Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of preliminary high-pressure processing for improving bioactive characteristics and reducing antigenicity of whey protein hydrolysates

This study investigated the use of Novo Pro-D® (NPD) and Ficin (FC) as alternative proteases for the production of bioactive peptides with reduced allergenicity from whey protein concentrate (WPC). In addition, the use of high hydrostatic pressure processing as pre-treatment of WPC and its impact on the final characteristics of hydrolysates were also evaluated. NPD treatments generated hydrolysates with a 98% reduction of soluble proteins, greater in vitro antioxidant capacity, and less immunoreactivity when compared to FC ones. However, pre-treatment was an essential tool to improve WPC hydrolysis when FC was used, resulting in hydrolysates with less soluble proteins, enhanced antioxidant capacity, and less allergenicity compared with conventional hydrolysis. As for NPD, the pre-treatment of WPC improved the in vitro antioxidant capacity and resulted in a 100% reduction in immunoreactivity to β-lactoglobulin in a shorter processing time. Importantly, bioactive peptides generated by FC displayed an improved ability to induce in vitro arterial relaxation, compared with those obtained from NPD process. Therefore, this study provides innovative evidence regarding how the proteases used for production of whey hydrolysates can improve its biological effects, and discloses the use of high hydrostatic pressure combined with enzymatic hydrolysis as a promising alternative to produce hydrolysates with improved properties.
Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy

Significance Statement Renal artery stenosis (RAS) engenders stenotic-kidney ischemia, dysfunction, and injury, but whether these are mediated by cellular senescence has not been elucidated. INK-ATTAC transgenic mice, high-resolution imaging, and unbiased single-cell RNA sequencing of murine kidneys demonstrated cellular senescence as an important mechanism of progressive injury to epithelial/stromal cells within poststenotic kidneys. Both p16-specific and broad quercetin/dasatinib interventions to blunt senescence improved renal function and structure, underscoring the central role of senescence in the pathogenesis. Furthermore, this mechanism was conserved in human subjects with RAS. These observations reveal new mechanisms that contribute to the pathogenesis of chronic ischemic renal injury, and support the development of senolytic therapy to reduce senescent cell burden and delay renal injury. Background Peripheral vascular diseases may induce chronic ischemia and cellular injury distal to the arterial obstruction. Cellular senescence involves proliferation arrest in response to stress, which can damage neighboring cells. Renal artery stenosis (RAS) induces stenotic-kidney dysfunction and injury, but whether these arise from cellular senescenceand their temporal pattern remain unknown. Methods Chronic renal ischemia was induced in transgenic INK-ATTAC and wild type C57BL/6 mice by unilateral RAS, and kidney function (in vivo micro-MRI) and tissue damage were assessed. Mouse healthy and stenotic kidneys were analyzed using unbiased single-cell RNA-sequencing. To demonstrate translational relevance, cellular senescence was studied in human stenotic kidneys. Results Using intraperitoneal AP20187 injections starting 1, 2, or 4 weeks after RAS, selective clearance of cells highly expressing p16Ink4a attenuated cellular senescence and improved stenotic-kidney function; however, starting treatment immediately after RAS induction was unsuccessful. Broader clearance of senescent cells, using the oral senolytic combination dasatinib and quercetin, in C57BL/6 RAS mice was more effective in clearing cells positive for p21 (Cdkn1a) and alleviating renal dysfunction and damage. Unbiased, single-cell RNA sequencing in freshly dissociated cells from healthy and stenotic mouse kidneys identified stenotic-kidney epithelial cells undergoing both mesenchymal transition and senescence. As in mice, injured human stenotic kidneys exhibited cellular senescence, suggesting this process is conserved. Conclusions Maladaptive tubular cell senescence, involving upregulated p16 (Cdkn2a), p19 (Cdkn2d), and p21 (Cdkn1a) expression, is associated with renal dysfunction and injury in chronic ischemia. These findings support development of senolytic strategies to delay chronic ischemic renal injury.
Morus alba: Host reaction for Meloidogyne javanica, biological nematicides assessment and study of these relationships with yield and quality of leaves, cocoon and health of the silkworm

