Advanced radar detection schemes under mismatched signal models

CERN Document Server

Bandiera, Francesco

2009-01-01

Adaptive detection of signals embedded in correlated Gaussian noise has been an active field of research in the last decades. This topic is important in many areas of signal processing such as, just to give some examples, radar, sonar, communications, and hyperspectral imaging. Most of the existing adaptive algorithms have been designed following the lead of the derivation of Kelly's detector which assumes perfect knowledge of the target steering vector. However, in realistic scenarios, mismatches are likely to occur due to both environmental and instrumental factors. When a mismatched signal

Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States.

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Ting, Alan; Edwards, Leah Bennett

2004-02-27

Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.

Spontaneous Improvement of Compensatory Knee Flexion After Surgical Correction of Mismatch Between Pelvic Incidence and Lumbar Lordosis.

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Cheng, Xiaofei; Zhang, Feng; Wu, Jigong; Zhu, Zhenan; Dai, Kerong; Zhao, Jie

2016-08-15

A retrospective study. The aim of this study was to investigate the correlation between pelvic incidence (PI) and lumbar lordosis (LL) mismatch and knee flexion during standing in patients with lumbar degenerative diseases and to examine the effects of surgical correction of the PI-LL mismatch on knee flexion. Only several studies focused on knee flexion as a compensatory mechanism of the PI-LL mismatch. Little information is currently available on the effects of lumbar correction on knee flexion in patients with the PI-LL mismatch. A group of patients with lumbar degenerative diseases were divided into PI-LL match group (PI-LL ≤ 10°) and PI-LL mismatch group (PI-LL > 10°). A series of radiographic parameters and knee flexion angle (KFA) were compared between the two groups. The PI-LL mismatch group was further subdivided into operative and nonoperative group. The changes in KFA with PI-LL were examined. The PI-LL mismatch group exhibited significantly greater sagittal vertical axis (SVA), pelvic tilt (PT) and KFA, and smaller LL, thoracic kyphosis (TK), and sacral slope than the PI-LL match group. PI-LL, LL, PI, SVA, and PT were significantly correlated with KFA in the PI-LL mismatch group. From baseline to 6-month follow-up, all variables were significantly different in the operative group with the exception of PI, although there was no significant difference in any variable in the nonoperative group. The magnitude of surgical correction in the PI-LL mismatch was significantly correlated with the degree of spontaneous changes in KFA, PT, and TK. The PI-LL mismatch would contribute to compensatory knee flexion during standing in patients with lumbar degenerative disease. Surgical correction of the PI-LL mismatch could lead to a spontaneous improvement of compensatory knee flexion. The degree of improvement in knee flexion depends in part on the amount of correction in the PI-LL mismatch. 3.

Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.

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Hirayasu, Y; Potts, G F; O'Donnell, B F; Kwon, J S; Arakaki, H; Akdag, S J; Levitt, J J; Shenton, M E; McCarley, R W

1998-09-01

The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

Science.gov (United States)

Joseph, Thomas T; Osman, Roman

2012-01-01

In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of

Impact of aortic prosthesis-patient mismatch on left ventricular mass regression.

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Alassal, Mohamed A; Ibrahim, Bedir M; Elsadeck, Nabil

2014-06-01

Prostheses used for aortic valve replacement may be small in relation to body size, causing prosthesis-patient mismatch and delaying left ventricular mass regression. This study examined the effect of prosthesis-patient mismatch on regression of left ventricular mass after aortic valve replacement. We prospectively studied 96 patients undergoing aortic valve replacement between 2007 and 2012. Mean and peak gradients and indexed effective orifice area were measured by transthoracic echocardiography at 3 and 6 months postoperatively. Patient-prosthesis mismatch was defined as indexed effective orifice area ≤0.85 cm(2)·m(-2). Moderate prosthesis-patient mismatch was present in 25% of patients. There were no significant differences in demographic and operative data between patients with and without prosthesis-patient mismatch. Left ventricular dimensions, posterior wall thickness, transvalvular gradients, and left ventricular mass decreased significantly after aortic valve replacement in both groups. The interventricular septal diameter and left ventricular mass index regression, and left ventricular ejection fraction were better in patients without prosthesis-patient mismatch. There was a significant positive correlation between the postoperative indexed effective orifice area of each valve prosthesis and the rate of left ventricular mass regression. Prosthesis-patient mismatch leads to higher transprosthetic gradients and impaired left ventricular mass regression. A small-sized valve prosthesis does not necessarily result in prosthesis-patient mismatch, and may be perfectly adequate in patient with small body size. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Unaccusative Mismatches in Japanese.

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Tsujimura, Natsuko

Two instances of unaccusative verb mismatches in Japanese are examined. An unaccusative mismatch is the situation in which a different accusative diagnostic singles out different classes of intransitive verbs within and across languages. One type of unaccusative mismatch has to do with group C verbs, or verbs of manner with protagonist control.…

Correlation of hepatospleno-scintigraphic findings with HBe antigenicity in chronic hepatitis B

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Song, K S; Chun, K S; Chung, S K; Bahk, Y W [Catholic Medical College, Seoul (Korea, Republic of)

1983-12-15

Radioimmunoassay plays an important role in diagnosing the hepatitis B and in clinical assessment of the course of the disease as well. Among a number of antigens, antibodies and enzymes related with hepatitis, HBe Ag, DNA polymerase, IgM-HBc-antibody, {delta} Ag have been known as useful indicators of ongoing infectivity of hepatitis B. The present study has been undertaken to correlate the HBe antigenicity with hepatospleno-scintigraphic findings in hepatitis. The study covered a 10 month period from September 1982 through to July 1983. We reviewed and analyzed the hepatospeno-scintgraphic findings and the results of radioimmuassays in 32 patients of chronic hepatitis seen at St. Mary Hospital, Catholic Medical College. Hepatitis B was diagnosed either when HBs Ag was positive or Anti-HBc wa positive even if HBs Ag was negative. We classified the HBe antigenicity into two groups of HBe Ag(+) and HBe(-) and analyzed the scintgraphic findings in terms of liver size, motting, splenomegaly and splenic shift. From the present study, it is concluded that the activity of hepatitis B can not be assessed by the findings of hepatospleno-scintigram so far as the activity is determined on the basis of the positive HBe Ag, which has been believed to indicated continuing viral replication.

Correlation of hepatospleno-scintigraphic findings with HBe antigenicity in chronic hepatitis B

International Nuclear Information System (INIS)

Song, K. S.; Chun, K. S.; Chung, S. K.; Bahk, Y. W.

1983-01-01

Radioimmunoassay plays an important role in diagnosing the hepatitis B and in clinical assessment of the course of the disease as well. Among a number of antigens, antibodies and enzymes related with hepatitis, HBe Ag, DNA polymerase, IgM-HBc-antibody, δ Ag have been known as useful indicators of ongoing infectivity of hepatitis B. The present study has been undertaken to correlate the HBe antigenicity with hepatospleno-scintigraphic findings in hepatitis. The study covered a 10 month period from September 1982 through to July 1983. We reviewed and analyzed the hepatospeno-scintgraphic findings and the results of radioimmuassays in 32 patients of chronic hepatitis seen at St. Mary Hospital, Catholic Medical College. Hepatitis B was diagnosed either when HBs Ag was positive or Anti-HBc wa positive even if HBs Ag was negative. We classified the HBe antigenicity into two groups of HBe Ag(+) and HBe(-) and analyzed the scintgraphic findings in terms of liver size, motting, splenomegaly and splenic shift. From the present study, it is concluded that the activity of hepatitis B can not be assessed by the findings of hepatospleno-scintigram so far as the activity is determined on the basis of the positive HBe Ag, which has been believed to indicated continuing viral replication

Immunohistochemical detection and correlation between MHC antigen and cell-mediated immune system in recurrent glioma by APAAP method.

Science.gov (United States)

Miyagi, K; Ingram, M; Techy, G B; Jacques, D B; Freshwater, D B; Sheldon, H

1990-09-01

As part of an on-going clinical trial of immunotherapy for recurrent malignant gliomas, using alkaline phosphatase-anti-alkaline phosphatase method with monoclonal antibodies, we investigated the correlation between expression of the major histocompatibility complex (MHC) and the subpopulation of tumor-infiltrating lymphocytes (TILs) in 38 glioma specimens (20 grade IV, 11 grade III, and 7 grade II) from 33 patients. Thirty specimens (78.9%) were positive to class I MHC antigen and 20 (52.6%) were positive to class II MHC antigen. The correlations between class I MHC antigen expression and the number of infiltrating T8 (p less than 0.01), and also between class II MHC antigen expression and the number of infiltrating T4 (p less than 0.05) were significant. We conclude that TILs are the result of immunoreaction (host-defense mechanism). 31.6% of specimens had perivascular infiltration of T cells. The main infiltrating lymphocyte subset in moderate to marked perivascular cuffing was T4. Our results may indicate that lack of MHC antigen on the glioma cell surface has a share in the poor immunogenicity in glioma-bearing patients. In addition, considering the effector/target ratio, the number of infiltrating lymphocytes against glioma cells was too small, so the immunological intervention seems to be essential in glioma therapy. Previous radiation therapy and chemotherapy, including steroid therapy, did not influence lymphocyte and macrophage infiltration.

Allorecognition of HLA-C mismatches by CD8+ T cells in hematopoietic stem cell transplantation is a complex interplay between mismatched peptide binding region residues, HLA-C expression and HLA-DPB1 disparities

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Florence Bettens

2016-12-01

Full Text Available HLA-C locus mismatches are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C mismatches we have developed a one-way in vitro mixed lymphocyte reaction (MLR assay allowing to quantify activated CD56-CD137+CD8+ lymphocytes in HLA-C incompatible combinations. T cell-mediated alloresponses were correlated with genetic markers such as HLA-C mRNA expression and the number of amino acid mismatches in the α1/α2 domains (peptide binding region. Because of the high rate of HLA-DPB1 incompatibilities in HLA-A, B, C, DRB1 and DQB1 matched unrelated HSCT patient/donor pairs, the impact of HLA-DPB1 mismatching, a potential bystander of CD4+ T cell activation, was also considered. Heterogeneous alloresponses were measured in 63 HLA-C mismatched pairs with a positive assay in 52% of the combinations (2.3-18.6% activated CTLs, representing 24 different HLA-A~B~DRB1~DQB1 haplotypes. There was no correlation between measured alloresponses and mRNA expression of the mismatched HLA-C alleles. The HLA-C*03:03/03:04 mismatch did not induce any positive alloresponse in 5 MLRs. We also identified HLA-C*02:02 and HLA-C*06:02 as mismatched alleles with lower immunogenicity, and HLA-C*14:02 as a more immunogenic mismatch. A difference of at least 10 amino acid residues known to impact peptide/TCR binding and a bystander HLA-DPB1 incompatibility had a significant impact on CTL alloreactivity (p=0.021. The same HLA-C mismatch, when recognized by two different responders with the same HLA haplotypes, was recognized differently, emphasizing the role of the T-cell repertoire of responding cells. In conclusion, mismatched HLA-C alleles differing by10 or more amino acids in the peptide/TCR binding

Patient - implant dimension mismatch in total knee arthroplasty: Is it worth worrying? An Indian scenario

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Jai Thilak

2016-01-01

Full Text Available Background: The correct sizing of the components in both anteroposterior and mediolateral (ML dimensions is crucial for the success of a total knee arthroplasty (TKA. The size of the implants selected is based on the intraoperative measurements. The currently used TKA implants available to us are based on morphometric measurements obtained from a Western/Caucasian population. Hence, the risk of component ML mismatch is more common in Asian sub-population, as they are of a smaller built and stature. This study aims to look into the following aspects agnitude of the ML mismatch between the femoral component and the patient′s anatomical dimension, evaluation of gender variations in distal femur dimensions, and gender-wise and implant-wise correlation of ML mismatch. Materials and Methods: Intraoperatively, the distal femoral dimensions were measured using sterile calipers after removing the osteophytes and compared with the ML dimension of the implant used. ML mismatch length thus obtained is correlated with the various parameters. Results: Males showed larger distal femoral dimensions when compared to females. Males had larger ML mismatch. None of the implants used perfectly matched the patient′s anatomical dimensions. Patients with larger mismatch had lower scorings at 2 years postoperative followup. Conclusion: Implant manufacturers need to design more options of femoral implants for a better fit in our subset of patients. The exact magnitude of mismatch which can cause functional implications need to be made out. The mismatch being one of the important factors for the success of the surgery, we should focus more on this aspect.

