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Okada, Hiroki, Shinsaku Kiyomoto, and Carlos Cid. "Integer-Wise Functional Bootstrapping on TFHE: Applications in Secure Integer Arithmetics." Information 12, no. 8 (July 26, 2021): 297. http://dx.doi.org/10.3390/info12080297.
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TFHE is a fast fully homomorphic encryption scheme proposed by Chillotti et al. in Asiacrypt’ 2018. Integer-wise TFHE is a generalized version of TFHE that can encrypt the plaintext of an integer that was implicitly presented by Chillotti et al., and Bourse et al. presented the actual form of the scheme in CRYPTO’ 2018. However, Bourse et al.’s scheme provides only homomorphic integer additions and homomorphic evaluations of a sign function. In this paper, we construct a technique for operating any 1-variable function in only one bootstrapping of the integer-wise TFHE. For applications of the scheme, we also construct a useful homomorphic evaluation of several integer arithmetics: division, equality test, and multiplication between integer and binary numbers. Our implementation results show that our homomorphic division is approximately 3.4 times faster than any existing work and that its run time is less than 1 second for 4-bit integer inputs.
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Chillotti, Ilaria, Nicolas Gama, Mariya Georgieva, and Malika Izabachène. "TFHE: Fast Fully Homomorphic Encryption Over the Torus." Journal of Cryptology 33, no. 1 (April 25, 2019): 34–91. http://dx.doi.org/10.1007/s00145-019-09319-x.
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Xu, Ying, Hongmei Xu, Yu Zhen, Xueting Sang, Hao Wu, Cong Hu, Zhanchuan Ma, Miaomiao Yu, and Huanfa Yi. "Imbalance of Circulatory T Follicular Helper and T Follicular Regulatory Cells in Patients with ANCA-Associated Vasculitis." Mediators of Inflammation 2019 (December 2, 2019): 1–9. http://dx.doi.org/10.1155/2019/8421479.
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Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is characterized by small-vessel inflammation in association with autoantibodies. Balance between T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells is critical for humoral immune responses. Accumulating evidence supports that Tfh and Tfr are involved in autoimmune diseases; however, their roles in AAV are unclear. In this study, we tested the changes of circulatory Tfh and Tfr in patients with AAV. Twenty patients with AAV and twenty healthy controls were enrolled. Sixteen AAV patients had kidney involvement. We found that the AAV patients had increased circulating Tfh cells (CD4+CXCR5+CD25−CD127interm-hi), decreased Tfr cells (CD4+CXCR5+CD25+CD127lo-interm), and elevated Tfh/Tfr ratios compared with healthy controls (P<0.01). The Tfh percentage and Tfh/Tfr ratio, but not Tfr percentage, were positively correlated to proteinuria levels and BVAS scores in patients with AAV (P<0.01). In addition, AAV patients had decreased circulating Tfh1 (CCR6-CXCR3+), but increased Tfh2 cells (CCR6-CXCR3-), compared with healthy controls (P<0.01), indicating a Tfh1-to-Tfh2 shift. Furthermore, remission achieved by immunosuppressive treatment markedly attenuated the increase of total Tfh (P<0.01) and Tfh2 cells (P<0.05), promoted the Tfh1 response (P<0.05), and recovered the balance between Tfh/Tfr cells (P<0.05) and between Tfh1/Tfh2 cells (P<0.05) in patients with AAV. Plasma levels of IL-21, a cytokine secreted by Tfh cells, were elevated in AAV patients compared with healthy controls (P<0.01), which was attenuated by immunosuppressive treatment (P<0.05). Taken together, our findings indicate that circulatory Tfh/Tfr ratios, Tfh2/Tfh1 shift, and plasma IL-21 levels are associated with AAV and disease activity.
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B., Paulin Boale, Simon Ntumba B., and Eugene Mbuyi M. "Performance of Adder Architectures on Encrypted Integers." International Journal of Engineering and Advanced Technology 10, no. 6 (August 30, 2021): 216–21. http://dx.doi.org/10.35940/ijeat.f3083.0810621.
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The fully Homomorphic encryption scheme is corner stone of privacy in an increasingly connected world. It allows to perform all kinds of computations on encrypted data. Although, time of computations is bottleneck of numerous applications of real life. In this paper, a brief description is made on the homomorphic encryption scheme TFHE of Illaria Chillota and the others. TFHE, implemented in c language in a library, improves the bootstrapping execution time of the FHEW scheme to 13 milliseconds. TFHE performs homomorphic processing on a multitude of logic gates. This variety made it possible to construct, implement five adder architectures and compare them in terms of the execution time of the bootstrapping per logic gate. In a singleprocessor computing environment, the Carry Look-ahead Adder completed a two-integer addition in 90 seconds, whereas the Ripple carry Adder did the same processing in 109 seconds. An improvement in processing time of 15% is observed. And, the same ratio of about 15% was obtained on four integers, respectively for 279 seconds for the first adder and 320 seconds for Wallace's dedicated adder. While in the dual-processor environment, a 50% improvement was seen on all adders in the same processing on integers. The Carry Look-ahead Adder saw his handling improved by the sum of two numbers from 90 seconds to 46 seconds and four numbers from 279 seconds to 139 seconds, respectively.
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Moon, Subin, and Younho Lee. "An Efficient Encrypted Floating-Point Representation Using HEAAN and TFHE." Security and Communication Networks 2020 (March 2, 2020): 1–18. http://dx.doi.org/10.1155/2020/1250295.
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As a method of privacy-preserving data analysis (PPDA), a fully homomorphic encryption (FHE) has been in the spotlight recently. Unfortunately, because many data analysis methods assume that the type of data is of real type, the FHE-based PPDA methods could not support the enough level of accuracy due to the nature of FHE that fixed-point real-number representation is supported easily. In this paper, we propose a new method to represent encrypted floating-point real numbers on top of FHE. The proposed method is designed to have analogous range and accuracy to 32-bit floating-point number in IEEE 754 representation. We propose a method to perform arithmetic operations and size comparison operations. The proposed method is designed using two different FHEs, HEAAN and TFHE. As a result, HEAAN is proven to be very efficient for arithmetic operations and TFHE is efficient in size comparison. This study is expected to contribute to practical use of FHE-based PPDA.
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Paul, Jestine, Benjamin Hong Meng Tan, Bharadwaj Veeravalli, and Khin Mi Mi Aung. "Non-Interactive Decision Trees and Applications with Multi-Bit TFHE." Algorithms 15, no. 9 (September 18, 2022): 333. http://dx.doi.org/10.3390/a15090333.
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Machine learning classification algorithms, such as decision trees and random forests, are commonly used in many applications. Clients who want to classify their data send them to a server that performs their inference using a trained model. The client must trust the server and provide the data in plaintext. Moreover, if the classification is done at a third-party cloud service, the model owner also needs to trust the cloud service. In this paper, we propose a protocol for privately evaluating decision trees. The protocol uses a novel private comparison function based on fully homomorphic encryption over the torus (TFHE) scheme and a programmable bootstrapping technique. Our comparison function for 32-bit and 64-bit integers is 26% faster than the naive TFHE implementation. The protocol is designed to be non-interactive and is less complex than the existing interactive protocols. Our experiment results show that our technique scales linearly with the depth of the decision tree and efficiently evaluates large decision trees on real datasets. Compared with the state of the art, ours is the only non-interactive protocol to evaluate a decision tree with high precision on encrypted parameters. The final download bandwidth is also 50% lower than the state of the art.
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Su, R., Y. Y. Wang, F. Y. Hu, X. Zheng, Y. Liu, X. Li, and C. Wang. "AB0043 THE IMBALANCE OF T FOLLICULAR REGULATORY CELL AND T FOLLICULAR HELPER CELL IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1324–25. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1311.
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Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease which can lead to severe joint damage and disability.The relationship between antibodies and rheumatoid arthritis has long been well established. Recently, many studies have found that T follicular regulatory cells(Tfr) and T follicular helper cells (Tfh) are closely related to antibody generation on lymphoid follicular germinal centers (GCs)[1-2]. Tfr cells can inhibite the GC reaction and suppress production of high-affinity antibodies. The dysregulation of Tfh cells can lead to the production of autoantibodies by B cells.Objectives:To examine the expression of circulating T follicular regulatory cell (Tfr) and T follicular helper cell and its subsets(Tfh1 Tfh2 Tfh17) in RA patients and healthy control group.Methods:Level of Tfr and Tfh1,Tfh2 and Tfh17 cells in the peripheral blood of 17 new RA patients, 30 treated RA patients and 18 healthy controls were deceted by flow cytomery. All patients were hospitalised at the Department of Rheumatology, Second Hospital of Shanxi Medical University.Results:We found that the level of Tfr (CD3+CD4+CD25+CXCR5+FOP3+) percent(P=0.020), in the peripheral blood in RA patients were significantly decreased compared with healthy controls. The percent of Tfh (CD3+CD4+CXCR5+CD45RA-) (P=0.039)and Tfh17 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6+) (P=0.000)were increased, but there are no statistical difference about Tfh1(CD3+CD4+CXCR5+CD45RA-CXCR3+CCR6-)(P=0.558) and Tfh2 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6-) percent(P=0.079). We compared the above indicators between new and treated RA patients, and the results indicated that the Tfr(P=0.013),Tfh (P=0.002) and Tfh1(P=0.034) were significantly increased in the new RA patients compared to the treated RA patients, there were no differences between the two groups in Tfh2(P=0.419) and Tfh17 percent(P=0.124).Conclusion:Our results indicated that disorder of Tfr and Tfh subsets were involved in RA, restoring the Tfr/Tfh balance may be the potential therapeutic targets.Fig. 1.Comparison of Tfr, Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the RA patients (n = 47) and healthy control group (n = 18) (*P < 0.05).Fig. 2.Comparison of Tfr,Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the new RA patients (n = 17) and treated RA patients(n = 30) (*P < 0.05).References:[1]Deng J, Wei Y, Fonseca VR, Graca L, Yu D.T follicular helper cells and T follicular regulatory cells in rheumatic diseases[J].Nat Rev Rheumatol. 2019, 15(8):475-490.[2]Chen Liu, Dongwei Wang, Songsong Lu, et al.Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.Arthritis Rheumatol. 2018, 70(5):711-721Disclosure of Interests:None declared
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Fan, Cunqun, Peiheng Jia, Manyun Lin, Lan Wei, Peng Guo, Xiangang Zhao, and Ximeng Liu. "Cloud-Assisted Private Set Intersection via Multi-Key Fully Homomorphic Encryption." Mathematics 11, no. 8 (April 8, 2023): 1784. http://dx.doi.org/10.3390/math11081784.
