Miracle-dz/UniFAR-FTUs huggingface dataset:
Ibrutinib Resistance Mechanisms and Treatment Strategies for B-Cell Lymphomas

Chronic activation of B-cell receptor (BCR) signaling via Bruton tyrosine kinase (BTK) is largely considered to be one of the primary mechanisms driving disease progression in B–Cell lymphomas. Although the BTK-targeting agent ibrutinib has shown promising clinical responses, the presence of primary or acquired resistance is common and often leads to dismal clinical outcomes. Resistance to ibrutinib therapy can be mediated through genetic mutations, up-regulation of alternative survival pathways, or other unknown factors that are not targeted by ibrutinib therapy. Understanding the key determinants, including tumor heterogeneity and rewiring of the molecular networks during disease progression and therapy, will assist exploration of alternative therapeutic strategies. Towards the goal of overcoming ibrutinib resistance, multiple alternative therapeutic agents, including second- and third-generation BTK inhibitors and immunomodulatory drugs, have been discovered and tested in both pre-clinical and clinical settings. Although these agents have shown high response rates alone or in combination with ibrutinib in ibrutinib-treated relapsed/refractory(R/R) lymphoma patients, overall clinical outcomes have not been satisfactory due to drug-associated toxicities and incomplete remission. In this review, we discuss the mechanisms of ibrutinib resistance development in B-cell lymphoma including complexities associated with genomic alterations, non-genetic acquired resistance, cancer stem cells, and the tumor microenvironment. Furthermore, we focus our discussion on more comprehensive views of recent developments in therapeutic strategies to overcome ibrutinib resistance, including novel BTK inhibitors, clinical therapeutic agents, proteolysis-targeting chimeras and immunotherapy regimens.
Turbine: Facebook’s Service Management Platform for Stream Processing

The demand for stream processing at Facebook has grown as services increasingly rely on real-time signals to speed up decisions and actions. Emerging real-time applications require strict Service Level Objectives (SLOs) with low downtime and processing lag—even in the presence of failures and load variability. Addressing this challenge at Facebook scale led to the development of Turbine, a management platform designed to bridge the gap between the capabilities of the existing general-purpose cluster management frameworks and Facebook’s stream processing requirements. Specifically, Turbine features a fast and scalable task scheduler; an efficient predictive auto scaler; and an application update mechanism that provides fault-tolerance, atomicity, consistency, isolation and durability.Turbine has been in production for over three years, and one of the core technologies that enabled a booming growth of stream processing at Facebook. It is currently deployed on clusters spanning tens of thousands of machines, managing several thousands of streaming pipelines processing terabytes of data per second in real time. Our production experience has validated Turbine’s effectiveness: its task scheduler evenly balances workload fluctuation across clusters; its auto scaler effectively and predictively handles unplanned load spikes; and the application update mechanism consistently and efficiently completes high scale updates within minutes. This paper describes the Turbine architecture, discusses the design choices behind it, and shares several case studies demonstrating Turbine capabilities in production.
Mechanism of Color and Photoacidity Tuning for the Protonated Green Fluorescent Protein Chromophore.

The neutral or A state of the green fluorescent protein (GFP) chromophore is a remarkable example of a photoacid naturally embedded in the protein environment and accounts for the large Stokes shift of GFP in response to near UV excitation. Its color tuning mechanism has been largely overlooked, as it is less preferred for imaging applications than the redder anionic or B state. Past studies, based on site-directed mutagenesis or solvatochromism of the isolated chromophore, have concluded that its color tuning range is much narrower than its anionic counterpart. However, as we performed extensive investigation on more GFP mutants, we found that the color of the neutral chromophore can be more sensitive to protein electrostatics than the anionic counterpart. Electronic Stark spectroscopy reveals a fundamentally different electrostatic color tuning mechanism for the neutral state of the chromophore that demands a three-form model compared with that of the anionic state, which requires only two forms. Specifically, an underlying zwitterionic charge transfer state is required to explain its sensitivity to electrostatics. As the Stokes shift is tightly linked to excited-state proton transfer (ESPT) of the protonated chromophore, we infer design principles of the GFP chromophore as a photoacid through the color tuning mechanisms of both protonation states. The three-form model could also be applied to similar biological and nonbiological dyes and complements the failure of two-form model for donor-acceptor systems with localized ground-state electronic distributions.
Adaptive auxiliary input extraction based on vanishing point detection for distant object detection in high-resolution railway scene

Object detection plays an important role in intrusion detection of railway safety monitoring system. Generally, high-resolution image has to be down-sampled in order to reduce the amount of computation, resulting in missed detections of distant objects. This paper proposes an auxiliary input framework based on vanishing point (VP) detection to preserve the image resolution of distant objects in railway alarm region. We improved the VP detection network based on CNN classification, which consists of two branches, estimating the x-y coordinates respectively. Auxiliary input based on VP can improve the accuracy of target detection, especially for distant targets. Experiments on public data sets show that the proposed model overperforms single-branch model and regression model.
Slot‐seeding investigations. 1. Effect of level of nitrogen fertilizer and row spacing on establishment, herbage growth and quality of perennial ryegrass

Three field experiments showed that perennial ryegrass can be successfully slot-seeded into an existing Festuca-Agrostis sward. Ryegrass survival was satisfactory in all cases but was improved on a low fertility site by the application of fertilizer N, P and K in the slot at sowing. The effect of varying inter-row spacing from 37·2 to 15 cm was measured in a 3-year experiment. In year one, involving seven cuts, slot-seeding increased total herbage dry matter harvested by a mean value of 17%; inter-row distances of 22·2-30 cm gave the optimal combination of ryegrass + old sward herbage. Differences in yield between inter-row spacings declined in the subsequent two years, as the rows of ryegrass thickened. Ryegrass digestibility (measured only in year two, from six cuts) was higher than that of the old sward; total metabolizable energy harvested from 15-cm rows was 20% higher than that from unsown controls. Increasing N input from 200 to 400 kg ha-1, starting in year two, only produced a significant increase in total herbage harvested in year three but proved effective in increasing the ryegrass contribution from the wider spaced rows.
Distributed variable stiffness joint assist mechanism based on giant magnetostrictive material

Exoskeleton assist technology is widely used in military and human rehabilitation and other fields, but joint assist mechanisms have problems such as high quality, concentrated drive source and poor flexibility. In this paper, a distributed variable stiffness joint assisting mechanism based on supermagnetic to telescopic material is proposed The giant magnetostrictive material is used as the driving source and the structural variable stiffness source. The distributed driving is realized by series and parallel connection of multiple driving units. Firstly, the curve of the stiffness of a single drive unit with the magnetic field is studied Then, the variation curve of the stiffness of the booster module with the number of the drive unit under the condition of no magnetic field excitation and saturation magnetic field excitation is studied when multiple drive units are connected in series or in parallel. By controlling the magnitude of the magnetic field to dynamically control the structural stiffness of the drive unit, and by using the data fitting to obtain a general formula, the number of drive units required under the excitation of the fixed magnetic field strength can be reversed according to the stiffness requirement, and the error can be guaranteed within 5%. The research results laid the foundation for further analysis of distributed variable stiffness joint assist technology.
HisRect: Features from Historical Visits and Recent Tweet for Co-Location Judgement

This study explores the problem of co-location judgement, i.e., to decide whether two Twitter users are co-located at some point-of-interest (POI). We extract novel features, named HisRect, from users’ historical visits and recent tweets: The former has impact on where a user visits in general, whereas the latter gives more hints about where a user is currently. To alleviate the issue of data scarcity, a semi-supervised learning (SSL) framework is designed to extract HisRect features. Moreover, we use an embedding neural network layer to decide co-location based on the difference between two users’ His-Rect features. Extensive experiments on real Twitter data suggest that our HisRect features and SSL framework are highly effective at deciding co-locations.
A study of the growth of plasmid bearing and plasmid cured strains of antibiotic resistantYersinia enterocoliticaserotype 0:3 on refrigerated beef, pork and lamb☆

