bluuebunny/crossref_metadata_2025 huggingface dataset:
Rietveld‐based quantitative phase analysis of B‐type starch crystals subjected to ultrasound and hydrolysis processes
Authors: Pinto Camila Costa , Campelo Pedro Henrique , Michielon de Souza Sérgio
Published: June 2020

The functional properties of starch could be improved with structural tuning through a number of processing techniques, intensely explored in the past few years by several industries such as food, pharmacology, paper and cosmetics. The current work proposes a model for determining the crystallinity of B‐type Starch based only on X‐ray diffraction (XRD) and Rietveld refinement method (RM). A sample of food grade potato starch (described as B‐type Starch) was submitted to structural modifications using high energy ultrasound followed by acid hydrolysis. The sample was thereby studied by powder XRD measurements and later refined using RM. Apparent crystallite sizes were found to be stable after ultrasound processing, while the crystallinity increased 10% after hydrolysis. Hence, this procedure provides an easy and alternative approach for estimating the crystallinity and the crystallite sizes of the starch sample.
New Medications Are Needed for Children With Juvenile Idiopathic Arthritis
Authors: Brunner Hermine I. , Schanberg Laura E. , Kimura Yukiko , Dennos Anne , Co Dominic O. , Colbert Robert A. , Fuhlbrigge Robert C. , Goldmuntz Ellen , Kingsbury Daniel J. , Patty‐Resk Cathy , Mintz Sandra , Onel Karen , Rider Lisa G. , Schneider Rayfel , Watts Allen , von Scheven Emily , Lovell Daniel J. , Beukelman Timothy ,   the PRCSG Advisory Council and the CARRA Registry Investigators
Published: June 2020

Objective

To document the need for additional Food and Drug Administration (FDA)–approved medications for the treatment of juvenile idiopathic arthritis (JIA).

Methods

The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0–10 scale, where 0 = inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well‐being ≥3 (on a 0–10 scale, where 0 = very well), despite sequential use of ≥2 biologic disease‐modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category.

Results

At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs.

Conclusion

Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.
Co‐Catalyst‐Free Chemical Fixation of CO2 into Cyclic Carbonates by using Metal‐Organic Frameworks as Efficient Heterogeneous Catalysts
Authors: Singh Dhankhar Sandeep , Ugale Bharat , Nagaraja C. M.
Published: June 2020

The concentration of carbon dioxide (CO2) in the atmosphere is increasing at an alarming rate resulting in undesirable environmental issues. To mitigate this growing concentration of CO2, selective carbon capture and storage/sequestration (CCS) are being investigated intensively. However, CCS technology is considered as an expensive and energy‐intensive process. In this context, selective carbon capture and utilization (CCU) as a C1 feedstock to synthesize value‐added chemicals and fuels is a promising step towards lowering the concentration of the atmospheric CO2 and for the production of high‐value chemicals. Towards this direction, several strategies have been developed to convert CO2, a Greenhouse gas (GHG) into useful chemicals by forming C−N, C−O, C−C, and C−H bonds. Among the various CO2 functionalization processes known, the cycloaddition of CO2 to epoxides has gained considerable interest owing to its 100% atom‐economic nature producing cyclic carbonates or polycarbonates in high yield and selectivity. Among the various classes of catalysts studied for cycloaddition of CO2 to cyclic carbonates, porous metal‐organic frameworks (MOFs) have gained a special interest due to their modular nature facilitating the introduction of a high density of Lewis acidic (LA) and CO2‐philic Lewis basic (LB) functionalities. However, most of the MOF‐based catalysts reported for cycloaddition of CO2 to respective cyclic carbonates in high yields require additional co‐catalyst, say tetra‐n‐butylammonium bromide (TBAB). On the contrary, the co‐catalyst‐free conversion of CO2 using rationally designed MOFs composed of both LA and LB sites is relatively less studied. In this review, we provide a comprehensive account of the research progress in the design of MOF based catalysts for environment‐friendly, co‐catalyst‐free fixation of CO2 into cyclic carbonates.
On discrete‐time LPV control using delayed Lyapunov functions
Authors: Peixoto Márcia L. C. , Lacerda Márcio J. , Palhares Reinaldo M.
Published: June 2020

This paper presents new stabilization conditions for discrete‐time linear parameter‐varying systems in the form of linear matrix inequalities. The use of Lyapunov functions with dependence on delayed scheduling parameters is introduced. In addition, a lifted condition based on a Lyapunov function with dependence on delayed scheduling parameters, constructed in terms of an augmented state vector that takes into account a generic number of higher‐order shifted states, is presented. Numerical examples are provided to illustrate the advantages of the proposed approach when compared to other techniques from the literature.
Maternal, pregnancy, and neonatal outcomes for women with Turner syndrome
Authors: Ramage Kaylee , Grabowska Kirsten , Silversides Candice , Quan Hude , Metcalfe Amy
Published: June 2020

Background

Turner syndrome (TS) occurs in approximately 1 in 2500 live female births and is caused by the partial or complete loss of one of the X chromosomes, resulting in abnormalities such as ovarian failure and infertility. However, pregnancy in women with TS may still occur via spontaneous pregnancy or through oocyte donation. Limited data exists on pregnancy in women with TS that could aid in clinical care.

