bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Analysis of N-methyl-2-pyridone-5-carboxamide and N-1-methylnicotinamide in Urine by HPLC with UV Detection
Authors: Nguyen Van Long , Saldanha Roxanne , Fitzpatrick Michael
Published: December 2020

N-methyl-2-pyridone-5-carboxamide (2PYr) and N-1-methylnicotinamide (NMN) are metabolites of the water soluble Vitamin B3 (Nicotinamide). Limited methodologies exist for their dual chromatographic analysis in urine samples. In this study, we developed a method for analysis of both 2PYr and NMN by ultraviolet detection. Urine samples were treated to a salting-out assisted liquid/liquid extraction for the extraction of 2PYr and cation exchange for NMN. Both analytes were separated on a Biphenyl 100 × 2.1 mm, 2.6-μm column. The new assay’s performance (specifically 2PYr) was compared against the existing testing protocol (based on a previously published method). Linearity for both analytes was above 0.99 (r  2) up to a concentration range of: 1500 μmol/L (2PYr) and 150 μmol/L (NMN). Intra-assay and inter-assay precision of the method was below 8% (coefficient of variation) except at the lower limit of quantification where it was below 20%. Recovery of 2PYr was above 80% and NMN above 90%. A significant positive bias was observed with 2PYr against the existing method. This new method allows for both 2PYr and NMN to be chromatographed and overcomes sample preparation issues in urine 2PYr analysis.
Human Immunodeficiency Virus (HIV) Care Models During the Coronavirus Disease 2019 (COVID-19) Era
Authors: Guaraldi Giovanni , Milic Jovana , Martinez Esteban , Kamarulzaman Adeeba , Mussini Cristina , Waters Laura , Pozniak Anton , Mallon Patrick , Rockstroh Jürgen K , Lazarus Jeffrey V
Published: December 2020

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending human immunodeficiency virus (HIV). At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) “three 90s” targets. It outlines how to enhance a patient-centered care approach, now known as the “fourth 90,” by integrating face-to-face patient–physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life, and to preserve intrinsic capacity in all people living with HIV.
Whiskers as a novel tissue for tracking reproductive and stress-related hormones in North Pacific otariid pinnipeds
Authors: Keogh Mandy J , Charapata Patrick , Fadely Brian S , Zeppelin Tonya , Rea Lorrie , Waite Jason N , Burkanov Vladimir , Marshall Chris , Jones Aubree , Sprowls Caitlin , Wooller Matthew J
Published: December 2020

Keratinized tissues, including whiskers, are ideal for acquiring a record of physiological parameters. Most tissues provide a snapshot of physiological status; however, whiskers may support longitudinal sampling for reproductive and stress-related hormones, if hormones are incorporated as whiskers grow and concentrations change with physiological state. Whiskers from female Steller sea lions (Eumetopias jubatus) and northern fur seals (Callorhinus ursinus) were serially sectioned and pulverized and steroid hormones were extracted. Standard methods were used to validate enzyme immunoassay kits for cortisol, progesterone, 17β-estradiol and testosterone. All hormones were measurable in whisker segments from both species with progesterone concentrations showing cyclical patterns, which appear to signify previous pregnancies or luteal phases. Yearly progesterone concentrations were greater in years a pup was produced compared with years when no pup was observed. Free-ranging female Steller sea lions had reproductive rates between 0 and 1.0 (0.53 ± 0.33, n = 12) using a yearly progesterone concentration of 30 pg/mg or greater to classify a reproductive year as producing a pup and below 30 pg/mg as non-reproductive. Cortisol concentrations were greater near the root and rapidly declined, lacking any obvious patterns, throughout the rest of the whisker. Progesterone and testosterone concentrations were able to help determine sex of unknown individuals. Immunohistochemistry revealed that steroid hormones most likely do not leach out of whiskers based on the deposition patterns of progesterone and cortisol being present throughout the whisker length. Overall, measuring steroid hormones in whiskers can reveal individual reproductive histories over multiple years in sea lions and fur seals. Cyclical patterns of δ15N were useful for identifying periods of up to ~10 years of growth within whiskers, and measuring both stable isotopes and hormones may be useful for differentiating periods of active gestation from diapause and potentially track multi-year reproductive histories of female otariids.
Do Viruses From Managed Honey Bees (Hymenoptera: Apidae) Endanger Wild Bees in Native Prairies?
Authors: Pritchard Zoe A , Hendriksma Harmen P , St Clair Ashley L , Stein David S , Dolezal Adam G , O’Neal Matthew E , Toth Amy L
Published: December 2020

