bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of Cu2+ and Fe3+ ions on in vitro amyloid formation of biologically-relevant α-synuclein variants
Authors: Lorentzon Emma , Kumar Ranjeet , Horvath Istvan , Wittung-Stafshede Pernilla
Published: March 2020

Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein α-synuclein in brain cells is a hallmark of Parkinson’s disease. α-Synuclein can bind several metal ions in vitro and such interactions may affect the assembly process. Here we used biophysical methods to study the effects of micromolar concentrations of Cu2+ and Fe3+ ions on amyloid formation of selected α-synuclein variants (wild-type and A53T α-synuclein, in normal and N-terminally acetylated forms). As shown previously, Cu2+ speeds up aggregation of normal wild-type α-synuclein, but not the acetylated form. However, Cu2+ has a minimal effect on (the faster) aggregation of normal A53T α-synuclein, despite that Cu2+ binds to this variant. Like Cu2+, Fe3+ speeds up aggregation of non-acetylated wild-type α-synuclein, but with acetylation, Fe3+ instead slows down aggregation. In contrast, for A53T α-synuclein, regardless of acetylation, Fe3+ slows down aggregation with the effect being most dramatic for acetylated A53T α-synuclein. The results presented here suggest a correlation between metal-ion modulation effect and intrinsic aggregation speed of the various α-synuclein variants.
Image-based stroke rat brain atrophy volume and infarct volume computation
Authors: Chan Yung-Kuan , Hong Chun-Fu , Tsai Meng-Hsiun , Chang Ya-Lan , Sun Ping-Hsuan
Published: March 2020

Stroke is one of the leading causes of death as well as results in a massive economic burden for society. Stroke is a cerebrovascular disease mainly divided into two types: ischemic stroke and hemorrhagic stroke, which, respectively, refer to the partial blockage and bleeding inside brain blood vessels. Both stroke types lead to nutrient and oxygen deprivation in the brain, which ultimately cause brain damage or death. This study focuses on ischemic stroke in rats with middle cerebral artery occlusion (MCAO) as experimental subjects, and the volumes of infarct and atrophy are calculated based on the brain slice images of rat brains stained with 2,3,5-triphenyl tetrazolium chloride. In this study, a stroke rat brain infarct and atrophy volumes computation system (SRBIAVC system) is developed to segment the infarcts and atrophies from the rat brain slice images. Based on the segmentation results, the infarct and atrophy volumes of a rat brain can be computed. In this study, 168 images of brain slices cut from 28 rat brains with MCAO are used as the test samples. The experimental results show that the segmentation results obtained by the SRBIAVC system are close to those obtained by experts.
Visfatin as a predictor of obstructive sleep apnea in atrial fibrillation patients
Authors: Szymanska Anna , Platek Anna E. , Sierdzinski Janusz , Szymanski Filip M.
Published: March 2020

Background

Obstructive sleep apnea (OSA) often coexists with atrial fibrillation (AF) and makes the course of AF worse. The negative impact of OSA on AF may be due to atrial stretch, hypoxia, hypertension, obesity, fibrosis, and inflammation. Several mediators are thought to be responsible for this correlation, among them adipokines such as visfatin. This study aimed to assess the association between visfatin concentrations and OSA in patients with AF.

Aims

This study aimed to assess the association between visfatin concentrations and OSA in AF patients.

Methods

In a tertiary Cardiology Department, hospitalized patients previously diagnosed with AF were enrolled in the study. Diagnosis of OSA was made based on a respiratory polygraphy and patients had blood samples taken for assessment of plasma visfatin concentration.

Results

A total of 266 patients with AF (65% men, age 57.6 ± 10.1) were enrolled, and 121 (45%) were diagnosed with OSA. Patients with OSA had higher visfatin concentrations than those without OSA (2.13 ± 0.17 vs. 1.70 ± 0.21 ng/mL; p = 0.04). Patients with mild OSA had visfatin levels equal to 1.77 ± 0.17 ng/mL, moderate OSA 2.38 ± 0.18 ng/mL, and severe OSA 3.55 ± 0.61 ng/mL (p for trend = 0.017). Multivariate regression analysis showed that increased visfatin concentrations were associated with the risk of OSA (odds ratio 1.92; 95% confidence interval 1.09–3.40).

Conclusions

Patients with AF who were diagnosed with OSA had significantly higher plasma visfatin levels which increased according to the severity of OSA. Furthermore, multivariate regression analysis identified visfatin concentration over 1.25 ng/mL, male sex, age over 59.1 years, and permanent AF as the factors showing independent correlation with OSA.
Status of contaminated marine sediments in four Nordic countries: assessments, regulations, and remediation approaches
Authors: Lehoux Alizée P. , Petersen Karina , Leppänen Matti T. , Snowball Ian , Olsen Marianne
Published: March 2020

Purpose

Since the 1960s, pollution of the marine environment has been observed around the world, and a general awareness of the potential environmental hazards from contaminants arose. This general awareness was followed by implementation of environmental regulations at the national and international levels regarding industrial discharges, and forcing the development of management programs to improve the environmental quality. This overview focuses on the status of assessments, regulations, and remediation actions of contaminated marine sediments in four North European countries: Sweden, Norway, Finland, and Denmark.

