The role of Hand2 in branchial arch and head-shoulder patterning

Comprehending gnathostome evolution requires insights into key cellular and molecular components of craniofacial and shoulder development. For the work of this PhD, I made use of genetically modified mouse models to study aspects of mammalian head and shoulder morphogenesis by triple fluorescent RNA in situ hybridisation, immunohistochemistry and high resolution imaging. First- I use a genetically defined sentinel cell population labelled by the Hand2-Cre transgene to establish the expansion of the distal-most branchial arch domain and correlate this by triple fluorescent RNA in situ hybridisation with the system controlling proximo-distal branchial arch patterning, the Dlx system. I find that the axis of the Dlx system does not correspond to the proximo-distal but an endodermal-ectodermal axis of the arch and rotates during development; the overall expansion of the arch is explicable by telescopic outgrowth along this new axis. Second- I study the cellular and molecular characteristics of head/ shoulder skeleto-muscular connectivity and the contribution of limb lateral plate mesoderm to the shoulder girdle, which allows me to identify part of the manubrium sterni as the ‘lost’ mammalian procoracoid and to demonstrate that the interaction between lateral plate mesodermal subpopulations is non-random. Third- I establish novel roles for Hand2 in lower incisor ameloblasts and in laminar dermal bone formation, suggesting a fundamental role for Hand2 in epithelial and mesenchymal cell layer arrangements. My detailed study of the murine frontal bone reveals that the establishment of an internal and an external layer initiates dermal bone formation; the latter shows intermediate molecular periosteal/ perichondrial characteristics and generates the intermediate layer by a Hand2-dependent invagination process. For a comparative amphibian data set, I begin to establish genetic lineage labelling as technique in Xenopus tropicalis. I generate and test a Xenopus Hand2-Cre transgene and establish a stable generic Xenopus tropicalis Cre-reporter line by I-SceI mediated transgenesis

Luttinger-Liquid Behavior in the Alternating Spin-Chain System Copper Nitrate

We determine the phase diagram of copper nitrate Cu(NO$_3$)$_2\cdot$2.5D$_2$O in the context of quantum phase transitions and novel states of matter. We establish this compound as an ideal candidate to study quasi-1D Luttinger liquids, 3D Bose-Einstein-Condensation of triplons, and the crossover between 1D and 3D physics. Magnetocaloric effect, magnetization, and neutron scattering data provide clear evidence for transitions into a Luttinger liquid regime and a 3D long-range ordered phase as function of field and temperature. Theoretical simulations of this model material allow us to fully establish the phase diagram and to discuss it in the context of dimerized spin systems.Comment: 5 pages, 4 figure

Formula for the nnth kk-Generalized Fibonacci-like Number

In this paper we provided a formula for the $n$th term of the $k$-generalized Fibonacci-like sequence, a generalization of the well-known Fibonacci sequence, having $k$ arbitrary initial terms, where the succeeding terms are obtained by adding its previous $k$ terms. The formula for the $n$th term of the $k$-generalized Fibonacci-like sequence was obtained by observing patterns in the derived formula for the nth term of the Fibonacci-like, Tribonacci-like, and Tetrabonacci-like sequence. The formula for the $k$-generalized Fibonacci sequence was also derived and was used in the process of proving the main result of this paper

Mutual induction of magnetic 3d and 4f order in multiferroic hexagonal ErMnO3

The complex interplay between the 3d and 4f moments in hexagonal ErMnO3 is investigated by magnetization, optical second harmonic generation, and neutron-diffraction measurements. We revise the phase diagram and provide a microscopic model for the emergent spin structures with a special focus on the intermediary phase transitions. Our measurements reveal that the 3d exchange between Mn^{3+} ions dominates the magnetic symmetry at 10 K < T < T_N with Mn^3+ order according to the Gamma_4 representation triggering 4f ordering according to the same representation on the Er^{3+}(4b) site. Below 10 K the magnetic order is governed by 4f exchange interactions of Er^{3+} ions on the 2a site. The magnetic Er^{3+}(2a) order according to the representation Gamma_2 induces a magnetic reorientation (Gamma_4 --> Gamma_2) at the Er^{3+}(4b) and the Mn^{3+} sites. Our findings highlight the fundamentally different roles the Mn^{3+}, R^{3+}(2a), and R^{3+}(4b) magnetism play in establishing the magnetic phase diagram of the hexagonal RMnO3 system

