Fundamental Open Questions Research Articles

Bone marrow niches for hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are the cornerstone of the hematopoietic system. HSCs sustain the continuous generation of mature blood derivatives while self-renewing to preserve a relatively constant pool of progenitors throughout life. Yet, long-term maintenance of functional HSCs exclusively takes place in association with their native tissue microenvironment of the bone marrow (BM). HSCs have been long proposed to reside in fixed and identifiable anatomical units found in the complex BM tissue landscape, which control their identity and fate in a deterministic manner. In the last decades, tremendous progress has been made in the dissection of the cellular and molecular fabric of the BM, the structural organization governing tissue function, and the plethora of interactions established by HSCs. Nonetheless, a holistic model of the mechanisms controlling HSC regulation in their niche is lacking to date. Here, we provide an overview of our current understanding of BM anatomy, HSC localization, and crosstalk within local cellular neighborhoods in murine and human tissues, and highlight fundamental open questions on how HSCs functionally integrate in the BM microenvironment.

Thermal and Coherent Spin Pumping by Noncollinear Antiferromagnets.

Antiferromagnets attract much interest because of their potential for spintronic applications and open fundamental physics questions, but especially noncollinear antiferromagnets remain relatively unexplored. Here, we formulate the thermal and coherent pumping of spins in noncollinear antiferromagnets|normal metal bilayers. We find that the spin current polarization is a vector with components along both the Néel vector and net magnetic moment. The spin mixing conductance for the coherent spin pumping is a tensor with elements depending on the degree of noncollinearity and interface spin configuration. We explain the controversial sign problem of the antiferromagnetic spin Seebeck effect by interface effects and suggest that interface engineering may enhance the spin pumping efficiency.

Quark matter and nuclear astrophysics: Recent developments

Does deconfined cold quark matter occur in nature? This is currently one of the fundamental open questions in nuclear astrophysics. In these proceedings, I review the current state-of-the-art techniques to address this question in a model-agnostic manner, by synthesizing inputs from astrophysical observations of neutron stars and their binary mergers, and first-principles calculations within nuclear and particle theory. I highlight recent improvements in perturbative calculations in asymptotically dense cold quark matter, as well as compelling evidence for a conformalizing transition within the cores of massive neutron stars.

Characterizing inertial particle clustering with 1D signals

Preferential concentration in turbulent flows laden with inertial particles still presents many open fundamental physics questions. These gaps hinder the reconciliation of different experimental and numerical studies into a coherent quantitative view, which is needed to enable accurate high resolution modeling. We examine the influence of the dimensionality of the measurement technique (1D line, 2D planes or 3D volumes) on the characterization of cluster properties/preferential concentration, and proposes an approach to disentangle the cluster-characterizing results from random contributions that could contaminate the cluster statistical analysis. We studied this effect by projecting 2D and 3D data snapshots containing inertial particle clusters onto a 1D axis. The objective was to simulate 1D sensors (widely used experimentally: hot wire, fiber optics probes, LDV/PDA, etc) with different sensing lengths. These projected records were analysed by means of one-dimensional Voronoï tessellations. For the experimental parameters explored in this study, our results retrieved average clustering properties, when the measuring window is equal or larger than the Kolmogorov length scale (η), and smaller than of the integral length scale of the turbulence . These observations are consistent with previous research using 2D and 3D datasets taken under similar experimental conditions. The raw probability density function (PDF) of the Voronoï length in 1D does not provide error-free information on the clusters size or local concentration. This measurement bias is corrected based on the histograms of the number of particles within each cluster. Importantly, the analysis of these histograms explains the well-known clusters size PDFs power law reported in previous numerical and experimental research using 2D and 3D datasets. This power-law behavior, however, spanning less than a decade, is not robust in 1D. To address this, we use conditioned statistics (on the number of particles inside each cluster) to discern between turbulence-driven clustering and random particle concentration fluctuations. This secondary analysis complements standard cluster identification algorithms that rely on Voronoï tessellations.

Membrane free-energy landscapes derived from atomistic dynamics explain nonuniversal cholesterol-induced stiffening.

