Search

Summary: Mammalian cells can die by apoptosis or by one of several non-apoptotic mechanisms, such as ferroptosis. Here, we present a protocol to distinguish ferroptosis from other cell death mechanisms in cultured cells. We describe steps for seeding cells, administering mechanism-specific cell death inducers and inhibitors, and measuring cell death and viability. We then detail the use of molecular markers to verify mechanisms of cell death. This protocol can be used to identify and distinguish ferroptosis in 2D and 3D cultures.For complete details on the use and execution of this protocol, please refer to Ko, et al. (2019),1 Magtanong, et al. (2022),2 and Armenta, et al. (2022).3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

We present a velocity-resolved reverberation mapping analysis of the hypervariable quasar RM160 (SDSS J141041.25+531849.0) at z = 0.359 with 153 spectroscopic epochs of data representing a 10 yr baseline (2013–2023). We split the baseline into two regimes based on the 3× flux increase in the light curve: a “low state” phase during the years 2013–2019 and a “high state” phase during the years 2022–2023. The velocity-resolved lag profiles (VRLPs) indicate that gas with different kinematics dominates the line emission in different states. The H β VRLP begins with a signature of inflow onto the broad-line region (BLR) in the low state, while in the high state it is flatter with less signature of inflow. The H α VRLP begins consistent with a virialized BLR in the low state, while in the high state shows a signature of inflow. The differences in the kinematics between the Balmer lines and between the low state and the high state suggests complex BLR dynamics. We find that the BLR radius and velocity (both FWHM and σ ) do not obey a constant virial product throughout the monitoring period. We find that the BLR lags and continuum luminosity are correlated, consistent with rapid response of the BLR gas to the illuminating continuum. The BLR kinematic profile changes in unpredictable ways that are not related to continuum changes and reverberation lag. Our observations indicate that nonvirial kinematics can significantly contribute to observed line profiles, suggesting caution for black hole mass estimation in luminous and highly varying quasars like RM160.

We present the results of an investigation of a highly variable C iv broad absorption line (BAL) feature in spectra of the quasar SBS 1408+544 ( z = 2.337) that shows a significant shift in velocity over time. This source was observed as a part of the Sloan Digital Sky Survey (SDSS) Reverberation Mapping project and the SDSS-V Black Hole Mapper Reverberation Mapping project, and has been included in two previous studies, both of which identified significant variability in a high-velocity C iv BAL on timescales of just a few days in the quasar rest frame. Using ∼130 spectra acquired over 8 yr of spectroscopic monitoring with SDSS, we have determined that this BAL is not only varying in strength, but is also systematically shifting to higher velocities. Using cross-correlation methods, we measure the velocity shifts (and corresponding acceleration) of the BAL over a wide range of timescales, measuring an overall velocity shift of ${\rm{\Delta }}v=-{683}_{-84}^{+89}$ km s ^−1 over the 8 yr monitoring period. This corresponds to an average rest-frame acceleration of a = 1.04 ${}_{-0.13}^{+0.14}$ cm s ^−2 , though the magnitude of the acceleration on shorter timescales is not constant throughout. We place our measurements in the context of BAL-acceleration models and examine various possible causes of the observed velocity shift.

“Changing-look” active galactic nuclei (CL-AGNs) challenge our basic ideas about the physics of accretion flows and circumnuclear gas around supermassive black holes. Using first-year Sloan Digital Sky Survey V (SDSS-V) repeated spectroscopy of nearly 29,000 previously known active galactic nuclei (AGNs), combined with dedicated follow-up spectroscopy, and publicly available optical light curves, we have identified 116 CL-AGNs where (at least) one broad emission line has essentially (dis-)appeared, as well as 88 other extremely variable systems. Our CL-AGN sample, with 107 newly identified cases, is the largest reported to date, and includes ∼0.4% of the AGNs reobserved in first-year SDSS-V operations. Among our CL-AGNs, 67% exhibit dimming while 33% exhibit brightening. Our sample probes extreme AGN spectral variability on months to decades timescales, including some cases of recurring transitions on surprisingly short timescales (≲2 months in the rest frame). We find that CL events are preferentially found in lower-Eddington-ratio ( f _Edd ) systems: Our CL-AGNs have a f _Edd distribution that significantly differs from that of a carefully constructed, redshift- and luminosity-matched control sample (Anderson–Darling test yielding p _AD ≈ 6 × 10 ^−5 ; median f _Edd ≈ 0.025 versus 0.043). This preference for low f _Edd strengthens previous findings of higher CL-AGN incidence at lower f _Edd , found in smaller samples. Finally, we show that the broad Mg ii emission line in our CL-AGN sample tends to vary significantly less than the broad H β emission line. Our large CL-AGN sample demonstrates the advantages and challenges in using multi-epoch spectroscopy from large surveys to study extreme AGN variability and physics.