Populations of wild and managed pollinators are declining in North America, and causes include increases in disease pressure and decreases in flowering resources. Tallgrass prairies can provide floral resources for managed honey bees (Hymenoptera: Apidae, Apis mellifera Linnaeus) and wild bees. Honey bees kept near prairies may compete with wild bees for floral resources, and potentially transfer viral pathogens to wild bees. Measurements of these potential interactions are lacking, especially in the context of native habitat conservation. To address this, we assessed abundance and richness of wild bees in prairies with and without honey bee hives present, and the potential spillover of several honey bee viruses to bumble bees (Hymenoptera: Apidae, Bombus Latrielle). We found no indication that the presence of honey bee hives over 2 yr had a negative effect on population size of wild bee taxa, though a potential longer-term effect remains unknown. All levels of viruses quantified in bumble bees were lower than those observed in honey bees. Higher levels of deformed wing virus and Israeli acute paralysis virus were found in Bombus griseocollis DeGeer (Hymenoptera: Apidae) collected at sites with hives than those without hives. These data suggest that the presence of honey bees in tallgrass prairie could increase wild bee exposure to viruses. Additional studies on cross-species transmission of viruses are needed to inform decisions regarding the cohabitation of managed bees within habitat utilized by wild bees.
Percutaneous coronary intervention in patients with cancer and readmissions within 90 days for acute myocardial infarction and bleeding in the USA
Authors: Kwok Chun Shing , Wong Chun Wai , Kontopantelis Evangelos , Barac Ana , Brown Sherry-Ann , Velagapudi Poonam , Hilliard Anthony A , Bharadwaj Aditya S , Chadi Alraies M , Mohamed Mohamed , Bhatt Deepak L , Mamas Mamas A
Published: December 2020

Aims

The post-discharge outcomes of patients with cancer who undergo PCI are not well understood. This study evaluates the rates of readmissions within 90 days for acute myocardial infarction (AMI) and bleeding among patients with cancer who undergo percutaneous coronary intervention (PCI).

Methods and results

Patients treated with PCI in the years from 2010 to 2014 in the US Nationwide Readmission Database were evaluated for the influence of cancer on 90-day readmissions for AMI and bleeding. A total of 1 933 324 patients were included in the analysis (2.7% active cancer, 6.8% previous history of cancer). The 90-day readmission for AMI after PCI was higher in patients with active cancer (12.1% in lung, 10.8% in colon, 7.5% in breast, 7.0% in prostate, and 9.1% for all cancers) compared to 5.6% among patients with no cancer. The 90-day readmission for bleeding after PCI was higher in patients with active cancer (4.2% in colon, 1.5% in lung, 1.4% in prostate, 0.6% in breast, and 1.6% in all cancer) compared to 0.6% among patients with no cancer. The average time to AMI readmission ranged from 26.7 days for lung cancer to 30.5 days in colon cancer, while the average time to bleeding readmission had a higher range from 38.2 days in colon cancer to 42.7 days in breast cancer.

Conclusions

Following PCI, patients with cancer have increased risk for readmissions for AMI or bleeding, with the magnitude of risk depending on both cancer type and the presence of metastasis.
Socioeconomic inequality in telephone triage on triage response, hospitalization and 30-day mortality
Authors: Gamst-Jensen Hejdi , Jensen Andrea Nedergaard , Christensen Erika Frischknecht , Lippert Freddy , Brabrand Mikkel , Egerod Ingrid , Thygesen Lau C , Tolstrup Janne S , Huibers Linda
Published: December 2020

We investigated socioeconomic inequality (measured by the indicators highest attained education level and household income) in telephone triage on triage response (face-to-face contact), hospitalization and 30-day mortality among Danish citizens calling the medical helpline 1813 between 23 January and 9 February 2017. The analysis included 6869 adult callers from a larger prospective cohort study and showed that callers with low socioeconomic status (SES) were less often triaged to a face-to-face contact and had higher 30-day mortality than callers with high SES.
Marine Ultrasmall Prokaryotes Likely Affect the Cycling of Carbon, Methane, Nitrogen, and Sulfur
Authors: Lannes Romain , Cavaud Louise , Lopez Philippe , Bapteste Eric
Published: December 2020

Recently, we uncovered the genetic components from six carbon fixation autotrophic pathways in cleaned ultrasmall size fractions from marine samples (<0.22 µm) gathered worldwide by the Tara Oceans Expedition. This first finding suggested that prokaryotic nanoorganisms, phylogenetically distantly related to the known CPR and DPANN groups, could collectively impact carbon cycling and carbon fixation across the world’s ocean. To extend our mining of the functional and taxonomic microbial dark matter from the ultrasmall size fraction from the Tara Oceans Expedition, we investigated the distribution of 28 metabolic pathways associated with the cycling of carbon, methane, nitrogen, and sulfur. For all of these pathways, we report the existence not only of novel metabolic homologs in the ultrasmall size fraction of the oceanic microbiome, associated with nanoorganisms belonging to the CPR and DPANN lineages, but also of metabolic homologs exclusively found in marine host taxa belonging to other (still unassigned) microbial lineages. Therefore, we conclude that marine nanoorganisms contribute to a greater diversity of key biogeochemical cycles than currently appreciated. In particular, we suggest that oceanic nanoorganisms may be involved in a metabolic loop around Acetyl-CoA, have an underappreciated genetic potential to degrade methane, contribute to sustaining redox-reactions by producing Coenzyme F420, and affect sulfur cycling, notably as they harbor a complete suite of homologs of enzymes of the SOX system.
The controls on earthquake ground motion in foreland-basin settings: the effects of basin and source geometry
Authors: O’Kane Aisling , Copley Alex
Published: December 2020