Results and discussion

We found that the extent of assessment surveys and the implementation of sediment remediation actions vary between the countries, with Norway the most advanced. Norway has initiated national pilot remediation tests, followed by full-scale site remediation by dredging and in situ capping in several projects along the coast. Sweden is following Norway’s example, although with fewer completed projects. In Finland, the tradition of maintenance dredging is still very strong although the main purpose has not been cleanup actions. Accordingly, in Denmark, dredging is primarily used to maintain sailing depths. All four countries have implemented the Water Framework Directive in addition to national regulations that provide the authority for imposing and implementing sediment remediation measures. However, only Norway has implemented a national strategy on remediation of contaminated sediments.

Conclusions

This overview highlights the need for enhanced communication and exchange of experiences between the four Nordic countries of concern with regard to sediment remediation strategy and management.
Sediment load variability in response to climate and land use changes in a Carpathian catchment (Raba River, Poland)
Authors: Szalińska Ewa , Orlińska-Woźniak Paulina , Wilk Paweł
Published: March 2020

Purpose

This study analyzes the variability of sediment loads under variant climate change and land use scenarios in a Carpathian catchment with a dam reservoir. The areas with the highest share of sediment loads are tracked to establish possible indications for future catchment management plans.

Materials and methods

Analyses were performed for the Raba River catchment (Poland, Carpathian Mountains) with use of the Macromodel DNS/SWAT. The RCP 4.5 climate forecast predictions (2021–2050 and 2071–2100), downscaled for the area of Poland, and land use predictions from the DYNA-Clue model for the Carpathian area, were taken into consideration. A total of seven scenarios were created, accounting for precipitation (P1 and P2), temperature (T1 and T2), land use (LU) changes, and combined effects (COMB1 and COMB2).

Results and discussion

The average load delivered to the dam reservoir was estimated as 2.43 Gg y−1, and its seasonal/yearly variability was followed by local meteorological phenomena. Among the tested factors, precipitation change, in terms of total amount and intensity, exerted the most impact on sediment loads causing their increase. Temperature and land use changes resulted in a slight decrease. Combined scenarios implied that changes of the catchment area use, such as increase of forest cover, can noticeably reduce sediment loads delivered into a dam reservoir.

Conclusions

The performed simulations revealed the importance of incorporating variant scenarios for catchment management plans, development of land use mitigation measures (erosion), and operational procedures for the dam reservoir. Particular attention should be paid to warmer winters with heavy rainfalls and temperatures above zero, which together with a lack of plant vegetation result in elevated annual sediment loads reaching the dam reservoir. Further changes must be mitigated by anti-erosion investments.
Fairness criteria for allocating scarce resources
Authors: Singh Bismark
Published: March 2020

We develop an optimization model to provide a fair allocation of multiple resources to multiple users. All resources might not be suitable to all users. We develop a notion of fairness, and then provide a general class of functions achieving it. Next, we develop more restricted notions of fairness—special cases of which exist in literature. Finally, we distinguish between scarce and abundant resources, and show that if a resource is abundant, all users seeking it achieve the maximum possible coverage.
Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection
Authors: Zou Xin , Chen Ke , Zou Jiawei , Han Peiyi , Hao Jie , Han Zeguang
Published: March 2020

It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.
A Combined Proteomics and Bioinformatics Approach Reveals Novel Signaling Pathways and Molecular Targets After Intracerebral Hemorrhage
Authors: Dasari Rajaneekar , Zhi Wenbo , Bonsack Frederick , Sukumari-Ramesh Sangeetha
Published: March 2020

Intracerebral hemorrhage (ICH) is a non-traumatic cerebrovascular disorder with very high morbidity and mortality and regarded as one of the deadliest stroke subtypes. Notably, there is no effective treatment for ICH. Despite an overall increase in preclinical studies, the pathophysiology of ICH is complex and remains enigmatic. To this end, ICH was induced in male CD-1 mice and the ipsilateral brain tissue was characterized in an unbiased manner using a combination of proteomics and bioinformatics approaches. A total of 4833 proteins were revealed by quantitative proteomic analysis. Of those, 207 proteins exhibited significantly altered expression after ICH in comparison to sham. It was found that 46 proteins were significantly upregulated and 161 proteins were significantly downregulated after ICH compared to sham. The quantitative proteomics approach combined with bioinformatics revealed several novel molecular targets (cyclin-dependent-like kinase 5, E3 ubiquitin-protein ligase, protein phosphatase 2A-alpha, protein phosphatase 2A-beta, serine/threonine-protein kinase PAK1, alpha-actinin-4, calpain-8, axin-1, NCK1, and septin-4), and related signaling pathways, which could play roles in secondary brain injury and long-term neurobehavioral outcomes after ICH warranting further investigation.
Hominid sexual nature
Authors: Mogielnicki Christopher , Pearl Katherine
Published: March 2020

