Miracle-dz/UniFAR-FTUs huggingface dataset:
Failure of Costimulatory Blockade-induced Regulatory T Cells to Sustain Long-term Survival of High Ischemic Allografts

Background. Costimulatory blockade–induced allograft tolerance has been achieved in rodent models, but these strategies do not translate well to nonhuman primate and clinical transplants. One confounder that may underlie this discrepancy is the greater ischemic inflammation imposed on the transplants. In mice, cardiac allografts subjected to prolonged cold ischemic storage (CIS) before transplant have increased ischemia–reperfusion injury, which amplifies infiltrating endogenous memory CD8 T-cell activation within hours after transplantation to mediate acute graft inflammation and cytotoxic lymphocyte-associated molecule-4 immunoglobulin–resistant rejection. This study tested strategies inhibiting memory CD8 T-cell activation within such high ischemic allografts to achieve long-term survival. Methods. A/J (H-2a) hearts subjected to 0.5 or 8 h of CIS were transplanted to C57BL/6 (H-2b) recipients and treatment with peritransplant costimulatory blockade. At 60 d posttransplant, regulatory T cells (Treg) were depleted in recipients of high ischemic allografts with anti-CD25 monoclonal antibody (mAb) or diphtheria toxin. Results. Whereas peritransplant (days 0 and +1) anti–lymphocyte function-associated antigen-1 mAb and anti-CD154 mAb prolonged survival of >60% allografts subjected to minimal CIS for >100 d, only 20% of allografts subjected to prolonged CIS survived beyond day 80 posttransplant and rejection was accompanied by high titers of donor-specific antibody. Peritransplant anti–lymphocyte function-associated antigen-1, anti–tumor necrosis factor-α, and anti-CD154 mAb plus additional anti-CD154 mAb on days 14 and 16 obviated this donor-specific antibody and promoted Treg-mediated tolerance and survival of 60% of high ischemic allografts beyond day 100 posttransplant, but all allografts failed by day 120. Conclusions. These studies indicate a strategy inducing prolonged high ischemic allograft survival through Treg-mediated tolerance that is not sustained indefinitely.
Sildenafil and Kidney Function in Heart Failure with Preserved Ejection Fraction

Key Points Sildenafil induced an acute effect on eGFR without change in the overall eGFR slope after 24 weeks in a heart failure with preserved ejection fraction (HFpEF) cohort. N-terminal pro–brain natriuretic peptide levels and baseline diuretic use were most strongly associated with eGFR decline in this HFpEF cohort. Long-term studies are required to determine sildenafil's influence on kidney function and outcomes in HFpEF. Background CKD worsens the prognosis for people with heart failure with preserved ejection fraction (HFpEF). In the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic HFpEF (RELAX) trial, sildenafil decreased eGFR compared with placebo despite favorable kidney effects in preclinical models. Since acute eGFR decline precedes long-term kidney benefits for select medications, we assessed the influence of sildenafil on acute and chronic eGFR slopes. Methods The RELAX trial randomized 216 participants to placebo or sildenafil and assessed 24-week changes in cardiopulmonary exercise testing, cardiovascular imaging, and laboratory data. We applied linear mixed modeling to calculate the total, acute (0–12 weeks), and chronic (3–24 weeks) eGFR slopes by treatment. Using regression modeling, we assessed respective associations between eGFR slope and baseline data and clinical end points. We repeated the analyses using a binary outcome on the basis of a substantial (≥20%) decline in eGFR. Results The mean baseline eGFR was 60.8 ml/min per 1.73 m2, and the mean eGFR slope during follow-up was −3.21 ml/min per 1.73 m2 per year. Sildenafil did not alter total eGFR slope compared with placebo (difference +0.47 ml/min per 1.73 m2 per year, 95% confidence interval [CI], −6.63 to 7.57 ml/min per 1.73 m2 per year). Sildenafil users tended to experience a more negative acute eGFR slope (difference −3.15 ml/min per 1.73 m2 per year) and more positive chronic slope (+2.06 ml/min per 1.73 m2 per year) compared with placebo, but neither difference reached statistical significance. Baseline N-terminal pro–B-type natriuretic peptide and loop diuretic use were associated with worse eGFR trajectory regardless of treatment. Substantial eGFR decline was associated with increase in endothelin-1 and a greater risk of hospitalization or death (HR, 2.34, 95% CI, 1.21 to 4.53, P=0.01). Conclusions Sildenafil induced an acute effect on eGFR without change in the overall eGFR slope after 24 weeks in an HFpEF cohort, suggesting lack of long-term risk related to early reduction in eGFR after initiating treatment. Long-term studies are needed to determine the effect of sildenafil on kidney function in HFpEF.
Transcranial Random Noise Stimulation Boosts Early Motion Perception Learning Rather than the Later Performance Plateau

Abstract The effect of transcranial random noise stimulation (tRNS) on visual perceptual learning has only been investigated during early training sessions, and the influence of tRNS on later performance is unclear. We engaged participants first in 8 days of training to reach a plateau (Stage 1) and then in continued training for 3 days (Stage 2). In the first group, tRNS was applied to visual areas of the brain while participants were trained on a coherent motion direction identification task over a period of 11 days (Stage 1 + Stage 2). In the second group, participants completed an 8-day training period without any stimulation to reach a plateau (Stage 1); after that, they continued training for 3 days, during which tRNS was administered (Stage 2). In the third group, participants completed the same training as the second group, but during Stage 2, tRNS was replaced by sham stimulation. Coherence thresholds were measured three times: before training, after Stage 1, and after Stage 2. Compared with sham simulation, tRNS did not improve coherence thresholds during the plateau period. The comparison of learning curves between the first and third groups showed that tRNS decreased thresholds in the early training stage, but it failed to improve plateau thresholds. For the second and third groups, tRNS did not further enhance plateau thresholds after the continued 3-day training period. In conclusion, tRNS facilitated visual perceptual learning in the early stage, but its effect disappeared as the training continued.
Formation and dynamics of nanoparticles in plasmas

• A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers.
Effects of physical property changes of expelled respiratory liquid on atomization morphology

Abstract A better understanding of the fluid dynamics of disease transmission by disintegrated respiratory droplets has been the focus of great attention since the recent outbreak of COVID-19. In particular, human respiratory activities such as coughing, sneezing and even talking and eating expel a large amount of pathogen-laden droplets. Particularly, during eating or drinking, the physical properties of saliva can be changed. In this study, we investigate the atomization morphology of expelled artificial saliva mixtures from the perspective of varying fluid physical properties, specifically surface tension and dynamic viscosity. Using high-speed shadowgraph experiments on artificial saliva, we visualize and analyse the disintegration of saliva liquid sheets into ligaments and droplets. We find that the viscosity and surface tension affect the droplet size formed from expelled saliva and follow scaling laws that have been previously observed and predicted for constant shear viscosity. We conclude that the changes in physical properties of saliva induced by eating and drinking tend to favour the formation of smaller droplets during sneezing or coughing, which could drive the airborne transmission pathway of pathogens. Furthermore, we derive a theoretical model based on scaling arguments that shows the breakup time of ligaments produced from the artificial saliva mixtures is dependent on the capillary number.
Community Involvement in Place-Making: Present Map Methodology

Abstract The aim this research was to develop and test the mapping methodology, that would be applicable in the process of community involvement into place-making process and would focus on functioning and usage of public spaces. The methodology is referred to a Present Map methodology and is structured as a one-day mapping workshop involving drawing from memory, fieldwork, identifying the locations in the geographical map, structuring of the collected information and entering data into interactive online Present Map. The application of the methodology in Sanciai historic district has demonstrated that this methodology allows both collecting the material about the people’s experiences in public spaces of the locality necessary for research and planning, as well as connecting community with the place and empowering it by providing the working tools for exploration and understanding of the place and platform for expression in a form of interactive online Present Map.
Authentication methods for voice services on smart speakers – a multi-method study on perceived security and ease of use

Abstract With the increasing proliferation of security-critical voice-based services such as voice banking, user authentication on smart speakers is becoming a vital requirement. Prior research on verifying the speaker’s identity has been taken a technical perspective predominantly, while respective user-centered research is scarce. To investigate authentication methods for smart speakers from a user’s perspective, we conducted a multi-method experiment. In a comprehensive online survey (n = 696) and a comparative lab study (n = 18) with an advanced functional prototype we studied 6 authentication methods (spoken PIN, biometrics, app with button/voice confirmation, card reader, sound authentication) regarding their perceived security and ease of use. While token-based authentication approaches (in particular an authenticator app on a smartphone) typically are perceived as more secure, they are found inferior when it comes to the ease of use. The currently most frequently used authentication method for smart speakers, the spoken PIN method, seems to represent a compromise between security and ease of use. The sophisticated sound authentication was appreciated for its ease of use, however, was rated worst regarding the perceived security.
Quantum Key Distribution: Basic Protocols and Threats

The last decade, the evolution in quantum computing has been enormous and real and reliable quantum computers are being developed quickly. One of the consequences of the upcoming quantum era is to make key distribution protocols insecure, as most of them are based on discrete algorithm problems. On the other hand, quantum computing provides a powerful and prominent tool for the safe transmission of information and cryptographic schemes and many of them have already been proposed. In this work, we discuss about quantum cryptography and we present certain quantum key distribution protocols. We also discuss about ‘potential attacks that can be performed against the quantum cryptographic schemes which are based on quantum system’s imperfections and loopholes.
Noisy technology, unhappy dogs: where technology might support caregiving in the home

While the advance of technology in our homes makes human lives easier, it also presents an ever growing source of sounds that may be confusing for the dogs that share our homes with us. To understand to what extent this may be a challenge, we present the findings of an empirical study (N=104) into the perception of dogs’ reactions to sound-producing technology in the home, and to what extent caregivers seem to have accurate understandings of dog body language. We found that dogs commonly react to any device in the home that produces sound, with some types of sounds seeming to lead to positive reactions, while others seem to trigger negative reactions consistent with anxiety and other fearful behavior. Our findings further indicated that caregivers seem to struggle with identifying dog body language indicative of such anxiety and fearful behavior, leading to the need for support in doing so. We present and discuss the initial design of technological support to identify when dogs are responding to sounds in the home in negative ways, and how this might be used to both inform caregiving towards dogs, as well as optimize home environments for multispecies co-existence.
Pushing the Limits of Video Game Performance: A Performance Engineering Perspective

Ubisoft constantly pushes the boundaries of game development to create immersive worlds that capture the imagination of millions of players worldwide. To achieve this, performance engineering plays a crucial role in ensuring that games run smoothly on various platforms and devices. In this talk, we will explore the latest advancements in the field of performance engineering for video games, focusing on runtime performance, network optimization, backend and database optimization, and cloud gaming. We will discuss how machine learning techniques enhance classical profiling and optimize game engine scheduling. Additionally, we will address the challenges of deterministic replication of assets between clients and optimizing micro-services for cloud gaming experiences. Lastly, we will touch on the importance of performance engineering for non-code aspects of game development, such as animation, textures, props, and assets.
A Survey on Signal Processing Methods for EEG-based Brain Computer Interface Systems

The development of human-computer interaction (HCI) systems that will efficiently capture the human brain, the so-called Brain-Computer Interaction (BCI) systems, will bring a new era in various disciplines (gaming, education, cultural heritage, etc). Actually, it is expected that the design and development of an electroencephalography (EEG) based-driven framework for intelligent real-time modelling of human cognitive abilities will provide groundbreaking technological advances in the delivery of human cognition-centred personalized systems and significantly advance the state-of-the-art research in human brain modelling. The aim of this paper is to make a concise and focused presentation of Signal Processing and Artificial Intelligence (AI) methods, including Machine Learning (ML) and Deep Learning (DL), and how these fields may help to model and thus predict human behaviour, emotion, cognitive state in different tasks.
Community Detection at scale: A comparison study among Apache Spark and Neo4j

The proliferation of data generation devices, including IoT and edge computing has led to the big data paradigm, which has considerably placed pressure on well-established relational databases during the last decade. Researchers have proposed several alternative database models in order to model the captured data more efficiently. Among these approaches, graph databases seem the most promising candidate to supplement relational schemes. Within this study, a comparison is performed among Neo4j, one of the leading graph databases, and Apache Spark, a unified engine for distributed large-scale data processing environment, in terms of processing limits. More specifically, the two frameworks are compared on their capacity to execute community detection algorithms.
Environmental DNA of aquatic macrophytes: the potential for reconstructing past and present vegetation and environments

Environmental DNA is increasingly being used to reconstruct past and present biodiversity including from freshwater ecosystems. Here, we first review and compare studies that use metagenomics, targeted capture, and various barcoding and metabarcoding markers, in order to explore how each of these methods can be used to capture aquatic vegetation diversity and change. We then investigate the extent to which such a record can be leveraged for reconstructing local environmental conditions, using a case study based on macrophyte ecological niches. We find that, with state-of-the-art DNA barcode reference libraries, using metabarcoding to target the P6 loop region of the chloroplast trnL (UAA) intron is optimal to maximise taxonomic resolution and the diversity of past macrophyte communities. Shotgun sequencing also retrieves a high proportion of aquatic macrophyte diversity, but has the lowest taxonomic resolution, and targeted capture needs to be more widely applied before comparisons can be made. From our case study, we infer past aquatic habitats from sedimentary ancient DNA records of macrophyte taxa. We reconstructed Holocene thermal range, continentality, water pH, trophic status, and light conditions in northern Fennoscandia. We show an overall stability since 9,000 years ago, even though individual lakes display different trends and variation in local climatic and physico-chemical conditions. Combined with the availability of near-exhaustive barcode and traits databases, metabarcoding data can support wider ecological reconstructions that are not limited to aquatic plant taxonomic inventories but can also be used to infer past changes in water conditions and their environmental drivers. Sedimentary DNA is also a powerful tool to measure present diversity, as well as to reconstruct past lacustrine and fluvial communities of aquatic macrophytes.
An essential role for miR-15/16 in Treg suppression and restriction of proliferation

The miR-15/16 family is a highly expressed group of tumor suppressor miRNAs that target a large network of genes in T cells to restrict their cell cycle, memory formation and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained immune response. Here, using conditional deletion of miR-15/16 in immunosuppressive regulatory T cells (Tregs) that express FOXP3, we identify new functions of the miR-15/16 family in T cell immunity. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16-deficiency alters Treg expression of critical functional proteins including FOXP3, IL2Rα/CD25, CTLA4, PD-1 and IL7Rα/CD127, and results in accumulation of functionally impaired FOXP3loCD25loCD127hi Tregs. Excessive proliferation in the absence of miR-15/16 inhibition of cell cycle programs shifts Treg diversity and produces an effector Treg phenotype characterized by low expression of TCF1, CD25 and CD62L, and high expression of CD44. These Tregs fail to control immune activation of CD4+ effector T cells, leading to spontaneous multi-organ inflammation and increased allergic airway inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance. Highlights Treg-specific miR-15/16 expression is essential to prevent systemic tissue inflammation miR-15/16 restrict Treg proliferation and regulate expression of the key functional Treg molecules FOXP3, IL2Rα, CTLA4, PD-1 and IL7Rα miR-15/16 limit formation of effector Tregs and is necessary for high suppressive capacity
Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia

Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of the cellular heterogeneity of tumors. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that can overcome the heterogeneity to prevent disease recurrence. Here, we characterized at the level of gene regulatory networks and at single-cell resolution the effect of G2/M cell cycle checkpoint inhibition in acute lymphoblastic leukemia (ALL) and demonstrate that WEE1 targeted therapy impinges on cell fate decision regulatory circuits. We found highest inhibition of recovery of proliferation in ALL cells with KMT2A-rearrangment (KMT2A-r), compared to cells of other leukemia subgroups. Single-cell transcriptome and chromatin accessibility profiling of (KMT2A::AFF1) RS4;11 cells treated with the WEE1 inhibitor AZD1775 revealed diversification of cell states at the fate decision points, with a fraction of cells exhibiting strong activation of p53-driven processes linked to induction of apoptosis and senescence, and disruption of a core KMT2A-RUNX1-MYC regulatory network through CDK1-mediated RUNX1 degradation. In RS4;11 cells and in patient-derived xenograft (PDX) model, we uncovered that in this cell state diversification induced by WEE1 inhibition, a subpopulation transitioned to a cell state characterized by activation of transcription factors regulating pre-B cell fate, lipid metabolism and pre-BCR signaling which supported a drug tolerance. Sequential treatment targeting the drug tolerant subpopulation with BCR-signaling inhibitors dasatinib, ibrutinib, or perturbing metabolism by fatostatin or AZD2014 after AZD1775 administration, effectively counteracted drug tolerance that drove recovery of leukemic cells. Collectively, our findings provide new insights into the tight connectivity of gene regulatory programs associated with cell cycle and cell fate regulation, and a rationale for sequential administration of WEE1 inhibitors with low toxicity inhibitors of pre-BCR signaling or metabolism.