bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-induction With Intravenous Ustekinumab in Patients With Crohn’s Disease and a Loss of Response to This Therapy
Authors: Bermejo Fernando , Jiménez Laura , Algaba Alicia , Vela Milagros , Bastida Guillermo , Merino Olga , López-García Alicia , Melcarne Luigi , Rodríguez-Lago Iago , de la Maza Saioa , Bouhmidi Abdel , Barreiro-de Acosta Manuel , López-Serrano Pilar , Carrillo-Palau Marta , Mesonero Francisco , Orts Beatriz , Bonillo Daniel , Granja Alicia , Guerra Iván
Published: February 2021

Background

A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn’s disease who have lost the response to the treatment.

Methods

This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected.

Results

Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed.

Conclusion

Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn’s disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.
What Is the Monumental?
Authors: Shapshay Sandra
Published: February 2021

The aesthetic category of the sublime has been theorized (especially in the Kantian tradition) as integrally intertwined with the moral. Paradigmatic experiences of the sublime, such as gazing up at the starry night sky, or out at a storm-whipped sea, lead in a moral or religious direction depending on the cognitive stock brought to the experience, since they typically involve a feeling of awe and reflection on the peculiar situation of the human being in nature. The monumental is a similar aesthetic category, integrally intertwined with the political, but, by contrast, has garnered almost no attention from aestheticians. My main goal in this paper is to sketch a theory of ‘the monumental’ as an aesthetic category—one that is a species of the sublime but differs qualitatively from the natural/environmental sublime in significant ways, and thus merits a distinctive label. In doing so, I aim to shed light on the nature and power of monuments specifically, and to begin to address a lacuna in our understanding of a long-standing and culturally important form of public art.
A novel particle swarm optimization-based grey model for the prediction of warehouse performance
Authors: Islam Md Rakibul , Ali Syed Mithun , Fathollahi-Fard Amir Mohammad , Kabir Golam
Published: February 2021

Warehouses constitute a key component of supply chain networks. An improvement to the operational efficiency and the productivity of warehouses is crucial for supply chain practitioners and industrial managers. Overall warehouse efficiency largely depends on synergic performance. The managers preemptively estimate the overall warehouse performance (OWP), which requires an accurate prediction of a warehouse’s key performance indicators (KPIs). This research aims to predict the KPIs of a ready-made garment (RMG) warehouse in Bangladesh with a low forecasting error in order to precisely measure OWP. Incorporating advice from experts, conducting a literature review, and accepting the limitations of data availability, this study identifies 13 KPIs. The traditional grey method (GM)—the GM (1, 1) model—is established to estimate the grey data with limited historical information but not absolute. To reduce the limitations of GM (1, 1), this paper introduces a novel particle swarm optimization (PSO)-based grey model—PSOGM (1, 1)—to predict the warehouse’s KPIs with less forecasting error. This study also uses the genetic algorithm (GA)-based grey model—GAGM (1, 1)—the discrete grey model—DGM (1, 1)—to assess the performance of the proposed model in terms of the mean absolute percentage error and other assessment metrics. The proposed model outperforms the existing grey models in projecting OWP through the forecasting of KPIs over a 5-month period. To find out the optimal parameters of the PSO and GA algorithms before combining them with the grey model, this study adopts the Taguchi design method. Finally, this study aims to help warehouse professionals make quick OWP estimations in advance to take control measures regarding warehouse productivity and efficiency.
Comparison of Fluctuating Thermal Regimes and Commercially Achievable Constant-Temperature Regimes for Short-Term Storage of the Alfalfa Leafcutting Bee (Hymenoptera: Megachilidae)
Authors: Yocum George D , Rajamohan Arun , Rinehart Joseph P
Published: February 2021

Interrupting the spring incubation of Megachile rotundata (F.) with a period of low-temperature storage for synchronizing the bees’ emergence with crop bloom is an essential part of M. rotundata management. Previously, we demonstrated that bees exposed to thermoperiods (TPs) during low-temperature storage have higher survival rates than bees exposed to constant temperatures. But changing the temperature in the large mass of bees commonly found in most commercial settings would place considerable stress on the chambers’ refrigeration system. Reducing the difference between a TP’s cryophase and thermophase would decrease the stress on the refrigeration system. Therefore, we investigated a range of TPs with cryophases (12 h) of 6, 12, or 15°C and thermophases (12 h) of 15 or 18°C and compared the survival rates of these bees against bees exposed to constant temperatures of 12, 15, or 18°C. For eye-pigmented pupae, the TP 6–18°C and the control fluctuating thermal regime (FTR; 6°C with a daily 1-h pulse at 20°C) had the highest survival rates for the 2 yr tested. For the constant-temperature storage protocols, constant 15 and 18°C were either equivalent or lower survival than the control FTR. For emergence-ready adults, the 6–18°C TP had the highest survival rates. The constant 15°C and the control FTR had equivalent survival rates. Under the current constraints imposed by a commercial chamber’s refrigeration system, interrupting M. rotundata spring incubation by exposing the developing bees to constant temperatures of 15–18°C is currently the best option for commercial operations.
The Economic Rationality of Religious-Based Medical Abstinence in the Early Twentieth Century: The Case of Philadelphia’s Faith Tabernacle Congregation
Authors: Mohr Adam
Published: February 2021