Mismatch repair genes in Lynch syndrome: a review

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Felipe Cavalcanti Carneiro da Silva

Full Text Available Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2; mutL homolog 1 (MLH1; mutS homolog 6 (MSH6; postmeiotic segregation increased 2 (PMS2; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade

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Sinda Bigenzahn

2016-01-01

Full Text Available Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT with costimulation blockade (CB, but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b mice received nonmyeloablative total body irradiation (3 Gy, costimulation blockade (anti-CD40L mAb and CTLA4Ig, and 2×107 bone marrow cells (BMC from either of three donor strains: Balb/c (H2d (MHC plus multiple minor histocompatibility antigen (mHAg mismatched, B10.D2 (H2d or B10.A (H2a (both MHC mismatched, but mHAg matched. Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p<0.05 for each donor strain versus B10.D2. Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p<0.05. Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

Science.gov (United States)

Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

2016-05-01

Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

Early CT perfusion mismatch in acute stroke is not time-dependent but relies on collateralization grade

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Baumgarten, Louisa von; Straube, Andreas [University of Munich Hospitals, Department of Neurology, Munich (Germany); Thierfelder, Kolja M.; Beyer, Sebastian E.; Baumann, Alena B.; Bollwein, Christine; Reiser, Maximilian F.; Sommer, Wieland H. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Janssen, Hendrik [Ludwig-Maximilians-University Hospital Munich, Department of Neuroradiology, Munich (Germany)

2016-04-15

Factors that determine the extent of the penumbra in the initial diagnostic workup using whole brain CT Perfusion (WB-CTP) remain unclear. The purpose of the current study was to determine a possible dependency of the initial mismatch size between cerebral blood flow (CBF) and cerebral blood volume (CBV) from time after symptom onset, leptomeningeal collateralization, and occlusion localization in acute middle cerebral artery (MCA) infarctions. Out of an existing cohort of 992 consecutive patients receiving multiparametric CT scans including WB-CTP due to suspected stroke, we included patients who had (1) a witnessed time of symptom onset, (2) an infarction of the MCA territory as documented by follow-up imaging, and (3) an initial CBF volume of >10 ml. CBF and CBV lesion sizes, collateralization grade, and the site of occlusion were determined. We included 103 patients. Univariate analysis showed that time from symptom onset (168 +/- 91.2 min) did not correlate with relative or absolute mismatch volumes (p = 0.458 and p = 0.921). Higher collateralization gradings were associated with small absolute mismatch volumes (p = 0.004 and p < 0.001). Internal carotid artery (ICA) occlusions were associated with large absolute mismatch volumes (p = 0.004). Multivariate analysis confirmed that ICA occlusion was associated with large absolute mismatch volumes (p = 0.005), and high collateral grade was associated with small absolute mismatch volumes (p = 0.017). There is no significant correlation between initial CTP mismatch and time after symptom onset. Predictors of mismatch size include the extent of the collaterals and a proximal location of the occlusion. (orig.)

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

Directory of Open Access Journals (Sweden)

Thomas T Joseph

Full Text Available In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the

Hydrophobic mismatch triggering texture defects in membrane gel domains

DEFF Research Database (Denmark)

Dreier, J.; Brewer, J.R.; Simonsen, Adam Cohen

2013-01-01

higher mismatch values correlate with a vortex-type texture. The defect pattern created during early growth persists in larger domains, and a minimal model incorporating the anisotropic line tension and the vortex energy can rationalize this finding. The results suggest that the lipid composition...

Educational Mismatch and Self-Employment

Science.gov (United States)

Bender, Keith A.; Roche, Kristen

2013-01-01

Previous research on educational mismatch concentrates on estimating its labor market consequences but with a focus on wage and salary workers. This paper examines the far less studied influence of mismatch on the self-employed. Using a sample of workers in science and engineering fields, results show larger earnings penalties for mismatch among…

Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

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Sayar, Ilyas; Akbas, Emin Murat; Isik, Arda; Gokce, Aysun; Peker, Kemal; Demirtas, Levent; Gürbüzel, Mehmet

2015-09-01

Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

Carcinoembryonic antigen (CEA)

International Nuclear Information System (INIS)

Ephraim, K.H.; Cox, P.H.; Hamer, C.J.A. v.d.; Berends, W.; Delhez, H.

1977-01-01

The carcinoembryonic antigen (CEA) is a complex of antigen determinants and also the carrier of these determinants. Chemically it is a glycoprotein. Its occurrence in blood serum or urine is correlated with malignant disease. Several radioimmunoassays (RIA) have been developed, one by Hoffmann-Laroche and one by the Rotterdam Radiotherapeutic Institute. Both methods and the Hoffmann assay kit are tested. Specifications are given for isolation of the antigen, preparation of the antiserum, and the execution of the RIA. Biochemical and clinical aspects are discussed

Entanglement verification with detection efficiency mismatch

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Zhang, Yanbao; Lütkenhaus, Norbert

Entanglement is a necessary condition for secure quantum key distribution (QKD). When there is an efficiency mismatch between various detectors used in the QKD system, it is still an open problem how to verify entanglement. Here we present a method to address this problem, given that the detection efficiency mismatch is characterized and known. The method works without assuming an upper bound on the number of photons going to each threshold detector. Our results suggest that the efficiency mismatch affects the ability to verify entanglement: the larger the efficiency mismatch is, the smaller the set of entangled states that can be verified becomes. When there is no mismatch, our method can verify entanglement even if the method based on squashing maps [PRL 101, 093601 (2008)] fails.

Correlation between CD16a binding and immuno effector functionality of an antigen specific immunoglobulin Fc fragment (Fcab).

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Kainer, Manuela; Antes, Bernhard; Wiederkum, Susanne; Wozniak-Knopp, Gordana; Bauer, Anton; Rüker, Florian; Woisetschläger, Max

2012-10-15

Antigen binding immunoglobulin Fc fragments (Fcab) are generated by engineering loop regions in the CH3 domain of human IgG1 Fc. Variants of an Fcab specific for Her-2 were designed to display either enhanced (S239D:A330L:I332E) or diminished (L234A:L235A) binding affinities to the Fc receptor CD16a based on mutations described previously. The two mutant Fcab proteins demonstrated the expected modulation of CD16a binding. Interaction with recombinant or cell surface expressed Her-2 was unaffected in both mutants compared to the parental Fcab. Binding affinities for CD16a correlated with the ADCC-potencies of the Fcab variants. Additional studies indicated that the L234A:L235A variant Fcab had equivalent structural features as the unmodified Fcab since their DSC profiles were similar and antigen binding after re-folding upon partial heat denaturation had not changed. Introduction of the S239D:A330L:I332E mutations resulted in a significant reduction of the CH2 domain melting temperature, a moderate decrease of the thermal transition of the CH3 domain and lower antigen binding after thermal stress compared to the parental Fcab. We conclude that the known correlation between CD16a binding affinity and ADCC potency is also valid in Fcab proteins and that antigen specific Fcab molecules can be further engineered for fine tuning of immuno effector functions. Copyright © 2012 Elsevier Inc. All rights reserved.

Heterogenous mismatch-repair status in colorectal cancer

DEFF Research Database (Denmark)

Joost, Patrick; Veurink, Nynke; Holck, Susanne

2014-01-01

BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

Correlative Light-Electron Microscopy of Lipid-Encapsulated Fluorescent Nanodiamonds for Nanometric Localization of Cell Surface Antigens.

Science.gov (United States)

Hsieh, Feng-Jen; Chen, Yen-Wei; Huang, Yao-Kuan; Lee, Hsien-Ming; Lin, Chun-Hung; Chang, Huan-Cheng

2018-02-06

Containing an ensemble of nitrogen-vacancy centers in crystal matrices, fluorescent nanodiamonds (FNDs) are a new type of photostable markers that have found wide applications in light microscopy. The nanomaterial also has a dense carbon core, making it visible to electron microscopy. Here, we show that FNDs encapsulated in biotinylated lipids (bLs) are useful for subdiffraction imaging of antigens on cell surface with correlative light-electron microscopy (CLEM). The lipid encapsulation enables not only good dispersion of the particles in biological buffers but also high specific labeling of live cells. By employing the bL-encapsulated FNDs to target CD44 on HeLa cell surface through biotin-mediated immunostaining, we obtained the spatial distribution of these antigens by CLEM with a localization accuracy of ∼50 nm in routine operations. A comparative study with dual-color imaging, in which CD44 was labeled with FND and MICA/MICB was labeled with Alexa Fluor 488, demonstrated the superior performance of FNDs as fluorescent fiducial markers for CLEM of cell surface antigens.

Standardized assessment to enhance the diagnostic value of prostate volume; Part II: Correlation with prostate-specific antigen levels

NARCIS (Netherlands)

Aarnink, R. G.; de la Rosette, J. J.; Huynen, A. L.; Giesen, R. J.; Debruyne, F. M.; Wijkstra, H.

1996-01-01

Standardized estimations of prostate volumes are used for interpretation of prostate specific antigen (PSA) levels. In 243 patients with clinically benign diagnosis, automated and reference prostate volumes and transition zone volumes are correlated to PSA levels. Besides, growth curves of PSA level

Potential radioimmunoassay system for detection of Hanganutziu-Deicher type heterophile antigen(s) and antibodies in tissues and fluids

Energy Technology Data Exchange (ETDEWEB)

Mukuria, J C; Naiki, Masaharu; Hashimoto, Masato; Nishiura, Katsumi; Okabe, Masahiro; Kato, Shiro

1985-06-12

A relatively simple, specific and sensitive radioimmunoassay system has been developed for the detection of heterophile Hanganutziu-Deicher (H-D) antigen(s) and antibodies. The SVI-labeled H-D antigen-active molecule used for the assay is a bovine erythrocyte major glycoprotein previously found to have a strong H-D antigen potency. Different H-D antigen-active molecules were compared for heterophile H-D antigen potency. Eight different lung cancer tissues were assayed for H-D antigen. The sera from the 8 lung cancer patients were also screened by ELISA and RIA in an attmept to correlate expression of H-D antigen on tissues with elevation of H-D antibodies.

Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism

NARCIS (Netherlands)

J.L.H.R. Bosch (Ruud); W.C.J. Hop (Wim); C.H. Bangma (Chris); W.J. Kirkels (Wim); F.H. Schröder (Fritz)

1995-01-01

textabstractThe correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men

Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers.

Science.gov (United States)

Thompson, Alexander J V; Nguyen, Tin; Iser, David; Ayres, Anna; Jackson, Kathy; Littlejohn, Margaret; Slavin, John; Bowden, Scott; Gane, Edward J; Abbott, William; Lau, George K K; Lewin, Sharon R; Visvanathan, Kumar; Desmond, Paul V; Locarnini, Stephen A

2010-06-01

Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker.

A teleofunctional account of evolutionary mismatch.

Science.gov (United States)

Cofnas, Nathan

When the environment in which an organism lives deviates in some essential way from that to which it is adapted, this is described as "evolutionary mismatch," or "evolutionary novelty." The notion of mismatch plays an important role, explicitly or implicitly, in evolution-informed cognitive psychology, clinical psychology, and medicine. The evolutionary novelty of our contemporary environment is thought to have significant implications for our health and well-being. However, scientists have generally been working without a clear definition of mismatch. This paper defines mismatch as deviations in the environment that render biological traits unable, or impaired in their ability, to produce their selected effects (i.e., to perform their proper functions in Neander's sense). The machinery developed by Millikan in connection with her account of proper function, and with her related teleosemantic account of representation, is used to identify four major types, and several subtypes, of evolutionary mismatch. While the taxonomy offered here does not in itself resolve any scientific debates, the hope is that it can be used to better formulate empirical hypotheses concerning the effects of mismatch. To illustrate, it is used to show that the controversial hypothesis that general intelligence evolved as an adaptation to handle evolutionary novelty can, contra some critics, be formulated in a conceptually coherent way.

[Constitutional mismatch repair deficiency syndrome

NARCIS (Netherlands)

Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

2015-01-01

BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

Circulating fibroblast activation protein activity and antigen levels correlate strongly when measured in liver disease and coronary heart disease

NARCIS (Netherlands)

S.U. de Willige; Keane, F.M. (Fiona M.); Bowen, D.G. (David G.); J.J.M.C. Malfliet (Joyce); Zhang, H.E. (H. Emma); Maneck, B. (Bharvi); G. McCaughan (Geoff); F.W.G. Leebeek (Frank); D.C. Rijken (Dingeman); Gorrell, M.D. (Mark D.)

