Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacterial DNA Activates Endothelial Cells and Promotes Neutrophil Adherence through TLR9 Signaling1

TLR9 detects bacterial DNA (CpG DNA) and elicits both innate and adoptive immunity. Recent evidence indicates that TLR9 is expressed in more diverse cell types than initially thought. In this study, we report that HUVECs constitutively express TLR9 and selectively recognize unmethylated CpG motifs in bacterial DNA and synthetic immune stimulatory CpG oligodeoxynucleotides. HUVECs respond to CpG DNA with rapid phosphorylation of IκB-α and NF-κB-mediated gene transcription and surface expression of the adhesion molecules ICAM-1 and E-selectin independent of MAPK signaling. The telomere-derived TLR9 inhibitory oligonucleotide 5′-TTT AGG GTT AGG GTT AGG G-3′, agents that block endosomal acidification such as chloroquine and bafilomycin A, and NF-κB inhibitors abrogated CpG DNA-induced signaling. HUVEC activation by CpG DNA led to markedly enhanced neutrophil adhesion under nonstatic conditions that was further enhanced when neutrophils were stimulated with CpG DNA. The adhesive interactions were blocked by Abs against CD18 and, to a lesser degree, by anti-E-selectin and anti-L-selectin Abs. Our findings demonstrate that bacterial DNA promotes β2 integrin and E-selectin-mediated HUVEC-neutrophil adherence, and indicate the ability of CpG DNA to initiate and/or maintain the inflammatory response.
Cytoprotective Function of Heme Oxygenase 1 Induced by a Nitrated Cyclic Nucleotide Formed during Murine Salmonellosis1

Signaling mechanisms of NO-mediated host defense are yet to be elucidated. In this study, we report a unique signal pathway for cytoprotection during Salmonella infection that involves heme oxygenase 1 (HO-1) induced by a nitrated cyclic nucleotide, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP). Wild-type C57BL/6 mice and C57BL/6 mice lacking inducible NO synthase (iNOS) were infected with Salmonella enterica serovar Typhimurium LT2. HO-1 was markedly up-regulated during the infection, the level being significantly higher in wild-type mice than in iNOS-deficient mice. HO-1 up-regulation was associated with 8-nitro-cGMP formation detected immunohistochemically in Salmonella-infected mouse liver and peritoneal macrophages. 8-Nitro-cGMP either exogenously added or formed endogenously induced HO-1 in cultured macrophages infected with Salmonella. HO-1 inhibition by polyethylene glycol-conjugated zinc-protoporphyrin IX impaired intracellular killing of bacteria in mouse liver and in both RAW 264 cells and peritoneal macrophages. Infection-associated apoptosis was also markedly increased in polyethylene glycol-conjugated zinc-protoporphyrin IX-treated mouse liver cells and cultured macrophages. This effect of HO-1 inhibition was further confirmed by using HO-1 short interfering RNA in peritoneal macrophages. Our results suggest that HO-1 induced by NO-mediated 8-nitro-cGMP formation contributes, via its potent cytoprotective function, to host defense during murine salmonellosis.
Lipoprotein profile, plasma Ischemia Modified Albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study

Abstract Postprandial lipemia is associated with elevated risk of cardiovascular disease. Very little data exists regarding postprandial response in subjects with metabolic syndrome (MetS). The current study was conducted within the LIPGENE EU Integrated Project. Patients were randomized to one of the four isocaloric fatty meals (Oral Fat Tolerance Tests, OFTT): (A) high-fat, saturated fatty acid (SFA)-rich (HFSA), (B) high-fat, monounsaturated fatty acid (MUFA)-rich (HFMUFA), (C) low-fat, high-complex carbohydrate with 1.24 g high oleic sunflower oil supplement (LFHCC) and (D) low-fat high-complex carbohydrate with 1.24 g long chain n-3 poly-unsaturated fatty acid (LC n-3 PUFA) supplement (LFHCCn-3). The total and incremental areas under the curve (tAUC and iAUC) of plasma lipid and lipoprotein, Ischemia Modified Albumin (IMA) and LDL density were examined in patients with MetS to define effect of OFTT. All types of OFTT transiently increased plasma triglyceride and LDL density (LDLdens). It was paralleled by temporal decrease in total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). This last effect was partly alleviated in LFHCCn-3 test. A reversible increase of IMA was statistically significant only in the course of HSFA and HMUFA tests. EPA and DHA supplement in combined high complex-carbohydrate meal may attenuate adverse effect of tested meal on LDL particle profile and plasma ischemia modified albumin. No expected associations between measures of central adiposity (waist, WHR), adipose tissue insulin resistance (Adipo-IR), and postprandial responses of TG, TC, LDL-C, HDL-C, LDLdens and IMA/Alb ratio were found in subgroup analysis. Trial registration: ClinicalTrials.gov identifier: NCT00429195.
International Conference on Computational Science , ICCS 2011 Parallel And SIMD Optimization Of Image Feature Extraction

