bluuebunny/crossref_metadata_2025 huggingface dataset:
Privacy-aware estimation of relatedness in admixed populations
Authors: Wang Su , Kim Miran , Li Wentao , Jiang Xiaoqian , Chen Han , Harmanci Arif
Published: November 2022

Background

Estimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in third-party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization.

Results

Here, we present SIGFRIED, which makes use of existing reference panels with a projection-based approach that simplifies kinship estimation in the admixed populations. We use simulated and real datasets to demonstrate the accuracy and efficiency of kinship estimation. We present a secure federated kinship estimation framework and implement a secure kinship estimator using homomorphic encryption-based primitives for computing relatedness between samples in two different sites while genotype data are kept confidential. Source code and documentation for our methods can be found at https://doi.org/10.5281/zenodo.7053352.

Conclusions

Analysis of relatedness is fundamentally important for identifying relatives, in association studies, and for estimation of population-level estimates of inbreeding. As the awareness of individual and group genomic privacy is growing, privacy-preserving methods for the estimation of relatedness are needed. Presented methods alleviate the ethical and privacy concerns in the analysis of relatedness in admixed, historically isolated and underrepresented populations.

Short Abstract

Genetic relatedness is a central quantity used for finding relatives in databases, correcting biases in genome wide association studies and for estimating population-level statistics. Methods for estimating genetic relatedness have high computational requirements, and occasionally do not consider individuals from admixed ancestries. Furthermore, the ethical concerns around using genetic data and calculating relatedness are not considered. We present a projection-based approach that can efficiently and accurately estimate kinship. We implement our method using encryption-based techniques that provide provable security guarantees to protect genetic data while kinship statistics are computed among multiple sites.
Ensembles of knowledge graph embedding models improve predictions for drug discovery
Authors: Rivas-Barragan Daniel , Domingo-Fernández Daniel , Gadiya Yojana , Healey David
Published: November 2022

Recent advances in Knowledge Graphs (KGs) and Knowledge Graph Embedding Models (KGEMs) have led to their adoption in a broad range of fields and applications. The current publishing system in machine learning requires newly introduced KGEMs to achieve state-of-the-art performance, surpassing at least one benchmark in order to be published. Despite this, dozens of novel architectures are published every year, making it challenging for users, even within the field, to deduce the most suitable configuration for a given application. A typical biomedical application of KGEMs is drug–disease prediction in the context of drug discovery, in which a KGEM is trained to predict triples linking drugs and diseases. These predictions can be later tested in clinical trials following extensive experimental validation. However, given the infeasibility of evaluating each of these predictions and that only a minimal number of candidates can be experimentally tested, models that yield higher precision on the top prioritized triples are preferred. In this paper, we apply the concept of ensemble learning on KGEMs for drug discovery to assess whether combining the predictions of several models can lead to an overall improvement in predictive performance. First, we trained and benchmarked 10 KGEMs to predict drug–disease triples on two independent biomedical KGs designed for drug discovery. Following, we applied different ensemble methods that aggregate the predictions of these models by leveraging the distribution or the position of the predicted triple scores. We then demonstrate how the ensemble models can achieve better results than the original KGEMs by benchmarking the precision (i.e., number of true positives prioritized) of their top predictions. Lastly, we released the source code presented in this work at https://github.com/enveda/kgem-ensembles-in-drug-discovery.
Sex bias in utero alters ovarian reserve but not uterine capacity in female offspring
Authors: Geijer-Simpson Annika V , Tinning Haidee , De Bem Tiago H C , Tsagakis Ioannis , Taylor Alysha S , Hume Laura , Collins Lisa M , Forde Niamh
Published: November 2022

Environmental stressors to which a fetus is exposed affect a range of physiological functions in postnatal offspring. We aimed to determine the in utero effect of steroid hormones on the reproductive potential of female offspring using a porcine model. Reproductive tracts of pigs from female-biased (>65% female, n = 15), non-biased (45–54.9% female, n = 15), and male-biased litters (<35% females, n = 9) were collected at slaughter (95–115 kg). Ovaries and uterine horns were processed for H&E or immunohistochemistry. Variability of data within groups was analyzed with a Levene’s test, while data were analyzed using mixed linear models in R. In the ovarian reserve, there was a significant birth weight by sex ratio interaction (P = 0.015), with low birth weight pigs from male-biased litters having higher numbers of primordial follicles with opposite trends seen in pigs from female-biased litters. Sex bias held no effect on endometrial gland development. A lower birth weight decreased the proportion of glands found in the endometrium (P = 0.045) and was more variable in both male-biased and female-biased litters (P = 0.026). The variability of primordial follicles from male-biased litters was greater than non- and female-biased litters (P = 0.014). Similarly, endometrial stromal nuclei had a greater range in male- and female-biased litters than non-biased litters (P = 0.028). A crucial finding was the greater variability in primordial follicles in the ovaries from females derived from male-biased litters and stromal cell count in the endometrium of females from male- and female-biased litters. This could be inflating the variability of reproductive success seen in females from male-biased litters.
Postoperative muscle loss, protein intake, physical activity and outcome associations
Authors: Hogenbirk Rianne N M , van der Plas Willemijn Y , Hentzen Judith E K R , van Wijk Laura , Wijma Allard G , Buis Carlijn I , Viddeleer Alain R , de Bock Geertruida H , van der Schans Cees P , van Dam Gooitzen M , Kruijff Schelto , Klaase Joost M
Published: November 2022

