Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantum Cosmology will need to become a Numerical Subject

The inhomogeneous fluctuations that underlie structure formation - galaxies and CMB hotspots - might have been seeded by quantum cosmological fluctuations, as magnified by some inflationary mechanism. The Halliwell-Hawking model for these, as a lower-energy semiclassical limit, is expected to be shared by many theories. E.g. an O((H/m_pl)^2) suppression of power at large scales results from this. This model contains/suppresses very many terms; we want a qualitative understanding of the meaning of these terms and of different regimes resulting from different combinations of them. I study this with toy models that have tractable mathematics: minisuperspace and, especially, relational particle mechanics. In the present Seminar, I consider in particular averaged terms with some lessons from Hartree-Fock approach to Atomic and Molecular Physics. One needs to anchor this on variational principles; treating the subsequent equations is a numerical venture.
A Relation-Attentive 3D Matrix Framework for Relational Triple Extraction

Extracting relational triples from unstructured 001 text is crucial for information extraction. Re-002 cent methods achieve considerable perfor-003 mance, but due to the insufﬁcient considera-004 tion of triple global information, there is an 005 obvious performance gap between triple (E1, 006 R, E2) and E1/R/E2, that is, some extracted 007 entities or relations fail to form a valid rela-008 tional triple. To break this bottleneck, we pro-009 pose a relation-attentive 3D matrix framework 010 (RA3D) composed of an encoder module, a 011 fusion module, and a 3D matrix module. In-012 stead of using a 2D table to align the sub-013 ject and object, we integrate clearly encoded 014 relation information to convert the 2D table 015 into a 3D matrix, so that the entries of the 016 3D matrix can capture the interaction in sub-017 jects, objects, and relations completely. To ex-018 tract relation and entity information required 019 for the 3D matrix reasonably, we design a 020 transformer-decoder-based fusion module that 021 updates the representation of relations and en-022 tities iteratively. Our model achieves state-of-023 the-art performance with F1 score up to 93.5% 024 and 94.3% on two public datasets and delivers 025 consistent performance gain on complex sce-026 narios of overlapping triples. 027
Contractile work and biarticular mechanisms of the triceps surae muscles facilitate net ankle mechanical work at high walking speeds

Increasing walking speed is accompanied by an enhancement of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential. We measured Achilles tendon (AT) elongation and, based on an experimentally determined AT-force-elongation relationship; we quantified AT-force as a proxy of the triceps surae muscle force at four walking speeds (slow 0.7 m.s-1, preferred 1.4 m.s-1, transition 2.0 m.s-1 and maximum 2.6±0.3 m.s-1). Further, we investigated the mechanical power and work of the triceps surae muscles at the ankle joint (TSA) and the mechanical power and work of the biarticular gastrocnemii at the ankle and knee joint. We found a ~21% decrease of maximum AT-force at the two higher speeds compared to the preferred; however, the net TSA-work increased as a function of walking speed. An earlier plantarflexion accompanied by increased activation of the triceps surae muscles and a knee-to-ankle energy transfer via the biarticular gastrocnemii enhanced the net TSA-mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speeds, respectively. Our findings provide first time evidence for different mechanistic participation of the monoarticular soleus muscle and the biarticular gastrocnemii for the speed-related enhancement of net TSA-work.
Positive, negative and engineered durotaxis

Cell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science. Specifically, the ability of cells to follow stiffness gradients, known as durotaxis, is ubiquitous across most cell types. Even so, certain cells follow positive stiffness gradients while others move along negative gradients. How the physical mechanisms involved in cell migration works to enable a wide range of durotactic responses is still poorly understood. Here, we provide a mechanistic rationale of durotaxis by integrating stochastic clutch models for cell adhesion with an active gel theory of cell migration. We show that positive and negative durotaxis found across cell types are explained by asymmetries in the cell adhesion dynamics. We rationalize durotaxis by an asymmetric mechanotransduction in the cell adhesion behavior that further polarizes the intracellular retrograde flow and the protruding velocity at the cell membrane. Our theoretical framework confirms previous experimental observations and explains positive and negative durotaxis. Moreover, we show how durotaxis can be engineer to manipulate cell migration, which has important implications in biology, medicine and bioengineering.
Involvement of superior colliculus in complex figure detection of mice

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is causally involved in figure detection based on differences in figure contrast, orientation and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.
Spontaneous neurotransmission at evocable synapses predicts their responsiveness to action potentials