Rapid urban growth has led to large population densities in foreland basin regions, and therefore a rapid increase in the number of people exposed to hazard from earthquakes in the adjacent mountain ranges. It is well known that earthquake-induced ground shaking is amplified in sedimentary basins. However, questions remain regarding the main controls on this effect. It is, therefore, crucial to identify the main controls on earthquake shaking in foreland basins as a step towards mitigating the earthquake risk posed to these regions. We model seismic-wave propagation from range-front thrust-faulting earthquakes in a foreland-basin setting. The basin geometry (depth and width) and source characteristics (fault dip and source-to-basin distance) were varied, and the resultant ground motion was calculated. We find that the source depth determines the amount of near-source ground shaking and the basin structure controls the propagation of this energy into the foreland basin. Of particular importance is the relative length scales of the basin depth and dominant seismic wavelength (controlled by the source characteristics), as this controls the amount of dispersion of surface-wave energy, and so the amplitude and duration of ground motion. The maximum ground motions occur when the basin depth matches the dominant wavelength set by the source. Basins that are shallow compared with the dominant wavelength result in low-amplitude and long-duration dispersed waveforms. However, the basin structure has a smaller effect on the ground shaking than the source depth and geometry, highlighting the need for understanding the depth distribution and dip angles of earthquakes when assessing earthquake hazard in foreland-basin settings.
Inpatient Therapy With Calcineurin Inhibitors in Severe Ulcerative Colitis
Authors: Dwadasi Sujaata , Zafer Maryam , Goens Donald , Paknikar Raghavendra , Dalal Sushila , Cohen Russell D , Pekow Joel , Rubin David T , Sakuraba Atsushi , Micic Dejan
Published: December 2020

Background

Inpatient management of severe ulcerative colitis is complicated by the use of prior immunosuppressant therapies. Our aim was to determine the rate of 1-year colectomy among individuals receiving inpatient calcineurin inhibitor (CNI)-based therapy stratified by prior biologic therapy.

Methods

A retrospective cohort study was performed between January 1, 2013 and April 1, 2018. Only individuals requiring inpatient administration of intravenous cyclosporine or oral tacrolimus were included in the analysis. Individuals were stratified according to prior biologic therapy exposure. The primary outcome of interest was 1-year risk of colectomy. Kaplan-Meier curves were generated for time-to-event data, and regression models were performed to examine the effects of covariates on the clinical endpoint.

Results

Sixty-nine (62.3% male) patients were treated with an inpatient CNI-based therapy and were included in the analysis. Fifteen (21.7%) patients were biologic-naïve, 42 (60.9%) patients had prior exposure to 1 class of biologic therapy, and 12 (17.4%) patients had prior exposure to 2 classes of biologic therapy (third-line CNI therapy). Third-line CNI therapy showed a greater risk of 1-year colectomy risk when compared with the risk for patients who were biologic-naïve (hazard ratio, 3.63; 95% confidence interval, 1.17-13.45; P = 0.025). In a multivariate proportional hazards model, third-line CNI therapy remained significantly associated with 1-year colectomy risk (hazard ratio, 7.94; 95% confidence interval, 1.97-39.76; P = 0.003).

Conclusions

The use of CNI-based therapy in individuals exposed to multiple classes of prior biologic therapies leads to a significantly increased risk of 1-year colectomy. Future studies will be required to compare inpatient management strategies with the expanding novel therapies in UC.
Genetic Diversity and Connectivity in Plant Species Differing in Clonality and Dispersal Mechanisms in Wetland Island Habitats
Authors: Lozada-Gobilard Sissi , Schwarzer Christian , Dyer Rodney , Tiedemann Ralph , Joshi Jasmin
Published: December 2020

In plants, long-distance dispersal is both attenuated and directed by specific movement vectors, including animals, wind, and/or water. Hence, movement vectors partly shape metapopulation genetic patterns that are, however, also influenced by other life-history traits such as clonal growth. We studied the relationship between area, isolation, plant-species richness, reproduction, and dispersal mechanisms with genetic diversity and divergence in 4 widespread wetland plant-species in a total of 20 island-like kettle-hole habitats surrounded by an intensive agricultural landscape. Our results showed that genetic parameters reflect the reproduction strategies with the highest genetic diversity being observed in the non-clonal, outcrossing Oenanthe aquatica compared to the clonal Lycopus europaeus, Typha latifolia, and Phragmites australis. Lycopus showed a positive relationship between genetic diversity and kettle-hole area, but a negative relationship with the number of neighboring kettle holes (less isolation). Genetic diversity increased with plant-species richness in the clonal species Phragmites and Lycopus; while it decreased in the non-clonal Oenanthe. Finally, genetic divergence and, therefore, connectivity differed between alternative dispersal strategies, where wind-dispersed Typha and Phragmites had a higher gene flow between the analyzed kettle holes compared with the insect-pollinated, hydrochorous Lycopus and Oenanthe. Our study provides information on genetic patterns related to reproduction and dispersal mechanisms of 4 common wetland species contributing to the understanding of the functioning of plant metacommunities occurring in kettle holes embedded in agricultural landscapes.
Medical costs of lung cancer care in Japan during the first one or two years after initial diagnosis
Authors: Awano Nobuyasu , Izumo Takehiro , Inomata Minoru , Kuse Naoyuki , Tone Mari , Takada Kohei , Muto Yutaka , Fujimoto Kazushi , Kimura Hitomi , Miyamoto Shingo , Igarashi Ataru , Kunitoh Hideo
Published: December 2020

Objectives

Japan’s healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer.

