bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of groundwater quality in Khulna city of Bangladesh in terms of water quality index for drinking purpose
Authors: Mahmud Asif , Sikder Shraboni , Joardar Jagadish Chandra
Published: October 2020

Valuation of water quality index (WQI) is one of the simplest, easily understandable, and efficacious techniques to evaluate the quality and suitability of water for drinking as well as other purposes. This research was aimed to investigate the drinking water quality of tube wells from different areas in Khulna City, Bangladesh, by developing the WQI. Water samples from 59 tube wells were collected from different locations during the pre-monsoon time. pH, electric conductivity (EC), dissolve oxygen (DO), total dissolved solid (TDS), chloride (Cl−), nitrate (NO3−), and total hardness of the collected water samples were analyzed for the calculation of WQI. The mean value for pH, EC, DO, TDS, Cl−1, NO3−, and total hardness was 7.30, 1650 μS/cm, 1.60 mg/l, 1188.7 mg/l, 414.6 mg/l, 0.029 mg/l, and 52.03 mg/l, respectively. The calculated WQI values for individual places were distributed spatially through mapping by using ArcGIS software. Based on the WQI values, the drinking water was categorized into excellent, good, poor, very poor, and unfit for drinking purposes. The calculated WQI values ranged from 40.11 to 454.37 with an average value of 108.94. Among all the groundwater samples, 11.86% were excellent, 54.24% were good, 23.73% were poor, 1.69% were very poor, and 8.47% were unfit for drinking purpose based on WQI. The results showed that the groundwater quality of most of the studied areas of Khulna city could be considered safe and suitable for drinking barring the elevated EC and chloride content in some areas. Since Khulna city is situated in the southwestern part of Bangladesh and gradually approaches toward the base level of the Bay of Bengal which might be the source of salt concentration in the groundwater of Khulna city, Bangladesh.
A predictive protocol to obtain maximum water-free oil production rate for perforated vertical wells
Authors: Adeleye James O. , Olamigoke Olugbenga , Mumuni Oluseun T.
Published: October 2020

Producing an oilfield in a cost-effective way depends on how long water production could be delayed in the reservoir. Many flow mechanisms, correlations, and methods to calculate maximum water-free oil production rate have been published, However, those methods have generally failed to not consider the skin effect which affects the flow into the wellbore. In this paper, the semi-analytical perforation skin model as presented by Karakas and Tariq is incorporated into the Meyer and Garder correlation for critical oil rate from a perforated vertical well interval to obtain the maximum water-free oil production rate and optimal perforation parameters. The resulting coupled computational model is used to determine the sensitivity of the maximum water-free oil production rate to wellbore perforation parameters. Whilst an increase in perforation length and decrease in spacing between perforation increase the critical flow rate, an increase in perforation radius did not translate to higher productivity. The optimal perforation angles are 45° and 60°, however, for the data used in this work the maximum water-free oil rate of 23.2 std/d was obtained at 45° of phasing angle, 1 in of spacing between perforation, 0.36 in of perforation radius and 48 in of perforation length. Thus, the perforation strategy can be optimized prior to drilling and completion operations to improve productivity using the computational model presented in this work.
Conceptualizing the National Group for the Crime of Genocide: Is Law Able to Account for Identity Fault Lines?
Authors: Lingaas Carola
Published: October 2020

“National group” is one of four victim groups that is explicitly protected by international criminal law from genocide. At the core of any genocide lies an element of identity. Yet, the fixed group categories that the law provides for seemingly do not conform to the fluidity of group identities. Is the law at all able to account for identity fault lines? By recourse to research on identity construction and otherness, this article argues that the interpretation of the law of genocide can benefit, structurally and legally, from insight into the forces at work before a genocide erupts. In recognizing the perpetrator’s definitional power over the victim group, the courts should increasingly focus their investigation into the mind of the génocidaires and their perception of the national victim group. In addition to discussing the dynamics of intergroup conflicts leading up to a genocide, this article also looks at the jurisprudence of criminal courts on the issues of nationality, national groups, and national identity for the crime of genocide.
Algorithmic Trading and Market Quality: International Evidence
Authors: Boehmer Ekkehart , Fong Kingsley , Wu Juan (Julie)
Published: October 2020

We study the effect of algorithmic trading (AT) on market quality between 2001 and 2011 in 42 equity markets around the world. We use an exchange colocation service that increases AT as an exogenous instrument to draw causal inferences about AT on market quality. On average, AT improves liquidity and informational efficiency but increases short-term volatility. Importantly, AT also lowers execution shortfalls for buy-side institutional investors. Our results are surprisingly consistent across markets and thus across a wide range of AT environments. We further document that the beneficial effect of AT is stronger in large stocks than in small stocks.
Shared intrinsic functional connectivity alterations as a familial risk marker for ADHD: a resting-state functional magnetic resonance imaging study with sibling design
Authors: Chiang Huey-Ling , Tseng Wen-Yih Isaac , Wey Hsiao-Ying , Gau Susan Shur-Fen
Published: October 2020

Background

Although aberrant intrinsic functional connectivity has been reported in attention-deficit/hyperactivity disorder (ADHD), we have a limited understanding of whether connectivity alterations are related to the familial risk of ADHD.