Abstract The growth of antibiotic-resistant strains of plasmid bearing (P+) and plasmid cured (P−) strains of Yersinia enterocolitica serotype O:3 on minced and whole pieces of beef, pork and lamb at 0, 5 and 10°C was examined. Yersinia grew on both meat forms and all species types at most storage temperatures examined. Similar growth rates were displayed by P+ and P− strains of Y. enterocolitica under each temperature and meat form, suggesting that the virulence plasmid had no significant effect on growth rates. It was noted, however, that initial Yersinia growth on pork was slightly faster than on beef or lamb although the final numbers observed were slightly lower than on the other two meat types. The study demonstrated that Yersinia was inhibited to a greater extent on pork than beef or lamb. This study has proposed that inhibition may be due to competition from the natural meat microflora, in particular, the Pseudomonads.
Polarized Expression of Ion Channels and Solute Carrier Family Transporters on Heterogeneous Cultured Human Corneal Endothelial Cells

Purpose To clarify the expression profiles of ion channels and transporters of metabolic substrates among heterogeneous cultured human corneal endothelial cells (cHCECs) distinct in their effectiveness in reconstituting the corneal endothelium. Methods Integrated proteomics for cell lysates by liquid chromatography–tandem mass spectrometry was carried out from three aliquots of cHCECs enriched in either cluster of definition (CD)44−/+ (mature) cHCECs or CD44++/+++ cell-state transition (CST) cHCECs. The expression profiles of cations/anions, monocarboxylic acid transporters (MCTs), and solute carrier (SLC) family proteins, as well as carbonic anhydrases (CAs), were investigated. Results The polarized expression of cations/anions, MCTs, and SLC family proteins, as well as CAs, was clarified for mature and CST cHCECs. Most SLC4 family members, including SLC4A11 and SLC4A4 (NBCe1), were upregulated in the CST cHCECs, whereas SLC9A1 (Na+/H+ exchanger isoform one [NHE1]) and CA5B were detected only in the mature cHCECs. In addition, SLC25A42, catalyzing the entry of coenzyme A into the mitochondria, and SLC25A18, functioning as a mitochondrial glutamate carrier 2 (both relevant for providing the substrates for mitochondrial bioenergetics), were selectively expressed in the mature cHCECs. Conclusions Our findings may suggest the relevance of qualifying the polarized expression of these ion channels and transporter-like proteins to ensure not only the suitability but also the in vivo biological functionality of cHCECs selected for use in a cell-injection therapy.
Automatic lung field segmentation based on the U-net deep neural network

Obtaining the lung region by automatic segmentation is a necessary step in lung analysis, and accurate lung segmentation is also useful for doctors to determine treatment options. In this paper, fully automatic lung field segmentation based on the U-net deep neural network is proposed. The proposed method is trained on a data set consisting of 200 CT images and tested on remaining 65 CT images. The network architecture consists of an encoder path to extract high-level feature and a symmetric decoder path to recover the image information wanted. We combine binary cross entropy and soft dice loss function as loss function to ameliorate the precise of segmentation. The final results show that our proposed method produces a significant DSC of 0.972 compared to other lung segmentation algorithms.
Hyperparameter Optimization for Multi-Layer Data Input Using Genetic Algorithm