Image feature extraction is widely used in content-based image retrieval(CBIR), computer version and all kinds of image processing applications. In this paper, we introduce some parallel and SIMD optimizations of image-feature extraction to overcome the disadvantages of original methods. We mainly use both thread-parallel optimization and Single Instruction Multiple Data (SIMD) optimizations. And especially, for some hot point, we use SIMD logical operations to eliminate the random conditional branches which cannot be effectively predicted by CPU Branch Prediction. We experimented our optimized implementation on multi-core systems, and various images were used to test the image-feature extraction results and performance. All the parallel and SIMD optimizations work out a good cumulative performance speedup.
Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident APCs at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that TLR7 and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly, both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 virus-like particles and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete proinflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV infections and HPV-induced cervical lesions.
SSERank: semantic search engine for page ranking based on the relations weight

Semantic search engines promise to provide more accurate results than current keywords search engines. However, it is useful to exploit ontological relations in search steps. In this paper, we present an approach which automatically exploits the keywords in a user query to find related concepts in domain ontology. Given an ontology and some annotated pages, the weights assigned to relations in a given page indicate its strength. However, in order to rank results, we assign a weight for each annotated page. This paper proposes a prototype (SSERank) relation-based page weighting and ranking with semantic search capability. The obtained results show that SSERank will have great utility although there is potential for improvement.
E-Metadata versioning system for data warehouse schema

In our proposal, E-Metadata is a combination of the technical metadata and the ontology. Whenever the data warehouse schema is modified, the changes are reflected in the technical metadata. As a consequence, a new version of E-Metadata has to be created. The E-Metadata versioning system proposed in this study creates the new version. The version creation process uses three steps to create the different versions of the E-Metadata. First, the changes in the technical metadata schema are identified. Towards this, we propose XSD-Diff algorithm which generates the difference between two XML schemas technical metadata. It generates the Delta file which contains the information that has changed. Second, the changed information in the Delta file is used to incorporate the changes in the ontology. Third, the version information dictionary is updated reflecting the new version of E-Metadata.
Unwanted Pregnancy and Associated Factors Among

METHODS: A community-based survey of 2,978 women aged 15‐49 was conducted in eight Nigerian states. Univariate analyses and multivariate logistic regression analyses were used to determine the incidence of unwanted pregnancy, the incidence of seeking an abortion among women with unwanted pregnancies and the factors associated with unwanted pregnancy and abortion-seeking behavior. Additional analyses examined the prevalence of contraceptive use and women’s reasons for seeking to terminate unwanted pregnancies and for not practicing contraception at the time their unwanted pregnancies were conceived. RESULTS: Twenty-eight percent of respondents reported ever having had an unwanted pregnancy; of those, half reported having attempted to end their last unwanted pregnancy. Forty-three percent of women who sought an abortion did so because they were not married, were too young or were still in school. Of the women who were not practicing contraception when they had the unwanted pregnancy, 44% said that they were unaware of family planning, and 22% that they either did not have access to contraceptive services, services were too expensive or they were afraid of side effects. At the time of the survey, 27% of all respondents were at risk of an unwanted pregnancy. Almost half were unaware of contraceptive methods. CONCLUSIONS: Nigerian women often turn to abortion to avoid unwanted births. The provision of family planning counseling and information could substantially reduce the incidence of unwanted pregnancy and induced abortion in Nigeria.
The Polarity Protein Par1b/EMK/MARK2 Regulates T Cell Receptor-Induced Microtubule-Organizing Center Polarization1