Synaptic transmission relies on presynaptic neurotransmitter (NT) release from synaptic vesicles (SVs) and on NT detection by postsynaptic receptors. Transmission exists in two principal modes: action-potential (AP) evoked and AP-independent, “spontaneous” transmission. AP-evoked neurotransmission is considered the primary mode of inter-neuronal communication, whereas spontaneous transmission is required for neuronal development, homeostasis, and plasticity. While some synapses appear dedicated to spontaneous transmission only, all AP-responsive synapses also engage spontaneously, but whether this encodes functional information regarding their excitability is unknown. Here we report on functional interdependence of both transmission modes at individual synaptic contacts of Drosophila larval neuromuscular junctions (NMJs) which were identified by the presynaptic scaffolding protein Bruchpilot (BRP) and whose activities were quantified using the genetically encoded Ca2+ indicator GCaMP. Consistent with the role of BRP in organizing the AP-dependent release machinery (voltage-dependent Ca2+ channels and SV fusion machinery), most active BRP-positive synapses (>85%) responded to APs. At these synapses, the level of spontaneous activity was a predictor for their responsiveness to AP-stimulation. AP-stimulation resulted in cross-depletion of spontaneous activity and both transmission modes were affected by the non-specific Ca2+ channel blocker cadmium and engaged overlapping postsynaptic receptors. Thus, by using overlapping machinery, spontaneous transmission is a continuous, stimulus independent predictor for the AP-responsiveness of individual synapses.
Cuticular wax, but not the cutin matrix, is renewed during the lifespan of Clusia rosea leaves 13CO2 labelling and gas exchange study

The plant cuticle, which aided the water-to-land transition of plants, provides various services to the plant surface, and its synthesis and maintenance represent substantial metabolic costs. Nevertheless, only limited information regarding cuticle dynamics is available. We determined the composition and dynamics of Clusia rosea cuticular waxes and matrix using 13CO2 labelling, compound-specific and bulk isotope ratio mass spectrometry. Collodion was used for wax collection; gas exchange techniques were employed to test for any collodion effects on living leaves. Cutin matrix (MX) area density did not vary between young and mature leaves and between leaf sides. Only young leaves incorporated new carbon into their MX. Collodion-based sampling discriminated between epicuticular (EW) and intracuticular wax (IW) effectively. EW differed in composition from IW. The newly synthetized wax was deposited in IW first and later in EW. Both young and mature leaves synthetized IW and EW; the faster dynamics in young leaves was not due to a faster synthesis rate but was the result of lower wax coverage. Longer-chain alkanes were deposited preferentially on the abaxial, stomatous leaf side, producing differences between leaf sides in wax composition. We introduce a new, sensitive isotope labelling method and demonstrate that cuticular wax is renewed during leaf ontogeny of Clusia rosea. We discuss the ecophysiological significance of the new insights.
Selection leads to remarkable variability in the outcomes of hybridization across replicate hybrid zones

Hybrid zones have been held up as an opportunity to see speciation in action, as windows into the evolutionary process. When hybrid zones are replicated, it is assumed that if the same genetic incompatibilities are maintaining reproductive isolation across all instances of secondary contact, those incompatibilities should be identifiable by consistent patterns in the genome. In contrast, changes in allele frequencies due to genetic drift should be idiosyncratic for each hybrid zone. To test this assumption, we simulated 20 replicates of each of 12 hybrid zone scenarios with varied genetic incompatibilities, rates of migration, and selection. We found remarkable variability in the outcomes of hybridization in replicate hybrid zones, particularly with Bateson-Dobzhansky-Muller incompatibilities and strong selection. We found substantial differences among replicates in the overall genomic composition of individuals, including admixture proportions, inter-specific ancestry complement, and number of ancestry junctions. Additionally, we found substantial variation in genomic clines among replicates at focal loci, regardless of locus-specific selection. From this, we conclude that processes other than selection are responsible for some consistent outcomes of hybridization, whereas selection on incompatibilities can lead to genomically widespread and highly variable outcomes. We use these results to highlight the challenge of mapping between pattern and process in hybrid zones and call attention to how selection against incompatibilities will commonly lead to unpredictable, variable outcomes. Our hope is that this study informs future research on replicate hybrid zones and encourages further development of statistical techniques, theoretical models, and exploration of additional axes of variation to understand the maintenance of reproductive isolation.
ATR protects centromere identity by promoting DAXX association with PML nuclear bodies