2017-01-01

textabstractBackground and aim: Circulating fibroblast activation protein (cFAP) is a constitutively active enzyme expressed by activated fibroblasts that has both dipeptidyl peptidase and endopeptidase activities. We aimed to assess the correlation between cFAP activity and antigen levels and to

antigen from irradiated Trypanosoma evansi and its correlation with antibody forming

International Nuclear Information System (INIS)

Sadi, Suharni; Arifin, Muchson

1998-01-01

In this research parasites of T. evansi was weakened by gamma irradiation dose of 300 Gy. This antigen being before being used was coupled/bounded with a carrier (Freund's adjuvant). West star rats of 3 months old were as used as treated animal. These animal were divided into 4 groups contained 5 rats. Group I (Control) was untreated animals, Group II (radiation) the animals were irradiated with a low dose 0.5 Gy. Group III Immunization) the animals were immunized with irradiated antigen, and Group IV (Immunization and radiation) the animal were immunized and then irradiated with a low dose of 0.5 Gy. Immunization were done by intraperitoneal route with irradiated antigen (0.5-1ml). These results were as follows : the polyclonal antibody forming of Group I (control), Group II (Radiation), Group III (Immunization), and Group IV (Immunization and radiation) were 6.34; 5.96; and 5.88 mg/ml, respectively. Group III (Immunization) Yielded polyclonal antibody a little higher than the other treated animals. Even though the antigen was coupled with a carrier, it seemed that it did not influence the parasites variant antigenic types (VTA). (author)

Localization by interaural time difference (ITD): Effects of interaural frequency mismatch

International Nuclear Information System (INIS)

Bonham, B.H.; Lewis, E.R.

1999-01-01

A commonly accepted physiological model for lateralization of low-frequency sounds by interaural time delay (ITD) stipulates that binaural comparison neurons receive input from frequency-matched channels from each ear. Here, the effects of hypothetical interaural frequency mismatches on this model are reported. For this study, the cat close-quote s auditory system peripheral to the binaural comparison neurons was represented by a neurophysiologically derived model, and binaural comparison neurons were represented by cross-correlators. The results of the study indicate that, for binaural comparison neurons receiving input from one cochlear channel from each ear, interaural CF mismatches may serve to either augment or diminish the effective difference in ipsilateral and contralateral axonal time delays from the periphery to the binaural comparison neuron. The magnitude of this increase or decrease in the effective time delay difference can be up to 400 μs for CF mismatches of 0.2 octaves or less for binaural neurons with CFs between 250 Hz and 2.5 kHz. For binaural comparison neurons with nominal CFs near 500 Hz, the 25-μs effective time delay difference caused by a 0.012-octave CF mismatch is equal to the ITD previously shown to be behaviorally sufficient for the cat to lateralize a low-frequency sound source. copyright 1999 Acoustical Society of America.

A Modified Protocol with Improved Detection Rate for Mis-Matched Donor HLA from Low Quantities of DNA in Urine Samples from Kidney Graft Recipients.

Directory of Open Access Journals (Sweden)

Janette Kwok

Full Text Available Urine from kidney transplant recipient has proven to be a viable source for donor DNA. However, an optimized protocol would be required to determine mis-matched donor HLA specificities in view of the scarcity of DNA obtained in some cases.In this study, fresh early morning urine specimens were obtained from 155 kidney transplant recipients with known donor HLA phenotype. DNA was extracted and typing of HLA-A, B and DRB1 loci by polymerase chain reaction-specific sequence primers was performed using tailor-made condition according to the concentration of extracted DNA.HLA typing of DNA extracted from urine revealed both recipient and donor HLA phenotypes, allowing the deduction of the unknown donor HLA and hence the degree of HLA mis-match. By adopting the modified procedures, mis-matched donor HLA phenotypes were successfully deduced in all of 35 tested urine samples at DNA quantities spanning the range of 620-24,000 ng.This urine-based method offers a promising and reliable non-invasive means for the identification of mis-matched donor HLA antigens in kidney transplant recipients with unknown donor HLA phenotype or otherwise inadequate donor information.

Carcinoembryonic Antigen Level in Liver Disease

Energy Technology Data Exchange (ETDEWEB)

Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1978-09-15

Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

Carcinoembryonic Antigen Level in Liver Disease

International Nuclear Information System (INIS)

Choi, Kyoo Ok; Kim, Ki Whang; Park, Chang Yun

1978-01-01

Carcinoembryonic antigen was initially known as tumor specific antigen and had a potential diagnostic value in the detection of digestive tract malignancies. However, subsequent studies showed CEA and CEA-like antigen present in benign disease, particularly in liver. We had collected sera from 58 patients who had liver scan and later were diagnosed clinically and histologically as liver disease. We estimated CEA values and correlations were made with liver function tests in liver cirrhosis cases. The results: 1) The raised plasma carcinoembryonic antigen level were found in 13 (68.4%) of 19 patients cirrhosis, 5 (27.8%) of 18 patients in hepatoma, 5 (71%) of 7 patients in chronic active hepatitis, all 3 patients in liver abscesses, 2 (66.7%) of 3 patients in liver abscesses, 2 (66.7%) of 3 patients in obstructive biliary disease and none in each one patient of traumatic liver hematoma, subphrenic abscess and clonorchiasis. 2) There is no linear correlation between carcinoembryonic antigen level and liver function tests including serum bilirubin, alkaline phosphatase, SGOT and prothrombin time in liver patients.

Investigating methods for determining mismatch in near side vehicle impacts - biomed 2009.

Science.gov (United States)

Loftis, Kathryn; Martin, R Shayn; Meredith, J Wayne; Stitzel, Joel

2009-01-01

occupants. By analyzing the vehicle information and occupant injuries, it was found that the vehicle mismatch problem involves differences in vehicle weights and heights and also results in severe injuries to multiple body regions for the near side occupant involved. There was a low correlation of vehicle height difference to occupant ISS.

Mutations in the prostate specific antigen (PSA/KLK3) correlate with male infertility.

Science.gov (United States)

Gupta, Nishi; Sudhakar, Digumarthi V S; Gangwar, Pravin Kumar; Sankhwar, Satya Narayan; Gupta, Nalini J; Chakraborty, Baidyanath; Thangaraj, Kumarasamy; Gupta, Gopal; Rajender, Singh

2017-09-11

Prostate specific antigen (PSA/KLK3) is known to be the chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility. Recent research has found that semenogelins also play significant roles in sperm fertility by affecting hyaluronidase activity, capacitation and motility, thereby making PSA important for sperm fertility beyond simple semen liquefaction. PSA level in semen has been shown to correlate with sperm motility, suggesting that PSA level/activity can affect fertility. However, no study investigating the genetic variations in the KLK3/PSA gene in male fertility has been undertaken. We analyzed the complete coding region of the KLK3 gene in ethnically matched 875 infertile and 290 fertile men to find if genetic variations in KLK3 correlate with infertility. Interestingly, this study identified 28 substitutions, of which 8 were novel (not available in public databases). Statistical comparison of the genotype frequencies showed that five SNPs, rs266881 (OR = 2.92, P  C, was more freuqent in the control group, showing protective association. Our findings suggest that polymorphisms in the KLK3 gene correlate with infertility risk.

Zero energy buildings and mismatch compensation factors

DEFF Research Database (Denmark)

Lund, Henrik; Marszal, Anna Joanna; Heiselberg, Per

2011-01-01

This paper takes an overall energy system approach to analysing the mismatch problem of zero energy and zero emission buildings (ZEBs). The mismatch arises from hourly differences in energy production and consumption at the building level and results in the need for exchange of electricity via...... the public grid even though the building has an annual net-exchange of zero. This paper argues that, when looked upon from the viewpoint of the overall electricity supply system, a mismatch can be both negative and positive. Moreover, there are often both an element of levelling out mismatches between...... of the energy production unit. Based on historical data for the electricity supply area in western Denmark, this paper makes a first attempt to quantify mismatch compensation factors. The results indicate that such compensation factors are a little below one for buildings with photovoltaics (PV) and a little...

Thickness dependent properties of CMR Manganite thin films on lattice mismatched substrates: Distinguishing Strain and Interface Effects

Science.gov (United States)

Davidson, Anthony, III; Kolagani, Rajeswari; Bacharova, Ellisaveta; Yong, Grace; Smolyaninova, Vera; Schaefer, David; Mundle, Rajeh

2007-03-01

Epitaxial thin films of CMR manganite materials have been known to show thickness dependent electrical and magnetic properties on lattice mismatched substrates. Below a critical thickness, insulator-metal transition is suppressed. These effects have been largely attributed to the role of bi-axial lattice mismatch strain. Our recent results of epitaxial thin films of La0.67Ca0.33MnO3 (LCMO) on two substrates with varying degrees of compressive lattice mismatch indicate that, in addition to the effect of lattice mismatch strain, the thickness dependence of the properties are influenced by other factors possibly related to the nature of the film substrate interface and defects such as twin boundaries. We have compared the properties of LCMO films on (100) oriented LaAlO3 and (001) oriented NdCaAlO4 both of which induce compressive bi-axial strain. Interestingly, the suppression of the insulator-metal transition is less in films on NCAO which has a larger lattice mismatch. We will present results correlating the electrical and magneto transport properties with the structure and morphology of the films.

Measurement of mismatch loss in CPV modul

Science.gov (United States)

Liu, Mingguo; Kinsey, Geoffrey S.; Bagienski, Will; Nayak, Adi; Garboushian, Vahan

2012-10-01

A setup capable of simultaneously measuring I-V curves of a full string and its individual cells has been developed. This setup enables us to measure mismatch loss from individual cells in concert with various string combinations under varying field conditions. Mismatch loss from cells to plates at different off-track angles and mismatch from plates to strings in Amonix system during normal operation have been investigated.

Correlation between the e-antigen, Pre-S2 antigen and DNA of hepatitis B virus

International Nuclear Information System (INIS)

Cai Changhui; Liang Jinsheng

2006-01-01

Objective: To study the relationship between the hepatitis B e-antigen (HBeAg), Pre-S1 antigen (Pre-S1), Pre-S2 antigen (Pre-S2) and DNA of hepatitis B virus (HBV). Methods: The blood samples of 268 cases of viral B hepatitis were collected. The HBV DNA of all samples were tested by fluorescent-quantitating PCR method, and HBeAg were assayed by time-resolved fluoro-immunoassay method, and their Pre-S1 and Pre-S2 were assayed by enzyme linked immunosorbentassay method. Results: The positive rates of HBeAg, Pre-S1 and Pre-S2 in HBV DNA positive group were 48.2%, 76.4% and 100% respectively, and 1.6%, 36.3% and 32.3% respectively in HBV DNA negative group. There was significantly difference between the HBeAg, Pre-S1 and Pre-S2 positive rates of the two groups (Chi-square test, P<0.01). Conclusions: There was positive relationship between the HBeAg, Pre-S1, Pre-S2 and DNA which all were indicators of HBV reproduction. Comparing to HBV DNA, Pre-S2 was the most, Pre-S1 the second, and HBeAg the third sensitive indicator for evaluating HBV reproduction. Pre-S1 and Pre-S2 could be used as the supplementary indicator for the reproduction of HBV. (authors)

Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD)

OpenAIRE

Ramchander, N. C.; Ryan, N. A. J.; Crosbie, E. J.; Evans, D. G.

2017-01-01

BackgroundConstitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of th...

Direct Mismatch Characterization of femto-Farad Capacitors

KAUST Repository

Omran, Hesham

2015-08-17

Reducing the capacitance of programmable capacitor arrays, commonly used in analog integrated circuits, is necessary for low-energy applications. However, limited mismatch data is available for small capacitors. We report mismatch measurement for a 2fF poly-insulator-poly (PIP) capacitor, which is the smallest reported PIP capacitor to the best of the authors’ knowledge. Instead of using complicated custom onchip circuitry, direct mismatch measurement is demonstrated and verified using Monte Carlo Simulations and experimental measurements. Capacitive test structures composed of 9 bit programmable capacitor arrays (PCAs) are implemented in a low-cost 0:35m CMOS process. Measured data is compared to mismatch of large PIP capacitors, theoretical models, and recently published data. Measurement results indicate an estimated average relative standard deviation of 0.43% for the 2fF unit capacitor, which is better than the reported mismatch of metal-oxide-metal (MOM) fringing capacitors implemented in an advanced 32nm CMOS process.

Direct Mismatch Characterization of femto-Farad Capacitors

KAUST Repository

Omran, Hesham; Elafandy, Rami T.; Arsalan, Muhammad; Salama, Khaled N.

2015-01-01

Reducing the capacitance of programmable capacitor arrays, commonly used in analog integrated circuits, is necessary for low-energy applications. However, limited mismatch data is available for small capacitors. We report mismatch measurement for a 2fF poly-insulator-poly (PIP) capacitor, which is the smallest reported PIP capacitor to the best of the authors’ knowledge. Instead of using complicated custom onchip circuitry, direct mismatch measurement is demonstrated and verified using Monte Carlo Simulations and experimental measurements. Capacitive test structures composed of 9 􀀀 bit programmable capacitor arrays (PCAs) are implemented in a low-cost 0:35m CMOS process. Measured data is compared to mismatch of large PIP capacitors, theoretical models, and recently published data. Measurement results indicate an estimated average relative standard deviation of 0.43% for the 2fF unit capacitor, which is better than the reported mismatch of metal-oxide-metal (MOM) fringing capacitors implemented in an advanced 32nm CMOS process.