The aim of the paper is to identify psychosomatic evolutionary adaptations of hominids, which direct them at maximizing their reproductive success, and on the basis of which their various social structures are built. Selected features of the hominid last common ancestor were extracted; by reducing the influence of the social structure, they were defined as the hominid “sexual nature”; these considerations were supported by the analysis of sexual jealousy as a function of socio-environmental conditions. The “sexuality core” of a hominid female was defined as “selective polyandry”—the female selects the best males among those available; and of a hominid male as “tolerant promiscuity”—the male strives for multi-male and multi-female copulations with sexually attractive females. The extracted “sexuality cores” condemn hominids to a patriarchal social structure and thus to sexual coercion and jealousy. The source of male sexual jealousy is limited access to females. Hominid female jealousy of the male results mainly from the need for protection and support. Hominids’ social structures are determined by females’ sexual selectivity or opportunism and by their continuous or periodic proceptivity and estrus signaling. Evolutionary functions developed by women: out-estrus sexuality, copulation calls, multiple orgasms, allow them to obtain the best possible spermatozoid. The institution of marriage blocks the influence of sexual selection in the species Homo sapiens.
Obstipation and diarrhoea in palliative care—a pharmacist’s view
Authors: Aretin Marie-Bernadette
Published: March 2020

This article is a brief overview of drugs, which are of use in the treatment of constipation and diarrhoea in palliative care. Whereas most of the drugs mentioned are widely used and known, the aspect of gastrointestinal symptoms as side effect of pharmacological treatments is often underestimated. Therefore, the article highlights the approach of deprescribing, as a tool to reduce both, pill burden and symptoms.
IoT-commerce - opportunities for customers through an affordance lens
Authors: Bayer Sarah , Gimpel Henner , Rau Daniel
Published: March 2020

Retail commerce is influenced by digital technologies at large scale. After electronic commerce and its evolution into mobile commerce, we now see that the Internet of Things (IoT), one of the most disruptive developments in recent times, is about to radically transform retail commerce from need recognition to post-purchase engagement and service. Extant literature mainly investigates technical features of IoT, missing out on a customer-centric perspective. Theoretically founded in Activity and Affordance Theories, this paper conceptualizes IoT-commerce, identifies opportunities for customers, and links them to the customer buying process. Based on an extensive literature review, twelve affordances are derived and evaluated with a sample of real-world IoT devices. All affordances offered by electronic and mobile commerce are still valid for IoT-commerce but extended by three affordances unique to IoT-commerce: context-aware services, natural interactions, and automated customer processes. Affecting all steps of the customer buying process, IoT-commerce is worth to be understood by researchers, customers, and companies.
Numerical and ANFIS modeling of flow over an ogee-crested spillway
Authors: Yildiz Ali , Yarar Alpaslan , Kumcu S. Yurdagul , Marti Ali Ihsan
Published: March 2020

The main aim of this study was to investigate the flow over an ogee spillway experimentally and simulating by both ANFIS and numerical model. An experimental study was conducted in order to obtain discharges and flow depths over an ogee spillway. Discharges and flow depths of flow in physical model were measured for 16 different total heads. A computational fluid dynamics program, which uses the Reynolds averaged Navier–Stokes equations to solve fluid problems, was used to simulate the flow over ogee spillway. As artificial intelligence methods have also been used with increasing the computer technology in all engineering problems, it was also used in this study in estimating the flow over the spillway. Finally, the flow parameters observed by physical study, numerical simulation and ANFIS model were compared with each other. Nondimensional discharge and flow depth curves are used to compare the results. Numerical and ANFIS models provide a cost-efficient simulating flow over spillways. The results show that there is reasonably good agreement between the physical, numerical and ANFIS models. Numerical solution methods and ANFIS models are also useful tools to design and analyze flow over an ogee spillway.
Parental Migration and Early Childhood Development in Rural China
Authors: Yue Ai , Bai Yu , Shi Yaojiang , Luo Renfu , Rozelle Scott , Medina Alexis , Sylvia Sean
Published: March 2020

Nearly one-quarter of all children under age 2 in China are left behind in the countryside as parents migrate to urban areas for work. We use a four-wave longitudinal survey following young children from 6 to 30 months of age to provide first evidence on the effects of parental migration on development, health, and nutritional outcomes in the critical first stages of life. We find that maternal migration has a negative effect on cognitive development: migration before children reach 12 months of age reduces cognitive development by 0.3 standard deviations at age 2. Possible mechanisms include reduced dietary diversity and engagement in stimulating activities, both known to be causally associated with skill development in early life. We find no effects on other dimensions of physical and social-emotional health.
Natural Hazards, Disasters, and Demographic Change: The Case of Severe Tornadoes in the United States, 1980–2010
Authors: Raker Ethan J.
Published: March 2020