Centromere protein A (CENP-A) defines centromere identity and nucleates kinetochore formation for mitotic chromosome segregation. Here, we show that Ataxia telangiectasia and Rad3-related (ATR) kinase, a master regulator of the DNA damage response, protects CENP-A occupancy at interphase centromeres in a DNA damage-independent manner. As ATR localizes to promyelocytic leukemia nuclear bodies (PML NBs) in unperturbed cells, we hypothesized that ATR protects CENP-A occupancy by regulating the localization of the histone H3.3 chaperone and PML NB component, DAXX. Indeed, we found that ATR inhibition reduces DAXX association with PML NBs, resulting in the DAXX-dependent loss of CENP-A from interphase centromeres. Lastly, we demonstrate that CENP-A occupancy is not restored until G1 of the following cell cycle, leading to increased mitotic chromosome segregation defects. These findings demonstrate a novel mechanism by which ATR protects centromere identity and genome stability.
Cadmium treatment induces endoplasmic reticulum stress and unfolded protein response in Arabidopsis thaliana

We report about the response of Arabidopsis thaliana to chronic and temporary Cd2+ stress, and the Cd2+ induced activation of ER stress and unfolded protein response (UPR). Cd2+-induced UPR proceeds mainly through the bZIP60 arm, which in turn activates relevant ER stress marker genes such as BiP3, CNX, PDI5 and ERdj3B in a concentration- (chronic stress) or time- (temporary stress) dependent manner. A more severe Cd-stress triggers programmed cell death (PCD) through the activation of the NAC089 transcription factor. Toxic effects of Cd2+ exposure are reduced in the Atbzip28/bzip60 double mutant in terms of primary root length and fresh shoot weight, likely due to reduced UPR and PCD activation. We also hypothesised that the enhanced Cd2+ resistance of the Atbzip28/bzip60 double mutant is due to an increase in brassinosteroids signaling, since the amount of the brassinosteroid insensitive1 receptor (BRI1) protein decreases under Cd2+ stress only in Wt plants. These data highlight the complexity of the UPR pathway, since the ER stress response is strictly related to the type of the treatment applied and the multifaceted connections of ER signaling. The reduced sensing of Cd2+ stress in plants with UPR defects can be used as a novel strategy for phytoremediation.
Latency-aware Load Balancing Virtual Network Embedding Algorithm

To overcome network ossification, network slicing has been proposed as a promising method in 5G network. Software defined networking (SDN) and network function virtualization (NFV) as emerging enabled technology support multiple logical networks sharing physical infrastructure. Virtual network embedding (VNE) is one of the main challenges for network slicing. To avoid link congestion and satisfy the latency requirement of virtual network requests, latency model of network and load balancing link weight formulation are proposed. Then we design a load balancing link reconfiguration embedding algorithm and latency-aware load balancing VNE algorithm. Compared with the baseline algorithms, simulation results show that our proposed algorithm has better performance.
A DDRESSING H IGH - DIMENSIONAL C ONTINUOUS A C - TION S PACE VIA D ECOMPOSED D ISCRETE P OLICY - C RITIC

Reinforcement learning (RL) methods for discrete action spaces like DQNs are being widely used in tasks such as Atari games. However, they encounter difficulties when addressing continuous control tasks, since discretizing continuous action space incurs the curse-of-dimensionality. To tackle continuous control tasks via discretized actions, we propose a decomposed discrete policy-critic (D2PC) architecture, which was inspired by multi-agent RL (MARL) and associates with each action dimension a discrete policy, while leveraging a single critic network to provide a shared evaluation. Building on D2PC, we advocate soft stochastic D2PC (SD2PC) and deterministic D2PC (D3PC) methods with a discrete stochastic or deterministic policy, which show comparable or superior training performances relative to even continuous actor-critic methods. Additionally, we design a mechanism that allows D3PC to interact with continuous actor-critic methods, contributing to the Q-policy-critic (QPC) algorithm, which inherits the training efficiency of discrete RL and the near-optimal final performance of continuous RL algorithms. Substantial experimental results on several continuous benchmark tasks validate our claims.
between enhanced after surgery and a Comparing outcomes between enhanced recovery after surgery and traditional protocols in total knee arthroplasty: a retrospective cohort study