At the turn of the twentieth century, Faith Tabernacle Congregation’s commitment to medical abstinence was an economically rational practice. To the working poor of Philadelphia, who constituted the earliest members, Faith Tabernacle’s therapy was financially attainable, psychologically supportive, and physically rejuvenating. Orthodox medicine was deficient in these three areas based on the patient narratives (i.e., testimonies) published in the church's monthly periodical Sword of the Spirit and testimony book Words of Healing. First, some early members spent all their money on orthodox medical care without relief causing significant financial hardship, while others found medical care prohibitive. Second, many early members experienced a great loss of hope because orthodox physicians ended treatment due to chronic or critical illness, both of which were interpreted as psychologically harmful. Third, early members of the church perceived getting physically worse by physicians because of low quality care, which was compounded by low access to orthodox medicine. Faith Tabernacle alternatively provided care that – in the patient narratives of the earliest members – helped them improve and get back to work faster.
Environmental and Human Rights Counterclaims in International Investment Arbitration: at the Crossroads of Domestic and International Law
Authors: Shao Xuan
Published: February 2021

Recently, environmental and human rights (EHR) counterclaims in investment arbitration have attracted much attention as a vehicle to recalibrate the investor–state relationship. However, until now, successful instances of EHR counterclaims have been admittedly rare. As explained in this paper, some of the major barriers to EHR counterclaims in investment arbitration, and some of the concerns associated with them, are rooted in the domestic law basis of such counterclaims. Contrary to the position of several commentators, this paper argues that the grounding of EHR counterclaims on international law is neither practical nor beneficial, and EHR counterclaims are necessarily based on domestic law. Therefore, when investment arbitral tribunals adjudicate EHR counterclaims, they essentially act as an alternative to domestic courts. This has several implications. First, on questions of jurisdiction and admissibility of EHR counterclaims, decisions of states and arbitral tribunals essentially turn on the pros and cons of having these claims adjudicated by investment arbitral tribunals as opposed to domestic courts. Second, weaknesses in domestic rules, including the difficulty of holding shareholders accountable, would carry over to EHR counterclaims. Such problems can only be efficiently tackled at the level of domestic law. Third, as revealed from the inconsistent decisions in Perenco and Burlington on the merits of the environmental counterclaims, having investment arbitral tribunals adjudicate domestic law-based EHR counterclaims may cause certain concerns. For EHR counterclaims to play a more beneficial role, decision-makers must bear in mind these factors and concerns when taking their policy choices.
Genuine use of a trade mark established where proprietor is offering second-hand or spare parts service
Authors: Scarlett Roland
Published: February 2021

Court of Justice of the European Union, Ferrari SpA v DU, Joined Cases C–720/18 and C–721/18, EU: C:2020:854

In Ferrari SpA v DU, the Court of Justice responded to a preliminary ruling request from the Dusseldorf Higher Court and confirmed that Ferrari could establish genuine use of its ‘Testarossa’ legacy brand across the category of goods for which it was registered, on the basis of the sale of spare parts and second-hand cars.
Underreporting of Symptomatic Adverse Events in Phase I Clinical Trials
Authors: Veitch Zachary W , Shepshelovich Daniel , Gallagher Christina , Wang Lisa , Abdul Razak Albiruni R , Spreafico Anna , Bedard Philippe L , Siu Lillian L , Minasian Lori , Hansen Aaron R
Published: February 2021

Background

Clinician reporting of symptomatic adverse events (AEs) in phase I trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PROs) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic AEs in phase I patients.

Methods

Phase I study–eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence or absence of patient- (PRO-CTCAE) or clinician-reported symptomatic AEs were compared (kappa) at defined timepoints and overall (BL+ mid-cycle 1 + C2).

Results

Of 292 patients approached from May 2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting as 10% or greater. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician reporting rate. Overall patient–clinician agreement for individual symptomatic AEs ranged from poor (κ = 0.00-0.19) to moderate (κ = 0.40-0.59), with discordance driven by lack of clinician reporting. Dyspnea (κ = 0.54) and peripheral neuropathy (κ = 0.63) at BL and limb edema (κ = 0.55) at C2 demonstrated the highest patient–clinician agreement.