This work studies the relationship between accretion-disk size and quasar properties, using a sample of 95 quasars from the Sloan Digital Sky Survey Reverberation Mapping Project with measured lags between the g and i photometric bands. Our sample includes disk lags that are both longer and shorter than predicted by the Shakura and Sunyaev model, requiring explanations that satisfy both cases. Although our quasars each have one lag measurement, we explore the wavelength-dependent effects of diffuse broad-line region (BLR) contamination through our sample’s broad redshift range, 0.1 < z < 1.2. We do not find significant evidence of variable diffuse Fe ii and Balmer nebular emission in the rms spectra, nor from Anderson–Darling tests of quasars in redshift ranges with and without diffuse nebular emission falling in the observed-frame filters. Contrary to previous work, we do not detect a significant correlation between the measured continuum and BLR lags in our luminous quasar sample, similarly suggesting that our continuum lags are not dominated by diffuse nebular emission. Similar to other studies, we find that quasars with larger-than-expected continuum lags have lower 3000 Å luminosities, and we additionally find longer continuum lags with lower X-ray luminosities and black hole masses. Our lack of evidence for diffuse BLR contribution to the lags indicates that the anticorrelation between continuum lag and luminosity is not likely to be due to the Baldwin effect. Instead, these anticorrelations favor models in which the continuum lag increases in lower-luminosity active galactic nuclei, including scenarios featuring magnetic coupling between the accretion disk and X-ray corona, and/or ripples or rims in the disk.

Abstract Experiences of positive affect (PA) are common when interacting with animals and may help to build resilience. This study explored how children’s relationships with pet dogs, parents, and friends are related to their experiences of PA with their pet dog. In addition, we examined whether greater PA with pet dogs was related to children’s thriving. The sample (n = 115, 57 girls, 58 boys) included children 9–14 years of age who reported the quality of relationships with their pet dog (Positive Relationship Qualities, Friction, Pets as Substitutes), attachment security to parents, and positive and negative friendship quality. PA was assessed with child self-report before and after interacting with their dog, observed child and dog PA during the interaction, and reports of daily PA when interacting with the dog from a 7-day daily log. Children completed questionnaires to assess attachment security relationship with parents and friendship relationship quality. Children’s relationships with parents and friends were related to PA in the interaction session, whereas relationships with pet dogs, parents, and friends were all related to the daily experiences of PA. Children’s experiences of PA in daily interactions with pet dogs, parent-child attachment, and positive friendship quality were all related to children’s thriving. The findings suggest that experiences of PA may be one mechanism that accounts for the effects of animals on children’s development.

Abstract Companion animals, including pet dogs, can be sources of support and potentially contribute to children’s competence and adjustment. The goal of this paper is to examine whether children’s pet dog relationships are related to their competence and adjustment after accounting for relationships with parents and friends and demographic factors. We distinguished three qualities of child-pet dog relationships – positive pet relationship qualities, friction, and pets as substitutes for people – and examined them in relation to children’s thriving, school academic performance, and internalizing and externalizing behavior problems. The sample included 115 children (M age = 10.93, 57 girls and 58 boys) who completed questionnaires about the quality of their relationship with a pet dog, the positive and negative qualities of a best friendship, and the security of attachments to parents. To measure child competence, children reported their thriving and parents reported children’s school academic performance. To measure adjustment, parents and teachers reported child internalizing and externalizing behavior problems. Positive pet relationship qualities were related to a higher competence. Friction and pets as substitutes were related to lower competence and adjustment, although some findings varied by the reporter or after controlling for other factors. Pet relationship quality uniquely contributed to some child outcomes, although moderation analyses did not provide any evidence that pet dog relationships compensate for low-quality friendships or insecure parental attachments. Collectively, the findings suggest that relationships with pets may augment but not override the impact of relationships with parents and friends.

Individual studies have been underpowered to draw clear associations between clonal heterogeneity and response to therapy in acute myeloid leukemia (AML). Here, the authors aggregate multiple AML cohorts and are able to correlate the clonal abundance of somatic mutations with clinical outcomes and drug sensitivity.

We present a high-cadence multiepoch analysis of dramatic variability of three broad emission lines (Mg ii , H β , and H α ) in the spectra of the luminous quasar ( λ L _λ (5100 Å) = 4.7 × 10 ^44 erg s ^−1 ) SDSS J141041.25+531849.0 at z = 0.359 with 127 spectroscopic epochs over nine years of monitoring (2013–2022). We observe anticorrelations between the broad emission-line widths and flux in all three emission lines, indicating that all three broad emission lines “breathe” in response to stochastic continuum variations. We also observe dramatic radial velocity shifts in all three broad emission lines, ranging from Δ v ∼ 400 km s ^−1 to ∼800 km s ^−1 , that vary over the course of the monitoring period. Our preferred explanation for the broad-line variability is complex kinematics in the gas in the broad-line region. We suggest a model for the broad-line variability that includes a combination of gas inflow with a radial gradient, an azimuthal asymmetry (e.g., a hot spot), superimposed on the stochastic flux-driven changes to the optimal emission region (“line breathing”). Similar instances of line-profile variability due to complex gas kinematics around quasars are likely to represent an important source of false positives in radial velocity searches for binary black holes, which typically lack the kind of high-cadence data we analyze here. The long-duration, wide-field, and many-epoch spectroscopic monitoring of SDSS-V BHM-RM provides an excellent opportunity for identifying and characterizing broad emission-line variability, and the inferred nature of the inner gas environment, of luminous quasars.

Background: Electrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations. Methods: All ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis. Results: Of the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48–71 years). The median QRS duration was 86 ms (IQR 80–94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2–31.8 kg/m2). When stratified according to the World Health Organization classification of BMI

Experiences of positive affect (PA) are common when interacting with animals and may help to build resilience. This study explored how children’s relationships with pet dogs, parents, and friends are related to their experiences of PA with their pet dog. In addition, we examined whether greater PA with pet dogs was related to children’s thriving. The sample (n = 115, 57 girls, 58 boys) included children 9–14 years of age who reported the quality of relationships with their pet dog (Positive Relationship Qualities, Friction, Pets as Substitutes), attachment security to parents, and positive and negative friendship quality. PA was assessed with child self-report before and after interacting with their dog, observed child and dog PA during the interaction, and reports of daily PA when interacting with the dog from a 7-day daily log. Children completed questionnaires to assess attachment security relationship with parents and friendship relationship quality. Children’s relationships with parents and friends were related to PA in the interaction session, whereas relationships with pet dogs, parents, and friends were all related to the daily experiences of PA. Children’s experiences of PA in daily interactions with pet dogs, parent-child attachment, and positive friendship quality were all related to children’s thriving. The findings suggest that experiences of PA may be one mechanism that accounts for the effects of animals on children’s development.

Companion animals, including pet dogs, can be sources of support and potentially contribute to children’s competence and adjustment. The goal of this paper is to examine whether children’s pet dog relationships are related to their competence and adjustment after accounting for relationships with parents and friends and demographic factors. We distinguished three qualities of child-pet dog relationships – positive pet relationship qualities, friction, and pets as substitutes for people – and examined them in relation to children’s thriving, school academic performance, and internalizing and externalizing behavior problems. The sample included 115 children (M age = 10.93, 57 girls and 58 boys) who completed questionnaires about the quality of their relationship with a pet dog, the positive and negative qualities of a best friendship, and the security of attachments to parents. To measure child competence, children reported their thriving and parents reported children’s school academic performance. To measure adjustment, parents and teachers reported child internalizing and externalizing behavior problems. Positive pet relationship qualities were related to a higher competence. Friction and pets as substitutes were related to lower competence and adjustment, although some findings varied by the reporter or after controlling for other factors. Pet relationship quality uniquely contributed to some child outcomes, although moderation analyses did not provide any evidence that pet dog relationships compensate for low-quality friendships or insecure parental attachments. Collectively, the findings suggest that relationships with pets may augment but not override the impact of relationships with parents and friends.

