Miracle-dz/UniFAR-FTUs huggingface dataset:
Entanglement in quantum impurity problems is nonperturbative

We study the entanglement entropy of a region of length 2L with the remainder of an infinite one-dimensional gapless quantum system in the case where the region is centered on a quantum impurity. The coupling to this impurity is not scale invariant, and the physics involves a crossover between weak- and strong-coupling regimes. While the impurity contribution to the entanglement has been computed numerically in the past, little is known analytically about it, since in particular the methods of conformal invariance cannot be applied because of the presence of a crossover length. We show in this paper that the small coupling expansion of the entanglement entropy in this problem is quite generally plagued by strong infrared divergences, implying a nonperturbative dependence on the coupling. The large coupling expansion turns out to be better behaved, thanks to powerful results from the boundary CFT formulation and, in some cases, the underlying integrability of the problem. However, it is clear that this expansion does not capture well the crossover physics. In the integrable case—which includes problems such as an XXZ chain with a modified link, the interacting resonant level model or the anisotropic Kondo model—a nonperturbative approach is in principle possible using form factors. We adapt in this paper the ideas of Cardy et al. [J. Stat. Phys. 130, 129 (2008)] and Castro-Alvaredo and Doyon [J. Stat. Phys. 134, 105 (2009)] to the gapless case and show that, in the rather simple case of the resonant level model, and after some additional renormalizations, the form-factors approach yields remarkably accurate results for the entanglement all the way from short to large distances. This is confirmed by detailed comparison with numerical simulations. Both our form factor and numerical results are compatible with a nonperturbative form at short distance.
Zero Overhead Monitoring for Cloud-native Infrastructure using RDMA

Cloud services have recently undergone a major shift from monolithic designs to microservices running on the cloud-native infrastructure, where monitoring systems are widely deployed to ensure the service level agreement (SLA). Nev-ertheless, the traditional monitoring system no longer fulﬁlls the demands of cloud-native monitoring, which is observed from the practical experience in Alibaba cloud. Speciﬁcally, the monitor occupies resources ( e.g. , CPU) of the monitored infrastructure, disturbing services running on it. For example, enabling monitor causes jitters/declines of online services in Alibaba’s “double eleven” shopping festival with high loads. On the other hand, the quality of service (QoS) of monitoring itself, which is vital to track and ensure SLA, is not guaranteed with the high loaded system. In this paper, we design and implement a novel monitoring system, named Z ERO , for cloud-native monitoring. First, Z ERO achieves zero overhead to collect raw metrics from the monitored hosts using one-sided remote direct memory access (RDMA) operations, thus avoiding any interferences to cloud services. Second, Z ERO adopts receiver-driven model to collect monitoring metrics with high QoS, where credit-based ﬂow control and hybrid I/O model are proposed to mitigate network congestion/interference and CPU bottlenecks. Z ERO has been deployed and evaluated in Alibaba cloud. Deployment results show that Z ERO achieves no CPU occupation at the monitored host and supports 1 ∼ 10 k hosts with 0 . 1 ∼ 1 s sampling interval using single thread for network I/O.
In vivo calcium imaging shows that satellite glial cells have increased activity in painful states

Satellite glial cells (SGCs) are important for proper neuronal function of primary sensory neurons to whom they provide homeostatic support. Most research of SGC function has been performed with in vitro studies, but recent advances in calcium imaging and transgenic mouse models have enabled this first in vivo study of single cell SGC function in mouse models of inflammation and neuropathic pain. We found that in naïve condition SGCs do not respond in a time-locked fashion to neuronal firing. In painful inflammatory and neuropathic states we detected time-locked signals in a subset of SGCs, but only with suprathreshold stimulation of the sciatic nerve. Surprisingly therefore, we conclude that most calcium signals in SGCs seem to develop at arbitrary intervals not directly linked to neuronal activity patterns. More in line with expectations, our experiments also revealed that the number of active SGCs was increased under conditions of inflammation or nerve injury. This could reflect the increased requirement for homeostatic support across dorsal root ganglion neuron populations, which are more active during such painful states.
Sprague-Dawley Rats Differ in Responses to Medial Perforant Path Paired Pulse and Tetanic Activation as a Function of Sex and Age