Conclusions

Poor to moderate patient–clinician agreement for symptomatic AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.
Is Uganda’s Progressive Refugee Policy Equalizing the Food Security of National and Refugee Households?
Authors: Bashaasha Bernard , Emegu Rosemary Isoto , Yamashita Miyuki
Published: February 2021

Uganda is the largest refugee hosting country in Africa and third in the world. The country operates a progressive refugee integration and self-reliance policy whereby refugees are allowed access to land and other productive resources. The effectiveness of this unique approach to refugee integration has not been empirically investigated. We estimate a multinomial logistic regression model to investigate whether the food security of refugee households is not significantly different from that of Ugandan nationals. We use cross sectional data collected in July 2019 from 2400 national and refugee households across 10 control and 10 World Food Program (WFP) intervention districts in Uganda using a randomized control trial (RCT) design. As we hypothesized, Ugandan citizenship together with size of land holding, livestock ownership and consumption of animal source food, marital status and geographical location enhance the food security of the household. However, our study found surprisingly that households currently receiving WFP support remain food insecure compared to those not receiving support, something we did not anticipate finding. Another surprising finding was that women headed households were more food secure than male-headed households across other socioeconomic parameters. Our findings hence suggest that in terms of equalizing the food security of refugees with that of Ugandan nationals, Uganda’s progressive policy on refugees remains work in progress.
To Donate or Not To Donate: Visual Framing of the Rohingya Refugees, Attitude Towards Refugees and Donation Intentions
Authors: Borah Porismita , Irom Bimbisar
Published: February 2021

Visual representations of refugees likely have a determinative function in the ways policies are written and aid is dispensed for crises resolution efforts. We use theoretical concepts from the visual framing literature and two studies—a content analysis and an experiment—to examine the effects of six visual frames. We study the content of newspapers from four countries for the following visual frames: ‘individual’, ‘massified’, ‘mother and child’, ‘father and child’, ‘receiving aid’ and ‘working refugees.’ Next, we examine the impact of these frames on intention to donate. Findings demonstrate that individuals with higher positive attitude towards refugees showed higher intention to donate. However, among these participants, intention to donate was highest in the ‘individual’ frame condition. On the other hand, among the participants with lower positive attitude towards refugees, the highest intention to donate was in the ‘working refugees’ frame condition. Implications are discussed.
Retooling the Energy Charter Treaty for climate change mitigation: lessons from investment law and arbitration
Authors: Cima Elena
Published: February 2021

In 2017, the Energy Charter Treaty (ECT) began a modernization process aimed at updating, clarifying, and modernizing a number of provisions of the Treaty. Considering the scope of application of the Treaty—cooperation in energy trade, transit, and investment—there is hardly any doubt that the modernization kicked off in 2017 offers a springboard for constructive reform and a unique opportunity to bring the Treaty closer in line with the objectives of the Paris Agreement. Although none of the items selected by the Energy Charter Conference and open for discussion and reform mention climate change or clean energy, a careful analysis of the relevant practice in both treaty drafting and adjudication can provide valuable insights as to how to steer the discussions on some of the existing items in a climate-friendly direction. The purpose of this article is to rely on this relevant practice to explore promising avenues to ‘retool’ the Treaty for climate change mitigation, in other words, to imagine a Treaty that would better reflect climate change concerns and clean energy transition goals.
The barrier to radial oxygen loss impedes the apoplastic entry of iron into the roots ofUrochloa humidicola
Authors: Jiménez Juan de la Cruz , Clode Peta L , Signorelli Santiago , Veneklaas Erik J , Colmer Timothy D , Kotula Lukasz
Published: February 2021

Lack of O2 and high concentrations of iron (Fe) and manganese (Mn) commonly occur in waterlogged soils. The development of a barrier to impede radial O2 loss (ROL) is a key trait improving internal O2 transport and waterlogging tolerance in plants. We evaluated the ability of the barrier to ROL to impede the entry of excess Fe into the roots of the waterlogging-tolerant grass Urochloa humidicola. Plants were grown in aerated or stagnant deoxygenated nutrient solution with 5 µM or 900 µM Fe. Quantitative X-ray microanalysis was used to determine cell-specific Fe concentrations at two positions behind the root apex in relation to ROL and the formation of apoplastic barriers. At a mature zone of the root, Fe was ‘excluded’ at the exodermis where a suberized lamella was evident, a feature also associated with a strong barrier to ROL. In contrast, the potassium (K) concentration was similar in all root cells, indicating that K uptake was not affected by apoplastic barriers. The hypothesis that the formation of a tight barrier to ROL impedes the apoplastic entry of toxic concentrations of Fe into the mature zones of roots was supported by the significantly higher accumulation of Fe on the outer side of the exodermis.
The Law of Investment Treaties
Authors: Salacuse Jeswald W
Published: February 2021