Impact of mismatched and misaligned laser light sheet profiles on PIV performance

Science.gov (United States)

Grayson, K.; de Silva, C. M.; Hutchins, N.; Marusic, I.

2018-01-01

The effect of mismatched or misaligned laser light sheet profiles on the quality of particle image velocimetry (PIV) results is considered in this study. Light sheet profiles with differing widths, shapes, or alignment can reduce the correlation between PIV images and increase experimental errors. Systematic PIV simulations isolate these behaviours to assess the sensitivity and implications of light sheet mismatch on measurements. The simulations in this work use flow fields from a turbulent boundary layer; however, the behaviours and impacts of laser profile mismatch are highly relevant to any fluid flow or PIV application. Experimental measurements from a turbulent boundary layer facility are incorporated, as well as additional simulations matched to experimental image characteristics, to validate the synthetic image analysis. Experimental laser profiles are captured using a modular laser profiling camera, designed to quantify the distribution of laser light sheet intensities and inform any corrective adjustments to an experimental configuration. Results suggest that an offset of just 1.35 standard deviations in the Gaussian light sheet intensity distributions can cause a 40% reduction in the average correlation coefficient and a 45% increase in spurious vectors. Errors in measured flow statistics are also amplified when two successive laser profiles are no longer well matched in alignment or intensity distribution. Consequently, an awareness of how laser light sheet overlap influences PIV results can guide faster setup of an experiment, as well as achieve superior experimental measurements.

Spatial Mismatch: A Third Generation Survey.

Science.gov (United States)

Eagan, J. Vincent

1999-01-01

The spatial mismatch argument hypothesizes that racial discrimination in the housing market, together with the suburbanization of low skilled jobs, contributes significantly to the high unemployment and/or low wages of inner city minority workers. Surveys recent spatial mismatch literature and discusses policy alternatives, focusing on areas…

Influence of excitation light rejection on forward model mismatch in optical tomography

International Nuclear Information System (INIS)

Hwang, K; Pan, T; Joshi, A; Rasmussen, J C; Bangerth, W; Sevick-Muraca, E M

2006-01-01

Fluorescence enhanced tomography for molecular imaging requires low background for detection and accurate image reconstruction. In this contribution, we show that excitation light leakage is responsible for elevated background and can be minimized with the use of gradient index (GRIN) lenses when using fibre optics to collect propagated fluorescence light from tissue or other biological media. We show that the model mismatch between frequency-domain photon migration (FDPM) measurements and the diffusion approximation prediction is decreased when GRIN lenses are placed prior to the interference filters to provide efficient excitation light rejection. Furthermore, model mismatch is correlated to the degree of excitation light leakage. This work demonstrates the importance of proper light filtering when designing fluorescence optical imaging and tomography

Visual-perceptual mismatch in robotic surgery.

Science.gov (United States)

Abiri, Ahmad; Tao, Anna; LaRocca, Meg; Guan, Xingmin; Askari, Syed J; Bisley, James W; Dutson, Erik P; Grundfest, Warren S

2017-08-01

The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p sensors showed no difference between the different groups. The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

Thermodynamic characterization of tandem mismatches found in naturally occurring RNA

Science.gov (United States)

Christiansen, Martha E.; Znosko, Brent M.

2009-01-01

Although all sequence symmetric tandem mismatches and some sequence asymmetric tandem mismatches have been thermodynamically characterized and a model has been proposed to predict the stability of previously unmeasured sequence asymmetric tandem mismatches [Christiansen,M.E. and Znosko,B.M. (2008) Biochemistry, 47, 4329–4336], experimental thermodynamic data for frequently occurring tandem mismatches is lacking. Since experimental data is preferred over a predictive model, the thermodynamic parameters for 25 frequently occurring tandem mismatches were determined. These new experimental values, on average, are 1.0 kcal/mol different from the values predicted for these mismatches using the previous model. The data for the sequence asymmetric tandem mismatches reported here were then combined with the data for 72 sequence asymmetric tandem mismatches that were published previously, and the parameters used to predict the thermodynamics of previously unmeasured sequence asymmetric tandem mismatches were updated. The average absolute difference between the measured values and the values predicted using these updated parameters is 0.5 kcal/mol. This updated model improves the prediction for tandem mismatches that were predicted rather poorly by the previous model. This new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA duplexes containing tandem mismatches, and, furthermore, should allow for improved prediction of secondary structure from sequence. PMID:19509311

"Clinical-CT mismatch" and the response to systemic thrombolytic therapy in acute ischemic stroke.

Science.gov (United States)

Kent, David M; Hill, Michael D; Ruthazer, Robin; Coutts, Shelagh B; Demchuk, Andrew M; Dzialowski, Imanuel; Wunderlich, Olaf; von Kummer, Rudiger

2005-08-01

Mismatch between clinical deficits and imaging lesions in acute stroke has been proposed as a method of identifying patients who have hypoperfused but still have viable brain, and may be especially apt to respond to reperfusion therapy. We explored this hypothesis using a combined database including 4 major clinical trials of intravenous (IV) thrombolytic therapy. To determine what the radiological correlates of a "matched" functional deficit are, we calculated the relationship between the ASPECT score of the 24-hour (follow-up) CT scan and the 24-hour National Institutes of Health Stroke Scale (NIHSS) score on the subsample with ASPECT scores performed at this time (n=820). Based on this empirical relationship, we computed the absolute difference between the observed baseline ASPECT score and the "expected" score (ie, matched) based on baseline NIHSS for all patients (n=2131). We tested whether patients with better than expected baseline ASPECTS were more likely to benefit from IV recombinant tissue plasminogen activation (rtPA). At 24 hours, there was a strong, linear, negative correlation between NIHSS and ASPECTS (r2=0.33, P<0.0001); on average, an increase of 10 points on NIHSS corresponded to a decrease of approximately 3 points on ASPECTS. At baseline, the average degree of mismatch between the observed and "expected" ASPECTS was 2.1 points (interquartile range, 1.0 to 3.4). However, multiple analyses failed to reveal a consistent relationship between the degree of clinical-CT mismatch at baseline and a patient's likelihood of benefiting from IV rtPA. Clinical-CT mismatch using ASPECT scoring does not reliably identify patients more or less likely to benefit from IV rtPA.

Angular correlation, spin alignment, and systematics of mis-matched {sup 12}C+{sup 12}C inelastic scattering resonances

Energy Technology Data Exchange (ETDEWEB)

Wuosmaa, A.H.; Wiedenhoever, I.; Caggiano, J.; Carpenter, M.P.; Devlin, M.; Heinz, A.; Janssens, R.V.F.; Kondev, F.; Lauritsen, T.; Sarantites, D.G.; Sobotka, L.G.; Battacharyya, P

2003-10-09

Particle gamma-ray angular correlation measurements have been used to study the spin alignment and magnetic-substate population parameters for the 2{sup +}{sub 1} (4.443 MeV) state in {sup 12}C, populated in the {sup 12}C({sup 12}C,{sup 12}C[0{sup +}{sub 2}]){sup 12}C(2{sup +}{sub 1}) inelastic scattering reaction in the vicinity of a prominent, narrow peak in the scattering excitation function. The data show a strong alignment of the spin with the orbital angular momentum, and suggest that the cross section peak corresponds to a spin 14{sup +} resonance at E{sub c.m.}=28.0 MeV. This energy is close to that where a strong peak is also observed in the 0{sup +}{sub 1}+0{sup +}{sub 2} excitation function. A comparison between the data for these two channels lends some support to recent theoretical calculations of resonance behavior for angular-momentum-mismatched channels in {sup 12}C+{sup 12}C inelastic scattering.

JOB MISMATCH – EFFECTS ON WORK PRODUCTIVITY

Directory of Open Access Journals (Sweden)

Magdalena Velciu

2017-12-01

Full Text Available Job matching and finding the best person to the right job inside the right company has become one of the most important and actual challenges of productivity. Not only full employment but the match between the employee and the job, in terms of educational level or field of activity, qualifications and skills of workforce; all have been the new gain of work productivity. Present article synthesizes the theoretical and empirical findings on effects of job mismatch by selecting the main findings about influence of job mismatches on work productivity including both employees and companies sides. on short term overeducation and overqualification could have a positive effect on productivity for one company, but on long term, mismatched worker would be affected by decreasing job satisfaction and lower wages. Also, at macroeconomic level, from a perspective of economy as a whole, job mismatches mean a loss of resources and human capital and could have negative effects on overall productivity. The opposite effects stay at the crossing between the employees, companies, policies and future development. In fact the effects of skill mismatch and productivity is a lost of work potential through inefficient resource (reallocation.

Donor-Recipient Size Mismatch in Paediatric Renal Transplantation

Directory of Open Access Journals (Sweden)

J. Donati-Bourne

2014-01-01

Full Text Available Introduction. End stage renal failure in children is a rare but devastating condition, and kidney transplantation remains the only permanent treatment option. The aim of this review was to elucidate the broad surgical issues surrounding the mismatch in size of adult kidney donors to their paediatric recipients. Methods. A comprehensive literature search was undertaken on PubMed, MEDLINE, and Google Scholar for all relevant scientific articles published to date in English language. Manual search of the bibliographies was also performed to supplement the original search. Results. Size-matching kidneys for transplantation into children is not feasible due to limited organ availability from paediatric donors, resulting in prolonged waiting list times. Transplanting a comparatively large adult kidney into a child may lead to potential challenges related to the surgical incision and approach, vessel anastomoses, wound closure, postoperative cardiovascular stability, and age-correlated maturation of the graft. Conclusion. The transplantation of an adult kidney into a size mismatched paediatric recipient significantly reduces waiting times for surgery; however, it presents further challenges in terms of both the surgical procedure and the post-operative management of the patient’s physiological parameters.

Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea.

Science.gov (United States)

Ishino, Sonoko; Nishi, Yuki; Oda, Soichiro; Uemori, Takashi; Sagara, Takehiro; Takatsu, Nariaki; Yamagami, Takeshi; Shirai, Tsuyoshi; Ishino, Yoshizumi

2016-04-20

The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus The corresponding gene revealed that the activity originates from PF0012, and we named this enzyme Endonuclease MS (EndoMS) as the mismatch-specific Endonuclease. The sequence similarity suggested that EndoMS is the ortholog of NucS isolated from Pyrococcus abyssi, published previously. Biochemical characterizations of the EndoMS homolog from Thermococcus kodakarensis clearly showed that EndoMS specifically cleaves both strands of double-stranded DNA into 5'-protruding forms, with the mismatched base pair in the central position. EndoMS cleaves G/T, G/G, T/T, T/C and A/G mismatches, with a more preference for G/T, G/G and T/T, but has very little or no effect on C/C, A/C and A/A mismatches. The discovery of this endonuclease suggests the existence of a novel mismatch repair process, initiated by the double-strand break generated by the EndoMS endonuclease, in Archaea and some Bacteria. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Currency Mismatch, Balance-sheet effect and Monetary Policy

OpenAIRE

Nakamura, Chikafumi

2011-01-01

This paper analyzes the impact of the currency mismatch between assets and liabilities on monetary policy. The currency mismatch causes macroeconomic instability through balance-sheet effects. To analyze the problem, we apply a small open economy dynamic stochastic general equilibrium model with international credit-market imperfections. As a result, despitethe currency mismatch and high trade openness, a targeting rule to address the terms of trade is not efficient. This result depends on...

Circuit mismatch influence on performance of paralleling silicon carbide MOSFETs

DEFF Research Database (Denmark)

Li, Helong; Munk-Nielsen, Stig; Pham, Cam

2014-01-01

This paper focuses on circuit mismatch influence on performance of paralleling SiC MOSFETs. Power circuit mismatch and gate driver mismatch influences are analyzed in detail. Simulation and experiment results show the influence of circuit mismatch and verify the analysis. This paper aims to give...... suggestions on paralleling discrete SiC MOSFETs and designing layout of power modules with paralleled SiC MOSFETs dies....

Constitutioneel ‘mismatch repair’-deficiëntiesyndroom

NARCIS (Netherlands)

Jongmans, Marjolijn C.; Gidding, Corrie E.; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

2015-01-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. Case description An 8yearold girl was

Mismatch-Shaping Serial Digital-to-Analog Converter

DEFF Research Database (Denmark)

Steensgaard-Madsen, Jesper; Moon, Un-Ku; Temes, Gabor C.

1999-01-01

A simple but accurate pseudo-passive mismatch-shaping D/A converter is described. A digital state machine is used to control the switching sequence of a symmetric two-capacitor network that performs the D/A conversion. The error caused by capacitor mismatch is uncorrelated with the input signal...

Mismatch-Shaped Pseudo-Passive Two-Capacitor DAC

DEFF Research Database (Denmark)

Steensgaard-Madsen, Jesper; Moon, Un-Ku; Temes, Gabor C.