Natural hazards and disasters distress populations and inflict damage on the built environment, but existing studies yielded mixed results regarding their lasting demographic implications. I leverage variation across three decades of block group exposure to an exogenous and acute natural hazard—severe tornadoes—to focus conceptually on social vulnerability and to empirically assess local net demographic change. Using matching techniques and a difference-in-difference estimator, I find that severe tornadoes result in no net change in local population size but lead to compositional changes, whereby affected neighborhoods become more White and socioeconomically advantaged. Moderation models show that the effects are exacerbated for wealthier communities and that a federal disaster declaration does not mitigate the effects. I interpret the empirical findings as evidence of a displacement process by which economically disadvantaged residents are forcibly mobile, and economically advantaged and White locals rebuild rather than relocate. To make sense of demographic change after natural hazards, I advance an unequal replacement of social vulnerability framework that considers hazard attributes, geographic scale, and impacted local context. I conclude that the natural environment is consequential for the sociospatial organization of communities and that a disaster declaration has little impact on mitigating this driver of neighborhood inequality.
A Computational Approach for Modeling the Allele Frequency Spectrum of Populations with Arbitrarily Varying Size
Authors: Chen Hua
Published: March 2020

The allele frequency spectrum (AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://chenlab.big.ac.cn/software/.
An emerging trend in English education in Korea: ‘Maternal English education’ (eommapyo yeongeo)
Authors: Seo Youngjoo
Published: March 2020

Korean parents are strongly committed to investing time, effort, and money into improving their children's English competence in order to maximize their human capital in the era of globalization, a phenomenon often referred to as ‘English fever’ (Park, 2009). However, because of the Korean socio-economic structure, there is considerable disparity among families in the financial investment they can afford. Therefore, in the educational privileges and especially English learning support that Korean children receive is an inequity often overlooked by the majority of Koreans. One response to this issue is the newly emerging movement among Korean mothers called ‘maternal English education’ (eommapyo yeongeo), which has become a widely used term throughout the country.
The Word is the Knife: Janus-Faced Communication in Sartre’s No Exit and Rose’s Twelve Angry Men
Authors: Church Scott Haden , Jones Jesse King
Published: March 2020

In this article the authors offer an analysis of Jean-Paul Sartre’s 1946 play Huis Clos (No Exit) and Reginald Rose’s 1954 play Twelve Angry Men, with particular attention paid to exploring the insights from each theatrical text about communication. The process of communication may be ambivalent or Janus-faced, and one of the objectives of this analysis is to consider communication in terms of its duality and incisive power. In doing so, the aim is to explore its antithetical tensions by amplifying the mythological, deliberative and philosophical dimensions of communication praxis. In particular, the archetype of the knife provides a useful metaphor for understanding the potentials and pitfalls of communication in human interaction. Scott Haden Church is an Assistant Professor in the School of Communications at Brigham Young University. He has recently published in Critical Studies in Media Communication. Jesse King Jones is in the Masters Programme of the School of Communications at Brigham Young University.
Estimates of healthcare utilisation and deaths from waterborne pathogen exposure in Ontario, Canada
Authors: Greco Susan Lavinia , Drudge Christopher , Fernandes Reisha , Kim JinHee , Copes Ray
Published: March 2020

Burden of disease analyses can quantify the relative impact of different exposures on population health outcomes. Gastroenteritis where the causative pathogen was not determined and respiratory illness resulting from exposure to opportunistic pathogens transmitted by water aerosols have not always been considered in waterborne burden of disease estimates. We estimated the disease burden attributable to nine enteric pathogens, unspecified pathogens leading to gastroenteritis, and three opportunistic pathogens leading primarily to respiratory illness, in Ontario, Canada (population ~14 million). Employing a burden of disease framework, we attributed a fraction of annual (year 2016) emergency department (ED) visits, hospitalisations and deaths to waterborne transmission. Attributable fractions were developed from the literature and clinical input, and unattributed disease counts were obtained using administrative data. Our Monte Carlo simulation reflected uncertainty in the inputs. The estimated mean annual attributable rates for waterborne diseases were (per 100 000 population): 69 ED visits, 12 hospitalisations and 0.52 deaths. The corresponding 5th–95th percentile estimates were (per 100 000 population): 13–158 ED visits, 5–22 hospitalisations and 0.29–0.83 deaths. The burden of disease due to unspecified pathogens dominated these rates: 99% for ED visits, 63% for hospitalisations and 40% for deaths. However, when a causative pathogen was specified, the majority of hospitalisations (83%) and deaths (97%) resulted from exposure to the opportunistic pathogens Legionella spp., non-tuberculous mycobacteria and Pseudomonas spp. The waterborne disease burden in Ontario indicates the importance of gastroenteritis not traced back to a particular pathogen and of opportunistic pathogens transmitted primarily through contact with water aerosols.
GLOBAL VS. GROUP-SPECIFIC BUSINESS CYCLES: THE IMPORTANCE OF DEFINING THE GROUPS
Authors: Berger Tino , Wortmann Marcus
Published: March 2020