Engagement of a T cell to an APC induces the formation of an immunological synapse as well as reorientation of the microtubule-organizing center (MTOC) toward the APC. How signals emanating from the TCR induce MTOC polarization is not known. One group of proteins known to play a critical role in asymmetric cell division and cell polarization is the partitioning defective (Par) family of proteins. In this study we found that Par1b, a member of the Par family of proteins, was inducibly phosphorylated following TCR stimulation. This phosphorylation resulted in 14-3-3 protein binding and caused the relocalization of Par1b from the membrane into the cytoplasm. Because a dominant-negative form of Par1b blocked TCR-induced MTOC polarization, our data suggest that Par1b functions in the establishment of T cell polarity following engagement to an APC.
A Single-Chain H-2Db Molecule Presenting an Influenza Virus Nucleoprotein Epitope Shows Enhanced Ability at Stimulating CD8+ T Cell Responses In Vivo 1

We have generated a construct encoding a single-chain H-2Db mouse MHC class I molecule in which an influenza virus nucleoprotein (NP) epitope, amino acid sequence ASNENMDAM, is fused to mouse β2-microglobulin and the Db H chain via flexible linker sequences. This single-chain trimer (SCT) was efficiently expressed at the cell surface independently of TAP and endogenous β2-microglobulin, and it was recognized directly and efficiently by specific T cells in vitro. A recombinant vaccinia virus encoding the Db NP SCT primed a CD8+ T cell response in C57BL/6 mice 4-fold greater than an equivalent virus expressing the NP epitope as a minigene, as shown by tetramer staining, whether or not the minigene was directed into the endoplasmic reticulum by a signal sequence. This response was functional as shown by in vivo lysis assays with peptide-pulsed target cells, and it was greatly expanded following secondary challenge in vivo with influenza virus. The SCT was also significantly more immunostimulatory for CD8+ cells than the NP minigene in adoptive transfer experiments using F5 TCR transgenic spleen cells, in which the magnitude of the T cell response was much greater. Our results extend previous DNA vaccination studies using SCTs, which demonstrated that such molecules are capable of generating functional CD8+ T cell responses. We have shown that class I SCTs are more immunogenic than even preprocessed Ag in the form of an epitope minigene, and they therefore should be considered for use when the generation of optimal CD8+ T cell responses is required.
Palmitoylation-Dependent Plasma Membrane Transport but Lipid Raft-Independent Signaling by Linker for Activation of T Cells1

Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane adaptor protein essential for T cell development and activation. However, whether LAT palmitoylation and/or lipid raft localization are required for its function is controversial. To address this question, we used a combination of biochemical, imaging, and genetic approaches, including LAT retrovirus-transduced mouse T cells and bone marrow chimeric mice. A nonpalmitoylated, non-lipid raft-residing mutant of transmembrane LAT could not reconstitute T cell development in bone marrow chimeric mice. This mutant was absent from the plasma membrane (PM) and was restricted mainly to the Golgi apparatus. A chimeric, nonpalmitoylated LAT protein consisting of the PM-targeting N-terminal sequence of Src kinase and the LAT cytoplasmic domain (Src-LAT) localized as a peripheral membrane protein in the PM, but outside lipid rafts. Nevertheless, Src-LAT restored T cell development and activation. Lastly, monopalmitoylation of LAT on Cys26 (but not Cys29) was required and sufficient for its PM transport and function. Thus, the function of LAT in T cells requires its PM, but not raft, localization, even when expressed as a peripheral membrane protein. Furthermore, LAT palmitoylation functions primarily as a sorting signal required for its PM transport.
Modulating the Expression of IFN Regulatory Factor 8 Alters the Protumorigenic Behavior of CD11b+Gr-1+ Myeloid Cells1