Methods

Fifty-three probands with ADHD, their unaffected siblings (n = 53) and typically developing controls (n = 53) underwent resting-state functional magnetic resonance imaging scans. A seed-based approach with the bilateral precuneus/posterior cingulate cortex (PCC) was used to derive a whole-brain functional connectivity map in each subject. The differences in functional connectivity among the three groups were tested with one-way ANOVA using randomized permutation. Comparisons between two groups were also performed to examine the increase or decrease in connectivity. The severity of ADHD symptoms was used to identify brain regions where symptom severity is correlated to the strength of intrinsic functional connectivity.

Results

When compared to controls, both probands and unaffected siblings showed increased functional connectivity in the left insula and left inferior frontal gyrus. The connectivity in these regions was linked to better performance in response inhibition in the control group but absent in other groups. Higher ADHD symptom severity was correlated with increased functional connectivity in bilateral fronto-parietal-temporal regions only noted in probands with ADHD.

Conclusions

Alterations in resting-state functional connectivities with the precuneus/PCC, hubs of default-mode network, account for the underlying familial risks of ADHD. Since the left insula and left inferior frontal gyri are key regions of the salience and frontoparietal network, respectively, future studies focusing on alterations of cross-network functional connectivity as the familial risk of ADHD are suggested.
Restrictive eating across a spectrum from healthy to unhealthy: behavioral and neural mechanisms
Authors: Foerde Karin , Schebendach Janet E. , Davis Lauren , Daw Nathaniel , Walsh B. Timothy , Shohamy Daphna , Steinglass Joanna E.
Published: October 2020

Background

Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear.

Methods

This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted.

Results

Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day.

Conclusions

A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.
The acquisition of noun inflection in Northern Pame (Xi'iuy): Comparing whole word and minimal word accounts
Authors: PYE Clifton , BERTHIAUME Scott , PFEILER Barbara
Published: October 2020

The study used naturalistic data on the production of nominal prefixes in the Otopamean language Northern Pame (autonym: Xi'iuy) to test Whole Word (constructivist) and Minimal Word (prosodic) theories for the acquisition of inflection. Whole Word theories assume that children store words in their entirety; Minimal Word theories assume that children produce words as binary feet. Northern Pame uses obligatory portmanteaux prefixes to inflect nouns for class, number, animacy and possessor. Singular nouns constitute 90 percent of the nouns that the children hear and yet all five two-year-old children frequently omitted the singular noun prefixes, but produced the low frequency noun suffixes for dual and animate plural. Neither the children's production of the noun-class prefixes nor their prefix overextensions correlated with the adult type and token frequencies of production. Northern Pame children constructed Minimal Words that contain binary feet and disfavor the production of initial, extrametrical prefixes.
Nightlife clusters of coronavirus disease in Tokyo between March and April 2020
Authors: Takaya S. , Tsuzuki S. , Hayakawa K. , Kawashima A. , Okuhama A. , Kanda K. , Suzuki T. , Akiyama Y. , Miyazato Y. , Ide S. , Nakamura K. , Nomoto H. , Nakamoto T. , Hikida S. , Tanuma J. , Ohara K. , Ito T. , Baba T. , Yamamoto K. , Ujiie M. , Saito S. , Morioka S. , Ishikane M. , Kinoshita N. , Kutsuna S. , Ohmagari N.
Published: October 2020

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.
The “American DREAM”: Understanding White Americans’ Support for the DREAM Act and Punitive Immigration Policies
Authors: Matos Yalidy
Published: October 2020