The literature on international business cycles has employed dynamic factor models (DFMs) to disentangle global from group-specific and national factors in countries’ macroeconomic aggregates. Therefore, the countries have simply been classified ex ante as belonging to the same region or the same level of development. This paper estimates a DFM for a sample of 106 countries and three variables (output, consumption, investment) over the period 1960–2014, in which the countries are classified according to the outcome of a cluster analysis. By comparing the results with those obtained by the previous grouping approaches, we show substantial deviations in the importance of global and group-specific factors. Remarkably, when the groups are defined properly, the “global business cycle” accounts for only a very small fraction of macroeconomic fluctuations, most evidently in the industrialized world. The group-specific factors, on the other hand, play a much greater role for national business cycles than previously thought—also in the pre-globalization period.
The Duality of Reforestation Impacts on Surface and Air Temperature
Authors: Novick Kimberly A. , Katul Gabriel G.
Published: March 2020

Evidence is mounting that temperate‐zone reforestation cools surface temperature (Tsurf), mitigating deleterious effects of climate warming. While Tsurf drives many biophysical processes, air temperature (Ta) is an equally important target for climate mitigation and adaptation. Whether reductions in Tsurf translate to reductions in Ta remains complex, fraught by several nonlinear and intertwined processes. In particular, forest canopy structure strongly affects near‐surface temperature gradients, complicating cross‐site comparison. Here the influence of reforestation on Ta is assessed by targeting temperature metrics that are less sensitive to local canopy effects. Specifically, we consider the aerodynamic temperature (Taero), estimated using a novel procedure that does not rely on the assumptions of Monin‐Obukhov similarity theory, as well as the extrapolated temperature into the surface layer (Textrap). The approach is tested with flux tower data from a grass field, pine plantation, and mature hardwood stand co‐located in the Duke Forest (North Carolina, USA). During growing season daytime periods, Tsurf is 4–6 °C cooler, and Taero and near‐surface Textrap are 2–3 °C cooler, in the forests relative to the grassland. During the dormant season, daytime differences are smaller but still substantial. At night, differences in Taero are small, and near‐surface Textrap is warmer over forests than grasslands during the growing season (by 0.5 to 1 °C). Finally, the influence of land cover on Textrap at the interface between the surface and mixed layer is small. Overall, reforestation appears to provide a meaningful opportunity for adaption to warmer daytime Ta in the southeastern United States, especially during the growing season.
A pilot window-of-opportunity study of preoperative fluvastatin in localized prostate cancer
Authors: Longo Joseph , Hamilton Robert J. , Masoomian Mehdi , Khurram Najia , Branchard Emily , Mullen Peter J. , Elbaz Mohamad , Hersey Karen , Chadwick Dianne , Ghai Sangeet , Andrews David W. , Chen Eric X. , van der Kwast Theodorus H. , Fleshner Neil E. , Penn Linda Z.
Published: March 2020

Background

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the effects of neoadjuvant fluvastatin treatment on markers of cell proliferation and apoptosis in men with localized PCa.

Methods

Thirty-three men were treated daily with 80 mg fluvastatin for 4–12 weeks in a single-arm window-of-opportunity study between diagnosis of localized PCa and radical prostatectomy (RP) (ClinicalTrials.gov: NCT01992042). Percent Ki67 and cleaved Caspase-3 (CC3)-positive cells in tumor tissues were evaluated in 23 patients by immunohistochemistry before and after treatment. Serum and intraprostatic fluvastatin concentrations were quantified by liquid chromatography-mass spectrometry.

Results

Baseline characteristics included a median prostate-specific antigen (PSA) level of 6.48 ng/mL (IQR: 4.21–10.33). The median duration of fluvastatin treatment was 49 days (range: 27–102). Median serum low-density lipoprotein levels decreased by 35% after treatment, indicating patient compliance. Median PSA decreased by 12%, but this was not statistically significant in our small cohort. The mean fluvastatin concentration measured in the serum was 0.2 μM (range: 0.0–1.1 μM), and in prostatic tissue was 8.5 nM (range: 0.0–77.0 nM). At these concentrations, fluvastatin induced PCa cell death in vitro in a dose- and time-dependent manner. In patients, fluvastatin treatment did not significantly alter intratumoral Ki67 positivity; however, a median 2.7-fold increase in CC3 positivity (95% CI: 1.9–5.0, p = 0.007) was observed in post-fluvastatin RP tissues compared with matched pre-treatment biopsy controls. In a subset analysis, this increase in CC3 was more pronounced in men on fluvastatin for >50 days.

Conclusions

Fluvastatin prior to RP achieves measurable drug concentrations in prostatic tissue and is associated with promising effects on tumor cell apoptosis. These data warrant further investigation into the anti-neoplastic effects of statins in prostate tissue.
FKBP5 haplotypes and PTSD modulate the resting-state brain activity in Han Chinese adults who lost their only child
Authors: Qi Rongfeng , Luo Yifeng , Zhang Li , Weng Yifei , Surento Wesley , Jahanshad Neda , Xu Qiang , Yin Yan , Li Lingjiang , Cao Zhihong , Thompson Paul M. , Lu Guang Ming
Published: March 2020

The stress-related gene FKBP5 has been related to dysregulated glucocorticoid receptor (GR) signaling, showing increased GR sensitivity in trauma-exposed subjects with post-traumatic stress disorder (PTSD) but not in those without PTSD. However, the neural mechanism underlying the effects of FKBP5 remains poorly understood. Two hundred and thirty-seven Han Chinese adults who had lost their only child were included. Four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. All 179 participants were successfully divided into three FKBP5 diplotype subgroups according to two major FKBP5 H1 and H2 yin yang haplotypes. Brain average spectral power was compared using a two-way (PTSD diagnosis and FKBP5 diplotypes) analysis of covariance within four separate frequency bands (slow-5, slow-4, slow-3, and slow-2). Adults with PTSD showed lower spectral power in bilateral parietal lobules in slow-4 and in left inferior frontal gyrus (IFG) in slow-5. There was significant FKBP5 diplotype main effect in anterior cingulate cortex (ACC) in slow-4 (H1/H1 higher than other two subgroups), and in precentral/postcentral gyri and middle cingulate cortex (MCC) in slow-3 (H2/H2 higher than other two subgroups). Also, there was a significant diagnosis × FKBP5 diplotype interaction effect in right parietal lobule in slow-3. These findings suggest that adults with PTSD have lower low-frequency power in executive control network regions. Lower power in ACC and greater power in the motor/sensory areas in FKBP5 high-risk diplotype group suggest a disturbance of emotional processing and hypervigilance/sensitization to threatening stimuli. The interaction effect of diagnosis × FKBP5 in parietal lobule may contribute to PTSD development.
Tunable phonon-induced steady-state coherence in a double-quantum-dot charge qubit
Authors: Purkayastha Archak , Guarnieri Giacomo , Mitchison Mark T. , Filip Radim , Goold John
Published: March 2020

Charge qubits can be created and manipulated in solid-state double-quantum-dot (DQD) platforms. Typically, these systems are strongly affected by quantum noise stemming from coupling to substrate phonons. This is usually assumed to lead to decoherence towards steady states that are diagonal in the energy eigenbasis. In this article, we show, to the contrary, that due to the presence of phonons the equilibrium steady state of the DQD charge qubit spontaneously exhibits coherence in the energy eigenbasis with high purity. The magnitude and phase of the coherence can be controlled by tuning the Hamiltonian parameters of the qubit. The coherence is also robust to the presence of fermionic leads. In addition, we show that this steady-state coherence can be used to drive an auxiliary cavity mode coupled to the DQD.
Approximate quantum Fourier transform with O(n log(n)) T gates
Authors: Nam Yunseong , Su Yuan , Maslov Dmitri
Published: March 2020

The ability to implement the Quantum Fourier Transform (QFT) efficiently on a quantum computer facilitates the advantages offered by a variety of fundamental quantum algorithms, such as those for integer factoring, computing discrete logarithm over Abelian groups, solving systems of linear equations, and phase estimation, to name a few. The standard fault-tolerant implementation of an n-qubit unitary QFT approximates the desired transformation by removing small-angle controlled rotations and synthesizing the remaining ones into Clifford+T gates, incurring the T-count complexity of $$O(n\,{\mathrm{log}}^{2}\,(n))$$

O

(

n

log

2

(

n

)

)

. In this paper, we show how to obtain approximate QFT with the T-count of $$O(n\,{\mathrm{log}}\,(n))$$

O

(

n

log

(

n

)

)

. For brevity, the above figures omit the dependence on the approximation error ε, assuming the error is fixed. Our approach relies on quantum circuits with measurements and feedforward, and on reusing a special quantum state that induces the phase gradient transformation. We report asymptotic analysis as well as concrete circuits, demonstrating significant advantages in both theory and practice.
Nonlocal Coulomb interaction and spin-freezing crossover as a route to valence-skipping charge order
Authors: Ryee Siheon , Sémon Patrick , Han Myung Joon , Choi Sangkook
Published: March 2020

Multiorbital systems away from global half-filling host intriguing physical properties promoted by Hund’s coupling. Despite increasing awareness of this regime dubbed Hund’s metal, effect of nonlocal interaction is still elusive. Here we study a three-orbital model with 1/3 filling (two electrons per site) including the intersite Coulomb interaction (V). Using the GW plus extended dynamical mean-field theory, the valence-skipping charge order transition is shown to be driven by V. Most interestingly, the instability to this transition is significantly enhanced in the spin-freezing crossover regime, thereby lowering the critical V to the formation of charge order. This behavior is found to be closely related to the population profile of the atomic multiplet states in the spin-freezing regime. In this regime, maximum spin states are dominant in each total charge subspace with substantial amount of one- and three-electron occupations, which leads to almost equal population of one- and the maximum spin three-electron state. Our finding unveils another feature of the Hund’s metal and has potential implications for the broad range of multiorbital systems as well as the recently discovered charge order in iron pnictides.
Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study
Authors: Pleguezuelos Olga , James Emma , Fernandez Ana , Lopes Victor , Rosas Luz Angela , Cervantes-Medina Adriana , Cleath Jason , Edwards Kristina , Neitzey Dana , Gu Wenjuan , Hunsberger Sally , Taubenberger Jeffery K. , Stoloff Gregory , Memoli Matthew J.
Published: March 2020