Methods

We conducted a population‐based cross‐sectional study using data from the Discharge Abstract Database (2004–2015), which contains all labor and delivery hospitalizations across Canada (excluding Quebec) where women delivered a live or stillborn infant. The odds of adverse maternal and neonatal outcomes for women with and without TS were calculated using backwards multivariable logistic regression with generalized estimating equations, adjusting for the Obstetric Comorbidity Index, mode of delivery, and year.

Results

Overall, 2,682,284 women delivered a live or stillborn infant during the study period and 44 birth events occurred for women with TS. No severe maternal morbidity or adverse cardiovascular events occurred for women with TS at their labor and delivery hospitalization. However, infants born to women with TS were 3.6 times more likely (95% CI: 1.7–7.8) to experience neonatal morbidity than those born to women without TS. These infants also were more likely to have had a preterm birth (aOR: 2.9, 95% CI: 1.6–5.4) and to be small‐for‐gestational‐age (aOR: 4.5, 95% CI: 2.4–8.4).

Conclusion

This study adds further understanding of the likelihood of adverse outcomes for pregnant women with TS.
LncRNA H19 aggravates TNF‐α‐induced inflammatory injury via TAK1 pathway in MH7A cells
Authors: Yang Jialiang , Li Yixuan , Wang Lili , Zhang Zhenchun , Li Zunzhong , Jia Qian
Published: June 2020

Rheumatoid arthritis (RA) is a common chronic autoimmune disease in women. This research aims to disclose the probable function of lncRNA H19 in MH7A cells.

The influences of tumor necrosis factor‐α (TNF‐α) on cell viability, apoptosis, and inflammatory factor expression were, respectively, detected through cell counting kit‐8 (CCK‐8), flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT‐PCR), enzyme‐linked immunosorbent assay (ELISA) assay and Western Blot. The levels of H19 and TAK1 were, respectively, tested through qRT‐PCR and Western blot. The expression of NF‐κB and JNK/p38MAPK pathway‐associated proteins was tested through Western blot. We found that TNF‐α reduced MH7A cell viability in a concentration‐dependent manner and facilitated apoptosis and IL‐8, IL‐1β, and IL‐6 production. Besides, TNF‐α treatment raised the level of H19 in MH7A cells. Moreover, H19 silence reduced the levels of inflammatory cytokines, while overexpression of H19 reversed this effect. TNF‐α treatment elevated the expression of inflammatory cytokines by up‐regulating H19. Furthermore, overexpression of H19 promoted TAK1 phosphorylation. Following studies revealed that H19 activated NF‐κB and JNK/p38 MAPK pathways by promoting TAK1 phosphorylation.
bFGF promotes neurological recovery from neonatal hypoxic–ischemic encephalopathy by IL‐1β signaling pathway‐mediated axon regeneration
Authors: Ma Zheng , Wang Fang , Xue Lu‐Lu , Niu Ying‐Jie , Hu Yue , Su Zhang‐Yu , Huang Jin , Niu Rui‐Ze , Wang Ting‐Hua , Ba Ying‐Chun , Xiong Liu‐Lin , Bai Xue
Published: June 2020

Introduction

Neonatal hypoxia–ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive.

Methods

We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen–glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL‐1β was examined in bFGF knockdown condition. IL‐1β knockout (KO) rats were generated using CRISPR/Cas9‐mediated technologies. We used an accepted rat model of HI, to assess the effect of IL‐1β deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level.

Results

We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin‐1β (IL‐1β). IL‐1β was up‐regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD‐mediated pathways. We found HI resulted in up‐regulation of IL‐1β mRNA in cortex and hippocampus. IL‐1β KO rats markedly attenuated the impairment of long‐term learning and memory induced by HI. Meanwhile, IL‐1β−/− (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up‐regulated in IL‐1β KO rats.

Conclusions

We showed that IL‐1β‐mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.
Gepants for abortive treatment of migraine: A network meta‐analysis
Authors: Hong Peiwei , Tan Tianlin , Liu Yao , Xiao Jing
Published: June 2020

Objectives

To evaluate and compare the efficacy and safety of gepants for abortive treatment of migraine by network meta‐analysis.

Materials & Methods

Publications, which were randomized controlled trials (RCTs) about gepants for abortive treatment of migraine, were acquired from Pubmed and Cochrane Library. The literatures screening and quality assessment followed the Cochrane handbook. Review manager 5.3 and Addis v1.16.8 were utilized for data analyzing.

Results

Totally, 15 RCTs were included in the network meta‐analysis. The trials enrolled were with high quality. There are 7 treatments were analyzed: BI 44370 TA, MK‐3207, olcegepant, rimegepant, telcagepant, ubrogepant, and placebo. Of these trials, 11,118 patients and 10,917 patients were assigned to one of 7 treatments randomly for efficacy assessment and safety assessment, respectively. In meta‐analysis of direct comparisons, all gepants were superior to placebo in achieving pain freedom 2 hr postdose and only rimegepant and telcagepant were higher than placebo in incidence of any adverse events. In network meta‐analysis, the rank best 3 drugs were olcegepant, BI 44370 TA, and MK‐3207 for efficacy outcomes. And the rank best 3 drugs were BI 44370 TA, placebo, and ubrogepant for safety outcomes.

