concept of social relations easily connects to Bertalanffy's concept of relations of organization. His way of thinking underlines that social relations, as any relations of organization, are unobservables that long for theoretical means of understanding. His conception of the world would assign social relations a special place in a hierarchy of processes internal to a social system—they represent the whole of the system that nonetheless emerges from the interaction of the actors as parts thereof. Last but not least, his world view would orient us towards an organization of social systems in which the dialectic of social relations and actors balances unity and diversity as an Ought. These three main ideas of Bertalanffy offer system theoretical pillars that can inspire current social theory.
Experimental investigation of seismic behavior of confined cavity walls retrofitted with reactive powder concrete overlays
Authors: Yang Kejia , Dai Tao , Li Wei , Huang Bin
Published: April 2019

Brick cavity wall structures are widely distributed in southeastern China; however, their integrity and seismic behavior are extremely poor. To solve this problem, a new technique is proposed to enhance the seismic behavior of brick cavity walls using steel fiber reactive powder concrete (SFRPC) overlays. Two unreinforced cavity walls and four cavity walls strengthened with SFRPC overlays (applied over the entire wall surface) were tested under cyclic loading. In this study, the damage and failure modes of the specimens were analyzed in terms of the load displacement curves; furthermore, a comparative investigation was performed considering the load capacity, ductility, stiffness degradation, and energy dissipation capacity to demonstrate the merits of brick cavity walls strengthened with SFRPC overlays. The effect of strengthening using different thicknesses of reinforcement was investigated. In addition, damage analyses of the walls were performed based on the modified Park–Ang damage assessment model.
RNA regulatory processes in RNA virus biology
Authors: Cross Shaun T. , Michalski Daniel , Miller Megan R. , Wilusz Jeffrey
Published: April 2019

Numerous post‐transcriptional RNA processes play a major role in regulating the quantity, quality and diversity of gene expression in the cell. These include RNA processing events such as capping, splicing, polyadenylation and modification, but also aspects such as RNA localization, decay, translation, and non‐coding RNA‐associated regulation. The interface between the transcripts of RNA viruses and the various RNA regulatory processes in the cell, therefore, has high potential to significantly impact virus gene expression, regulation, cytopathology and pathogenesis. Furthermore, understanding RNA biology from the perspective of an RNA virus can shed considerable light on the broad impact of these post‐transcriptional processes in cell biology. Thus the goal of this article is to provide an overview of the richness of cellular RNA biology and how RNA viruses use, usurp and/or avoid the associated machinery to impact the outcome of infection.

This article is categorized under:

RNA in Disease and Development > RNA in Disease
Circadian rhythms and proteomics: It's all about posttranslational modifications!
Authors: Mauvoisin Daniel
Published: April 2019

The circadian clock is a molecular endogenous timekeeping system and allows organisms to adjust their physiology and behavior to the geophysical time. Organized hierarchically, the master clock in the suprachiasmatic nuclei, coordinates peripheral clocks, via direct, or indirect signals. In peripheral organs, such as the liver, the circadian clock coordinates gene expression, notably metabolic gene expression, from transcriptional to posttranslational level. The metabolism in return feeds back on the molecular circadian clock via posttranslational‐based mechanisms. During the last two decades, circadian gene expression studies have mostly been relying primarily on genomics or transcriptomics approaches and transcriptome analyses of multiple organs/tissues have revealed that the majority of protein‐coding genes display circadian rhythms in a tissue specific manner. More recently, new advances in mass spectrometry offered circadian proteomics new perspectives, that is, the possibilities of performing large scale proteomic studies at cellular and subcellular levels, but also at the posttranslational modification level. With important implications in metabolic health, cell signaling has been shown to be highly relevant to circadian rhythms. Moreover, comprehensive characterization studies of posttranslational modifications are emerging and as a result, cell signaling processes are expected to be more deeply characterized and understood in the coming years with the use of proteomics. This review summarizes the work studying diurnally rhythmic or circadian gene expression performed at the protein level. Based on the knowledge brought by circadian proteomics studies, this review will also discuss the role of posttranslational modification events as an important link between the molecular circadian clock and metabolic regulation.