Magnetic Hamiltonian and phase diagram of the quantum spin liquid Ca10Cr7O28

A spin liquid is a new state of matter with topological order where the spin moments continue to fluctuate coherently down to the lowest temperatures rather than develop static long range magnetic order as found in conventional magnets. For spin liquid behavior to arise in a material the magnetic Hamiltonian must be frustrated , where the combination of lattice geometry, interactions, and anisotropies gives rise to competing spin arrangements in the ground state. Theoretical Hamiltonians which produce spin liquids are spin ice, the Kitaev honeycomb model, and the kagome antiferromagnet. Spin liquid behavior, however, in real materials is rare because they can only approximate these Hamiltonians and often have weak higher order terms that destroy the spin liquid state. Ca10Cr7O28 is a new quantum spin liquid candidate with magnetic Cr5 ions that possess quantum spin number S . The spins are entirely dynamic in the ground state and the excitation spectrum is broad and diffuse, as is typical of spinons which are the excitations of a spin liquid. In this paper we determine the Hamiltonian of Ca10Cr7O28 using inelastic neutron scattering under high magnetic field to induce a field polarized paramagnetic ground state and spin wave excitations that can be fitted to extract the interactions. We further explore the phase diagram by using inelastic neutron scattering and heat capacity measurements and establish the boundaries of the spin liquid phase as a function of magnetic field and temperature. Our results show that Ca10Cr7O28 consists of distorted kagome bilayers with several isotropic ferromagnetic and antiferromagnetic interactions where, unexpectedly, the ferromagnetic interactions are stronger than the antiferromagnetic ones. This complex Hamiltonian does not correspond to any known spin liquid model and points to new directions in the search for quantum spin liquid behavio

Phonons in mesoporous silicon The influence of nanostructuring on the dispersion in the Debye regime

We present a comprehensive scattering study of nanostructured silicon. Neutron and x ray scattering experiments elucidate structural and dynamical properties of electrochemically etched, porous silicon membranes with pores roughly 8 nm across. In particular, inelastic cold neutron scattering techniques reveal the phonon dispersion of the nanostructured, single crystalline samples in the linear Debye regime for energy transfers up to 4 meV. A modified dispersion relation characterized by systematically reduced sound velocities manifests itself in altered elastic properties of porous silicon when compared to bulk silicon. Its relevance for nanostructured silicon as thermoelectric material of interest is discusse

The magnetic phase diagram of the frustrated spin chain compound linarite, PbCuSO4_4(OH)2_2, as seen by neutron diffraction and 1^1H-NMR

We report on a detailed neutron diffraction and $^1$H-NMR study on the frustrated spin-1/2 chain material linarite, PbCuSO$_4$(OH)$_2$, where competing ferromagnetic nearest neighbor and antiferromagnetic next-nearest neighbor interactions lead to frustration. From the magnetic Bragg peak intensity studied down to 60 mK, the magnetic moment per Cu atom is obtained within the whole magnetic phase diagram for $H \parallel b$ axis. Further, we establish the detailed configurations of the shift of the SDW propagation vector in phase V with field and temperature. Finally, combining our neutron diffraction results with those from a low-temperature/high-field NMR study we find an even more complex phase diagram close to the quasi-saturation field suggesting that bound two-magnon excitations are the lowest energy excitations close to and in the quasi-saturation regime. Qualitatively and semi-quantitatively, we relate such behavior to $XYZ$ exchange anisotropy and contributions from the Dzyaloshinsky-Moriya interaction to affect the magnetic properties of linarite

Weighted ergodic theorems for Banach-Kantorovich lattice Lp(∇^,μ^)L_{p}(\hat{\nabla},\hat{\mu})

In the present paper we prove weighted ergodic theorems and multiparameter weighted ergodic theorems for positive contractions acting on $L_p(\hat{\nabla},\hat{\mu})$. Our main tool is the use of methods of measurable bundles of Banach-Kantorovich lattices.Comment: 11 page

The impact of COVID-19 on cancer care and oncology clinical research: an experts' perspective

The coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care

Thermodynamic Properties of the Anisotropic Frustrated Spin-chain Compound Linarite PbCuSO4_4(OH)2_2

We present a comprehensive macroscopic thermodynamic study of the quasi-one-dimensional (1D) $s = \tfrac{1}{2}$ frustrated spin-chain system linarite. Susceptibility, magnetization, specific heat, magnetocaloric effect, magnetostriction, and thermal-expansion measurements were performed to characterize the magnetic phase diagram. In particular, for magnetic fields along the b axis five different magnetic regions have been detected, some of them exhibiting short-range-order effects. The experimental magnetic entropy and magnetization are compared to a theoretical modelling of these quantities using DMRG and TMRG approaches. Within the framework of a purely 1D isotropic model Hamiltonian, only a qualitative agreement between theory and the experimental data can be achieved. Instead, it is demonstrated that a significant symmetric anisotropic exchange of about 10% is necessary to account for the basic experimental observations, including the 3D saturation field, and which in turn might stabilize a triatic (three-magnon) multipolar phase.Comment: 20 pages, 17 figure