Explore the vast range of titles available.

Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

We present a theoretical method to generate a highly accurate time-independent Hamiltonian governing the finite-time behavior of a time-periodic system. The method exploits infinitesimal unitary transformation steps, from which renormalization-group–like flow equations are derived to produce the effective Hamiltonian. Our tractable method has a range of validity reaching into frequency—and drive strength—regimes that are usually inaccessible via high-frequencyωexpansions in the parameterh/ω, wherehis the upper limit for the strength of local interactions. We demonstrate exact properties of our approach on a simple toy model and test an approximate version of it on both interacting and noninteracting many-body Hamiltonians, where it offers an improvement over the more well-known Magnus expansion and other high-frequency expansions. For the interacting models, we compare our approximate results to those found via exact diagonalization. While the approximation generally performs better globally than other high-frequency approximations, the improvement is especially pronounced in the regime of lower frequencies and strong external driving. This regime is of special interest because of its proximity to the resonant regime where the effect of a periodic drive is the most dramatic. Our results open a new route towards identifying novel nonequilibrium regimes and behaviors in driven quantum many-particle systems.

Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 Å crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of β-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species.

The Loschmidt amplitude is a popular quantity that allows making predictions about the stability of quantum states under time evolution. In our work, we present an approach that allows us to find a differential equation that can be used to compute the Loschmidt amplitude. This approach, while in essence perturbative, has the advantage that it converges at finite order. We demonstrate that the approach for generically chosen matrix Hamiltonians often offers advantages over Taylor and cumulant expansions even when we truncate at finite order. We then apply the approach to two ordinary band Hamiltonians (multi-Weyl semimetals and AB bilayer graphene) to obtain the Loschmidt amplitude after a quench for an arbitrary starting state and find that the results readily generalize to find transmission amplitudes and specific contributions to the partition function, too. We then test our methods on many-body spin and fermionic Hamiltonians and find that while the approach still offers advantages, more care has to be taken than in a generic case. We also provide an estimate for a breakdown time of the approximation.

Restoration of neuronal connectivity after lesion of the central nervous system, such as spinal cord injury, is one of the biggest challenges in modern medicine. In particular, the accumulation of axon growth inhibitory factors at the site of injury constitutes a major obstacle to structural and thus functional repair. We previously investigated a group of prenylflavonoids derived from hops for their capacity to promote neuroregeneration. We identified a molecule called ENDF1 that was very potent to enhance regrowth and branching of neurites from dorsal root ganglion neurons in culture on growth promoting substrates. In the present study, we investigated ENDF1's capacity to promote regeneration of rat dorsal root ganglion neurons in the presence of three main components of the extracellular matrix acting as axon growth inhibitors: Semaphorin 3A, Ephrin A4 and mixed chondroitin sulfate proteoglycans. We report that ENDF1 application significantly promoted the percentages of sensory neurons able to regrow their neurites regardless of the presence of those inhibitors, and this to an extent similar to the one obtained after NGF treatment. Moreover, ENDF1 strongly enhanced the total neurite length and the complexity of neurites extending from neurons challenged with axon growth inhibitors. Although the impact of NGF and ENDF1 on the regeneration of neurons was similar, the activity of ENDF1 was not mediated by signaling through the TrkA receptor, indicating that each molecule act through different signaling pathways. In addition, ENDF1 did not decrease the phosphorylation of cofilin, a downstream effector of the regeneration-associated RhoA/ROCK signaling pathway. Hence, ENDF1 is a potent pro-neuroregenerative factors that could help in identifying new efficient targets for regenerative therapies of the nervous system.

HIV-1 groups M and N emerged within the last century following two independent cross-species transmissions of SIVcpz from chimpanzees to humans. In contrast to pandemic group M strains, HIV-1 group N viruses are exceedingly rare, with only about a dozen infections identified, all but one in individuals from Cameroon. Poor adaptation to the human host may be responsible for this limited spread of HIV-1 group N in the human population. Here, we analyzed the function of Vpu proteins from seven group N strains from Cameroon, the place where this zoonosis originally emerged. We found that these N-Vpus acquired four amino acid substitutions (E15A, V19A and IV25/26LL) in their transmembrane domain (TMD) that allow efficient interaction with human tetherin. However, despite these adaptive changes, most N-Vpus still antagonize human tetherin only poorly and fail to down-modulate CD4, the natural killer (NK) cell ligand NTB-A as well as the lipid-antigen presenting protein CD1d. These functional deficiencies were mapped to amino acid changes in the cytoplasmic domain that disrupt putative adaptor protein binding sites and an otherwise highly conserved ßTrCP-binding DSGxxS motif. As a consequence, N-Vpus exhibited aberrant intracellular localization and/or failed to recruit the ubiquitin-ligase complex to induce tetherin degradation. The only exception was the Vpu of a group N strain recently discovered in France, but originally acquired in Togo, which contained intact cytoplasmic motifs and counteracted tetherin as effectively as the Vpus of pandemic HIV-1 M strains. These results indicate that HIV-1 group N Vpu is under strong host-specific selection pressure and that the acquisition of effective tetherin antagonism may lead to the emergence of viral variants with increased transmission fitness.

