@article{12330, abstract = {The design and implementation of efficient concurrent data structures has seen significant attention. However, most of this work has focused on concurrent data structures providing good worst-case guarantees, although, in real workloads, objects are often accessed at different rates. Efficient distribution-adaptive data structures, such as splay-trees, are known in the sequential case; however, they often are hard to translate efficiently to the concurrent case. We investigate distribution-adaptive concurrent data structures, and propose a new design called the splay-list. At a high level, the splay-list is similar to a standard skip-list, with the key distinction that the height of each element adapts dynamically to its access rate: popular elements “move up,” whereas rarely-accessed elements decrease in height. We show that the splay-list provides order-optimal amortized complexity bounds for a subset of operations, while being amenable to efficient concurrent implementation. Experiments show that the splay-list can leverage distribution-adaptivity for performance, and can outperform the only previously-known distribution-adaptive concurrent design in certain workloads.}, author = {Aksenov, Vitalii and Alistarh, Dan-Adrian and Drozdova, Alexandra and Mohtashami, Amirkeivan}, issn = {1432-0452}, journal = {Distributed Computing}, pages = {395--418}, publisher = {Springer Nature}, title = {{The splay-list: A distribution-adaptive concurrent skip-list}}, doi = {10.1007/s00446-022-00441-x}, volume = {36}, year = {2023}, } @article{12159, abstract = {The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relationship between haplotype blocks and ancestral structure, emphasizing the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical data set. While the advent of new, computationally efficient methods makes it possible to apply these concepts broadly, they (and additional new methods) could benefit from adding features to explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.}, author = {Shipilina, Daria and Pal, Arka and Stankowski, Sean and Chan, Yingguang Frank and Barton, Nicholas H}, issn = {1365-294X}, journal = {Molecular Ecology}, keywords = {Genetics, Ecology, Evolution, Behavior and Systematics}, number = {6}, pages = {1441--1457}, publisher = {Wiley}, title = {{On the origin and structure of haplotype blocks}}, doi = {10.1111/mec.16793}, volume = {32}, year = {2023}, } @article{12114, abstract = {Probing the dynamics of aromatic side chains provides important insights into the behavior of a protein because flips of aromatic rings in a protein’s hydrophobic core report on breathing motion involving a large part of the protein. Inherently invisible to crystallography, aromatic motions have been primarily studied by solution NMR. The question how packing of proteins in crystals affects ring flips has, thus, remained largely unexplored. Here we apply magic-angle spinning NMR, advanced phenylalanine 1H-13C/2H isotope labeling and MD simulation to a protein in three different crystal packing environments to shed light onto possible impact of packing on ring flips. The flips of the two Phe residues in ubiquitin, both surface exposed, appear remarkably conserved in the different crystal forms, even though the intermolecular packing is quite different: Phe4 flips on a ca. 10–20 ns time scale, and Phe45 are broadened in all crystals, presumably due to µs motion. Our findings suggest that intramolecular influences are more important for ring flips than intermolecular (packing) effects.}, author = {Gauto, Diego F. and Lebedenko, Olga O. and Becker, Lea Marie and Ayala, Isabel and Lichtenecker, Roman and Skrynnikov, Nikolai R. and Schanda, Paul}, issn = {2590-1524}, journal = {Journal of Structural Biology: X}, keywords = {Structural Biology}, publisher = {Elsevier}, title = {{Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD}}, doi = {10.1016/j.yjsbx.2022.100079}, volume = {7}, year = {2023}, } @article{12163, abstract = {Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.