Conclusion

Gepants were effective for abortive treatment of migraine. The most effective treatment of gepants for migraine might be olcegepant which were administrated transvenously. And all of gepants were safe for migraine treatment with single dose.
Multi‐voxel pattern analysis of amygdala functional connectivity at rest predicts variability in posttraumatic stress severity
Authors: Fitzgerald Jacklynn M. , Belleau Emily L. , Miskovich Tara A. , Pedersen Walker S. , Larson Christine L.
Published: June 2020

Introduction

Resting state functional magnetic resonance imaging (rsfMRI) studies demonstrate that individuals with posttraumatic stress disorder (PTSD) exhibit atypical functional connectivity (FC) between the amygdala, involved in the generation of emotion, and regions responsible for emotional appraisal (e.g., insula, orbitofrontal cortex [OFC]) and regulation (prefrontal cortex [PFC], anterior cingulate cortex). Consequently, atypical amygdala FC within an emotional processing and regulation network may be a defining feature of PTSD, although altered FC does not seem constrained to one brain region. Instead, altered amygdala FC involves a large, distributed brain network in those with PTSD. The present study used a machine‐learning data‐driven approach, multi‐voxel pattern analysis (MVPA), to predict PTSD severity based on whole‐brain patterns of amygdala FC.

Methods

Trauma‐exposed adults (N = 90) completed the PTSD Checklist‐Civilian Version to assess symptoms and a 5‐min rsfMRI. Whole‐brain FC values to bilateral amygdala were extracted and used in a relevance vector regression analysis with a leave‐one‐out approach for cross‐validation with permutation testing (1,000) to obtain significance values.

Results

Results demonstrated that amygdala FC predicted PCL‐C scores with statistically significant accuracy (r = .46, p = .001; mean sum of squares = 130.46, p = .001; R2 = 0.21, p = .001). Prediction was based on whole‐brain amygdala FC, although regions that informed prediction (top 10%) included the OFC, amygdala, and dorsolateral PFC.

Conclusion

Findings demonstrate the utility of MVPA based on amygdala FC to predict individual severity of PTSD symptoms and that amygdala FC within a fear acquisition and regulation network contributed to accurate prediction.
Efficacy and safety of carbon‐ion radiotherapy for the malignant melanoma: A systematic review
Authors: Li Chengcheng , Zhang Qiuning , Li Zheng , Feng Shuangwu , Luo Hongtao , Liu Ruifeng , Wang Lina , Geng Yichao , Zhao Xueshan , Yang Zhen , Li Qiang , Yang Kehu , Wang Xiaohu
Published: June 2020

Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs.
Rethinking clinical oncology drug research in an era of value‐based cancer care: A role for chemotherapy pathways
Authors: Hoverman J. Russell
Published: June 2020

The United States spends nearly 1/5th of its GDP on healthcare. Yet, to achieve value‐based care, the Economist describes the US healthcare system as handicapped by multiple, disparate silos that prevent the organization and sharing of data. This paper explores the current state of clinical oncology drug research and its relationship to value‐based cancer care. Clinical Chemotherapy Pathways are proposed as a unifying structure to bring together disparate sources of data to increase value.
Iatrogenic air embolism
Authors: Stringer Bryan , Henry Lucie , Foley Raymond
Published: June 2020

Air embolism should be treated promptly with high fraction of supplemental oxygen and repositioning to help facilitate reabsorption of the air bubble. Hyperbaric oxygen therapy should be given to those with severe disease.
High Performance Catalysts BaCoO3−CeO2 Prepared by the One‐Pot Method for NO Direct Decomposition
Authors: Xie Pingping , Yong Xin , Wei Miao , Li Yongdan , Zhang Cuijuan
Published: June 2020

NO direct decomposition is the most promising but also the most challenging approach for nitrogen oxides mitigation. Developing high performance catalysts is greatly desirable to promote the application of this technology. The present catalysts BaCoO3−CeO2 prepared by the one‐pot method show superior activity towards NO direct decomposition, robust oxygen resistance and decent durability. The NO conversion to N2 of 5 %BaCoO3−CeO2 catalyst is 57.2 %, 70.1 % and 75.6 % at 700, 750 and 800 °C, respectively. It still maintains at 54.3 % even in the presence of 10 vol % O2 at 800 °C and is stable in 1 vol % O2 at least for 24 h at 750 °C. Such impressive performance is ascribed to the unique properties of CeO2, strong interaction between perovskite and CeO2, and microstructure of the catalysts rendered by the citric acid‐nitrate one‐pot method.
Anode materials for potassium‐ion batteries: Current status and prospects
Authors: Sha Mo , Liu Long , Zhao Huaping , Lei Yong
Published: June 2020