This article is categorized under:

Laboratory Methods and Technologies > Proteomics Methods

Physiology > Mammalian Physiology in Health and Disease

Biological Mechanisms > Cell Signaling
Thraxions: ultralight throat axions
Authors: Hebecker Arthur , Leonhardt Sascha , Moritz Jakob , Westphal Alexander
Published: April 2019

Abstract

We argue that a new type of extremely light axion is generically present in the type IIB part of the string theory landscape. Its mass is suppressed by the third power of the warp factor of a strongly warped region (Klebanov-Strassler throat), suggesting the name thraxion. Our observation is based on the generic presence of several throats sharing the same 2-cycle. This cycle shrinks to zero volume at the end of each throat. It is hence trivial in homology and the corresponding C2 axion is massive. However, the mass is warping-suppressed since, if one were to cut off the strongly warped regions, a proper 2-cycle would re-emerge. Since the kinetic term of the axion is dominated in the UV, an even stronger, quadratic mass suppression results. Moreover, if the axion is excited, the angular modes of the throats backreact. This gives our effective C2 axion a finite monodromy and flattens its potential even further. Eventually, the mass turns out to scale as the third power of the warp factor. We briefly discuss possible implications for phenomenology and potential violations of the Weak Gravity Conjecture for axions. Moreover we identify a mechanism for generating super-Planckian axionic field ranges which we call drifting monodromies. However, in the examples we consider, the potential oscillates on sub-Planckian distances in field space, preventing us from building a natural inflation model on the basis of this idea.
A new approach to gauge coupling unification and proton decay
Authors: Pokorski Stefan , Rolbiecki Krzysztof , Ross Graham G. , Sakurai Kazuki
Published: April 2019

Abstract

An analytical formalism, including RG running at two loop order, is used to link the supersymmetric and GUT spectra in any GUT model in which the three gauge couplings unify. In each specific GUT model, one can then fully explore the interplay between the pattern of supersymmetry breaking and the prediction for the proton lifetime. With this formalism at hand, we study three concrete GUT models: (i) Minimal SU(5) SUSY GUT, (ii) Missing Partner SU(5) SUSY GUT, and (iii) an orbifold SU(5) SUSY GUT. In each case we derive interesting conclusions about the possible patterns of the supersymmetric spectrum once the present limits on the proton lifetime are imposed, and vice versa, we obtain the predictions for the proton lifetime for specific viable choices of the SUSY spectrum.
Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction
Authors: Wang Si , Min Zheying , Ji Qianzhao , Geng Lingling , Su Yao , Liu Zunpeng , Hu Huifang , Wang Lixia , Zhang Weiqi , Suzuiki Keiichiro , Huang Yu , Zhang Puyao , Tang Tie-Shan , Qu Jing , Yu Yang , Liu Guang-Hui , Qiao Jie
Published: April 2019

Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic gene-corrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and NSCs) in the absence or presence of ultraviolet (UV) and replicative stresses, revealing that defects in DNA repair account for CS pathologies. Moreover, we generate autologous GC-MSCs free of pathogenic mutation under a cGMP (Current Good Manufacturing Practice)-compliant condition, which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS. Collectively, our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.
Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials
Authors: Coley Nicola , Ngandu Tiia , Lehtisalo Jenni , Soininen Hilkka , Vellas Bruno , Richard Edo , Kivipelto Miia , Andrieu Sandrine ,   HATICE, FINGER, and MAPT/DSA groups
Published: April 2019

Introduction

Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable.

Methods

We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2‐year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3‐year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega‐3 supplement or placebo.

Results

Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega‐3 supplement, and lowest for unsupervised computer‐based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms.