The American public has overwhelmingly supported the Development, Relief, and Education for Alien Minors (DREAM) Act since 2001. The support is widespread and cuts across race, ethnic, and party lines. Given the United States’ anti-immigrant/immigration sentiment in the wake of the September 11, 2001 terrorist attacks, support for the DREAM Act is perplexing. To that end, political scientists, sociologists, and education scholars, among others, have pointed to the exceptional framing of the DREAM Act as the primary predictor of support. However, a significant portion of non-Hispanic white Americans who support the DREAM Act also support restrictive and often punitive immigration policies. What influences most white Americans to support DREAM Act legislation? And what leads a subset of these same individuals to simultaneously support restrictive immigration policies that hurt DREAMers and their families? I argue that predispositions explain these two contradictory policy preferences. Data from the 2012 American National Election Studies (ANES) and the 2018 Cooperative Congressional Election Studies (CCES) demonstrates that white Americans use racial resentment and egalitarianism as justifications to support both policies. However, the effects are conditioned on partisanship.
Endovascular versus medical treatment of venous compression syndrome of the iliac vein – a systematic review
Authors: Bashar Khalid , Shalan Ahmed , Sharafat Ali Sana , Tang Tjun , Tiwari Alok
Published: October 2020

Summary: The treatment of non-thrombotic iliac vein lesions (NIVL) remains debatable with many advocating conservative treatments, whilst others offering venous stenting. The objective of this review was to systematically assess the treatment options for symptomatic iliac vein compression syndrome (IVCS) in patients without evidence of thrombotic disease at the time of diagnosis. An online search of published literature looking for randomised controlled trials and observational studies that evaluated the treatment for symptomatic NIVL was performed. Nine studies were included with a total 953 patients of which 782 patients had NIVL. Patency rates ranged between 94.8%–100% in the first month, 88.2%–94.1% in six months and 73.4%–98% in 12 months, in patients with NIVL post stenting. Longer follow-up of up to 5 years shows promising patency rates of 94% in patients with IVCS. Patients with IVCS are likely to benefit from a combination of endovenous treatment at the time of diagnosis including stent placement to maintain lumen patency and prevent recurrent deep venpus thrombosis and/or postthrombotic syndrome.
Differences in the Quantity and Quality of Organic Matter Exported From Greenlandic Glacial and Deglaciated Watersheds
Authors: Pain Andrea J. , Martin Jonathan B. , Martin Ellen E. , Rahman Shaily , Ackermann Philip
Published: October 2020

Riverine input of terrestrial dissolved organic matter (DOM) is an important component of the marine carbon cycle and drives net carbon dioxide production in coastal zones. DOM exports to the Arctic Ocean are likely to increase due to melting of permafrost and the Greenland Ice Sheet, but the quantity and quality of DOM exports from deglaciated watersheds in Greenland, as well as expected changes with future melting, are unknown. We compare DOM quantity and quality in Greenland over the melt seasons of 2017–2018 between two rivers directly draining the Greenland Ice Sheet (meltwater rivers) and four streams draining deglaciated catchments that are disconnected from the ice (nonglacial streams). We couple these data with discharge records to compare dissolved organic carbon (DOC) exports. DOM sources and quality differ significantly between watershed types: fluorescence characteristics and organic molar C:N ratios suggest that DOM from deglaciated watersheds is derived from terrestrial vegetation and soil organic matter, while that in glacial watersheds contains greater proportions of algal and/or freshly produced biomass and may be more reactive. DOC specific yield is similar for nonglacial streams (0.1–1.2 Mg/km2/year) compared to a glacial meltwater river (0.2–1.1 Mg/km2/year), despite orders of magnitude differences in instantaneous discharge. Upscaling based on land cover leads to an estimate of total DOC contributions from Greenland between 0.2 and 0.5 Tg/year, much of which is derived from deglaciated watersheds. These results suggest that future warming and ice retreat may increase DOC fluxes from Greenland with consequences for the Arctic carbon cycle.
Rates of Olivine Grain Growth During Dynamic Recrystallization and Postdeformation Annealing
Authors: Speciale P. A. , Behr W. M. , Hirth G. , Tokle L.
Published: October 2020

We performed deformation and grain growth experiments on natural olivine aggregates with olivine water contents (COH = 600 ± 300 H/106 Si) similar to upper mantle olivine, at 1000–1200°C and 1,400 ± 100 MPa confining pressure. Our experiments differ from published grain growth studies in that most were (1) conducted on natural olivine cores rather than hot‐pressed aggregates and (2) dynamically recrystallized prior to or during grain growth. We combine our results with similar experiments performed at 1200–1300°C and fit the data to a grain growth relationship, yielding a growth exponent (p) of 3.2, activation energy (EG) 620 ± 145 kJ mol−1 (570 ± 145 kJ mol−1 when accounting for the role of temperature on water content), activation volume (VG) ~5 × 10−6 m3 mol−1, and rate constant (k0) 1.8 × 103 mp s−1. Our EG is within uncertainty of that predicted for dislocation creep of wet olivine (E* = 480 ± 40 kJ mol−1). Grain size in strain rate‐stepping samples adjusted to the olivine piezometer within 1.3–7.9% strain. The active grain boundary migration processes during deformation and dynamic recrystallization affect the kinetics of postdeformation grain growth, as grain boundary migration driven by strain energy density (ρGBM) may delay the onset of grain growth driven by interfacial energy (γGBM). We compared our postdeformation grain growth rates with data from previously published hydrostatic annealing experiments on synthetic olivine. At geologic timescales, the growth rates are much slower than predicted by the existing wet olivine grain growth law.
Life-history strategies of soil microbial communities in an arid ecosystem
Authors: Chen Yongjian , Neilson Julia W , Kushwaha Priyanka , Maier Raina M , Barberán Albert
Published: October 2020

