9,054 research outputs found
JC virus evolution and its association with human populations
Full text linkThe ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed codivergence with humans, JCV has been used as a genetic marker for human evolution and migration. Codivergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus codivergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of codivergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for codivergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited sampling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the codivergence hypothesis.</p
Phenoloxidase activity of hemocytes derived from Penaeus monodon and Macrobrachium rosenbergii.
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Algorithm automation for nuclear power plant Loose Parts Monitoring System
No full textLoose Parts Monitoring signals in the control room of the nuclear power plant come in through multiple channels and are presented as graphs on the display devices. It involves a lengthy and complicated process to determine the size, mass, speed, and impact location of the loose part when the signals are collected and processed. In this work, a simple and efficient model for determining the impact location of the loose part using the Least-Sum-of-Square-Errors (LSSEs) method combined with iteration has been developed based on the phase distortion of the impact signal envelopes. The signal peak point shifts to the right on the time axis when the sensor is located farther away from the impact location. This method provides a good estimation of the impact location and can be used as an alternative to existing calculations based on other attributes of the impacting signal. To automate the backend portion of the LPMS algorithm, interpolation was used for compensating the impact attenuation effect and log-log regression was also employed to determine the impacting part size and impact velocity, and the result turned out to be well in line with the manual calculations. The automated algorithm will improve the efficiency of the LPMS software. (C) 2003 Published by Elsevier B.V
Pilot-test scale affinity chromatographic purification of trypsin and chymotrypsin from hog pancreas.
No full textNeuropsychiatric disturbances and hypopituitarism after traumatic brain injury in an elderly man
No full textApplication of an integrated power line signal analysis methodology to the detection of major rotating machine abnormalities in nuclear power plants
No full textAn integrated and improved method to detect and identify the abnormality of motor driven rotating machinery in nuclear power plants (NPPs) using power line signal analysis is suggested in this work. The primary goal of this work is to improve the motor current signature analysis (MCSA) method that has been used as an alternative or supplement of the conventional vibration monitoring system (VMS). Through this work, the integrated system using both modulated flux density model (MFDM) and rotating flux model (RFM) is proposed. The MFDM is based on the fact that the major mechanical vibration of rotating machines can be normalized to the motor air-gap eccentricity and the modulation of air-gap flux density. Therefore, if the major defect such as bearing defect or the shaft deformation is present, it is identifiable through the power line signal resulting from the modulated magnetic density. Moreover, the broken rotor bar state or rotor eccentricity due to electrical imbalance can be analyzed using the RFM. The other important feature of this system is an automated abnormality detection and diagnosis algorithm. It is possible to diagnose the abnormality without relying on experts in NPPs. The verification is done through varying load/torque test experiment as well as via computer simulation in this work. The experimental results show that they are in good agreement with the simulated results. (C) 2004 Elsevier B.V. All rights reserved
JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract
No full textBackground & Aims: JC virus (JCV), a human polyomavirus, has been found in a limited number of normal human tissues and cancers, The oncogenic potential of this virus is mediated by a transforming protein, the T antigen (TAg). We have previously demonstrated the presence of JCV-TAg in colorectal cancers, in adjacent normal colonic mucosa from these patients, and in the human colon cancer cell line SW480. The mode of transmission of this virus is unclear, and we hypothesized that the gastrointestinal (GI) tract may be a reservoir for the virus. Methods: DNA was extracted from 129 normal GI tissue samples collected from 33 patients. Topoisomerase I-assisted polymerase chain reaction (PCR) was used to detect the virus using exact and degenerate primers. Nested PCR and Southern blot analysis confirmed the identity of the PCR products. Single-stranded conformation polymorphism (SSCP) analysis and sequencing were used to evaluate the presence of viral quasispecies. Results: JCV sequences were found in 75.8% of patients (70.6% of upper Gi and 81.2% of colonic samples); no significant differences in rates of infection were found by site. The use of degenerate primers combined with topoisomerase I treatment led to viral detection in 58.9% of samples, compared with 27.9% of samples using exact primers and topoisomerase I (P < 0.01), SSCP and sequencing analysis confirmed the amplification of viral quasispecies and the authenticity of TAg sequences. Conclusions: The results show that JCV DNA sequences are highly prevalent in the human upper and lower gastrointestinal tract of immunocompetent individuals
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
Abstract ES6-1: ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy
No full textAbstract
Breast cancer is a highly heterogeneous disease with various molecular subtypes that differ in regard to treatment approach as well as unresolved treatment issues.
In women with HER2-amplified breast tumors, standard neoadjuvant therapy consisting of dual HER2 blockade with trastuzumab/pertuzumab plus chemotherapy can induce a high pathologic complete response (pCR) rate (60%), which translates into better overall survival (&gt;90% at 3 years). A critical unresolved issue in the neoadjuvant treatment of HER2-amplified tumors is minimizing toxicity in select patients. Selection of non-cardiogenic regimens and chemotherapy-free or lighter chemotherapy regimens should be the focus for women whose disease is highly addicted to the HER2 pathway. New research directions are also exploring ways to minimize the extent of local surgery in the breast and axilla.
Approximately 30% of patients with triple-negative breast cancer (TNBC) achieve pCR after neoadjuvant chemotherapy. While these patients tend to have a favorable prognosis, those with residual disease (RD) at the time of surgical resection may expect significantly worse outcomes and, at present, do not have targeted therapeutic options. Molecular analysis of tumor tissue from such patients may be used to identify the genetic alterations responsible for disease recurrence and to help individualize treatment with available agents. Transcriptome and sequencing analyses have identified important pathways and aberrations in the majority of residual tumors. Targeting these molecular abnormalities in conjunction with the tumor immune microenvironment may represent an effective therapeutic avenue to improve the outcomes of TNBC patients who have RD after standard neoadjuvant therapy. Adaptive clinical trials investigating neoadjuvant treatments directed against key pathways active in residual tumors are underway.
Citation Format: Chang JC. ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES6-1.</jats:p
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