All lipid membranes have inherent morphological preferences and resist deformation. Yet adaptations in membrane shape can and do occur at multiple length scales. While this plasticity is crucial for cellular physiology, the factors controlling the morphological energetics of lipid bilayers and the dominant mechanisms of membrane remodeling remain to be fully understood. An ongoing debate regarding the universality of the stiffening effect of cholesterol underscores the challenges facing this field, both experimentally and theoretically, even for simple lipid mixtures. On the computational side, we have argued that enhanced-sampling all-atom molecular dynamics simulations are uniquely suited for the quantification of membrane conformational energetics, as they minimize a priori assumptions and permit analysis of bilayers in deformed states. To showcase this approach, we examine reported inconsistencies between alternative experimental measurements of bending moduli for cholesterol-enriched membranes. Specifically, we analyze lipid bilayers with different chain saturation and compute free-energy landscapes for curvature deformations distributed over areas from ∼5 to ∼60 nm. These enhanced simulations, totaling over 100 μs of sampling time, enable us to directly quantify both bending and tilt moduli and to dissect the contributing factors and molecular mechanisms of curvature generation at each length scale. Our results show that the effects of cholesterol on bending rigidity are lipid-specific and suggest that this specificity arises from differences in the torsional dynamics of the acyl chains. In summary, we demonstrate that quantitative relationships can now be established between lipid structure and bending energetics, paving the way for addressing open fundamental questions in cell membrane mechanics.

Layer-Dependent Interaction Effects in the Electronic Structure of Twisted Bilayer Graphene Devices.

Near the magic angle, strong correlations drive many intriguing phases in twisted bilayer graphene (tBG) including unconventional superconductivity and chern insulation. Whether correlations can tune symmetry breaking phases in tBG at intermediate (≳ 2°) twist angles remains an open fundamental question. Here, using ARPES, we study the effects of many-body interactions and displacement field on the band structure of tBG devices at an intermediate (3°) twist angle. We observe a layer- and doping-dependent renormalization of bands at the K points that is qualitatively consistent with moiré models of the Hartree-Fock interaction. We provide evidence of correlation-enhanced inversion symmetry-breaking, manifested by gaps at the Dirac points that are tunable with doping. These results suggest that electronic interactions play a significant role in the physics of tBG even at intermediate twist angles and present a new pathway toward engineering band structure and symmetry-breaking phases in moiré heterostructures.

Tissue specificity of DNA damage and repair.

DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution. Nonetheless, the emergence of multicellular organisms led to profound differences in cellular context and physiology, leading to large variations in the predominant sources of DNA damage between different cell types, and in the relative contribution of different DNA repair pathways towards genome maintenance in different tissues. While we continue to make large strides into understanding how individual DNA repair mechanisms operate on a molecular level, much less attention is given to these cell type-specific differences. This short review aims to provide a broad overview of DNA damage and repair mechanism to non-specialists, and to highlight some fundamental open questions in tissue and cell-type-specificity of these processes, which may have profound implications for our understanding of important pathophysiological processes such as cancer, neurodegeneration and aging.

Investigating Mammalian Formins with SMIFH2 Fifteen Years in: Novel Targets and Unexpected Biology.

The mammalian formin family comprises fifteen multi-domain proteins that regulate actin dynamics and microtubules in vitro and in cells. Evolutionarily conserved formin homology (FH) 1 and 2 domains allow formins to locally modulate the cell cytoskeleton. Formins are involved in several developmental and homeostatic processes, as well as human diseases. However, functional redundancy has long hampered studies of individual formins with genetic loss-of-function approaches and prevents the rapid inhibition of formin activities in cells. The discovery of small molecule inhibitor of formin homology 2 domains (SMIFH2) in 2009 was a disruptive change that provided a powerful chemical tool to explore formins' functions across biological scales. Here, I critically discuss the characterization of SMIFH2 as a pan-formin inhibitor, as well as growing evidence of unexpected off-target effects. By collating the literature and information hidden in public repositories, outstanding controversies and fundamental open questions about the substrates and mechanism of action of SMIFH2 emerge. Whenever possible, I propose explanations for these discrepancies and roadmaps to address the paramount open questions. Furthermore, I suggest that SMIFH2 be reclassified as a multi-target inhibitor for its appealing activities on proteins involved in pathological formin-dependent processes. Notwithstanding all drawbacks and limitations, SMIFH2 will continue to prove useful in studying formins in health and disease in the years to come.

