Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRank: End-to-End Latency Issue Localization with Extended Spectrum Analysis in Microservice Environments

With the advantages of flexible scalability and fast delivery, microservice has become a popular software architecture in the modern IT industry. However, the explosion in the number of service instances and complex dependencies make the troubleshooting extremely challenging in microservice environments. To help understand and troubleshoot a microservice system, the end-to-end tracing technology has been widely applied to capture the execution path of each request. Nevertheless, the tracing data are not fully leveraged by cloud and application providers when conducting latency issue localization in the microservice environment. This paper proposes a novel system, named MicroRank, which analyzes clues provided by normal and abnormal traces to locate root causes of latency issues. Once a latency issue is detected by the Anomaly Detector in MicroRank, the cause localization procedure is triggered. MicroRank first distinguishs which traces are abnormal. Then, MicroRank’s PageRank Scorer module uses the abnormal and normal trace information as its input and differentials the importance of different traces to extended spectrum techniques . Finally, the spectrum techniques can calculate the ranking list based on the weighted spectrum information from PageRank Scorer to locate root causes more effectively. The experimental evaluations on a widely-used open-source system and a production system show that MicroRank achieves excellent results not only in one root cause situation but also in two issues that happen at the same time. Moreover, MicroRank makes 6% to 22% improvement in recall in localizing root causes compared to current state-of-the-art methods.
Insurance Assistant: An Intelligent Platform for Video Insurance Assessment

In the insurance industry, the assessor’s role is essential and requires significant efforts conversing with the claimant. This is a highly professional process that involves many complex operations to make a final insurance report. In order to save the cost, the previous offline insurance assessment procedure is gradually moved online. However, for the junior assessor often lacking in practical experience, it is not easy to quickly handle such an online procedure, yet this is important as the insurance company decides how much compensation the claimant should receive based on the assessor’s feedback. In this paper, we present an insurance assistant that applies NLP technologies to help junior insurance assessors do their job better. The insurance assistant recommends appropriate inquiring policies and auto-completes the case report during the insurance assessment procedure. Here, we demonstrate the system via a short video 1.
How Fair is Fairness-aware Representative Ranking?

It has been observed in several works that the ranking of candidates based on their score can be biased for candidates belonging to the minority community. In recent works, the fairness-aware representative ranking was proposed for computing fairness-aware re-ranking of results. The proposed algorithm achieves the desired distribution of top-ranked results with respect to one or more protected attributes. In this work, we highlight the bias in fairness-aware representative ranking for an individual and for a group if the group is sub-active on the platform. We define individual unfairness and group unfairness from two different perspectives. We further propose methods to generate ideal individual and group fair representative ranking if the universal representation ratio is known. The paper is concluded with open challenges and further directions.
Lifetime risk of suicide among survivors of the atomic bombings of Japan

Abstract Aims The long-term physical health effects of the atomic bombings of Hiroshima and Nagasaki are well characterised, but the psychological effects remain unclear. Therefore, we sought to determine whether measures of exposure severity, as indirect measures of psychological trauma arising from exposure to the atomic bombings, are associated with suicide mortality among atomic bomb survivors. Methods The Life Span Study is a prospective cohort study of 93 741 Japanese atomic bomb survivors who were located within 10 km of the hypocentre in Hiroshima or Nagasaki at the time of the bombings in 1945, and 26 579 residents of Hiroshima and Nagasaki who were not in either city at the time of the bombings, matched to survivors on city, sex and age. Measures of exposure severity included: proximity to the hypocentre, type of shielding between the survivor and the blast and self-reported occurrence of acute radiation and thermal injuries. Date of death was obtained from the Japanese National Family Registry system. Cause of death was obtained from death certificates. Adjusted hazard ratios (HRs) were estimated from Cox regression models overall and stratified by sex and age. Results During the 60-year follow-up period (1950–2009), 1150 suicide deaths were recorded among 120 231 participants (23.6 per 100 000 person-years): 510 among 70 092 women (17.2 per 100 000 person-years) and 640 among 50 139 men (33.6 per 100 000 person-years). Overall, there was no association of proximity, type of shielding or the occurrence of acute injuries with suicide mortality. Among those <25 years of age at the time of the bombings, increased suicide risk was observed for survivors outside v. shielded inside any structure (HR: 1.24; 95% confidence interval (CI): 1.03, 1.48; interaction p = 0.054) and for those who reported flash burns (HR: 1.32; 95% CI: 1.00, 1.73; interaction p = 0.025). Sex-stratified analyses indicated that these associations were limited to men. Among women, closer proximity to the hypocentre was associated with a non-significant increase in suicide risk, with a positive association between proximity and suicide risk observed among women <15 years of age (HR: 1.09 per km; 95% CI: 1.00, 1.18; interaction p = 0.067). Conclusions Proximity to the hypocentre, shielding and acute injury presence do not generally appear to influence suicide mortality among atomic bomb survivors. However, heterogeneity may exist by age and sex, with younger survivors potentially more sensitive to psychological trauma. Coupled with other studies, our results suggest the importance of long-term monitoring of mental health among young populations exposed to catastrophic events or mass trauma.
Are serum molecular markers more effective than the invasive methods used in the diagnosis of breast cancers?

Abstract Objectives The most effective method currently used in breast cancer diagnosis is fine-needle aspiration biopsy. However, if the superiority of serum molecular markers to invasive diagnostic methods can be proven, it will have a great impact on the diagnostic approach and screening programs for breast cancer. The aim of this study is to demonstrate the efficacy of the serum molecular markers in the diagnosis of breast cancer with respect to invasive methods. Materials and Methods In this study, the literature on serum molecular markers and tissue molecular markers obtained using fine needle aspiration biopsy were collected. The absolute sensitivity rates obtained for serum molecular markers and for invasive needle biopsy methods were compared by systematic biostatistical analysis. Results In the diagnosis of breast cancer, the absolute sensitivity rates of serum molecular markers (90.6%) were found to be significantly higher than the absolute sensitivity rates of invasive methods (80.7%) (p<0.001). Conclusions These results indicate that, serum molecular markers, can be used safely in breast cancer screening, definitive diagnosis and follow-up. Therefore, in the near future, serum molecular markers are likely to take a higher priority in breast cancer diagnosis and screening.
A comparison of volatile compounds in fish sauces prepared from silver carp by use of soy sauce koji and lactic acid bacteria with those in Chinese commercial fish sauces

Yasuhiro FUNATSU*, Ken-Ichi KAWASAKI*, Chunhong YUAN**, Motoharu UCHIDA***, Masataka SATOMI*** and Yutaka FUKUDA*** * Toyama Prefectural Food Research Institute , 360, Yoshioka, Toyama, 939-8153 ** Faculty of Food Science and Technology , Shanghai Fisheries University, 334, Jungong Road, Shanghai 200090, China *** Notional Research Institute of Fisheries Science , 2-12-4, Fukuura, Kanazawa-Ku, Yokohama, Kanagawa 236-8648
Probing Interactions of Therapeutic Antibodies with Serum via Second Virial Coefficient Measurements

Antibody-based therapeutics are the fastest growing drug class on the market, used to treat aggressive forms of cancer, chronic autoimmune conditions, and numerous other disease states. While the specificity, affinity, and versatility of therapeutic antibodies can provide an advantage over traditional small molecule drugs, their development and optimization can be much more challenging and time-consuming. This is, in part, because the ideal formulation buffer systems used for in vitro characterization inadequately reflect the crowded biological environments (serum, endosomal lumen, etc.) that these drugs experience once administered to a patient. Such environments can perturb the binding of antibodies to their antigens and receptors, as well as homo- and hetero-aggregation, in ways that are incompletely understood, thereby altering therapeutic effect and disposition. While excluded volume effects are classically thought to favor binding, weak interactions with co-solutes in crowded conditions can inhibit binding. The second virial coefficient (B2) parameter quantifies such weak interactions and can be determined by a variety of techniques in dilute solution, but analogous methods in complex biological fluids are not well established. Here, we demonstrate that fluorescence correlation spectroscopy (FCS) is able to measure diffusive B2 values directly in undiluted serum. Apparent second virial coefficient (B2,app) measurements of antibodies in serum reveal that changes in the balance between attractive and repulsive interactions can dramatically impact global nonideality. Furthermore, our findings suggest that the common approach of isolating specific components and completing independent cross-term virial coefficient measurements is an incomplete representation of nonideality in serum. The approach presented here could enrich our understanding of the effects of biological environments on proteins in general, and advance the development of therapeutic antibodies and other protein-based therapeutics. STATEMENT OF SIGNIFICANCE We present FCS as an orthogonal method to traditional methods for characterizing weak, nonspecific homo- and hetero-interactions through determination of self- and cross-term second virial coefficients, respectively. We also characterize weak interactions between therapeutic antibodies and serum components through determination of an apparent second virial coefficient (B2,app) directly in undiluted serum. Our results suggest that global nonideality effects are antibody-dependent, and that attractive and repulsive interactions with co-solutes are occurring simultaneously. This approach could advance our understanding of the impact of nonideality to the biophysical and pharmacological properties of therapeutic antibodies and other engineered proteins in relevant biological environments, and could accelerate the development and optimization of protein-based therapeutics.
Stat3 co-operates with mutant Ezh2Y641F to regulate gene expression and limit the anti-tumor immune response in melanoma

One of the most frequently genetically altered chromatin modifiers in melanoma is the Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which methylates lysine 27 on histone 3 (H3K27me3), a chromatin mark associated with transcriptional repression. Genetic alterations in EZH2 in melanoma include amplifications and activating point mutations at tyrosine 641 (Y641). The oncogenic role of EZH2 in melanoma has previously been identified; however, its downstream mechanisms remain underexplored. We found that in genetically engineered mouse models, Ezh2Y641F expression causes upregulation of a subset of interferon-regulated genes in melanoma cells, suggesting a potential role of the immune system in the pathogenesis of these mutations. Upregulation of these interferon genes was not a result of changes in H3K27me3, but through a direct and non-canonical interaction between Ezh2 and Signal Transducer and Activator of Transcription 3 (Stat3). Ezh2 directly binds Stat3, and, in the presence of Ezh2Y641F, Stat3 protein is hypermethylated. Expression of Stat3 was required to maintain an anti-tumor immune response and its depletion resulted in faster melanoma progression and disease recurrence. Molecularly, Stat3 and Ezh2 bind together at many genomic loci, and can both activate and repress gene expression in association with the rest of the PRC2 complex. These results suggest that Ezh2 can mediate melanomagenesis through evasion of the anti-tumor immune response, and that the immunomodulatory properties of Stat3 are context dependent.
The Rab11-family interacting proteins reveal selective interaction of mammalian recycling endosomes with the Toxoplasma parasitophorous vacuole in a Rab11- and Arf6-dependent manner

After invasion of mammalian cells, the parasite Toxoplasma gondii multiplies in a self-made membrane-bound compartment, the parasitophorous vacuole (PV). We previously showed that intravacuolar Toxoplasma interacts with many host cell organelles, especially recycling endosomes, and further manipulates the host endocytic recycling through the sequestration of Rab11 vesicles into the PV. Mammalian Rab-PV interactions are likely mediated by Toxoplasma and host proteins that remain to be identified. In this context, we have examined the specificity of host Rab vesicle interaction with the PV by monitoring the recruitment of subtypes of Rab11 vesicles differing in their composition in Rab11-Family Interacting Proteins (FIPs). We found that vesicles with FIPs from Class I (FIP1C, FIP2, FIP5) or Class II (FIP3, FIP4) are distributed at the PV and detected to varying degrees inside the PV. The PV delivery of vesicles with FIPs from Class I, but not Class II, is Rab11-dependent. In addition to Rab11, FIP3 binds to Arf6, and vesicles associated with FIP3-Arf6 complexes are observed within the PV. Binding of FIP3 to either Rab11 or Arf6 significantly increases the internalization of vesicles into the PV. These data point to a selective process of host recycling endosome recognition and scavenging mediated by Toxoplasma.
Arousal-dependent auditory responses in the brain of Bengalese finches measured by gene expression

Songbirds use auditory feedback to maintain their own songs. Juveniles also memorize a tutor song and use memory as a template to make up their own songs through auditory feedback. A recent electrophysiological study revealed that HVC neurons respond to BOS playback only in low arousal, sleeping, or anesthetized conditions. One outstanding question is how does auditory suppression occur in the brain? Here, we determined how arousal affects auditory responses simultaneously in the whole brain and over the song neural circuit in Bengalese finches, using the immediate early gene egr-1 as a marker of neural activity. Our results showed that auditory responses in the low-arousal state were less susceptible to gating, which was also confirmed by gene expression, and that the suppression may be weaker than observed in previous zebra finch studies. This may be because the Bengalese finch is a domesticated species. In addition, our results suggest that information may flow from the MLd.I of the midbrain to higher auditory regions. Altogether, this study presents a new attempt to explore the auditory suppression network by simultaneously investigating the whole brain using molecular biology methods.
Multilocus adaptation to vaccination

Pathogen adaptation to public health interventions, such as vaccination, may take tortuous routes and involve multiple mutations at distinct locations in the pathogen genome, acting on distinct phenotypic traits. Despite its importance for public health, how these multilocus adaptations jointly evolve is poorly understood. Here we consider the joint evolution of two adaptations: the pathogen’s ability to escape the vaccine-induced immune response and adjustments to the pathogen’s virulence and transmissi-bility. We elucidate the role played by epistasis and recombination, with an emphasis on the different protective effects of vaccination. We show that vaccines reducing transmission and/or increasing clearance generate positive epistasis between the vaccine-escape and virulence alleles, favouring strains that carry both mutations, whereas vaccines reducing virulence mortality generate negative epistasis, favouring strains that carry either mutation, but not both. High rates of recombination can affect these predictions. If epistasis is positive, frequent recombination can lead to the sequential fixation of the two mutations and prevent the transient build-up of more virulent escape strains. If epistasis is negative, frequent recombination between loci can create an evolutionary bistability, such that whichever adaptation is more accessible tends to be favoured in the long-term. Our work provides a timely alternative to the variant-centered perspective on pathogen adaptation and captures the effect of different types of vaccines on the interference between multiple adaptive mutations.
The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response