Investment treaties grant special international protection to foreign investors, and give them a means to enforce those rights against States in which they have invested. This book examines systematically the law of international investment treaties. Although the precise provisions of investment treaties are not uniform, virtually all investment treaties address the same issues. This book examines those issues in detail, including the scope of application, conditions for the entry of foreign investment, and general standards of treatment of foreign investments. Investment treaty law has continued to evolve rapidly and dramatically since publication of the second edition of this work in 2015. The field has seen considerable growth in the number and scope of investment treaties, now estimated at 3300, and investor-state arbitrations cases, which reached over 1000 in 2020. Beyond growth, the field has also experienced significant changes and reforms. In 2018, eleven Pacific Basin Countries, despite the withdrawal of the United States, forged ahead to conclude the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTTP), a potentially far reaching regional trade and investment agreement. The next year, the three north American nations replaced the North American Free Trade Agreement (NAFTA) with the United States-Mexico-Canada Agreement (USMCA). And in 2020, European Union member states terminated over 100 intra-EU BITs, leaving intra-EU investors to rely on EU law and legal processes alone for protection from unfavourable government acts. This edition incorporates a consideration of all of these and other reforms into its analysis of the body of law created by investment treaties since World War II.
Treatment of State Obligations (the ‘Umbrella Clause’)
Authors: Salacuse Jeswald W
Published: February 2021

This chapter explores umbrella clauses. In order to protect investor–state commitments and obligations from obsolescence, many investment treaties contain a clause defining the treatment that the host state will give to obligations it has made to investors or investments covered by the treaty. Known commonly as ‘umbrella clauses’, such provisions generally stipulate that ‘each Contracting Party shall observe any obligation it may have entered into with regard to the investments of investors of the other Contracting Party’. The umbrella clause creates an exception to a well-established principle of international law concerning state contracts with, and obligations to, foreign investors. Its intent is to impose an international treaty obligation on host countries that requires them to respect obligations they have entered into with respect to investments protected by the treaty. This places such obligations under the protective umbrella of international law, not just the domestic law that would otherwise normally apply exclusively. The chapter then looks at the formulations and application of the umbrella clause.
Discharge of Primary Obligations
Authors: Stannard John E , Capper David
Published: February 2021

This chapter examines discharge of primary obligations, considering Lord Diplock's classic analysis of the termination process. The first and most important consequence of termination is that both parties are, as a general rule, discharged from their outstanding primary obligations under the contract. This applies both to the innocent party and to the party in default. Though Lord Diplock speaks in terms of the primary obligations of both parties being discharged in so far as they are not already performed at the time of termination, this is not always the case. On the contrary, such obligations can still remain binding in so far as they have already accrued. Given that most the cases on this point concern obligations to pay money, the issue here is the extent to which either party can sue for the relevant sum as a liquidated debt despite termination having taken place. The chapter then looks at the effect of termination on ‘ancillary’ terms, most notably dispute resolution clauses and clauses excluding or limiting the liability of one or other of the parties.
Damages on Termination
Authors: Stannard John E , Capper David
Published: February 2021

This chapter focuses on damages on termination for breach of contract. Though there may be other measures used, ‘loss of bargain’ damages is the normal rule in cases of termination. The purpose of loss of bargain damages is to give the injured party the market value of the benefit of which he has been deprived through the breach. The phrase ‘loss of bargain’ can be used in two different senses. The first, and more general sense, is to denote the loss suffered by the claimant through being deprived of the benefit of the promise broken. However, the term is also used more precisely to denote the loss of the benefits of future performance of obligations released following discharge or termination. The chapter then examines when such damages are available following termination and how loss of bargain damages are calculated in such cases. Though most cases of termination will lead to loss of bargain damages, there may be situations where this is not an appropriate measure. These situations include the recovery of reliance loss and the recovery for non-pecuniary losses.
Contentious Cases before ITLOS and the Seabed Disputes Chamber
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter examines what constitutes a dispute under the 1982 United Nations Convention on the Law of the Sea (UNCLOS). The International Tribunal for the Law of the Sea (ITLOS) concurs with the International Court of Justice that a dispute is a disagreement on a point of law or fact, a conflict of legal views or interests, or the positive opposition of the claim of one party by the other, which need not necessarily be stated expressis verbis, and that, in the determination of the existence of a dispute, the position or the attitude of a party can be established by inference, whatever the professed view of that party. When there is a dispute between the parties at the time of the institution of proceedings, the dispute must be one over which ITLOS has jurisdiction. To determine whether a dispute between the disputing parties in a particular case concerns the interpretation or application of UNCLOS, ITLOS must establish a link between the facts advanced by the applicant and the provisions of UNCLOS referred to by it and show that such provisions can sustain the claims submitted by the applicant. In contentious cases, the Seabed Disputes Chamber shall be open to States Parties to UNCLOS, the International Seabed Authority, the Enterprise, State enterprises, and State-sponsored natural legal persons carrying out activities in the Area.
VINTERGATAN – II. The history of the Milky Way told by its mergers
Authors: Renaud Florent , Agertz Oscar , Read Justin I , Ryde Nils , Andersson Eric P , Bensby Thomas , Rey Martin P , Feuillet Diane K
Published: February 2021