The Role of Women’s and Men’s Body Shapes in Explicit and Implicit Fat Stigma

Beyond being painful, fat stigma might facilitate pernicious consequences; over and above one’s weight, fat stigma is associated with lesser wellbeing, poorer health, greater all-cause mortality, and weight gains that perpetuate the weight-stigma cycle. To combat fat stigma effectively requires an understanding of the perceptual calculus underlying it. Here, we seized upon new work asserting that importance of a previously overlooked variable in this calculus—fat deposition location (body shape)—and we examine basic but fundamental open questions about the role of body shape in fat stigma via two experiments (one pre-registered). We replicate and extend work investigating how body shape—over and above body size—drives stigma toward women, using a figure set created specifically to test predictions about the role of body shape as well as size. We asked: (1) Are findings of greater explicit stigma toward adult women with abdominal (gut) versus gluteofemoral fat depositions (hips, thighs, buttocks) replicated—and (2) does this same finding hold for implicit stigma?; (3) Are male targets similarly stigmatized as a function of shape? (4) Do individual difference factors known to predict anti-fat stigma, e.g., Protestant Work Ethic, play a role here? We examined these questions by presenting American participants with women and men targets varying in both body size and shape—assessing participants’ explicit stigma (via self-report) and implicit stigma (via the Attitude Misattribution Procedure; AMP). We replicated the pattern that explicit fat stigma toward women is shape-sensitive and extend that to implicit stigma—finding, for example, that, of two women with the same exact heights and higher weights, the woman with abdominal fat deposition is more stigmatized than the woman with gluteofemoral fat deposition. We found no consistent results regarding the role of body shape in driving fat stigma toward men. We also found that some individual difference factors predicting anti-fat stigma were also attuned to body shape as well as body size. The results underscore the importance of integrating body shape into future work on fat stigma (toward women).

A future interstellar probe on the dynamic heliosphere and its interaction with the very local interstellar medium: In-situ particle and fields measurements and remotely sensed ENAs

The recently published Interstellar Probe (ISP) study report describes a pragmatic mission concept with a launch window that starts in 2036 and is expected to reach several hundreds of astronomical units past the heliopause within a time frame of ≥50 years (https://interstellarprobe.jhuapl.edu/Interstellar-Probe-MCR.pdf). Following the ISP report, this paper, that will also be accessible from the Bulletin of the AAS (BAAS) in the framework of the Decadal Survey for Solar and Space Physics (Heliophysics) 2024–2033 (Dialynas et al., A future Interstellar Probe on the dynamic heliosphere and its interaction with the very local interstellar medium: In-situ particle and fields measurements and remotely sensed ENAs, 2022a), aims to highlight the importance of studying the physics of the interactions pertaining to the expanding solar wind that meets the plasma, gas and dust flows of the very local interstellar medium, forming the complex and vast region of our astrosphere. We focus on three fundamental open science questions that reveal the dynamical nature of the heliosphere A) Where are the heliosphere boundaries and how thick is the heliosheath B) Is there a “missing” pressure component towards exploring the dynamics of the global heliosheath and its interaction with the very local interstellar medium C) Why does the shape and size of the global heliosphere appear different in different Energetic Neutral Atom energies? We argue that these questions can only be addressed by exploiting a combination of in-situ charged particle, plasma waves and fields measurements with remotely sensed Energetic Neutral Atoms that can be measured simultaneously from the instruments of a future Interstellar Probe mission, along its trajectory from interplanetary space through the heliosheath and out to the very local interstellar medium.

Rare weak decays and neutrino mass

The question whether neutrinos are Majorana fermions (i.e., their own anti-particles) remains among the most fundamental open questions of subatomic physics. If neutrinos are Majorana particles it would revolutionize our understanding of physics. Although neutrinoless double beta decay, 0νββ, was proposed more than 80 years ago to establish the nature of neutrinos, it remains the most sensitive probe into the non-conservation of lepton number. 0νββ-decay is a postulated extremely slow and yet unobserved radioactive process in which two neutrons (or protons) inside a nucleus transform into two protons (or neutrons) emitting two electrons (or positrons), respectively, but no neutrinos. Its observation would be a breakthrough in the description of elementary particles and would provide fundamental information on the neutrino masses, their nature, and origin. In this paper double beta decay, its connection to neutrino mass, and mechanisms beyond the standard mass mechanism are discussed from a theoretical point of view. The current situation is then addressed by combining theoretical results with recent experimental limits.