Methods

We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis—Cohort 1: 2008–2010, Cohort 2: 2011–2014 and Cohort 3: 2015–2018—and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis.

Results

Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P < 0.001), with a median incremental cost of Japanese Yen 6 million during the initial two years. The proportion of outpatient costs increased over time, especially for NSCLC patients (P < 0.001). No changes in costs or survival were observed in SCLC patients.

Conclusions

In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.
Law Development by the International Criminal Court as a Way to Enhance the Protection of Minorities—the Case for Intersectional Consideration of Mass Atrocities
Authors: Maučec Gregor
Published: December 2020

Mass atrocities almost invariably involve the targeting of racial, ethnic, religious and/or political groups. Other groups, such as homosexuals, have also been vulnerable to targeted destruction. Both experience and international case law demonstrate that atrocity crimes have mostly been inflicted on minorities within minorities. With individuals being targeted on several personal grounds or due to overlapping identities (for example, women and girls belonging to ethnic or religious minorities) there is a strong case for both scholarship and international criminal judiciary to develop an expertise on intersectional discrimination in the context of international crimes that implicate discriminatory intent of a perpetrator. Yet, the International Criminal Court (ICC or Court) has tended to consider atrocities motivated by discrimination on isolated discriminatory grounds and independently from each other. As a prescriptive contribution, the present article challenges this trend by arguing that in more complex criminal cases the protected characteristics need to be considered together with, and not separately from, one another, in order to capture the multi-faceted experiences of mass abuses. Underlying the treatment of the subject matter are thus two basic questions: first, given a full respect for the principle of legality (nullum crimen sine lege), what are the possible avenues for international criminal adjudication to recognize intersectionality so as to overcome conceptual flaws and limitations of single-issue analysis of discrimination in cases involving core international crimes against minorities? For example, can Article 21(3) of the Rome Statute on the interpretation and application of substantive international criminal law in light of international human rights standards serve as a viable tool for the Court to evolve its jurisprudence on this particular issue? Second, how and to what extent should the Court take intersectionality into consideration in the formulation of charges; identification and interpretation of applicable law; determination of criminal sentence; ordering adequate remedies (reparations) for victims; and in considering such aspects as the gravity assessment, or the contextualisation of crimes? Answering these questions, the article shows that by applying, interpreting and, when need be, developing international criminal law in a way that utilizes intersectionality the ICC can make in these areas important jurisprudential contributions with far-reaching socio-legal implications.
Changes in soil microbial community structure and function following degradation in a temperate grassland
Authors: Yu Yang , Zheng Lang , Zhou Yijun , Sang Weiguo , Zhao Jianing , Liu Lu , Li Chao , Xiao Chunwang
Published: December 2020

Aims

Grassland degradation represents a major challenge in the maintenance of grassland productivity. This process has dramatic impacts on energy flows and soil nutrient dynamics, thus directly or indirectly influencing soil microbes. Here, we aim to (i) examine changes in soil microbial composition, diversity and functionality in response to different levels of grassland degradation (i.e. non-degraded, moderately and severely degraded) in a temperate grassland in Inner Mongolia, and (ii) elucidate biotic and abiotic factors that are responsible for these changes.

Methods

The composition structure of soil microbial community was determined by high-throughput sequencing. The functionality of bacterial communities was examined using the tool of FAPROTAX, and functional guilds of fungal communities were quantified using the FUNGuild pipeline.

Important Findings

Grassland degradation significantly decreased soil bacterial diversity but it did not affect fungal diversity. Belowground biomass, soil organic carbon and total nitrogen were positively related to changes in diversity of bacterial community. Grassland degradation significantly increased the relative abundance of Chloroflexi (from 2.48% to 8.40%) and decreased Firmicutes (from 3.62% to 1.08%) of bacterial community. Degradation also significantly increased the relative abundance of Glomeromycota (from 0.17% to 1.53%) and decreased Basidiomycota (from 19.30% to 4.83%) of fungal community. The relative abundance of pathogenic fungi (Didymella and Fusarium) was decreased significantly by degradation. In addition, degradation had a significant impact on putative functionality of soil bacteria related to soil carbon and nitrogen cycling. Our results suggest that soil bacterial community is more sensitive than fungal community in response to degradation in the temperate grassland.
Development of raster scanning IMRT using a robotic radiosurgery system
Authors: Shiomi Hiroya , Akino Yuichi , Sumida Iori , Masai Norihisa , Oh Ryoong-Jin , Ogawa Kazuhiko
Published: December 2020

