IST Austria: PubRep (Institute of Science and Technology)
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Causes and consequences of sex-chromosome turnovers in Diptera
Sex-chromosome systems are highly variable across animals, but how they transition from one to another is not well understood. Diptera have undergone multiple sex-chromosome turnovers and expansions while maintaining their general chromosomal content, which makes them an ideal clade to study such transitions. We analysed more than 100 dipteran whole-genome assemblies and identified 4 new lineages that underwent sex-chromosome turnover (in addition to the 5 previously reported). We find the majority of turnovers happened in the group Schizophora, which tend to have fewer genes on the F element (the chromosome homologous to the ancestral insect X chromosome) than lower dipterans, a factor previously hypothesized to facilitate turnover. Most derived X chromosomes have higher GC content than autosomes, consistent with a high prevalence of male-achiasmy in Diptera. In addition, an excess of gene movement out of the X is detected for most of these new X chromosomes, and many of these moved genes have high testis expression in Drosophila, suggesting that out-of-X gene movement contributes to the long-term demasculinization of X chromosomes
PMLR
The high computational costs of large language models (LLMs) have led to a flurry of research on LLM compression, via methods such as quantization, sparsification, or structured pruning. A new frontier in this area is given by dynamic, non-uniform compression methods, which adjust the compression levels (e.g., sparsity) per-block or even per-layer in order to minimize accuracy loss, while guaranteeing a global compression threshold. Yet, current methods rely on estimating the "importance" of a given layer, implicitly assuming that layers contribute independently to the overall compression error. We begin from the motivating observation that this independence assumption does not generally hold for LLM compression: pruning a model further may even significantly recover performance. To address this, we propose EvoPress, a novel evolutionary framework for dynamic LLM compression. By formulating dynamic compression as a general optimization problem, EvoPress identifies optimal compression profiles in a highly efficient manner, and generalizes across diverse models and compression techniques. Via EvoPress, we achieve state-of-the-art performance for dynamic compression of Llama, Mistral, and Phi models, setting new benchmarks for structural pruning (block/layer dropping), unstructured sparsity, and quantization with dynamic bitwidths
ISTA Thesis
Life on Earth emerged when biomacromolecules were membrane-enclosed in a confined space where many essential chemical reactions were more likely to happen and thereby accelerate evolution. These kinds of membranes separated internal reactions from the outside chaos while staying flexible so that those primordial cells can move, adopt their shape and, most importantly, propagate. Such membrane plasticity still remains a defining feature of all modern cell types. This remarkable ability to change their shape is most prominently observed during their propagation (i.e., cell division). Throughout division, a cell undergoes drastic change in its shape, usually at the middle of the cell, pulling the two opposite membrane sides inward, closer to each other, and, finally, culminating in pinching off to separate the cell into two daughter cells. To achieve this, a cell needs to employ a protein machinery, usually termed divisome, that can coordinate all necessary intracellular processes with membrane remodelling and synthesis of other extracellular structures that decorate a cell. The focus of this dissertation is a membrane-remodelling FtsZ system that is present across all domains of life. FtsZ forms filaments that further self-organize into ring-like structures at the cell septum and together with other division proteins perform cell envelope synthesis and constriction. However, there are still knowledge gaps in our mechanistic understanding of division in both archaea and bacteria. My work presented in this dissertation centres around a simple yet not well understood question: How is the divisome positioned correctly at the mid-cell? To achieve the proper positioning, the divisome needs to (i) be recruited to the mid-cell and (ii) localized orthogonally to the long cell axis. I tackle these processes in two different systems by applying an in vitro biochemical bottom-up reconstitution approach. I use purified components of Haloferax volcanii and Escherichia coli divisome to explore how divisome is recruited to the mid-cell in archaea and how the Z-ring positions orthogonally to the long cell axis in bacteria, respectively.
Firstly, I collaborate with archaeal cell and structural biologists to explore the assembly of early division proteins in two FtsZ-containing archaeon H. volcanii, a standard model system for understudied archaeal organisms. I particularly address the hierarchy of interactions that allow a tripartite complex formation (SepF-CdpB1-CdpB2) and how the hierarchy of interactions ultimately leads to the recruitment of FtsZ filaments to the septum. This part of work has been published in (Nußbaum et al., 2024). In collaboration with evolutionary biologists, I shed light on ancient features that archaeal divisome has retained to this day and also speculate on a property that it might have lost during the course of evolution.
Next, I switch my attention to E. coli divisome. Particularly, I address the FtsZ’s intrinsic biophysical property that drives the Z-ring diameter, and thereby the perpendicular orientation of the Z-ring to the long cell axis based on suggested membrane curvature sensing mechanism (Vanhille-Campos et al., 2024). This property allows formation of different Z-ring diameters that match the variety of cell diameters present in prokaryotes. The results showcase that the distribution of charged amino acids in the intrinsically disordered linker at the C-terminus (CTL) of FtsZ is the major determining factor of Z-ring diameter with inter-CTL interactions as an underlying mechanism.
