Dissipationless Formation and Evolution of the Milky Way Nuclear Star Cluster

Abridged: In one widely discussed model for the formation of nuclear star clusters (NSCs), massive globular clusters spiral into the center of a galaxy and merge to form the nucleus. It is now known that at least some NSCs coexist with supermassive black holes (SBHs); this is the case, for instance, in the Milky Way (MW). In this paper, we investigate how the presence of a SMBH at the center of the MW impacts the merger hypothesis for the formation of its NSC. Starting from a model consisting of a low-density nuclear stellar disk and the SMBH, we use N-body simulations to follow the successive inspiral and merger of globular clusters. The clusters are started on circular orbits of radius 20 pc, and their initial masses and radii are set up in such a way as to be consistent with the galactic tidal field at that radius. The total accumulated mass by ~10 clusters is about 1.5x10^7 Solar masses. Each cluster is disrupted by the SMBH at a distance of roughly one parsec. The density profile that results after the final inspiral event is characterized by a core of roughly this radius, and an envelope with density that falls off as 1/r^2. These properties are similar to those of the MW NSC, with the exception of the core size, which in the MW is a little smaller. But by continuing the evolution of the model after the final inspiral event, we find that the core shrinks substantially via gravitational encounters in a time (when scaled to the MW) of 10 Gyr as the stellar distribution evolves toward a Bahcall-Wolf cusp. We also show that the luminosity function of the MW NSC is consistent with the hypothesis that a large fraction of the mass comes from (~10Gyr) old stars, brought in by globular clusters. We conclude that a model in which a large fraction of the mass of the MW NSC arose from infalling globular clusters is consistent with existing observational constraints.Comment: 15 pages, 13 figures. ApJ accepte

Subcutaneous Administration of D-Luciferin is an Effective Alternative to Intraperitoneal Injection in Bioluminescence Imaging of Xenograft Tumors in Nude Mice

Currently, intraperitoneal (IP) injection of D-luciferin is the preferred method of providing substrate for bioluminescence imaging (BLI); however it has a failure rate of 3–10% due to accidental intestinal injection. The present study evaluates the quality of BLI after subcutaneous (SC) injection of D-luciferin and demonstrates the effectiveness of SC injection in anatomically disparate tumor models. Mice bearing luciferase-expressing tumors underwent BLI after SC or IP injection of D-luciferin. The average time to maximal luminescence was 6 min (range 5–9 min) after SC injection and 8 min (range 5–8 min) after IP injection. Within 7 minutes of injection, SC and IP routes yielded similar luminescence in subcutaneous, intracranial, tongue, and lung xenograft tumor models. In a model of combined subcutaneous and intracranial xenografts, SC injection resulted in proportional luminescence at all sites, confirming that preferential delivery of substrate does not occur. While tumors were occasionally not visualized with IP injection, all tumors were visualized reliably with SC injection. Thus, SC injection of D-luciferin is a convenient and effective alternative to IP injection for BLI in nude mice. It may be a preferable approach, particularly for tumors with weaker signals and/or when greater precision is required

Testing causality violation on spacetimes with closed timelike curves

Generalized quantum mechanics is used to examine a simple two-particle scattering experiment in which there is a bounded region of closed timelike curves (CTCs) in the experiment's future. The transitional probability is shown to depend on the existence and distribution of the CTCs. The effect is therefore acausal, since the CTCs are in the experiment's causal future. The effect is due to the non-unitary evolution of the pre- and post-scattering particles as they pass through the region of CTCs. We use the time-machine spacetime developed by Politzer [1], in which CTCs are formed due to the identification of a single spatial region at one time with the same region at another time. For certain initial data, the total cross-section of a scattering experiment is shown to deviate from the standard value (the value predicted if no CTCs existed). It is shown that if the time machines are small, sparsely distributed, or far away, then the deviation in the total cross-section may be negligible as compared to the experimental error of even the most accurate measurements of cross-sections. For a spacetime with CTCs at all points, or one where microscopic time machines pervade the spacetime in the final moments before the big crunch, the total cross-section is shown to agree with the standard result (no CTCs) due to a cancellation effect.Comment: 28 pages, 8 figures, late