FLU-v, developed by PepTcell (SEEK), is a peptide vaccine aiming to provide a broadly protective cellular immune response against influenza A and B. A randomized, double-blind, placebo-controlled, single-center, phase IIb efficacy and safety trial was conducted. One hundred and fifty-three healthy individuals 18–55 years of age were randomized to receive one or two doses of adjuvanted FLU-v or adjuvanted placebo subcutaneously on days −43 and −22, prior to intranasal challenge on day 0 with the A/California/04/2009/H1N1 human influenza A challenge virus. The primary objective of the study was to identify a reduction in mild to moderate influenza disease (MMID) defined as the presence of viral shedding and clinical influenza symptoms. Single-dose adjuvanted FLU-v recipients (n = 40) were significantly less likely to develop MMID after challenge vs placebo (n = 42) (32.5% vs 54.8%p = 0.035). FLU-v should continue to be evaluated and cellular immunity explored further as a possible important correlate of protection against influenza.
Benefits of organic manure combined with biochar amendments to cotton root growth and yield under continuous cropping systems in Xinjiang, China
Authors: Zhang Zhiyong , Dong Xiuxiu , Wang Shaoming , Pu Xiaozhen
Published: March 2020

Organic manure and biochar amendments have been used in agriculture to improve soil fertility and enhance crop productivity. Plant roots play an important role in the functionality of individual plants, and although the addition of organic manure and biochar reportedly affect roots, it remains unclear how root morphology and physiology respond. We conducted a field experiment to test the hypothesis that organic manure combined with biochar amendment could also enhance the productivity of continuous cropping systems in Xinjiang cotton plantations. Different levels of organic manure and biochar were applied. Organic manure and biochar significantly affected root morphology and physiology by improving soil nutrients. In the absence of biochar, organic manure amendment increased Root TTC reducing capacity, glutamine synthetase and nitrate reductase activity. Furthermore, morphological and physiological parameters peaked with 6% organic manure combined with 1% biochar. A significant increase in root physiology was recognized with an increase in soil nutrient content at the bud stage and a negative relationship between root physiology and soil total K content at the harvesting stage. Thus, our results indicate that organic manure combined with biochar positively influenced cotton roots, and therefore should be used to improve root health in continuous cropping systems.
The hazardous 2017–2019 surge and river damming by Shispare Glacier, Karakoram
Authors: Bhambri Rakesh , Watson C. Scott , Hewitt Kenneth , Haritashya Umesh K. , Kargel Jeffrey S. , Pratap Shahi Arjun , Chand Pritam , Kumar Amit , Verma Akshaya , Govil Himanshu
Published: March 2020

In 2017–2019 a surge of Shispare Glacier, a former tributary of the once larger Hasanabad Glacier (Hunza region), dammed the proglacial river of Muchuhar Glacier, which formed an ice-dammed lake and generated a small Glacial Lake Outburst Flood (GLOF). Surge movement produced the highest recorded Karakoram glacier surface flow rate using feature tracking (~18 ± 0.5 m d−1) and resulted in a glacier frontal advance of 1495 ± 47 m. The surge speed was less than reports of earlier Hasanabad advances during 1892/93 (9.3 km) and 1903 (9.7 km). Surges also occurred in 1973 and 2000–2001. Recent surges and lake evolution are examined using feature tracking in satellite images (1990–2019), DEM differencing (1973–2019), and thermal satellite data (2000–2019). The recent active phase of Shispare surge began in April 2018, showed two surface flow maxima in June 2018 and May 2019, and terminated following a GLOF on 22–23 June 2019. The surge likely had hydrological controls influenced in winter by compromised subglacial flow and low meltwater production. It terminated during summer probably because increased meltwater restored efficient channelized flow. We also identify considerable heterogeneity of movement, including spring/summer accelerations.
Association between cystatin C gene polymorphism and the prevalence of white matter lesion in elderly healthy subjects
Authors: Maniwa Kyohei , Yano Shozo , Sheikh Abdullah Md. , Onoda Keiichi , Mitaki Shingo , Isomura Minoru , Mishima Seiji , Yamaguchi Shuhei , Nabika Toru , Nagai Atsushi
Published: March 2020