Treatment time with the CyberKnife frameless radiosurgery system is prolonged due to the motion of the robotic arm. We have developed a novel scanning irradiation method to reduce treatment time. We generated treatment plans mimicking eight-field intensity-modulated radiotherapy (IMRT) plans generated for the Novalis radiosurgery system. 2D dose planes were generated with multiple static beam spots collimated by a fixed circular cone. The weights of the uniformly distributed beam spots in each dose plane were optimized using the attraction–repulsion model. The beam spots were converted to the scanning speed to generate the raster scanning plan. To shorten treatment time, we also developed a hybrid scanning method which combines static beams with larger cone sizes and the raster scanning method. Differences between the Novalis and the scanning plan’s dose planes were evaluated with the criterion of a 5% dose difference. The mean passing rates of three cases were > 85% for cone sizes ≤ 12.5 mm. Although the total monitor units (MU) increased for smaller cone sizes in an inverse-square manner, the hybrid scanning method greatly reduced the total MU, while maintaining dose distributions comparable to those with the Novalis plan. The estimated treatment time of the hybrid scanning with a 12.5 mm cone size was on average 22% shorter than that of the sequential plans. This technique will be useful in allowing the CyberKnife with conventional circular cones to achieve excellent dose distribution with a shortened treatment time.
Molecular and functional analysis of a brown planthopper resistance protein with two nucleotide-binding site domains
Authors: Wang Zhizheng , Huang Jin , Nie Lingyun , Hu Yinxia , Zhang Ning , Guo Qin , Guo Jianping , Du Bo , Zhu Lili , He Guangcun , Chen Rongzhi
Published: December 2020

The brown planthopper (Nilaparvata lugens Stål, BPH) resistance gene BPH9 encodes an unusual coiled-coil (CC) nucleotide-binding leucine-rich repeat (LRR) protein with two nucleotide-binding site (NBS) domains. To understand how this CC–NBS–NBS–LRR (CNNL) protein regulates defense signaling and BPH resistance, we dissected each domain’s functions. The CC domain of BPH9 self-associated and was sufficient to induce cell death. The region of 97–115 residues in the CC domain is crucial for self-association and activation. NBS2, which contains a complete set of NBS function motifs and inhibits CC domain activation, rather than NBS1, acts as a molecular switch to regulate the activity of BPH9. We demonstrated that the CC domain, the NBS domain, and the LRR domain of BPH9 associate with each other and themselves in planta. Further domain swapping experiments revealed that the CC domains of BPH9 and susceptible alleles were similarly competent to induce resistance and the hypersensitive response, while the LRR domain of BPH9 confers resistance specificity to BPH. These findings provide new insights into the regulatory mechanisms governing the activity of CNNL proteins.
One Trend, a Patchwork of Laws. An Exploration of Why Cohabitation Law is so Different throughout the Western World
Authors: Goossens Elise
Published: December 2020

Western jurisdictions have adopted remarkably diverging legal approaches to address unmarried cohabitation, ranging between contractual approaches, registered partnerships, and default regimes. This article explores to what extent the large diversity in cohabitation law is prompted by socio-demographic factors, legal tradition and family ideology. The experiences from Belgium, Sweden, England and Wales, New Zealand, and the United States suggest that cohabitation law is mostly ideologically motivated, with socio-demographic factors only having a minor impact. Diverging views on the preservation of the traditional family and the autonomy versus protection of the vulnerable partner-spectrum, in particular, seem to form the backbone of a jurisdiction’s preference for a contractual approach, a registered partnership, or a default regime. Path dependency brings an important nuance to this model. Because existing rights and benefits often prove difficult to turn back, a shift in policy generally fails to eliminate all traces of the former legal framework.
Type inhabitation of atomic polymorphism is undecidable
Authors: Protin M Clarence
Published: December 2020

Atomic polymorphism $\mathbf{F_{at}}$ is a restriction of Girard and Reynold’s system $\mathbf{F} $(or $\lambda 2$) which was first introduced in Ferreira [ 2] in the context of a philosophical commentary on predicativism. $\lambda 2$ is a well-known and powerful formal tool for studying polymorphic functional programming languages and formal methods in program specification and development, but its computational power far exceeds the recursive level of interest in applications. Hence, the interest of studying subsystems of $\lambda 2$ with weaker computational power. $\mathbf{F_{at}}$ is defined by restricting instantiation to atomic variables only. It turns out that the type system is still sufficiently powerful to possess embeddings of full intuitionistic propositional calculus [ 3, 4], and since the calculus has fewer connectives and strong normalizability is simple to prove [ 3], this result allows us to circumvent many of the extra computational complexities present when dealing with the proof theory of IPC. It is natural to inquire whether type inhabitation, i.e. provability in the corresponding fragment of second-order intuitionistic propositional logic, is decidable or not and in general to see whether the negative results involving the undecidability of type inhabitation, typability and type-checking for $\mathbf{F}$ still hold in this fragment. A further theme would be to study the result of adding type constructors, recursors or even dependent types to $\mathbf{F_{at}}$. In this paper, we show that type inhabitation for $\mathbf{F_{at}}$ is undecidable by codifying within it an undecidable fragment of first-order intuitionistic predicate calculus, adapting and modifying the technique of Urzyczyn’s [ 1, 7] purely syntactic proof of the undecidability of type inhabitation for $\mathbf{F}$.
Dissecting the stellar content of Leo I: a dwarf irregular caught in transition
Authors: Ruiz-Lara T , Gallart C , Monelli M , Fritz T K , Battaglia G , Cassisi S , Aznar M Luis , Russo Cabrera A V , Rodríguez-Martín I , Salazar-González J J
Published: December 2020

Leo I is considered one of the youngest dwarf spheroidals (dSph) in the Local Group. Its isolation, extended star formation history (SFH), and recent perigalacticon passage (∼1 Gyr ago) make Leo I one of the most interesting nearby stellar systems. Here, we analyse deep photometric Hubble Space Telescope data via colour–magnitude diagram fitting techniques to study its global and radially resolved SFH. We find global star formation enhancements in Leo I ∼13, 5.5, 2.0, and 1.0 Gyr ago, after which it was substantially quenched. Within the context of previous works focused on Leo I, we interpret the most ancient and the youngest ones as being linked to an early formation (surviving reionization) and the latest perigalacticon passage (transition from dIrr to dSph), respectively. We clearly identify the presence of very metal poor stars ([Fe/H] ∼ −2) ageing ∼5–6 and ∼13 Gyr old. We speculate with the possibility that this metal-poor population in Leo I is related to the merging with a low-mass system (possibly an ultra-faint dwarf). This event would have triggered star formation (peak of star formation ∼5.5 Gyr ago) and accumulated old, metal-poor stars from the accreted system in Leo I. Some of the stars born during this event would also form from accreted gas of low-metallicity (giving rise to the 5–6 Gyr low-metallicity tail). Given the intensity and extension of the 2.0 Gyr burst, we hypothesize that this enhancement could also have an external origin. Despite the quenching of star formation around 1 Gyr ago (most probably induced by ram pressure stripping with the Milky Way halo at pericentre), we report the existence of stars as young as 300–500 Myr. We also distinguish two clear spatial regions: the inner ∼190 pc presents a homogeneous stellar content (size of the gaseous star forming disc in Leo I from ∼4.5 to 1 Gyr ago), whereas the outer regions display a clear positive age gradient.
The twisted dark matter halo of the Milky Way
Authors: Shao Shi , Cautun Marius , Deason Alis , Frenk Carlos S
Published: December 2020

We analyse systems analogous to the Milky Way (MW) in the eagle cosmological hydrodynamics simulation in order to deduce the likely structure of the MW’s dark matter (DM) halo. We identify MW mass haloes in the simulation whose satellite galaxies have similar kinematics and spatial distribution to those of the bright satellites of the MW, specifically systems in which the majority of the satellites (8 out of 11) have nearly coplanar orbits that are also perpendicular to the central stellar disc. We find that the normal to the common orbital plane of the coplanar satellites is well aligned with the minor axis of the host DM halo, with a median misalignment angle of only 17.3°. Based on this result, we infer that the minor axis of the Galactic DM halo points towards (l, b) = (182°, −2°), with an angular uncertainty at the 68 and 95 percentile confidence levels of 22° and 43°, respectively. Thus, the inferred minor axis of the MW halo lies in the plane of the stellar disc. The halo, however, is not homologous and its flattening and orientation vary with radius. The inner parts of the halo are rounder than the outer parts and well aligned with the stellar disc (that is the minor axis of the halo is perpendicular to the disc). Further out, the halo twists and the minor axis changes direction by 90°. This twist occurs over a very narrow radial range and reflects variations in the filamentary network along which mass was accreted into the MW.
Stability constrained characterization of multiplanet systems
Authors: Tamayo Daniel , Gilbertson Christian , Foreman-Mackey Daniel
Published: December 2020

Many discovered multiplanet systems are tightly packed. This implies that wide parameter ranges in masses and orbital elements can be dynamically unstable and ruled out. We present a case study of Kepler-23, a compact three-planet system where constraints from stability, transit timing variations (TTVs), and transit durations can be directly compared. We find that in this tightly packed system, stability can place upper limits on the masses and orbital eccentricities of the bodies that are comparable to or tighter than current state of the art methods. Specifically, stability places 68 per cent upper limits on the orbital eccentricities of 0.09, 0.04, and 0.05 for planets b, c, and d, respectively. These constraints correspond to radial velocity signals ≲ 20 cm s−1, are significantly tighter to those from transit durations, and comparable to those from TTVs. Stability also yields 68 per cent upper limits on the masses of planets b, c, and d of 2.2, 16.1, and 5.8 M⊕, respectively, which were competitive with TTV constraints for the inner and outer planets. Performing this stability constrained characterization is computationally expensive with N-body integrations. We show that SPOCK, the Stability of Planetary Orbital Configurations Klassifier, is able to faithfully approximate the N-body results over 4000 times faster. We argue that such stability constrained characterization of compact systems is a challenging ‘needle-in-a-haystack’ problem (requiring removal of 2500 unstable configurations for every stable one for our adopted priors) and we offer several practical recommendations for such stability analyses.
Intracellular nickel accumulation induces apoptosis and cell cycle arrest in human astrocytic cells
Authors: Yubolphan Ruedeemars , Phuagkhaopong Suttinee , Sangpairoj Kant , Sibmooh Nathawut , Power Christopher , Vivithanaporn Pornpun
Published: December 2020