The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts

Bioluminescence imaging (BLI) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models. BLI involves the generation of light by luciferase-expressing cells following administration of the substrate luciferin in the presence of oxygen and ATP. In the present study, the effects of hypoxia, hypoperfusion, and pH on BLI signal (BLS) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice. The intensity of the BLS was significantly reduced in the presence of acute and chronic hypoxia. Changes in cell density, viability, and pH also affected BLS. Although BLI is a convenient non-invasive tool for tumor assessment, these factors should be considered when interpreting BLS intensity, especially in solid tumors that could be hypoxic due to rapid growth, inadequate blood supply, and/or treatment

Trajectories of loneliness during adolescence predict subsequent symptoms of depression and positive wellbeing

There is a need to identify the outcomes of changes in loneliness during adolescence, and to consider this within a multidimensional framework of loneliness. This study considered the effects of different trajectories of change in Isolation Loneliness and in Friendship Loneliness upon both positive wellbeing and symptoms of depression. To achieve this, 1782 (43% female; 12.92 years old at the start of the study, SD = 1.60) young people took part in a longitudinal study with four data points across 2 years. Four Isolation Loneliness trajectories and five Friendship Loneliness trajectories were identified. Youth who experienced low levels of Isolation Loneliness that subsequently increased appear to be at particular risk for poor outcomes. Similarly, initially high levels of Friendship Loneliness that decreased rapidly, or which began at a low level and only increased marginally, seem to also be a risk. Loneliness is a multi-dimensional construct and its development during adolescence impacts upon young people’s depressive symptomatology and positive mental wellbeing

Understanding how, why, for whom, and under what circumstances opt-out blood-borne virus testing programmes work to increase test engagement and uptake within prison: a rapid-realist review.

BACKGROUND: Prisons represent a unique opportunity to diagnose blood-borne viruses. Opt-out testing is receiving increasing interest, as a result of mounting evidence to suggest that the manner in which a test offer is delivered, affects test uptake. Although the effectiveness of opt-out testing within the prison setting has been established, robust explanations are required for the variation in outcomes reported. METHODS: Rapid-realist review methodology was used to synthesise the literature on prison-based opt-out testing. The review was carried out in three phases. Phase one: An expert panel provided literature relevant to the implementation of opt-out testing within the English prison estate. Unstructured searches were also conducted to identify other social programmes where "opt-out" had been used to increase uptake. Phase two: a systematic search of six peer-review and five grey literature databases was carried out to identify empirical data on opt-out testing within the prison setting. Phase three: Additional non-exhaustive searches were carried out to identify literature that reinforced emergent concepts. The development of programme theory took place with each iteration and was validated in consultation with stakeholders. RESULTS: Programme theory was constructed for two outcomes: the proportion of intake offered a test and the proportion offered that accepted testing. The proportion of intake offered testing was influenced by the timing of the test offer, which was often delayed due to barriers to prisoner access. The decision to accept testing was influenced by concerns about confidentiality, fear of a positive diagnosis, a prisoner's personal interpretation of risk, discomfort with invasive procedures, trust in healthcare, and the fidelity of the opt-out offer. CONCLUSIONS: This review identified important implementation considerations that moderate the effectiveness of opt-out testing programmes. It also highlighted a lack of appreciation for the theoretical underpinnings of opt-out programmes and tension around how to implement testing in a manner that adheres to both default theory and informed consent. It is anticipated that results will be used to inform the design and implementation of subsequent versions of these programmes, as well as catalyse further in-depth analysis into their operation within the unique context of prison. REVIEW REGISTRATION: CRD42017068342

STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum (ER) stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. Yet little is known about STIM1 in excitable cells such as striated muscle where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to exhibit SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide novel insight to the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells