bluuebunny/crossref_metadata_2025 huggingface dataset:
Attosecond-precision balanced timing detector with a single photodiode
Authors: Wang Tong , Li Mingzhe , Zhang Yi , Xin Ming
Published: September 2023

We experimentally demonstrate a novel and practical timing detector based on a double-pass acousto-optic frequency shifter. With time and frequency multiplexing, for the first time to our knowledge, a balanced detection is realized using only a single photodiode, which greatly decreases the excess electronic noise during photodetection. With a total input optical power of 1.4 mW (0.35 mW per pulse train), an almost shot-noise-limited detection floor of 28.3 zs/√Hz is achieved, and the timing jitter integrated from 1 kHz to 1 MHz is reduced from 99.0 as (without eliminating the photodetector electronic noise) to only 30.4 as. Even with an input power of 50 µW per pulse train, 221.4 zs/√Hz detection floor and 268.0 as integrated timing jitter at [1 kHz and 1 MHz] are still maintained. This timing detector provides a powerful tool for high-precision metrology, ultra-long-distance ranging, and large-scale timing synchronization.
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi
Authors: Bosch-Navarrete Cristina , Pérez-Moreno Guiomar , Annang Frederick , Diaz-Gonzalez Rosario , García-Hernández Raquel , Rocha Hedy , Gamarro Francisco , Cordón-Obras Carlos , Navarro Miguel , Rodriguez Ana , Genilloud Olga , Reyes Fernando , Vicente Francisca , Ruiz-Pérez Luis M. , González-Pacanowska Dolores
Published: September 2023

Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for identifying new drug candidates. We recently reported the discovery and bioassay-guided isolation of a novel family of macrolides with antiplasmodial activity. The novel family of four potent antimalarial macrolides, strasseriolides A-D, was isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues. In the present study, we analyze these strasseriolides for activity against kinetoplastid protozoan parasites, namely, Trypanosoma brucei brucei, Leishmania donovani and Trypanosoma cruzi. Compounds exhibited mostly low activities against T. b. brucei, yet notable growth inhibition and selectivity were observed for strasseriolides C and D in the clinically relevant intracellular T. cruzi and L. donovani amastigotes with EC50 values in the low micromolar range. Compound C is fast-acting and active against both intracellular and trypomastigote forms of T. cruzi. While cell cycle defects were not identified, prominent morphological changes were visualized by differential interference contrast microscopy and smaller and rounded parasites were visualized upon exposure to strasseriolide C. Moreover, compound C lowers parasitaemia in vivo in acute models of infection of Chagas disease. Hence, strasseriolide C is a novel natural product active against different forms of T. cruzi in vitro and in vivo. The study provides an avenue for blocking infection of new cells, a strategy that could additionally contribute to avoid treatment failure.
The image-based ultrasonic cell shaking test
Authors: Ballard Miranda , Marek Aleksander , Pierron Fabrice
Published: September 2023

Mechanical signals play a vital role in cell biology and is a vast area of research. Thus, there is motivation to understand cell deformation and mechanobiological responses. However, the ability to controllably deform cells in the ultrasonic regime and test their response is a noted challenge throughout the literature. Quantifying and eliciting an appropriate stimulus has proven to be difficult, resulting in methods that are either too aggressive or oversimplified. Furthermore, the ability to gain a real-time insight into cell deformation and link this with the biological response is yet to be achieved. One application of this understanding is in ultrasonic surgical cutting, which is a promising alternative to traditional methods, but with little understanding of its effect on cells. Here we present the image based ultrasonic cell shaking test, a novel method that enables controllable loading of cells and quantification of their response to ultrasonic vibrations. Practically, this involves seeding cells on a substrate that resonates at ultrasonic frequencies and transfers the deformation to the cells. This is then incorporated into microscopic imaging techniques to obtain high-speed images of ultrasonic cell deformation that can be analysed using digital image correlation techniques. Cells can then be extracted after excitation to undergo analysis to understand the biological response to the deformation. This method could aid in understanding the effects of ultrasonic stimulation on cells and how activated mechanobiological pathways result in physical and biochemical responses.
Inducible overexpression of a FAM3C/ILEI transgene has pleiotropic effects with shortened life span, liver fibrosis and anemia in mice
Authors: Schmidt Ulrike , Uluca Betül , Vokic Iva , Malik Barizah , Kolbe Thomas , Lassnig Caroline , Holcmann Martin , Moreno-Viedma Veronica , Robl Bernhard , Mühlberger Carina , Gotthardt Dagmar , Sibilia Maria , Rülicke Thomas , Müller Mathias , Csiszar Agnes
Published: September 2023

FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression and metastasis. Overexpressed in many cancers, elevated ILEI levels and secretion correlate with poor patient survival. Although ILEI’s causative role in invasive tumor growth and metastasis has been demonstrated in several cellular tumor models, there are no available transgenic mice to study these effects in the context of a complex organism. Here, we describe the generation and initial characterization of a Tet-ON inducible Fam3c/ILEI transgenic mouse strain. We find that ubiquitous induction of ILEI overexpression (R26-ILEIind) at weaning age leads to a shortened lifespan, reduced body weight and microcytic hypochromic anemia. The anemia was reversible at a young age within a week upon withdrawal of ILEI induction. Vav1-driven overexpression of the ILEIind transgene in all hematopoietic cells (Vav-ILEIind) did not render mice anemic or lower overall fitness, demonstrating that no intrinsic mechanisms of erythroid development were dysregulated by ILEI and that hematopoietic ILEI hyperfunction did not contribute to death. Reduced serum iron levels of R26-ILEIind mice were indicative for a malfunction in iron uptake or homeostasis. Accordingly, the liver, the main organ of iron metabolism, was severely affected in moribund ILEI overexpressing mice: increased alanine transaminase and aspartate aminotransferase levels indicated liver dysfunction, the liver was reduced in size, showed increased apoptosis, reduced cellular iron content, and had a fibrotic phenotype. These data indicate that high ILEI expression in the liver might reduce hepatoprotection and induce liver fibrosis, which leads to liver dysfunction, disturbed iron metabolism and eventually to death. Overall, we show here that the novel Tet-ON inducible Fam3c/ILEI transgenic mouse strain allows tissue specific timely controlled overexpression of ILEI and thus, will serve as a versatile tool to model the effect of elevated ILEI expression in diverse tissue entities and disease conditions, including cancer.
Estimated standard values of aerobic capacity according to sex and age in a Japanese population: A scoping review
Authors: Akiyama Hiroshi , Watanabe Daiki , Miyachi Motohiko
Published: September 2023

Aerobic capacity is a fitness measure reflecting the ability to sustain whole-body physical activity as fast and long as possible. Identifying the distribution of aerobic capacity in a population may help estimate their health status. This study aimed to estimate standard values of aerobic capacity (peak oxygen uptake [V˙O2peak]/kg and anaerobic threshold [AT]/kg) for the Japanese population stratified by sex and age using a meta-analysis. Moreover, the comparison of the estimated standard values of the Japanese with those of other populations was performed as a supplementary analysis. We systematically searched original articles on aerobic capacity in the Japanese population using PubMed, Ichushi-Web, and Google Scholar. We meta-analysed V˙O2peak/kg (total: 78,714, men: 54,614, women: 24,100) and AT (total: 4,042, men: 1,961, women: 2,081) data of healthy Japanese from 21 articles by sex and age. We also searched, collected and meta-analysed data from other populations. Means and 95% confidence intervals were calculated. The estimated standard values of V˙O2peak/kg (mL/kg/min) for Japanese men and women aged 4–9, 10–19, 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years were 47.6, 51.2, 43.2, 37.2, 34.5, 31.7, 28.6, and 26.3, and 42.0, 43.2, 33.6, 30.6, 27.4, 25.6, 23.4, and 23.1, respectively. The AT/kg (mL/kg/min) for Japanese men and women aged 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years were 21.1, 18.3, 16.8, 15.9, 15.8, and 15.2, and 17.4, 17.0, 15.7, 15.0, 14.5, and 14.2, respectively. Herein, we presented the estimated standard values of aerobic capacity according to sex and age in a Japanese population. In conclusion, aerobic capacity declines with ageing after 20–29 years of age. Additionally, aerobic capacity is lower in the Japanese population than in other populations across a wide range of age groups. Standard value estimation by meta-analysis can be conducted in any country or region and for public health purposes.
Copper infused fabric attenuates inflammation in macrophages
Authors: Zangiabadi Safoura , Chamoun Khalil P. , Nguyen Khang , Tang Yitian , Sweeney Gary , Abdul-Sater Ali A.
Published: September 2023

While inflammation is an important immune response for protection from infections, excessive or prolonged inflammation can lead to a variety of debilitating diseases including skin disease, diabetes, heart disease, stroke, autoimmune diseases and cancer. Inflammation is a graded response that is typically initiated when resident macrophages sense the presence of pathogens or damage in the tissue and produce inflammatory cytokines and chemokines to kill the pathogen, clear debris and dead tissue, and initiate tissue repair. Here we show that copper-infused fabrics can prevent inflammation by blocking the production of inflammatory cytokines from macrophages after being exposed to LPS, a component of bacterial cell wall. Mechanistically, we show that copper-infused fabrics can significantly reduce the NF-κB and IRF3 activation in LPS-stimulated macrophages. Given the importance of excessive inflammation in diabetes, we show that copper can reduce insulin resistance mediated by inflammatory cytokines in muscle cells. Our data show that copper infused fabrics may be useful to reduce excessive inflammation in macrophages and improve insulin sensitivity in skeletal muscles.
Nanomaterial genotoxicity evaluation using the high-throughput p53-binding protein 1 (53BP1) assay
Authors: Fontaine Maelle , Bartolami Eline , Prono Marion , Béal David , Blosi Magda , Costa Anna L. , Ravagli Costanza , Baldi Giovanni , Sprio Simone , Tampieri Anna , Fenoglio Ivana , Tran Lang , Fadeel Bengt , Carriere Marie
Published: September 2023

Toxicity evaluation of engineered nanomaterials is challenging due to the ever increasing number of materials and because nanomaterials (NMs) frequently interfere with commonly used assays. Hence, there is a need for robust, high-throughput assays with which to assess their hazard potential. The present study aimed at evaluating the applicability of a genotoxicity assay based on the immunostaining and foci counting of the DNA repair protein 53BP1 (p53-binding protein 1), in a high-throughput format, for NM genotoxicity assessment. For benchmarking purposes, we first applied the assay to a set of eight known genotoxic agents, as well as X-ray irradiation (1 Gy). Then, a panel of NMs and nanobiomaterials (NBMs) was evaluated with respect to their impact on cell viability and genotoxicity, and to their potential to induce reactive oxygen species (ROS) production. The genotoxicity recorded using the 53BP1 assay was confirmed using the micronucleus assay, also scored via automated (high-throughput) microscopy. The 53BP1 assay successfully identified genotoxic compounds on the HCT116 human intestinal cell line. None of the tested NMs showed any genotoxicity using the 53BP1 assay, except the positive control consisting in (CoO)(NiO) NMs, while only TiO2NMs showed positive outcome in the micronucleus assay. Only Fe3O4NMs caused significant elevation of ROS, not correlated to DNA damage. Therefore, owing to its adequate predictivity of the genotoxicity of most of the tested benchmark substance and its ease of implementation in a high throughput format, the 53BP1 assay could be proposed as a complementary high-throughput screening genotoxicity assay, in the context of the development of New Approach Methodologies.
New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance
Authors: Cabral Fernanda V. , Cerone Michela , Persheyev Saydulla , Lian Cheng , Samuel Ifor D. W. , Ribeiro Martha S. , Smith Terry K.
Published: September 2023

The emergence of drug resistance in cutaneous leishmaniasis (CL) has become a major problem over the past decades. The spread of resistant phenotypes has been attributed to the wide misuse of current antileishmanial chemotherapy, which is a serious threat to global health. Photodynamic therapy (PDT) has been shown to be effective against a wide spectrum of drug-resistant pathogens. Due to its multi-target approach and immediate effects, it may be an attractive strategy for treatment of drug-resistantLeishmaniaspecies. In this study, we sought to evaluate the activity of PDTin vitrousing the photosensitizer 1,9-dimethyl methylene blue (DMMB), against promastigotes of twoLeishmania amazonensisstrains: the wild-type (WT) and a lab induced miltefosine-resistant (MFR) strain. The underlying mechanisms of DMMB-PDT action upon the parasites was focused on the changes in the lipid metabolism of both strains, which was conducted by a quantitative lipidomics analysis. We also assessed the production of ROS, mitochondrial labeling and lipid droplets accumulation after DMMB-PDT. Our results show that DMMB-PDT produced high levels of ROS, promoting mitochondrial membrane depolarization due to the loss of membrane potential. In addition, both untreated strains revealed some differences in the lipid content, in which MFR parasites showed increased levels of phosphatidylcholine, hence suggesting this could also be related to their mechanism of resistance to miltefosine. Moreover, the oxidative stress and consequent lipid peroxidation led to significant phospholipid alterations, thereby resulting in cellular dysfunction and parasite death. Thus, our results demonstrated that DMMB-mediated PDT is effective to killL.amazonensisMFR strain and should be further studied as a potential strategy to overcome antileishmanial drug resistance.
Using portraits to quantify the changes of generalized social trust in European history: A replication study
Authors: Guillou Léonard , Safra Lou , Baumard Nicolas
Published: September 2023

A portrait is an exercise of impression management: the sitter can choose the impression she or he wants to create in the eyes of others’: competence, trustworthiness, dominance, etc. Indirectly, this choice informs us about the qualities that were specifically valued at the time the portrait was created. In a previous paper, we have shown that cues of perceived trustworthiness in portraits increased in time during the modern period in Europe, meaning that people probably granted more importance to be seen as a trustworthy person. Moreover, this increase is correlated to economic development. In this study, we aim to replicate this result, using more controlled databases: 1) a newly created database of European head-of-state sovereigns (N = 966, from 1400 to 2020), that is a database of individuals holding the same social position across time and countries, and 2) a database of very high-quality portraits digitized with the same technique, and coming from the same Museum, the Chateau de Versailles database (N = 2,291, from 1483 to 1938). Using mixed effects linear models, we observed in the first dataset that the modeled perceived facial trustworthiness of these sovereigns’ faces increased over time (b= 0.182 ± 0.04 s.e.m.,t(201) = 4.40,p< 0.001). On the opposite, no effect of time was detected on the portraits of the Château de Versailles (b = − 0.02 ± 0.03 s.e.m., t(759) = − 0.85, p > .250). We conclude by discussing the potential of this new technique to uncover long-term behavioral changes in history, as well as its limitations.
Neuroprognostication value of serum neurofilament light chain for out-of-hospital cardiac arrest: A systematic review and meta-analysis
Authors: Fu Yu , Fan Xiao-Tian , Li Hui , Zhang Ran , Zhang Ding-Ding , Jiang Hao , Chen Zhi-Guo , Zhang Jiang-Tao
Published: September 2023

Background

Neurofilament light chain (NfL) is a novel biomarker for the assessment of neurological function after cardiac arrest (CA). Although meta-analysis has confirmed its predictive value, it has not conducted a more detailed analysis of its research. We conducted a meta-analysis to evaluate the relationship between serum NfL level and neurological prognosis in patients with spontaneous circulation recovery after CA, and subgroup analysis was conducted according to sample collection time, time to assess neurological function, study design, whether TTM was received, the method of specimen determination, and the presence of neurological disease in patients. To analyze the influence of these factors on the predictive value of serum NfL.

Methods

Published Cochrane reviews and an updated, extended search of MEDLINE, Cochrane Library, Embase, Scopus, ClinicalKey, CINAHL, and Web of Science for relevant studies until March 2022 were assessed through inclusion and exclusion criteria. The standard mean difference and 95% confidence interval were calculated using the random-effects model or fixed-effects model to assess the association between one variable factor NfL level and the outcome of CA patients. Subgroup analysis according to sample collection time was performed. The prognosis analysis and publication bias were also assessed using Egger’s and Begg’s tests.

Results

Among 1209 related articles for screening, 6 studies (1360 patients) met the inclusion criteria and were selected for meta-analysis. The level of serum NfL in the good prognosis group (CPC1-2, CPC: cerebral performance category score) was significantly lower than that in the poor prognosis group (CPC3-5)SMD(standardized mean difference) = 0.553, 95%CI(confidence interval) = 0.418–0.687, I2 = 65.5% P<0.05). And this relationship also exists at each sampling time point (NfL specimens were collected on admission: SMD:0.48,95%CI:0.24–0.73; Samples were collected 24 hours after CA: SMD:0.60,95%CI:0.32–0.88;Specimens were obtained 48 hours after CA: SMD:0.51, 95%CI:0.18–0.85;Specimens were obtained 72 hours after CA: SMD:0.59, 95%CI:0.38–0.81).

Conclusion

NfL may play a potential neuroprognostication role in postcardiac arrest patients with spontaneous circulation, regardless of when the sample was collected after CA.
Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children
Authors: Yu Angela , Jansen Maria A. C. , Dalmeijer Geertje W. , Bruijning-Verhagen Patricia , van der Ent Cornelis K. , Grobbee Diederick E. , Burgner David P. , Uiterwaal Cuno S. P. M.
Published: September 2023

Background

Severe childhood infection has a dose-dependent association with adult cardiovascular events and with adverse cardiometabolic phenotypes. The relationship between cardiovascular outcomes and less severe childhood infections is unclear.

Aim

To investigate the relationship between common, non-hospitalised infections, antibiotic exposure, and preclinical vascular phenotypes in young children.

Design

A Dutch prospective population-derived birth cohort study.

Methods

Participants were from the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort. We collected data from birth to 5 years on antibiotic prescriptions, general practitioner (GP)-diagnosed infections, and monthly parent-reported febrile illnesses (0–1 years). At 5 years, carotid intima-media thickness (CIMT), carotid artery distensibility, and blood pressure (BP) were measured. General linear regression models were adjusted for age, sex, smoke exposure, birth weight z-score, body mass index, and socioeconomic status.

Results

Recent antibiotic exposure was associated with adverse cardiovascular phenotypes; each antibiotic prescription in the 3 and 6 months prior to vascular assessment was associated with an 18.1 μm (95% confidence interval, 4.5–31.6, p = 0.01) and 10.7 μm (0.8–20.5, p = 0.03) increase in CIMT, respectively. Each additional antibiotic prescription in the preceding 6 months was associated with an 8.3 mPa-1 decrease in carotid distensibility (-15.6– -1.1, p = 0.02). Any parent-reported febrile episode (compared to none) showed weak evidence of association with diastolic BP (1.6 mmHg increase, 0.04–3.1, p = 0.04). GP-diagnosed infections were not associated with vascular phenotypes.

Conclusions

Recent antibiotics are associated with adverse vascular phenotypes in early childhood. Mechanistic studies may differentiate antibiotic-related from infection-related effects and inform preventative strategies.
Detecting trends and shocks in terrorist activities
Authors: Prieto-Curiel Rafael , Walther Olivier , Davies Ewan
Published: September 2023

Although there are some techniques for dealing with sparse and concentrated discrete data, standard time-series analyses appear ill-suited to understanding the temporal patterns of terrorist attacks due to the sparsity of the events. This article addresses these issues by proposing a novel technique for analysing low-frequency temporal events, such as terrorism, based on their cumulative curve and corresponding gradients. Using an iterative algorithm based on a piecewise linear function, our technique detects trends and shocks observed in the events associated with terrorist groups that would not necessarily be visible using other methods. The analysis leverages disaggregated data on political violence from the Armed Conflict Location & Event Data Project (ACLED) to analyse the intensity of the two most violent terrorist organisations in Africa: Boko Haram (including its splinter group, the Islamic State West Africa Province), and Al-Shabaab. Our method detects moments when terrorist groups change their capabilities to conduct daily attacks and, by taking into account the directionality of attacks, highlights major changes in the government’s strategies. Results suggest that security policies have largely failed to reduce both groups’ forces and restore stability.
Instructional illustrations in children’s learning between normative and realism: An evaluation study
Authors: AlAli Rommel Mahmoud , Al-Barakat Ali Ahmad
Published: September 2023

Many studies indicate the importance of including the instructional illustrations (pictures, drawings, concrete objects …etc.) in childhood education learning materials and employing them in a way that suits the psychological and cognitive levels of young children. In this context, the current study aimed to develop a list of standards to be considered and adopted in designing instructional illustrations, and to reveal the perceptions of childhood teachers about the extent to which these standards are considered in instructional illustrations used in children’s learning materials. The participants were childhood education teachers in the Jordanian region of Irbid, who were randomly selected. Two hundred thirty-four teachers completed the questionnaire online. The scale consisted of a total of 34 items distributed over four dimensions. The results showed that the scores of teachers’ estimation about employing design standards in the instructional illustrations used in childhood education came at low levels, ranging from average to low, and did not reach high ratings. The study also revealed that there is an impact attributed to teaching experience on teachers’ perceptions about the extent to which these standards are employed in instructional illustrations, while there is no impact of gender, academic qualification, or the classes taught by the teachers.
Interventions promoting recovery from depression for patients transitioning from outpatient mental health services to primary care: Protocol for a scoping review
Authors: Aggestrup Anne Sofie , Martiny Frederik , Faurholt-Jepsen Maria , Hvenegaard Morten , Christensen Robin , Davidsen Annette Sofie , Martiny Klaus
Published: September 2023

Introduction

Patients with severe Major Depressive Disorder (MDD) have an increasing risk of new psychiatric hospitalizations following each new episode of depression highlighting the recurrent nature of the disorder. Furthermore, patients are not fully recovered at the end of their treatment in outpatient mental health services, and residual symptoms of depression might explain why patients with MDD have a high risk of relapse. However, evidence of methods to promote recovery after discharge from outpatient mental health services is lacking. The proposed scoping review aims to systematically scope, map and identify the evidence and knowledge gaps on interventions that aims to promote recovery from MDD for patients transitioning from outpatient mental health services to primary care.

Materials and methods

The proposed scoping review will follow the latest methodological guidance by the Joanna Briggs Institute (JBI) in tandem with the Preferred Reporting Items for Systematic reviews and Meta-Analysis—extension for Scoping Reviews (PRISMA-ScR) checklist. The review is ongoing. Four electronic databases (Medline via PubMed, PsycINFO, CINAHL, and Sociological Abstracts) were systematically searched from 20 January 2022 till 29 March 2022 using keywords and text words. The review team consists of three independent screeners. Two screeners have completed the initial title and abstract screening for all studies retrieved by the search strategy. Currently, we are in the full text screening phase. Reference lists of included studies will be screened, and data will be independently extracted by the review team. Results will be analyzed qualitatively and quantitatively.

Discussion

The chosen methodology is based on the use of publicly available information and does not require ethical approval. Results will be published in an international peer reviewed scientific journal, at national and international conferences and shared with relevant authorities.

Registration

A pre-print has been registered at the medRxiv preprint server for health sciences (doi.org/10.1101/2022.10.06.22280499).
Ion exchange chromatography as a simple and scalable method to isolate biologically active small extracellular vesicles from conditioned media
Authors: Malvicini Ricardo , Santa-Cruz Diego , Tolomeo Anna Maria , Muraca Maurizio , Yannarelli Gustavo , Pacienza Natalia
Published: September 2023

In the last few years, extracellular vesicles (EVs) have become of great interest due to their potential as biomarkers, drug delivery systems, and, in particular, therapeutic agents. However, there is no consensus on which is the best way to isolate these EVs. The choice of the isolation method depends on the starting material (i.e., conditioned culture media, urine, serum, etc.) and their downstream applications. Even though there are numerous methods to isolate EVs, few are compatible with clinical applications as they are not scalable. In the present work, we set up a protocol to isolate EVs from conditioned media by ion exchange chromatography, a simple, fast, and scalable method, suitable for clinical production. We performed the isolation using an anion exchange resin (Q sepharose) and eluted the EVs using 500 mM NaCl. We characterized the elution profile by measuring protein and lipid concentration, and CD63 by ELISA. Moreover, we immunophenotyped all the eluted fractions, assessed the presence of TSG101, calnexin, and cytochrome C by western blot, analyzed nanoparticle size and distribution by tRPS, and morphology by TEM. Finally, we evaluated the immunomodulatory activity in vitro. We found that most EVs are eluted and concentrated in a single peak fraction, with a mean particle size of <150nm and expression of CD9, CD63, CD81, and TSG101 markers. Moreover, sEVs in fraction 4 exerted an anti-inflammatory activity on LPS-stimulated macrophages. In summary, we set up a chromatographic, scalable, and clinically compatible method to isolate and concentrate small EVs from conditioned media, which preserves the EVs biological activity.
Evaluation of the hoof centre-of-pressure path in horses affected by chronic osteoarthritic pain
Authors: Buser Larissa Irina , Torelli Nathan , Andreis Sabrina , Witte Stefan , Spadavecchia Claudia
Published: September 2023

Introduction

The Centre of Pressure (COP) is the single point summarising all forces transferred to the hoof during the stance phase of a stride. COP path (COPp) is the trajectory that COP follows from footstrike to lift-off. Aim of the present study was to characterize the COP and COPp in horses affected by osteoarthritis and chronic lameness.

Materials and methods

Seventeen adult horses with a diagnosis of osteoarthritis and single limb chronic lameness were recruited. The COP was recorded using a wireless pressure measuring system (TekScan®) with sensors taped to the hooves (either fore- or hind limb, depending on lameness location). The COPp coordinates were further processed. Procrustes analysis was performed to assess the variability of single strides COPp and average COPp among strides, gaits, and limbs by calculating Procrustes distances (D-values). A linear mixed-effects model was run to analyse D-values differences for lame and sound limbs. Additionally, average COPp D-values and COPp hoofprint shape indices were compared for lame and sound limbs with the Signed Rank Test.