In the training process of the deep learning algorithm, the hyperparameter optimization consumes the most time. This yields a problem that the development time of the model is extended. In previous studies, hyperparameters were changed without strict criteria. In contrast, in this study, the method using a genetic algorithm is proposed. Since the algorithm generates the fitness function through model's verification time and accuracy, the algorithm can find their optimal value. In addition, the number of populations of genetic algorithms is adjusted to reduce the time required for deep learning training process. In order to evaluate the performance of the proposed algorithm, the X, Y-axis vibration dataset is used to diagnose motor fault. As a result, it was confirmed that the proposed algorithm can obtain the proper verification time and accuracy when the hyperparameter optimization of the deep learning algorithm using the multi-layer is used as input data.
The Effect of Mycorrhizal Fungi on the Fate of PCBs in Two Vegetated Systems

ABSTRACT The objective of this study was to investigate the effects of mycorrhizal infection on vegetative uptake of polychlorinated biphenyls. Feltleaf willow (Salix alaxensis) and balsam poplar (Populus balsamifera) were grown in soil spiked with 6 mg/kg 3,3′,4,4′-tetrachlorobiphenyl-(UL-14C). The fungicide Daconil2787® was employed to suppress indigenous mycorrhizal infection. After 100 days of greenhouse incubation in semienclosed phytoreactors, mycorrhizal infection was found to be approximately threefold higher in the untreated willows vs. the fungicide-amended willows. Radio-label uptake was found to correlate most highly with mycorrhizal infection in the willow roots (R = 0.83). Over the same time period, mycorrhizal infection in the poplars was not significantly affected by fungicide addition. In the poplar phytoreactors, radiolabel uptake was most highly correlated with water use (R = 0.70). The overall vegetative radiolabel uptake was low (≈ 1%), but the limited uptake was attributed to soil sorption processes rather than vegetative limitations.
Semantics column

In this quarter's column, Andrzej Murawski and Nikos Tzevelekos offer us an invitation to game semantics. This approach to giving semantics originated in work of the philosopher and mathematician Paul Lorenzen in the late 1950s [10], who viewed the meaning of a proposition φ as a dialogue between two players, a proponent who asserts φ, and an opponent, who denies φ. A proof of φ is then a winning strategy for proponent. The approach was used by Andreas Blass [5] to give a semantics to Girard's linear logic [7]. Noting some shortcomings in Blass's model, Abramsky and Jagadeesan [2] refined the model to devise a more expressive game semantics for multiplicative linear logic.
Inflammatory Networks Linking Oral Microbiome with Systemic Health and Disease

The dance between microbes and the immune system takes place in all biological systems, including the human body, but this interaction is especially complex in the primary gateway to the body: the oral cavity. Recent advances in technology have enabled deep sequencing and analysis of members and signals of these communities. In a healthy state, the oral microbiome is composed of commensals, and their genes and phenotypes may be selected by the immune system to survive in symbiosis. These highly regulated signals are modulated by a network of microbial and host metabolites. However, in a diseased state, host-microbial networks lead to dysbiosis and considerable burden to the host prior to systemic impact that extends beyond the oral compartment. Interestingly, we presented data demonstrating similarities between human and mice immune dysbiosis and discussed how this affects the host response to similar pathobionts. The host and microbial signatures of a number of disease states are currently being examined to identify potential correlations. How the oral microbiome interacts with inflammation and the immune system to cause disease remains an area of active research. In this review, we summarize recent advancements in understanding the role of oral microbiota in mediating inflammation and altering systemic health and disease. In line with these findings, it is possible that existing conditions may be resolved by targeting specific immune-microbial markers in a positive way.
Rous Sarcoma Virus Genomic RNA Dimerization Capability In Vitro Is Not a Prerequisite for Viral Infectivity

Retroviruses package their full-length, dimeric genomic RNA (gRNA) via specific interactions between the Gag polyprotein and a “Ψ” packaging signal located in the gRNA 5′-UTR. Rous sarcoma virus (RSV) gRNA has a contiguous, well-defined Ψ element, that directs the packaging of heterologous RNAs efficiently. The simplicity of RSV Ψ makes it an informative model to examine the mechanism of retroviral gRNA packaging, which is incompletely understood. Little is known about the structure of dimerization initiation sites or specific Gag interaction sites of RSV gRNA. Using selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE), we probed the secondary structure of the entire RSV 5′-leader RNA for the first time. We identified a putative bipartite dimerization initiation signal (DIS), and mutation of both sites was required to significantly reduce dimerization in vitro. These mutations failed to reduce viral replication, suggesting that in vitro dimerization results do not strictly correlate with in vivo infectivity, possibly due to additional RNA interactions that maintain the dimers in cells. UV crosslinking-coupled SHAPE (XL-SHAPE) was next used to determine Gag-induced RNA conformational changes, revealing G218 as a critical Gag contact site. Overall, our results suggest that disruption of either of the DIS sequences does not reduce virus replication and reveal specific sites of Gag–RNA interactions.
A QTL Cluster for Plant Architecture and Its Ecological Significance in Asian Wild Rice

The wild progenitor (Oryza rufipogon) of Asian rice (Oryza sativa) shows a wide range of variations in life-history traits, forming an annual-perennial continuum. A conspicuous feature of an annual type of wild rice is represented by its adaptability to disturbed habitats, and its short stature with many tillers and a prostrate growth habit. The present study was carried out to examine the genetic differentiation between wild annual and cultivated (Japonica type) rice strains by quantitative trait locus (QTL) analysis. In total, 20 adaptive and/or domestication-related traits were evaluated in recombinant inbred lines (RILs). A total of 28 putative QTLs were detected across the genome. Six QTLs responsible for plant architecture were located on the short arm of chromosome 7. The near-isogenic line with the region containing the QTL cluster confirmed that the QTLs exerted a significant effect on the plant architecture in the genetic background of cultivated rice. A similar QTL cluster was also found in another annual strain of a different origin, suggesting that the QTL cluster might be predominant in annual wild rice. Furthermore, a QTL for tolerance to disturbance (simulated trampling) was detected within the region of the cluster on chromosome 7. These results are discussed in relation to their ecological significance in wild annuals of rice.
Isolation and characterization of thermophilic bacteria from natural and artificial habitats

Several thermophilic Bacillus Strains were isolated from natural as well as artificial habitats. They grow optimally on a carbohydrate-containing medium at a temperature of 65 to 68°C and a pH value of 6 to 7 under aerobic conditions. They utilize glucose, sucrose and sodium acetate as carbon and energy sources. They can be differentiated by acid formation and composition of intracellular fatty acid fraction as well as growth on xylose, lactose, starch, cellobiose, ribose and galactose.
Ultrasonic Assessment of Optic Nerve Sheath Diameter in Patients at Risk of Sepsis-Associated Brain Dysfunction: A Preliminary Report

Sepsis-associated brain dysfunction (SABD) with increased intracranial pressure (ICP) is a complex pathology that can lead to unfavorable outcome. Ultrasonographic measurement of optic nerve sheath diameter (ONSD) is used for non-invasive assessment of ICP. We aimed to assess the role of ONSD as a SABD screening tool. This prospective preliminary study covered 10 septic shock patients (5 men; aged 65, IQR 50–78 years). ONSD was measured bilaterally from day 1 to 10 (n = 1), until discharge (n = 3) or death (n = 6). The upper limit for ONSD was set at 5.7 mm. Sequential organ failure assessment score was calculated on a daily basis as a surrogate formulti-organ failure due to sepsis in the study population. On day 1, the medians of right and left ONSD were 5.56 (IQR 5.35–6.30) mm and 5.68 (IQR 5.50–6.10) mm, respectively, and four subjects had bilaterally elevated ONSD. Forty-nine out of 80 total measurements performed (61%) exceeded 5.7 mm during the study period. We found no correlations between ONSD and sequential organ failure assessment (SOFA) during the study period (right: R = −0.13–0.63; left R = −0.24–0.63). ONSD measurement should be applied for screening of SABD cautiously. Further research is needed to investigate the exact role of this non-invasive method in the assessment of brain dysfunction in these patients.