Using the VINTERGATAN cosmological zoom simulation, we explore the contributions of the in situ and accreted material, and the effect of galaxy interactions and mergers in the assembly of a Milky Way-like galaxy. We find that the initial growth phase of galaxy evolution, dominated by repeated major mergers, provides the necessary physical conditions for the assembly of a thick, kinematically hot disc populated by high-[α/Fe] stars, formed both in situ and in accreted satellite galaxies. We find that the diversity of evolutionary tracks followed by the simulated galaxy and its progenitors leads to very little overlap of the in situ and accreted populations for any given chemical composition. At a given age, the spread in [α/Fe] abundance ratio results from the diversity of physical conditions in VINTERGATAN and its satellites, with an enhancement in [α/Fe] found in stars formed during starburst episodes. Later, the cessation of the merger activity promotes the in situ formation of stars in the low-[α/Fe] regime, in a radially extended, thin and overall kinematically colder disc, thus establishing chemically bimodal thin and thick discs, in line with observations. We draw links between notable features in the [Fe/H]-[α/Fe] plane with their physical causes, and propose a comprehensive formation scenario explaining self-consistently, in the cosmological context, the main observed properties of the Milky Way.
Galaxy evolution across environments as probed by the ages, stellar metallicities, and [α /Fe] of central and satellite galaxies
Authors: Gallazzi Anna R , Pasquali A , Zibetti S , Barbera F La
Published: February 2021

We explore how the star formation and metal enrichment histories of present-day galaxies have been affected by environment combining stellar population parameter estimates and group environment characterization for SDSS DR7. We compare stellar ages, stellar metallicities, and crucially, element abundance ratios $\rm [\alpha /Fe]$ of satellite and central galaxies, as a function of their stellar and host group halo mass, controlling for the current star formation rate and for the infall epoch. We confirm that below M* ∼ 1010.5 M⊙ satellites are older and slightly metal richer than equally massive central galaxies. In contrast, we do not detect any difference in their $\rm [\alpha /Fe]$: $\rm [\alpha /Fe]$ depends primarily on stellar mass and not on group hierarchy nor host halo mass. We also find that the differences in the median age and metallicity of satellites and centrals at stellar mass below $\rm 10^{10.5}\,M_\odot$ are largely due to the higher fraction of passive galaxies among satellites and as a function of halo mass. We argue that the observed trends at low masses reveal the action of satellite-specific environmental effects in a ‘delayed-then-rapid’ fashion. When accounting for the varying quiescent fraction, small residual excess in age, metallicity and $\rm [\alpha /Fe]$ emerge for satellites dominated by old stellar populations and residing in haloes more massive than 1014 M⊙, compared to equally massive central galaxies. This excess in age, metallicity, and $\rm [\alpha /Fe]$ pertain to ancient infallers, i.e. satellites that have accreted on to the current halo more than 5 Gyr ago. This result points to the action of environment in the early phases of star formation in galaxies located close to cosmic density peaks.
An ALMA survey of the S2CLS UDS field: optically invisible submillimetre galaxies
Authors: Smail Ian , Dudzevičiūtė U , Stach S M , Almaini O , Birkin J E , Chapman S C , Chen Chian-Chou , Geach J E , Gullberg B , Hodge J A , Ikarashi S , Ivison R J , Scott D , Simpson Chris , Swinbank A M , Thomson A P , Walter F , Wardlow J L , van der Werf P
Published: February 2021

