8,766 research outputs found
JC and BK polyomavirus-like particles as targets of innate and adaptive humoral immunity
Full text linkJC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) were identified as the first of now more than 12 human polyomaviruses (HPyVs). The average JCPyV and BKPyV seroprevalence rates in adults are 70% and 90%, respectively. After asymptomatic infection both viruses persist in the renourinary tract. In fact, asymptomatic viruria is detectable in one-third of general population. However, in immunocompromised patients, JCPyV and BKPyV replication may progress to significant diseases. Hence, JCPyV can cause progressive multifocal leukoencephalopathy (PML) in patients with HIV-AIDS, malignancies or autoimmune diseases under immunosuppressive treatment. BKPyV can be a cause of polyomavirus-associated nephropathy (PyVAN) in kidney transplant recipients or hemorrhagic cystitis (PyVHC) after allogeneic hematopoietic stem cell transplantation. Due to more frequent application of immunosuppression, the risk of developing these diseases has increased in the last few decades. The risk of PML development is estimated to be 100-fold higher for JCPyV-seropositive patients in comparison to JCPyV-seronegatives. Most cases of PyVAN and PyVHC have been tested positive for BKPyV at the moment of disease diagnosis. Unfortunately, there is no specific antiviral therapy against any of these HPyV diseases. Thus, current strategies to avert PyVAN or PyVHC aim at identifying patients with BKPyV viremia and reducing immunosuppression. Similar strategies for PML have not been effective, since JCPyV viremia is usually not detected prior to or at the diagnosis of disease. The fate of BKPyV and JCPyV virus-like particles (VLPs) was examined in an animal model corresponding to primary viremia in non-immune host. Radioactively labeled VLPs were used to assess blood decay, organ, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and cytochemistry. Rapid distribution of both BKPyV and JCPyV VLPs to the liver was observed, with lesser uptake in kidney and spleen. Liver uptake was predominantly observed in LSECs. Blood half-life and tissue distribution of both wild-type JCPyV VLPs and two mutant JCPyV VLPs (L55F and S269F), lacking sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. We concluded that LSECs very effectively cleared a large fraction of blood-borne BKPyV and JCPyV VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. Moreover, we observed that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism (Simon-Santamaria et al., p. 54). Giving the increasing clinical need to reliably determine JCPyV and BKPyV IgG levels in patients at risk, we first reviewed and optimized serological tools for JCPyV and BKPyV IgG detection including virus-like particle (VLP)-based ELISA. We demonstrated that although no statistically significant differences in intraassay and interassay variability were revealed for JCPyV serology of 400-fold diluted sera from healthy donors, qualitative differences were seen in the identification of the individual JCPyV serostatus. The cause of discordance for approximately 10% of sera resulted from a low IgG activity close to the cutoff of the assay. Therefore we standardized the ELISA using reference serum for normalization. Moreover, we developed a preadsorption assay with cutoff of 35% reduction of the JCPyV IgG activity after preincubation with JCPyV VLPs. Importantly, we excluded BKPyV antibody cross-reactivity by testing JCPyV IgG positive sera in preadsorption assay using BKPyV VLPs. In conclusion, we showed that VLP-based ELISA with normalization can serve as a reliable tool for JCPyV IgG serology. Additionally, the preadsorption assay can help with unequivocal determination of JCPyV serostatus for samples with low IgG levels. (Kardas et al., p. 72). We also normalized this VLP-based ELISA for BKPyV IgG detection and showed that for seroepidemiology studies, normalized JCPyV and BKPyV IgG ELISA at 1:200 serum dilution provides optimal sensitivity and specificity with the lowest false-positive and false-negative rate. However, for individual risk assessment, 100-, 200-, and 400-fold dilutions combined with preadsorption for low-reactive sera might be the most appropriate (Kardas et al., p. 82). This improved ELISA was used to investigate JCPyV and BKPyV specific antibody levels in several clinical studies: (1) one case of PML patient where positive JCPyV IgG status was compatible with other PML-indicating symptoms (Kurmann et al., p. 90); (2) one case of PyVAN caused by JCPyV rather than BKPyV, as confirmed by JCPyV IgG/IgM positive and BKPyV IgG/IgM negative results (Lautenschlager et al., 99); (3) one case of PyVHC patient after allogeneic hematopoietic stem cell transplantation where increasing BKPyV IgG activities were in line with progression of BKPyV viremia (Koskenvuo et al., p. 106). Further, by serological testing of 122 immunocompetent and 63 immunocompromised patients we demonstrated that the BKPyV IgG level is age-dependent, with the highest values between 20 and 30 years (Schmidt et al., p. 119). In another study we compared serological outcomes of ELISA utilizing two different antigens in terms of prognostic value in prostate cancer development. To accomplish this we utilized improved ELISA for BKPyV IgG activity to both BKPyV VLPs and BKPyV LTag. Testing of 226 patients undergoing radical prostatectomy for primary prostate cancer revealed that BKPyV VP1 serostatus, in contrast to BKPyV LTag, has no prognostic value in prostate cancer progression (Keller et al., p. 125). In conclusion, we provided a new input into knowledge about tropism and clearance of polyomaviruses from blood. Moreover, we established a reliable and sensitive VLP-based assay for specific detection of JCPyV and BKPyV IgG and IgM. Serostatus based on ELISA results was compatible with other symptoms of BKPyV- and JCPyV-related diseases
