Miracle-dz/UniFAR-FTUs huggingface dataset:
FlexSFC: Flexible Resource Allocation and VNF Parallelism for Improved SFC Placement

To reduce the processing delay from the sequentially running virtual network functions (VNFs) in a service function chain (SFC), network function parallelism (NFP) is introduced that allows VNFs of the SFC to run in parallel. Existing NFP solutions only focused on improving parallelism benefits without paying much attention to resource utilization while deploying VNFs of SFCs. We take advantage of resource-delay dependency to propose a flexible and efficient parallelized SFC placement mechanism called FlexSFC which determines the optimal SFC placement while reducing resource usage and meeting end-to-end delay guarantees of the SFCs deployed. Initial results show that FlexSFC guarantees the end-to-end delay requirement with better resource utilization and SFC acceptance rate than the state-of-the-art approaches.
From Category Theory to Functional Programming: A Formal Representation of Intent

The possibility of managing network infrastructures through software-based programmable interfaces is becoming a cornerstone in the evolution of communication networks. The Intent-Based Networking (IBN) paradigm is a novel declarative approach towards network management proposed by a few Standards Developing Organizations. This paradigm offers a high-level interface for network management that abstracts the underlying network infrastructure and allows the specification of network directives using natural language. Since the IBN concept is based on a declarative approach to network management and programmability, we argue that the use of declarative programming to achieve IBN could uncover valuable insights for this new network paradigm. This paper proposes a formalization of this declarative paradigm obtained with concepts from category theory. Taking this approach to Intent, an initial implementation of this formalization is presented using Haskell, a well-known functional programming language.
Rethinking Population Bottlenecks: Intrinsic Fluctuations, Mutation and Dynamical Demographic Phases

By abruptly changing the size and composition of a population, bottlenecks can dramatically alter evolutionary trajectories. In the traditional picture, the faster a population recovers from a bottleneck, the more rapidly finite-size intrinsic fluctuations are suppressed and therefore the greater the likelihood of fixation to the attractor within whose basin the bottleneck constrained the population, initially. We now argue that this intuition is misleading; demonstrating that precisely the opposite behaviour is also possible. Depending critically on the rate of mutation, increased population growth can drive fixation to attractors that are different to that from whose basin it started. These findings are explained in terms of statistically distinct regimes of demographic behaviour, drawing parallels with the notion of non-equilibrium phase transitions. Such dynamical demographic phases are delimited by sharp transitions in time, as a population grows, and ultimately result from a time-dependent antagonism between mutation and the stochastically-induced effects of frequency-dependent birth.
Genomic evidence of natural selection for ash dieback 1 resistance 2

15 Evolutionary responses to sudden changes in the environment can, in theory, be particularly rapid if they involve small shifts in allele frequencies at many loci. However, such responses are 17 hard to characterise in wild populations. The invasive alien fungal pathogen Hymenoscyphus 18 fraxineus represents a strong novel selective challenge to European ash ( Fraxinus excelsior ). A 19 degree of quantitative resistance to the fungus exists in natural populations. A genome-wide 20 association study on field trials identified many single nucleotide polymorphism (SNP) loci 21 associated with resistance. Here, using whole genome resequencing of an infected natural ash 22 tree population in England, we survey the presence of alleles associated with resistance at 23 10,000 loci. Of these, 7,985 were variable within the population. We used SNP effect sizes 24 inferred in field trials to calculate the average genetic merit of each tree, as a Genomic 25 Estimated Breeding Value (GEBV). The GEBV of trees established after the start of the 26 epidemic was significantly higher than that of related adults from the pre-epidemic generation. 27 To produce a GEBV shift of this magnitude, would require truncation selection eliminating at 28 least 13% of the juvenile population. The changes in allele frequencies that we observe 29 correspond to their effect sizes. Thus, we document a heritable micro-evolutionary adaptive 30 change involving very many loci, occurring over a single generation. This rapid rate of for
Reduced γ-glutamyl hydrolase activity likely contributes to high folate levels in Periyakulam-1 tomato