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With the development of cloud computing and big data, secure multi-party computation, which can collaborate with multiple parties to deal with a large number of transactions, plays an important role in protecting privacy. Private set intersection (PSI), a form of multi-party secure computation, is a formidable cryptographic technique that allows the sender and the receiver to calculate their intersection and not reveal any more information. As the data volume increases and more application scenarios emerge, PSI with multiple participants is increasingly needed. Homomorphic encryption is an encryption algorithm designed to perform a mathematical-style operation on encrypted data, where the decryption result of the operation is the same as the result calculated using unencrypted data. In this paper, we present a cloud-assisted multi-key PSI (CMPSI) system that uses fully homomorphic encryption over the torus (TFHE) encryption scheme to encrypt the data of the participants and that uses a cloud server to assist the computation. Specifically, we design some TFHE-based secure computation protocols and build a single cloud server-based private set intersection system that can support multiple users. Moreover, security analysis and performance evaluation show that our system is feasible. The scheme has a smaller communication overhead compared to existing schemes.
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Abe, S., H. Tsuboi, H. Toko, F. Honda, A. Koido, H. Miki, H. Asashima, Y. Kondo, and I. Matsumoto. "POS0810 T FOLLICULAR HELPER CELLS IN BLOOD MIRROR SALIVARY GLAND-INFILTRATING T CELLS IN PRIMARY SJÖGREN’S SYNDROME." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 699.1–700. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2906.
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BackgroundAlthough clonal expansion of autoreactive T cells have been identified in the peripheral blood and salivary gland of primary Sjögren’s syndrome (pSS) (1), the relationship between peripheral immune environments and inflammatory organs remains still unclear.ObjectivesHere, we examined which T cell subsets in blood share the same T cell receptor (TCR) αβ with T cells infiltrated at labial salivary gland (LSG) in patients with pSS, and evaluated mechanisms of their differentiation.Methods:1) TCR repertoires of each effector memory T cell subset (Th1, Th17, Tfh1, Tfh2, Tfh17) in blood, and LSG-infiltrating T cells obtained from the same pSS patient were analyzed by TCR sequence (n=1).2) The proportion of each T cell subset in blood was compared between patients with pSS (n=30) and healthy controls (HC) by flow cytometry (n=20).3) The proportion of each T cell subset between blood and LSG was evaluated in patients with pSS by flow cytometry (n=7).4) Based on the above results, by focusing on Tfh cells, Tfh-related gene mRNA expressions (CXCR5, Bcl6, TGF-β, IL-6, IL-12, IL-21) were evaluated in LSG of pSS (n=11) and HC (n=3).5) The conditions of Tfh cell differentiation in pSS were examined.6) Cytokine production from CD4+T cells cultured under determined Tfh cell differentiation condition in pSS were examined.7) pSS derived peripheral CD4+T cells were co-cultured with HC derived naïve B cells under Tfh cell differentiation condition, and effect on B cells differentiation was analyzed.Results:1) LSG-infiltrating T cells, and blood Th1, Tfh1, and Tfh2 cells showed higher clonality than Th17, and Tfh17 cells (Figure 1). Blood Tfh1, and Tfh2 cells were the two most frequent subsets comprised by the same T cell clones infiltrating in LSG.2) Blood Tfh subsets were all significantly increased in patients with pSS than in HC. Among Tfh subsets, both PD-1 and ICOS expression was highest in Tfh1 subsets. Furthermore, the proportion of PD-1+ICOS+Tfh1 cells correlated with titers of anti-nuclear antibody, anti-SS-A antibody, and anti-SS-B antibody in pSS.3) The proportions of memory Tfh subsets, especially Tfh1, was significantly increased in LSG compared with matched peripheral blood in pSS.4) Expression levels of CXCR5, IL-6, IL-21, and TGF-β in LSG were significantly higher in pSS than HC. TGF-β positively correlated with CXCR5 expression in pSS.5) CD4+T cells cultured under CD3/28 and TGF-β stimulation significantly increased CXCR5 expression, and Tfh1 population.6) Production of IL-21, IL-2, and TNF-α were significantly increased after CD3/28 and TGF-β stimulation.7) HC derived naïve B cells after co-culturing with pSS derived CD4+T cells, under Tfh differentiation condition (CD3/28 and TGF-β stimulation) expressed higher CD19, and CD19+CD38+B cell population was increased.ConclusionTfh1 cells in blood not only frequently showed high clonal expansion, but also highly shared the same TCRαβ with LSG-infiltrating T cells in pSS. Tfh1 cell proportion was expanded among pSS at both peripheral blood and LSGs, and furthermore, they positively correlated with autoantibody production. They proliferated under TGF-β-enriched environment, such as seen in LSG of pSS. Thus, we conclude that blood Tfh1 subsets has the potential to reflect inflammatory organ immune environment, possibly taking a role on autoantibody production at LSG.Reference[1]Joachims ML, et al. Single-cell analysis of glandular T cell receptors in Sjögren’s syndrome.JCI Insight.2016 Jun 2;1(8):e85609Figure 1.T cell clonality of each sample, is shown. LSG infiltrating T cells, blood Th1, Tfh1, and Tfh2 shows higher clonality compared to blood Th17, and Tfh17 population.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Aziz, Md Momin Al, Md Toufique Morshed Tamal, and Noman Mohammed. "Secure Genomic String Search with Parallel Homomorphic Encryption." Information 15, no. 1 (January 11, 2024): 40. http://dx.doi.org/10.3390/info15010040.
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Fully homomorphic encryption (FHE) cryptographic systems enable limitless computations over encrypted data, providing solutions to many of today’s data security problems. While effective FHE platforms can address modern data security concerns in unsecure environments, the extended execution time for these platforms hinders their broader application. This project aims to enhance FHE systems through an efficient parallel framework, specifically building upon the existing torus FHE (TFHE) system chillotti2016faster. The TFHE system was chosen for its superior bootstrapping computations and precise results for countless Boolean gate evaluations, such as AND and XOR. Our first approach was to expand upon the gate operations within the current system, shifting towards algebraic circuits, and using graphics processing units (GPUs) to manage cryptographic operations in parallel. Then, we implemented this GPU-parallel FHE framework into a needed genomic data operation, specifically string search. We utilized popular string distance metrics (hamming distance, edit distance, set maximal matches) to ascertain the disparities between multiple genomic sequences in a secure context with all data and operations occurring under encryption. Our experimental data revealed that our GPU implementation vastly outperforms the former method, providing a 20-fold speedup for any 32-bit Boolean operation and a 14.5-fold increase for multiplications.This paper introduces unique enhancements to existing FHE cryptographic systems using GPUs and additional algorithms to quicken fundamental computations. Looking ahead, the presented framework can be further developed to accommodate more complex, real-world applications.
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Marshall, Aaron J., Christine Zhang, Sen Hou, and Xun Wu. "Abnormal T follicular helper cell subsets in Chronic Lymphocytic Leukemia." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 166.28. http://dx.doi.org/10.4049/jimmunol.200.supp.166.28.
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Abstract The B cell malignancy Chronic Lymphocytic Leukemia (CLL) is a slow progressing disease of monoclonal B cell expansion and immune dysfunction associated with recurrent infections and second malignancies. CD4+ CXCR5+ T cells, known as follicular helper T cells (Tfh), have specialized properties in promoting B cell activation but their role in CLL is unknown. Here we examine the phenotype, activation status, clinical relevance and potential function of circulating Tfh cell subsets in CLL patients. We find that the percentage of Tfh cells is significantly increased in CLL patients compared to healthy age-matched controls. Tfh frequencies are significantly increased in advanced stage CLL patients compared to early stage disease. CLL patients also exhibited different composition of Tfh1, Tfh2 and Th17 subsets and show differential expression of activation markers compared to healthy controls. Our results indicate that the Tfh1 subset is particularly activated and expanded in CLL patients with more progressive disease. Tfh subset expansion and activation correlated with specific cytokine and chemokine levels and with decline in serum immunoglobulin levels. A large proportion of CD4+ T cells in CLL bone marrow express activated Tfh1 phenotype, suggesting that these cells are present within lymphoid tissues where CLL cells proliferate. Lastly, we found that treatment of CLL patients with the Btk inhibitor Ibrutinib lead to normalization of Tfh populations and reduced Tfh activation markers. Our results indicate that Tfh subset profiles could serve as useful biomarker to evaluate the progression of CLL and suggest selective expansion of Tfh1 cells may help drive CLL proliferation and immune dysfunction.
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Xia, Changsheng, Caoyi Liu, Yanying Liu, Yan Long, Lijuan Xu, and Chen Liu. "Increased Circulating Th1 and Tfh1 Cell Numbers Are Associated with Disease Activity in Glucocorticoid-Treated Patients with IgG4-Related Disease." Journal of Immunology Research 2020 (November 27, 2020): 1–8. http://dx.doi.org/10.1155/2020/3757015.
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Background. This study is aimed at exploring the changes and significance of circulating Th and Tfh cell subsets in glucocorticoid-treated IgG4-RD patients. Methods. 39 glucocorticoid-treated IgG4-RD patients and 22 healthy controls (HC) were enrolled. Peripheral blood mononuclear cells were separated, and circulating Th and Tfh cell subsets were examined by flow cytometry according to the surface and intranuclear markers. Disease activity was accessed by the IgG4-RD responder index (RI) score. Correlation analyses were conducted between Th/Tfh subset numbers and clinical indicators. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of Th and Tfh subsets to distinguish active IgG4-RD patients from remission IgG4-RD patients. Results. Circulating Th1, Th17, Tfh1, and Tfh17 cells were significantly increased in active IgG4-RD patients compared with HC. Th1 and Tfh1 numbers were positively correlated with serum IgG4 levels in patients with IgG4-RD. Meanwhile, the absolute numbers of circulating Th1 and Tfh1 cells were positively correlated with IgG4-RD RI scores. The areas under the curve (AUC) were 0.8276 for Th1 and 0.7310 for Tfh1, 0.5862 for Tfh2, and 0.6810 for Tfh17. Conclusion. Increased circulating Th1 and Tfh1 subsets are related to elevated serum IgG4 levels in active IgG4-RD patients during glucocorticoid treatment, which may play an important role in the course of IgG4-RD disease, and could be potential biomarkers for monitoring disease activity of IgG4-RD.
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Zhao, Gang, Jianxiao Liang, Jingjing Cao, Shanyong Jiang, Jianshu Lu, and Baoen Jiang. "Abnormal Function of Circulating Follicular Helper T Cells Leads to Different Manifestations of B Cell Maturation and Differentiation in Patients with Osteosarcoma." Journal of Healthcare Engineering 2022 (April 19, 2022): 1–9. http://dx.doi.org/10.1155/2022/3724033.