The overwhelming taxonomic diversity and metabolic complexity of microorganisms can be simplified by a life-history classification; copiotrophs grow faster and rely on resource availability, whereas oligotrophs efficiently exploit resource at the expense of growth rate. Here, we hypothesize that community-level traits inferred from metagenomic data can distinguish copiotrophic and oligotrophic microbial communities. Moreover, we hypothesize that oligotrophic microbial communities harbor more unannotated genes. To test these hypotheses, we conducted metagenomic analyses of soil samples collected from copiotrophic vegetated areas and from oligotrophic bare ground devoid of vegetation in an arid-hyperarid region of the Sonoran Desert, Arizona, USA. Results supported our hypotheses, as we found that multiple ecologically informed life-history traits including average 16S ribosomal RNA gene copy number, codon usage bias in ribosomal genes and predicted maximum growth rate were higher for microbial communities in vegetated than bare soils, and that oligotrophic microbial communities in bare soils harbored a higher proportion of genes that are unavailable in public reference databases. Collectively, our work demonstrates that life-history traits can distill complex microbial communities into ecologically coherent units and highlights that oligotrophic microbial communities serve as a rich source of novel functions.
Propranolol-induced inhibition of unconditioned stimulus-reactivated fear memory prevents the return of fear in humans
Authors: Deng Jiahui , Shi Le , Yuan Kai , Yao Ping , Chen Sijing , Que Jianyu , Gong Yimiao , Bao Yanping , Shi Jie , Han Ying , Sun Hongqiang , Lu Lin
Published: October 2020

Fear memories can be reactivated by a fear-associated conditioned stimulus (CS) or unconditioned stimulus (US) and then undergo reconsolidation. Propranolol administration during CS retrieval-induced reconsolidation can impair fear memory that is specific to the reactivated CS. However, from a practical perspective, the US is often associated with multiple CSs, and each CS can induce a fear response. The present study sought to develop and test a US-based memory retrieval interference procedure with propranolol to disrupt the original fear memory and eliminate all CS-associated fear responses in humans. We recruited 127 young healthy volunteers and conducted three experiments. All of the subjects acquired fear conditioning, after which they received the β-adrenergic receptor antagonist propranolol (40 mg) or placebo (vitamin C) and were exposed to the US or CS to reactivate the original fear memory. Fear responses were measured. Oral propranolol administration 1 h before US retrieval significantly decreased subsequent fear responses and disrupted associations between all CSs and the US. However, propranolol administration before CS retrieval only inhibited the fear memory that was related to the reactivated CS. Moreover, the propranolol-induced inhibition of fear memory reconsolidation that was retrieved by the US had a relatively long-lasting effect (at least 2 weeks) and was also effective for remote fear memory. These findings indicate that the US-based memory retrieval interference procedure with propranolol can permanently decrease the fear response and prevent the return of fear for all CSs in humans. This procedure may open new avenues for treating fear-related disorders.
Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids
Authors: Arzua Thiago , Yan Yasheng , Jiang Congshan , Logan Sarah , Allison Reilly L. , Wells Clive , Kumar Suresh N. , Schäfer Richard , Bai Xiaowen
Published: October 2020

Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.
PERK controls bone homeostasis through the regulation of osteoclast differentiation and function
Authors: Guo Jiachao , Ren Ranyue , Sun Kai , Yao Xudong , Lin Jiamin , Wang Genchun , Guo Zhou , Xu Tao , Guo Fengjing
Published: October 2020