Knee replacement surgery was traditionally associated with prolonged recovery and rehabilitation programmes in hospital. Enhanced recovery after surgery (ERAS) protocols have been shown to be cost effective while not compromising patient safety or functional outcome. Despite this proven efficacy, ERAS has not been widely adopted in South African orthopaedic practices. The aim of this study is to determine if it is possible to practise these guidelines in South Africa so as to decrease the length of stay (LOS) without an increase in complication rate or compromise in functional outcome. Included in the study were 119 patients undergoing elective total knee arthroplasty between 2013 and 2017. They were divided into two cohorts. The first group was treated with a traditional protocol and included 59 patients. The second group was treated with ERAS and included 60 patients, following implementation of the ERAS protocol in 2015. The functional outcome was assessed using the Oxford Knee Score (OKS). The 30-day readmission rate was used to assess safety of early discharge. LOS and patient demographics were also collected to compare the cohorts. Results There was no clinically significant difference between the cohorts with regards to OKS or readmission rate. Two sample t-tests were used to compare these parameters. The mean OKS for the traditional group was 59.1 (SD 2.4), and for the ERAS group, 58.7 (SD 5.0) (p = 0.73). The readmission rate was 8.5% in the traditional group and 10% in the ERAS group (p = 1.00). The LOS was significantly decreased in the ERAS group, with a mean of 2.3 days (SD 1.8) compared to 5.0 (SD 2.2) in the traditional group (p < 0.001). Conclusion ERAS protocols used in the South African context in elective total knee arthroplasty significantly decrease the LOS without compromising patient safety or functional outcome.
The FAIR and CARE Data Principles Influence Who Counts As a Participant in Biodiversity Science by Governing the Fitness-for-Use of Data

: Biodiversity scientists often describe their field as aiming to save life and humanity, but the field has yet to reckon with the history and contemporary practices of colonialism and systematic racism inherited from natural history. The online data portals scientists use to store and share biodiversity data are a growing class of organizations whose governance can address or perpetuate and further institutionalize the implicit assumptions and inequitable social impacts from this extensive history. In this context, researchers and Indigenous Peoples are developing and implementing new strategies to examine and change assumptions about which agents should count as salient participants to scientific projects, especially projects that build and manage large digital data portals. Two notable efforts are the FAIR (Findable Accessible Interoperable Reusable) and CARE (Collective benefit, Authority, Responsibility, Ethics) Principles for scientific data management and governance. To characterize how these influence the governance of biodiversity data portals, we develop an account of fitness-for-use that makes explicit its social as well as technical conditions in relation to agents and purposes. The FAIR Principles, already widely adopted by biodiversity data projects, prioritize machine agents and efficient computation, while the CARE Principles prioritize Indigenous Peoples and their data sovereignty. Both illustrate the potency of an emerging general strategy by which groups of actors craft and implement governance principles for data fitness-of-use to change assumptions about salient participants to data science.
Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening

Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature—specifically in pulmonary vascular lesions—as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs). Previous studies suggest that altered hemodynamic forces cause lung endothelial dysfunction and, in turn, adherence of immune cells and release of inflammatory mediators, while the resulting perivascular inflammation, in turn, promotes vascular remodeling and the progression of PH. As such, a vicious cycle of endothelial activation, inflammation, and vascular remodeling may develop and drive the disease process. PA stiffening constitutes an emerging research area in PH, with relevance in PH diagnostics, prognostics, and as a therapeutic target. With respect to its prognostic value, PA stiffness rivals the well-established measurement of pulmonary vascular resistance as a predictor of disease outcome. Vascular remodeling of the arterial extracellular matrix (ECM) as well as vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis contribute to PA stiffening. While associations between inflammation and vascular stiffening are well-established in systemic vascular diseases such as atherosclerosis or the vascular manifestations of systemic sclerosis, a similar connection between inflammatory processes and PA stiffening has so far not been addressed in the context of PH. In this review, we discuss potential links between inflammation and PA stiffening with a specific focus on vascular calcification and ECM remodeling in PH.
Signals of adaptation to agricultural stress in the genomes of two European bumblebees

Human-induced environmental impacts on wildlife are widespread, causing major biodiversity losses. One major threat is agricultural intensification, typically characterised by large areas of monoculture, mechanical tillage, and the use of agrochemicals. Intensification leads to the fragmentation and loss of natural habitats, native vegetation, and nesting and breeding sites. Understanding the adaptability of insects to these changing environmental conditions is critical to predicting their survival. Bumblebees, key pollinators of wild and cultivated plants, are used as model species to assess insect adaptation to anthropogenic stressors. We investigated the effects of agricultural pressures on two common European bumblebees, Bombus pascuorum and B. lapidarius. Restriction-site Associated DNA Sequencing was used to identify loci under selective pressure across agricultural-natural gradients over 97 locations in Europe. 191 unique loci in B. pascuorum and 260 in B. lapidarius were identified as under selective pressure, and associated with agricultural stressors. Further investigation suggested several candidate proteins including several neurodevelopment, muscle, and detoxification proteins, but these have yet to be validated. These results provide insights into agriculture as a stressor for bumblebees, and signal for conservation action in light of ongoing anthropogenic changes.