We present a case of a tubulovillous adenoma arising in a neobladder that was managed by cystoscopic resection. A 64 year-old male underwent a cystectomy with creation of an ileocolic neobladder urinary diversion for T2 urothelial carcinoma of the bladder. Nine years following his surgery, the patient noted several episodes of gross hematuria. Cystoscopic evaluation revealed the rare occurrence of a 3 cm tubulovillous adenoma with high-grade dysplasia at the neck of the neobladder.

Emotion modulation is achieved through various strategies. We further validated a measure of emotion regulation (ER), the Negative Emotion Regulation Inventory (NERI), designed by Zimmermann and Iwanski (2014) to assess emotions and ER strategies in situations intended to induce sadness, fear, or anger. U.S. children 9-14 years old (n = 105) completed an adapted version of the NERI and measures of anxiety symptoms and attachment security. We replicated Zimmermann and Iwanski's (2014) finding that ER strategies (adaptive regulation, social support seeking, dysfunctional rumination, expressive suppression) varied by emotion situation. We extended their study by showing that specific ER strategies were related to both anxiety symptoms and secure parent-child attachment. This cross-cultural replication and extension study provided some evidence for the reliability and validity of the adapted NERI in U.S. preadolescents.

Parent-child attachment is robustly associated with typical patterns of emotion regulation but rarely examined in relation to changes in emotion in response to events. We studied how attachment is related to emotion reactivity to positive and negative events and to immediate and delayed emotion recovery from social exclusion. The sample (78% White, 46% girls) included 110 children (9-12 years). Children completed a story stem measure that was scored for security, avoidance, ambivalence, and disorganization. Emotion reactivity and recovery were assessed with child-reported and observer positive affect and negative affect ratings. Parents rated child temperament. More avoidant children showed dampened emotion responding (low reactivity and recovery), whereas more ambivalent children showed heightened emotion responding (high reactivity and recovery). Attachment security, disorganization, and temperament were not consistently related to emotion reactivity or recovery. The findings highlight that emotion regulation occurs in response to contextual changes and is related to attachment.

Writing has been often viewed as a cognitive or social task and instructional practices are influenced by one or the other perspective. However, alternatives may need to be considered that are not as polarized and consider individuals, their environment, their development, their needs, and the role of community (Graham, in press). The purpose of this paper is to provide instructional guidelines for the application of an approach to teaching stories that stems from self-regulated strategy instruction and emphasizes social interactions and oral discourse through oral retellings of stories that are read during read alouds, oral production of stories, drama, and perspective taking (Moore & Caldwell, 1993) Philippakos, Robinson, & Munsell, 2017; Philippakos, 2017b; Philippakos, Robinson, & Munsel, under review; Philippakos & MacArthur, in preparation). The approach was developed through design research (Brown, 1992; Collins, 1999; Reinking & Bradley, 2008) and was evaluated across one cycle of implementation from November to December with 12 teachers and 219 students (across grades Kindergarten to 2). Students were asked to compose stories at pretest and posttest, and papers were evaluated using a 5-point holistic rubric (r = 0.90). The results showed statistically significant differences on the writing quality of students' papers (p <0.001). Teachers positively commented on the systematic and structured instruction of the writing process and on the use of oral discourse through retellings, drama, and dialogic interactions. Teachers acknowledged that even though Kindergarten and first-grade students were not -yet- all able to effectively apply phonics and knowledge of orthography in order to compose, they were able to learn the steps of the writing process, how to navigate through it, and how to use sentence structures relevant to the genre of story writing to develop their stories. In the following section the authors explain the instructional components of the process and provide guidelines for classroom application.

ABSTRACT We examine whether estimated taxable income provides incremental information about firms' operating risk. We develop taxable income-based measures that should be useful in assessing risk in a simple earnings predictability model. In our empirical tests these taxable income-based measures explain cross-sectional variation in the predictability and variability of future pre-tax financial performance. Further, these measures are associated with predictable variation in market-based measures of firm risk. Our findings shed light on how accounting information—specifically, book income and tax income—impacts investors' assessment of firm risk as well as improving our understanding of the extent and nature of information contained in estimated taxable income.