CD11b+Gr-1+-expressing cells, termed myeloid-derived suppressor cells, can mediate immunosuppression and tumor progression. However, the intrinsic molecular events that drive their protumorigenic behavior remain to be elucidated. Although CD11b+Gr-1+ cells exist at low frequencies in normal mice, it also remains unresolved whether they are biologically distinct from those of tumor-bearing hosts. These objectives were investigated using CD11b+Gr-1+ cells from both implantable (4T1) and autochthonous (mouse mammary tumor virus-polyomavirus middle T Ag (MMTV-PyMT)) mouse models of mammary carcinoma. Limited variation was observed in the expression of markers associated with immunoregulation between CD11b+Gr-1+ cells of both tumor models, as well as with their respective controls (Cnt). Despite limited differences in phenotype, tumor-induced CD11b+Gr-1+ cells were found to produce a more immunosuppressive cytokine profile than that observed by Cnt CD11b+Gr-1+ cells. Furthermore, when admixed with tumor cells, CD11b+Gr-1+ cells from tumor-bearing mice significantly enhanced neoplastic growth compared with counterpart cells from Cnt mice. However, the protumorigenic behavior of these tumor-induced CD11b+Gr-1+ cells was significantly diminished when the expression of IFN regulatory factor 8, a key myeloid-associated transcription factor, was enhanced. The loss of this protumorigenic effect occurred independently of the host immune system and correlated with a CD11b+Gr-1+ cytokine/chemokine production pattern that resembled cells from nontumor-bearing Cnt mice. Overall, our data indicate that 1) tumor-induced CD11b+Gr-1+ cells from both cancer models were phenotypically similar, but biologically distinct from their nontumor-bearing counterparts and 2) modulation of IFN regulatory factor 8 levels in tumor-induced CD11b+Gr-1+ cells can significantly abrogate their protumorigenic behavior, which may have important implications for cancer therapy.
Soluble B and T Lymphocyte Attenuator Possesses Antitumor Effects and Facilitates Heat Shock Protein 70 Vaccine-Triggered Antitumor Immunity against a Murine TC-1 Cervical Cancer Model In Vivo1

B and T lymphocyte attenuator (BTLA)-herpesvirus entry mediator (HVEM) signaling coinhibitory pathway is believed to impair antitumor immune competences. An intriguing unresolved question is whether blockade of BTLA-HVEM guides an effective therapeutic tool against established tumors. To address this issue, we constructed a eukaryotic expression plasmid (psBTLA) that expressed the extracellular domain of murine BTLA (soluble form of BTLA), which could bind HVEM, the ligand of BTLA, and block BTLA-HVEM interactions. The data in this study showed that treatment by injection of psBTLA resulted in down-regulation of IL-10 and TGF-β and promotion of dendritic cell function by increasing the expression of B7-1 and IL-12, but the adaptive antitumor immune responses achieved by psBTLA administration alone were limited and could not eradicate the tumor effectively. Next, we evaluated the immunotherapeutic efficacy and mechanism of combination therapy of heat shock protein 70 (HSP70) vaccine/psBTLA by using murine TC-1 cervical cancer mice as an ectopic tumor model. Our in vivo studies revealed that treatment with HSP70 vaccine alone did not lead to satisfactory tumor growth inhibition, whereas cotreatment with psBTLA significantly improved antitumor immunity and compensated the deficiency of HSP70 vaccine by increasing the expression of Th1 cytokines, IL-2, and IFN-γ and decreasing transcription levels of IL-10, TGF-β, and Foxp3 in the tumor microenvironment. Taken together, our findings indicate that blocking the BTLA-HVEM interaction with sBTLA enhances antitumor efficacy and results in a significant synergistic effect against existent tumor cells in vivo when combined with the HSP70 vaccine.
Detection of ROS1 gene fusions using next-generation sequencing for patients with malignancy in China