1999-01-01

A simple mismatch-shaping scheme is proposed for a two-capacitor DAC. Unlike in other mismatch-shaping systems, the shaped error is generated by direct filtering of a well-defined bounded signal, which can be generated as white noise. The operation is closely related to a specific digital...

Red blood cell antigen genotype analysis for 9087 Asian, Asian American, and Native American blood donors.

Science.gov (United States)

Delaney, Meghan; Harris, Samantha; Haile, Askale; Johnsen, Jill; Teramura, Gayle; Nelson, Karen

2015-10-01

There has yet to be a comprehensive analysis of blood group antigen prevalence in Asian Americans and Native Americans. There may be ethnic differences in blood group frequencies that would result in clinically important mismatches through transfusion. Blood donors who self-identified as Asian or Native American were tested using a single-nucleotide polymorphism (SNP) DNA array (HEA BeadChip kit, Bioarray Solutions Ltd) that predicts expression of 38 human erythrocyte antigens (HEAs) and by serology for ABO, D, C, M, N, Jk(a) , and Jk(b) . The prevalence of blood group antigens was compared to published European prevalence. Discrepancies between SNP-predicted and serology-detected antigens were tallied. A total of 9087 blood donors were tested from nine Asian and Native American heritages. The predicted prevalence of selected antigens in the RHCE, JK, FY, MNS, LU, CO, and DO blood group systems were variable between Asian populations, but overall not significantly different than Europeans. Compared to European frequencies, Kell blood group allele frequencies were significantly different in the Chinese, Native American, Hawaiian/Pacific Islander, South Asian, and Southeast Asian heritage blood donors; Diego antigens Di(a) and Di(b) were different in donors of Native American and South Asian ancestries (p Asian and Native Americans donors. Several ethnic groups exhibited differences in HEA frequencies compared to Europeans. Genotype-serotype discrepancies were detected in all systems studied. © 2015 AABB.

Selective nanoscale growth of lattice mismatched materials

Science.gov (United States)

Lee, Seung-Chang; Brueck, Steven R. J.

2017-06-20

Exemplary embodiments provide materials and methods of forming high-quality semiconductor devices using lattice-mismatched materials. In one embodiment, a composite film including one or more substantially-single-particle-thick nanoparticle layers can be deposited over a substrate as a nanoscale selective growth mask for epitaxially growing lattice-mismatched materials over the substrate.

Impact of valve prosthesis-patient mismatch estimated by echocardiographic-determined effective orifice area on long-term outcome after aortic valve replacement.

Science.gov (United States)

Florath, Ines; Albert, Alexander; Rosendahl, Ulrich; Ennker, Ina Carolin; Ennker, Jrgen

2008-06-01

The impact of valve prosthesis-patient mismatch on long-term outcome after aortic valve replacement estimated by various variables such as projected indexed effective orifice area and internal geometric orifice area obtained from in vivo or in vitro published data is still controversial. The effective orifice area was measured by echocardiography in 533 patients. The mean age of the patients was 71 +/- 9 years; mean follow-up time was 4.7 +/- 2.2 years. The impact of severe (indexed effective orifice area regression. Severe mismatch (hazard ratio: 1.9 [1.08-3.21]) was a significant predictor of survival time after adjustment for age, left ventricular ejection fraction, atrial fibrillation, New York Heart Association class, serum creatinine, and hemoglobin level. The 5- and 7-year survival rates were 71% +/- 4% and 54% +/- 8% for patients with severe mismatch and 83% +/- 4% and 80% +/- 8% for patients with mild mismatch, respectively. The correlation between projected and measured indexed effective orifice area was of medium strength (r = 0.49), and the frequency of observed mismatch depended linearly on the projected indexed effective orifice area. Although projected indexed effective orifice area and indexed internal geometric orifice area were significant predictors of severe mismatch, the sensitivity and specificity for severe prosthesis-patient mismatch were only 75% and 52%, using an optimal threshold of projected indexed effective orifice area defined by the Youden index. Severe prosthesis-patient mismatch estimated by effective orifice area measured within 10 days was an independent risk factor of survival time. Projected indexed effective orifice area determined at surgery does not sufficiently predict mismatch.

BatMis: a fast algorithm for k-mismatch mapping.

Science.gov (United States)

Tennakoon, Chandana; Purbojati, Rikky W; Sung, Wing-Kin

2012-08-15

Second-generation sequencing (SGS) generates millions of reads that need to be aligned to a reference genome allowing errors. Although current aligners can efficiently map reads allowing a small number of mismatches, they are not well suited for handling a large number of mismatches. The efficiency of aligners can be improved using various heuristics, but the sensitivity and accuracy of the alignments are sacrificed. In this article, we introduce Basic Alignment tool for Mismatches (BatMis)--an efficient method to align short reads to a reference allowing k mismatches. BatMis is a Burrows-Wheeler transformation based aligner that uses a seed and extend approach, and it is an exact method. Benchmark tests show that BatMis performs better than competing aligners in solving the k-mismatch problem. Furthermore, it can compete favorably even when compared with the heuristic modes of the other aligners. BatMis is a useful alternative for applications where fast k-mismatch mappings, unique mappings or multiple mappings of SGS data are required. BatMis is written in C/C++ and is freely available from http://code.google.com/p/batmis/

Bifunctional rhodium intercalator conjugates as mismatch-directing DNA alkylating agents.

Science.gov (United States)

Schatzschneider, Ulrich; Barton, Jacqueline K

2004-07-21

A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covalent modification was established on the basis of the enhanced depurination associated with N-alkylation. The site-selective alkylation at mismatched DNA renders these conjugates useful tools for the covalent tagging of DNA base pair mismatches and new chemotherapeutic design.

NMR and molecular modeling evidence for a G·A mismatch base pair in a purine-rich DNA duplex

International Nuclear Information System (INIS)

Li, Ying; Wilson, W.D.; Zon, G.

1991-01-01

1 H NMR experiments indicate that the oligomer 5'-d(ATGAGCGAATA) forms an unusual 10-base-pair duplex with 4 G·A base pairs and a 3' unpaired adenosine. NMR results indicate that guanoxine imino protons of the F·A mismatches are not hydrogen bonded but are stacked in the helix. A G→ I substitution in either G·A base pair causes a dramatic decrtease in duplex stability and indicates that hydrogen bonding of the guanosine amino group is critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional correlated spectroscopy (COSY) results indicate that the overall duplex conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY spectra between a mismatched AH2 and an AH1' of the other mismatched base pair and between a mismatched GH8 and GNH1 of the other mismatch establish a purine-purine stacking pattern, adenosine over adenosine and guanosine over guanosine, which strongly stabilizes the duplex. A computer graphics molecular model of the ususual duplex was constructed with G·A base pairs containing A-NH 2 to GN3 and G-NH 2 to AN7 hydrogen bonds and B-form base pairs on both sides of the G·A pairs [5'-d(ATGAGC)]. The energy-minimized duplex satisfies all experimental constraints from NOESY and COSY results. A hydrogen bond from G-NH 2 of the mismatch to a phosphate oxygen is predicted

Efficient and reproducible identification of mismatch repair deficient colon cancer

DEFF Research Database (Denmark)

Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

2013-01-01

BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

Scale Mismatches in Social-Ecological Systems: Causes, Consequences, and Solutions

Directory of Open Access Journals (Sweden)

Graeme S. Cumming

2006-06-01

Full Text Available Scale is a concept that transcends disciplinary boundaries. In ecology and geography, scale is usually defined in terms of spatial and temporal dimensions. Sociological scale also incorporates space and time, but adds ideas about representation and organization. Although spatial and temporal location determine the context for social and ecological dynamics, social-ecological interactions can create dynamic feedback loops in which humans both influence and are influenced by ecosystem processes. We hypothesize that many of the problems encountered by societies in managing natural resources arise because of a mismatch between the scale of management and the scale(s of the ecological processes being managed. We use examples from southern Africa and the southern United States to address four main questions: (1 What is a "scale mismatch?" (2 How are scale mismatches generated? (3 What are the consequences of scale mismatches? (4 How can scale mismatches be resolved? Scale mismatches occur when the scale of environmental variation and the scale of social organization in which the responsibility for management resides are aligned in such a way that one or more functions of the social-ecological system are disrupted, inefficiencies occur, and/or important components of the system are lost. They are generated by a wide range of social, ecological, and linked social-ecological processes. Mismatches between the scales of ecological processes and the institutions that are responsible for managing them can contribute to a decrease in social-ecological resilience, including the mismanagement of natural resources and a decrease in human well-being. Solutions to scale mismatches usually require institutional changes at more than one hierarchical level. Long-term solutions to scale mismatch problems will depend on social learning and the development of flexible institutions that can adjust and reorganize in response to changes in ecosystems. Further research is

Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

Science.gov (United States)

Berglund, A K; Schnabel, L V

2017-07-01

Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

Wavelength mismatch effect in electromagnetically induced absorption

International Nuclear Information System (INIS)

Bharti, Vineet; Wasan, Ajay; Natarajan, Vasant

2016-01-01

We present a theoretical investigation of the phenomenon of electromagnetically induced absorption (EIA) in a 4-level system consisting of vee and ladder subsystems. The four levels are coupled using one weak probe field, and two strong control fields. We consider an experimental realization using energy levels of Rb. This necessitates dealing with different conditions of wavelength mismatch—near-perfect match where all three wavelengths are approximately equal; partial mismatch where the wavelength of one control field is less than the other fields; and complete mismatch where all three wavelengths are unequal. We present probe absorption profiles with Doppler averaging at room temperature to account for experiments in a room temperature Rb vapor cell. Our analysis shows that EIA resonances can be studied using Rydberg states excited with diode lasers. - Highlights: • Wavelength mismatch effect is investigated in electromagnetically induced absorption (EIA). • An experimental realization of 4-level vee + ladder system using energy levels of rubidium atom is presented. • EIA resonances are studied under different conditions of wavelength mismatch. • Possibility of observation of EIA using Rydberg states excited with diode lasers.

Wavelength mismatch effect in electromagnetically induced absorption

Energy Technology Data Exchange (ETDEWEB)

Bharti, Vineet [Department of Physics, Indian Institute of Science, Bangalore 560012 (India); Wasan, Ajay [Department of Physics, Indian Institute of Technology, Roorkee 247667 (India); Natarajan, Vasant [Department of Physics, Indian Institute of Science, Bangalore 560012 (India)

2016-07-15

We present a theoretical investigation of the phenomenon of electromagnetically induced absorption (EIA) in a 4-level system consisting of vee and ladder subsystems. The four levels are coupled using one weak probe field, and two strong control fields. We consider an experimental realization using energy levels of Rb. This necessitates dealing with different conditions of wavelength mismatch—near-perfect match where all three wavelengths are approximately equal; partial mismatch where the wavelength of one control field is less than the other fields; and complete mismatch where all three wavelengths are unequal. We present probe absorption profiles with Doppler averaging at room temperature to account for experiments in a room temperature Rb vapor cell. Our analysis shows that EIA resonances can be studied using Rydberg states excited with diode lasers. - Highlights: • Wavelength mismatch effect is investigated in electromagnetically induced absorption (EIA). • An experimental realization of 4-level vee + ladder system using energy levels of rubidium atom is presented. • EIA resonances are studied under different conditions of wavelength mismatch. • Possibility of observation of EIA using Rydberg states excited with diode lasers.

Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea

OpenAIRE

Ishino, Sonoko; Nishi, Yuki; Oda, Soichiro; Uemori, Takashi; Sagara, Takehiro; Takatsu, Nariaki; Yamagami, Takeshi; Shirai, Tsuyoshi; Ishino, Yoshizumi

2016-01-01

The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus. The corresponding gene revealed that the act...

Clinical predictors of prosthesis-patient mismatch after aortic valve replacement for aortic stenosis

Directory of Open Access Journals (Sweden)

Luis M Astudillo

2012-01-01

Full Text Available OBJECTIVE: We sought to ascertain predictors of Patient Prosthesis Mismatch, an independent predictor of mortality, in patients with aortic stenosis using bioprosthetic valves. METHOD: We analyzed 2,107 sequential surgeries. Patient Prosthesis Mismatch was calculated using the effective orifice area of the prosthesis divided by the patient's body surface area. We defined nonsignificant, moderate, and severe Patient Prosthesis Mismatch as effective orifice area indexes of .0.85 cm²/m, 0.85-0.66 cm²/m², and <0.65 cm²/m², respectively. RESULTS: A total of 311 bioprosthetic patients were identified. The incidence of nonsignificant, moderate, and severe Patient Prosthesis Mismatch was 41%, 42, and 16%, respectively. Severe Patient Prosthesis Mismatch was significantly more prevalent in females (82%. In severe Patient Prosthesis Mismatch, the perfusion and the crossclamp times were considerably lower when compared with nonsignificant Patient Prosthesis Mismatch and moderate Patient Prosthesis Mismatch. Patients with severe Patient Prosthesis Mismatch had a significantly higher likelihood of spending time in the intensive care unit and a significantly longer length of stay in the hospital. Body surface area was not different in severe Patient Prosthesis Mismatch when compared with nonsignificant Patient Prosthesis Mismatch. In-hospital mortality in patients with nonsignificant, moderate, and severe Patient Prosthesis Mismatch was 2.3%, 6.1%, and 8%, respectively. Minimally invasive surgery was significantly associated with moderate Patient Prosthesis Mismatch in 49% of the patients, but not with severe Patient Prosthesis Mismatch. CONCLUSION: Severe Patient Prosthesis Mismatch is more common in females, but not in those with minimal available body surface area. Though operative times were shorter in these patients, intensive care unit and hospital lengths of stay were longer. Surgeons and cardiologists should be cognizant of these clinical

The Effect of Basepair Mismatch on DNA Strand Displacement.