}, author = {Loose, Martin and Auer, Albert and Brognara, Gabriel and Budiman, Hanifatul R and Kowalski, Lukasz M and Matijevic, Ivana}, issn = {1873-3468}, journal = {FEBS Letters}, keywords = {Cell Biology, Genetics, Molecular Biology, Biochemistry, Structural Biology, Biophysics}, number = {6}, pages = {762--777}, publisher = {Wiley}, title = {{In vitro reconstitution of small GTPase regulation}}, doi = {10.1002/1873-3468.14540}, volume = {597}, year = {2023}, } @article{12164, abstract = {A shared-memory counter is a widely-used and well-studied concurrent object. It supports two operations: An Inc operation that increases its value by 1 and a Read operation that returns its current value. In Jayanti et al (SIAM J Comput, 30(2), 2000), Jayanti, Tan and Toueg proved a linear lower bound on the worst-case step complexity of obstruction-free implementations, from read-write registers, of a large class of shared objects that includes counters. The lower bound leaves open the question of finding counter implementations with sub-linear amortized step complexity. In this work, we address this gap. We show that n-process, wait-free and linearizable counters can be implemented from read-write registers with O(log2n) amortized step complexity. This is the first counter algorithm from read-write registers that provides sub-linear amortized step complexity in executions of arbitrary length. Since a logarithmic lower bound on the amortized step complexity of obstruction-free counter implementations exists, our upper bound is within a logarithmic factor of the optimal. The worst-case step complexity of the construction remains linear, which is optimal. This is obtained thanks to a new max register construction with O(logn) amortized step complexity in executions of arbitrary length in which the value stored in the register does not grow too quickly. We then leverage an existing counter algorithm by Aspnes, Attiya and Censor-Hillel [1] in which we “plug” our max register implementation to show that it remains linearizable while achieving O(log2n) amortized step complexity.}, author = {Baig, Mirza Ahad and Hendler, Danny and Milani, Alessia and Travers, Corentin}, issn = {1432-0452}, journal = {Distributed Computing}, keywords = {Computational Theory and Mathematics, Computer Networks and Communications, Hardware and Architecture, Theoretical Computer Science}, pages = {29--43}, publisher = {Springer Nature}, title = {{Long-lived counters with polylogarithmic amortized step complexity}}, doi = {10.1007/s00446-022-00439-5}, volume = {36}, year = {2023}, } @article{12172, abstract = {In industrial reactors and equipment, non-ideality is quite a common phenomenon rather than an exception. These deviations from ideality impact the process's overall efficiency and the effectiveness of the equipment. To recognize the associated non-ideality, one needs to have enough understanding of the formulation of the equations and in-depth knowledge of the residence time distribution (RTD) data of real reactors. In the current work, step input and pulse input were used to create RTD data for Cascade continuous stirred tank reactors (CSTRs). For the aforementioned configuration, experiments were run at various flow rates to validate the developed characteristic equations. To produce RTD data, distilled water was utilized as the flowing fluid, and NaOH was the tracer substance. The ideal behavior of tracer concentration exits age distribution, and cumulative fraction for each setup and each input was plotted and experimental results were compared with perfect behavior. Deviation of concentration exit age distribution and cumulative fractional distribution from ideal behavior is more in pulse input as compared to a step input. For ideal cases, the exit age distribution curve and cumulative fraction curves are independent of the type of input. But a significant difference was observed for the two cases, which may be due to non-measurable fluctuations in volumetric flow rate, non-achievement of instant injection of tracer in case of pulse input, and slight variations in the sampling period. Further, with increasing flow rate, concentration, exit age, and cumulative fractional curves shifted upward, and this behavior matches with the actual case.}, author = {Khatoon, Bushra and Kamil, Shoaib and Babu, Hitesh and Siraj Alam, M.}, issn = {2214-7853}, journal = {Materials Today: Proceedings}, keywords = {General Medicine}, number = {Part 1}, pages = {40--47}, publisher = {Elsevier}, title = {{Experimental analysis of Cascade CSTRs with step and pulse inputs}}, doi = {10.1016/j.matpr.2022.11.037}, volume = {78}, year = {2023}, } @article{12515, abstract = {Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents. Methods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques. Results: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity. Discussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.