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Objective. The objective of this study is to investigate the effect of dysfunctional circulating follicular helper T cells (Tfh) on B cell maturation and differentiation in patients with osteosarcoma (OS). Method. Data from 30 OS patients who underwent diagnosis and treatment in our hospital, as well as those of 30 healthy subjects (HC), were collected at the same time. Flow cytometry was employed to identify proportions of CD4+CXCR5+Tfh cells and Tfh cell subtypes Tfh17, Tfh1, and Tfh2 in the patient’s peripheral blood. CD40 L and IFNγ levels were detected after stimulating Tfh cells with an influenza antigen; the positive rates of CD27 and CD38 in B cells were detected before and after coculture with Tfh cells. qRT-PCR was carried out for Blimp-1 expression in B cells, and ELISA was employed to identify the levels of IgM, IgG, and IgA in B cells and IL-2, IL-10, and IL-4 in Tfh cells before and after coculture. Results. The percentage of CD4+CXCR5+Tfh cells in OS patients’ peripheral blood increased significantly. The Tfh cell ratio increased along with the TNM stage, and the Tfh cell ratio in OS metastasis patients is greater than that in nonmetastatic patients. In addition, Tfh2 and Tfh17 cells increased drastically in OS patients, and no meaningful change was seen in Tfh1 cells. CD40 L levels of Tfh cells in OS patients were less than those of the HC group, and IFNγ was substantially increased. After coculturing the OS group’s B cells with Tfh cells, the CD27+ and CD38+ cells of B cells were drastically greater, and Blimp-1 expression was also significantly increased. In addition, the levels of IL-21, IL-4, and IL-10 of Tfh cells in the OS group and the levels of IgA, IgG, and IgM in B cells were significantly reduced after coculture. Conclusion. Dysfunctional Tfh in OS patients can severely inhibit B cell development, maturation, and differentiation.
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Iliashenko, Ilia, and Vincent Zucca. "Faster homomorphic comparison operations for BGV and BFV." Proceedings on Privacy Enhancing Technologies 2021, no. 3 (April 27, 2021): 246–64. http://dx.doi.org/10.2478/popets-2021-0046.
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Abstract Fully homomorphic encryption (FHE) allows to compute any function on encrypted values. However, in practice, there is no universal FHE scheme that is effi-cient in all possible use cases. In this work, we show that FHE schemes suitable for arithmetic circuits (e.g. BGV or BFV) have a similar performance as FHE schemes for non-arithmetic circuits (TFHE) in basic comparison tasks such as less-than, maximum and minimum operations. Our implementation of the less-than function in the HElib library is up to 3 times faster than the prior work based on BGV/BFV. It allows to compare a pair of 64-bit integers in 11 milliseconds, sort 64 32-bit integers in 19 seconds and find the minimum of 64 32-bit integers in 9.5 seconds on an average laptop without multi-threading.
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Boale B., Paulin, Simon Ntumba, and Eugene Mbuyi M. "Improved Bootstrapping by FFT on Encrypted Multi Operands Homomorphic Addition." International Journal of Engineering and Advanced Technology 11, no. 1 (October 30, 2021): 126–31. http://dx.doi.org/10.35940/ijeat.a3177.1011121.
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Bootstrapping is a technique that was introduced by Gentry in 2009. It is based on reencryption which allows an encryption scheme to perform an unlimited number of processing on encrypted data. It is a bottleneck in the practicability of these schemes because of multiplication operations which are costly in complexity. This complexity was reduced in TFHE by processing bootstrapping on the result of a two-bit logic gate in thirteen milliseconds using the Fast Fourier Transform. Building on this advance, an implementation of the addition of ten (10) numbers of 32-bits was performed based on the 32-bit Carry Look ahead Adder and was executed in less than 35 seconds using the configured SPQLIOS Fast Fourier transform to manipulate AVX and FMA instructions. This connector improves performance to a higher level than FFTW3 and NAYUKI.
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Abd-Elhameed, Waleed Mohamed, and Hany Mostafa Ahmed. "Spectral solutions for the time-fractional heat differential equation through a novel unified sequence of Chebyshev polynomials." AIMS Mathematics 9, no. 1 (2023): 2137–66. http://dx.doi.org/10.3934/math.2024107.
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<abstract><p>In this article, we propose two numerical schemes for solving the time-fractional heat equation (TFHE). The proposed methods are based on applying the collocation and tau spectral methods. We introduce and employ a new set of basis functions: The unified Chebyshev polynomials (UCPs) of the first and second kinds. We establish some new theoretical results regarding the new UCPs. We employ these results to derive the proposed algorithms and analyze the convergence of the proposed double expansion. Furthermore, we compute specific integer and fractional derivatives of the UCPs in terms of their original UCPs. The derivation of these derivatives will be the fundamental key to deriving the proposed algorithms. We present some examples to verify the efficiency and applicability of the proposed algorithms.</p></abstract>
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Liu, Yan, Xinwang Yuan, Xiaofang Li, Dawei Cui, and Jue Xie. "Constitutive Changes in Circulating Follicular Helper T Cells and Their Subsets in Patients with Graves’ Disease." Journal of Immunology Research 2018 (December 24, 2018): 1–10. http://dx.doi.org/10.1155/2018/8972572.
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Background. Follicular helper T (Tfh) cells are critical for high-affinity antibody generation and B cell maturation and differentiation, which play important roles in autoimmune diseases. Graves’ disease (GD) is one prototype of common organ-specific autoimmune thyroid diseases (AITD) characterized by autoreactive antibodies, suggesting a possible role for Tfh cells in the pathogenesis of GD. Our objective was to explore the role of circulating Tfh cell subsets and associated plasma cells (PCs) in patients with GD. Methods. Thirty-six patients with GD and 20 healthy controls (HC) were enrolled in this study. The frequencies of circulating Tfh cell subsets and PCs were determined by flow cytometry, and plasma cytokines, including interleukin- (IL-) 21, IL-4, IL-17A, and interferon- (IFN-) γ, were measured using an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of transcription factors (Bcl-6, T-bet, GATA-3, and RORγt) in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time quantitative PCR. Results. Compared with HC, the frequencies of circulating CD4+CXCR5+CD45RA−Tfh (cTfh) cells with ICOS and PD-1 expression, the Tfh2 subset (CXCR3−CCR6−Tfh) cells, and PCs (CD19+CD27highCD38high) were significantly increased in the GD patients, but the frequencies of Tfh1 (CXCR3+CCR6−Tfh) and Tfh17 (CXCR3−CCR6+Tfh) subset cells among CD4+T cells were significantly decreased in GD patients. The plasma concentrations of IL-21, IL-4, and IL-17A were elevated in GD patients. Additionally, a positive correlation was found between the frequency of PD-1+Tfh cells (Tfh2 or PCs) and plasma IL-21 concentration (or serum TPO-Ab levels). The mRNA levels of transcription factors (GATA-3 and RORγt) were significantly increased, but T-bet and Bcl-6 mRNA expression was not obviously varied in PBMCs from GD patients. Interestingly, Tfh cell subsets and PCs from GD patients were partly normalized by treatment. Conclusion. Circulating Tfh cell subsets and PCs might play an important role in the pathogenesis of GD, which are potential clues for GD patients’ interventions.
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Boura, Christina, Nicolas Gama, Mariya Georgieva, and Dimitar Jetchev. "CHIMERA: Combining Ring-LWE-based Fully Homomorphic Encryption Schemes." Journal of Mathematical Cryptology 14, no. 1 (August 7, 2020): 316–38. http://dx.doi.org/10.1515/jmc-2019-0026.
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AbstractThis paper proposes a practical hybrid solution for combining and switching between three popular Ring-LWE-based FHE schemes: TFHE, B/FV and HEAAN. This is achieved by first mapping the different plaintext spaces to a common algebraic structure and then by applying efficient switching algorithms. This approach has many practical applications. First and foremost, it becomes an integral tool for the recent standardization initiatives of homomorphic schemes and common APIs. Then, it can be used in many real-life scenarios where operations of different nature and not achievable within a single FHE scheme have to be performed and where it is important to efficiently switch from one scheme to another. Finally, as a byproduct of our analysis we introduce the notion of a FHE module structure, that generalizes the notion of the external product, but can certainly be of independent interest in future research in FHE.
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Brenna, Lars, Isak Sunde Singh, Håvard Dagenborg Johansen, and Dag Johansen. "TFHE-rs: A library for safe and secure remote computing using fully homomorphic encryption and trusted execution environments." Array 13 (March 2022): 100118. http://dx.doi.org/10.1016/j.array.2021.100118.
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Kim, Taeyun, Yongwoo Oh, and Hyoungshick Kim. "Efficient Privacy-Preserving Fingerprint-Based Authentication System Using Fully Homomorphic Encryption." Security and Communication Networks 2020 (February 13, 2020): 1–11. http://dx.doi.org/10.1155/2020/4195852.
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To help smartphone users protect their phone, fingerprint-based authentication systems (e.g., Apple’s Touch ID) have increasingly become popular in smartphones. In web applications, however, fingerprint-based authentication is still rarely used. One of the most serious concerns is the lack of technology for securely storing fingerprint data used for authentication. Because scanned fingerprint data are not exactly the same each time, the use of a traditional cryptographic hash function (e.g., SHA-256) is infeasible to protect raw fingerprint data. In this paper, we present an efficient privacy-preserving fingerprint authentication system using a fully homomorphic encryption scheme in which fingerprint data are always stored and processed in an encrypted form. We implement a fully working fingerprint authentication system with a fingerprint database (containing 4,000 samples) using the Fast Fully Homomorphic Encryption over the Torus (TFHE) library. The proposed system can perform the fingerprint matching process within about 166 seconds (±0.564 seconds) on average.
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Chen, Ya, Wei Xu, Qian Zhou, and Zhixiang Zhou. "Total Factor Energy Efficiency, Carbon Emission Efficiency, and Technology Gap: Evidence from Sub-Industries of Anhui Province in China." Sustainability 12, no. 4 (February 14, 2020): 1402. http://dx.doi.org/10.3390/su12041402.
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The phenomena of “large energy consumption, high carbon emission, and serious environmental pollution” are against the goals of “low energy consumption, low emissions” in China’s industrial sector. The key to solving the problem lies in improving total factor energy efficiency (TFEE) and carbon emission efficiency (TFCE). Considering the heterogeneity of different sub-industries, this paper proposes a three-stage global meta-frontier slacks-based measure (GMSBM) method for measuring TFEE and TFCE, as well as the technology gap by combining meta-frontier technology with slacks-based measure (SBM) using data envelopment analysis (DEA). DEA can effectively avoid the situation where the technology gap ratio (TGR) is larger than unity. This paper uses the three-stage method to empirically analyze TFEE and TFCE of Anhui’s 38 industrial sub-industries in China from 2012 to 2016. The main findings are as follows: (1) Anhui’s industrial sector has low TFEE and TFCE, which has great potential for improvement. (2) TFEE and TFCE of light industry are lower than those of heavy industry under group-frontier, while they are higher than those of heavy industry under meta-frontier. There is a big gap in TFEE and TFCE among sub-industries of light industry. Narrowing the gap among different sub-industries of light industry is conducive to the overall improvement in TFEE and TFCE. (3) The TGR of light industry is significantly higher than that of heavy industry, indicating that there are sub-industries with the most advanced energy use and carbon emission technologies in light industry. And there is a bigger carbon-emitting technology gap in heavy industry, so it needs to encourage technology spillover from light industry to heavy industry. (4) The total performance loss of industrial sub-industries in Anhui mainly comes from management inefficiency, so it is necessary to improve management and operational ability. Based on the findings, some policy implications are proposed.
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Iliashenko, Ilia, Malika Izabachène, Axel Mertens, and Hilder V. L. Pereira. "Homomorphically counting elements with the same property." Proceedings on Privacy Enhancing Technologies 2022, no. 4 (October 2022): 670–83. http://dx.doi.org/10.56553/popets-2022-0127.