Nickel, a heavy metal found in electronic wastes and fume from electronic cigarettes, induces neuronal cell death and is associated with neurocognitive impairment. Astrocytes are the first line of defense against nickel after entering the brain; however, the effects of nickel on astrocytes remain unknown. Herein, we investigated the effect of nickel exposure on cell survival and proliferation and the underlying mechanisms in U-87 MG human astrocytoma cells and primary human astrocytes. Intracellular nickel levels were elevated in U-87 MG cells in a dose- and time-dependent manner after exposure to nickel chloride. The median toxic concentrations of nickel in astrocytoma cells and primary human astrocytes were 600.60 and >1000 µM at 48 h post-exposure, respectively. Nickel exposure triggered apoptosis in concomitant with the decreased expression of anti-apoptotic B-cell lymphoma protein (Bcl-2) and increased caspase-3/7 activity. Nickel induced reactive oxygen species formation. Additionally, nickel suppressed astrocyte proliferation in a dose- and time-dependent manner by delaying G2 to M phase transition through the upregulation of cyclin B1 and p27 protein expression. These results indicate that nickel-induced cytotoxicity of astrocytes is mediated by the activation of apoptotic pathway and disruption of cell cycle regulation.
Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells
Authors: Bonner Erin R , Waszak Sebastian M , Grotzer Michael A , Mueller Sabine , Nazarian Javad
Published: December 2020

ONC201 is the first member of the imipridone family of anticancer drugs to enter the clinic for the treatment of diverse solid and hematologic cancers. A subset of pediatric and adult patients with highly aggressive brain tumors has shown remarkable clinical responses to ONC201, and recently, the more potent derivative ONC206 entered clinical trials as a single agent for the treatment of central nervous system (CNS) cancers. Despite the emerging clinical interest in the utility of imipridones, their exact molecular mechanisms are not fully described. In fact, the existing literature points to multiple pathways (e.g. tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) signaling, dopamine receptor antagonism, and mitochondrial metabolism) as putative drug targets. We have performed a comprehensive literature review and highlighted mitochondrial metabolism as the major target of imipridones. In support of this, we performed a meta-analysis of an ONC201 screen across 539 human cancer cell lines and showed that the mitochondrial caseinolytic protease proteolytic subunit (ClpP) is the most significant predictive biomarker of response to treatment. Herein, we summarize the main findings on the anticancer mechanisms of this potent class of drugs, provide clarity on their role, and identify clinically relevant predictive biomarkers of response.
Epidemiology of brainstem high-grade gliomas in children and adolescents in the United States, 2000-2017
Authors: Patil Nirav , Kelly Michael E , Yeboa Debra Nana , Buerki Robin A , Cioffi Gino , Balaji Sweta , Ostrom Quinn T , Kruchko Carol , Barnholtz-Sloan Jill S
Published: December 2020

Background

Limited population-based data exist for the brainstem gliomas for children ages ≤19 years, which includes high-grade aggressively growing tumors such as diffuse intrinsic pontine glioma (DIPG). We examined the overall incidence and survival patterns in children with brainstem high-grade glioma (HGG) by age, sex, and race and ethnicity.

Methods

We used data from Central Brain Tumor Registry of the United States (CBTRUS), obtained through data use agreements with the Centers for Disease Control (CDC) and the National Cancer Institute (NCI) from 2000 to 2017, and survival data from the CDCs National Program of Cancer Registries (NPCR), from 2001 to 2016 for malignant brainstem HGG for ages ≤19 years (per WHO ICD-O-3 codes). HGG was determined by established histologic and/or imaging criteria. Age-adjusted incidence rates and survival data were used to assess differences overall and by age, sex race, and ethnicity.

Results

The incidence of brainstem HGG was higher among the female and Non-Hispanic population. Majority (69.8%) of these tumors were diagnosed radiographically. Incidence was higher in children aged 1-9 years compared to older children. Whites had a higher incidence compared to Blacks. However, the risk of death was higher among Blacks and Other race compared to Whites. There was no difference in survival by sex.

Conclusions

We report the most comprehensive incidence and survival data on these lethal brainstem HGGs. Incidence and survival among patients with brainstem HGGs differed significantly by race, ethnicity, age-groups, and grade.
Acute Effects of Heated Tobacco Product (IQOS) Aerosol Inhalation on Lung Tissue Damage and Inflammatory Changes in the Lungs
Authors: Bhat Tariq A , Kalathil Suresh G , Leigh Noel , Muthumalage Thivanka , Rahman Irfan , Goniewicz Maciej L , Thanavala Yasmin M
Published: December 2020

Introduction

Emerging heated tobacco products (HTPs) were designed to reduce exposure to toxicants from cigarette smoke (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP called IQOS, on lung damage and immune-cell recruitment to the lungs in mice.

Methods

Numerous markers of lung damage and inflammation including albumin and lung immune-cell infiltrates, proinflammatory cytokines, and chemokines were quantified in lungs and bronchoalveolar (BAL) fluid from IQOS, CS, or air-exposed (negative control) mice.