We analyse a robust sample of 30 near-infrared-faint (KAB > 25.3, 5σ) submillimetre galaxies (SMGs) selected from a 0.96 deg2 field to investigate their properties and the cause of their faintness in optical/near-infrared wavebands. Our analysis exploits precise identifications based on Atacama Large Millimeter Array (ALMA) 870-μm continuum imaging, combined with very deep near-infrared imaging from the UKIDSS Ultra Deep Survey. We estimate that SMGs with KAB > 25.3 mag represent 15 ± 2 per cent of the total population brighter than S870 = 3.6 mJy, with a potential surface density of ∼450 deg−2 above S870 ≥ 1 mJy. As such, they pose a source of contamination in surveys for both high-redshift ‘quiescent’ galaxies and very high redshift Lyman-break galaxies. We show that these K-faint SMGs represent the tail of the broader submillimetre population, with comparable dust and stellar masses to KAB ≤ 25.3 mag SMGs, but lying at significantly higher redshifts (z = 3.44 ± 0.06 versus z = 2.36 ± 0.11) and having higher dust attenuation (AV = 5.2 ± 0.3 versus AV = 2.9 ± 0.1). We investigate the origin of the strong dust attenuation and find indications that these K-faint galaxies have smaller dust continuum sizes than the KAB ≤ 25.3 mag galaxies, as measured by ALMA, which suggests their high attenuation is related to their compact sizes. We identify a correlation of dust attenuation with star formation rate surface density (ΣSFR), with the K-faint SMGs representing the higher ΣSFR and highest AV galaxies. The concentrated, intense star formation activity in these systems is likely to be associated with the formation of spheroids in compact galaxies at high redshifts, but as a result of their high obscuration these galaxies are completely missed in ultraviolet, optical, and even near-infrared surveys.
Detectability of gravitational waves from a population of inspiralling black holes in Milky Way-mass galaxies
Authors: Emami Razieh , Loeb Abraham
Published: February 2021

We estimate the rate of inspiral for a population of stellar mass black holes in the star cluster around the supermassive black hole (SMBHs) at the centre of Milky Way mass galaxies. Our approach is based on an orbit averaged Fokker Planck approach. This is then followed by a post-processing approach, which incorporates the impact of the angular momentum diffusion and the GW dissipation in the evolution of system. We make a sample of 104 BHs with different initial semimajor and eccentricities with the distribution of fc(a)/a and e, respectively, where fc(a) refers to the phase–space distribution function for cth species. Angular momentum diffusion leads to an enhancement in the eccentricity of every system in the above sample and so increases the rate of inspiral. We compute the fraction of time that every system spends in the LISA band with the signal-to-noise ratio $\rm {S/N} \ge 8$. Every system eventually approaches the loss-cone with a replenishment rate given by the diffusion rate of the cluster, $\mu / \rm {Gyr}^{-1} \lesssim 1$. This small rate reduces the total rate of the inspiral for individual MW mass galaxies with an estimate Robs ≲ 10−6−10−5 yr−1. A large collection of galaxies (Ngal > 104 MW) may lead to an observable GW signal in the LISA band.
Survey2Survey: a deep learning generative model approach for cross-survey image mapping
Authors: Buncher Brandon , Sharma Awshesh Nath , Carrasco Kind Matias
Published: February 2021

During the last decade, there has been an explosive growth in survey data and deep learning techniques, both of which have enabled great advances for astronomy. The amount of data from various surveys from multiple epochs with a wide range of wavelengths, albeit with varying brightness and quality, is overwhelming, and leveraging information from overlapping observations from different surveys has limitless potential in understanding galaxy formation and evolution. Synthetic galaxy image generation using physical models has been an important tool for survey data analysis, while deep learning generative models show great promise. In this paper, we present a novel approach for robustly expanding and improving survey data through cross survey feature translation. We trained two types of neural networks to map images from the Sloan Digital Sky Survey (SDSS) to corresponding images from the Dark Energy Survey (DES). This map was used to generate false DES representations of SDSS images, increasing the brightness and S/N while retaining important morphological information. We substantiate the robustness of our method by generating DES representations of SDSS images from outside the overlapping region, showing that the brightness and quality are improved even when the source images are of lower quality than the training images. Finally, we highlight images in which the reconstruction process appears to have removed large artefacts from SDSS images. While only an initial application, our method shows promise as a method for robustly expanding and improving the quality of optical survey data and provides a potential avenue for cross-band reconstruction.
Exploring the hydrostatic mass bias in MUSIC clusters: application to the NIKA2 mock sample
Authors: Gianfagna Giulia , De Petris Marco , Yepes Gustavo , De Luca Federico , Sembolini Federico , Cui Weiguang , Biffi Veronica , Kéruzoré Florian , Macías-Pérez Juan , Mayet Frédéric , Perotto Laurence , Rasia Elena , Ruppin Florian
Published: February 2021