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We propose homomorphic algorithms for privacy-preserving applications where we are given an encrypted dataset and we want to compute the number of elements that share a common property. We consider a two party scenario between a client and a server, where the storage and computation is outsourced to the server. We present two new efficient methods to solve this problem by homomorphically evaluating a selection function encoding the desired property, and counting the number of elements which evaluates to the same value. Our first method programs the homomorphic computation in the style of the the functional bootstrapping of TFHE and can be instantiated with essentially any homomorphic encryption scheme that operates on polynomials, like FV or BGV. Our second method relies on new homomorphic operations and ciphertext formats, and it is more suitable for applications where the number of possible inputs is much larger than the number of possible values for the property. We illustrate the feasibility of our methods by presenting a publicly available proof-ofconcept implementation in C++ and using it to evaluate a heatmap function over encrypted geographic points.
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Ma, Shihe, Tairong Huang, Anyu Wang, Qixian Zhou, and Xiaoyun Wang. "Fast and Accurate: Efficient Full-Domain Functional Bootstrap and Digit Decomposition for Homomorphic Computation." IACR Transactions on Cryptographic Hardware and Embedded Systems 2024, no. 1 (December 4, 2023): 592–616. http://dx.doi.org/10.46586/tches.v2024.i1.592-616.
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The functional bootstrap in FHEW/TFHE allows for fast table lookups on ciphertexts and is a powerful tool for privacy-preserving computations. However, the functional bootstrap suffers from two limitations: the negacyclic constraint of the lookup table (LUT) and the limited ability to evaluate large-precision LUTs. To overcome the first limitation, several full-domain functional bootstraps (FDFB) have been developed, enabling the evaluation of arbitrary LUTs. Meanwhile, algorithms based on homomorphic digit decomposition have been proposed to address the second limitation. Although these algorithms provide effective solutions, they are yet to be optimized. This paper presents four new FDFB algorithms and two new homomorphic decomposition algorithms that improve the state-of-the-art. Our FDFB algorithms reduce the output noise, thus allowing for more efficient and compact parameter selection. Across all parameter settings, our algorithms reduce the runtime by up to 39.2%. Our homomorphic decomposition algorithms also run at 2.0x and 1.5x the speed of prior algorithms. We have implemented and benchmarked all previous FDFB and homomorphic decomposition algorithms and our methods in OpenFHE.
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Kudryavtsev, Igor V., Natalia A. Arsentieva, Oleg K. Batsunov, Zoia R. Korobova, Irina V. Khamitova, Dmitrii V. Isakov, Raisa N. Kuznetsova, et al. "Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents." Current Issues in Molecular Biology 44, no. 1 (December 30, 2021): 194–205. http://dx.doi.org/10.3390/cimb44010014.
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Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.
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Gaspar, P., A. R. Cruz-Machado, F. Ribeiro, V. C. Romão, and L. Graca. "POS0008 STRATIFICATION OF NEGATIVE, SEROCONVERTED AND PERSISTENTLY POSITIVE THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME PATIENTS WITH DISTINCT FOLLICULAR HELPER T CELLS SUBSETS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 209.2–209. http://dx.doi.org/10.1136/annrheumdis-2023-eular.6295.
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BackgroundPrimary antiphospholipid syndrome (PAPS) is caused by autoantibodies targeting protein-binding phospholipids (aPL)[1]. Follicular helper T (Tfh) and follicular regulatory T cells (Tfr) are critical for antibody production in germinal centres[2], but their role in PAPS is scarcely studied. Some patients remain persistently positive for aPL, while others become seronegative during disease progression[3]. Whether aPL status mirror immunological changes over time is not known.ObjectivesTo phenotypically characterize Tfh/Tfr subsets in PAPS and explore the association with previous/current aPL status.MethodsWe prospectively recruited 73 adult thrombotic PAPS patients (Sidney criteria; ≥1 year disease duration) and 24 age- and sex-matched healthy donors (HD). Regardless of lupus anticoagulant (LA) status, patients were categorized in three groups according to aPL (anticardiolipin [ACL] IgM and/or IgG; ß2-glycoprotein [ß2GPI] IgM and/or IgG) profile:NN– previous and current aPL negative, ie, only positive for LA (n=40);PP– previous and current aPL positive (n=20); andPN– previous aPL positive, currently aPL negative (n=13). We considered aPL <30 UQ as negative (ELISA immunoassays). Tfh (CD4+FoxP3-CD25-CD45RO+CXCR5+), activated Tfh (PD1+ICOS+Tfh), Tfh1-like (CXCR3+CCR6-Tfh), Tfh2-like (CXCR3-CCR6-Tfh), Tfh17-like (CXCR3+CCR6+Tfh), Treg (CD4+CD25+FoxP3+), and Tfr (CD4+CD25+FoxP3+CXCR5+) cells were analysed by flow cytometry using cryopreserved peripheral blood mononuclear cells. GraphPad Prism version 8 software was used for statistical analysis and p values <0,05 were considered significant.ResultsMost patients were women (n=43, 59%), with a mean age at disease onset of 42±13 years, and a mean disease duration of 8±7 years. Venous thrombosis was the most common first manifestation (53%), and pregnancy comorbidity were present 10% of women. At presentation, aPL positivity were as follows: LA, 70%; ACL IgG and/or IgM, 44%; ß2GPI IgG and/or IgM, 33%; triple positive, 16%. Circulating Tfh and Treg cells were comparable between HD and all APS patients (Figure 1A and 1B). Among APS, PP patients had higher frequency of Tfh compared to NN (p=0.047) but not with PN patients. Within the Tfh subset, activated Tfh cells were significantly increased in PP compared to NN (p=0.005) and PN patients (p=0.049), whereas no difference was seen between the latter group and NN patients, and between HD and all APS patients (Figure 1C). The frequencies of Tfh1-like and Tfh17-like cells were comparable between all groups, but Tfh2-like cells were decreased in PP compared to NN patients (p=0.008), and similarly distributed among all other groups (Figure 1D to F). In the regulatory compartment, circulating Tfr and Tfr/Tfh ratio were significantly increased in PP patients compared to NN (p<0.001; p=0.001) and PN patients (p=0.004; p=0.042) (Figure 1G and 1H). No difference was observed between NN and PN patients nor between HD and all APS patients.ConclusionOur preliminary results show that in thrombotic PAPS, imbalance of circulating Tfh and Tfr subsets change according to aPL profile. Increased PD1+ICOS+Tfh and Tfr cells, and Tfr/Tfh ratio indicates ongoing humoral response in persistently positive patients. These changes are lost after seroconversion with T follicular cells subsets being similar to persistently negative PAPS patients.References[1]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295–306.[2]Crotty S. T Follicular Helper Cell Biology: A Decade of Discovery and Diseases. Immunity. 2019 May;50(5):1132–48[3]Donohoe S, Quenby S, Mackie I, et al. Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal andheparin-treated antiphospholipid syndrome pregnancies. Lupus. 2002 Jan;11(1):11–20.Figure 1.T follicular cells subsets distribution.AcknowledgementsWe are grateful to all patients who promptly participated in the study. We would also like to acknowledge all our dear colleagues who follow these patients in the clinic.Disclosure of InterestsNone Declared.
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Li, Huixian, Deng Pan, Jinglei Li, and Hao Wang. "Parallel Accelerating Number Theoretic Transform for Bootstrapping on a Graphics Processing Unit." Mathematics 12, no. 3 (January 31, 2024): 458. http://dx.doi.org/10.3390/math12030458.
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The bootstrapping procedure has become the main bottleneck affecting the efficiency of all known fully homomorphic encryption (FHE) schemes. The state-of-the-art scheme for efficient bootstrapping, which is called fully homomorphic encryption over the torus (TFHE), accelerates polynomial multiplication by leveraging number theoretic transform (NTT) and implementing NTT in parallel on a GPU. Unfortunately, almost none of the recent advancements in NTT take full advantage of a GPU, leading to the need for more time. With this in mind, in this work, a novel faster number theoretic transform based on a GPU is proposed, in which matrix multiplication is used to implement a decomposed small-point NTT. When implementing matrix multiplication, we introduce a merging preprocessing method to merge multiple inputs of the small-point NTT, aiming to effectively minimize the count of modulo operations. Subsequently, when the merged result is multiplied by rotation factors, we use logical left shift rather than arithmetic multiplication to improve the computational efficiency. Our scheme can easily be used to realize a 1024-point NTT and the results of the experiments show that the speedup ratio of our method over the butterfly algorithm is about 2.49.
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Powell, Michael Duane, Kaitlin Read, Bharath Sreekumar, and Kenneth J. Oestreich. "IL-12 signaling drives the differentiation and function of a TH1-derived TFH1-like cell population." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 188.7. http://dx.doi.org/10.4049/jimmunol.202.supp.188.7.
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Abstract CD4+ T follicular helper (TFH) cells play key roles in the generation of humoral immunity, as they provide T cell help to B cells that ultimately results in the production of pathogen-specific antibodies. A subset of TFH cells that shares features with TH1 cells, referred to as (TH1)-biased TFH (TFH1) cells, has recently been shown to play key roles in responses to chronic infections including HIV and malaria, as well as the onset of some autoimmune diseases. Despite the apparent importance of these cells to comprehensive immune responses and human health, many questions remain regarding their origin, including the molecular mechanisms that regulate their differentiation. Here, we describe a population of TH1-derived TFH1-like cells that produce both the TH1 cytokine interferon-γ and the TFH-associated cytokine interleukin-21 (IL-21). Interestingly, this TFH1-like population exhibits increased B cell helper activity compared to IL-6 derived TFH-like cells. We further demonstrate that IL-12 signaling is required for both the differentiation and functional properties of the TFH1-like cell population. Specifically, IL-12-dependent activation of STAT4, and unexpectedly STAT3, result in both the upregulation of the TFH lineage-defining transcription factor Bcl-6, as well as the increased production of IL-21. Finally, we show that IL-12 signaling is required for TFH1-like cell expression of Icos, a receptor that is critical for the ability of T cells to provide help to B cells. Taken together, our findings provide potential insight into the genesis and regulatory requirements of recently described TFH1 cells with emerging roles in human health and disease.
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Martín-Nares, Eduardo, Gabriela Hernández-Molina, Ángel A. Priego-Ranero, Isela Chan-Campos, Gladys S. Herrera-Noguera, Fidel López-Verdugo, and Janette Furuzawa-Carballeda. "Peripheral Immunophenotype in IgG4-Related Disease and Its Association with Clinical Phenotypes and Disease Activity." Cells 12, no. 4 (February 20, 2023): 670. http://dx.doi.org/10.3390/cells12040670.