Root-knot nematodes cause damage to several crops and the importance of each species can vary according with the crop and the agricultural region. In Brazil, Meloidogyne javanica is one of the most important nematode species parasitizing mulberry. To define management strategies, it is important to know if the crop species is damaged by the parasitism of the nematode and the best choices for control, as the use of nematicides. Biological nematicides have been extensively used in Brazil, but no information regarding its efficiency to control M. javanica in mulberry is available. Besides, it is not known if biological nematicides could improve the quality of leaves or if they alter the nutrient composition of leaves, which could interfere in the development of the silkworms that are feed with these leaves or in the quality of the silk produced. With the aim to address these questions, we propose a study that will start in the phenotyping of the main Brazilian mulberry cultivars to Meloidogyne species, passing through the test of efficiency of biological nematicides in the control of M. javanica in mulberry cultivar Miura, evaluation of the amount and quality of leaves produced and, using these leaves to feed silkworms, in the analyzes of the impact of these diet in the health of silkworms, and in the production and quality of the silk.
Spatiotemporally resolved subcellular phosphoproteomics

Significance As one of the most important post-translational modifications, phosphorylation is both highly abundant and dynamically regulated in cells. Characterizing subcellular phosphoproteome with high temporal resolution should shed light on their contributions to diverse cellular processes. By integrating an activatable proximity labeling enzyme with an orthogonal phosphorylation enrichment scheme, we have developed the SubMAPP strategy for mapping the phosphorylation dynamics of subcellular proteome in living systems. The high sensitivity of SubMAPP enabled the identification of phosphoproteins and phosphorylation sites in the endoplasmic reticulum (ER), revealing ER-to-mitochondria protein translocation under ER stress. Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing subcellular phosphoproteome with high spatial–temporal resolution has remained challenging. Herein, we developed a subcellular-specific uncaging-assisted biotinylation and mapping of phosphoproteome (SubMAPP) strategy to monitor the phosphorylation dynamics of subcellular proteome in living cells and animals. Our method capitalizes on the genetically encoded bioorthogonal decaging strategy, which enables the rapid activation of subcellular localized proximity labeling biotin ligase through either light illumination or small-molecule triggers. By further adopting an integrated orthogonal pull-down strategy with quantitative mass spectrometry, SubMAPP allowed for the investigation of subcellular phosphoproteome dynamics, revealing the altered phosphorylation patterns of endoplasmic reticulum (ER) luminal proteins under ER stress. Finally, we further expanded the scope of the SubMAPP strategy to primary neuron culture and living mice.
Finite-Time Stabilization of Competitive Neural Networks With Time-Varying Delays

This article investigates finite-time stabilization of competitive neural networks with discrete time-varying delays (DCNNs). By virtue of comparison strategies and inequality techniques, finite-time stabilization of the underlying DCNNs is analyzed by designing a discontinuous state feedback controller, which simplifies the controller design and proof processes of some existing results. Meanwhile, global exponential stabilization of the DCNNs is provided under a continuous state feedback controller. In addition, global exponential stability of the DCNNs is shown as an M-matrix, which contains some published outcomes as special cases. Finally, three examples are given to illuminate the validity of the theories.
Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans.

Persistent inward currents (PICs) play an essential role in setting motor neuron gain and shaping motor unit firing patterns. Estimates of PICs in humans can be made using the paired motor unit analysis technique, which quantifies the difference in discharge rate of a lower-threshold motor unit at the recruitment onset and offset of a higher-threshold motor unit (∆F). Because PICs are highly dependent on the level of neuromodulatory drive, ∆F represents an estimate of level of neuromodulation at the level of the spinal cord. Most of the estimates of ∆F are performed under constrained, isometric, seated conditions. In the present study, we used high-density surface EMG arrays to discriminate motor unit firing patterns during isometric seated conditions with torque or EMG visual feedback and during unconstrained standing anterior-to-posterior movements with RMS EMG visual feedback. We were able to apply the paired motor unit analysis technique to the decomposed motor units in each of the three conditions. We hypothesized that ∆F would be higher during unconstrained standing anterior-to-posterior movements compared to the seated conditions, reflecting an increase in the synaptic input to MNs drive while standing. In agreement with previous work, we found that there was no evidence of a difference in ∆F between the seated and standing postures, although slight differences in the initial and peak discharge rates were observed. Taken together, our results suggest that both the standing and seated postures are likely not sufficiently different--both being "upright" postures--to result in large changes in neuromodulatory drive.
Isolation and Structure Detection of Fungicidal Components from Cuminum cyminum Seed