Background

Skeletal muscle loss is often observed in intensive care patients. However, little is known about postoperative muscle loss, its associated risk factors, and its long-term consequences. The aim of this prospective observational study is to identify the incidence of and risk factors for surgery-related muscle loss (SRML) after major abdominal surgery, and to study the impact of SRML on fatigue and survival.

Methods

Patients undergoing major abdominal cancer surgery were included in the MUSCLE POWER STUDY. Muscle thickness was measured by ultrasound in three muscles bilaterally (biceps brachii, rectus femoris, and vastus intermedius). SRML was defined as a decline of 10 per cent or more in diameter in at least one arm and leg muscle within 1 week postoperatively. Postoperative physical activity and nutritional intake were assessed using motility devices and nutritional diaries. Fatigue was measured with questionnaires and 1-year survival was assessed with Cox regression analysis.

Results

A total of 173 patients (55 per cent male; mean (s.d.) age 64.3 (11.9) years) were included, 68 of whom patients (39 per cent) showed SRML. Preoperative weight loss and postoperative nutritional intake were statistically significantly associated with SRML in multivariable logistic regression analysis (P < 0.050). The combination of insufficient postoperative physical activity and nutritional intake had an odds ratio of 4.00 (95 per cent c.i. 1.03 to 15.47) of developing SRML (P = 0.045). No association with fatigue was observed. SRML was associated with decreased 1-year survival (hazard ratio 4.54, 95 per cent c.i. 1.42 to 14.58; P = 0.011).

Conclusion

SRML occurred in 39 per cent of patients after major abdominal cancer surgery, and was associated with a decreased 1-year survival.
Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder
Authors: Barber Thomas R , Muhammed Kinan , Drew Daniel , Bradley Kevin M , McGowan Daniel R , Klein Johannes C , Manohar Sanjay G , Hu Michele T M , Husain Masud
Published: November 2022

Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson’s disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson’s disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Furthermore, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. Patients with iRBD present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state.

Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson’s disease by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools.

Using a recently developed incentivized eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with iRBD and compared this with data from 40 patients with Parkinson’s disease and 41 healthy controls. Patients with iRBD also underwent neuroimaging with dopamine transporter SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared with controls and was not significantly different to that in patients with Parkinson’s disease. However, in iRBD patients with normal dopamine transporter SPECT/CT imaging, reward sensitivity was not significantly different from healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals.
Digital Image Anti-Forensic Model Using Exponential Chaotic Biogeography-Based Optimization Algorithm
Authors: Sudhakar Dr R , Rao Dr P V Venkateswara
Published: November 2022

The innovation in visual imagery has led to massive growth in technologies, wherein digital cameras are obtainable at affordable prices. Thus, the digital images are easily captured and processed due to the internet connectivity. On the other hand, the development of strong image editing software facilitated the forgers to manipulate the accessible images with different tampering operations. Several techniques are devised for detecting the forgeries. Accordingly, this paper devises an anti-forensic model, namely Exponentially Weighted Moving Average-Chaotic Biography Based Optimization (E-CBBO) for joint photographic experts group (JPEG) compression to mitigate the forgeries occurred on the internet while transmitting data. The proposed E-CBBO is designed by integrating the properties of the exponentially weighted moving average (EWMA) with the chaotic biography-based optimization (CBBO). The suggested JPEG anti-forensic model is used to eliminate JPEG compression artifacts through the use of unique deblocking, smoothing with dither and decalibration operations. In addition, the goal is to balance visual quality and forensic undetectability when compressing the JPEG image. The fitness function is developed using the structural similarity index (SSIM), universal image quality index (UIQI) and histogram deviation parameters. With a maximum accuracy of 93.2%, a minimal MSE of 0.110, a maximum SSIM of 0.932 and a maximum UIQI of 0.890, the suggested E-CBBO beat existing approaches.
Survival impact of the number of lymph nodes dissection in patients receiving neoadjuvant chemotherapy for esophageal squamous cell carcinoma
Authors: Jiang Duo , Liu Xian-Ben , Xing Wen-Qun , Chen Pei-Nan , Feng Shao-Kang , Yan Sen , Lerut Toni , Sun Hai-Bo
Published: November 2022