Tomato cultivars show wide variation in nutraceutical folate in ripe fruits, yet the loci regulating folate levels in fruits remain unexplored. To decipher regulatory points, we compared two contrasting tomato cultivars: Periyakulam-1 (PKM-1) with high folate and Arka Vikas (AV) with low folate. The progression of ripening in PKM-1 was nearly similar to AV but had substantially lower ethylene emission. In parallel, the levels of phytohormones salicylic acid, ABA, and jasmonic acid were substantially lower than AV. The fruits of PKM-1 were also metabolically distinct from AV, with upregulation of several amino acids. Consistent with higher °Brix levels, the red ripe fruits also showed upregulation of sugars and sugar-derived metabolites. In parallel with higher folate, PKM-1 fruits also had higher carotenoid levels, especially lycopene and β-carotene. Transcript levels of genes encoding folate biosynthesis did not show a perceptible difference in relative expression. The proteome analysis showed upregulation of carotenoid sequestration and folate metabolism-related proteins in PKM-1. The deglutamylation pathway mediated by γ-glutamyl hydrolase (GGH) was substantially reduced in PKM-1 at the red-ripe stage. The red-ripe fruits had reduced transcript levels of GGHs and lower GGH activity than AV. Conversely, the percent polyglutamylation of folate was much higher in PKM-1. Our analysis indicates the regulation of GGH activity as a potential target to elevate folate levels in tomato fruits.
Known phyla dominate the RNA virome in Tara Oceans data, not new phyla as claimed

The Tara Oceans project claimed to identify five new RNA virus phyla, two of which “are dominant in the oceans”. However, their own assignments classify 28,353 of their putative RdRp-containing contigs to known phyla but only 886 (2.8%) to the five claimed new phyla combined. I mapped their reads to their contigs, finding that known phyla also account for a large majority (93.8%) of reads. I show that 510 of their putative viral contigs contain cellular proteins and further that predicted polymerase structures for their claimed phyla have incomplete and malformed palm domains, contradicting viral polymerase function and calling into question whether their putative polymerase sequences are derived from viruses.
MitoStores: chaperone‐controlled protein granules store mitochondrial precursors in the cytosol

Hundreds of mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational reaction. The early processes associated with mitochondrial protein targeting remain poorly understood. Here we show that in baker’s yeast, the cytosol has the capacity to transiently store matrix-destined precursors in dedicated deposits which we named MitoStores. MitoStores are strongly enhanced when protein import into mitochondria is competitively inhibited by a clogging of mitochondrial import sites, but also formed under physiological conditions when cells grow on non-fermentable carbon sources. MitoStores are enriched for a specific subset of nuclear encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. MitoStore formation is controlled by the heat shock proteins Hsp42 and Hsp104, potentially to suppress the toxic potential of accumulating mitochondrial precursor proteins. Thus, the cytosolic protein quality control system plays an active role during early stages in mitochondrial protein targeting by the coordinated and localized sequestration of mitochondrial precursor proteins. Summary The yeast cytosol can deposit precursors of mitochondrial proteins in specific granules called MitoStores. MitoStores are controlled by the cytosolic chaperone system, in particular by Hsp42 and Hsp104. MitoStore formation suppresses the toxicity arising from non-imported mitochondrial precursor proteins.
Identify non-mutational p53 functional deficiency in human cancers

An accurate assessment of TP53’s functional status is critical for cancer genomic medicine. However, there is a significant challenge in identifying tumors with non-mutational p53 inactivations that are not detected through DNA sequencing. These undetected cases are often misclassified as p53-normal, leading to inaccurate prognosis and downstream association analyses. To address this issue, we build the support vector machine (SVM) models to systematically evaluate p53’s functional status in multiple TCGA cancer cohorts. Cross-validation demonstrates the excellent performance of the SVM models with mean AUC of 0.9845, precision of 0.9844, and recall of 0.9825. Our model reveals that a significant proportion (87-100%) of wild-type TP53 (TP53WT) tumors actually have compromised p53 function. Further analyses reveal that these genetically normal but functionally deficient tumors (predicted reduced function of p53, TP53WT-pRF) share genomic characteristics with tumors carrying p53 mutants. Specifically, they exhibit significantly increased tumor mutation burden, copy number variation burden, aneuploidy score, and hypoxia score. Clinically, patients with TP53WT-pRF tumors experience significantly shorter overall survival and disease-free survival compared to those with TP53WT-pN (predicted normal function of p53) tumors, and these patients also display heightened sensitivity to platinum-based chemotherapy and radiation therapy. The increased sensitivity to radiation therapy is further validated in glioblastoma patient-derived xenografts models.
Impairments in the mechanical effectiveness of reactive balance control strategies during walking in people post-stroke