Results

At walk and trot the single-stride COPp D-values were significantly lower in lame than in sound limbs (marginal effects p<0.001). Analysis of the average COPp D-values confirmed that each hoof COPp is highly consistent with itself over subsequent trials but is different from the contralateral. COPp and hoofprint shape indices did not differ between sound and lame limbs. Footstrike and lift-off within the hoofprint showed that most horses had lateral footstrike and lift-off, independently of the lameness location.

Conclusion

Our findings are in line with previous observations that COPp are highly repetitive and characteristic for each horse and limb. There seems to be a further decrease in COPp variability in the presence of a painful limb pathology.
A magyar kis- és középvállalkozások digitális érettsége : A digiméter index: elméleti megalapozás
Authors: Pintér Róbert
Published: September 2023

A cikk a vállalati digitalizáció, KKV-digitalizáció és ezek mérése kapcsán elvégzett irodalomkutatás eredményein alapul.Egy kétrészes cikksorozat első darabja, a KKV-digitalizációt kutató Digiméter kutatássorozat tág értelemben vett elméleti megalapozása. A KKV-k kapcsán az egyik leggyakrabban vizsgált témának számít a digitalizáció, a digitális fejlettség és az érettség mérése. Ugyanakkor a KKV-digitalizáció kutatása számos kihívással küzd. Egyrészt a digitalizáció a vállalatok működésének egészét érinti, másrészt a KKV-k a nagyobb cégekhez képest inkább élhetik meg nehézségként ezt a folyamatot. A cikk bemutatja, hogy mennyire sokszínű a vállalati digitalizáció területe, aminek következtében nem létezik egyetlen átfogó, általánosan elfogadott definíciója. Emiatt nem egyértelmű a KKV-digitalizáció mérése sem a szakirodalom, sem a gyakorlat alapján. A beazonosított mérések között több az eltérés, mint a hasonlóság, nem létezik bevett módszertan a KKV-érettség vagy fejlettség mérésére.
Využitelnost dohody o vině a trestu a prohlášení viny v jednotlivých stadiích trestního řízení
Authors: Ščerba Filip
Published: September 2023

The article deals with the possibilities of using an agreement upon guilt and punishment and a statement of guilt during individual phases of criminal proceedings, primarily, during trial and after the commencement of proof. This problem is solved from the point of view of legal admissibility and from the point of view of its usefulness when the current practice of the courts is taken into consideration. Attention is also paid to the punishment imposed in agreement upon guilt and punishment or following a statement of guilt, with respect to the stage in which this procedure is applied. The article also offers some consideration regarding the validity of entering into the agreement upon guilt and punishment at the very beginning of an investigation.
Taurus MM: Bringing Multi-Master to the Cloud
Authors: Depoutovitch Alex , Chen Chong , Larson Per-Ake , Ng Jack , Lin Shu , Xiong Guanzhu , Lee Paul , Boctor Emad , Ren Samiao , Wu Lengdong , Zhang Yuchen , Sun Calvin
Published: September 2023

A single-master database has limited update capacity because a single node handles all updates. A multi-master database potentially has higher update capacity because the load is spread across multiple nodes. However, the need to coordinate updates and ensure durability can generate high network traffic. Reducing network load is particularly important in a cloud environment where the network infrastructure is shared among thousands of tenants. In this paper, we present Taurus MM, a shared-storage multi-master database optimized for cloud environments. It implements two novel algorithms aimed at reducing network traffic plus a number of additional optimizations. The first algorithm is a new type of distributed clock that combines the small size of Lamport clocks with the effective support of distributed snapshots of vector clocks. The second algorithm is a new hybrid page and row locking protocol that significantly reduces the number of lock requests sent over the network. Experimental results on a cluster with up to eight masters demonstrate superior performance compared to Aurora multi-master and CockroachDB.
StreamOps: Cloud-Native Runtime Management for Streaming Services in ByteDance
Authors: Mao Yancan , Chen Zhanghao , Zhang Yifan , Wang Meng , Fang Yong , Zhang Guanghui , Shi Rui , Ma Richard T. B.
Published: September 2023

Stream processing is widely used for real-time data processing and decision-making, leading to tens of thousands of streaming jobs deployed in ByteDance cloud. Since those streaming jobs usually run for several days or longer and the input workloads vary over time, they usually face diverse runtime issues such as processing lag and varying failures. This requires runtime management to resolve such runtime issues automatically. However, designing a runtime management service on the ByteDance scale is challenging. In particular, the service has to concurrently manage cluster-wide streaming jobs in a scalable and extensible manner. Furthermore, it should also be able to manage diverse streaming jobs effectively.