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Diverse immune cell subsets have been described in IgG4-related disease (IgG4-RD). If there is a different immunophenotype according to clinical phenotype and activity status is not known. Levels of IL-4-, IL-13-, IL-5-, and IL-21-producing CD4+ T cells (Th2 subsets), CD4+ cytotoxic T lymphocytes (CD4+CTLs), T helper 9 cells, T follicular helper cells (Tfh; Tfh1/Tfh2/Tfh17/Tf regulatory [Tfr]), Foxp3+ regulatory T cells, Type 1 regulatory T cells (Tr1), T helper 3 regulatory cells (Th3), IL-10-producing regulatory B cells (Bregs), IL-10-expressing regulatory plasmacytoid dendritic (pDC IL-10+) cells, and M1 and M2 monocytes were determined by flow cytometry in 43 IgG4-RD patients and 12 controls. All immune subsets were higher in patients vs. controls. CD4+/IL-4+, CD4+/IL-5+, CD4+CTLs, Tfh2, Tfh17, Tfr, and M1 monocyte cell number was different among IgG4-RD clinical phenotypes. The pancreato-hepato-biliary phenotype was characterized by a higher CD4+CTLs, Tfh17, Tfh2, and Tfr and lower M1 cell number. An increased CD4+CTLs and Th3 cell number distinguished the head and neck-limited phenotype, while the retroperitoneal/aortic and Mikulicz/systemic phenotypes were characterized by increased Th2 subsets. Tfh17, Tr1, Th3, pDC, M1, and M2 monocytes were augmented in active patients. In summary, the clinical heterogeneity of IgG4-RD might be driven by the participation of different immunophenotypes and, consequently, by a different fibroinflammatory process.
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Haq, Syed Ijaz Ul, Muhammad Naveed Tahir, and Yubin Lan. "Weed Detection in Wheat Crops Using Image Analysis and Artificial Intelligence (AI)." Applied Sciences 13, no. 15 (July 31, 2023): 8840. http://dx.doi.org/10.3390/app13158840.
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In the present study, we used device visualization in tandem with deep learning to detect weeds in the wheat crop system in actual time. We selected the PMAS Arid Agriculture University research farm and wheat crop fields in diverse weather environments to collect the weed images. Some 6000 images were collected for the study. Throughout the season, tfhe databank was assembled to detect the weeds. For this study, we used two different frameworks, TensorFlow and PyTorch, to apply deep learning algorithms. PyTorch’s implementation of deep learning algorithms performed comparatively better than that of TensorFlow. We concluded that the neural network implemented through the PyTorch framework achieves a superior outcome in speed and accuracy compared to other networks, such as YOLO variants. This work implemented deep learning models for weed detection using different frameworks. While working on real-time detection models, it is very important to consider the inference time and detection accuracy. Therefore, we have compared the results in terms of execution time and prediction accuracy. In particular, the accuracy of weed removal from wheat crops was judged to be 0.89 and 0.91, respectively, with inference times of 9.43 ms and 12.38 ms on the NVIDIA RTX2070 GPU for each picture (640 × 640).
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Krenács, László, Dóra Krenács, Zita Borbényi, Erika Tóth, Anna Nagy, Klára Piukovics, and Enikő Bagdi. "Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas." International Journal of Molecular Sciences 25, no. 1 (December 28, 2023): 428. http://dx.doi.org/10.3390/ijms25010428.
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Peripheral T-cell lymphomas (PTCLs) expressing multiple follicular T helper (TFH) cell-related antigens are now classified as TFH lymphomas (TFHL), including angioimmunoblastic, follicular, and not otherwise specified (NOS) types. CXCR5 is the TFH cell-defining chemokine receptor that, together with its ligand CXCL13, plays a critical role in the development of follicles and the positioning of TFH and B cells within follicles. A comprehensive immunomorphologic study was performed to investigate the expression pattern of CXCR5 in a large cohort of nodal PTCLs, particularly those with a TFH cell phenotype, and to compare its expression with six other TFH cell-related antigens. We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network.
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Quinn, James L., Agnieshka Agasing, Rose Ko, and Robert C. Axtell. "Follicular T helper cells and T helper 17 cells cooperate in promoting B-cell responses in neuro-inflammation." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 47.7. http://dx.doi.org/10.4049/jimmunol.196.supp.47.7.
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Abstract Both T-cells and B-cells are implicated in the pathology of multiple sclerosis, but how these cells cooperate to drive disease activity is still unclear. Recent studies using experimental autoimmune encephalomyelitis (EAE) demonstrated that the T helper 17 (TH17) pathway is correlated with increased numbers of ectopic B-cell follicles in the CNS. As follicular T helper (TFH) cells are mediators of B-cell response, our hypothesis was that TH17 cells and TFH cells cooperate to drive pathogenic B-cell responses in the CNS and contribute to the severity of EAE. Therefore, the main objective of this project was to examine the role of TFHs in EAE induced by the transfer of myelin-specific TH17s (TH17 EAE). At the peak of TH17 EAE, we saw 5.6–18.6% of CD4 cells in the CNS were CXCR5+PD1+ TFHs. Furthermore, the number of TFHs in the CNS was strongly correlated with the number of infiltrating B-cells and disease severity. We next transferred TH17s from congenic CD45.1 mice into CD45.2 recipient mice to determine whether the TFH cells were donor or recipient derived. We observed that the TFHs were CD45.2 recipient-derived whereas IL-17+ cells were CD45.1 donor-derived. We next assessed whether myelin-specific TFHs transferred into recipient mice were capable of migrating to the CNS and causing EAE. We found that TFHs transferred alone failed to traffic to the CNS. However, when TFHs were co-transferred with TH17s into recipient mice, we found increased numbers of TFHs in the CNS compared to the CNS of mice transferred with only TH17s. These results show that TH17s migrate to the CNS to initiate neuro-inflammation in EAE and mediate of a second wave of CNS-infiltrating TFHs that facilitate a B-cell response in the CNS and contributes to disease severity.
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Ding, Yanna, Hui-Chen Hsu, Qi Wu, Pingar Yang, and John Mountz. "Sequential effects of IL-21 and IL-17 to regulate spleen CXCR5+ follicular T helper cells in autoimmune BXD2 mice (101.44)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 101.44. http://dx.doi.org/10.4049/jimmunol.186.supp.101.44.
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Abstract CXCR5+ follicular T helper (Tfh) cells locate in the light zone (LZ) of germinal centers (GCs) to help differentiation of antibody producing B cells. Both IL-17 and IL-21 have been associated with the development of GCs but their effects on Tfh have not been clear. Autoimmune BXD2 mice developed spontaneous GCs and displayed increased number of Tfh in the spleen. In BXD2-Il21-/- or BXD2-Il17ra-/- mice, there were significantly reduced PNA+Fas+ GC B cells in the spleen and autoantibody titers in sera. This is not exclusively related to Tfh development since the percentage of CXCR5+ICOS+ Tfhs is 2-fold lower in BXD2-Il21-/- but is 1.5-fold higher in BXD2-Il17ra-/- mice compared to wild type. Confocal images, however, showed dramatically diminished CD4 T cells in GC LZ of BXD2-Il17ra-/- spleen. In vitro treatment of CD4 T cells with IL-21 increased the percent of CXCR5+ICOS+ Tfhs and the expression of IL17R on them. qRT-PCR confirmed that IL-21 treatment increased the expression of Cxcr5, Icos and Il21 on CD4 T cells. In contrast, IL-17 treatment increased Rgs16 but decreased Cxcr5 and diminished CXCL13-mediated chemotaxis on CD4 T cells. Our study suggests that IL-21 and IL-17 act sequentially on Tfhs in BXD2 mice. IL-21 first promotes differentiation of Tfhs and prepared these cells for IL17 stimulation by upregulating IL-17R. Subsequently, IL-17 is required to upregulated the expression of Rgs16 and stabilizes Tfh in GC LZ to promote spontaneous development of GCs.
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Yuan, Minghao, Dongdong Wang, Feng Zhang, Shenqing Wang, Shan Ji, and Yongjun Ren. "An Examination of Multi-Key Fully Homomorphic Encryption and Its Applications." Mathematics 10, no. 24 (December 9, 2022): 4678. http://dx.doi.org/10.3390/math10244678.
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With the rapid development of the Internet of Things (IoT) technology, the security problems it faces are increasingly prominent and have attracted much attention in industry and the academy. Traditional IoT architecture comes with security risks. Illegal intrusion of attackers into the network layer disrupts the availability of data. The untrusted transmission environment increases the difficulty of users sharing private data, and various outsourced computing and application requirements bring the risk of privacy leakage. Multi-key fully homomorphic encryption (MKFHE) realizes operations between ciphertexts under different key encryption and has great application potential. Since 2012, the first MKFHE scheme LTV12 has been extended from fully homomorphic encryption (FHE) and has ignited the enthusiasm of many cryptographic researchers due to its lattice-based security and quantum-resistant properties. According to its corresponding FHE scheme, the MKFHE schemes can be divided into four kinds: Gentry–Sahai–Water (GSW), number theory research unit (NTRU), Brakerski–Gentry–Vaikuntanathan (BGV), and FHE over the tour (TFHE). Efficiency and cost are urgent issues for MKFHE. New schemes are mainly improved versions of existing schemes. The improvements are mostly related to the four parts of MKFHE: security assumption, key generation, plaintext encryption, and ciphertext processing. We classified MKFHE schemes according to the improved partial schemes, and we present some improved techniques and the applications of MKFHE.
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Ding, Yanna, Hui-Chen Hsu, Kirk Druey, Qi Wu, Jun Li, PingAr Yang, Allan Zajac, and John Mountz. "IL-17-induced Rgs16 expression is essential for follicular T helper cell localization in the germinal centers of autoimmune BXD2 mice (123.44)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 123.44. http://dx.doi.org/10.4049/jimmunol.188.supp.123.44.
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Abstract Autoimmune BXD2 mice developed spontaneous germinal centers (GCs) and displayed increased number of CXCR5+ICOS+follicular T helper (Tfh) cells in the spleen. Although IL-21 but not IL-17 has been reported to be essential for the development of Tfh, there were significantly reduced PNA+Fas+GC B cells in the spleen of BXD2-Il21-/- and BXD2-Il17ra-/- mice. Interestingly, the frequency of Tfhs was 2.5-fold lower in BXD2-Il21-/- but 1.5-fold higher in BXD2-Il17ra-/- mice compared to wild type. Although increased, CXCR5+CD4 T cells were not specifically localized to the GCs in BXD2-Il17ra-/- spleens. Administration of AdIL-21 increased IL-17 levels in Tfhs and serum but had minimal effect on GC B cell frequencies in BXD2-Il17ra-/- spleens. In contrast, administration of AdIL-17 to BXD2-Il21-/- mice partially expanded GC B cells, suggesting that IL-17 acts downstream of IL-21 to facilitate the GC response. IL-21 stimulation of spleen CD4 T cells in vitro increased the frequency of Tfhs and upregulated expression of IL17R on Tfhs. IL-17 stimulated expression of Rgs16 and diminished CXCL13-mediated chemotaxis of CD4 T cells in vitro. Consistent with this, there were fewer GC CD4 T cells in BXD2-Rgs16-/- spleens in vivo. Our study suggests that IL-21 and IL-17 are required to promote the maximal autoreactive GC responses. IL-21 is important for Tfh development whereas IL-17 induced Rgs16 expression is required for Tfh localization in GCs to promote GC B-cell development.
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Kudryavtsev, I. V., M. K. Serebriakova, A. A. Starshinova, Yu S. Zinchenko, N. Yu Basantsova, E. N. Belyaeva, M. V. Pavlova, and P. K. Yablonskiy. "Altered peripheral blood Th17 and follicular T-helper subsets in patients with pulmonary tuberculosis." Russian Journal of Infection and Immunity 9, no. 2 (July 12, 2019): 304–14. http://dx.doi.org/10.15789/2220-7619-2019-2-304-314.
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Tuberculosis (TB) is one of the most common infections worldwide. Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages. Along with Th1 cells, various subsets of Th17 and follicular T-helper cells (Tfh) able to secrete a broad range of cytokines, including IFNγ, can also be involved in eliminating bacterial pathogens. It justified analyzing in this study changes in percentage of various peripheral blood Th subsets, including Th1, Th2, Th17 and Tfh cells, in TB patients. For this, major CD3+CD4+T cell subsets were assessed by using multicolor flow cytometry in TB patients (n = 40) and healthy volunteers (n = 30). It was found that in TB patients vs. control group percentage of peripheral blood CD45RA–CCR7+ central memory (CM) Th was decreased also affecting frequency of some functional T cell subsets, e.g. either lowering Th2 cells (9.11% (6.95; 13.77) vs. 7.21% (5.64; 9.84), p = 0.012) or elevating CCR6+ Th17 subsets (35.92% (27.72; 41.06) vs. 40.39% (35.41; 47.79; p = 0.016), respectively, but not influencing Th1 and Tfh subsets frequencies. Moreover, percentage of total CCR6+CM Th cells in TB patients vs. control was decreased in CCR4–CXCR3+Th17.1 cell subset (42.87% (33.64; 49.45) vs. 52.26% (46.45; 56.95), p < 0.001), whereas standard CCR4+CXCR3–Th17 and CCR6+ DP Th17 subsets were elevated (p = 0.005 and p = 0.002, respectively). In addition, altered Tfh subset composition associated with the increased (p = 0.021) percentage of CXCR3–CCR6–Tfh2 cells, but decreased CXCR3+CCR6–Tfh1 cells (p = 0.036) was observed. Finally, frequency of peripheral blood Th subsets noted above was also analyzed within effector memory (CD45RA–CCR7–) cells. It was found that in TB patients vs. volunteers frequency of Th17.1 cells was also significantly lower (p = 0.006) in CCR6+EM Th (54.43% (41.19; 91.92) vs. 61.76% (54.01; 65.63), whereas percentage of double-positive Th17 was significantly increased (20.83% (15.12; 30.87) and 12.93 % (9.80; 19.01), respectively, p < 0.001). Thus, it suggests that during M. tuberculosis infection percentage of IFNγ-producing Th17 and Tfh cells was reduced compared to control group also affecting both central memory Th cells patrolling peripheral lymphoid organs as well as effector memory Th cells able to exit to site of infection.
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Ding, Yanna, Hui-Chen Hsu, Jun Li, PingAr Yang, Allan Zajac, and John Mountz. "IL-21 promotes autoreactive germinal center development in BXD2 mice partially by regulating TFR. (P4116)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 191.4. http://dx.doi.org/10.4049/jimmunol.190.supp.191.4.
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Abstract Follicular regulatory T cells (TFR) are a regulatory CD4 (Treg) subset that suppress germinal center (GC) B cell differentiation. Interleukin 21 (IL-21) promotes T follicular helper (TFH) differentiation. In the present study we investigated the modulatory effects of IL-21 on TFR in autoimmune BXD2 mice that develop spontaneous GCs with accumulation of IL-21+TFH cells in the spleen. In BXD2-Il21-/- mice, GL-7+Fas+GC B cells and CXCR5+ICOS+TFHs were significantly reduced, but the frequency of TFR cells was 2-fold higher than that in wild-type BXD2 mice. Most CXCR5+ICOS+CD4 T cells in BXD2-Il21-/- mice highly expressed Treg markers including FoxP3, CTLA4, TGF-β1 and GITR. FoxP3+TFR cells were localized in spleen follicular areas of BXD2-Il21-/- mice. Surprisingly, transfer of TFRs from BXD2-Il21-/- mice into BXD2 mice reduced IgM but not IgG autoantibody producing B cells in the spleen. This may be due to the suppressive effects of IL-21 on TFRs as administration of AdIL-21 increased GC B cells and decreased the ratio of TFR/TFH in the spleen of BXD2-Il21-/- mice in vivo. In vitro, IL-21 increased TFH but decreased TFR cells and significantly reduced Tgfb expression by TFRs. IL-21 also counteracted TFR-induced B cells death and inhibition of TFHs. The present study suggests that IL-21 positively promotes autoreactive GC reactions in BXD2 mice at least partially by decreasing TFRs and compromising the suppressive function of TFRs on B cells and TFHs.
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Narsai, Tejal, Houfen Su, David Braxton, and Sudhir Gupta. "Collagenous Gastritis in Primary Selective IgM Deficiency: Transition to EBV+ Gastric Adenocarcinoma." Case Reports in Immunology 2021 (May 25, 2021): 1–8. http://dx.doi.org/10.1155/2021/5574944.
Full textAbstract:
Selective IgM deficiency (SIgMD) and isolated collagenous gastritis are two independent rare disorders. Our purpose is to report the 1st case of SIgMD and isolated collagenous gastritis and collagenous gastritis that has transitioned to EBV + gastric adenocarcinoma. Gastric biopsy tissue was analyzed by EBV-related encoded RNA in situ hybridization assay. Subsets of CD4, CD8, T follicular helper cells (TFH), and members of the “regulatory lymphocytes club” were measured with multiple panels of monoclonal antibodies and isotype controls by multicolor flow cytometry. The patient was diagnosed with SIgMD (extremely low serum IgM 9 mg/dl and normal IgG and IgA and exclusion of secondary causes of low IgM). Soon after SIgMD diagnosis, the patient developed collagenous gastritis and, 8 years later, developed gastric adenocarcinoma that was positive for EBV. An extensive immunological analysis revealed reduced naïve CD4 and CD8 effector memory T cells and increased naïve and central memory CD8 T cells. Among the circulating follicular helper T cells (cTFH), TFH1 and TFH2 were increased whereas TFH17 was decreased. CD4 Treg cells and TFR cells were increased, whereas Breg and CD8 Treg were comparable to control. In conclusion, SIgMD may be associated with isolated collagenous gastritis, and collagenous gastritis may transition to EBV + gastric adenocarcinoma. A role of regulatory lymphocytes in gastric cancer is discussed.
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Li, Lingwu, and Ruwei Huang. "Multi-Key Homomorphic Encryption Scheme with Multi-Output Programmable Bootstrapping." Mathematics 11, no. 14 (July 24, 2023): 3239. http://dx.doi.org/10.3390/math11143239.
Full textAbstract:
Multi-key Homomorphic Encryption (MKHE) scheme can homomorphically evaluate ciphertexts encrypted by different keys, which can effectively protect the privacy information of data holders in the joint computing of cloud services. Since the first full Homomorphic encryption scheme was proposed, bootstrapping is the only way to realize the arbitrary depth homomorphic computation of MKHE schemes. But bootstrap operation is quite expensive. In order to implement fast bootstrapping in MKHE schemes, previous works proposed multi-key TFHE schemes to implement low-latency bootstrapping and output a univariate function of messages after bootstrapping, called Programmable Bootstrapping (PBS). However, these schemes can only encrypt single-bit messages. PBS only outputs a function. And after a homomorphic operation, a bootstrap is required, which undoubtedly results in an increase in the cost of the whole multi-key homomorphic encryption operation. In this paper, we propose a MKHE scheme for multi-output PBS. For this purpose, we study the encryption method and homomorphic operation steps of MKHE, and add BFV homomorphic encryption multiplication and multi-key ciphertext relinearization. We separate the homomorphic operation from bootstrapping. We homomorphically evaluate test polynomials for multiple functions. In contrast to previous MKHE schemes, we support the output of multiple message-related functions with a single bootstrapping operation on the ciphertext. It is no longer limited to encrypting single-bit plaintext, and an effective ciphertext packaging technology is added. According to the analysis given in this paper, it is known that in the scenario of multi-party joint computation, the proposed scheme can be implemented with less bootstrapping when the same number of functions are homomorphically operated. This will effectively reduce the computational overhead.
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Kamekura, Ryuta, Katsunori Shigehara, Sumito Jitsukawa, Koji Kawata, Tetsuo Himi, and Shingo Ichimiya. "Alteration of human blood type 2 follicular helper T cells and regulatory B cells underlies comorbid association of allergic rhinitis with bronchial asthma (HYP2P.338)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 53.19. http://dx.doi.org/10.4049/jimmunol.194.supp.53.19.
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Abstract Allergic rhinitis (AR) is the most common allergic inflammatory disorder of the airway and its increasing worldwide prevalence has made it a global health problem. AR frequently precedes bronchial asthma (in 10 to 40% of cases), and the presence of AR is considered to be a risk factor for new onset of asthma. However, little is known about the mechanism by which AR advances to a state of AR with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients. The results demonstrated polarization of Tfh2 cells within Tfh cell subsets in both AR and AR+Asthma cases. Interestingly, Breg cells were decreased in AR cases and, more extensively, in AR+Asthma cases. Addtionally, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that depletion of Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma.
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Khan, Samina, Rohaida Nordin, and Muhamad Sayuti Hassan. "A ROUTINE ACTIVITY APPROACH TO UNDERSTANDING THE REASONS FOR TECHNOLOGY-FACILITATED HARASSMENT AGAINST WOMEN IN INDIA." IIUM Law Journal 31, no. 2 (December 11, 2023): 229–52. http://dx.doi.org/10.31436/iiumlj.v31i2.851.
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The rapid increase in technologies is forcing more people to be online, which is offering perpetrators to commit technology-facilitated harassment (TFH). This paper explores various reasons associated with the rise of TFH cases against women in India by employing routine activity theory (RAT). A conceptual framework is proposed to understand the reasons for technology facilitated- harassment against women (TFHW) in India. This paper adopted a qualitative methodology and observed that accessibility, anonymity, anger, revenge, and political agenda were the vital sources of motivation among perpetrators. The sharing of personal data, underreporting, lack of awareness of laws, negligence, less awareness of technology, gender perception in using the technology, and patriarchal society made women in India suitable targets. Lastly, a lack of effective laws, careless enforcement agencies, and no privacy settings materialised in the absence of a capable guardian. Thus, this paper provides a new perspective on RAT by utilising it on TFHW in India. Further, it will serve as a platform to locate how TFH incidents can be minimised by addressing the reasons in the context of a motivated offender, a suitable target, and a capable guardian.
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Mancuso, G., T. Jofra, M. Lanzillotta, J. Gerosa, G. DI Colo, L. Dagna, G. Fousteri, and E. Della Torre. "POS1356 PERSISTENCE OF TFH CELLS AFTER RITUXIMAB IS ASSOCIATED WITH IGG4-RELATED DISEASE RELAPSE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 960.2–960. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2715.
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Background:Clinical improvement after B-cell depletion with rituxmab suggests a prominent pathogenic role of B-lymphcytes in IgG4-related disease (IgG4-RD). IgG4-RD, however, relapses in most cases together with re-expansion of clonally divergent plasmablasts indicating that treatment with rituximab does not completely abrogates T follicular helper (Tfh)-cells dependent germinal center reactions leading to de-novo plasmablast differentiation.Objectives:In the present work we aim to study the effects of B-cell depletion therapy with rituximab on circulating Tfh cells and on the levels of CXCL13 - a chemotactic factor for B-lymphocytes produced by Tfh cells - in patients with IgG4-RD.Methods:Thirty patients with IgG4-RD, diagnosed according to the “Consensus Statement on the Pathology of IgG4-RD” and fulfilling the “2019 ACR/EULAR Classification Criteria” were included in the present study. Ten patients with relapsing disease were treated with the anti-CD20 monoclonal antibody rituximab (two 1g infuxions 15 days apart). Peripheral blood mononuclear cells and serum were collected before rituximab and three months after infusion. Tfh cells subsets in the peripheral blood were measured by flow cytometry and CXCL13 plasma levels were measured by ELISA assay.Results:No changes in total Tfh cells and Tfh cells subsets were observed three months after rituximab neither in absolute counts nor in percentage of CD4+ T cells. In particular, no difference in Tfh1, Tfh2, Tfh17, T follicular regulatory and highly functional Tfh cells counts was observed before and after treatment. The serum level of CXCL13 was significantly higher in active untreated IgG4-RD patients compared to healthy controls (151.94 pg/ml vs 66.98 pg/ml, p value = 0.0026), but was not affected by rituximab treatment (p value = 0.41).Conclusion:In relapsing patients with IgG4-RD rituximab does not affect circulating Tfh cells numbers and serum levels of CXCL13. Persistence of Tfh cells after rituximab and reconstitution of germinal center reactions likely drives IgG4-RD flare.References:[1]Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. BMJ. 2020 Jun 16;369:m1067. doi: 10.1136/bmj.m1067. PMID: 32546500.[2]Lanzillotta M, Della-Torre E, Stone JH. Roles of Plasmablasts and B Cells in IgG4-Related Disease: Implications for Therapy and Early Treatment Outcomes. Curr Top Microbiol Immunol. 2017;401:85-92. doi: 10.1007/82_2016_58. PMID: 28091934.[3]Campochiaro C, Ramirez GA, Bozzolo EP, Lanzillotta M, Berti A, Baldissera E, Dagna L, Praderio L, Scotti R, Tresoldi M, Roveri L, Mariani A, Balzano G, Castoldi R, Doglioni C, Sabbadini MG, Della-Torre E. IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients. Scand J Rheumatol. 2016;45(2):135-45. doi: 10.3109/03009742.2015.1055796. Epub 2015 Sep 23. PMID: 26398142.[4]Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, Deshpande V, Stone JH, Pillai S. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol. 2014 Sep;134(3):679-87. doi: 10.1016/j.jaci.2014.03.034. Epub 2014 May 6. PMID: 24815737; PMCID: PMC4149918.Disclosure of Interests:None declared
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Vaca, Alicia, Mariela Sivina, Karen Clise-Dwyer, Ekaterina Kim, Michael J. Keating, Alessandra Ferrajoli, William G. Wierda, Dan Li, Qing Ma, and Jan A. Burger. "Expansion of T Helper Cell Subsets in Chronic Lymphocytic Leukemia Cell Co-Cultures with Nurselike Cells." Blood 134, Supplement_1 (November 13, 2019): 1746. http://dx.doi.org/10.1182/blood-2019-125827.
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Background: In secondary lymphatic organs (SLO), chronic lymphocytic leukemia (CLL) cells form characteristic pseudo-follicles, also called proliferation centers, in which proliferating CLL cells are in intimate contact with CD4+ T helper cells. Despite evidence for a co-evolution of CLL cells and counterpart T helper cells, the prevalence and dynamics of T cell subsets, such as T follicular helper cells (TFH), T regulatory helper cells (TRegs) and IL-17-producing T helper cells (Th17) has not been characterized in detail. The CLL nurselike cell (NLC) model recapitulates key cellular and molecular interactions between CLL cells and the microenvironment in SLO, based on functional and gene expression studies, and represents a valid in vitro model for the SLO microenvironment in CLL. To gain insight into the potential role of T cells in CLL SLO, we utilized the NLC model to characterize T helper cell subsets and their dynamics in NLC co-cultures. Methods and Results: First, we quantified CD4+ and CD8+ T cell subsets in fresh peripheral blood mononuclear cell (PBMC) samples from 14 patients and then placed 1x107 PBMCs/ml in culture to establish NLC. We rechecked the relative proportion of CD4+ and CD8+ T cells, as well as absolute T cell counts, and their viability after 3, 6, 9, 12 and 14 days in NLC co-culture conditions. Interestingly, throughout the 14 days of culture, the number of T helper cells remained stable when compared to baseline samples. Next, we characterized T helper cell subsets in 25 different CLL samples, comparing CD4+ T cell subsets in freshly isolated CLL PBMC with matched samples harvested after 14 days of NLC culture. Samples were stained with subset-specific fluorescence-labeled antibody combinations, and analyzed by flow cytometry. NLC co-culture resulted in a significant expansion of TFH and TReg cells. TFH absolute cell counts assessed by flow cytometry using counting beads, increased from 9.4±2.2/μl at baseline to 29.0±5.9/μl in NLC co-cultures (n=14, p=0.001) and TReg from 17.0±3.3/μl to 51.0±15.0/μl (n=14, p=0.027). In contrast, Th17 absolute cell counts declined after 14 days of culture from 113.0±21.0/μl to 68.0±13.0/μl (n=14, p=0.001). Moreover, TH2 cells declined from 42.0±7.4/μl to 30.0±8.2/μl (n=14, p=0.005). Next, we analyzed for changes in TFH subsets (TFH1, TFH2 and TFH17). When compared to TFH cells from CLL PBMC, NLC culture resulted in a relative increase in TFH2 from 17.0±2.4% to 26.0±1.7% (n=25, p=0.013), and in TFH17 from 12.0±1.6% to 21.0±2.7% (n=25, p=0.006) In contrast, TFH1 frequency decreased after 14 days of culture (54.0±3.5% versus 34.0±2.9%, n=25, p=0.001). T follicular regulatory (TFr) cells also increase under co-culture conditions from undetectable to 4.8±1.9% (n=25, p=0.025)(Figure1). Looking at the maturity of CD4+ cells we noted a relative increase of central memory cells from 42.0±3.2% to 50.0±3.2% (n=25, p=0.023), whereas effector memory cells decreased from 34.0±3.4% to 26.0±2.7% (n=25, p=0.009), the fraction of naïve CD4+ cells remained unchanged. Next, we assessed the activation status of co-inhibitory receptors on CD3+CD4+ cells. We found a significant relative increase in CD4+ T cells expressing PD1 and CTLA-4 after 14 days of culture. Additionally, the TFH and TReg subsets demonstrated a significantly higher CTLA-4 expression after culture while TReg cells also addressed an increase in PD1 frequency. Furthermore, we observed a significantly higher CD28 expression on TFH and TReg subsets after 14 days of co-culture. Following, to address the residence and migration capacity of T cells in NLC co-cultures, we analyzed the CD69 and CD62L expression. Our results revealed significantly higher expression of CD69 in NLC co-cultures, whereas CD62L levels remained unchanged. Conclusion: The expansion of TFH and TReg cells in NLC co-cultures suggests the selection and clonal expansion of T cells that may support and engage in crosstalk with CLL cells. Additionally, the expansion of TFr and TFH17 cells could reflect a milieu of immune tolerance establishing in NLC co-cultures. Ongoing TCR sequencing of serial CD4+ T cell samples (baseline versus 14 days under NLC conditions) will characterize changes of clonal architecture in the T helper cell compartment, and will further improve our understanding of co-evolution of CLL and T helper cells. Disclosures Wierda: Gilead Sciences: Research Funding; Juno Therapeutics: Research Funding; KITE pharma: Research Funding; Sunesis: Research Funding; Miragen: Research Funding; Janssen: Research Funding; Xencor: Research Funding; Acerta Pharma Inc: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; GSK/Novartis: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Cyclcel: Research Funding; Loxo Oncology Inc.: Research Funding. Burger:Aptose Biosciences, Inc: Research Funding; BeiGene: Research Funding; Gilead Sciences: Research Funding; AstraZeneca: Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Pharmacyclics, an AbbVie company: Research Funding.
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Liu, Zhi-Qin, Mei-Yin Lu, Ru-Liang Sun, Zhi-nan Yin, Bin Liu, and Yang-zhe Wu. "Characteristics of Peripheral Immune Function in Reproductive Females with Uterine Leiomyoma." Journal of Oncology 2019 (October 24, 2019): 1–12. http://dx.doi.org/10.1155/2019/5935640.
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Inflammation and immunity are thought as risk factors for uterine leiomyoma; however, detailed reports on this topic are scarce. The present study aimed to analyze the characteristics of immune function and clinical significance of circulating CD4/CD8 T, NK, and γδ T cells in reproductive females with uterine leiomyoma. We analyzed the above-mentioned cells in 30 reproductive females with uterine leiomyoma and 68 healthy females using flow cytometry. After that, the correlation between function of immune cells and clinical phenotypes was analyzed. Compared with healthy controls, central memory (CM) CD4/CD8 T cells as well as Treg and Tfh cells were notably increased in leiomyoma patients; however, NK and γδ T cells were decreased in patients. Moreover, such alterations of these cells in patients with leiomyoma were associated with shorter menstrual cycles, longer menstrual period, anemia, pelvic lesions, more and larger myomas, and higher levels of CA125. Additionally, the increased Tfh1/Tfh2 ratio and Tfh17 were significantly associated with longer menstrual period, more myomas, and higher CA125 levels independent of age in patients with uterine leiomyoma. In conclusion, hallmarks of peripheral immune function are remarkably correlated with clinical phenotypes in reproductive females with uterine leiomyoma. This preliminary work may provide proof-of-concept for evaluating efficacy of treatment and prognosis of reproductive females with uterine leiomyoma with the help of quantitative analysis of peripheral immune function, which may inspire performing further investigations on the relevance of immune function with different diseases.
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Herman, Edward, Jason Weinstein, Begoña Lainez, Paula Licona-Limón, Enric Esplugues, Richard Flavell, and Joseph Craft. "Progressive differentiation of follicular B helper T cells regulates the germinal center response (IRC11P.430)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 197.12. http://dx.doi.org/10.4049/jimmunol.194.supp.197.12.