People post-stroke have an increased risk of falls compared to neurotypical individuals, partly resulting from an inability to generate appropriate reactions to restore balance. However, few studies investigated the effect of paretic deficits on the mechanics of reactive control strategies following forward losses of balance during walking. Here, we characterized the biomechanical consequences of reactive control strategies following perturbations induced by the treadmill belt accelerations. Thirty-eight post-stroke participants and thirteen age-matched and speed-matched neurotypical participants walked on a dual-belt treadmill while receiving perturbations that induced a forward loss of balance. We computed whole-body angular momentum and angular impulse using segment kinematics and reaction forces to quantify the effect of impulse generation by both the leading and trailing limbs in response to perturbations in the sagittal plane. We found that perturbations to the paretic limb led to larger increases in forward angular momentum during the perturbation step than perturbations to the non-paretic limb or to neurotypical individuals. To recover from the forward loss of balance, neurotypical individuals coordinated reaction forces generated by both legs to decrease the forward angular impulse relative to the pre-perturbation step. They first decreased the forward pitch angular impulse during the perturbation step. Then, during the first recovery step, they increased the backward angular impulse by the leading limb and decreased the forward angular impulse by the trailing limb. In contrast to neurotypical participants, people post-stroke did not reduce the forward angular impulse generated by the stance limb during the perturbed step. They also did not increase leading limb angular impulse or decrease the forward trailing limb angular impulse using their paretic limb during the first recovery step. Lastly, post-stroke individuals who scored poorer on clinical assessments of balance and had greater motor impairment made less use of the paretic limb to reduce forward momentum. Overall, these results suggest that paretic deficits limit the ability to recover from forward loss of balance. Future perturbation-based balance training targeting reactive stepping response in stroke populations may benefit from improving the ability to modulate paretic ground reaction forces to better control whole-body dynamics.
NF-κB inhibitor alpha has a cross-variant role during SARS-CoV-2 infection in ACE2-overexpressing human airway organoids

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that accurately recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. NF-κB inhibitor alpha was consistently upregulated in infected epithelial cells, and its mRNA expression positively correlated with infection levels. Confocal microscopy showed more IκBα expression in infected than bystander cells, but found concurrent nuclear translocation of NF-κB that IκBα usually prevents. Overexpressing a nondegradable IκBα mutant reduced NF-κB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and identify an incomplete NF-κB feedback loop as a rheostat of viral infection that may promote inflammation and severe disease.
Emergence of CC17 vancomycin variable Enterococcus faecium in India

Vancomycin variable enterococci (VVE) are those isolates that are susceptible to glycopeptide like vancomycin but harbour the resistance determinants like vanA gene. Globally the emergence of such strains was reported, and from India our centre was the first to report them. The present study focussed on analysing genome content of these strains from India to assess their genetic diversity. While the five isolates belonged to three sequence types, all the isolates were of clonal complex CC17. This supports that VVE from India are genetically closely related and are emerging from a single clone.
Nonlinear System Identification: NARMAX Methods in the Time, Frequency, and Spatio-Temporal Domains

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Transcranial electrical stimulation modulates emotional experience and metabolites in the prefrontal cortex in a donation task