To this end, we propose
StreamOps
to enable cloud-native runtime management for streaming jobs in ByteDance.
StreamOps
has three main designs to address the challenges. 1) To allow for scalability,
StreamOps
is running as a standalone lightweight control plane to manage cluster-wide streaming jobs. 2) To enable extensible runtime management,
StreamOps
abstracts control policies to identify and resolve runtime issues. New control policies can be implemented with a detect-diagnose-resolve programming paradigm. Each control policy is also configurable for different streaming jobs according to the performance requirements. 3) To mitigate processing lag and handling failures effectively,
StreamOps
features three control policies, i.e., auto-scaler, straggler detector, and job doctor, that are inspired by state-of-the-art research and production experiences at ByteDance. In this paper, we introduce the design decisions we made and the experiences we learned from building
StreamOps.
We evaluate
StreamOps
in our production environment, and the experiment results have further validated our system design.
FEBench: A Benchmark for Real-Time Relational Data Feature Extraction
Authors: Zhou Xuanhe , Chen Cheng , Li Kunyi , He Bingsheng , Lu Mian , Liu Qiaosheng , Huang Wei , Li Guoliang , Zheng Zhao , Chen Yuqiang
Published: September 2023

As the use of online AI inference services rapidly expands in various applications (e.g., fraud detection in banking, product recommendation in e-commerce), real-time feature extraction (RTFE) systems have been developed to compute the requested features from incoming data tuples in ultra-low latency. Similar to relational databases, these RTFE procedures can be expressed using SQL-like languages. However, there is a lack of research on the workload characteristics and specialized benchmarks for RTFE, especially in comparison with existing database workloads and benchmarks (e.g., concurrent transactions in TPC-C). In this paper, we study the RTFE workload characteristics using over one hundred real datasets from open repositories (e.g. Kaggle, Tianchi, UCI ML, KiltHub) and those from 4Paradigm. The study highlights the significant differences between RTFE workloads and existing database benchmarks in terms of application scenarios, operator distributions, and query structures. Based on these findings, we propose to develop a realtime feature extraction benchmark named FEBench based on the four important criteria for a domain-specific benchmark proposed by Jim Gray. FEBench consists of selected representative datasets, query templates, and an online request simulator. We use FEBench to evaluate the effectiveness of feature extraction systems including OpenMLDB and Flink and find that each system exhibits distinct advantages and limitations in terms of overall latency, tail latency, and concurrency performance.
Anser: Adaptive Information Sharing Framework of AnalyticDB
Authors: Lin Liang , Li Yuhan , Wu Bin , Mai Huijun , Lou Renjie , Tan Jian , Li Feifei
Published: September 2023

The surge in data analytics has fostered burgeoning demand for
AnalyticDB
on Alibaba Cloud, which has well served thousands of customers from various business sectors. The most notable feature is the diversity of the workloads it handles, including batch processing, real-time data analytics, and unstructured data analytics. To improve the overall performance for such diverse workloads, one of the major challenges is to optimize long-running complex queries without sacrificing the processing efficiency of short-running interactive queries. While existing methods attempt to utilize runtime dynamic statistics for adaptive query processing, they often focus on specific scenarios instead of providing a holistic solution.

To address this challenge, we propose a new framework called
Anser
, which enhances the design of traditional distributed data warehouses by embedding a new information sharing mechanism. This allows for the efficient management of the production and consumption of various dynamic information across the system. Building on top of
Anser
, we introduce a novel scheduling policy that optimizes both data and information exchanges within the physical plan, enabling the acceleration of complex analytical queries without sacrificing the performance of short-running interactive queries. We conduct comprehensive experiments over public and in-house workloads to demonstrate the effectiveness and efficiency of our proposed information sharing framework.
Lindorm TSDB: A Cloud-Native Time-Series Database for Large-Scale Monitoring Systems
Authors: Shen Chunhui , Ouyang Qianyu , Li Feibo , Liu Zhipeng , Zhu Longcheng , Zou Yujie , Su Qing , Yu Tianhuan , Yi Yi , Hu Jianhong , Zheng Cen , Wen Bo , Zheng Hanbang , Xu Lunfan , Pan Sicheng , Wu Bin , He Xiao , Li Ye , Tan Jian , Wang Sheng , Pei Dan , Zhang Wei , Li Feifei
Published: September 2023

Internet services supported by large-scale distributed systems have become essential for our daily life. To ensure the stability and high quality of services, diverse metric data are constantly collected and managed in a time-series database to monitor the service status. However, when the number of metrics becomes massive, existing time-series databases are inefficient in handling high-rate data ingestion and queries hitting multiple metrics. Besides, they all lack the support of machine learning functions, which are crucial for sophisticated analysis of large-scale time series. In this paper, we present Lindorm TSDB, a distributed time-series database designed for handling monitoring metrics at scale. It sustains high write throughput and low query latency with massive active metrics. It also allows users to analyze data with anomaly detection and time series forecasting algorithms directly through SQL. Furthermore, Lindorm TSDB retains stable performance even during node scaling. We evaluate Lindorm TSDB under different data scales, and the results show that it outperforms two popular open-source time-series databases on both writing and query, while executing time-series machine learning tasks efficiently.
OceanBase Paetica: A Hybrid Shared-Nothing/Shared-Everything Database for Supporting Single Machine and Distributed Cluster
Authors: Yang Zhifeng , Xu Quanqing , Gao Shanyan , Yang Chuanhui , Wang Guoping , Zhao Yuzhong , Kong Fanyu , Liu Hao , Wang Wanhong , Xiao Jinliang
Published: September 2023

