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The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogs with Bub1 being a kinase, while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this spatial separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here, we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1-PP2A-B56 complex can support chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation, resulting in the reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the spatial separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment.

The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogs with Bub1 being a kinase, while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this spatial separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here, we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1-PP2A-B56 complex can support chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation, resulting in the reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the spatial separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment.

The goal of this study is to evaluate the BruinHub one year after its opening in Fall 2021. BruinHub is a space dedicated to serve long-distance commuter students at UCLA. Primary research questions for this project are:1. Does BruinHub serve the intended target audience of long-distance commuters, including commuters who experience some form of housing insecurity?2. What changes to the current and proposed BruinHub program(s) would further benefit the intended audience?For this study, I analyzed the BruinHub Passholder registration data, conducted one-on-one interviews with UCLA students and staff, and conducted on site observations in the BruinHub space.BruinHub is the first step in the right direction in addressing the needs of long-distance commuters. However, there are more improvements that can be implemented in order to reach its full potential, especially by prioritizing and directly serving its intended audience.Recommendations to come out of this study involve spatial recommendations, programming recommendations, and recommendations for outreach and data collection. While many of the suggested improvements will be challenging to implement, students and staff must actively advocate for the changes. The newly opened second location, BruinHub Strathmore, presents an opportunity to address many of the current concerns and service gaps that BruinHub experiences.

The faithful segregation of chromosomes into daughter cells is essential for cellular and organismal viability. Errors in this process cause aneuploidy, a hallmark of cancer and several congenital diseases. For proper separation, chromosomes attach to microtubules of the mitotic spindle via their kinetochores, large protein structures assembled on centromeric chromatin. Kinetochores are also crucial for a cell cycle feedback mechanism known as the spindle assembly checkpoint (SAC). The SAC forces cells to remain in mitosis until all chromosomes are properly attached to microtubules. At the beginning of mitosis, the SAC proteins - Mad1, Mad2, Bub1, Bub3, BubR1, Mps1, and Cdc20 - are recruited to kinetochores in a hierarchical and interdependent fashion (Fig A). There they monitor, in ways that are not fully clarified, the formation of kinetochore-microtubule attachments. Two studies recently published in EMBO reports by the groups of Silke Hauf and Jakob Nilsson, and a recent study by London and Biggins in Genes & Development, shed new light on the conserved SAC protein Mad1. Two recent studies in EMBO reports identify a new role for Mad1 in the spindle assembly checkpoint (SAC), which prevents cells from dividing until all chromosomes are attached to the spindle. These findings are integrated into an updated model of SAC activation.

The need for social marketing research in the area of breastfeeding is highlighted by the failure of campaigns to increase breastfeeding rates over the past two decades in developed countries. This is despite evidence of the health benefits of longer breastfeeding duration to both baby and mother, and the high levels of expenditure on these campaigns. Whilst past campaign approaches typically focus on baby-oriented factors, breastfeeding is a complex behaviour that for many women involves barriers that influence their commitment to continued breastfeeding. Using social marketing, this research investigates the role of mother-centred factors on loyalty to breastfeeding. A sample of 405 Australian women completed an online survey. The data were analysed using structural equation modelling, which revealed that mother-oriented, rather than baby-oriented, factors influence attitudinal and behavioural loyalty to breastfeeding.

This is a book review. To be published in Studies in History and Philosophy of Modern Physics.

How much do non-medical factors affect the timing of conceptions, births and deaths? To test this, we estimate the effect of the millennium on conceptions, births and deaths. With a highly flexible empirical specification, we find large and significant increases in conceptions and births, and suggestive evidence of an effect on deaths.

How much do non-medical factors affect the timing of conceptions, births and deaths? To test this, we estimate the effect of the millennium on conceptions, births and deaths. With a highly flexible empirical specification, we find large and significant increases in conceptions and births, and suggestive evidence of an effect on deaths.

von Siegfried Eck

Bub Walker

Bub Walker and Ernie Gesell.

Bub Walker

Bub Walker in car number 5, a Curtis Riley Special.

Anglais, Palmaro Collections Pouchet

We construct the phase space of a spherically symmetric causal diamond in $(d+2)$-dimensional Minkowski spacetime. Utilizing the covariant phase space formalism, we identify the relevant degrees of freedom that localize to the $d$-dimensional bifurcate horizon and, upon canonical quantization, determine their commutators. On this phase space, we find two Iyer-Wald charges. The first of these charges, proportional to the area of the causal diamond, is responsible for shifting the null time along the horizon and has been well-documented in the literature. The second charge is much less understood, being integrable for $d \geq 2$ only if we allow for field-dependent diffeomorphisms and is responsible for changing the size of the causal diamond., Comment: 9 pages, 2 figures

Titre uniforme : [Rockin'in rhythm], Titre uniforme : [Black and tan fantasy], Titre uniforme : [Rockin'in rhythm], Titre uniforme : [Black and tan fantasy], Titre uniforme : [Rockin' in rhythm], BnF-Partenariats, Collection sonore - Believe, Contient une table des matières

William Wilson discusses cattle and horse ranching on Rapid Creek in Perkins County, South Dakota in the late 1800's and early 1900's, and the effects of the Depression in the area.