Objective: This study aimed to identify ROS1 fusion partners in Chinese patients with solid tumors. Methods: Next-generation sequencing (NGS) analysis was used to detect ROS1 rearrangement in 45,438 Chinese patients with solid tumors between 2015 and 2020, and the clinical characteristics and genetic features of gene fusion were evaluated. H&E staining of the excised tumor tissues was conducted. Samples with a tumor cell content ≥ 20% were included for subsequent DNA extraction and sequencing analysis. Results: A total of 92 patients with ROS1 rearrangements were identified using next-generation sequencing, and the most common histological type lung cancer. From the 92 ROS1 fusion cases, 24 ROS1 fusion partners had been identified, including 14 novel partners and 10 reported partners. Of these, CD74, EZR, SDC4, and TPM3 were the four most frequently occurring partners. Fourteen novel ROS1 fusion partners were detected in 16 patients, including DCBLD1-ROS1, FRK-ROS1, and VGLL2-ROS1. In many patients, the ROS1 breakpoint was located between exons 32 and 34. Conclusion: This study describes 14 novel ROS1 fusion partners based on the largest ROS1 fusion cohort, and the ROS1 breakpoint was mostly located between exons 32 and 34. Additionally, next-generation sequencing is an optional method for identifying novel ROS1 fusions.
Ambulatory arterial stiffness index in chronic kidney disease stage 2–5. Reproducibility and relationship with pulse wave parameters and kidney function

Background. Arterial stiffness contributes to the increased cardiovascular risk in patients with chronic kidney disease (CKD). Reproducible and easily obtainable indices of arterial stiffness are needed in order to monitor therapeutic strategies. The ambulatory arterial stiffness index (AASI) has been proposed as such a marker. The present study investigated the day-to-day reproducibility of AASI in CKD stage 2–5 and its relationship with other markers of arterial stiffness as well as with kidney function. Methods. Eighty-three patients (29% female, median age 62 years) were studied by 24 h ambulatory blood pressure monitoring (ABPM), aortic pulse wave velocity (aPWV), augmentation index (AIx) and estimated glomerular filtration rate (eGFR) at a median interval of 7 days. Individual AASIs were calculated from 24 h ABPMs as 1 minus the regression slope of diastolic blood pressure over systolic blood pressure. Results. Mean AASI, aPWV, AIx and 24 h pulse pressure (PP) were similar on repeated measurements. The intraclass correlation coefficients were between 72% and 78% for AASI calculated by three different methods, 87% for aPWV, 88% for AIx, and 96% for 24 h PP. The correlation coefficients between AASI and aPWV were from 0.48 to 0.53; with AIx it was between 0.19 and 0.34. After adjustment for covariates none of the arterial stiffness indices were significantly correlated to eGFR. Conclusions. In patients with CKD stage 2–5 AASI had a moderate, but acceptable reproducibility. The correlation between AASI and aPWV was good whilst the correlation between AASI and AIx was considerably lower. There was no significant correlation between AASI and eGFR.
Regulation of Murine Splenic B Cell CR3 Expression by Complement Component 31

Complement component C3 has established roles in both innate and adaptive immune responses. C3 cleavage products function in B cell activation through the complement receptors CD21/35. Phenotypes of Ab production between CD21/35−/− and C3−/− mice are not always congruent, implicating additional roles for C3 in B cell responses. To further characterize complement and complement receptors, we have identified a role for C3 in the regulation of CR3 on splenic B cells. Splenic B2 cells are not defined as expressing CR3, yet the analysis of splenic B cells from C3−/− animals demonstrate cell surface expression of CR3. B cells from both wild-type (WT) and C3−/− animals express CR3/CD11b/Itgam (integrin α M) gene transcripts although the level of such transcripts is 2- to 3-fold higher in B cells from the C3−/− animal vs WT cells. C3−/− and WT animals have similar B cell subpopulations with identical CR3 expression on B220− cells from the spleen, marrow, and lymph nodes. The C3-deficient environment is responsible for altered CR3 expression as WT splenic B cells transferred into C3−/− animals expressed cell surface CR3 within 48 h while transfer of C3−/− splenic B cells into WT animals depressed surface expression of CR3. Furthermore, transfer of C3-producing splenic macrophages into C3−/− mice depressed CR3 expression by resident B cells. These data suggest a role for C3 in influencing the level of expression of CR3 by modulating the transcript levels encoding the CD11b α integrin protein.