Finally, I thoroughly explain the methodology I used to address the abovementioned projects, and I finish with a discussion on how early archaeal divisome assembly and curvature sensing mechanism in bacteria, at first sight unrelated topics, are interconnected and important groundwork for both fundamental and translational research
Research Data for: 'One-milligram torsional pendulum toward experiments at the quantum-gravity interface'
Probing the possibility of entanglement generation through gravity offers a path to tackle the question of whether gravitational fields possess a quantum mechanical nature. A potential realization necessitates systems with low-frequency dynamics at an optimal mass scale, for which the microgram-to-milligram range is a strong contender. Here, after refining a figure-of-merit for the problem, we present a 1-milligram torsional pendulum operating at 18 Hz. We demonstrate laser cooling its motion from room temperature to 240~microkelvins, surpassing by over 20-fold the coldest motions attained for oscillators ranging from micrograms to kilograms. We quantify and contrast the utility of the current approach with other platforms. The achieved performance and large improvement potential highlight milligram-scale torsional pendulums as a powerful platform for precision measurements relevant to future studies at the quantum-gravity interface
Sensitized disequilibration of water-soluble azopolymers
Photo-responsive systems based on azobenzenes usually require UV light for E→Z isomerization, limiting their applicability, especially in biomedical contexts. Disequilibration by sensitization of azobenzene under confinement (DESC) has recently emerged as a supramolecular strategy to bypass this limitation without the need to derivatize the azobenzene scaffold. Here, we expand DESC to water-soluble azopolymers obtained by RAFT polymerization and systematically investigate the interplay between the polymer structure and DESC efficiency. Using this approach, we achieved as much as 85% of the direct photoexcitation (UV) switching efficiency, while utilizing low-energy (yellow) light. These results establish general design principles for combining DESC with polymeric systems, opening new opportunities for the development of functional materials driven with low-energy light
Hypernode automata
In this work, we present hypernode automata as a specification formalism for hyperproperties of systems whose executions may be misaligned among themselves, such as concurrent systems. These automata consist of nodes labeled with hypernode logic formulas and transitions marked with synchronizing actions. Hypernode logic formulas establish relations between sequences of variable values among different system executions. This logic enables both synchronous and asynchronous analysis of traces. In its asynchronous view on execution traces, hypernode formulas establish relations on the order of value changes for each variable without correlating their timing. In both views, the analysis of different execution traces is synchronized through the transitions of hypernode automata. By combining logic’s declarative nature with automata’s procedural power, hypernode automata seamlessly integrate asynchronicity requirements at the node level with synchronicity between node transitions. We show that the model-checking problem for hypernode automata is decidable for specifications where each node specifies either a synchronous or an asynchronous requirement for the system’s executions, but not both
On modulo ℓ cohomology of p-adic Deligne–Lusztig varieties for GLn
In 1976, Deligne and Lusztig realized the representation theory of finite groups of Lie type inside étale cohomology of certain algebraic varieties. Recently, a p-adic version of this theory started to emerge: there are p-adic Deligne–Lusztig spaces, whose cohomology encodes representation theoretic information for p-adic groups – for instance, it partially realizes the local Langlands correspondence with characteristic zero coefficients. However, the parallel case of coefficients of positive characteristic ℓ≠p has not been inspected so far. The purpose of this article is to initiate such an inspection. In particular, we relate cohomology of certain p-adic Deligne–Lusztig spaces to Vignéras's modular local Langlands correspondence for GLn
Bridging basic science and applied diagnostics: Comprehensive viral diagnostics enabled by graphene-based electronic biosensor technology advancements
This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making
Microplastics settling in turbid water: Impacts of sediments-induced flow patterns on particle deposition rates
When microplastics (MPs) enter water bodies, they undergo various transport processes, including sedimentation, which can be influenced by factors such as particle size, density, and interactions with other particles. Surface waters contain suspended natural particles (e.g., clay and silt), which may impact MP settling rates. Here, we investigated how the presence of suspended sediments (SS) influenced the deposition patterns and rates of MPs in turbid waters. We systematically analyzed the settling velocities of particles, including different MP sizes and SS concentrations, in a plexiglass column with a camera array. For each experimental variant, we collected data on thousands of individual MPs, strengthening the statistical analysis of the particles’ velocities. Simultaneous measurements of the SS flow and MPs trajectories revealed that the SS induced complex flow patterns, with MPs spending more time in downwelling flow regions, thereby accelerating MPs sedimentation. This effect was more pronounced when SS were aggregated. Additionally, we found that smaller MP fragments were more affected by the fluctuations than spheres or larger fragments. Collectively, our results provide valuable data for future MP fate models and help to understand the sedimentation processes of MPs in natural waters, which is crucial for assessing their environmental transport and impact
Variability of central stars of planetary nebulae with the zwicky transient facility. I. Methods, short-timescale variables, and the unusual nucleus of WeSb 1
A complete understanding of the central stars of planetary nebulae (CSPNe) remains elusive. Over the past several decades, time-series photometry of CSPNe has yielded significant results including, but not limited to, discoveries of nearly 100 binary systems, insights into pulsations and winds in young white dwarfs, and studies of stars undergoing very late thermal pulses. We have undertaken a systematic study of optical photometric variability of cataloged CSPNe, using the light curves from the Zwicky Transient Facility (ZTF). By applying appropriate variability metrics, we arrive at a list of 94 highly variable CSPN candidates. Based on the timescales of the light-curve activity, we classify the variables broadly into short- and long-timescale variables. In this first paper in this series, we focus on the former, which is the majority class comprising 83 objects. We report periods for six sources for the first time, and recover several known periodic variables. Among the aperiodic sources, most exhibit a jitter around a median flux with a stable amplitude, and a few show outbursts. We draw attention to WeSb 1, which shows a different kind of variability: prominent deep and aperiodic dips, resembling transits from a dust/debris disk. We find strong evidence for a binary nature of WeSb 1 (possibly an F-type subgiant companion). The compactness of the emission lines and inferred high electron densities make WeSb 1 a candidate for either an EGB 6-type planetary nucleus, or a symbiotic system inside an evolved planetary nebula, both of which are rare objects. To demonstrate further promise with ZTF, we report three additional newly identified periodic sources that do not appear in the list of highly variable sources. Finally, we also introduce a two-dimensional metric space defined by the von Neumann statistics and Pearson Skew and demonstrate its effectiveness in identifying unique variables of astrophysical interest, like WeSb 1