Nonlinear dynamics of flux compactification Corman, Maxence; East, William E.; Johnson, Matthew C.
The journal of high energy physics,
09/2021, Letnik:
2021, Številka:
9
Journal Article
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A
bstract
We study the nonlinear evolution of unstable flux compactifications, applying numerical relativity techniques to solve the Einstein equations in
D
dimensions coupled to a
q
-form field and ...positive cosmological constant. We show that initially homogeneous flux compactifications are unstable to dynamically forming warped compactifications. In some cases, we find that the warping process can serve as a toy-model of slow-roll inflation, while in other instances, we find solutions that eventually evolve to a singular state. Analogous to dynamical black hole horizons, we use the geometric properties of marginally trapped surfaces to characterize the lower dimensional vacua in the inhomogeneous and dynamical settings we consider. We find that lower-dimensional vacua with a lower expansion rate are dynamically favoured, and in some cases find spacetimes that undergo a period of accelerated expansion followed by contraction.
The outcomes of patients with SCLC have not yet been substantially impacted by the revolution in precision oncology, primarily owing to a paucity of genetic alterations in actionable driver ...oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. Although, these results are encouraging, many patients do not respond to, or rapidly recur after, current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion, is a snapshot of the current biomarker and clinical trial landscapes for SCLC. Finally, we identify key knowledge gaps that should be addressed to advance the field in pursuit of reduced SCLC mortality. This review largely summarizes work presented at the Third Biennial International Association for the Study of Lung Cancer SCLC Meeting.
We have prepared a series of samples with the ligand 6,13-bistri(iso-propyl)silylethynyl tetracene 2-carboxylic acid (TIPS-Tc-COOH) attached to PbS quantum dot (QD) samples of three different sizes ...in order to monitor and control the extent and time scales of energy flow after photoexcitation. Fast energy transfer (∼1 ps) to the PbS QD occurs upon direct excitation of the ligand for all samples. The largest size QD maintains the microsecond exciton lifetime characteristic of the as-prepared oleate terminated PbS QDs. However, two smaller QD sizes with lowest exciton energies similar to or larger than the TIPS-Tc-COO− triplet energy undergo energy transfer between QD core and ligand triplet on nanosecond to microsecond timescales. For the intermediate size QDs in particular, energy can be recycled many times between ligand and core, but the triplet remains the dominant excited species at long times, living for ∼3 μs for fully exchanged QDs and up to 30 μs for partial ligand exchange, which is revealed as a method for controlling the triplet lifetime. A unique upconverted luminescence spectrum is observed that results from annihilation of triplets after exclusive excitation of the QD core.
Repair of large nerve defects with acellular nerve allografts (ANAs) is an appealing alternative to autografting and allotransplantation. ANAs have been shown to be similar to autografts in ...supporting axonal regeneration across short gaps, but fail in larger defects due to a poorly-understood mechanism. ANAs depend on proliferating Schwann cells (SCs) from host tissue to support axonal regeneration. Populating longer ANAs places a greater proliferative demand on host SCs that may stress host SCs, resulting in senescence. In this study, we investigated axonal regeneration across increasing isograft and ANA lengths. We also evaluated the presence of senescent SCs within both graft types. A sciatic nerve graft model in rats was used to evaluate regeneration across increasing isograft (~autograft) and ANA lengths (20, 40, and 60mm). Axonal regeneration and functional recovery decreased with increased graft length and the performance of the isograft was superior to ANAs at all lengths. Transgenic Thy1-GFP rats and qRT-PCR demonstrated that failure of the regenerating axonal front in ANAs was associated with increased levels of senescence related markers in the graft (senescence associated β-galactosidase, p16INK4A, and IL6). Lastly, electron microscopy (EM) was used to qualitatively assess senescence-associated changes in chromatin of SCs in each graft type. EM demonstrated an increase in the presence of SCs with abnormal chromatin in isografts and ANAs of increasing graft length. These results are the first to suggest that SC senescence plays a role in limited axonal regeneration across nerve grafts of increasing gap lengths.
•Regeneration decreases with increased nerve graft length.•No regeneration occurs in acellular grafts greater than 4cm in length.•The number of senescent cells within nerve grafts increases with length.•Cessation of axonal regeneration is associated with senescent cells in long grafts.
The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSRBC) program in improving psychological and physical symptoms and ...quality of life among breast cancer survivors (BCSs) who completed treatment. Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe.
A total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects.
Results demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P < .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC).
The MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes.
Modular self-assembly of biomolecules in two dimensions (2D) is straightforward with DNA but has been difficult to realize with proteins, due to the lack of modular specificity similar to ...Watson–Crick base pairing. Here we describe a general approach to design 2D arrays using de novo designed pseudosymmetric protein building blocks. A homodimeric helical bundle was reconnected into a monomeric building block, and the surface was redesigned in Rosetta to enable self-assembly into a 2D array in the C12 layer symmetry group. Two out of ten designed arrays assembled to micrometer scale under negative stain electron microscopy, and displayed the designed lattice geometry with assembly size up to 100 nm under atomic force microscopy. The design of 2D arrays with pseudosymmetric building blocks is an important step toward the design of programmable protein self-assembly via pseudosymmetric patterning of orthogonal binding interfaces.
The notion of a U shape in happiness—that well-being is highest for people in their 20s, decreases to its nadir in midlife, and then rises into old age—has captured the attention of the media, which ...often cite it as evidence for a midlife crisis. We argue that support for the purported U shape is not as robust and generalizable as is often assumed and present our case with the following arguments: (a) Cross-sectional studies are inadequate for drawing conclusions about within-person change in happiness across the life span; (b) cross-sectional evidence with respect to the ubiquity and robustness of the U shape in general levels of happiness and life satisfaction is mixed; (c) longitudinal support for the U shape in happiness and life satisfaction is also mixed; (d) longitudinal research on subjective indicators of well-being other than general levels of happiness and life satisfaction challenges the U shape; (e) when asked to reflect on their lives, older adults tend to recall midlife as one of the more positive periods; and (f) a focus on a single trajectory of well-being is of limited scientific and applied value because it obscures the diversity in pathways throughout life as well as its sources. Understanding happiness across the life course and moving the research field forward require a multidisciplinary, collaborative approach.