Potassium‐ion batteries (KIBs) as one of the most promising alternatives to lithium‐ion batteries have been highly valued in recent years. However, progress in KIBs is largely restricted by the sluggish development in anode materials. Therefore, it is imperative to systematically outline and evaluate the recent research advances in the field of anode materials for KIBs toward promoting the development of high‐performance anode materials for KIBs. In this review, the recent achievements in anode materials for KIBs are summarized. The electrochemical properties (ie. charge storage mechanism, capacity, rate performance, and cycling stability) of these reported anode materials, as well as their advantages/disadvantages, are discerned and analyzed, enabling high‐performance KIBs to meet the requirements for practical applications. Finally, technological developments, scientific challenges, and future research opportunities of anode materials for KIBs are briefly reviewed.
Applicability of electrical resistance tomography to the analysis of fluid distribution in haemodialysis modules
Authors: Paglianti Alessandro , Marotta Gaspare , Montante Giuseppina
Published: June 2020

This work aims to explore the applicability of electrical resistance tomography (ERT) in the analysis of fluid distribution in haemodialysis modules, which is not straightforward due to the complex geometry of the hollow fibre bundles and the small sizes of the modules. On the other hand, ERT is potentially a suitable and convenient technique for investigation in this field due to its cost‐effectiveness and capacity to perform measurements in opaque systems. After a preliminary estimation of the fibre bundle local distribution, the assessment of the technique is performed by observing the time evolution of the measured conductivity maps during the module filling and emptying operations with water and air, which are alternatively fed inside or outside the fibre bundle. Reliable conductivity maps are obtained by placing the module vertically or horizontally. Additional experimental data collected by feeding liquid mixtures of different sodium chloride concentrations show that the technique is suitable for detecting concentration variations, due to the mass transfer through the fibres, and flow maldistribution, due to the specific geometry of the module. From the preliminary results collected in this work, the technique appears to be adequate for the collection of data that can support the optimization of the module geometry and computational model validation.
Nonlinear ion acoustic waves in dissipative and dispersive magneto‐rotating relativistic plasmas with two temperature superthermal electrons
Authors: Abbasi M.M. , Masood W. , Khan Majid , Ahmad Ali
Published: June 2020

A study has been presented for the nonlinear features of ion‐acoustic (IA) shock waves in a magnetorotating plasma consisting of warm viscous streaming ions along with kappa‐distributed electrons having two different temperatures. In this regard, we have employed the reductive perturbation technique to derive the Zakharov‐Kuznetsov‐Burgers (ZKB) equation that governs the dynamics of IA shock waves. The solution obtained by the hyperbolic tangent method has been shown to depend on various plasma parameters such as spectral index (κc), density fraction (f), effective rotation frequency (Ωc), ion kinematic viscosity (ηo), and temperature ratio (σ). In the limiting case when dissipative coefficient D → 0, we have also examined the solitary potential distributions, which are the solutions of Zakharov Kuznetsov (ZK) equation. It is found that both rarefactive and compressive structures exist for the system under consideration. The transition in the nature of such profiles is due to the enhancement in the density of cold electrons. The importance of present theoretical investigations has been carried out with regard to Saturn's magnetosphere, where two temperature superthermal electron populations have been observed by various satellite missions.
MAFB modulates the maturation of lymphatic vascular networks in mice
Authors: Rondon‐Galeano Maria , Skoczylas Renae , Bower Neil I. , Simons Cas , Gordon Emma , Francois Mathias , Koltowska Katarzyna , Hogan Benjamin M.
Published: June 2020

Background

Lymphatic vessels play key roles in tissue fluid homeostasis, immune cell trafficking and in diverse disease settings. Lymphangiogenesis requires lymphatic endothelial cell (LEC) differentiation, proliferation, migration, and co‐ordinated network formation, yet the transcriptional regulators underpinning these processes remain to be fully understood. The transcription factor MAFB was recently identified as essential for lymphangiogenesis in zebrafish and in cultured human LECs. MAFB is activated in response to VEGFC‐VEGFR3 signaling and acts as a downstream effector. However, it remains unclear if the role of MAFB in lymphatic development is conserved in the mammalian embryo.

Results

We generated a Mafb loss‐of‐function mouse using CRISPR/Cas9 gene editing. Mafb mutant mice presented with perinatal lethality associated with cyanosis. We identify a role for MAFB in modifying lymphatic network morphogenesis in the developing dermis, as well as developing and postnatal diaphragm. Furthermore, mutant vessels displayed excessive smooth muscle cell coverage, suggestive of a defect in the maturation of lymphatic networks.

Conclusions

This work confirms a conserved role for MAFB in murine lymphatics that is subtle and modulatory and may suggest redundancy in MAF family transcription factors during lymphangiogenesis.
Demographic trends in community functional tolerance reflect tree responses to climate and altered fire regimes
Authors: Marshall L. A. , Falk D. A.
Published: June 2020

Forests of the western United States are undergoing substantial stress from fire exclusion and increasing effects of climate change, altering ecosystem functions and processes. Changes in broad‐scale drivers of forest community composition become apparent in their effect on survivorship and regeneration, driving demographic shifts. Here we take a community functional approach to forest demography, by investigating mean drought or shade functional tolerance in community assemblages. We created the Community Mean Tolerance Index (CMTI), a response metric utilizing drought/shade tolerance trade‐offs to identify communities undergoing demographic change from a functional trait perspective. We applied the CMTI to Forest Inventory and Analysis data to investigate demographic trends in drought and shade tolerance across the southern Rocky Mountains. To find the major drivers of change in community tolerance within and across forest types, we compared index trends to climate and fire‐exclusion‐driven disturbance, and identified areas where demographic change was most pronounced. We predicted that greater shifts in drought tolerance would occur at lower forest type ecotones where climate stress is limiting and that shifts in shade tolerance would correspond to excursions from the historic fire regime leading to greater changes in forest types adapted to frequent, low‐intensity fire. The CMTI was applied spatially to identify sites likely to transition to oak shrubfield, where disturbance history combined with a species‐driven demographic shift toward drought tolerance. Within forest types, lower elevations are trending toward increased drought tolerance, while higher elevations are trending toward increased shade tolerance. Across forest types, CMTI difference peaked in mid‐elevation ponderosa pine and mixed‐conifer forests, where fire exclusion and autecology drive demographic changes. Peak CMTI difference was associated with fire exclusion in forest types adapted to frequent fire. At higher elevations, site‐level stand dynamics appear to be influencing demographic tolerance trends more than broad climate drivers. Through a community demographic approach to functional traits, the CMTI highlights areas and forest types where ecosystem function is in the process of changing, before persistent vegetation type change occurs. Applied to regional plot networks, the CMTI provides an early warning of shifts in community functional processes as climate change pressures continue.
The mathematical influence on global patterns of biodiversity
Authors: Beaugrand Gregory , Kirby Richard , Goberville Eric
Published: June 2020

Although we understand how species evolve, we do not appreciate how this process has filled an empty world to create current patterns of biodiversity. Here, we conduct a numerical experiment to determine why biodiversity varies spatially on our planet. We show that spatial patterns of biodiversity are mathematically constrained and arise from the interaction between the species’ ecological niches and environmental variability that propagates to the community level. Our results allow us to explain key biological observations such as (a) latitudinal biodiversity gradients (LBGs) and especially why oceanic LBGs primarily peak at midlatitudes while terrestrial LBGs generally exhibit a maximum at the equator, (b) the greater biodiversity on land even though life first evolved in the sea, (c) the greater species richness at the seabed than at the sea surface, and (d) the higher neritic (i.e., species occurring in areas with a bathymetry lower than 200 m) than oceanic (i.e., species occurring in areas with a bathymetry higher than 200 m) biodiversity. Our results suggest that a mathematical constraint originating from a fundamental ecological interaction, that is, the niche–environment interaction, fixes the number of species that can establish regionally by speciation or migration.
Accounting for imperfect detection in observational studies: modeling wolf sightability in Yellowstone National Park
Authors: Metz Matthew C. , SunderRaj Jeremy , Smith Douglas W. , Stahler Daniel R. , Kohl Michel T. , Cassidy Kira A. , Hebblewhite Mark
Published: June 2020

Imperfect detection is ubiquitous among wildlife research and is therefore commonly included in abundance estimation. Yet, the factors that affect observation success are largely unknown for rare and elusive species, such as large carnivores. Here, we took advantage of intensive ground‐based monitoring effort and an extensive GPS data set (2000–2018) and developed a winter sightability model for gray wolves (Canis lupus) in northern Yellowstone National Park, Wyoming, USA. Our resulting sightability model indicated that observation success was positively affected by the topographic nature of where wolves were in relation to observer locations (viewshed), areas being less forested (openness), and wolf group size, and negatively affected by distance from observer locations. Of these, viewshed had the strongest effect on the probability of observing a wolf, with the odds of observing a wolf being four times more likely when wolves were in the predicted viewshed. Openness was the next most influential covariate, and group size was the least influential. We also tested whether a wolf being harvested from a pack when they were outside of Yellowstone National Park had an effect on wolf sightability. We did not, however, find support for human‐induced mortality affecting wolf sightability inside of Yellowstone National Park. Our results indicate that the ability to observe wolves was greatly affected by ecological and landscape‐level factors, a finding that is likely to generally extend to other large carnivores. As such, our sightability model highlights the importance of considering landscape structure and variation in large carnivore use of the landscape when conducting observational‐based studies.
Time‐lagged impacts of extreme, multi‐year drought on tidal salt marsh plant invasion
Authors: Wigginton Rachel D. , Kelso Megan A. , Grosholz Edwin D.
Published: June 2020

Climate change is projected to increase the frequency of extreme drought events, which can have dramatic consequences for ecosystems. Extreme drought may interact with other stressors such as invasion by non‐native species, yet little research has explored these dynamics. Here, we examine the physical mechanisms and temporal scale underlying a dieback of an invasive non‐native plant,Lepidium latifolium,in tidal salt marshes of the San Francisco Bay, California, USA, during an extreme, multi‐year drought occurring from 2012 to 2015. Using generalized additive mixed models (GAMMs), we explored the relationship between eight years of estuarine salinity data and five years ofL. latifoliumdensity data from three marshes spanning a gradient of salinity across the San Francisco Bay. We found a significant time‐lagged (3 yr) effect of estuarine salinity onL. latifoliumdensity, with high salinities preceding reductions inL. latifoliumdensities and low salinities preceding increases. The most dramatic change in stem density, a 54% reduction in 2015, was preceded by a salinity increase of 43% from 2011 to 2012. We found theL. latifoliumdecline was driven by impacts on mature, rather than young, plants. Additionally, we tested the importance of local precipitation in drivingL. latifoliumdensities in a one‐season rain exclusion experiment. We found 100% exclusion of precipitation during one rainy season (January–mid‐May) did not have a significant impact on densities of mature stands ofL. latifolium. Our finding that estuarine salinity was a key driver ofL. latifoliuminvasion dynamics suggests sea level rise, like extreme drought, may hinderL. latifoliuminvasion, as it will also raise estuarine salinities. Further, our study highlights the importance of temporal lags in understanding climate change impacts on biological invasions, which has received very little study to date.
Negative control of diacylglycerol kinase ζ‐mediated inhibition of T cell receptor signaling by nuclear sequestration in mice
Authors: Xie Danli , Zhang Shimeng , Chen Pengcheng , Deng Wenhai , Pan Yun , Xie Jinhai , Wang Jinli , Liao Bryce , Sleasman John W. , Zhong Xiao‐Ping
Published: June 2020

Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)‐mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKζ function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKζ function are still poorly understood. We report here that DGKζ dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKζ mutant defective in nuclear localization displayed enhanced ability to inhibit TCR‐induced DAG‐mediated signaling in primary T cells, maturation of conventional αβT and iNKT cells, and activation of peripheral T cells compared with WT DGKζ. Our study reveals for the first time nuclear sequestration of DGKζ as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKζ nucleus‐cytosol shuttling as a novel strategy to modulate DGKζ activity and immune responses for treatment of autoimmune diseases and cancer.
Milling Activation for the Solvent‐Free Synthesis of the Zeolite Mordenite
Authors: Kornas Agnieszka , Olszówka Joanna E. , Urbanova Martina , Mlekodaj Kinga , Brabec Libor , Rathousky Jiri , Dedecek Jiri , Pashkova Veronika
Published: June 2020

Milling by a planetary mill was applied as a pretreatment of a reagent mixture for the solvent‐free synthesis of the zeolite mordenite. This method was compared with both manual grinding and standard hydrothermal synthesis. The comprehensive characterization of the obtained products was complemented by thorough studies of activated synthesis mixtures before crystallization steps (by Magic Angle Spinning Nuclear Magnetic Resonance and Scanning Electron Microscopy). This experimental approach gave insight into processes behind the synthesis mixture activation by milling. The characteristics of solvent‐free zeolite product were comparable with material obtained by the classic hydrothermal route. The automated milling activation made the crystallization possible due to higher energetic impact in comparison to manual grinding. The solvent‐free process allowed minimization of the contribution of water to a role of the agent catalyzing silica transformation; as a result, less than 5 % water (compared to the classical synthesis) was necessary to perform the crystallization.
Efficient Thiophene Synthesis Mediated by 1,3‐Bis(carboxymethyl)imidazolium Chloride: C‐C and C‐S Bond Formation
Authors: Gisbert Patricia , Pastor Isidro M.
Published: June 2020

Thiophene derivatives have been prepared by means of a functionalized imidazolium salt [1,3‐bis(carboxymethyl)imidazolium chloride] acting as a catalyst. The heterogeneous catalyst has allowed to carry out the reactions with no solvent or inert atmosphere. Different aryl methyl ketones have reacted with elemental sulfur to selective produce 2,4‐substituted thiophenes. Furthermore, the reaction of sulfur with cyclic ketones has enabled the preparation of polycyclic compounds. This protocol is simple and effective for preparing thiophene derivatives, even in a preparative scale. The thiophene synthesis described presents remarkable sustainability with an E‐factor of 7.4, the solvent‐free conditions being crucial for this feature. The catalyst is straightforwardly prepared, and it is easily separated from the reaction mixture, making its reuse possible.
Enantioselective Synthesis of cis and trans 4‐Aminopipecolic Acids as γ‐Amino Acids for the Construction of Cyclic RGD‐Containing Peptidomimetics Antagonists of αVβ3 Integrin
Authors: Dordoni Francesca , Scarpi Dina , Bianchini Francesca , Contini Alessandro , Occhiato Ernesto G.
Published: June 2020

A stereodivergent strategy to obtain enantiopure cis and trans 4‐aminopipecolic acids (4‐APAs) in a suitably protected form for peptide synthesis has been devised starting from a common, known precursor in turn easily prepared from commercial (R)‐4‐cyano‐3‐hydroxybutyric acid ethyl ester. The two isomers were efficiently obtained in 40 % and 23 % overall yields, respectively, in seven and ten steps. To demonstrate their usefulness in peptidomimetic synthesis, both 4‐APA isomers were incorporated as γ‐amino acids in a cyclic RGD‐containing sequence, although for the trans 4‐APA isomer a further amino acid in the sequence (L‐Phe) was needed to allow ring closure. The two cyclopeptides were tested as αVβ3 integrin antagonists in comparison with cilengitide.
Electrokinetic flow and electric conduction of salt‐free solutions in a capillary
Authors: Luo Ren H. , Keh Huan J.
Published: June 2020

The electrokinetic flow and accompanied electric conduction of a salt‐free solution in the axial direction of a charged circular capillary are analyzed. No assumptions are made about the surface charge density (or surface potential) and electrokinetic radius of the capillary, which are interrelated. The Poisson–Boltzmann equation and modified Navier–Stokes equation are solved for the electrostatic potential distribution and fluid velocity profile, respectively. Closed‐form formulas for the electroosmotic mobility and electric conductivity in the capillary are derived in terms of the surface charge density. The relative surface potential, electroosmotic mobility, and electric conductivity are monotonic increasing functions of the surface charge density and electrokinetic radius. However, the rises of the relative surface potential and electroosmotic mobility with an increase in the surface charge density are suppressed substantially when it is high due to the effect of counterion condensation. The analytical prediction that the electroosmotic mobility grows with increases in the surface charge density and electrokinetic radius agrees with the experimental results for salt‐free solutions in circular microchannels in the literature.
A full three‐dimensional fracture propagation model for supercritical carbon dioxide fracturing
Authors: He Yuting , Yang Zhaozhong , Jiang Yanfang , Li Xiaogang , Zhang Yongqing , Song Rui
Published: June 2020

Supercritical carbon dioxide fracturing is an environmentally friendly anhydrous method. To study the propagation process during supercritical carbon dioxide fracturing, a full three‐dimensional model, coupled rock deformation, fluid transport, heat conduction, dynamic changes of carbon dioxide physical parameters, to investigate the process of fracture propagation during supercritical carbon dioxide fracturing, is established by the three‐dimensional boundary element method, the finite volume method, and finite difference method. And to solve the multiple physics coupling problems, a fully implicit solution and Newton‐Raphson iteration method are used. On the basis of this model established in this paper, the influential factors of supercritical carbon dioxide fracturing are analyzed. The results show that both of the reservoir temperature and the original in situ stress are important for carbon dioxide fracturing; The higher the reservoir temperature and the lower the initial in situ stress is, the longer and wider the fracture will be. The temperature of carbon dioxide at bottom is of no significance to the fracture length, fracture width, and the bottom hole pressure. A growing injection rate will lead to the increase of the fracture length and fracture width. This study would provide a reference for the fluid phase control of supercritical carbon dioxide fracturing technology.
Advances in structures required of polyphenols for xanthine oxidase inhibition
Authors: Liu Liangliang , Zhang Li , Ren Licheng , Xie Yixi
Published: June 2020

Polyphenols have been used as natural medicaments for the management of hyperuricemia for a long history. They have been attracted many interests because of the little side effects in curing hyperuricemia, which is an important advantage over the antihyperuricemic drugs. In this review, the structure–activity relationships for polyphenols as xanthine oxidase (XO) inhibitors were discussed. It is concluded that the presence of hydroxyl groups, which influences the inhibitory effects, is closely related to whether the substitutions increase the steric hindrance or disturb the interaction of flavonoid with the catalytic site of XO, and the increased size of the molecule after glycosylation may increase the steric hindrance between flavonoid and XO, and consequently reducing the competitive inhibition behaviors. However, there is no obtained simple general rule that can comprehensively describe the effects of structural alteration on the inhibition activity because the results are varied among different subclasses of polyphenols. In addition, the inhibition mechanisms are mainly assumed as polyphenol binding to the active site of XO and hindering the entrance of xanthine or the discharge of uric acid and diffusion of O2−radical.
Serum phytosterols associate with T helper 1 cytokine concentration in pregnant women
Authors: Liu Yuwei , Li Wenyun , Qian Jiaye , Wu Min , Du Hongyi , Xu Linji , Liu Shuping , Yi Jianping , He Gengsheng
Published: June 2020

The dietary phytosterols have been demonstrated to modulate CD4+ T‐cell polarization in cells, animals, and humans. However, T helper (Th)1/Th2 dichotomy has rarely been correlated with phytosterols during pregnancy. The present study investigated associations between the serum cytokines and serum phytosterols in 100 pregnant women at 34‐ to 37‐week gestation and their offspring. The results showed that serum concentrations of interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, and total Th1 cytokines were positively associated with serum β‐sitosterol level, adjusting for age, BMI, and serum cholesterol. Serum IFN‐γ and total Th1 cytokine concentrations positively correlated with total phytosterol concentration, controlling age, BMI, and serum cholesterol. Moreover, none of the cytokines measured correlated with phytosterol concentration in the newborns. Our results show that serum Th1 cytokine concentrations, but not Th2 levels, are positively associated with serum phytosterols in pregnant women. These findings implicate that phytosterols modulate Th1/Th2 balance by inducing Th1 secretions in pregnant women.
Clockwise hairpin‐type metamorphic pressure–temperature (P–T) path recorded in the Shangla blueschist along the Indus Suture Zone, Pakistan Himalaya
Authors: Iqbal Muhammad Zahoor , Li Weimin , Ali Asghar , Liu Yongjiang , Zhang Duo
Published: June 2020