A long-standing practice in the treatment of cancer is that of hitting hard with the maximum tolerated dose to eradicate tumors. This continuous therapy, however, selects for resistant cells, leading to the failure of the treatment. A different type of treatment strategy, adaptive therapy, has recently been shown to have a degree of success in both preclinical xenograft experiments and clinical trials. Adaptive therapy is used to maintain a tumor’s volume by exploiting the competition between drug-sensitive and drug-resistant cells with minimum effective drug doses or timed drug holidays. To further understand the role of competition in the outcomes of adaptive therapy, we developed a 2D on-lattice agent-based model. Our simulations show that the superiority of the adaptive strategy over continuous therapy depends on the local competition shaped by the spatial distribution of resistant cells. Cancer cell migration and increased carrying capacity accelerate the progression of the tumor under both types of treatments by reducing the spatial competition. Intratumor competition can also be affected by fibroblasts, which produce microenvironmental factors that promote cancer cell growth. Our simulations show that the spatial architecture of fibroblasts modulates the benefits of adaptive therapy. Finally, as a proof of concept, we simulated the outcomes of adaptive therapy in multiple metastatic sites composed of different spatial distributions of fibroblasts and drug-resistant cell populations.
Bio-elicitation of β-carboline alkaloids in Cell Suspension Culture of Peganum harmala L.

Background: Sustainable and commercial production of secondary metabolites is a critical issue when dealing with its clinical application. Efforts are still being made to look for biotic or abiotic elicitors with more efficient and universal effects on the improvement of secondary metabolites. Objective: In order to evaluate the suitability of different biotic elicitors on P. harmala L. cell suspension cultures was established to enhance the β-carboline alkaloids (harmaline and harmine) production. Methods: The elicitation of cell suspension cultures of Peganum harmala L. was done by adding various fungal mycelium homogenates (Aspergillus flavus, Alternaria alternate, Coriolus versicolor, Fusarium oxysporum, Mucor sp, Penicillium notatum, and Rhizopus stonifer), Casein hydrolysate and Saccharomyces cerevisiae at different concentrations. The cell cultures of P. harmala L. were subcultured on MS medium with optimal treatment of biotic elicitor. CAMAG analytical HPTLC system was used for estimation of harmaline and harmine after extraction of β-carboline alkaloids. Results: The maximum harmine production (91.2±1.8 μg g DW) was observed at 1000 mg l S. cerevisiae in cell suspension culture of P. harmala L. (1.68 fold over than the control). Also the results showed that supplement of 75-100 mg l casein hydrolysate in cell cultures media increased biomass of cell culture and harmaline and harmine production (1.61 and 1.46 times over than the control, respectively). Conclusion: The conclusion of the research showed that by applying biotic elicitors, we can reach to higher secondary metabolites (harmaline and harmine) in cell suspension culture of P. harmala L. We suggest future investigation on using other elicitors like bacterial extract or signal transduction compounds in cell suspension culture of P. harmala L. in order to increase the production of different kind of secondary metabolites.
Structural basis for SARS-CoV-2 Nucleocapsid protein recognition by single-domain antibodies

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is the most severe public health event of the twenty-first century. While effective vaccines against SARS-CoV-2 have been developed, there remains an urgent need for diagnostics to quickly and accurately detect infections. Antigen tests, particularly those that detect the abundant SARS-CoV-2 Nucleocapsid protein, are a proven method for detecting active SARS-CoV-2 infections. Here we report high-resolution crystal structures of three llama-derived single-domain antibodies that bind the SARS-CoV-2 Nucleocapsid protein with high affinity. Each antibody recognizes a specific folded domain of the protein, with two antibodies recognizing the N-terminal RNA binding domain and one recognizing the C-terminal dimerization domain. The two antibodies that recognize the RNA binding domain affect both RNA binding affinity and RNA-mediated phase separation of the Nucleocapsid protein. All three antibodies recognize highly-conserved surfaces on the Nucleocapsid protein, suggesting that they could be used to develop affordable diagnostic tests to detect all circulating SARS-CoV-2 variants.
Study on preparation and main drug content determination of baicalin liposomes

Objective:To prepare and establish a method for the determination of baicalin liposomes.Methods:Baicalin liposome was prepared by reverse evaporating method,the content of baicalin in baicalin lipsomes was determined by HPLC.Results:The mean diameter and entrapment efficiency of baicalin lipsomes were 350nm and 60.1%. The linear range of baicalin was 0.29～1. 45μg(r=0.9997) and the average recovery rate was 100.1%,RSD=0.2%(n=6). Conclusion:The preparation of baicalin lipsomes is simple and the content determination is simple,reliable and reproducible,which can be used in the quality control of baicalin lipsomes.