In the ongoing evolution of the OceanBase database system, it is essential to enhance its adaptability to small-scale enterprises. The OceanBase database system has demonstrated its stability and effectiveness within the Ant Group and other commercial organizations, besides through the TPC-C and TPC-H tests. In this paper, we have designed a stand-alone and distributed integrated architecture named Paetica to address the overhead caused by the distributed components in the stand-alone mode, with respect to the OceanBase system. Paetica enables adaptive configuration of the database that allows OceanBase to support both serial and parallel executions in stand-alone and distributed scenarios, thus providing efficiency and economy. This design has been implemented in version 4.0 of the OceanBase system, and the experiments show that Paetica exhibits notable scalability and outperforms alternative stand-alone or distributed databases. Furthermore, it enables the transition of OceanBase from primarily serving large enterprises to truly catering to small and medium enterprises, by employing a single OceanBase database for the successive stages of enterprise or business development, without the requirement for migration. Our experiments confirm that Paetica has achieved linear scalability with the increasing CPU core number within the stand-alone mode. It also outperforms MySQL and Greenplum in the Sysbench and TPC-H evaluations.
PyTorch FSDP: Experiences on Scaling Fully Sharded Data Parallel
Authors: Zhao Yanli , Gu Andrew , Varma Rohan , Luo Liang , Huang Chien-Chin , Xu Min , Wright Less , Shojanazeri Hamid , Ott Myle , Shleifer Sam , Desmaison Alban , Balioglu Can , Damania Pritam , Nguyen Bernard , Chauhan Geeta , Hao Yuchen , Mathews Ajit , Li Shen
Published: September 2023

It is widely acknowledged that large models have the potential to deliver superior performance across a broad range of domains. Despite the remarkable progress made in the field of machine learning systems research, which has enabled the development and exploration of large models, such abilities remain confined to a small group of advanced users and industry leaders, resulting in an implicit technical barrier for the wider community to access and leverage these technologies. In this paper, we introduce PyTorch Fully Sharded Data Parallel (FSDP) as an industry-grade solution for large model training. FSDP has been closely co-designed with several key PyTorch core components including Tensor implementation, dispatcher system, and CUDA memory caching allocator, to provide non-intrusive user experiences and high training efficiency. Additionally, FSDP natively incorporates a range of techniques and settings to optimize resource utilization across a variety of hardware configurations. The experimental results demonstrate that FSDP is capable of achieving comparable performance to Distributed Data Parallel while providing support for significantly larger models with near-linear scalability in terms of TFLOPS.
A Tutorial on Visual Representations of Relational Queries
Authors: Gatterbauer Wolfgang
Published: September 2023

Query formulation is increasingly performed by systems that need to guess a user's intent (e.g. via spoken word interfaces). But how can a user know that the computational agent is returning answers to the "right" query? More generally, given that relational queries can become pretty complicated,
how can we help users understand existing relational queries
, whether human-generated or automatically generated? Now seems the right moment to revisit a topic that predates the birth of the relational model: developing visual metaphors that help users understand relational queries.

This lecture-style tutorial surveys the key
visual metaphors developed for visual representations of relational expressions.
We will survey the history and state-of-the art of relationally-complete diagrammatic representations of relational queries, discuss the key visual metaphors developed in over a century of investigating diagrammatic languages, and organize the landscape by mapping their used visual alphabets to the syntax and semantics of Relational Algebra (RA) and Relational Calculus (RC).
A Demonstration of DLBD: Database Logic Bug Detection System
Authors: Tang Xiu , Wu Sai , Zhang Dongxiang , Wang Ziyue , Yuan Gongsheng , Chen Gang
Published: September 2023

Database management systems (DBMSs) are prone to logic bugs that can result in incorrect query results. Current debugging tools are limited to single table queries and struggle with issues like lack of ground-truth results and repetitive query space exploration. In this paper, we demonstrate DLBD, a system that automatically detects logic bugs in databases. DLBD offers holistic logic bug detection by providing automatic schema and query generation and ground-truth query result retrieval. Additionally, DLBD provides minimal test cases and root cause analysis for each bug to aid developers in reproducing and fixing detected bugs. DLBD incorporates heuristics and domain-specific knowledge to efficiently prune the search space and employs query space exploration mechanisms to avoid the repetitive search. Finally, DLBD utilizes a distributed processing framework to test database logic bugs in a scalable and efficient manner. Our system offers developers a reliable and effective way to detect and fix logic bugs in DBMSs.
On-the-Fly Data Transformation in Action
Authors: Mun Ju Hyoung , Karatsenidis Konstantinos , Papon Tarikul Islam , Roozkhosh Shahin , Hoornaert Denis , Drepper Ulrich , Sanaullah Ahmed , Mancuso Renato , Athanassoulis Manos
Published: September 2023

Transactional and analytical database management systems (DBMS) typically employ different data layouts: row-stores for the first and column-stores for the latter. In order to bridge the requirements of the two without maintaining two systems and two (or more) copies of the data, our proposed system
Relational Memory
employs specialized hardware that transforms the base row table into arbitrary column groups at query execution time. This approach maximizes the cache locality and is easy to use via a simple abstraction that allows transparent on-the-fly data transformation. Here, we demonstrate how to deploy and use Relational Memory via four representative scenarios. The demonstration uses the full-stack implementation of Relational Memory on the Xilinx Zynq UltraScale+ MPSoC platform. Conference participants will interact with Relational Memory deployed in the actual platform.