This study aimed to investigate the survival impact of the number of lymph nodes dissection (LND) in patients receiving neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed the clinical pathological data and survival of 407 ESCC patients who underwent esophagectomy after NCT between January 2015 and December 2016. The relationship between the number of LNDs and 5-year overall survival (OS) or disease-free survival (DFS) was plotted by using restricted cubic spline analysis. A Cox proportional hazards regression model was used to identify prognostic factors of OS and DFS. We observed an obvious non-linear relationship between LND and the hazard ratios (HRs) for OS (P = 0.0015) and DFS (P < 0.001) of all the patients. In the multivariate analysis of OS and DFS, the number of LNDs (greater than 28 and less than 46) had a significant protective effect on survival (OS: HR: 0.61, 95% CI: 0.42–0.88, P = 0.007; DFS: HR: 0.50, 95% CI: 0.36–0.70, P < 0.001). For patients with nodal metastases, it was also an independent prognostic factor for OS (HR, 0.56, 95% CI, 0.35–0.90, P = 0.017) and DFS (HR, 0.42, 95% CI, 0.28–0.65, P < 0.001). Some degree of lymphadenectomy after NCT was beneficial in improving 5-year OS and DFS for ESCC patients with nodal metastases. For patients with nodal negativity, more extended lymphadenectomy did not improve patient survival.
Trends in smoking-attributable mortality in Spain: 1990–2018
Authors: Rey-Brandariz Julia , Pérez-Ríos Mónica , Santiago-Pérez María Isolina , Galán Iñaki , Schiaffino Anna , Varela-Lema Leonor , Montes Agustín , López-Vizcaíno María Esther , Giraldo-Osorio Alexandra , Candal-Pedreira Cristina , Ruano-Ravina Alberto
Published: November 2022

Background

This study sought to analyse the trend in smoking-attributable mortality (SAM) in Spain among the population aged ≥35 years across the period 1990–2018.

Methods

SAM was estimated by applying a prevalence-independent method, which uses lung cancer (LC) mortality as a proxy of tobacco consumption. We sourced observed mortality from the National Institute of Statistics (Spain), LC mortality rates in smokers and never smokers from the Cancer Prevention Study I–II, and relative risks from 5 US cohorts. Estimates of annual SAM by cause of death, sex and age are shown, along with crude and annual standardised SAM rates. The trend in standardised all-cause and LC rates was analysed using a joinpoint regression model.

Results

Tobacco caused 1 717 150 deaths in Spain in the period 1990–2018. Among men, cancers replaced cardiovascular diseases–diabetes mellitus (CVD–DM) as the leading group of tobacco-related cause of death in 1994. Among women, CVD–DM remained the leading cause of death throughout the period. Trend analysis of standardised SAM rates due to all causes and LC showed a decrease in men and an increase in women.

Conclusions

The tobacco epidemic in Spain across the period 1990–2018 has had an important impact on mortality and has evolved differently in both genders. SAM is expected to increase dramatically in women in the coming years. SAM data highlight the importance of including a gender perspective in SAM analyses, in designing more effective and comprehensive public health interventions and in developing gender-specific tobacco control policies to curb tobacco consumption.
Constitutionalizing care: How can we expand our constitutional imaginary after Covid-19?
Authors: Neo Jaclyn L
Published: November 2022

The Covid-19 pandemic has no doubt caused serious disruptions to lives across the globe. These range from minor inconveniences to major consequences to personal, social, political, economic, and constitutional aspects. With the pandemic still present but its biggest effects waning, this framing article for our symposium on Covid-19 seeks to address the question of whether constitutional law should be rethought, recalibrated to create a more resilient, more egalitarian, and more protective constitutional order. It offers a series of provocations centered around the idea of care as a constitutionalist ideal by which to organize a refreshed post-Covid constitutional order. By care, I mean that which is necessary for the health, welfare, maintenance, and safety of persons. The constitutionalization of care could mean a further reorientation of our constitutional focus from the usual “hard” subjects of constitutionalism, i.e. emergency power, pandemic regulation, and the continued working of the legislature, towards what may, so far, have been marginalized as “soft” constitutional subjects like social relations and families. These, I argue, are critical as Covid-19 has shown us that it is these “soft” constitutional subjects that have had the widest and deepest impact on the ground. This article therefore seeks to reconsider our constitutional epistemology.
Analysis of thermal stress, fatigue life and allowable flux density for the molten salt receiver in solar power tower plants
Authors: Luo Yan , Li Gen , Lu Tao , Wang Ruixing
Published: November 2022