Near-future discovery of the diffuse flux of ultrahigh-energy cosmic neutrinos

Ultrahigh-energy (UHE) neutrinos, with EeV-scale energies, carry with them unique insight into fundamental open questions in astrophysics and particle physics. For 50 years, they have evaded discovery, but maybe not for much longer, thanks to new UHE neutrino telescopes, presently under development. We capitalize on this upcoming opportunity by producing state-of-the-art forecasts of the discovery of a diffuse flux of UHE neutrinos in the next 10--20 years. By design, our forecasts are anchored in often-overlooked nuance from theory and experiment; we gear them to the radio array of the planned IceCube-Gen2 detector. We find encouraging prospects: even under conservative analysis choices, most benchmark UHE neutrino flux models from the literature may be discovered within 10 years of detector exposure---many sooner---and may be distinguished from each other. Our results validate the transformative potential of next-generation UHE neutrino telescopes.

Autonomy and mobility simulation time reduction through machine learning while considering uncertainty and reliability prediction

Modeling and simulation (M&S) tools are used extensively throughout the Ground Vehicle Systems Center and the U.S. Army to perform an analysis of ground vehicles more quickly and less expensively than through physical testing. The Computational Research and Engineering Acquisition Tools and Environments-Ground Vehicles (CREATE-GV) project is an M&S software effort that focuses on mobility and autonomous vehicle simulation and analysis, using physics-based three-dimensional modeling to accurately calculate a variety of ground vehicle metrics and parameters of interest. However, because these simulations are high fidelity, they often require a great deal of computational power and time. One approach to reducing simulation time that has proved effective in certain contexts is the creation of “surrogate models” through machine learning (ML) algorithms. However, it is often very challenging to accurately predict the mobility of a ground vehicle system in general, and there is no existing model that can predict the mobility of autonomous systems. A great deal of uncertainty exists in the mobility and autonomy area of physics-based simulation models related to modeling assumptions, terrain conditions, and insufficient knowledge of interactions between the vehicle and terrain. Understanding how the uncertainties inherent in autonomous mobility prediction affect model accuracy is still an open fundamental research question. We present a surrogate modeling approach leveraging ML algorithms to work with CREATE-GV to increase the computation speed of mobility assessments while still considering the reliability of the mobility predictions under uncertainty.

The light detection system of the ICARUS detector in the Short Baseline Neutrino program at Fermilab

The Short Baseline Neutrino (SBN) program at Fermilab is an extensive experimental programme aiming at searching for sterile neutrino(s) [1], whose existence is one of the fundamental open questions of neutrino physics. It employs three Liquid Argon Time Projection Chamber (LArTPC) detectors, called ICARUS, MicroBooNE and SBND, sampling the Booster Neutrino Beam (BNB) at different locations from its target. The SBN detectors, working near the Earth’s surface, are subjected to a substantial cosmic background, which can mimic genuine neutrino interactions. Thus, it is essential to distinguish the signals related to the neutrino beams from those induced by the cosmic rays. The light detection system is a vital part of LArTPCs, but its role is even more critical for surface-operating detectors like ICARUS. The ICARUS light detection system is based on 360 Photomultiplier Tubes (PMTs). Its main role is to provide an efficient trigger and contribute to the 3D reconstruction of detected events. The light detection system calibration and further trigger system improvements were performed for the final detector configuration during the detector commissioning at Fermilab. The trigger system effectively exploits the information given by the PMTs. To further increase that system’s efficiency in event filtering, an alternative method based on Convolutional Neural Network (CNN) has been developed. Simulation-based results show that this technique can reduce the cosmic background by up to 76% with a neutrino selection efficiency of 99%. However, to filter the real data cases, which are usually not identical to the simulated ones, this method was improved by applying Domain Adversarial Neural Network (DANN). The results prove that adversarial training through a DANN can alleviate the simulation bias, demonstrating the first successful application of DANN for CNN as an event classifier for a LArTPC.

Understanding stochastic and deterministic assembly processes in microbial communities along temporal, spatial and environmental scales.