Science.gov (United States)

Broadwater, D W Bo; Kim, Harold D

2016-04-12

DNA strand displacement is a key reaction in DNA homologous recombination and DNA mismatch repair and is also heavily utilized in DNA-based computation and locomotion. Despite its ubiquity in science and engineering, sequence-dependent effects of displacement kinetics have not been extensively characterized. Here, we measured toehold-mediated strand displacement kinetics using single-molecule fluorescence in the presence of a single basepair mismatch. The apparent displacement rate varied significantly when the mismatch was introduced in the invading DNA strand. The rate generally decreased as the mismatch in the invader was encountered earlier in displacement. Our data indicate that a single base pair mismatch in the invader stalls branch migration and displacement occurs via direct dissociation of the destabilized incumbent strand from the substrate strand. We combined both branch migration and direct dissociation into a model, which we term the concurrent displacement model, and used the first passage time approach to quantitatively explain the salient features of the observed relationship. We also introduce the concept of splitting probabilities to justify that the concurrent model can be simplified into a three-step sequential model in the presence of an invader mismatch. We expect our model to become a powerful tool to design DNA-based reaction schemes with broad functionality. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A rhodium(III) complex for high-affinity DNA base-pair mismatch recognition

Science.gov (United States)

Junicke, Henrik; Hart, Jonathan R.; Kisko, Jennifer; Glebov, Oleg; Kirsch, Ilan R.; Barton, Jacqueline K.

2003-01-01

A rhodium(III) complex, rac-[Rh(bpy)2phzi]3+ (bpy, 2,2′-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a sterically demanding intercalator targeted to destabilized mismatched sites in double-helical DNA. The complex is readily synthesized by condensation of the phenazine quinone with the corresponding diammine complex. Upon photoactivation, the complex promotes direct strand scission at single-base mismatch sites within the DNA duplex. As with the parent mismatch-specific reagent, [Rh(bpy)2(chrysi)]3+ [chrysene-5,6-quinone diimine (chrysi)], mismatch selectivity depends on the helix destabilization associated with mispairing. Unlike the parent chrysi complex, the phzi analogue binds and cleaves with high affinity and efficiency. The specific binding constants for CA, CC, and CT mismatches within a 31-mer oligonucleotide duplex are 0.3, 1, and 6 × 107 M−1, respectively; site-specific photocleavage is evident at nanomolar concentrations. Moreover, the specificity, defined as the ratio in binding affinities for mispaired vs. well paired sites, is maintained. The increase in affinity is attributed to greater stability in the mismatched site associated with stacking by the heterocyclic aromatic ligand. The high-affinity complex is also applied in the differential cleavage of DNA obtained from cell lines deficient in mismatch repair vs. those proficient in mismatch repair. Agreement is found between photocleavage by the mismatch-specific probes and deficiency in mismatch repair. This mismatch-specific targeting, therefore, offers a potential strategy for new chemotherapeutic design. PMID:12610209

Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

Science.gov (United States)

Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

2014-10-01

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlation between ovarian chocolate cyst and serum carbohydrate antigen 125 level and the effect of ultrasound-guided interventional sclerotherapy on serum carbohydrate antigen 125 level.

Science.gov (United States)

Wang, Si-Ming; Cai, Huai-Qiu; Dong, Xiao-Qiu; Fan, Qiu-Lan; Wang, Lu-Lu; Shao, Xiao-Hui; Zhang, Li-Wei

2015-01-01

This study was to investigate the correlation between ovarian chocolate cysts and serum carbohydrate antigen (CA)-125 levels and to demonstrate the effect of ultrasound-guided interventional sclerotherapy (UGIS) on serum CA-125 levels. Based on the serum CA-125 level, as determined by chemiluminescence detection prior to UGIS, 105 patients with ovarian chocolate cysts were divided into the normal group (CA-125 ≤ 35 U/mL, 45 patients) and the abnormal group (35 U/mL history, child-bearing history, abortion history and surgical history. The ultrasonography characteristics were cyst diameter, cyst wall thickness and the side on which the cyst occurred. The correlations between serum CA-125 levels pretreatment and the clinical indicators and ultrasonography characteristics was analyzed. The serum CA-125 levels pretreatment, 3 months post-treatment and 6 months post-treatment were compared. The pretreatment serum CA-125 levels of the 105 patients positively correlated with disease duration (r = 0.3932, P = 0.0040), dysmenorrhea history (r = 0.2351, P = 0.0111), cyst diameter (r = 0.3415, P chocolate cysts. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Addressing the Resource Requirements Mismatch

National Research Council Canada - National Science Library

Braun, William

2003-01-01

... on the other, appear to be developing a requirements-resource mismatch. The goals and objectives of the transformation rhetoric intuitively resonate with the military's increasingly technologic culture...

Selective Cytotoxicity of Rhodium Metalloinsertors in Mismatch Repair-Deficient Cells†

Science.gov (United States)

Ernst, Russell J.; Komor, Alexis C.; Barton, Jacqueline K.

2011-01-01

Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anti-cancer agents. PMID:22103240

Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage

Science.gov (United States)

Zimova, Marketa; Mills, L. Scott; Lukacs, Paul M.; Mitchell, Michael S.

2014-01-01

As duration of snow cover decreases owing to climate change, species undergoing seasonal colour moults can become colour mismatched with their background. The immediate adaptive solution to this mismatch is phenotypic plasticity, either in phenology of seasonal colour moults or in behaviours that reduce mismatch or its consequences. We observed nearly 200 snowshoe hares across a wide range of snow conditions and two study sites in Montana, USA, and found minimal plasticity in response to mismatch between coat colour and background. We found that moult phenology varied between study sites, likely due to differences in photoperiod and climate, but was largely fixed within study sites with only minimal plasticity to snow conditions during the spring white-to-brown moult. We also found no evidence that hares modify their behaviour in response to colour mismatch. Hiding and fleeing behaviours and resting spot preference of hares were more affected by variables related to season, site and concealment by vegetation, than by colour mismatch. We conclude that plasticity in moult phenology and behaviours in snowshoe hares is insufficient for adaptation to camouflage mismatch, suggesting that any future adaptation to climate change will require natural selection on moult phenology or behaviour.

Spatial mismatch, wages and unemployment in metropolitan areas in Brazil

Directory of Open Access Journals (Sweden)

Ana Maria Bonomi Barufi

2017-12-01

Full Text Available The spatial mismatch hypothesis states that a lack of connection to job opportunities may affect an individual’s prospects in the labour market, especially for low-skilled workers. This phenomenon is especially observed in large urban areas, in which low-skilled minorities tend to live far away from jobs and face geographical barriers to finding and keeping jobs. This paper aims to investigate whether this negative relationship between spatial mismatch and labour market outcomes is valid in Brazil after controlling for individual characteristics. Our conclusions indicate that there is no clear relation between different measures of accessibility to jobs and the probability of being unemployed. However, for wages there is a clear correlation, which is stronger in larger metropolitan areas in the country. Given the exploratory nature of this work, our results still rely on strong identification hypotheses to avoid potential bias related to simultaneous location decisions of workers and firms within the city. Even if these conditions do not hold, the results are still meaningful as they provide a better understanding of the conditional distribution of wages and the unemployment rate in the biggest metropolitan areas of Brazil.

Replication infidelity via a mismatch with Watson-Crick geometry.

Science.gov (United States)

Bebenek, Katarzyna; Pedersen, Lars C; Kunkel, Thomas A

2011-02-01

In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA.

Replication infidelity via a mismatch with Watson–Crick geometry

Science.gov (United States)

Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.

2011-01-01

In describing the DNA double helix, Watson and Crick suggested that “spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms.” Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson–Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base–base mismatch with Watson–Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson–Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson–Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G•T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA. PMID:21233421

Frontal Theta Activity Supports Detecting Mismatched Information in Visual Working Memory.

Science.gov (United States)

Liang, Tengfei; Hu, Zhonghua; Liu, Qiang

2017-01-01

During the comparison stage of visual working memory (VWM) processing, detecting the mismatch between the external sensory input and internal representations is a crucial cognitive ability for human, but the neural mechanism behind it remains largely unclear. The present study investigated the role of frontal theta power in detecting the mismatched information in VWM in a delayed matching task. A control task required to compare two simultaneously presented visual figures was also designed as a contrast to exclude the possibility that frontal theta activity just reflecting the non-memory-related behavioral conflicts. To better characterize the control mechanisms shaped by the frontal theta oscillation in human VWM, colored shapes were adopted as materials while both the task-relevant shape feature and task-irrelevant color feature could be mismatched. We found that the response times of participants were significantly delayed under the relevant- and irrelevant-mismatch conditions in both tasks and the conjunction-mismatch condition in delayed matching task. While our EEG data showed that increased frontal theta power was only observed under the relevant- and conjunction-mismatch conditions in the delayed matching task, but not the control task. These findings suggest that the frontal distributed theta activity observed here reflects the detection of mismatched information during the comparison stage of VWM, rather than the response-related conflicts. Furthermore, it is consistent with the proposal that theta-band oscillation can act as a control mechanism in working memory function so that the target-mismatched information in VWM could be successfully tracked. We also propose a possible processing structure to explain the neural dynamics underlying the mismatch detection process in VWM.

Frontal Theta Activity Supports Detecting Mismatched Information in Visual Working Memory

Directory of Open Access Journals (Sweden)

Tengfei Liang

2017-10-01

Full Text Available During the comparison stage of visual working memory (VWM processing, detecting the mismatch between the external sensory input and internal representations is a crucial cognitive ability for human, but the neural mechanism behind it remains largely unclear. The present study investigated the role of frontal theta power in detecting the mismatched information in VWM in a delayed matching task. A control task required to compare two simultaneously presented visual figures was also designed as a contrast to exclude the possibility that frontal theta activity just reflecting the non-memory-related behavioral conflicts. To better characterize the control mechanisms shaped by the frontal theta oscillation in human VWM, colored shapes were adopted as materials while both the task-relevant shape feature and task-irrelevant color feature could be mismatched. We found that the response times of participants were significantly delayed under the relevant- and irrelevant-mismatch conditions in both tasks and the conjunction-mismatch condition in delayed matching task. While our EEG data showed that increased frontal theta power was only observed under the relevant- and conjunction-mismatch conditions in the delayed matching task, but not the control task. These findings suggest that the frontal distributed theta activity observed here reflects the detection of mismatched information during the comparison stage of VWM, rather than the response-related conflicts. Furthermore, it is consistent with the proposal that theta-band oscillation can act as a control mechanism in working memory function so that the target-mismatched information in VWM could be successfully tracked. We also propose a possible processing structure to explain the neural dynamics underlying the mismatch detection process in VWM.

The Effect of Codon Mismatch on the Protein Translation System.

Directory of Open Access Journals (Sweden)

Dinglin Zhang

Full Text Available Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

The Effect of Codon Mismatch on the Protein Translation System.

Science.gov (United States)

Zhang, Dinglin; Chen, Danfeng; Cao, Liaoran; Li, Guohui; Cheng, Hong

2016-01-01

Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

Positive correlation between Aeromonas salmonicida vaccine antigen concentration and protection in vaccinated rainbow trout Oncorhynchus mykiss evaluated by a tail fin infection model

DEFF Research Database (Denmark)

Marana, M. H.; Skov, J.; Chettri, Jiwan Kumar

2017-01-01

Rainbow trout, Oncorhynchus mykiss (Walbaum), are able to raise a protective immune response against Aeromonas salmonicida subsp. salmonicida (AS) following injection vaccination with commercial vaccines containing formalin-killed bacteria, but the protection is often suboptimal under Danish...... mariculture conditions. We elucidated whether protection can be improved by increasing the concentration of antigen (formalin-killed bacteria) in the vaccine. Rainbow trout juveniles were vaccinated by intraperitoneal (i.p.) injection with a bacterin of Aeromonas salmonicida subsp. salmonicida strain 090710...... bacteria. The infection method proved to be efficient and could differentiate efficacies of different vaccines. It was shown that protection and antibody production in exposed fish were positively correlated to the AS antigen concentration in the vaccine....