The solar power tower (SPT) receiver design should be able to stand with fatigue damage caused by the passage of clouds, start-up and shut-down. In this paper, to investigate the impacts of incident heat flux distribution and SPT site weather data on the thermal stress, fatigue life and allowable flux density (AFD) of the molten salt receiver, the relationship between the fatigue life and AFD of the tube wall is developed based on the coupled thermal–structural analysis and Miner linear damage theory. The results show that the cosine effect of the circumferential heat flux distribution considered has a significant influence on the location and magnitude of the maximum thermal stress of the tube wall, which lead to the difference in the tube wall fatigue damage. The AFD are, respectively, 829 kW/m2 and 1037 kW/m2 under uniform and cosine circumferential heat flux distributions for the site of Barstow, USA, when the design lifetime of the tube is 30 years. Compared with the SPT site of Barstow, USA, the fatigue damage of the tube wall in Sevilla, Spain, and Delingha, China, are lower under the same conditions due to lower insolation hours of direct normal irradiation in the range of 750–1100 W/m2. The AFD are, respectively, 829 kW/m2, 973 kW/m2 and 997 kW/m2 for the site of Barstow, USA, Sevilla, Spain, and Delingha, China, with 30 years design life. These findings give guidelines for the operation reliability of the SPT molten salt receiver tube.
Lithium-ion battery-supercapacitor energy management for DC microgrids
Authors: Chen Haomeng
Published: November 2022

The energy storage system can sufficiently alleviate the shortage of new energy such as photovoltaic/wind that is greatly affected by the environment. Higher-capacity lithium-ion batteries and higher-power supercapacitors (SCs) are considered ideal energy storage systems for direct current (DC) microgrids, and their energy management is critical. In this paper, a new control strategy is proposed, which adds the feedback compensation of the bus voltage to ensure that the bus voltage can be maintained in a more appropriate range after the energy storage system suppresses the load fluctuation process, meanwhile, considering there are many lithium-ion battery packs in the energy storage system, based on the traditional droop control strategy, the droop coefficient is optimized, so that the battery pack with the higher state of charge (SOC) bears more power to achieve SOC balance with other battery packs. In this paper, the simulation verification is carried out on MATLAB/SIMULINK, the simulation results show that the optimized strategy can effectively suppress the DC bus voltage fluctuation and achieve the SOC of the battery pack balance.
Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients
Authors: Leuzinger Karoline , Kaur Amandeep , Wilhelm Maud , Frank Konstantin , Hillenbrand Caroline A , Weissbach Fabian H , Hirsch Hans H
Published: November 2022

Background

High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis.

Methods

To identify molecular markers of BKPyV replication and disease, we scrutinized BKPyV DNA-loads in longitudinal urine and plasma pairs from 20 HCT patients using quantitative nucleic acid testing (QNAT), DNase-I treatment prior to QNAT, next-generation sequencing (NGS), and tested cell-mediated immunity.

Results

We found that larger QNAT amplicons led to under-quantification and false-negatives results (P < .001). DNase-I reduced urine and plasma BKPyV-loads by >90% (P < .001), indicating non-encapsidated BKPyV genomes. DNase-resistant urine BKPyV-loads remained infectious in cell culture. BKPyV genome fragmentation of ≤250 bp impaired NGS coverage of genetic variation using 1000-bp and 5000-bp amplicons. Conversely, 250-bp amplicons captured viral minority variants. We identified genotype-specific and genotype-independent changes in capsid Vp1 or T-antigen predicted to escape from antibody neutralization or cytotoxic CD8 T-cells, respectively. Genotype-specific changes in immunodominant 9mers were associated with reduced or absent CD8 T-cell responses. Thus, failure to control BKPyV replication in HCT Patients may involve insufficient genotype-specific cytotoxic CD8 T-cell responses, potentially predictable by low neutralizing antibodies as well as genotype-independent immune escape.

Conclusions

Our results provide new insights for patient evaluation and for designing immune protection through neutralizing antibodies, adoptive T-cell therapy, or vaccines.
Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness
Authors: Lind Margaret L , Copin Richard , McCarthy Shane , Coppi Andreas , Warner Fred , Ferguson David , Duckwall Chelsea , Borg Ryan , Muenker M Catherine , Overton John , Hamon Sara , Zhou Anbo , Cummings Derek A T , Ko Albert I , Hamilton Jennifer D , Schulz Wade L , Hitchings Matt D T
Published: November 2022

Background

The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period–based classification as a WGS alternative.

Methods

We conducted a test-negative case-control study among people tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 April and 24 August 2021. Variants were classified using WGS and calendar period.