}, author = {Ortiz-Leal, Irene and Torres, Mateo V. and Vargas Barroso, Victor M and Fidalgo, Luis Eusebio and López-Beceiro, Ana María and Larriva-Sahd, Jorge A. and Sánchez-Quinteiro, Pablo}, issn = {1662-5129}, journal = {Frontiers in Neuroanatomy}, publisher = {Frontiers}, title = {{The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway}}, doi = {10.3389/fnana.2022.1097467}, volume = {16}, year = {2023}, } @article{12106, abstract = {Regulation of chromatin states involves the dynamic interplay between different histone modifications to control gene expression. Recent advances have enabled mapping of histone marks in single cells, but most methods are constrained to profile only one histone mark per cell. Here, we present an integrated experimental and computational framework, scChIX-seq (single-cell chromatin immunocleavage and unmixing sequencing), to map several histone marks in single cells. scChIX-seq multiplexes two histone marks together in single cells, then computationally deconvolves the signal using training data from respective histone mark profiles. This framework learns the cell-type-specific correlation structure between histone marks, and therefore does not require a priori assumptions of their genomic distributions. Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single cells across a range of mark combinations. Modeling dynamics of in vitro macrophage differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq unlocks systematic interrogation of the interplay between histone modifications in single cells.}, author = {Yeung, Jake and Florescu, Maria and Zeller, Peter and De Barbanson, Buys Anton and Wellenstein, Max D. and Van Oudenaarden, Alexander}, issn = {1546-1696}, journal = {Nature Biotechnology}, pages = {813–823}, publisher = {Springer Nature}, title = {{scChIX-seq infers dynamic relationships between histone modifications in single cells}}, doi = {10.1038/s41587-022-01560-3}, volume = {41}, year = {2023}, } @article{12183, abstract = {We consider a gas of n bosonic particles confined in a box [−ℓ/2,ℓ/2]3 with Neumann boundary conditions. We prove Bose–Einstein condensation in the Gross–Pitaevskii regime, with an optimal bound on the condensate depletion. Moreover, our lower bound for the ground state energy in a small box [−ℓ/2,ℓ/2]3 implies (via Neumann bracketing) a lower bound for the ground state energy of N bosons in a large box [−L/2,L/2]3 with density ρ=N/L3 in the thermodynamic limit.}, author = {Boccato, Chiara and Seiringer, Robert}, issn = {1424-0637}, journal = {Annales Henri Poincare}, pages = {1505--1560}, publisher = {Springer Nature}, title = {{The Bose Gas in a box with Neumann boundary conditions}}, doi = {10.1007/s00023-022-01252-3}, volume = {24}, year = {2023}, } @article{12544, abstract = {Geometry is crucial in our efforts to comprehend the structures and dynamics of biomolecules. For example, volume, surface area, and integrated mean and Gaussian curvature of the union of balls representing a molecule are used to quantify its interactions with the water surrounding it in the morphometric implicit solvent models. The Alpha Shape theory provides an accurate and reliable method for computing these geometric measures. In this paper, we derive homogeneous formulas for the expressions of these measures and their derivatives with respect to the atomic coordinates, and we provide algorithms that implement them into a new software package, AlphaMol. The only variables in these formulas are the interatomic distances, making them insensitive to translations and rotations. AlphaMol includes a sequential algorithm and a parallel algorithm. In the parallel version, we partition the atoms of the molecule of interest into 3D rectangular blocks, using a kd-tree algorithm. We then apply the sequential algorithm of AlphaMol to each block, augmented by a buffer zone to account for atoms whose ball representations may partially cover the block. The current parallel version of AlphaMol leads to a 20-fold speed-up compared to an independent serial implementation when using 32 processors. For instance, it takes 31 s to compute the geometric measures and derivatives of each atom in a viral capsid with more than 26 million atoms on 32 Intel processors running at 2.7 GHz. The presence of the buffer zones, however, leads to redundant computations, which ultimately limit the impact of using multiple processors. AlphaMol is available as an OpenSource software.}, author = {Koehl, Patrice and Akopyan, Arseniy and Edelsbrunner, Herbert}, issn = {1549-960X}, journal = {Journal of Chemical Information and Modeling}, number = {3}, pages = {973--985}, publisher = {American Chemical Society}, title = {{Computing the volume, surface area, mean, and Gaussian curvatures of molecules and their derivatives}}, doi = {10.1021/acs.jcim.2c01346}, volume = {63}, year = {2023}, }