Osteoclasts are multinucleated giant cells with the ability to degrade bone tissue, and are closely related to abnormal bone metabolic diseases. Endoplasmic reticulum (ER) is an organelle responsible for protein modification, quality control, and transportation. The accumulation of unfolded or misfolded proteins in ER cavity induces ER stress. Double-stranded RNA-dependent protein kinase-like ER kinase (PERK) is an ER stress-sensing protein, which is ubiquitous in eukaryotic cells. Systemic PERK knockout mice show severe bone loss, suggesting that PERK is of great significance for maintaining the normal growth and development of bone tissue, but the role of PERK in osteoclastogenesis is still unclear. In this study, we found that PERK was significantly activated during RANKL-induced osteoclast differentiation; knockdown of PERK by siRNA and inhibition of PERK by GSK2606414, respectively, had significant negative regulatory effects on the formation and bone resorption of osteoclasts. PERK inhibitor GSK2606414 down-regulated the mRNA levels and protein expression of osteoclast differentiation marker genes, and inhibited RANKL-induced activation of Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Treatment with PERK inhibitor GSK2606414 in ovariectomized mouse model significantly suppressed bone loss and osteoclast formation. Thapsigargin activated ER stress to enhance autophagy, while GSK2606414 had a significant inhibitory effect on autophagy flux and autophagosome formation. Antioxidant N-acetylcysteine (NAC) could inhibit the expression of PERK phosphorylation, osteoclast-related proteins and autophagy-related proteins, but the use of PERK activator CCT020312 can reverse inhibition effect of NAC. Our findings demonstrate a key role for PERK in osteoclast differentiation and suggest its therapeutic potential.
CB13, a novel PPARγ ligand, overcomes radio-resistance via ROS generation and ER stress in human non-small cell lung cancer
Authors: Kim Tae Woo , Hong Da-Won , Hong Sung Hee
Published: October 2020

Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-known therapeutic target for type 2 diabetes as well as is a potential target for effective anti-cancer drug, since PPARγ ligands such as ciglitazone (Cig) frequently cause cell death in many types of cancer cells and suppress tumor growth. However, many cancer patients acquire chemo-resistance or radio-resistance after chemo or radiotherapy, and it is still unclear. In the difficulty of well-known anti-cancer drugs, we developed a novel PPARγ agonist CB13 (1-benzyl-5-(4-methylphenyl) pyrido [2,3-d]pyrimidine-2,4(1H,3H)-dione) and investigated the anti-cancer effect and cell death mechanism on human non-small cell lung cancer (NSCLC) cells. With anti-cancer effect of Cig, CB13 also causes inhibition of cell growth by decreasing cell viability, increasing the release of LDH, and increasing caspase-3, and caspase-9 activities. CB13 generates reactive oxygen species (ROS) and causes cell death via ER stress in NSCLC and radio-resistant NSCLC cells (A549R and H460R), and a combination of CB13 and radiation induces greater ER stress and cell death when compared to CB13 alone. Taken together, our results suggest that a combination of CB13 and radiation may overcome radio-resistance caused by radiotherapy.
Unconventional oil and gas development and ambient particle radioactivity
Authors: Li Longxiang , Blomberg Annelise J. , Spengler John D. , Coull Brent A. , Schwartz Joel D. , Koutrakis Petros
Published: October 2020

Unconventional oil and natural gas development (UOGD) expanded extensively in the United States from the early 2000s. However, the influence of UOGD on the radioactivity of ambient particulate is not well understood. We collected the ambient particle radioactivity (PR) measurements of RadNet, a nationwide environmental radiation monitoring network. We obtained the information of over 1.5 million wells from the Enverus database. We investigated the association between the upwind UOGD well count and the downwind gross-beta radiation with adjustment for environmental factors governing the natural emission and transport of radioactivity. Our statistical analysis found that an additional 100 upwind UOGD wells within 20 km is associated with an increase of 0.024 mBq/m3 (95% confidence interval [CI], 0.020, 0.028 mBq/m3) in the gross-beta particle radiation downwind. Based on the published health analysis of PR, the widespread UOGD could induce adverse health effects to residents living close to UOGD by elevating PR.
Well-being as a function of person-country fit in human values
Authors: Hanel Paul H. P. , Wolfradt Uwe , Wolf Lukas J. , Coelho Gabriel Lins de Holanda , Maio Gregory R.
Published: October 2020

It is often assumed that incongruence between individuals’ values and those of their country is distressing, but the evidence has been mixed. Across 29 countries, the present research investigated whether well-being is higher if people’s values match with those of people living in the same country or region. Using representative samples, we find that person-country and person-region value congruence predict six well-being measures (e.g., emotional well-being, relationship support; N = 54,673). Crucially, however, value type moderates whether person-country fit is positively or negatively associated with well-being. People who value self-direction, stimulation, and hedonism more and live in countries and regions where people on average share these values report lower well-being. In contrast, people who value achievement, power, and security more and live in countries and regions where people on average share these values, report higher well-being. Additionally, we find that people who moderately value stimulation report the highest well-being.
Equatorial mountains on Pluto are covered by methane frosts resulting from a unique atmospheric process
Authors: Bertrand Tanguy , Forget François , Schmitt Bernard , White Oliver L. , Grundy William M.
Published: October 2020