Perancangan Sistem Informasi Pengelola Barang/Inventaris Di Jc Komp
Full text linkInventory information system is a system used to enter inventory data into the database, so that there are no errors in input, output data, and reporting based on the desired data. based on surveys and interviews with jc comp personnel, information was obtained that the existing system in the jc comp warehouse section is still manual. therefore, the system that will be created by the author is the result of a replication of the existing system in the jc comp warehouse section. in addition to the process of input and output of goods, this information system is also equipped with features for creating data reports, input and output of goods, and searching for goods data by item name. with the inventory information system is expected to be useful for the warehouse parts jc comp. By implementing this system in the jc comp warehouse, it is hoped that it can reduce errors that may occur. this system is also expected to further speed up the process of input, output, and report generation, which in turn will help the jc comp warehouseSistem Informasi Persediaan Barang adalah sebuah sistem yang digunakan untuk memasukkan data-data persediaan barang ke dalam database, sehinggga tidak terjadi kesalahan dalam input, output data, dan pembuatan laporan berdasarkan data yang diinginkan. Berdasarkan survey dan wawancara dengan bagian personalia Jc Komp, didapatkan informasi bahwa sistem yang ada dibagian gudang Jc Komp masih manual. Oleh karena itu, sistem yang akan dibuat oleh penulis adalah hasil replikasi dari sistem yang telah ada dibagian gudang Jc Comp. Selain proses input dan output barang, pada sistem informasi ini juga dilengkapi fitur pembuatan laporan data, input, dan output barang, dan pencarian data barang berdasarkan nama barang. Dengan adanya Sistem Informasi persediaan barang ini diharapkan dapat bermanfaat bagi bagian gudang Jc Komp. Dengan diterapkannya sistem ini pada bagian gudang Jc Comp, maka diharapkan dapat mengurangi kesalahan-kesalahan yang mungkin terjadi. Sistem ini juga diharapkan dapat lebih mempercepat proses input, output, dan pembuatan laporan yang pada akhirnya dapat membantu bagian gudang Jc Komp
Amenable L-2-Theoretic Methods and Knot Concordance
No full textWe reveal new structures in the topological knot concordance group. As a key ingredient, we develop obstructions using L-2-theoretic methods for amenable groups in Strebel's class recently introduced by Orr and the author. Concerning (h)-solvable knots, which are defined in terms of certain Whitney towers of height h in bounding 4-manifolds, we show the following: for any n>1, there are (n)-solvable but non-(n. 5)-solvable (and therefore nonslice) knots, which are not detected by prior methods using Cochran-Orr-Teichner L-2-signature obstructions as well as Levine algebraic obstructions and Casson-Gordon invariants.X1197sciescopu
Dynamics of Network Formation Processes in the Co-Author Model
Full text linkThis article studies the dynamics in the formation processes of a mutual consent network in game theory setting: the Co-Author Model. In this article, a limited observation is applied and analytical results are derived. Then, 2 parameters are varied: the number of individuals in the network and the initial probability of the links in the network in its initial state. A simulation result shows a finding that is consistent with an analytical result for a state of equilibrium while it also shows different possible equilibria.Dynamics, Network, Game Theory, Model,Simulation, Equilibrium, Complexity
High-level polyomavirus JC viruria following long-term steroid therapy
No full textCASE REPORT JC virus is a highly seroprevalent ubiquitous polyomavirus which is acquired at an early age through respiratory or oral route, Thereafter JCV establishes persistent, but mainly asymptomatic, infections in various tissues, including the genitourinary tract and brain Corresponding author Cristina Costa, MD S.C.D.U. Virologia Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino Via Santena, 9 -10126 Torino E-mail: [email protected] increasing with age, with adult prevalence rate often between 15% and 60
Engineering Framework to Utilize Miniaturized Charpy Type SE(B) Specimens to Predict Jc of Full Sized Specimens
No full textAbstractThis paper introduces our experience of using miniature Charpy type SE(B) specimen in obtaining fracture toughness Jc of a material in the ductile to brittle transition temperature (DBTT) region. Width W x thickness B of 2 x 2 mm, 3 x 3 mm and 10 x 10 mm were chosen as miniature specimens and 25 x 25 mm were chosen as full sized specimen. 0.55% carbon steel JIS S55C, whose tensile to yield stress ratio σTS/σYS was equal to 1.8 was chosen as a material to simulate a degraded (embrittled) material in the DBTT region. Focus was placed on whether cleavage fracture could be predicted for these miniaturized specimens. Another focus was placed on whether the Jc of full sized specimen is predictable from the test results of the miniature sized specimens, in case cleavage fracture were observed. The results showed that the modified Ritch-Knott-Rice (RKR) failure criterion (which predicts the onset of cleavage fracture when the crack opening stress measured at 4 times the crack-tip opening displacement exceeds this σ22c) could predict whether cleavage fracture would occur or not. Another finding was that, in case cleavage fracture was observed though, the critical value σ22c in the modified RKR failure criterion was independent of specimen size, and thus, Jc of the full sized specimen is predictable from the miniature specimen test results, though M = (W-a)σYS/Jc was smaller than ASTM E1921 requirement of 30. Here, a and σYS are crack length and yield strength, respectively
The Chinese medicine JC-001 enhances the chemosensitivity of Lewis lung tumors to cisplatin by modulating the immune response
No full textAbstract Background JC-001 is a Chinese medicine that can modulate the immunity in Hepa 1-6 tumor-bearing mice, and we questioned whether JC-001 can serve as efficient adjuvant chemotherapy. We aimed to identify a novel approach for enhancing cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy by immunomodulation. Methods The anti-tumor activity in vitro was determined based on foci formation and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A LLC1 tumor xenograft model was used to analyze the activity of tumor rejection in vivo. The tumors were analyzed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and cytokine arrays. Results JC-001 suppressed foci formation and reduced the viability of Lewis lung carcinoma (LLC1) cells in vitro. JC-001 suppressed LLC1 tumor growth in immunodeficient BALB/c nude mice and in immunocompetent C57BL/6 mice to an even greater extent. Furthermore, JC-001 up-regulated interferon-γ expression in the tumor microenvironment, enhanced the Th1 response in tumor-bearing mice, and increased the chemosensitivity of LLC1 tumors to CDDP chemotherapy. The results of our study suggest that JC-001 is associated with low cytotoxicity and can significantly suppress tumor growth by enhancing the Th1 response. Conclusion JC-001 is a Chinese medicine with potential clinical applications in CDDP-based chemotherapeutic regimens
Extended investigation of the test specimen thickness (TST) effect on the fracture toughness (Jc) of a material in the ductile-to-brittle transition temperature region as a difference in the crack tip constraint − What is the loss of constraint in the TST effects on Jc?
No full textAbstractThis paper answers a question that was raised from our recent work [1] for the non-standard single-edge notched bend (SE(B)) specimens, which exhibited the test specimen thickness effect on Jc (TST effect on Jc) together with the bounded nature for increasing TST in the ductile-to-brittle transition temperature region. The question was “what is the loss of constraint in the TST effect on Jc, because the crack opening stress σ22 distribution scaled with CTOD at fracture load was approximately same for different TSTs?”To answer this question, several well-known constraint parameters were investigated to determine their correlations with the TST effect and the bounded nature of Jc for increasing TST. Based on the elastic–plastic finite element analysis results, it was demonstrated that the well-known stress triaxiality factor Θ=(hydrostatic stress)/(von Mises stress), measured at 4δtc (crack-tip opening displacement at fracture load Pc), exhibited a good correlation with the decreasing and subsequently bounded nature of Jc for increasing TST. Θ started to decrease at some load level before fracture for relatively thin specimens, and this was the loss of constraint in the TST effects on Jc
Improvement of Jc and Hc2 in MgB2 superconductor with citric acid addition
No full textThis paper reports on the fabrication and characterization of citric acid (CA)-C6H8O7 added MgB 2superconductor. The relationships between microstructures, critical current density (Jc), critical temperature (Tc), upper critical field (Hc2), irreversibility field (Hirr), and normal state resistivity for 10 wt% C6H8O7added MgB2samples sintered at temperatures from 650°C to 950°C were systematically studied. A reduction in Tc and in lattice parameter a due to the C substitution and possible oxygen (O) effects occurs with C6H8O7 addition. Jc, H c2, and Hirr are significantly enhanced, however, with the addition of C6H8O7. All the samples exhibit Jc above 104A/cm2 at 5 K and 8 T. This value is higher than for the un-doped MgB2 by a factor of 9. The significant improvement in the superconducting properties is attributed to the lattice distortion due to the C and possible oxygen (O) substitution for boron, with the C and O coming from the decomposition of C6H8O 7
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