Identifying the main drivers of community assembly remains an open fundamental question in ecology. Dispersal processes introduce randomness in community composition while selection for particular environments creates predictable assemblages. However, the interaction between selection and dispersal processes is still poorly understood. Here, we address this question in bacterial and microeukaryotic communities inhabiting a highly dynamic system of ephemeral (hyper)saline lakes. We show that the combination of beta-diversity decomposition methods and a temporal approach based on colonization and extinction dynamics yields new insights into the relative effect of selection and dispersal along environmental gradients. Selective pressure and dispersal-related processes simultaneously shape each local community with variable strength and effect. The dominance of selection vs. dispersal shifted from stochastic to deterministic assembly as salinity increased along the gradient. This transition also had an impact on the temporal dynamics of the lakes as community turnover decreased at high salinities because both colonization and extinction rates slowed down. Only microeukaryotic richness decreased along the gradient due to lower effective colonization at higher salinities, suggesting that the net effect of selection and dispersal is determined by both environmental conditions and the idiosyncrasy of the different microbial ecologies. Our results emphasize the use of temporal approaches in combination with standard statistical methods for a better understanding of the dynamic processes underlying community assembly.

Foundation of the Unicentric Model of the Observable Universe—UNIMOUN

In view of the growing difficulties of ΛCDM-cosmologies to compete with recent highly accurate cosmological observations, I propose the alternative model: the Unicentric Model of the Observable UNiverse (UNIMOUN). The model relies on employing a new time-dependent -metric for the GR field equations, which enables reversible phase transitions between normal compressible fluids and incompressible quantum superfluids, necessary for studying the cosmic evolution of the observable universe. The main properties of UNIMOUN read: 1) The observable universe was born in a flat spacetime environment, which is a tiny fraction of our infinitely large and flat parent universe, 2) Our big bang (BB) happened to occur in our neighbourhood, thereby endowing the universe the observed homogeneity and isotropy, 3) The energy density in the universe is upper-bounded by the universal critical density , beyond which matter becomes purely incompressible, rendering formation of physical singulareties, and in particular black holes, impossible, 4) Big bangs are neither singular events nor invoked by external forces, but rather, they are common self-sustaining events in our parent universe, 5) The progenitors of BBs are created through the merger of cosmically dead and inactive neutron stars and/or through “supermassive black holes” that are currently observed at the centres of most massive galaxies, 6) The progenitors are made up of purely incompressible entropy-free superconducting gluon- quark superfluids with (SuSu-matter), which endows these giant objects measurable sizes, 7) Spacetimes embedding SuSu-matter are conformally flat. It is shown that UNIMOUN is capable of dealing with or providing answers to several fundamental open questions in astrophysics and cosmology without invoking inflation, dark matter or dark energy.

Reconstructing the Genomic History of Multiple Myeloma Precursor Disease: Novel Insights and Clinical Applicability

Introduction Early indolent stages of Multiple Myeloma (MM), which include monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), are heterogeneous diseases with overall rates of progression of 1% to 10% per year. Mutations present in MGUS and SMM have been characterized by our group and others and improve current risk models. However, whether any genomic events are sufficient for an MGUS or SMM to transform to MM remains an open fundamental question. To address this, we sequenced the largest cohort of MGUS and SMM genomes to date starting with a low-input DNA template, enriching for low burden of disease compared to previous studies. We report the translational implications of a large-scale characterization of indolent stages of MM after 2 years of follow-up. Methods Bone marrow (BM) samples were collected from 130 patients with MGUS and SMM after informed consent for research use (IRB #14-174). Plasma cells were selected from BM samples using CD138+ magnetic beads before DNA purification and library construction. Tumor and matched germline libraries were whole-genome sequenced (WGS) to 60X and 30X coverage respectively on NovaSeq 6000 S4 flowcells at the Genomics Platform of the Broad Institute. Analysis was performed with methods from the Cancer Program of the Broad Institute. All structural variants were manually reviewed and compared to fluorescence in situ hybridization (FISH) clinical laboratory reports. Results The median age of participants was 62 (range, 37 to 87), with 52% female. At the time of BM sampling, all patients were untreated; 24 patients diagnosed with MGUS (18%) and 106 diagnosed with SMM (82%) were homogeneously distributed across the IMWG 2/20/20 risk stratification stages (Low-risk: 32%, Intermediate-risk: 34%, High-risk: 34%). Somatic mutation burden increased with progressive disease staging, with a median of 2,666 single-nucleotide variants in MGUS (range 429-6546), and 3,233, 4,080, and 5,111 in low, intermediate, and high-risk SMM, respectively (range 463-11083, 161-8408, and 2549-7218, respectively, P=0.007). Compared to non-progressors, progressors were found to have an increase of molecular clock signature, symbolizing continuous accumulation of mutations over time (Fold change 2.40, P=0.002), and this difference was independent of patient age and disease stage. Confirming previous studies, APOBEC signature was strongly associated with patients with MAF alterations (t(14;16), t(14;20), median in MAF, 24%, non-MAF, 5.8%, P=3E-5), and uniquely identified in one patient with MMSET t(4;14) translocation. Catastrophic structural variants (SV) such as chromothripsis and chromoplexy were found in 7% of patients across 2/20/20 stages. Complex SVs were strongly associated with clinical progression to symptomatic MM (Odds Ratio (OR) 9.83, CI95%[1.91, 53]). Being statistically independent of risk staging, these events are a potential new risk factor not captured by current clinical models, but successfully characterized by an unbiased genomic assay. In our cohort, MYC was found rearranged with IgL, IgH, and other partners in 9% of patients. Strikingly, all but one case also harbored a RAS hotspot mutation, showing a strong non-random cooperation between RAS and MYC (P=0.005), not previously observed, which translated into increased risk of clinical progression (OR 7.75, CI95%[1.26, 48.8]). Moreover, most MYC-abnormal tumors (translocation or complex rearrangement) were missed by clinical FISH testing. WGS detected >99% of translocations and copy number abnormalities reported by FISH. In clinical reports with unknown translocations, WGS could identify translocation partners, including IgH-MYC and rare IgH-MAFA. In 82% of patients, an increased diagnostic yield was found by WGS compared to FISH using existing models, showing clinical applicability to replace molecular cytogenetics. Conclusion Analysis of the largest cohort of MGUS and SMM genomes to date was able to decipher the genomic history of MM, unraveling events including molecular clock signature, APOBEC, complex SVs, and MYC/RAS cooperation. This can further define a genomic risk model of disease progression independent of clinical tumor burden markers such as 2/20/20. This highlights the potential of WGS to solve the "missing predictability" of current clinical models of progression.