Abstract Network plasticity in the medial perforant path (MPP) of adult (five to nine months) and aged (18–20 months) urethane-anesthetized male and female Sprague Dawley rats was characterized. Paired pulses probed recurrent networks before and after a moderate tetanic protocol. Adult females exhibited greater EPSP-spike coupling suggesting greater intrinsic excitability than adult males. Aged rats did not differ in EPSP-spike coupling but aged females had larger spikes at high currents than males. Paired pulses suggested lower GABA-B inhibition in females. Absolute population spike (PS) measures were larger post-tetani in female rats than male rats. Relative population spike increases were greatest in adult males relative to females and to aged males. EPSP slope potentiation was detected with normalization in some post-tetanic intervals for all groups except aged males. Tetani shortened spike latency across groups. Tetani-associated NMDA-mediated burst depolarizations were larger for the first two trains in each tetanus in adult males than other groups. EPSP slopes over 30 min post-tetani predicted spike size in female rats but not in males. Replicating newer evidence MPP plasticity in adult males was mediated by increased intrinsic excitability. Female MPP plasticity was related to synaptic drive increases, not excitability increases. Aged male rats were deficient in MPP plasticity.
Pangenome Graph Construction from Genome Alignment with Minigraph-Cactus

Reference genomes provide mapping targets and coordinate systems but introduce biases when samples under study diverge sufficiently from them. Pangenome references seek to address this by storing a representative set of diverse haplotypes and their alignment, usually as a graph. Alternate alleles determined by variant callers can be used to construct pangenome graphs, but thanks to advances in long-read sequencing, high-quality phased assemblies are becoming widely available. Constructing a pangenome graph directly from assemblies, as opposed to variant calls, leverages the graph’s ability to consistently represent variation at different scales and reduces biases introduced by reference-based variant calls. Pangenome construction in this way is equivalent to multiple genome alignment. Here we present the Minigraph-Cactus pangenome pipeline, a method to create pangenomes directly from whole-genome alignments, and demonstrate its ability to scale to 90 human haplotypes from the Human Pangenome Reference Consortium (HPRC). This tool was designed to build graphs containing all forms of genetic variation while still being practical for use with current mapping and genotyping tools. We show that this graph is useful both for studying variation within the input haplotypes, but also as a basis for achieving state of the art performance in short and long read mapping, small variant calling and structural variant genotyping. We further measure the effect of the quality and completeness of reference genomes used for analysis within the pangenomes, and show that using the CHM13 reference from the Telomere-to-Telomere Consortium improves the accuracy of our methods, even after projecting back to GRCh38. We also demonstrate that our method can apply to nonhuman data by showing improved mapping and variant detection sensitivity with a Drosophila melanogaster pangenome.
Surface glia predominantly contribute to the development of ALS/FTD in Drosophila model

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration in the primary motor neurons. C9orf72 repeat expansion mutation is the most prevalent genetic causes of ALS/FTD. Due to the complexity of ALS, there has been no successful therapy for the condition. The traditional neurocentric concept of ALS derives in part from the assumption that the degradation of motor neuron (MN) cells in ALS is driven by cell-autonomous mechanisms, however, recent research has focused on the non-cell-autonomous pathogenic mechanisms such as glial, immune cells and blood-brain barriers participate in the degeneration of MNs in ALS. Drosophila melanogaster is widely used as a genetic model for ALS, giving essential mechanistic data on disease onset and development. Using newly developed genetic tools to individually mark each subtype of the adult glial system in the fruit fly, we demonstrate that surface glia are the major glial subtypes for the pathogenesis of C9orf72-mediated ALS/FTD.
Auxiliary fields in open gauge theories

We show that for open gauge theories, it is possible to build an off-shell Becchi-Rouet-Stora-Tyutin algebra together with an invariant extension of the classical action. This is based on the introduction of auxiliary fields, after having defined an on-shell invariant quantum action, where the gauge-fixing action is written as in Yang\char21{}Mills type theories up to a modified Becchi-Rouet-Stora-Tyutin operator. An application to simple supergravity is performed.
Quantifying noise modulation from coupling of stochastic expression to cellular growth: An analytical approach

The overexpression of many proteins can often have a detrimental impact on cellular growth. This expression-growth coupling leads to positive feedback - any increase of intracellular protein concentration reduces the growth rate of cell size expansion that in turn enhances the concentration via reduced dilution. We investigate how such feedback amplifies intrinsic stochasticity in gene expression to drive a skewed distribution of the protein concentration. Our results provide an exact solution to this distribution by analytically solving the Chapman-Kolmogorov equation, and we use it to quantify the enhancement of noise/skewness as a function of expression-growth coupling. This analysis has important implications for the expression of stress factors, where high levels provide protection from stress, but come at the cost of reduced cellular proliferation. Finally, we connect these analytical results to the case of an actively degraded gene product, where the degradation machinery is working close to saturation.
Predicting anti-cancer drug combination responses with a temporal cell state network model