Clusters of galaxies are useful tools to constrain cosmological parameters, only if their masses can be correctly inferred from observations. In particular, X-ray and Sunyaev–Zeldovich (SZ) effect observations can be used to derive masses within the framework of the hydrostatic equilibrium. Therefore, it is crucial to have a good control of the possible mass biases that can be introduced when this hypothesis is not valid. In this work, we analysed a set of 260 synthetic clusters from the MUSIC simulation project at redshifts 0 ≤ z ≤ 0.82. We estimate the hydrostatic mass of the MUSIC clusters from X-ray only (temperature and density) and from X-ray and SZ (density and pressure). Then, we compare them with the true 3D dynamical mass. The biases are of the order of 20 per cent. We find that using the temperature instead of the pressure leads to a smaller bias, although the two values are compatible within 1σ. Non-thermal contributions to the total pressure support, arising from bulk motion and turbulence of the gas, are also computed and show that they are sufficient to account for this bias. We also present a study of the correlation between the mass bias and the dynamical state of the clusters. A clear correlation is shown between the relaxation state of the clusters and the bias factor. We applied the same analysis on a subsample of 32 objects, already selected for supporting the NIKA2 SZ Large Program.
Exploring the epoch of hydrogen reionization using FRBs
Authors: Beniamini Paz , Kumar Pawan , Ma Xiangcheng , Quataert Eliot
Published: February 2021

We describe three different methods for exploring the hydrogen reionization epoch using fast radio bursts (FRBs) and provide arguments for the existence of FRBs at high redshift (z). The simplest way, observationally, is to determine the maximum dispersion measure (DMmax) of FRBs for an ensemble that includes bursts during the reionization. The DMmax provides information regarding reionization much like the optical depth of the cosmic microwave background to Thomson scattering does, and it has the potential to be more accurate than constraints from Planck, if DMmax can be measured to a precision better than 500 pccm−3. Another method is to measure redshifts of about 40 FRBs between z of 6 and 10 with ${\sim}10{{\ \rm per\ cent}}$ accuracy to obtain the average electron density in four different z-bins with ${\sim}4{{\ \rm per\ cent}}$ accuracy. These two methods do not require knowledge of the FRB luminosity function and its possible redshift evolution. Finally, we show that the reionization history is reflected in the number of FRBs per unit DM, given a fluence limited survey of FRBs that includes bursts during the reionization epoch; we show using FIRE simulations that the contribution to DM from the FRB host galaxy and circumgalactic medium during the reionization era is a small fraction of the observed DM. This third method requires no redshift information but does require knowledge of the FRB luminosity function.
Anomaly detection in the Zwicky Transient Facility DR3
Authors: Malanchev K L , Pruzhinskaya M V , Korolev V S , Aleo P D , Kornilov M V , Ishida E E O , Krushinsky V V , Mondon F , Sreejith S , Volnova A A , Belinski A A , Dodin A V , Tatarnikov A M , Zheltoukhov S G ,   (The SNAD Team)
Published: February 2021

We present results from applying the SNAD anomaly detection pipeline to the third public data release of the Zwicky Transient Facility (ZTF DR3). The pipeline is composed of three stages: feature extraction, search of outliers with machine learning algorithms, and anomaly identification with followup by human experts. Our analysis concentrates in three ZTF fields, comprising more than 2.25 million objects. A set of four automatic learning algorithms was used to identify 277 outliers, which were subsequently scrutinized by an expert. From these, 188 (68 per cent) were found to be bogus light curves – including effects from the image subtraction pipeline as well as overlapping between a star and a known asteroid, 66 (24 per cent) were previously reported sources whereas 23 (8 per cent) correspond to non-catalogued objects, with the two latter cases of potential scientific interest (e.g. one spectroscopically confirmed RS Canum Venaticorum star, four supernovae candidates, one red dwarf flare). Moreover, using results from the expert analysis, we were able to identify a simple bi-dimensional relation that can be used to aid filtering potentially bogus light curves in future studies. We provide a complete list of objects with potential scientific application so they can be further scrutinised by the community. These results confirm the importance of combining automatic machine learning algorithms with domain knowledge in the construction of recommendation systems for astronomy. Our code is publicly available.1
Recent Evolutionary History of Tigers Highlights Contrasting Roles of Genetic Drift and Selection
Authors: Armstrong Ellie E , Khan Anubhab , Taylor Ryan W , Gouy Alexandre , Greenbaum Gili , Thiéry Alexandre , Kang Jonathan T , Redondo Sergio A , Prost Stefan , Barsh Gregory , Kaelin Christopher , Phalke Sameer , Chugani Anup , Gilbert Martin , Miquelle Dale , Zachariah Arun , Borthakur Udayan , Reddy Anuradha , Louis Edward , Ryder Oliver A , Jhala Yadvendradev V , Petrov Dmitri , Excoffier Laurent , Hadly Elizabeth , Ramakrishnan Uma
Published: February 2021