Results

We included 2029 cases (positive, sequenced samples) and 343 727 controls (negative tests). VE 14–89 days after second dose was significantly higher against Alpha (84.4%; 95% confidence interval [CI], 75.6%–90.0%) than Delta infection (68.9%; 95% CI, 58.0%–77.1%). The odds of Delta infection were significantly higher 90–149 than 14–89 days after second dose (P value = .003). Calendar-period–classified VE estimates approximated WGS-classified estimates; however, calendar-period–based classification was subject to misclassification (35% Alpha, 4% Delta).

Conclusions

Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While calendar-period–classified VE estimates mirrored WGS-classified estimates, our analysis highlights the need for WGS when variants are cocirculating and misclassification is likely.
Russian Discourse on International Criminal Law
Authors: Sayapin Sergey
Published: November 2022

This article argues that Russia’s continued use of force against Ukraine since 2014 has virtually ended the scholarly debate on international criminal law (ICL) in the Russian scholarly community. As shall be seen, mainstream legal and political discourse overlooks the crimes under international law — genocide, crimes against humanity, war crimes and the crime of aggression — allegedly committed by Russian nationals, and effectively reduces ICL to a propaganda tool. Furthermore, Russia is reluctant to cooperate with the International Criminal Court (ICC). Ongoing international and transnational investigations and prosecutions against Russian nationals on charges of alleged crimes under ICL are likely to reinforce Russia’s isolation.
Noetherian Gödel logics
Authors: Aguilera Juan Pablo , Bydžovský Jan , Fernández-Duque David
Published: November 2022

We introduce Noetherian Gödel logics, Gödel logics where the set of truth values is a closed subset of $[0,1]$ containing $0$ and $1$ and without any infinite ascending sequences. There are infinitely many such logics, including the well-known logic $\textsf {G}^\downarrow $ whose set of truth values is $T_\downarrow = \{0\}\cup \{1/n:n\in \mathbb {N}\setminus \{0\}\}$. We compute the complexity of satisfiability and validity for each Noetherian Gödel logic and, in particular, in the logic $\textsf {G}^\downarrow $. This yields optimal strengthening of the results of Baaz–Leitsch–Zach and Hájek
Propagating spatially varying multiplicative shear bias to cosmological parameter estimation for stage-IV weak-lensing surveys
Authors: Cragg Casey , Duncan Christopher A J , Miller Lance , Alonso David
Published: November 2022

We consider the bias introduced by a spatially varying multiplicative shear bias (m-bias) on tomographic cosmic shear angular power spectra. To compute the bias in the power spectra, we estimate the mode-coupling matrix associated with an m-bias map using a computationally efficient pseudo-Cℓ method. This allows us to consider the effect of the m-bias to high ℓ. We then conduct a Fisher matrix analysis to forecast resulting biases in cosmological parameters. For a Euclid-like survey with a spatially varying m-bias, with zero mean and rms of 0.01, we find that parameter biases reach a maximum of $\sim 10 {{\ \rm per\ cent}}$ of the expected statistical error, if multipoles up to ℓmax = 5000 are included. We conclude that the effect of the spatially varying m-bias may be a subdominant but potentially non-negligible contribution to the error budget in forthcoming weak lensing surveys. We also investigate the dependence of parameter biases on the amplitude and angular scale of spatial variations of the m-bias field, and conclude that requirements should be placed on the rms of spatial variations of the m-bias, in addition to any requirement on the mean value. We find that, for a Euclid-like survey, biases generally exceed $\sim 30 {{\ \rm per\ cent}}$ of the statistical error for m-bias rms ∼0.02–0.03 and can exceed the statistical error for rms ∼0.04–0.05. This allows requirements to be set on the permissible amplitude of spatial variations of the m-bias that will arise due to systematics in forthcoming weak lensing measurements.
matryoshka II: accelerating effective field theory analyses of the galaxy power spectrum
Authors: Donald-McCann Jamie , Koyama Kazuya , Beutler Florian
Published: November 2022

In this paper, we present an extension to the matryoshka suite of neural-network-based emulators. The new editions have been developed to accelerate effective field theory of large-scale structure (EFTofLSS) analyses of galaxy power spectrum multipoles in redshift space. They are collectively referred to as the EFTEMU. We test the EFTEMU at the power spectrum level and achieve a prediction accuracy of better than 1 per cent with BOSS-like bias parameters and counterterms on scales 0.001 ≤ k ≤ 0.19 h Mpc−1. We also run a series of mock full-shape analyses to test the performance of the EFTEMU when carrying out parameter inference. Through these mock analyses, we verify that the EFTEMU recovers the true cosmology within 1σ at several redshifts (z = [0.38, 0.51, 0.61]), and with several noise levels (the most stringent of which is Gaussian covariance associated with a volume of 50003 Mpc3 h−3). We compare the mock inference results from the EFTEMU to those obtained with a fully analytic EFTofLSS model and again find no significant bias, whilst speeding up the inference by three orders of magnitude. The EFTEMU is publicly available as part of the matryoshkaPython package.
The Pristine Inner Galaxy Survey (PIGS) – V. A chemo-dynamical investigation of the early assembly of the Milky Way with the most metal-poor stars in the bulge
Authors: Sestito Federico , Venn Kim A , Arentsen Anke , Aguado David , Kielty Collin L , Lardo Carmela , Martin Nicolas F , Navarro Julio F , Starkenburg Else , Waller Fletcher , Carlberg Raymond G , François Patrick , González Hernández Jonay I , Kordopatis Georges , Vitali Sara , Yuan Zhen
Published: November 2022