Cystatin C (CST3) is a cysteine protease inhibitor abundant in the central nervous system, and demonstrated to have roles in several pathophysiological processes including vascular remodeling and inflammation. Previously, we showed a relation of CST3 gene polymorphisms with deep and subcortical white matter hyperintensity (DSWMH) in a small case-control study. In this study, we aimed to investigate the relation in a larger cross-sectional study. Participants of a brain health examination program were recruited (n = 1795) in the study, who underwent routine blood tests and cognitive function tests. Cerebral white matter changes were analyzed by MRI. Additionally, 7 single nucleotide polymorphisms (SNPs) (−82G/C, −78T/G, −5G/A, +4A/C, +87C/T, +148G/A and +213G/A) in the promoter and coding regions of CST3 gene were examined. Among them, carriers of the minor allele haplotype −82C/+4C/+148A were significantly associated with decreased CST3 concentration in the plasma. Unadjusted analysis did not show significant relation between carriers of the minor allele haplotype and periventricular hyperintensity (PVH), but DSWMH was marginally (p < 0.054) increased in this group. After adjusting the effects of other variables like age and kidney function, logistic regression analysis revealed that carriers of the minor allele haplotype were at a significantly increased risk of developing both PVH and DSWMH. Thus, our results suggest that carriers of the minor allele haplotype −82C/+4C/+148A of CST3 gene could be at an increased risk to develop cerebral white matter disturbance.
Local inhomogeneous state in multiferroic SmCrO3
Authors: Oliveira G. N. P. , Teixeira R. C. , Moreira R. P. , Correia J. G. , Araújo J. P. , Lopes A. M. L.
Published: March 2020

Rare-earth orthochromites with distorted perovskite structure (e.g. RCrO3, R = Sm, Gd) have been under strong debate with respect to the origin of their ferroelectric order. Of particular interest is the question of whether such orthochromites are, in fact, magnetically driven improper ferroelectrics, as many rare-earth manganites or orthoferrites. Here we show, by studying at the atomic scale the rare-earth SmCrO3 system that a distortion of the Sm local environment emerges within the paramagnetic phase, near room temperature. Our Electric Field Gradient measurements combined with first-principles calculations show that the emergent phase cannot be simply ascribed to the Pna21 structure as reported for GdCrO3 or SmCrO3. Instead a local inhomogeneous state, where regular non-polar and polar distorted environments coexist, develops at low temperatures.
Bacterioplankton reveal years-long retention of Atlantic deep-ocean water by the Tropic Seamount
Authors: Giljan Greta , Kamennaya Nina A. , Otto Andreas , Becher Dörte , Ellrott Andreas , Meyer Volker , Murton Bramley J. , Fuchs Bernhard M. , Amann Rudolf I. , Zubkov Mikhail V.
Published: March 2020

Seamounts, often rising hundreds of metres above surrounding seafloor, obstruct the flow of deep-ocean water. While the retention of deep-water by seamounts is predicted from ocean circulation models, its empirical validation has been hampered by large scale and slow rate of the interaction. To overcome these limitations we use the growth of planktonic bacteria to assess the retention time of deep-ocean water by a seamount. The selected Tropic Seamount in the North-Eastern Atlantic is representative for the majority of isolated seamounts, which do not affect the surface ocean waters. We prove deep-water is retained by the seamount by measuring 2.4× higher bacterial concentrations in the seamount-associated or ‘sheath’-water than in deep-ocean water unaffected by seamounts. Genomic analyses of flow-sorted, dominant sheath-water bacteria confirm their planktonic origin, whilst proteomic analyses of the sheath-water bacteria, isotopically labelled in situ, indicate their slow growth. According to our radiotracer experiments, it takes the sheath-water bacterioplankton 1.5 years to double their concentration. Therefore, the seamount should retain the deep-ocean water for 1.8 years for the deep-ocean bacterioplankton to grow to the 2.4× higher concentration in the sheath-water. We propose that turbulent mixing of the seamount sheath-water stimulates bacterioplankton growth by increasing cell encounter rate with ambient dissolved organic molecules.
Cell-bound IgE and plasma IgE as a combined clinical diagnostic indicator for allergic patients
Authors: Qiu Chuanghua , Zhong Lihong , Huang Chunxiu , Long Jia , Ye Xuejun , Wu Jingbo , Dai Wenjie , Lv Wei , Xie Chongwei , Zhang Junfang
Published: March 2020

Allergic responses are mainly caused by IgE, which is often located on the cell surface. The current diagnostic method detects both allergen-specific IgE and total IgE levels, but a number of allergic patients have a normal serum IgE level, which is a poor clinical correlate for allergy. Here, we developed a simple method to detect the level of cell-bound IgE by dissociating it from blood cells with lactic acid. Dissociated cell-bound IgE and plasma IgE levels were detected using the same ELISA kit at the same time. We established two clinical cohorts: an allergic patient group and a healthy participant group. In general, cell-bound IgE correlated well with plasma IgE; however, some patients exhibited high cell-bound IgE levels but low plasma IgE levels. We recommended 350 ng/mL peripheral blood total IgE (cell-bound IgE + plasma IgE) as the cut-off value for allergy diagnosis. Using this indicator, 90.32% of our allergic patients were correctly diagnosed. The peripheral blood total IgE level is a promising clinical diagnostic indicator in allergic patients and will provide more guidance for allergy diagnosis and therapeutic evaluation.