Most general class of quasiprobability distributions of work.

How to give a statistical description of the thermodynamics in quantum systems is an open fundamental question. Concerning the work, the presence of initial quantum coherence in the energy basis can give rise to a quasiprobability of work, which can take negative values. Our aim is to identify the most general quasiprobability of work satisfying some fundamental conditions. By doing so, we introduce a general notion of quasiprobability in analogy to Gleason's theorem. Then, we use these quasiprobabilities to define the quasiprobability of work, and finally we discuss the contextuality of the protocol.

A Schmidt Decomposition Approach to Quantum Thermodynamics.

The development of a self-consistent thermodynamic theory of quantum systems is of fundamental importance for modern physics. Still, despite its essential role in quantum science and technology, there is no unifying formalism for characterizing the thermodynamics within general autonomous quantum systems, and many fundamental open questions remain unanswered. Along these lines, most current efforts and approaches restrict the analysis to particular scenarios of approximative descriptions and semi-classical regimes. Here, we propose a novel approach to describe the thermodynamics of arbitrary bipartite autonomous quantum systems based on the well-known Schmidt decomposition. This formalism provides a simple, exact, and symmetrical framework for expressing the energetics between interacting systems, including scenarios beyond the standard description regimes, such as strong coupling. We show that this procedure allows straightforward identification of local effective operators suitable for characterizing the physical local internal energies. We also demonstrate that these quantities naturally satisfy the usual thermodynamic notion of energy additivity.

Solitary waves explore the quantum-to-classical transition

How the classical appearance of our environment arises from the underlying quantum many-body theory is an open fundamental question. We propose that phenomena involved in the quantum-to-classical transition can be probed in collisions of bright solitary waves in Bose-Einstein condensates, where thousands of atoms form a large compound object at ultra cold temperatures. For the experimentally most relevant quasi-1D regime, where integrability is broken through effective three-body interactions, we find that ensembles of solitary waves exhibit complex interplay between phase coherence and entanglement generation in beyond mean-field simulations using the truncated Wigner method: An initial state of two solitons with a well-defined relative phase looses that phase coherence in the ensemble, with its single-particle two-mode density matrix exhibiting similar dynamics as a decohering two-mode superposition. This apparent decoherence is a prerequisite for the formation of entangled superpositions of different atom numbers in a subsequent soliton collision. The necessity for the solitons to first decohere is explained based on the underlying phase-space of the quintic mean-field equation. We show elsewhere that superpositions of different atom numbers later further evolve into spatially entangled solitons. Loss of ensemble phase coherence followed by system internal entanglement generation appear in an unusual order in this closed system, compared to a typical open quantum system.