We present the synthesis and characterization of the iridium-based sulfide Ca1−xIr4S6(S2). Quality and phase analysis were conducted by means of energy-dispersive X-ray spectroscopy (EDXS) and powder X-ray diffraction (XRD) techniques. Structure analysis reveals a monoclinic symmetry with the space group C 1 2/m 1 (No. 12), with the lattice constants a = 15.030 (3) Å, b = 3.5747 (5) Å and c = 10.4572 (18) Å. Both X-ray diffraction and EDXS suggest an off-stoichiometry of calcium, leading to the empirical composition Ca1−xIr4.0S6(S2) [x = 0.23–0.33]. Transport measurements show metallic behavior of the compound in the whole range of measured temperatures. Magnetic measurements down to 1.8 K show no long range order, and Curie–Weiss analysis yields θCW = −31.4 K, suggesting that the compound undergoes a magnetic state with short range magnetic correlations. We supplement our study with calculations of the band structure in the framework of the density functional theory.

Background The acquisition of effective Vpu-mediated anti-tetherin activity to promote virion release following transmission of SIVcpz Ptt from central chimpanzees ( Pan troglodytes troglodytes ) to humans distinguishes pandemic HIV-1 group M strains from non-pandemic group N, O and P viruses and may have been a prerequisite for their global spread. Some functional motifs in the cytoplasmic region of HIV-1 M Vpus proposed to be important for anti-tetherin activity are more frequently found in the Vpu proteins of SIVcpz Ptt than in those of SIVcpz Pts infecting eastern chimpanzees ( P. t. schweinfurthii), that have not been detected in humans, and SIVgor from gorillas, which is closely related to HIV-1 O and P. Thus, SIVcpz Ptt strains may require fewer adaptive changes in Vpu than SIVcpz Pts or SIVgor strains to counteract human tetherin. Results To examine whether SIVcpz Ptt may only need changes in the transmembrane domain (TMD) of Vpu to acquire anti-tetherin activity, whereas SIVcpz Pts and SIVgor may also require changes in the cytoplasmic region, we analyzed chimeras between the TMD of an HIV-1 M Vpu and the cytoplasmic domains of SIVcpz Ptt (n = 2), SIVcpz Pts (n = 2) and SIVgor (n = 2) Vpu proteins. Unexpectedly, all of these chimeras were capable of counteracting human tetherin to enhance virion release, irrespective of the presence or absence of the putative adaptor protein binding sites and the DSGxxS β-TrCP binding motif reported to be critical for effective anti-tetherin activity of M Vpus. It was also surprising that in three of the six chimeras the gain of anti-tetherin function was associated with a loss of the CD4 degradation activity since this function was conserved among all parental HIV-1, SIVcpz and SIVgor Vpu proteins. Conclusions Our results show that changes in the TMD of SIVcpz Ptt , SIVcpz Pts and SIVgor Vpus are sufficient to render them active against human tetherin. Thus, several previously described domains in the extracellular region of Vpu are not absolutely essential for tetherin antagonism but may be required for other Vpu functions.

Strategies for psychological tools use and techniques to enhance motivation in older adults are underrepresented within sport and performance psychology research. The purpose of this qualitative study was to develop an older adult profile of mental skills use by adults aged 50- 65 who participate in CrossFit. By creating a baseline understanding of mental skills use, this study could potentially be used by older adults outside of CrossFit to start or increase their levels of physical activity through the use of psychological tools. This study included 25 CrossFit participants from 10 different CrossFit gyms in the greater Denver area. Semi- structured open-ended interviews were conducted to provide a baseline understanding of the older CrossFit adults’ understanding of mental skills and their use, provide recommendations for practical psychological tools application by sport psychology professionals with older adults, and identify potential areas for future research. The participant profile consists of multiple internal motivational characteristics and suggestions for how this understanding can benefit others outside of CrossFit.

In the different chapters of this dissertation we investigate multiple non-perturbative approaches that allow the study of solids subjected to time dependent fields.In the second chapter, we develop a very general non-perturbative and flexible approach that allows to study periodically driven quantum systems via an effective time-independent theory. It makes use of renormalization-group-like flow equations to find highly accurate effective Hamiltonians. The range of validity of the approach is checked numerically for various 1D spin systems and confirmed to be beyond the reaches of ordinary perturbative methods. It also compares favorably to another non-perturbative approach.In the third chapter we examine the wealth of different approximations to the time evolution operator that are known from the literature. Inspired by Hamilton-Jacobi theory we find a useful reformulation of the equation for the time evolution operator. This allows us to find the various known approximations of the time evolution operator in a unified fashion and new ones. Interestingly the RG-like flow equations from the second chapter are found to be one specific limit of the more general approach developed here. A periodically driven Ising model is used to verify the range of validity of the different approximations. This allows us to put them into a hierarchy.Up until here the methods that were explored are most valid in the high to mid frequency regime. In the fourth chapter we show how for the case of a weakly driven system a simple approach can be used to treat the low frequency regime. To achieve this we derive a quasi-energy dependent Hamiltonians and very crucially require self-consistency for the quasi-energies. For the simple two band example of single layer graphene it is found to be highly accurate approach that also allows for accurate descriptions of even sensitive quantities like Chern numbersFor the last fifth chapter of the thesis we switch gears and consider a specific system of much recent interest - twisted bilayer graphene. We investigate how light that is altered by the boundary conditions of a metallic waveguide can change the strength of interlayer couplings [arXiv:2001.04416 (2020)]. We investigate how this change affects the twist angles at which flat bands appear and find very simple analytic results that are in good agreement with a numerical treatment.In the sixth chapter of the thesis, we investigate the effects circularly polarized light has on twisted bilayer graphene. We derive two effective Hamiltonians valid in different driving regimes. One is valid for weak drives but low frequencies and the other for relatively strong drives. The Hamiltonian for the strongly driven regime is compared to exact numeric results and found to perform better than other common methods. We analyze the newly generated terms in both Hamiltonians for their symmetry.