Pluto is covered by numerous deposits of methane, either diluted in nitrogen or as methane-rich ice. Within the dark equatorial region of Cthulhu, bright frost containing methane is observed coating crater rims and walls as well as mountain tops, providing spectacular resemblance to terrestrial snow-capped mountain chains. However, the origin of these deposits remained enigmatic. Here we report that they are composed of methane-rich ice. We use high-resolution numerical simulations of Pluto’s climate to show that the processes forming them are likely to be completely different to those forming high-altitude snowpack on Earth. The methane deposits may not result from adiabatic cooling in upwardly moving air like on our planet, but from a circulation-induced enrichment of gaseous methane a few kilometres above Pluto’s plains that favours methane condensation at mountain summits. This process could have shaped other methane reservoirs on Pluto and help explain the appearance of the bladed terrain of Tartarus Dorsa.
Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits
Authors: Benamer Najate , Vidal Marie , Balia Maddalena , Angulo María Cecilia
Published: October 2020

Myelination of projection neurons by oligodendrocytes is key to optimize action potential conduction over long distances. However, a large fraction of myelin enwraps the axons of parvalbumin-positive fast-spiking interneurons (FSI), exclusively involved in local cortical circuits. Whether FSI myelination contributes to the fine‐tuning of intracortical networks is unknown. Here we demonstrate that FSI myelination is required for the establishment and maintenance of the powerful FSI-mediated feedforward inhibition of cortical sensory circuits. The disruption of GABAergic synaptic signaling of oligodendrocyte precursor cells prior to myelination onset resulted in severe FSI myelination defects characterized by longer internodes and nodes, aberrant myelination of branch points and proximal axon malformation. Consequently, high-frequency FSI discharges as well as FSI-dependent postsynaptic latencies and strengths of excitatory neurons were reduced. These dysfunctions generated a strong excitation-inhibition imbalance that correlated with whisker-dependent texture discrimination impairments. FSI myelination is therefore critical for the function of mature cortical inhibitory circuits.
Gap between pediatric and adult approvals of molecular targeted drugs
Authors: Nishiwaki Satoshi , Ando Yuichi
Published: October 2020

To clarify the approval status of molecular targeted antineoplastic drugs in the United States (U.S.), the European Union (E.U.), and Japan (JP), we checked the status of pediatric indications according to the package insert of each drug. A total of 103 drugs were approved for adult patients in at least one of the three regions whereas only 19 drugs were approved for pediatric patients. Sixty-six of 103 drugs (64.1%) had adult indications in the U.S., the E.U., and JP, whereas only three drugs had pediatric indications in all three regions. Abnormalities in six genes (NRAS, ABL1, JAK2, KIT, ALK and BRAF) were common in childhood cancers as well as adult cancers, for which at least one approved drug could be a potentially actionable drug. Although there were 16 candidate drugs that had adult indications for these abnormalities, only three drugs (18.8%) had pediatric indications. We confirmed that there were few molecular targeted antineoplastic drugs with pediatric indications in the U.S., the E.U., and JP compared with the number of approved drugs for adults. Drugs targeting genomic abnormalities which were common in both adult and pediatric cancers were considered to be good candidates for expansion of their indication for pediatric patients.
Lead (Pb) bioaccumulation and antioxidative responses in Tetraena qataranse
Authors: Usman Kamal , Abu-Dieyeh Mohammed H. , Zouari Nabil , Al-Ghouti Mohammad A.
Published: October 2020

Lead (Pb) is the second most toxic metal on Earth and is toxic to humans and other living things. In plants, Pb commonly inhibits growth when it is at a concentration in the soil of 30 mg/kg or more but several Pb tolerant plants have been reported. However, few studies have focused on plant response to Pb exposure, particularly at concentrations higher than 30 mg/kg. The assessment and evaluation of metal dose-dependent plant responses will assist in future phytoremediation studies. Therefore, this work documents the Pb concentration-dependent antioxidative response in Tetraena qataranse. Young seedlings were irrigated with 0, 25, 50, and 100 mg/L Pb every 48 h for seven weeks under greenhouse conditions. A phytotoxicity test showed that at the lowest treatment concentration, Pb stimulates growth. However, at 100 mg/L (1600 mg/kg Pb in the growth medium at harvest), the metal disrupted healthy growth in T. qataranse, particularly root development. Metal accumulation in the root was higher (up to 2784 mg/kg) than that of the shoot (1141.6 mg/kg). Activity assays of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione reductase (GR) showed a progressive increase in enzymatic activities due to Pb treatment. Together, the results of this study suggest that T. qataranse is a Pb hyperaccumulator. Increased antioxidant enzyme activity was essential to maintaining cellular homeostasis and assisted in the arid plant’s tolerance to Pb stress.
The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population
Authors: Halama Anna , Suleiman Noor N. , Kulinski Michal , Bettahi Ilham , Hassoun Shaimaa , Alkasem Meis , Abdalhakam Ibrahem , Iskandarani Ahmad , Samra Tareq A. , Atkin Stephen L. , Suhre Karsten , Abou-Samra Abdul Badi
Published: October 2020

Metabolic pathways that are corrupted at early stages of insulin resistance (IR) remain elusive. This study investigates changes in body metabolism in clinically healthy and otherwise asymptomatic subjects that may become apparent already under compromised insulin sensitivity (IS) and prior to IR. 47 clinically healthy Arab male subjects with a broad range of IS, determined by hyperinsulinemic-euglycemic clamp (HIEC), were investigated. Untargeted metabolomics and complex lipidomics were conducted on serum samples collected under fasting and HIEC conditions. Linear models were used to identify associations between metabolites concentrations and IS levels. Among 1896 identified metabolites, 551 showed significant differences between fasting and HIEC, reflecting the metabolic switch in energy utilization. At fasting, 336 metabolites, predominantly di- and tri-acylglycerols, showed significant differences between subjects with low and high levels of IS. Changes in amino acid, carbohydrate and fatty acid metabolism in response to insulin were impaired in subjects with low IS. Association of altered mannose and amino acids with IS was also replicated in an independent cohort of T2D patients. We identified metabolic phenotypes that characterize clinically healthy Arab subjects with low levels of IS at their fasting state. Our study is providing further insights into the metabolic pathways that precede IR.
Perceiving amputee gait from biological motion: kinematics cues and effect of experience level
Authors: Lee I.-Chieh , Pacheco Matheus M. , Lewek Michael D. , Huang He
Published: October 2020

Physical therapists (PT) and clinicians must be skilled in identifying gait features through observation to assess motor deficits in patients and intervene appropriately. Inconsistent results in the literature have led researchers to question how clinical experience influences PT’s gait perception and to seek the key kinematic features that should be trained to enhance PT’s skill. Thus, this study investigated (1) what are the informative kinematic features that allow gait-deviation perception in amputee gait and (2) whether there are differences in observational gait skills between PT and individuals with less clinical experience (PT students [PTS] and Novices). We introduced a new method that combines biological motion and principal component analysis to gradually mesh amputee and typical walking patterns. Our analysis showed that on average the accuracy rate in identifying gait deviations between PT and PTS was similar and better than Novices. Also, we found that PT’s experience was demonstrated by their better perception of gait asymmetry. The extracted principal components demonstrated that the major gait deviation of amputees was the medial–lateral body sway and spatial gait asymmetry.
Ectothermy and cardiac shunts profoundly slow the equilibration of inhaled anaesthetics in a multi-compartment model
Authors: Williams Catherine J. A. , Malte Christian Lind , Malte Hans , Bertelsen Mads F. , Wang Tobias
Published: October 2020

The use of inhalational anaesthesia is ubiquitous in terrestrial vertebrates. Given the dependence of these agents on delivery by the cardiorespiratory system, we developed a new computational model predicting equilibration of inhaled anaesthetics in mammalian and ectotherm conditions including the ability of reptiles to maintain vascular shunts. A multi-compartment model was constructed from simultaneously-solved equations, verified by comparison to the literature for endo and ectotherm physiology. The time to 90% equilibration of anaesthetic in arterial blood (t90) is predicted and used to compare anaesthetics and physiologies. The five to tenfold lower cardiac output and minute ventilation of ectothermic vertebrates is predicted to slow equilibration times by five to ten times leading to 90% equilibration in ectotherm arterial blood of over 200 min, compounded by reduction in body temperature, and the extent of right-to-left vascular shunts. The impact of these findings is also influenced by the solubility coefficient of the anaesthetic, such that at net right-to-left shunt fractions of over 0.8, sevoflurane loses the advantage of faster equilibration, in comparison with isoflurane. We explore clinical strategies to regulate anaesthetic uptake in ectotherms by managing convectional flow especially by supportive ventilation and reduction of the right-to-left shunt.
Spirochetes isolated from arthropods constitute a novel genus Entomospira genus novum within the order Spirochaetales
Authors: Graña-Miraglia Lucía , Sikutova Silvie , Vancová Marie , Bílý Tomáš , Fingerle Volker , Sing Andreas , Castillo-Ramírez Santiago , Margos Gabriele , Rudolf Ivo
Published: October 2020