Discussion

Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face‐to‐face contacts, and taking into account participant characteristics may increase adherence in future trials.
Inflammatory biomarkers in Alzheimer's disease plasma
Authors: Morgan Angharad R. , Touchard Samuel , Leckey Claire , O'Hagan Caroline , Nevado‐Holgado Alejo J. ,   NIMA Consortium, Barkhof Frederik , Bertram Lars , Blin Olivier , Bos Isabelle , Dobricic Valerija , Engelborghs Sebastiaan , Frisoni Giovanni , Frölich Lutz , Gabel Silvey , Johannsen Peter , Kettunen Petronella , Kłoszewska Iwona , Legido‐Quigley Cristina , Lleó Alberto , Martinez‐Lage Pablo , Mecocci Patrizia , Meersmans Karen , Molinuevo José Luis , Peyratout Gwendoline , Popp Julius , Richardson Jill , Sala Isabel , Scheltens Philip , Streffer Johannes , Soininen Hikka , Tainta‐Cuezva Mikel , Teunissen Charlotte , Tsolaki Magda , Vandenberghe Rik , Visser Pieter Jelle , Vos Stephanie , Wahlund Lars‐Olof , Wallin Anders , Westwood Sarah , Zetterberg Henrik , Lovestone Simon , Morgan B. Paul ,   Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer's Disease
Published: April 2019

Introduction

Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a “Holy Grail” of AD research and intensively sought; however, there are no well‐established plasma markers.

Methods

A hypothesis‐led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.

Results

Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP‐1, eotaxin‐1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP‐1, eotaxin‐1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).

Discussion

Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.
Structure optimization of connection frames based on frequency sensitivity in macro-micro motion platforms
Authors: Zhang Lufan , Li Xueli , Zhang Haihong , Li Haixin , Li Hu , Wu Jun
Published: April 2019

High-performance connection frames are of great significance for ultra-high acceleration and ultra-precision positioning in macro-micro motion platforms. This paper first takes the connection frame as a research object, builds a finite element model (FEM) of the natural frequency of the frame, and then verifies the correctness of this model. The frequency sensitivity method is then used to perturb the structural parameters of the FEM of the connection frame, and the sensitivities of the first-order natural frequency and mass of the corresponding structural parameters are obtained by calculation and analysis. The design variables are also determined. The natural frequency is used as the optimization objective, and the design parameters and mass of the connection frame are constrained. The structural parameters of the connecting frame are obtained through optimization, and the model is built and verified by experiments. The results show that the first-order natural frequency of the connecting frame is effectively improved by the frequency sensitivity method, avoids resonance between the connecting frame and the voice coil motor, and realizes the lightweight design of the connection frame. This research provides a reliable basis for the stable operation and ultra-precision positioning of ultra-high acceleration macro-motion platforms.
The response of glyphosate-resistant and glyphosate-susceptible biotypes of junglerice (Echinochloa colona) to mungbean interference
Authors: Mutti Navneet Kaur , Mahajan Gulshan , Jha Prashant , Chauhan Bhagirath S.
Published: April 2019

Glyphosate-resistant junglerice [Echinochloa colona(L.) Link] is a problematic weed in mungbean [Vigna radiata(L.) R. Wilczek] crops in Australia. Due to limited herbicide options in mungbean, there is an increased interest in developing integrated management strategies for the sustainable control ofE. colona. Pot experiments were conducted in a screenhouse in 2017 and 2018 by growingE. colonaplants (glyphosate-resistant [GR] and glyphosate-susceptible [GS] biotypes) alone (1 plant pot−1) and in competition with 4 and 8 mungbean plants pot−1. Both biotypes were developed from a single population using the clone method. The growth and seed production of both GR and GS biotypes were similar in response to mungbean competition. Averaged over biotypes, there was a reduction in the growth and seed production ofE. colonaas crop plants increased. Compared with the weed plants grown alone, crop interference reducedE. colonaheight by 17% to 19%, tiller numbers by 69% to 82%, total shoot biomass by 85% to 91%, and inflorescence numbers by 74% to 91%. WhenE. colonawas grown with 8 mungbean plants pot−1, leaf weight ratio increased by 42% compared with plants grown alone. Compared with weed plants grown alone, mungbean interference (4 and 8 plants pot−1) reduced weed seed production by 85% to 95%. These reductions were similar for both biotypes (GR and GS), suggesting that there was no fitness penalty associated with resistance. The results of this study suggest that mungbean interference can reduceE. colonagrowth and seed production, but it should not be considered as a stand-alone strategy to manageE. colonaand similar species in mungbean. These results also highlight the need for integrating crop competition with other management strategies to achieve complete and sustainable management of this weed.
Charting the Unknown: Islamic Cartography and Visions of Africa in the ‘Abbasid Era
Authors: Shea Ryan W. , Bell Dianna
Published: April 2019