Mismatch characteristics of optical parametric chirped pulse amplification

Czech Academy of Sciences Publication Activity Database

Novák, Ondřej; Turčičová, Hana; Divoký, Martin; Huynh, Jaroslav; Straka, Petr

2014-01-01

Roč. 11, č. 2 (2014), 1-7 ISSN 1612-2011 R&D Projects: GA ČR GA202/06/0814; GA MŠk(CZ) LC528 Institutional support: RVO:68378271 Keywords : phase matching * phase mismatch * beam mismatch * broadband amplification * parametric amplifiers * OPCPA * iodine laser Subject RIV: BH - Optics , Masers, Lasers Impact factor: 2.458, year: 2014

Burnout: implications of the organizational sources of job-person mismatches in nursing workers / Burnout: implicações das fontes organizacionais de desajuste indivíduo-trabalho em profissionais da enfermagem

Directory of Open Access Journals (Sweden)

Mauricio Robayo Tamayo

2009-01-01

Full Text Available This research investigated the relation between burnout and the organizational sources of job-person mismatches. One hundred ninety nursing professionals answered a scale of burnout and one questionnaire of organizational sources of mismatches. High, medium and low levels of burnout were verified. Direct and significant correlations were verified between sources of mismatch and the three factors of burnout. The mismatches sources Absence of Team Spirit, Work Overload and Conflict of Values and Organizational Practices were significant predictors of Emotional Exhaustion. The Dehumanization factor was only predicted by the Work Overload factor. The Deception factor was predicted by the factors Absence of Team Spirit and Work Overload. The relationship between burnout and organizational sources of mismatches was evidenced.

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

Science.gov (United States)

Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2017-08-01

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen baseline prostate-specific antigen level baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

Bifunctional Rhodium Intercalator Conjugates as Mismatch-Directing DNA Alkylating Agents

OpenAIRE

Schatzschneider, Ulrich; Barton, Jacqueline K.

2004-01-01

A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covale...

Alignment to natural and imposed mismatches between the senses

NARCIS (Netherlands)

van der Kooij, K.; Brenner, E.; van Beers, R.J.; Schot, W.D.; Smeets, J.B.J.

2013-01-01

Does the nervous system continuously realign the senses so that objects are seen and felt in the same place? Conflicting answers to this question have been given. Research imposing a sensory mismatch has provided evidence that the nervous system realigns the senses to reduce the mismatch. Other

[Constitutional mismatch repair deficiency syndrome].

Science.gov (United States)

Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

2015-01-01

Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

Influence of halo doping profiles on MOS transistor mismatch

NARCIS (Netherlands)

Andricciola, P.; Tuinhout, H.

2009-01-01

Halo implants are used in modern CMOS technology to reduce the short channel effect. However, the lateral non-uniformity of the channel doping has been proven to degenerate the mismatch performance. With this paper we want to discuss the influence of the halo profile on MOS transistor mismatch. The

Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

Science.gov (United States)

Cybis, Gabriela B; Sinsheimer, Janet S; Bedford, Trevor; Rambaut, Andrew; Lemey, Philippe; Suchard, Marc A

2018-01-30

Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Speaking Self-Assessment: Mismatches between Learners' and Teachers' Criteria

Science.gov (United States)

Babaii, Esmat; Taghaddomi, Shahin; Pashmforoosh, Roya

2016-01-01

Perceptual (mis)matches between teachers and learners are said to affect learning success or failure. Self-assessment, as a formative assessment tool, may, inter alia, be considered a means to minimize such mismatches. Therefore, the present study investigated the extent to which learners' assessment of their own speaking performance, before and…

Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD).

Science.gov (United States)

Ramchander, N C; Ryan, N A J; Crosbie, E J; Evans, D G

2017-04-05

Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Constitutional mismatch repair

Collocation mismatch uncertainties in satellite aerosol retrieval validation

Science.gov (United States)

Virtanen, Timo H.; Kolmonen, Pekka; Sogacheva, Larisa; Rodríguez, Edith; Saponaro, Giulia; de Leeuw, Gerrit

2018-02-01

Satellite-based aerosol products are routinely validated against ground-based reference data, usually obtained from sun photometer networks such as AERONET (AEROsol RObotic NETwork). In a typical validation exercise a spatial sample of the instantaneous satellite data is compared against a temporal sample of the point-like ground-based data. The observations do not correspond to exactly the same column of the atmosphere at the same time, and the representativeness of the reference data depends on the spatiotemporal variability of the aerosol properties in the samples. The associated uncertainty is known as the collocation mismatch uncertainty (CMU). The validation results depend on the sampling parameters. While small samples involve less variability, they are more sensitive to the inevitable noise in the measurement data. In this paper we study systematically the effect of the sampling parameters in the validation of AATSR (Advanced Along-Track Scanning Radiometer) aerosol optical depth (AOD) product against AERONET data and the associated collocation mismatch uncertainty. To this end, we study the spatial AOD variability in the satellite data, compare it against the corresponding values obtained from densely located AERONET sites, and assess the possible reasons for observed differences. We find that the spatial AOD variability in the satellite data is approximately 2 times larger than in the ground-based data, and the spatial variability correlates only weakly with that of AERONET for short distances. We interpreted that only half of the variability in the satellite data is due to the natural variability in the AOD, and the rest is noise due to retrieval errors. However, for larger distances (˜ 0.5°) the correlation is improved as the noise is averaged out, and the day-to-day changes in regional AOD variability are well captured. Furthermore, we assess the usefulness of the spatial variability of the satellite AOD data as an estimate of CMU by comparing the

Advancing the match-mismatch framework for large herbivores in the Arctic: Evaluating the evidence for a trophic mismatch in caribou.

Directory of Open Access Journals (Sweden)

David Gustine

Full Text Available Climate-induced shifts in plant phenology may adversely affect animals that cannot or do not shift the timing of their reproductive cycle. The realized effect of potential trophic "mismatches" between a consumer and its food varies with the degree to which species rely on dietary income and stored capital. Large Arctic herbivores rely heavily on maternal capital to reproduce and give birth near the onset of the growing season but are they vulnerable to trophic mismatch? We evaluated the long-term changes in the temperatures and characteristics of the growing seasons (1970-2013, and compared growing conditions and dynamics of forage quality for caribou at peak parturition, peak lactation, and peak forage biomass, and plant senescence between two distinct time periods over 36 years (1977 and 2011-13. Despite advanced thaw dates (7-12 days earlier, increased growing season lengths (15-21 days longer, and consistent parturition dates, we found no decline in forage quality and therefore no evidence within this dataset for a trophic mismatch at peak parturition or peak lactation from 1977 to 2011-13. In Arctic ungulates that use stored capital for reproduction, reproductive demands are largely met by body stores deposited in the previous summer and autumn, which reduces potential adverse effects of any mismatch between food availability and timing of parturition. Climate-induced effects on forages growing in the summer and autumn ranges, however, do correspond with the demands of female caribou and their offspring to gain mass for the next reproductive cycle and winter. Therefore, we suggest the window of time to examine the match-mismatch framework in Arctic ungulates is not at parturition but in late summer-autumn, where the multiplier effects of small changes in forage quality are amplified by forage abundance, peak forage intake, and resultant mass gains in mother-offspring pairs.

Reverse ventilation--perfusion mismatch

International Nuclear Information System (INIS)

Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

1984-01-01

Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients

Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: relationship to smoking

DEFF Research Database (Denmark)

Nandi, S; Yu, J; Reinert, Line

2006-01-01

leukemia (CLL/SLL), that have transformed to diffuse-large B-cell lymphoma (DLBCL). We correlated the presence or absence of DNA-mismatch repair enzymes by immunostaining as well as the p53 status to smoking history. Of all patients (n = 30), 37% showed negative immunostaining of MLH1, 16% showed negative...... for either MLH1 or MSH2 was 2.2 times higher in smokers than non-smokers (relative risk = 2.2041, 95% confidence interval: 0.89714, 5.41491). No direct correlation was found between smoking and the mutations in the p53 gene. These results suggest that cigarette smoking may play a role in the development...

Tolerance of DNA Mismatches in Dmc1 Recombinase-mediated DNA Strand Exchange*

Science.gov (United States)

Borgogno, María V.; Monti, Mariela R.; Zhao, Weixing; Sung, Patrick; Argaraña, Carlos E.; Pezza, Roberto J.

2016-01-01

Recombination between homologous chromosomes is required for the faithful meiotic segregation of chromosomes and leads to the generation of genetic diversity. The conserved meiosis-specific Dmc1 recombinase catalyzes homologous recombination triggered by DNA double strand breaks through the exchange of parental DNA sequences. Although providing an efficient rate of DNA strand exchange between polymorphic alleles, Dmc1 must also guard against recombination between divergent sequences. How DNA mismatches affect Dmc1-mediated DNA strand exchange is not understood. We have used fluorescence resonance energy transfer to study the mechanism of Dmc1-mediated strand exchange between DNA oligonucleotides with different degrees of heterology. The efficiency of strand exchange is highly sensitive to the location, type, and distribution of mismatches. Mismatches near the 3′ end of the initiating DNA strand have a small effect, whereas most mismatches near the 5′ end impede strand exchange dramatically. The Hop2-Mnd1 protein complex stimulates Dmc1-catalyzed strand exchange on homologous DNA or containing a single mismatch. We observed that Dmc1 can reject divergent DNA sequences while bypassing a few mismatches in the DNA sequence. Our findings have important implications in understanding meiotic recombination. First, Dmc1 acts as an initial barrier for heterologous recombination, with the mismatch repair system providing a second level of proofreading, to ensure that ectopic sequences are not recombined. Second, Dmc1 stepping over infrequent mismatches is likely critical for allowing recombination between the polymorphic sequences of homologous chromosomes, thus contributing to gene conversion and genetic diversity. PMID:26709229

Mismatch and noise in modern IC processes

CERN Document Server

Marshall, Andrew

2009-01-01

Component variability, mismatch, and various noise effects are major contributors to design limitations in most modern IC processes. Mismatch and Noise in Modern IC Processes examines these related effects and how they affect the building block circuits of modern integrated circuits, from the perspective of a circuit designer.Variability usually refers to a large scale variation that can occur on a wafer to wafer and lot to lot basis, and over long distances on a wafer. This phenomenon is well understood and the effects of variability are included in most integrated circuit design with the use

Influences of Device and Circuit Mismatches on Paralleling Silicon Carbide MOSFETs

DEFF Research Database (Denmark)

Li, Helong; Munk-Nielsen, Stig; Wang, Xiongfei

2016-01-01

This paper addresses the influences of device and circuit mismatches on paralleling the Silicon Carbide (SiC) MOSFETs. Comprehensive theoretical analysis and experimental validation from paralleled discrete devices to paralleled dies in multichip power modules are first presented. Then, the influ......This paper addresses the influences of device and circuit mismatches on paralleling the Silicon Carbide (SiC) MOSFETs. Comprehensive theoretical analysis and experimental validation from paralleled discrete devices to paralleled dies in multichip power modules are first presented. Then......, the influence of circuit mismatch on paralleling SiC MOSFETs is investigated and experimentally evaluated for the first time. It is found that the mismatch of the switching loop stray inductance can also lead to on-state current unbalance with inductive output current, in addition to the on-state resistance...... of the device. It further reveals that circuit mismatches and a current coupling among the paralleled dies exist in a SiC MOSFET multichip power module, which is critical for the transient current distribution in the power module. Thus, a power module layout with an auxiliary source connection is developed...

Measurement errors in multifrequency bioelectrical impedance analyzers with and without impedance electrode mismatch

International Nuclear Information System (INIS)

Bogónez-Franco, P; Nescolarde, L; Bragós, R; Rosell-Ferrer, J; Yandiola, I

2009-01-01

The purpose of this study is to compare measurement errors in two commercially available multi-frequency bioimpedance analyzers, a Xitron 4000B and an ImpediMed SFB7, including electrode impedance mismatch. The comparison was made using resistive electrical models and in ten human volunteers. We used three different electrical models simulating three different body segments: the right-side, leg and thorax. In the electrical models, we tested the effect of the capacitive coupling of the patient to ground and the skin–electrode impedance mismatch. Results showed that both sets of equipment are optimized for right-side measurements and for moderate skin–electrode impedance mismatch. In right-side measurements with mismatch electrode, 4000B is more accurate than SFB7. When an electrode impedance mismatch was simulated, errors increased in both bioimpedance analyzers and the effect of the mismatch in the voltage detection leads was greater than that in current injection leads. For segments with lower impedance as the leg and thorax, SFB7 is more accurate than 4000B and also shows less dependence on electrode mismatch. In both devices, impedance measurements were not significantly affected (p > 0.05) by the capacitive coupling to ground

Interobserver variability in the evaluation of mismatch repair protein immunostaining

DEFF Research Database (Denmark)

Klarskov, Louise Laurberg; Ladelund, Steen; Holck, Susanne

2010-01-01

Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliabi......Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data...... on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein...... variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance...