Cancer chemotherapy combines multiple drugs, but predicting the effects of drug combinations on cancer cell proliferation remains challenging. We hypothesized that by combining knowledge of single drug dose responses and cell state transition network dynamics, we could predict how a population of cancer cells will respond to drug combinations. We tested this hypothesis here using three targeted inhibitors of different cell cycle states in two different cell lines. We formulated a Markov model to capture temporal cell state transitions between different cell cycle phases, with single drug data constraining how drug doses affect transition rates. This model was able to predict the landscape of all three different pairwise drug combinations across all dose ranges for both cell lines with no additional data. This work shows how currently available or attainable information could be combined to predict how cancer cell populations respond to drug combinations.
THE SPLIT RED CLUMP OF THE GALACTIC BULGE FROM OGLE-III

The red clump (RC) is found to be split into two components along several sightlines toward the Galactic bulge. This split is detected with high significance toward the areas (−3.5 < l < 1, b < −5) and (l, b) = (0, + 5.2), i.e., along the bulge minor axis and at least 5 deg off the plane. The fainter (hereafter “main”) component is the one that more closely follows the distance–longitude relation of the bulge RC. The main component is ∼0.5 mag fainter than the secondary component and with an overall approximately equal population. For sightlines further from the plane, the difference in brightness increases, and more stars are found in the secondary component than in the main component. The two components have very nearly equal (V − I) color.
A switch in jaw form–function coupling during the evolution of mammals

The evolutionary shift from a single-element ear, multi-element jaw to a multi-element ear, single-element jaw during the transition to crown mammals marks one of the most dramatic structural transformations in vertebrates. Research on this transformation has focused on mammalian middle-ear evolution, but a mandible comprised of only the dentary is equally emblematic of this evolutionary radiation. Here we show that the remarkably diverse jaw shapes of crown mammals are coupled with surprisingly stereotyped jaw stiffness. This strength-based morphofunctional regime has a genetic basis and allowed mammalian jaws to effectively resist deformation as they radiated into highly disparate forms with markedly distinct diets. The main functional consequences for the mandible of decoupling hearing and mastication were a trade-off between higher jaw stiffness versus decreased mechanical efficiency and speed compared to non-mammals. This fundamental and consequential shift in jaw form-function underpins the ecological and taxonomic diversification of crown mammals.
An optimized gene knock-out strategy for human CD34+ hematopoietic stem and progenitor cells .

Human CD34 + hematopoietic stem and progenitor cells (HSPCs) are a standard source of cells for clinical HSC transplantations as well as experimental xenotransplantation studies. To further extend the range of applications of these humanized mice, we developed a protocol to efficiently edit the genomes of human CD34 + HSPCs before transplantation. In the past, manipulating HSPCs has been complicated by the fact that they are inherently difficult to transduce with lentivectors, and rapidly lose their stemness and engraftment potential during in vitro culture. However, with optimized nucleofection of sgRNA:Cas9 ribonucleoprotein complexes, we are now able to edit a candidate gene in CD34 + HSPCs with almost 100% efficiency, and without affecting their potential for engraftment and multilineage differentiation in mice. The result is a humanized mouse from which we knocked out a gene of interest from their human immune system.
Towards modelling cold-water coral reef-scale crumbling: Including morphological variability in mechanical surrogate models

The structural complexity of cold-water corals is threatened by ocean acidification. Increased porosity and weakening of structurally critical parts of the reef framework may lead to rapid physical collapse on an ecosystem scale, reducing their potential for biodiversity support. We can use computational models to describe the mechanisms leading to reef-crumbling. How-ever, the implementation of such models into an efficient predictive tool that allows us to determine risk and timescales of reef collapse is missing. Here, we identified possible surrogate models to represent the branching architecture of the cold-water coral species Lophelia pertusa. For length scales greater than 13 cm, a continuum finite element mechanical approach can be used to analyse mechanical competence whereas at smaller length scales, mechanical surrogate models need to explicitly account for the statistical differences in the structure. We showed large morphological variations between L. pertusa colonies and branches, as well as dead and live skeletal structures, which need to be considered for the development of rapid monitoring tools for predicting risk of cold-water coral reefs crumbling. This will allow us to investigate timescales of changes, including the impact of exposure times to acidified waters on reef-crumbling.
Enhanced STAT5a activation rewires exhausted CD8 T cells during chronic stimulation to acquire a hybrid durable effector like state