Species conservation can be improved by knowledge of evolutionary and genetic history. Tigers are among the most charismatic of endangered species and garner significant conservation attention. However, their evolutionary history and genomic variation remain poorly known, especially for Indian tigers. With 70% of the world’s wild tigers living in India, such knowledge is critical. We re-sequenced 65 individual tiger genomes representing most extant subspecies with a specific focus on tigers from India. As suggested by earlier studies, we found strong genetic differentiation between the putative tiger subspecies. Despite high total genomic diversity in India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding or founding events, possibly due to small and fragmented protected areas. We suggest the impacts of ongoing connectivity loss on inbreeding and persistence of Indian tigers be closely monitored. Surprisingly, demographic models suggest recent divergence (within the last 20,000 years) between subspecies and strong population bottlenecks. Amur tiger genomes revealed the strongest signals of selection related to metabolic adaptation to cold, whereas Sumatran tigers show evidence of weak selection for genes involved in body size regulation. We recommend detailed investigation of local adaptation in Amur and Sumatran tigers prior to initiating genetic rescue.
B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse
Authors: Ichiyanagi Tomoko , Katoh Hirokazu , Mori Yoshinobu , Hirafuku Keigo , Boyboy Beverly Ann , Kawase Masaki , Ichiyanagi Kenji
Published: February 2021

More than one million copies of short interspersed elements (SINEs), a class of retrotransposons, are present in the mammalian genomes, particularly within gene-rich genomic regions. Evidence has accumulated that ancient SINE sequences have acquired new binding sites for transcription factors (TFs) through multiple mutations following retrotransposition, and as a result have rewired the host regulatory network during the course of evolution. However, it remains unclear whether currently active SINEs contribute to the expansion of TF binding sites. To study the mobility, expression, and function of SINE copies, we first identified about 2,000 insertional polymorphisms of SINE B1 and B2 families within Mus musculus. Using a novel RNA sequencing method designated as melRNA-seq, we detected the expression of SINEs in male germ cells at both the subfamily and genomic copy levels: the vast majority of B1 RNAs originated from evolutionarily young subfamilies, whereas B2 RNAs originated from both young and old subfamilies. DNA methylation and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses in liver revealed that polymorphic B2 insertions served as a boundary element inhibiting the expansion of DNA hypomethylated and histone hyperacetylated regions, and decreased the expression of neighboring genes. Moreover, genomic B2 copies were enriched at the boundary of various histone modifications, and chromatin insulator protein, CCCTC-binding factor, a well-known chromatin boundary protein, bound to >100 polymorphic and >10,000 non-polymorphic B2 insertions. These results suggest that the currently active B2 copies are mobile boundary elements that can modulate chromatin modifications and gene expression, and are likely involved in epigenomic and phenotypic diversification of the mouse species.
Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding
Authors: Cao Chen , He Jingni , Mak Lauren , Perera Deshan , Kwok Devin , Wang Jia , Li Minghao , Mourier Tobias , Gavriliuc Stefan , Greenberg Matthew , Morrissy A Sorana , Sycuro Laura K , Yang Guang , Jeffares Daniel C , Long Quan
Published: February 2021

DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or “haplotypes.” However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.
Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma
Authors: Otani Yoshihiro , Sur Hannah P , Rachaiah Guruprasad , Namagiri Sriya , Chowdhury Ashis , Lewis Cole T , Shimizu Toshihiko , Gangaplara Arunakumar , Wang Xiang , Vézina Amélie , Maric Dragan , Jackson Sadhana , Yan Yuanqing , Zhengping Zhuang , Ray-Chaudhury Abhik , Kumar Sachin , Ballester Leomar Y , Chittiboina Prashant , Yoo Ji Young , Heiss John , Kaur Balveen , Banasavadi-Siddegowda Yeshavanth Kumar
Published: February 2021

Background

Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, the median survival of glioblastoma (GBM) patients is less than 15 months. Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric dimethylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor cells. LB100, a first-in-class small molecular inhibitor of protein phosphatase 2A (PP2A), can sensitize therapy-resistant tumor cells. Here, we tested the anti-GBM effect of concurrent PRMT5 and PP2A inhibition.

Methods

Patient-derived primary GBM neurospheres (GBMNS), transfected with PRMT5 target-specific siRNA, were treated with LB100 and subjected to in vitro assays including PP2A activity and western blot. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination treatment.

Results

We found that PRMT5 depletion increased PP2A activity in GBMNS. LB100 treatment significantly reduced the viability of PRMT5-depleted GBMNS compared to PRMT5-intact GBMNS. LB100 enhanced G1 cell cycle arrest induced by PRMT5 depletion. Combination therapy also increased the expression of phospho-MLKL. Necrostatin-1 rescued PRMT5-depleted cells from the cytotoxic effects of LB100, indicating that necroptosis caused the enhanced cytotoxicity of combination therapy. In the in vivo mouse tumor xenograft model, LB100 treatment combined with transient depletion of PRMT5 significantly decreased tumor size and prolonged survival, while LB100 treatment alone had no survival benefit.

Conclusion

Overall, combined PRMT5 and PP2A inhibition had significantly greater antitumor effects than PRMT5 inhibition alone.