The investigation of the metal-poor tail in the Galactic bulge provides unique information on the early Milky Way assembly and evolution. A chemo-dynamical analysis of 17 very metal-poor stars (VMP, [Fe/H]<−2.0) selected from the Pristine Inner Galaxy Survey was carried out based on Gemini/GRACES spectra. The chemistry suggests that the majority of our stars are very similar to metal-poor stars in the Galactic halo. Orbits calculated from Gaia EDR3 imply these stars are brought into the bulge during the earliest Galactic assembly. Most of our stars have large [Na,Ca/Mg] abundances, and thus show little evidence of enrichment by pair-instability supernovae. Two of our stars (P171457 and P184700) have chemical abundances compatible with second-generation globular cluster stars, suggestive of the presence of ancient and now dissolved globular clusters in the inner Galaxy. One of them (P171457) is extremely metal-poor ([Fe/H]<−3.0) and well below the metallicity floor of globular clusters, which supports the growing evidence for the existence of lower-metallicity globular clusters in the early Universe. A third star (P180956, [Fe/H]∼−2) has low [Na,Ca/Mg] and very low [Ba/Fe] for its metallicity, which are consistent with formation in a system polluted by only one or a few low-mass supernovae. Interestingly, its orbit is confined to the Galactic plane, like other very metal-poor stars found in the literature, which have been associated with the earliest building blocks of the Milky Way.
High-resolution atmospheric retrievals of WASP-121b transmission spectroscopy with ESPRESSO: Consistent relative abundance constraints across multiple epochs and instruments
Authors: Maguire Cathal , Gibson Neale P , Nugroho Stevanus K , Ramkumar Swaetha , Fortune Mark , Merritt Stephanie R , de Mooij Ernst
Published: November 2022

Recent progress in high-resolution transmission spectroscopy has offered new avenues in which to characterize the atmospheres of transiting exoplanets. High-resolution cross-correlation spectroscopy allows for the unambiguous detection of molecules/atoms. It has also been used to map both atmospheric dynamics and longitudinal variations in the abundance of species across the morning and evening limbs. We present multiple Very Large Telescope (VLT)/Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations (ESPRESSO) observations of the ultrahot Jupiter WASP-121b, from which we constrain relative abundances of various neutral metals consistently across all observations, whilst accounting for the distortion of the exoplanet’s signal caused by traditional data processing techniques. We also constrain planetary orbital velocities and T–P profiles. We compare our abundance constraints with previous constraints using VLT/Ultraviolet and Visual Echelle Spectrograph (UVES) transmission spectroscopy of WASP-121b, and find our results to be consistent between observations, and also in agreement with stellar values for species previously detected in the atmosphere of WASP-121b. Our retrieval framework can also be used to identify potential exospheric species, resulting in extended absorption features beyond the transit equivalent Roche limit of WASP-121b (ReqRL ∼ 1.3 Rp). Hα, Fe ii, and Ca ii were found to extend to high altitudes (1.54 ± 0.04 Rp, 1.17 ± 0.01 Rp, and 2.52 ± 0.34 Rp, respectively), which are broadly consistent with literature values. The consistency of our constraints across multiple high-resolution observations is a strong validation of our model filtering and retrieval framework, as well as the stability of the atmosphere over the time-scales of months/years, and could allow for planet formation processes to be inferred from future ground-based observations of exoplanetary atmospheres.
Challenging the Importance of Plastid Genome Structure Conservation: New Insights From Euglenophytes
Authors: Maciszewski Kacper , Fells Alicja , Karnkowska Anna
Published: November 2022