This article explores cartographic methods during the ninth and tenth century of the ‘Abbasid Caliphate, with a focus on the deformation of Sub-Saharan Africa in world maps produced during the early era. It reviews the preceding influences that factored into how ‘Abbasid cartographers understood and mapped out unknown regions alongside pieces of the folkloric fear that accompanied the idea of al-Wāq-Wāq, that is the uncharted and unknown areas of inland Africa south of the Sahara. By reviewing the methods and techniques of map making alongside information that circulated about al-Wāq-Wāq, this article offers a contribution to knowledge about cartographic practices during the ‘Abbassid era and reviews the work of prominent geographers alongside the deformations in their maps and social assumptions they carried about what and who rested within the interiors of Africa.
Investigation of the factors contributing to Indigenous students’ retention and attrition rates at the University of Adelaide
Authors: Hearn Shane , Benton Madeleine , Funnell Sarah , Marmolejo-Ramos Fernando
Published: April 2019

Abstract
Aboriginal and Torres Strait Islander peoples remain significantly under-represented in higher education systems. There are significant disparities in university completion rates for Aboriginal and Torres Strait Islander students compared with their non-Indigenous counterparts. The poor-retention and high-attrition rates among Aboriginal and Torres Strait Islander students come at significant financial and personal cost for the individual, families, community, universities and governments. Existing evidence in relation to attrition has identified complex and multifaceted reasons including ill health, family and community responsibilities, financial difficulties, lack of social support, academic disadvantage and issues surrounding personal well-being. The current study aimed to add to evidence of the academic, financial, social support and well-being factors affecting Aboriginal and Torres Strait Islander student's decision to continue or withdraw from their university studies. Contrary to expectation, students' decision to withdraw was not related to academic and social factors. It was found that students between 22 and 25 years old strongly agreed they were likely to withdraw from studies. There was a significant association between withdrawal and type of enrolment. This study provided important insights into the factors that contribute to a students' decision to withdraw from their university studies, with implications for future educational interventions.
Lachish Fortifications and State Formation in the Biblical Kingdom of Judah in Light of Radiometric Datings
Authors: Garfinkel Yosef , Hasel Michael G , Klingbeil Martin G , Kang Hoo-Goo , Choi Gwanghyun , Chang Sang-Yeup , Hong Soonhwa , Ganor Saar , Kreimerman Igor , Ramsey Christopher Bronk
Published: April 2019

When and where the process of state formation took place in the biblical kingdom of Judah is heavily debated. Our regional project in the southwestern part of Judah, carried out from 2007 to the present, includes the excavation of three Iron Age sites: Khirbet Qeiyafa, Tel Lachish, and Khirbet al-Ra’i. New cultural horizons and new fortification systems have been uncovered, and these discoveries have been dated by 59 radiometric determinations. The controversial question of when the kingdom was able to build a fortified city at Lachish, its foremost center after Jerusalem, is now resolved thanks to the excavation of a previously unknown city wall, dated by radiocarbon (14C) to the second half of the 10th century BCE.
Casein composition and differential translational efficiency of casein transcripts in donkey's milk
Authors: Cosenza Gianfranco , Mauriello Rosalba , Garro Giuseppina , Auzino Barbara , Iannaccone Marco , Costanzo Angela , Chianese Lina , Pauciullo Alfredo
Published: April 2019