Six plant pathogens(Pyricularia grisea,Sclerotinia sclerotiorum,Phytophthora capsici,etc.) were used to screen fungicidal components from Cuminum cyminum L.seed. Cumin seeds were distilled by alcohol,and then extracted by petroleum ether,chloroform,ethyl ester,and n-butanol in sequence.Two compounds were isolated from petroleum ether extract by column chromatography.Their structures were identified as p-isopropyl benzoic acid and p-isopropyl benzaldehyde by MS and NMR.The inhibitive rate against the mycelial growth of S.sclerotiorum,P.capsici were tested.The EC50 of p-isopropyl benzaldehyde against S.sclerotiorum and P.capsici were 2.093 and 15.40 mg/L,respectively.The EC50 of p-isopropyl benzoic acid against S.sclerotiorum and P.capsici were 7.298 and 19.66 mg/L,respectively.
Myopericarditis in a previously healthy adolescent male following COVID‐19 vaccination: A case report

We report the case of a previously healthy 16‐year‐old male who developed myopericarditis following the second dose of his Pfizer‐BioNTech COVID‐19 vaccine, with no other identified triggers. Adolescents and young adults experiencing chest pain after COVD‐19 vaccination should seek emergent medical care, and emergency providers should have a low threshold to consider and evaluate for myopericarditis. More data are needed to better understand the potential association between COVID‐19 vaccines and myopericarditis. If a true causal link is identified, the risk must also be viewed in context with the millions of patients who have been safely vaccinated and the known morbidity and mortality from COVID‐19 infection. As we see widespread vaccine rollout, it is important that all potential adverse reactions are reported as we continue to monitor for more rare but potentially serious side effects not identified in vaccination trials.
Spatially structured inhibition defined by polarized parvalbumin interneuron axons promotes head direction tuning

Anatomical organization of an inhibitory cortical microcircuit suggests an intrinsic compass supporting spatial navigation. In cortical microcircuits, it is generally assumed that fast-spiking parvalbumin interneurons mediate dense and nonselective inhibition. Some reports indicate sparse and structured inhibitory connectivity, but the computational relevance and the underlying spatial organization remain unresolved. In the rat superficial presubiculum, we find that inhibition by fast-spiking interneurons is organized in the form of a dominant super-reciprocal microcircuit motif where multiple pyramidal cells recurrently inhibit each other via a single interneuron. Multineuron recordings and subsequent 3D reconstructions and analysis further show that this nonrandom connectivity arises from an asymmetric, polarized morphology of fast-spiking interneuron axons, which individually cover different directions in the same volume. Network simulations assuming topographically organized input demonstrate that such polarized inhibition can improve head direction tuning of pyramidal cells in comparison to a “blanket of inhibition. ” We propose that structured inhibition based on asymmetrical axons is an overarching spatial connectivity principle for tailored computation across brain regions.
Afraid of the dark: Light acutely suppresses activity in the human amygdala

Light improves mood. The amygdala plays a critical role in regulating emotion, including fear-related responses. In rodents the amygdala receives direct light input from the retina, and light may play a role in fear-related learning. A direct effect of light on the amygdala represents a plausible mechanism of action for light’s mood-elevating effects in humans. However, the effect of light on activity in the amygdala in humans is not well understood. We examined the effect of passive dim-to-moderate white light exposure on activation of the amygdala in healthy young adults using the BOLD fMRI response (3T Siemens scanner; n = 23). Participants were exposed to alternating 30s blocks of light (10 lux or 100 lux) and dark (<1 lux), with each light intensity being presented separately. Light, compared with dark, suppressed activity in the amygdala. Moderate light exposure resulted in greater suppression of amygdala activity than dim light. Furthermore, functional connectivity between the amygdala and ventro-medial prefrontal cortex was enhanced during light relative to dark. These effects may contribute to light’s mood-elevating effects, via a reduction in negative, fear-related affect and enhanced processing of negative emotion.
Knowledge into action: proposing an evidence-based group prenatal exercise prescription

Aims: In accordance with the American College of Obstetricians and Gynaecologists recommendations for exercise during pregnancy, this article provides an evidence-based prescription for a group-based prenatal exercise programme. Methods: This prescription has been tested in 21 randomized controlled trials. This short report outlines in detail the seven components included in each session (warm-up, aerobic training, resistance training, coordination and balance, pelvic floor training, cool-down, and final discussion). Results: Using the 26-item behaviour change taxonomy proposed by Abraham and Michie, we identified common techniques that are employed in each session to provide a rationale for the high-programme adherence. Conclusions: This session model can be replicated to design prenatal exercise programmes with high adherence and that can be offered by trained exercise professionals.
Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.
Modeling an aspirational connected network of protected areas across North America

Abstract Connecting protected areas remains an important global conservation strategy in the face of ongoing and future threats to biodiversity. Amid our growing understanding of how species’ distributions will respond to climate change, conservation scientists need to plan for connectivity conservation across entire continents. We modeled multiscale connectivity priorities based on the least human‐modified lands between large protected areas of North America using least‐cost and circuit theory approaches. We first identified priority corridors between large protected areas, then characterized the network’s structure to unveil priority linkages most important for maintaining network‐ and regional‐level connectivity. Agreement between least‐cost corridors and current flow varied throughout North America, reflecting permeable landscape conditions and “pinch points” where potential ecological flows may concentrate between protected areas. Priority network‐level linkages derived from each approach were similar throughout the continental network (e.g., Rocky Mountains and Canadian boreal), but critical linkages that bridged regional protected‐area networks varied. We emphasize the importance of planning for connectivity at continental scales and demonstrate the utility of multiple methods when mapping connectivity priorities across large spatial extents with wide gradients in landscape conditions.
SAKE

Katz centrality is a fundamental concept to measure the influence of a vertex in a social network. However, existing approaches to calculating Katz centrality in a large-scale network are unpractical and computationally expensive. In this article, we propose a novel method to estimate Katz centrality based on graph sampling techniques, which object to achieve comparable estimation accuracy of the state-of-the-arts with much lower computational complexity. Specifically, we develop a Horvitz–Thompson estimate for Katz centrality by using a multi-round sampling approach and deriving an unbiased mean value estimator. We further propose SAKE, a Sampling-based Algorithm for fast Katz centrality Estimation. We prove that the estimator calculated by SAKE is probabilistically guaranteed to be within an additive error from the exact value. Extensive evaluation experiments based on four real-world networks show that the proposed algorithm can estimate Katz centralities for partial vertices with low sampling rate, low computation time, and it works well in identifying high influence vertices in social networks.
Technical Perspective

One of the most important functionalities of a database system is to answer queries. We are interested in the following question: If there exists more than one answer to the given query, which one should the database report? There are two apparent choices: to return all the valid answers or to return one of them. The problem with the former choice is that it is often time-prohibitive to search for all valid answers. In the latter choice, fairness may become an issue, since the index built for fast search may introduce bias to the query result. For example, the index may favor a certain portion of the input data (e.g., nodes near the root of a tree index) and with a higher chance, output an answer related to that portion than other portions. Such bias can sometimes lead to undesirable consequences.
Chiller

Distributed transactions on high-overhead TCP/IP-based networks were conventionally considered to be prohibitively expensive. In fact, the primary goal of existing partitioning schemes is to minimize the number of cross-partition transactions. However, with the new generation of fast RDMAenabled networks, this assumption is no longer valid. In this paper, we first make the case that the new bottleneck which hinders truly scalable transaction processing in modern RDMA-enabled databases is data contention, and that optimizing for data contention leads to different partitioning layouts than optimizing for the number of distributed transactions. We then present Chiller, a new approach to data partitioning and transaction execution, which aims to minimize data contention for both local and distributed transactions.
Deep Compressive Offloading

Future mobile and embedded systems will be smarter and more user-friendly. They will perceive the physical environment, understand human context, and interact with end-users in a human-like fashion. Daily objects will be capable of leveraging sensor data to perform complex estimation and recognition tasks, such as recognizing visual inputs, understanding voice commands, tracking objects, and interpreting human actions. This raises important research questions on how to endow low-end embedded and mobile devices with the appearance of intelligence despite their resource limitations.
PerfLens: a data-driven performance bug detection and fix platform

The wealth of open-source software development artifacts available online creates a great opportunity to learn the patterns of performance improvements from data. In this paper, we present a data-driven approach to software performance improvement in C#. We first compile a large dataset of hundreds of performance improvements made in open source projects. We then leverage this data to build a tool called PerfLens for performance improvement recommendations via code search. PerfLens indexes the performance improvements, takes a codebase as an input and searches a pool of performance improvements for similar code. We show that when our system is further augmented with profiler data information our recommendations are more accurate. Our experiments show that PerfLens can suggest performance improvements with 90% accuracy when profiler data is available and 55% accuracy when it analyzes source code only.