Plastids, similar to mitochondria, are organelles of endosymbiotic origin, which retained their vestigial genomes (ptDNA). Their unique architecture, commonly referred to as the quadripartite (four-part) structure, is considered to be strictly conserved; however, the bulk of our knowledge on their variability and evolutionary transformations comes from studies of the primary plastids of green algae and land plants. To broaden our perspective, we obtained seven new ptDNA sequences from freshwater species of photosynthetic euglenids—a group that obtained secondary plastids, known to have dynamically evolving genome structure, via endosymbiosis with a green alga. Our analyses have demonstrated that the evolutionary history of euglenid plastid genome structure is exceptionally convoluted, with a patchy distribution of inverted ribosomal operon (rDNA) repeats, as well as several independent acquisitions of tandemly repeated rDNA copies. Moreover, we have shown that inverted repeats in euglenid ptDNA do not share their genome-stabilizing property documented in chlorophytes. We hypothesize that the degeneration of the quadripartite structure of euglenid plastid genomes is connected to the group II intron expansion. These findings challenge the current global paradigms of plastid genome architecture evolution and underscore the often-underestimated divergence between the functionality of shared traits in primary and complex plastid organelles.
Preparing European Nephrology for the next pandemic: lessons from the ERACODA collaboration
Authors: Vart Priya , Duivenvoorden Raphaël , Franssen Casper F M , Hemmelder Marc H , Jager Kitty J , Hilbrands Luuk B , Noordzij Marlies , Abramowicz Daniel , Basile Carlo , Covic Adrian , Crespo Marta , Massy Ziad A , Ortiz Alberto , Emilio Sanchez J , Petridou Emily , White Colin , Gansevoort Ron T
Published: November 2022

Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of a similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss the challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators and researchers.
RAGE ablation attenuates glioma progression and enhances tumor immune responses by suppressing galectin-3 expression
Authors: Zhang Ian Y , Liu Shunan , Zhang Leying , Liang Rongrui , Fang Qingxiao , Zhao Jie , Ren Lyuzhi , Medina Eric F , Filippov Aleksandr , Bonjoc Kimberley-Jane , Chaudhry Ammar , Dayyani Mojtaba , Bild Andrea H , Badie Behnam
Published: November 2022

Background

Malignant gliomas consist of heterogeneous cellular components that have adopted multiple overlapping escape mechanisms that overcome both targeted and immune-based therapies. The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that is activated by diverse proinflammatory ligands present in the tumor microenvironment. Activation of RAGE by its ligands stimulates multiple signaling pathways that are important in tumor growth and invasion. However, treatment strategies that only target the interaction of RAGE with its ligands are ineffective as cancer therapies due to the abundance and diversity of exogenous RAGE ligands in gliomas.

Methods

As an alternative approach to RAGE ligand inhibition, we evaluated the genetic ablation of RAGE on the tumorigenicity of 2 syngeneic murine glioma models. RAGE expression was inhibited in the GL261 and K-Luc gliomas by shRNA and CRSPR/Cas9 techniques prior to intracranial implantation. Tumor growth, invasion, and inflammatory responses were examined by histology, survival, Nanostring, and flow cytometry.

Results

Intracellular RAGE ablation abrogated glioma growth and invasion by suppressing AKT and ERK1/2 activities and by downregulating MMP9 expression. Interestingly, RAGE inhibition in both glioma models enhanced tumor inflammatory responses by downregulating the expression of galectin-3 and potentiated immunotherapy responses to immune checkpoint blockade.

Conclusions

We demonstrated that intracellular RAGE ablation suppresses multiple cellular pathways that are important in glioma progression, invasion, and immune escape. These findings strongly support the development of RAGE ablation as a treatment strategy for malignant gliomas.
Introduction
Authors: Gibson-Light Michael
Published: November 2022

This chapter introduces the reader to Sunbelt State Penitentiary (SSP), the site of eighteen months of ethnographic fieldwork and the setting of this book. Central figures, including working prisoners and correctional staff, are presented. After detailing current knowledge on pre- and post-prison inequalities in the United States, the chapter outlines the book’s central focus: an investigation into how on-the-ground realities in prison—and especially the realities of prison labor—contribute to stratification behind bars. It situates this argument in a historical overview of the importance of labor to American punishment. The book’s theoretical framework is discussed, and chapter summaries are provided.
It’s Like Its Own City
Authors: Gibson-Light Michael
Published: November 2022

This chapter draws on eighteen months of observations behind bars to offer a tour of a medium-security American prison. Through rich ethnographic description, it illuminates the many workplaces where incarcerated men labor today. It then marshals accounts from the imprisoned themselves for insights into what factors are desired—or derided—across diverse prison jobs. These ethnographic and interview data inform a typology of prison jobs. This sets the stage for future chapters to examine how penal laborers navigate the hierarchical prison employment system. Finally, the author details the primary motivations of this research: to unpack the lived experience of contemporary penal labor, to document the factors that influence prison job assignments, and to uncover how inequalities at work behind bars may shape experiences and outlooks for the hundreds of thousands who perform such labor.
Capitals and Punishment
Authors: Gibson-Light Michael
Published: November 2022