The amount of the four caseins (αs1, αs2, β and κ-CN) in donkey milk was evaluated by Urea-PAGE analysis at pH 8.6, followed by immuno-detection with polyclonal antibodies, coupled to densitometric analysis. The results showed the percentage of each casein in decreasing order: β (54.28) > αs1(35.59) > αs2(7.19) > κ-CN (2.79). The mRNA quantification of donkey casein transcripts, carried out by RT-qPCR, showed that the average percentage of corresponding gene transcripts (CSN2,CSN1S1,CSN1S2I andCSN3) was 70.85, 6.28, 14.23 and 8.65, respectively. The observed translation efficiency, assessed as percentage of single milk casein fraction out of single percentage of transcript, was 0.76, 5.66, 0.50 and 0.32, respectively. The analysis of the sequences flanking the start codon, the codon usage frequencies and the coding sequence length might explain, at least in part, the differential transcriptional and translational rate observed among the casein transcripts.
Review of the status and conservation of tenrecs (Mammalia: Afrotheria: Tenrecidae)
Authors: Stephenson P. J. , Soarimalala Voahangy , Goodman Steven M. , Nicoll Martin E. , Andrianjakarivelo Vonjy , Everson Kathryn M. , Hoffmann Michael , Jenkins Paulina D. , Olson Link E. , Raheriarisena Martin , Rakotondraparany Felix , Rakotondravony Daniel , Randrianjafy Vololomboahangy , Ratsifandrihamanana Nanie , Taylor Andrew
Published: April 2019

The mammal family Tenrecidae (Afrotheria: Afrosoricida) is endemic to Madagascar. Here we present the conservation priorities for the 31 species of tenrec that were assessed or reassessed in 2015–2016 for the IUCN Red List of Threatened Species. Six species (19.4%) were found to be threatened (4 Vulnerable, 2 Endangered) and one species was categorized as Data Deficient. The primary threat to tenrecs is habitat loss, mostly as a result of slash-and-burn agriculture, but some species are also threatened by hunting and incidental capture in fishing traps. In the longer term, climate change is expected to alter tenrec habitats and ranges. However, the lack of data for most tenrecs on population size, ecology and distribution, together with frequent changes in taxonomy (with many cryptic species being discovered based on genetic analyses) and the poorly understood impact of bushmeat hunting on spiny species (Tenrecinae), hinders conservation planning. Priority conservation actions are presented for Madagascar's tenrecs for the first time since 1990 and focus on conserving forest habitat (especially through improved management of protected areas) and filling essential knowledge gaps. Tenrec research, monitoring and conservation should be integrated into broader sustainable development objectives and programmes targeting higher profile species, such as lemurs, if we are to see an improvement in the conservation status of tenrecs in the near future.
Crafting the Financial-Subject: A Qualitative Study of Young Workers’ Experiences in Financialised Pension Investment in Hong Kong
Authors: AU-YEUNG TAT CHOR , CHAN KA KI
Published: April 2019

This article applies the concepts of the financial-subject and micro-foundation of financialisation to young workers’ experiences with Hong Kong’s financialised pension regime. The results of our qualitative analysis show that many respondents doubt and belittle their financial investment for retirement. In response to the compulsory investment required by the government and the fact that their aspirations for security in later life seemed unfulfilled, some young workers undertook ‘uninformed’ investment and ‘age-led’ risk taking. The findings also show that employment precarity translates into investment precarity owing to workers’ unstable incomes and contributions; labour inequalities are reflected in financial inequalities. Arguably, the neoliberal crafting of the young financial-subject, including constructions of financial irresponsibility, irrationality, and illiteracy, is fraught with tensions, turning workers into investors and using finance to satisfy socio-economic needs. It contributes to social policy studies by connecting selfhood and institutions, and calls for questions about the future of financialised pensions.
Mealtimes in Head Start pre-k classrooms: examining language-promoting opportunities in a hybrid space
Authors: BARNES Erica M. , GRIFENHAGEN Jill F. , DICKINSON David K.
Published: April 2019

In this study we sought to identify profiles of talk during Head Start preschool mealtime conversations involving teachers and students. Videos of 44 Head Start classrooms’ lunch interactions were analyzed for the ratio of teacher–child talk and amount of academic vocabulary, and then coded for instances of academic/food, social/personal, and management talk to highlight the degree of hybridity of talk within this unique setting. Cluster analysis revealed four distinct patterns of teacher–child mealtime interactions in 44 Head Start preschool classrooms: classroom discourse, home discourse, hybrid-low, and hybrid-high. Multilevel models further demonstrated a relationship among these clusters of teacher–child interactions and children's end-of-year expressive vocabulary scores controlling for ratio of teacher–child talk and pre-test scores. Children in classrooms displaying a hybrid style of mealtime discourse made the greatest gains on measures of expressive vocabulary in contrast to their peers in classrooms displaying other discourse styles.