Spirochetal bacteria were successfully isolated from mosquitoes (Culex pipiens, Aedes cinereus) in the Czech Republic between 1999 and 2002. Preliminary 16S rRNA phylogenetic sequence analysis showed that these strains differed significantly from other spirochetal genera within the family Spirochaetaceae and suggested a novel bacterial genus in this family. To obtain more comprehensive genomic information of these isolates, we used Illumina MiSeq and Oxford Nanopore technologies to sequence four genomes of these spirochetes (BR151, BR149, BR193, BR208). The overall size of the genomes varied between 1.68 and 1.78 Mb; the GC content ranged from 38.5 to 45.8%. Draft genomes were compared to 36 publicly available genomes encompassing eight genera from the class Spirochaetes. A phylogeny generated from orthologous genes across all taxa and the percentage of conserved proteins (POCP) confirmed the genus status of these novel spirochetes. The genus Entomospira gen. nov. is proposed with BR151 selected as type species of the genus. For this isolate and the closest related isolate, BR149, we propose the species name Entomospira culicis sp. nov. The two other isolates BR208 and BR193 are named Entomospira nematocera sp. nov. (BR208) and Entomospira entomophilus sp. nov. (BR193). Finally, we discuss their interesting phylogenetic positioning.
Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex
Authors: Manzo Nicoletta , Guerra Andrea , Giangrosso Margherita , Belvisi Daniele , Leodori Giorgio , Berardelli Alfredo , Conte Antonella
Published: October 2020

Near-threshold tactile stimuli perception and somatosensory temporal discrimination threshold (STDT) are encoded in the primary somatosensory cortex (S1) and largely depend on alpha and beta S1 rhythm. Transcranial alternating current stimulation (tACS) is a non-invasive neurophysiological technique that allows cortical rhythm modulation. We investigated the effects of tACS delivered over S1 at alpha, beta, and gamma frequencies on near-threshold tactile stimuli perception and STDT, as well as phase-dependent tACS effects on near-threshold tactile stimuli perception in healthy subjects. In separate sessions, we tested the effects of different tACS montages, and tACS at the individualised S1 μ-alpha frequency peak, on STDT and near-threshold tactile stimuli perception. We found that tACS applied over S1 at alpha, beta, and gamma frequencies did not modify STDT or near-threshold tactile stimuli perception. Moreover, we did not detect effects of tACS phase or montage. Finally, tACS did not modify near-threshold tactile stimuli perception and STDT even when delivered at the individualised μ-alpha frequency peak. Our study showed that tACS does not alter near-threshold tactile stimuli or STDT, possibly due to the inability of tACS to activate deep S1 layers. Future investigations may clarify tACS effects over S1 in patients with focal dystonia, whose pathophysiology implicates increased STDT.
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Authors: Chaccour Carlos , Abizanda Gloria , Irigoyen-Barrio Ángel , Casellas Aina , Aldaz Azucena , Martínez-Galán Fernando , Hammann Felix , Gil Ana Gloria
Published: October 2020

Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80–90 mg/kg), higher dose (110–140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
PIK3CA mutation enrichment and quantitation from blood and tissue
Authors: Keraite Ieva , Alvarez-Garcia Virginia , Garcia-Murillas Isaac , Beaney Matthew , Turner Nicholas C. , Bartos Clare , Oikonomidou Olga , Kersaudy-Kerhoas Maïwenn , Leslie Nicholas R.
Published: October 2020

PIK3CA is one of the two most frequently mutated genes in breast cancers, occurring in 30–40% of cases. Four frequent ‘hotspot’ PIK3CA mutations (E542K, E545K, H1047R and H1047L) account for 80–90% of all PIK3CA mutations in human malignancies and represent predictive biomarkers. Here we describe a PIK3CA mutation specific nuclease-based enrichment assay, which combined with a low-cost real-time qPCR detection method, enhances assay detection sensitivity from 5% for E542K and 10% for E545K to 0.6%, and from 5% for H1047R to 0.3%. Moreover, we present a novel flexible prediction method to calculate initial mutant allele frequency in tissue biopsy and blood samples with low mutant fraction. These advancements demonstrated a quick, accurate and simple detection and quantitation of PIK3CA mutations in two breast cancer cohorts (first cohort n = 22, second cohort n = 25). Hence this simple, versatile and informative workflow could be applicable for routine diagnostic testing where quantitative results are essential, e.g. disease monitoring subject to validation in a substantial future study.