In this study we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and right dorsolateral prefrontal cortex (DLPFC, cathode) can be used to induce changes in self-reported emotions and modulate metabolite concentrations under both electrodes. We employed in vivo quantitative MR Spectroscopy (MRS) in healthy adult participants and quantified the changes in GABA and Glx complex (Glutamate and Glutamine) before and after five sessions of tDCS stimulation. tDCS was delivered at 2mA intensity for 20 minutes for the active group and 1 minute for the sham group. tDCS was applied over five days while participants were engaged in a charitable donation task, known to engage the reward network. We observed increased levels of GABA in vmPFC, but not in DLPFC. Glx levels were decreased in both vmPFC and DLPFC. We found that self-reported happiness increased significantly over time only in the active group. There was a decrease in self-reported guiltiness in both active and sham groups. Altogether, the results indicate that self-reported emotions can be modulated by prefrontal stimulation. This may be because the changes in GABA and Glx concentrations following repeated stimulation induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.
Host Bypassing: Let your GPU speak Ethernet

Hardware acceleration of network functions is essential to meet the challenging Quality of Service requirements in nowadays computer networks. Graphical Processing Units (GPU) are a widely deployed technology that can also be used for computing tasks, including acceleration of network functions. In this work, we demonstrate how commodity GPUs, which do not provide any network interfaces, can be used to accelerate network functions. Our approach leverages PCIe peer-to-peer capabilities and allows the GPU to control the network interface card directly, without any assistance from the operating system or control application. The presented evaluation results demonstrate the feasibility of our approach and its performance of up to 10 Gbit/s, even for small packets.
Breathing and tilting: mesoscale simulations illuminate influenza glycoprotein vulnerabilities

Influenza virus has resurfaced recently from inactivity during the early stages of the COVID-19 pandemic, raising serious concerns about the nature and magnitude of future epidemics. The main antigenic targets of influenza virus are two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Whereas the structural and dynamical properties of both glycoproteins have been studied previously, the understanding of their plasticity in the whole-virion context is fragmented. Here, we investigate the dynamics of influenza glycoproteins in a crowded protein environment through mesoscale all-atom molecular dynamics simulations of two evolutionary-linked glycosylated influenza A whole-virion models. Our simulations reveal and kinetically characterize three main molecular motions of influenza glycoproteins: NA head tilting, HA ectodomain tilting, and HA head breathing. The flexibility of HA and NA highlights antigenically relevant conformational states, as well as facilitates the characterization of a novel monoclonal antibody, derived from human convalescent plasma, that binds to the underside of the NA head. Our work provides previously unappreciated views on the dynamics of HA and NA, advancing the understanding of their interplay and suggesting possible strategies for the design of future vaccines and antivirals against influenza. One-Sentence Summary In situ dynamics of influenza glycoproteins expose antigenically relevant states and a new site of vulnerability in neuraminidase.
SVR-based Multimodal Active Subspace Analysis for the Brain using Neuroimaging Data

Understanding the patterns of changes in brain function and structure under the influence of various disorders is of utmost importance. There have been numerous efforts towards successful biomarker discovery for complex brain disorders by utilizing neuroimaging datasets accompanied by analytical frameworks. However, due to the multi-faceted nature of the disorders involving a wide and overlapping range of symptoms as well as complex changes in structural and functional brain networks, it is increasingly important to devise computational frameworks that can take into account underlying patterns of heterogeneous changes with specific target assessments, at the same time producing a summarizing output from the high-dimensional neuroimaging data. While various machine learning approaches focus on diagnostic frameworks, many learning frameworks have been utilized to break down the neuroimaging features into lower dimensional components using unsupervised methods, as well as to analyze important features at the level of brain regions involved in prediction using supervised methods. However, most frameworks either do not take into account the target assessment information while extracting brain subspaces, or are able to extract only higher dimensional importance associations as an ordered list of involved features, making manual interpretation at the level of subspaces difficult. We present a novel multimodal active subspace learning framework to understand various subspaces within the brain that are associated with changes in particular biological and cognitive traits. Our framework decomposes the multimodal feature importances associated with a battery of biological and cognitive assessments to extract robust multimodal subspaces that define the highest change in a given assessment. Through a repeated sub-sampling procedure on an Alzheimer’s dataset, we show that our framework is able to extract subspaces covering both functional and structural modalities, which are specific to a given group assessment and also retain predictive performance in standard machine learning algorithms.
High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

Sequencing of most Treponema pallidum (T. pallidum) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modelling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β- sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.