Rewiring exhausted CD8 T cells (TEX) towards more functional states is a major goal of cancer immunotherapy but has proven challenging due to the epigenetic stability of TEX. Indeed, TEX are epigenetically programmed by the transcription factor Tox. However, epigenetic changes continue to occur as TEX transition from progenitor (TEXprog), to intermediate (TEXint) and terminal (TEXterm) subsets, suggesting potential developmental flexibility in mature TEX subsets. By examining the transition of TEXprog into TEXint cells, we discovered a reciprocally antagonistic circuit between Stat5a and Tox in TEX cells. Stat5-activity controlled TEXint development, antagonized Tox, and instigated partial effector biology. Stat5 was also essential for TEX reinvigoration by PD-1 blockade. Indeed, temporal induction of Stat5-activity in TEX using an orthogonal IL-2/IL2Rβ-pair fostered TEXint cell accumulation and synergized with PD-L1 blockade. Constitutive Stat5a activity (STAT5CA) antagonized Tox-dependent TEX epigenetic programming to generate a durable hybrid effector/NK-like population with enhanced tumor control. Finally, enforcing Stat5-signals in established TEXprog partially rewired the TEX epigenetic landscape towards the effector/memory lineage. Together, these data highlight therapeutic opportunities of manipulating Stat5 to rewire TEX towards a durably protective hybrid program.
Conformational and oligomeric states of SPOP from small-angle X-ray scattering and molecular dynamics simulations

Speckle-type POZ protein (SPOP) is a substrate adaptor in the ubiquitin proteasome system, and plays important roles in cell-cycle control, development, and cancer. SPOP forms linear higher-order oligomers following an isodesmic self-association model. Oligomerization is essential for SPOP’s multivalent interactions with substrates, which facilitate phase separation and localization to biomolecular condensates. Structural characterization of SPOP in its oligomeric state and in solution is, however, challenging due to the inherent conformational and compositional heterogeneity of the oligomeric species. Here, we develop an approach to simultaneously and self-consistently characterize the conformational ensemble and the distribution of oligomeric states of SPOP by combining small-angle X-ray scattering (SAXS) and molecular dynamics simulations. We build initial conformational ensembles of SPOP oligomers using coarse-grained molecular dynamics simulations, and use a Bayesian/maximum entropy approach to refine the ensembles, along with the distribution of oligomeric states, against a concentration series of SAXS experiments. Our results suggest that SPOP oligomers behave as rigid, helical structures in solution, and that a flexible linker region allows SPOP’s substrate binding domains to extend away from the core of the oligomers. Additionally, our results are in good agreement with previous characterization of the isodesmic self-association of SPOP. In the future, the approach presented here can be extended to other systems to simultaneously characterize structural heterogeneity and self-assembly.
Mechanical stimuli such as shear stress and piezo1 stimulation generate red blood cell extracellular vesicles

Circulating red blood cell extracellular vesicles (RBC-EVs) are a promising biomarker for vascular health. However, generating, isolating, and characterizing physiologically relevant RBC-EVs with sufficient yield and purity for biological studies is non-trivial. Here, we present and rigorously characterize an in vitro model to mimic RBC-EV production during shear stress via mechanosensitive piezo1 ion channel stimulation. We optimize our RBC-EV isolation protocol to minimize hemolysis, maximize RBC-EV yield and purity, and improve the ease of EV characterization. RBC-EV purity was measured by quantifying protein (e.g., particles/μg), large particle (e.g., protein aggregates), and platelet EV contamination. This study compared RBC-EV isolation performance using membrane-based affinity (e.g., exoEasy), ultrafiltration (e.g., Amicon Ultra-15), and ultracentrifugation, with and without size exclusion chromatography purification. We found that treating 6% hematocrit with 10 μM piezo1-agonist yoda1 for 30 minutes and isolating RBC-EVs using ultracentrifugation minimized RBC hemolysis and maximized RBC-EV yield (~1012 particles/mL) and purity, provided the most consistent RBC-EV preparations, and improved ease of RBC-EV characterization. Our pressure myography experiments suggest that co-isolated protein contaminants, but not piezo1 RBC-EVs, induce rapid mouse carotid artery vasodilation. These results underscore the importance of characterizing EV purity for biological experiments. The standardized methods outlined here enable mechanistic studies of how RBC-EVs generated in physiological flow affect vascular response.