The Shangla blueschist, exposed along the Indus Suture Zone, Pakistan Himalaya, have been petrologically investigated in order to elucidate their tectono‐metamorphic evolution, and to better understand the geodynamic scenario of intra‐oceanic subduction between the Indian Plate and Kohistan‐Ladakh Arc. Representative mineral assemblages identified from the Shangla blueschist, contain amphiboles (glaucophane, magnesioriebeckite, winchite, actinolite, edenite, and magnesiohornblende), epidote, phengite, albite, chlorite, titanite, rutile, quartz, and haematite. Three distinct metamorphic stages are recognized for the Shangla blueschist. An early prograde (pre‐peak) metamorphic stage (M1) is characterized by the presence of winchite as the core part of zoned amphiboles, together with inclusions of epidote, albite, chlorite, quartz, titanite, and haematite in epidote porphyroblasts. This stage roughly reveals a temperature range of 300–450°C and pressures of 0.4–0.7 GPa. The equilibrium minerals of peak (M2) metamorphic stage consist of matrix, schistosity‐forming minerals including amphiboles (glaucophane, magnesioriebeckite), epidote and phengite, with fine‐grained rutile, titanite, and haematite in albite porphyroblasts, suggesting P–T condition of 350–520°C and 0.9–1.2 GPa. The retrograde (M3) metamorphic stage involved overgrowth of winchite and actinolite along glaucophane rims, and chlorite replacement of amphibole as well as growth of albite porphyroblasts, representing the greenschist‐facies metamorphism. Our obtained peak P–T metamorphic condition (epidote‐blueschist facies) is significantly higher than previously estimated P–T ranges of 400°C/0.7 GPa. Moreover, the retrograde approximately reversed prograde trajectory defines a hairpin‐type P–T path for the Shangla blueschist, similar to the Franciscan‐type metamorphism that is characterized by relatively slow exhumation after peak stage with the decompression accompanied by cooling process. Taking the published geochronological data into account, these new results provide insights into the metamorphic evolution of the Shangla blueschist during ca. 80 Ma (Late Cretaceous) from burial by cold subduction of the Neo‐Tethys to subsequent post‐peak exhumation. Furthermore, the exhumation mechanism of the Shangla blueschist is most likely driven by a combined effect of both underplating and later thrust faulting, probably during the collision of the Indian Plate and Kohistan‐Ladakh Arc.
Biophysical basis for Kv1.3 regulation of membrane potential changes induced by P2X4‐mediated calcium entry in microglia
Authors: Nguyen Hai M. , di Lucente Jacopo , Chen Yi‐Je , Cui Yanjun , Ibrahim Rania H. , Pennington Michael W. , Jin Lee‐Way , Maezawa Izumi , Wulff Heike
Published: June 2020

Microglia‐mediated inflammation exerts adverse effects in ischemic stroke and in neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the voltage‐gated potassium channel Kv1.3 is required for microglia activation. Both genetic deletion and pharmacological inhibition of Kv1.3 are effective in reducing microglia activation and the associated inflammatory responses, as well as in improving neurological outcomes in animal models of AD and ischemic stroke. Here we sought to elucidate the molecular mechanisms underlying the therapeutic effects of Kv1.3 inhibition, which remain incompletely understood. Using a combination of whole‐cell voltage‐clamp electrophysiology and quantitative PCR (qPCR), we first characterized a stimulus‐dependent differential expression pattern for Kv1.3 and P2X4, a major ATP‐gated cationic channel, both in vitro and in vivo. We then demonstrated by whole‐cell current‐clamp experiments that Kv1.3 channels contribute not only to setting the resting membrane potential but also play an important role in counteracting excessive membrane potential changes evoked by depolarizing current injections. Similarly, the presence of Kv1.3 channels renders microglia more resistant to depolarization produced by ATP‐mediated P2X4 receptor activation. Inhibiting Kv1.3 channels with ShK‐223 completely nullified the ability of Kv1.3 to normalize membrane potential changes, resulting in excessive depolarization and reduced calcium transients through P2X4 receptors. Our report thus links Kv1.3 function to P2X4 receptor‐mediated signaling as one of the underlying mechanisms by which Kv1.3 blockade reduces microglia‐mediated inflammation. While we could confirm previously reported differences between males and females in microglial P2X4 expression, microglial Kv1.3 expression exhibited no gender differences in vitro or in vivo.

Main Points

The voltage‐gated K+ channel Kv1.3 regulates microglial membrane potential.

Inhibition of Kv1.3 depolarizes microglia and reduces calcium entry mediated by P2X4 receptors by dissipating the electrochemical driving force for calcium.