Results

Importantly, as a surrogate marker of lung epithelial-cell damage, we detected significantly increased levels of albumin in the BAL fluid of both HTP- and CS-exposed mice compared with negative controls. Total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS aerosols and CS inhalation and significantly increased compared with air-exposed controls. We also observed significantly increased numbers of CD4+IL-17A+ T cells, a marker of a T-cell immune response, in both groups compared with air controls; however, numbers were the highest following CS exposure. Finally, the numbers of CD4+RORγt+ T cells, an inflammatory T-cell subtype expressing the transcription factor that is essential for promoting differentiation into proinflammatory Th17 cells, were significantly augmented in both groups compared with air-exposed controls. Levels of several cytokines in BAL were significantly elevated, reflecting a proinflammatory milieu.

Conclusions

Our study demonstrates that short-term inhalation of aerosols from IQOS generates damage and proinflammatory changes in the lung that are substantially similar to that elicited by CS exposure.

Implications

Exposure of mice to IQOS, one of the candidate modified-risk tobacco products, induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the BAL fluid. Such an exacerbated pulmonary proinflammatory microenvironment is associated with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function.
The Japan-South Korea Rift
Authors: Sakaki Alexandra
Published: December 2020

Although Japan–South Korea relations have been volatile throughout the postwar era, ties deteriorated to an unprecedented degree after 2011, with mutual mistrust hitting unseen heights. Focusing on this time period, the chapter analyzes the causes of the downturn. Previous studies show that bilateral tensions stem from clashes in the two countries’ national identity conceptions and historical disagreements more generally. While this chapter acknowledges the continuing relevance of these underlying sources of friction, it argues that ties have come under additional pressure from two spheres. First, pressure has built from the “inside”—the domestic-societal contexts—pushing the respective political leaders, who are mindful of public support and electoral effects, toward more nationalist positions vis-à-vis the other country. Consequently, the political room for mutual accommodation and compromise has shrunk. Second, pressure has built from the “outside”—from changes in the international arena. Tokyo and Seoul hold differing views on how to prioritize and respond to key international challenges, sowing mutual strategic mistrust. At the same time, Japan’s relative importance to Korea has fallen amid shifting economic ties in the region. With rising pressure from both “inside” and “outside,” the traditional bonds underpinning mutual cooperation have eroded, sending relations to their lowest point in the history of bilateral normalized relations since 1965.
For a Sociology of Sectarianism
Authors: Majed Rima
Published: December 2020

This chapter offers an overview of the study of sectarianism in the Middle East. It argues that, because it has often been treated as an area studies topic, the study of sectarianism has long been absent from mainstream sociological literature. By bridging between disciplinary knowledge production and the area-specific research agenda, this chapter proposes some conceptual and methodological notes to advance an understanding of the sectarian phenomenon in the Middle East. This chapter is a call for the development of a “sociology of sectarianism,” one that moves beyond Middle East exceptionalism to study the phenomenon of sectarianism in its complexity by locating it historically and analyzing it globally within the broader interlocking systems of social stratification.
The Transformation of Islamic Law in Modernity
Authors: March Andrew F.
Published: December 2020

In the process of modernizing Muslim majority states in the 19th and 20th centuries, Islamic law was often replaced with foreign legal codes. But in many areas of the law, Islamic legal norms were not replaced but rather transformed from an uncodified “jurists’ law” applied by qadis into legal codes applied by sovereign states. This process involved the transformation of not only many aspects of the substance of Islamic law, but also the methods, agents, and epistemologies by which Islamic law is known and enforced. This chapter explores this revolution in Islamic law from the 19th-century Ottoman Tanzimat reforms to the 20th-century national appropriations of Islamic law in a few select areas, particularly family and personal status law.
Peaceful Change in Northeast Asia
Authors: Singh Bhubhindar
Published: December 2020

Northeast Asia is usually associated with conflict and war. Out of the five regional order transitions from the Sinocentric order to the present post–Cold War period, only one was peaceful, the Cold War to post–Cold War transition. In fact, the peaceful transition led to a state of minimal peace in post–Cold War Northeast Asia. As the chapter discusses, this was due to three realist-liberal factors: America’s hegemonic role, strong economic interdependence, and a stable institutional structure. These factors not only ensured development and prosperity but also mitigated the negative effects of political and strategic tensions between states. However, this minimal peace is in danger of unraveling. Since 2010, the region is arguably in the early stages of another transition fueled by the worsening Sino-US competition. While the organizing ideas of liberal internationalism—economic interdependence and institutional building—will remain resilient, whether or not minimal peace is sustainable will be determined by the outcome of the US-China competition.
Trash: Language, Sexuality, and Social Class
Authors: Barrett Rusty
Published: December 2020

This chapter considers four linguistic areas related to the intersection of sexuality and social class. The first is the link among sexual promiscuity, stereotypes of working-class sexuality, and ideologies of “vulgar” or “obscene” language. The second area considers the role of class in patterns of language change and changes in sexual normativity, both of which show movement from the middle class outward. The third area considered is the relationship between stereotypes of social class and LGBTQ+ identities, where negative portrayals of the working class remain constant across contrasting views of LGBTQ+ identities. The final area considered is the way in which language related to sexuality reproduces social forms of class inequality, particularly though diminishing the potential for sexual pleasure among the working class.