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Abstract Initiation of a thymus-dependent humoral immune response requires interaction of activated B cells and follicular B helper T (Tfh) cells, a specialized subset of CD4 T cells. Differentiation of Tfh cells results in their localization to the B-cell follicle and germinal center (GC) of secondary lymphoid organs and expression of the transcription factor Bcl6. Here we show Tfh cells differentiate further within the follicle and GC, with development of discrete subsets that regulate distinct aspects of B-cell maturation. Using mice expressing reporter genes for IL-21 and IL-4, we found that Tfh cells initially produce IL-21 mRNA and protein and support selection of high-affinity B cell mutations. Gradually, Tfh cells began to produce IL-4 and while ceasing production of IL-21, and demonstrated the ability to induce class-switch recombination and development of antibody-secreting cells. These changes in phenotype and function occurred as these Tfh21- and Tfh4-subsets exhibited differences in global gene expression as well as localization within the GC. These data support a model in which ongoing Tfh-cell differentiation orchestrates the formation of an effective antibody response.
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Ripamonti, A., E. Provasi, M. Lorenzo, M. De Simone, V. Ranzani, S. Vangelisti, S. Curti, et al. "Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells." Proceedings of the National Academy of Sciences 114, no. 48 (November 13, 2017): 12797–802. http://dx.doi.org/10.1073/pnas.1705364114.
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Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa–miR-31–5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.
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Holm Hansen, Rikke, Jacob Talbot, Helene Højsgaard Chow, Malene Bredahl Hansen, Sophie Buhelt, Sebastian Herich, Nicholas Schwab, et al. "Increased Intrathecal Activity of Follicular Helper T Cells in Patients With Relapsing-Remitting Multiple Sclerosis." Neurology - Neuroimmunology Neuroinflammation 9, no. 5 (July 14, 2022): e200009. http://dx.doi.org/10.1212/nxi.0000000000200009.
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Background and ObjectivesFollicular helper T (Tfh) cells play a critical role in protective immunity helping B cells produce antibodies against foreign pathogens and are likely implicated in the pathogenesis of various autoimmune diseases. The purpose of this study was to investigate the role of Tfh cells in the pathogenesis of multiple sclerosis (MS).MethodsUsing flow cytometry, we investigated phenotype, prevalence, and function of Tfh cells in blood and CSF from controls and patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). In addition, an in vitro blood-brain barrier coculture assay of primary human astrocytes and brain microvascular endothelial cells grown in a Boyden chamber was used to assess the migratory capacity of peripheral Tfh cells.ResultsThis study identified 2 phenotypically and functionally distinct Tfh cell populations: CD25− Tfh cells (Tfh1-like) and CD25int Tfh cells (Tfh17-like). Whereas minor differences in Tfh cell populations were found in blood between patients with MS and controls, we observed an increased frequency of CD25− Tfh cells in CSF of patients with RRMS and PPMS and CD25int Tfh cells in patients with RRMS, compared with controls. Increasing frequencies of CSF CD25− Tfh cells and the CD25− Tfh/Tfr ratio scaled with increasing IgG index in patients with RRMS. Despite an increased prevalence of intrathecal Tfh cells in patients with MS, no difference in the migratory capacity of circulating Tfh cells was observed between controls and patients with MS. Instead, CSF concentrations of CXCL13 scaled with total counts of Tfh and Tfr cell subsets in the CSF.DiscussionOur study indicates substantial changes in intrathecal Tfh dynamics, particularly in patients with RRMS, and suggests that the intrathecal inflammatory environment in patients with RRMS promotes recruitment of peripheral Tfh cells rather than the Tfh cells having an increased capacity to migrate to CNS.
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Yu, Xiaopeng, Fagen Li, Wei Zhao, Zhengyi Dai, and Dianhua Tang. "Multiparty Threshold Private Set Intersection Protocol with Low Communication Complexity." Security and Communication Networks 2022 (September 27, 2022): 1–12. http://dx.doi.org/10.1155/2022/9245516.
Full textAbstract:
Multiparty threshold private set intersection (MP-TPSI) protocol allows n mutually untrusted parties P 1 , P 2 , … , P n holding data sets A 1 , A 2 , … , A n of size m respectively to jointly compute the intersection I = A 1 ∩ A 2 ∩ ⋯ ∩ A n over all their private data sets only if the size of intersection is larger than m − t , while ensuring that no other private information of the data sets other than the intersection is revealed, where t is the threshold. In the MP-TPSI protocol, multiple parties first decide whether the size of the intersection is larger than the threshold t ; then, they compute the intersection if the size of the intersection is larger than the threshold t . However, the existing MP-TPSI protocols use different forms of evaluation polynomials in the cardinality testing and intersection computing phases, so that parties need to transmit and calculate a large number of evaluation values, which leads to high communication and computational complexity. In addition, the existing MP-TPSI protocols cannot guarantee the security and the correctness of the results, that is, an adversary can know the additional information beyond the intersection, and the elements that are not in the intersection are calculated as the intersection. To solve these issues, based on the threshold fully homomorphic encryption (TFHE) and sparse polynomial interpolation, we propose an MP-TPSI protocol. In the star network topology, the theoretical communication complexity of the proposed MP-TPSI protocol depends on the threshold t and the number of parties n , not on the size of set m . Moreover, the proposed MP-TPSI protocol outperforms other related MP-TPSI protocols in terms of computational and communication overheads. Furthermore, the proposed MP-TPSI protocol tolerates up to n − 1 corrupted parties in the semi-honest model, where no set of colluding parties can learn the input of an honest party in the strictest dishonest majority setting.
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Rignot, Eric, and Douglas R. MacAyeal. "Ice-shelf dynamics near the front of the Filchner—Ronne Ice Shelf, Antarctica, revealed by SAR interferometry." Journal of Glaciology 44, no. 147 (1998): 405–18. http://dx.doi.org/10.3189/s0022143000002732.
Full textAbstract:
AbstractFifteen synthetic aperture radar (SAR) images of the Ronne Ice Shelf (also referred to as the Filchner-Ronne Ice Shelf), Antarctica, obtained by the European remote-sensing satellites ERS-1 and -2, are used to study ice-shelf dynamics near two ends of the iceberg-calving front. Interferograms constructed from these SAR images are used to resolve the ice-shelf displacement along several directions in response to both ocean tide and long-term creep flow. Tidal motion is separated from creep flow using differential interferometry, i.e. two or more interferograms in which fringe patterns common to all are predominantly associated with creep flow. Creep-flow velocities thus determined compare well with prior ice-shelf velocity surveys. Using these data, we studied the influence of large-scale rifts, ice rises and coastal separation on the ice-shelf flow. Many of the large rifts that appear to form the boundaries where tabular icebergs may eventually detach from the ice shelf are filled with a melange of sea ice, ice-shelf debris and wind-blown snow. The interferograms show that this melange tends to deform coherently in response to the ice-shelf flow and has sufficient strength to trap large tabular ice-shelf fragments for several decades before the fragments eventually become icebergs. In many instances, the motion of the tabular fragments is a rigid-body rotation about a vertical axis that is driven by velocity shear within the melange. Tfhe mechanical role of the rift-filling melange may be to bind tabular ice-shelf fragments to the main ice shelf before they calve. This suggests two possible mechanisms by which climate could influence tabular iceberg calving. First, spatial gradients in oceanic and atmospheric temperature may determine where the melange melts and, thus, the location of the iceberg-caking margin. Second, melting or weakening of ice melange as a consequence of climate change could trigger a sudden or widespread release of tabular icebergs and lead to rapid ice-shelf disintegration.
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Rignot, Eric, and Douglas R. MacAyeal. "Ice-shelf dynamics near the front of the Filchner—Ronne Ice Shelf, Antarctica, revealed by SAR interferometry." Journal of Glaciology 44, no. 147 (1998): 405–18. http://dx.doi.org/10.1017/s0022143000002732.
Full textAbstract:
AbstractFifteen synthetic aperture radar (SAR) images of the Ronne Ice Shelf (also referred to as the Filchner-Ronne Ice Shelf), Antarctica, obtained by the European remote-sensing satellites ERS-1 and -2, are used to study ice-shelf dynamics near two ends of the iceberg-calving front. Interferograms constructed from these SAR images are used to resolve the ice-shelf displacement along several directions in response to both ocean tide and long-term creep flow. Tidal motion is separated from creep flow using differential interferometry, i.e. two or more interferograms in which fringe patterns common to all are predominantly associated with creep flow. Creep-flow velocities thus determined compare well with prior ice-shelf velocity surveys. Using these data, we studied the influence of large-scale rifts, ice rises and coastal separation on the ice-shelf flow. Many of the large rifts that appear to form the boundaries where tabular icebergs may eventually detach from the ice shelf are filled with a melange of sea ice, ice-shelf debris and wind-blown snow. The interferograms show that this melange tends to deform coherently in response to the ice-shelf flow and has sufficient strength to trap large tabular ice-shelf fragments for several decades before the fragments eventually become icebergs. In many instances, the motion of the tabular fragments is a rigid-body rotation about a vertical axis that is driven by velocity shear within the melange. Tfhe mechanical role of the rift-filling melange may be to bind tabular ice-shelf fragments to the main ice shelf before they calve. This suggests two possible mechanisms by which climate could influence tabular iceberg calving. First, spatial gradients in oceanic and atmospheric temperature may determine where the melange melts and, thus, the location of the iceberg-caking margin. Second, melting or weakening of ice melange as a consequence of climate change could trigger a sudden or widespread release of tabular icebergs and lead to rapid ice-shelf disintegration.
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Syed, Fahim, Wei Li, and Qigui Yu. "GC Tfh Cell Metabolism and Survival of HIV-1 Infection." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 182.29. http://dx.doi.org/10.4049/jimmunol.208.supp.182.29.
Full textAbstract:
Abstract CD4 T cells are the primary targets for HIV-1 infection and their loss is a hallmark of HIV-1 disease. However, T follicular helper (Tfh) cells, a distinct subset of CD4 T cells that are specialized in helping B cells form germinal centers (GCs) for the generation of high-affinity class-switched antibodies, undergo expansion in people living with HIV-1 (PLHIV). Indeed, Tfh cells with latent HIV-1 are enriched in PLHIV, whether the PLHIV are on antiretroviral therapy (ART) or not. This shows that Tfh cells are preferentially infected by HIV-1 and are able to survive infection. Through total RNAseq of tonsillar subsets of T cells, including Tfh cells, our lab was able to find a sharp upregulation of an inhibitor of apoptosis family member gene (BIRC5) and a distinct metabolic gene profile in Tfhs compared to the other subsets. We further were able to find and confirm that (1) BIRC5 was highly expressed in human tonsil Tfh cells and the expression was upregulated upon HIV-1 infection, (2) human tonsil Tfh cells had high levels of Fatty Acid Oxidation related genes, but low levels of glycolytic genes, when compared with non-Tfh CD4 T cells, and (3) inhibition of FaO and BIRC5 led to changes in the survival of Tfh cells following HIV-1 infection. Our results show that Tfh survival of HIV-1 is associated with both the metabolic profile and expression of BIRC5 due to their ability to inhibit virus-induced direct and bystander apoptosis. Supported by grants from the NIH T32: Immunology and Infectious Disease Training Program