This chapter documents various sorting mechanisms through which the prison classifies working prisoners and assigns jobs. It unpacks how individuals with certain arrangements of capital—including prior work experiences, knowledge of labor market conventions, educational certifications, valued presentation styles, and ties to influential others—are privileged in the pursuit of desirable, higher-paying jobs. Groups possessing valued characteristics, knowledge, and resources experience greater mobility in the carceral employment system. Conversely, those lacking in such areas may face additional hurdles to ascending the labor hierarchy behind bars. The chapter thus examines how procedures and practices in the prison job search contribute to social reproduction.
I Owe My Soul to the Commissary Store
Authors: Gibson-Light Michael
Published: November 2022

This chapter examines material disparities resulting from unequal prison labor sorting. It describes the formal economy—centered on the commissary store and institutional services—and the informal economy—comprised of black-market stores, shadow labor, and its own informal currency—within the prison. Across these internal marketplaces, those atop the status hierarchy of prison jobs are often better positioned to provide for themselves, avoid additional scrutiny from security staff, and potentially prepare for their eventual release. Those in less privileged positions, on the other hand, frequently struggle against additional hardships in the face of cost-shifting and other predatory practices. Labor processes thus impact carceral experiences in several overlapping ways.
Conclusion
Authors: Gibson-Light Michael
Published: November 2022

In this concluding chapter, the author extends out from ground-level ethnographic insights to situate the prison fieldsite, Sunbelt State Penitentiary, in its broader political-economic context. It describes historical evolutions in American penology from the old penology of emphasizing crime control through the new penology of prioritizing population control, culminating in the present day’s neoliberal approach to penal punishment and labor. Finally, the chapter presents three possible changes to address issues in contemporary punishment institutions. The prescriptions for change offered here are guided by the insights of imprisoned workers themselves. These range from incremental reform-based approaches to pathways toward more radical transformation.
Toward Nature
Authors: Dews Peter
Published: November 2022

This chapter begins by examining the background to Schelling’s early work in Kant and Fichte. The key influence on a whole generation, Fichte seeks to makes Kant’s approach consistent, by deriving the conditions of experience simply from the self-positing “I.” However, his early philosophy is troubled by the problem of the relation between “transcendental idealism” and “empirical realism.” Fichte cannot decide whether the transcendental standpoint has metaphysical priority over the standpoint of life or is merely an explanatory device. Schelling’s early work seeks to resolve this oscillation, arguing that the structure of being and the structure of knowing must be identical, regarded absolutely. Correspondingly, in his emerging philosophy of nature, he shows, against Kant, that nature must be objectively teleological. Schelling’s “twin-track” conception, in which transcendental philosophy and the philosophy of nature are complementary, leads to a conflict with Fichte, which is fought out in their correspondence around the turn of the century. The two philosophers make valid criticisms of one another, which will influence their subsequent thinking.
Freedom
Authors: Dews Peter
Published: November 2022

In his Philosophical Investigations into the Essence of Human Freedom, published in 1809, Schelling outlines a new approach in which freedom and necessity, and the experiential and the rational, are seen as locked in a relation of productive conflict. He still strives to resolve the conflict, but the concept he ultimately deploys to do so, the “un-ground,” remains problematic. In response, in The Ages of the World (1811–1815), Schelling reconfigures the relation between the a priori logic of modes of being and the temporal world in a quasi-mythological mode and begins to develop a new conception of freedom as “liberation” (Befreyung). However, this conception results in the subjectivity at the heart of the world process becoming trapped in a compulsive “rotary movement.” In his Erlangen lectures of the early 1820s, Schelling seeks to overcome this problem by elaborating a radically transcendent conception of freedom. Eventually he grasps that the move from mythological compulsion to divine or transcendent freedom in his thinking in fact replicates what was originally a world-historical shift in human consciousness, thereby anticipating Karl Jaspers’ notion of an “Axial Age” in world history.
Thinking and Being
Authors: Dews Peter
Published: November 2022

The late stage of Schelling’s philosophy begins toward the end of the 1820s, when he starts to draw a distinction between “positive” and “negative” philosophy. This chapter begins by reviewing Schelling’s historical account of the relation between positive and negative philosophy, from Plato and Aristotle to Kant. It then examines how Schelling theorizes the beginning of the process of a priori thinking, which he terms “negative philosophy.” This leads to a comparison of Schelling’s conception of being, non-being, and nothing with Hegel’s account of the relation between being and nothing at the beginning of his Science of Logic. In contrast to Hegel, Schelling avoids the regress produced when one understands the beginning of pure thinking as an act of radical abstraction, yet must also abstract from the abstraction to establish a positive starting point. The chapter concludes by exploring the basic dialectic of potentialities which provides the framework for Schelling’s late philosophy, showing how this dialectic is generated from the concept of “being-ness” as such.