William Wilson discusses cattle and horse ranching on Rapid Creek in Perkins County, South Dakota in the late 1800's and early 1900's, and the effects of the Depression in the area.

Anmerkung aus Katalog 'Die Frankfurter Hobrecker-Sammlung' : 'Frühere Ausgabe des um 1900 bei Scholz in Mainz wieder aufgelegten Bilderbuches ...', Titelblatt fehlt, ergänzt durch Vergleich mit 1900 in Mainz erschienener Ausgabe

[2], 6 p., Item at reel 196:1 and 265:E238, no. 14 identified as T427 (number cancelled in Wing 2nd ed.)., Reproduction of original in Thomason Collection, British Library., (DLPS) A64152.0001.001, (stc) Wing A3060B, http://quod.lib.umich.edu/t/text/accesspolicy.html, To the extent possible under law, the Text Creation Partnership has waived all copyright and related or neighboring rights to this keyboarded and encoded edition of the work described above, according to the terms of the CC0 1.0 Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/). This waiver does not extend to any page images or other supplementary files associated with this work, which may be protected by copyright or other license restrictions. Please go to http://www.textcreationpartnership.org/ for more information.

[2], 6 p., Item at reel 196:1 and 265:E238, no. 14 identified as T427 (number cancelled in Wing 2nd ed.)., Reproduction of original in Thomason Collection, British Library., (DLPS) A64152.0001.001, (stc) Wing A3060B, http://quod.lib.umich.edu/t/text/accesspolicy.html, To the extent possible under law, the Text Creation Partnership has waived all copyright and related or neighboring rights to this keyboarded and encoded edition of the work described above, according to the terms of the CC0 1.0 Public Domain Dedication (http://creativecommons.org/publicdomain/zero/1.0/). This waiver does not extend to any page images or other supplementary files associated with this work, which may be protected by copyright or other license restrictions. Please go to http://www.textcreationpartnership.org/ for more information.

An American World War II propaganda poster encouraging conservative use of Army-Navy standard fasteners. Poster shows a man scooping screws into a large bag., Title from item. Artist's signature at lower right corner of image. Conjectural dates based on United States participation in World War II. At foot of sheet: "Chance Vought Aircraft, Division of United Aircraft Corp., Stratford, Connecticut." Dimensions: 55.8 x 43.1 cm., United States--Connecticut--Stratford.

Human astrovirus is a positive-sense, single-stranded RNA virus. Astrovirus infection causes gastrointestinal symptoms and can lead to encephalitis in immunocompromised patients. Positive-strand RNA viruses typically utilize host intracellular membranes to form replication organelles, which are potential antiviral targets. Many of these replication organelles are double-membrane vesicles (DMVs). Here, we show that astrovirus infection leads to an increase in DMV formation through a replication-dependent mechanism that requires some early components of the autophagy machinery. Results indicate that the upstream class III phosphatidylinositol 3-kinase (PI3K) complex, but not LC3 conjugation machinery, is utilized in DMV formation. Both chemical and genetic inhibition of the PI3K complex lead to significant reduction in DMVs, as well as viral replication. Elucidating the role of autophagy machinery in DMV formation during astrovirus infection reveals a potential target for therapeutic intervention for immunocompromised patients. IMPORTANCE These studies provide critical new evidence that astrovirus replication requires formation of double-membrane vesicles, which utilize class III phosphatidylinositol 3-kinase (PI3K), but not LC3 conjugation autophagy machinery, for biogenesis. These results are consistent with replication mechanisms for other positive-sense RNA viruses suggesting that targeting PI3K could be a promising therapeutic option for not only astrovirus, but other positive-sense RNA virus infections.

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.

We study the effects of geontropic vacuum fluctuations in quantum gravity on next-generation terrestrial gravitational wave detectors. If the VZ effect proposed in Ref. [1], as modeled in Refs. [2, 3], appears in the upcoming GQuEST experiment, we show that it will be a large background for astrophysical gravitational wave searches in observatories like Cosmic Explorer and the Einstein Telescope., Comment: 19 pages, 9 figures

We study the effects of geontropic vacuum fluctuations in quantum gravity on next-generation terrestrial gravitational wave detectors. If the VZ effect proposed in Ref. [1], as modeled in Refs. [2, 3], appears in the upcoming GQuEST experiment, we show that it will be a large background for astrophysical gravitational wave searches in observatories like Cosmic Explorer and the Einstein Telescope., Comment: 19 pages, 9 figures

The Snowmass report on rare processes and precision measurements recommended Mu2e-II and a next generation muon facility at Fermilab (Advanced Muon Facility) as priorities for the frontier. The Workshop on a future muon program at FNAL was held in March 2023 to discuss design studies for Mu2e-II, organizing efforts for the next generation muon facility, and identify synergies with other efforts (e.g., muon collider). Topics included high-power targetry, status of R&D for Mu2e-II, development of compressor rings, FFA and concepts for muon experiments (conversion, decays, muonium and other opportunities) at AMF. This document summarizes the workshop discussions with a focus on future R&D tasks needed to realize these concepts., Comment: 68 pages, 36 figures

Procedures for environmental risk assessment for pesticides are under continuous development and subject to debate, especially at higher tier levels. Spatiotemporal dynamics of both pesticide exposure and effects at the landscape scale are largely ignored, which is a major flaw of the current risk assessment system. Furthermore, concrete guidance on risk assessment at landscape scales in the regulatory context is lacking. In this regard, we present an integrated modular simulation model system that includes spatiotemporally explicit simulation of pesticide application, fate, and effects on aquatic organisms. As a case study, the landscape model was applied to the Rummen, a river catchment in Belgium with a high density of pome fruit orchards. The application of a pyrethroid to pome fruit and the corresponding drift deposition on surface water and fate dynamics were simulated. Risk to aquatic organisms was quantified using a toxicokinetic/toxicodynamic model for individual survival at different levels of spatial aggregation, ranging from the catchment scale to individual stream segments. Although the derivation of landscape-scale risk assessment end points from model outputs is straightforward, a dialogue within the community, building on concrete examples as provided by this case study, is urgently needed in order to decide on the appropriate end points and on the definition of representative landscape scenarios for use in risk assessment.

Die Verbindung von postulierter metaphysischer Leere und einem radikal geleugneten und doch wieder herbeizitieren Gott, in deren Kontext der Gedanke erschreckender körperlicher Verstümmlung eine Rolle spielt, kennzeichnet in bewusst outrierter Weise einzelne Texte aus dem literarischen Werk, darunter der wenig bekannten Lyrik des Philosophen und Schriftstellers Georges Bataille, der wie kaum ein anderer Autor des 20. Jahrhunderts quasi unausgesetzt in immer neuen Anläufen eine Daseinserfahrung umkreist, die an Radikalität und Abgründigkeit ihresgleichen sucht. Bataille imaginiert die willentliche Selbstzerstörung des Ichs auf der Suche nach einem Absoluten, die sich speziell in rauschhaft-transgredierenden Erfahrungen von Leid, Versehrung, Obszönität und Ekel vollzieht. In einer Aufzeichnung aus der 1939-1943 entstandenen Sammlung "Le Coupable" (1944), welche zur gleichen Schaffensperiode wie die meisten seiner lyrischen Texte gehört, spricht Bataille in einer prägnanten Begriffsfügung von seiner Konzeption eines "anthropomorphisme déchiré". So wie es gelte, in jeglichem Sein "le lieu sacrificiel, la blessure" (OC V, S. 261) zu suchen, wird das in "Le Coupable" meditierende Ich (nur) in der Erfahrung des versehrten lebendigen Opfers eines Göttlichen habhaft: "Un être n'est touché qu'au point où il succombe, une femme sous la robe, un dieu à la gorge de l'animal du sacrifice" (OC V, S. 261). In der geistigen Auseinandersetzung mit einer christlichen Theologie, die "jusque dans la nuit du Golgotha" (OC V, S. 262) an der Vorstellung einer vollendeten Welt festhält, erkennt Bataille: "Il faut tuer Dieu pour apercevoir le monde dans l'infirmité de l'inachèvement" (OC V, S. 262). Die imaginierte Tötung Gottes lässt dann an die Stelle eines abwesenden Gottes einen versehrten Gott treten.

Many natural and man-made systems are prone to critical transitions -- abrupt and potentially devastating changes in dynamics. Deep learning classifiers can provide an early warning signal (EWS) for critical transitions by learning generic features of bifurcations (dynamical instabilities) from large simulated training data sets. So far, classifiers have only been trained to predict continuous-time bifurcations, ignoring rich dynamics unique to discrete-time bifurcations. Here, we train a deep learning classifier to provide an EWS for the five local discrete-time bifurcations of codimension-1. We test the classifier on simulation data from discrete-time models used in physiology, economics and ecology, as well as experimental data of spontaneously beating chick-heart aggregates that undergo a period-doubling bifurcation. The classifier outperforms commonly used EWS under a wide range of noise intensities and rates of approach to the bifurcation. It also predicts the correct bifurcation in most cases, with particularly high accuracy for the period-doubling, Neimark-Sacker and fold bifurcations. Deep learning as a tool for bifurcation prediction is still in its nascence and has the potential to transform the way we monitor systems for critical transitions.

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.