Tolerance of DNA Mismatches in Dmc1 Recombinase-mediated DNA Strand Exchange.

Science.gov (United States)

Borgogno, María V; Monti, Mariela R; Zhao, Weixing; Sung, Patrick; Argaraña, Carlos E; Pezza, Roberto J

2016-03-04

Recombination between homologous chromosomes is required for the faithful meiotic segregation of chromosomes and leads to the generation of genetic diversity. The conserved meiosis-specific Dmc1 recombinase catalyzes homologous recombination triggered by DNA double strand breaks through the exchange of parental DNA sequences. Although providing an efficient rate of DNA strand exchange between polymorphic alleles, Dmc1 must also guard against recombination between divergent sequences. How DNA mismatches affect Dmc1-mediated DNA strand exchange is not understood. We have used fluorescence resonance energy transfer to study the mechanism of Dmc1-mediated strand exchange between DNA oligonucleotides with different degrees of heterology. The efficiency of strand exchange is highly sensitive to the location, type, and distribution of mismatches. Mismatches near the 3' end of the initiating DNA strand have a small effect, whereas most mismatches near the 5' end impede strand exchange dramatically. The Hop2-Mnd1 protein complex stimulates Dmc1-catalyzed strand exchange on homologous DNA or containing a single mismatch. We observed that Dmc1 can reject divergent DNA sequences while bypassing a few mismatches in the DNA sequence. Our findings have important implications in understanding meiotic recombination. First, Dmc1 acts as an initial barrier for heterologous recombination, with the mismatch repair system providing a second level of proofreading, to ensure that ectopic sequences are not recombined. Second, Dmc1 stepping over infrequent mismatches is likely critical for allowing recombination between the polymorphic sequences of homologous chromosomes, thus contributing to gene conversion and genetic diversity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Humming along or buzzing off? The elusive consequences of plant-pollinator mismatches

Directory of Open Access Journals (Sweden)

Jason Ryan Straka

2014-08-01

Full Text Available Temporal mismatches among plants and pollinators, driven by climate change, are considered a potential cause of population declines of these mutualists. However, field studies demonstrating population declines as a result of climate-driven phenological mismatches are uncommon, and the extent to which mismatches will be a problem in the future remains unclear. We revisit predicted consequences of climate-driven phenological mismatch in plant-pollinator systems by identifying nine previously-applied assumptions that are violated or insufficiently understood in real systems. Briefly, the assumptions are: (1 Dates of first-flowering (DFF or dates of first activity (DFA correctly describe phenology, and disparities between DFF and DFA represent the magnitude of mismatch. (2 “Optimal” matches are measured correctly. (3 Advancement of DFF or DFA will be the primary phenological change in the future. (4 Future phenological shifts will be independent for each species. (5 All plant-pollinator interactions are equally effective. (6 Populations of plants and pollinators are limited by mutualistic interactions. Some previous models have also assumed that the effects of future mismatches will not be influenced by (7 emergence of novel interactions, (8 competition or facilitation from altered co-flowering and co-flight, and (9 phenotypic plasticity and rapid adaptive evolution of phenology. Those assumptions affect the direction, extent, and accuracy of predicted consequences of future phenological mismatch. In discussing them, we identify important topics for future research in pollination ecology.

Contribuição do Mismatch Negativity na avaliação cognitiva de indivíduos portadores de esclerose múltipla Mismatch Negativity contribution in Multiple Sclerosis patients

Directory of Open Access Journals (Sweden)

Marco Aurélio Rocha Santos

2006-12-01

Full Text Available O Mismatch Negativity (MMN é um potencial evocado auditivo endógeno, gerado por mudanças no processo de discriminação que ocorrem no córtex auditivo que avalia a memória sensorial auditiva. OBJETIVOS: Avaliar se, quando presente, o MMN pode ser utilizado como um índice funcional do córtex auditivo supratemporal e correlacionar com comprometimento cognitivo, avaliado pelo Teste Auditivo Compassado de Adição Seriada (PASAT. MATERIAL E MÉTODOS: Um grupo controle e outro com diagnóstico definido de EM foram submetidos ao registro do MMN com estímulos auditivos com variação de duração e de freqüência. O grupo de EM foi submetido ao PASAT. As latências e as amplitudes negativas do MMN foram comparadas entre os grupos. Os escores do PASAT foram correlacionados com a presença ou ausência do MMN nos dois protocolos de estimulação auditiva. RESULTADOS: O MMN esteve presente em 60% dos indivíduos no grupo de EM no protocolo de estimulação auditiva com variação de duração, e em 45% no protocolo de estimulação auditiva com variação de freqüência. Encontrou-se uma correlação estatisticamente significante entre a ausência da onda do MMN com a presença de comprometimento cognitivo avaliado pelo PASAT. CONCLUSÕES: A ausência do MMN se correlaciona com comprometimento cognitivo avaliado pelo PASAT.Mismatch Negativity is a functional index of the supratemporal auditory cortex. AIM: The aim of the present study on Mismatch Negativity (MMN in multiple sclerosis (MS patients was to evaluate if the MMN can be correlated with cognitive deficits assessed by the Paced Auditory Addition Task - PASAT. METHOD: a clinical study in forty females and 20 males separated in two groups: control individuals and those with a definite diagnosis of MS underwent a duration and frequncy MMN. The MMN latencies and negative amplitudes obtained from the MS group were compared to the ones from the control group. The scores from the Paced Auditory

Quality of Experience for Large Ultra-High-Resolution Tiled Displays with Synchronization Mismatch

Directory of Open Access Journals (Sweden)

Deshpande Sachin

2011-01-01

Full Text Available This paper relates to quality of experience when viewing images, video, or other content on large ultra-high-resolution displays made from individual display tiles. We define experiments to measure vernier acuity caused by synchronization mismatch for moving images. The experiments are used to obtain synchronization mismatch acuity threshold as a function of object velocity and as a function of occlusion or gap width. Our main motivation for measuring the synchronization mismatch vernier acuity is its relevance in the application of tiled display systems, which create a single contiguous image using individual discrete panels arranged in a matrix with each panel utilizing a distributed synchronization algorithm to display parts of the overall image. We also propose a subjective assessment method for perception evaluation of synchronization mismatch for large ultra-high-resolution tiled displays. For this, we design a synchronization mismatch measurement test video set for various tile configurations for various interpanel synchronization mismatch values. The proposed method for synchronization mismatch perception can evaluate tiled displays with or without tile bezels. The results from this work can help during design of low-cost tiled display systems, which utilize distributed synchronization mechanisms for a contiguous or bezeled image display.

Educational mismatch and health status among foreign-born workers in Sweden.

Science.gov (United States)

Dunlavy, A C; Garcy, A M; Rostila, M

2016-04-01

Foreign-born workers have been shown to experience poorer working conditions than native-born workers. Yet relationships between health and educational mismatch have been largely overlooked among foreign-born workers. This study uses objective and self-reported measures of educational mismatch to compare the prevalence of educational mismatch among native (n = 2359) and foreign-born (n = 1789) workers in Sweden and to examine associations between educational mismatch and poor self-rated health. Findings from weighted multivariate logistic regression which controlled for social position and individual-level demographic characteristics suggested that over-educated foreign-born workers had greater odds ratios for poor-self rated health compared to native-born matched workers. This association was particularly evident among men (OR = 2.14, 95% CI: 1.04-4.39) and women (OR = 2.13, 95% CI: 1.12-4.03) from countries outside of Western Europe, North America, and Australia/New Zealand. Associations between under-education and poor-self rated health were also found among women from countries outside of Western Europe, North America, and Australia/New Zealand (OR = 2.02, 95% CI: 1.27-3.18). These findings suggest that educational mismatch may be an important work-related social determinant of health among foreign-born workers. Future studies are needed to examine the effects of long-term versus short-term states of educational mismatch on health and to study relationships over time. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of mismatch repair in small-cell lung cancer cells

DEFF Research Database (Denmark)

Hansen, L T; Thykjaer, T; Ørntoft, T F

2003-01-01

The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

A Direct Adaptive Control Approach in the Presence of Model Mismatch

Science.gov (United States)

Joshi, Suresh M.; Tao, Gang; Khong, Thuan

2009-01-01

This paper considers the problem of direct model reference adaptive control when the plant-model matching conditions are violated due to abnormal changes in the plant or incorrect knowledge of the plant's mathematical structure. The approach consists of direct adaptation of state feedback gains for state tracking, and simultaneous estimation of the plant-model mismatch. Because of the mismatch, the plant can no longer track the state of the original reference model, but may be able to track a new reference model that still provides satisfactory performance. The reference model is updated if the estimated plant-model mismatch exceeds a bound that is determined via robust stability and/or performance criteria. The resulting controller is a hybrid direct-indirect adaptive controller that offers asymptotic state tracking in the presence of plant-model mismatch as well as parameter deviations.

The Effect of Basepair Mismatch on DNA Strand Displacement

OpenAIRE

Broadwater, D.?W.?Bo; Kim, Harold?D.

2016-01-01

DNA strand displacement is a key reaction in DNA homologous recombination and DNA mismatch repair and is also heavily utilized in DNA-based computation and locomotion. Despite its ubiquity in science and engineering, sequence-dependent effects of displacement kinetics have not been extensively characterized. Here, we measured toehold-mediated strand displacement kinetics using single-molecule fluorescence in the presence of a single base pair mismatch. The apparent displacement rate varied si...

Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiae by cell-free nuclear extracts.

Science.gov (United States)

Yuan, Fenghua; Lai, Fangfang; Gu, Liya; Zhou, Wen; El Hokayem, Jimmy; Zhang, Yanbin

2009-05-01

Mismatch repair corrects biosynthetic errors generated during DNA replication, whose deficiency causes a mutator phenotype and directly underlies hereditary non-polyposis colorectal cancer and sporadic cancers. Because of remarkably high conservation of the mismatch repair machinery between the budding yeast (Saccharomyces cerevisiae) and humans, the study of mismatch repair in yeast has provided tremendous insights into the mechanisms of this repair pathway in humans. In addition, yeast cells possess an unbeatable advantage over human cells in terms of the easy genetic manipulation, the availability of whole genome deletion strains, and the relatively low cost for setting up the system. Although many components of eukaryotic mismatch repair have been identified, it remains unclear if additional factors, such as DNA helicase(s) and redundant nuclease(s) besides EXO1, participate in eukaryotic mismatch repair. To facilitate the discovery of novel mismatch repair factors, we developed a straightforward in vitro cell-free repair system. Here, we describe the practical protocols for preparation of yeast cell-free nuclear extracts and DNA mismatch substrates, and the in vitro mismatch repair assay. The validity of the cell-free system was confirmed by the mismatch repair deficient yeast strain (Deltamsh2) and the complementation assay with purified yeast MSH2-MSH6.

Correlation of serum prostate specific antigen levels and Tc-99m mdp bone scintigraphy in newly diagnosed patients with prostrate cancer (abstract)

International Nuclear Information System (INIS)

Rauf, M.; Khan, S.M.; Khan, A.A.; Ahmad, S.; Knob, G.; Shah, S.; Khan, A.A.

1998-01-01

The aim of the study was to evaluate the correlation between serum prostate specific antigen (PSA) level and bone scintigraphy in newly diagnosed untreated prostate cancer patients. The probability of a positive bone scan for metastases was analyzed for different threshold values of prostate specific antigen (PSA), acid phosphastase and alkaline phosphates. Fifty four newly diagnosed untreated prostate cancer patients (mean age, 67 years range, 41 to 94) were included in this study. In each case serum PSA, acid phosphatase and alkaline phosphatase measurements were performed followed by whole body Technetium-99m MDP bone scan. The positive predictive value of serum PSA level for bone metastases at the threshold of 10 ng/ml was 70% whereas the same threshold level of PSA gave a negative predictive value of 100%. We used receiver operating characteristics (ROC) analysis to examine the power of predictive value of each serum test, in predicting the results of the bone scan. We also applied regression analysis for the assessment of correlation between the levels of tumor markers and the extent of bone pathology. It was concluded that bone scintigraphy seems to be unnecessary in evaluation of newly diagnosed untreated prostate cancer in patients with no clinical signs of bone pathology and serum PSA levels of equal to or less than 10 ng/ml. (author)

Response of mouse splenic lymphocytes to timothy pollen antigens in a microculture system.

Science.gov (United States)

Fairchild, S S; Malley, A

1975-12-01

Spleen cells from LAF1 mice were stimulated in a microculture system with T and B cell mitogens or antigens of timothy pollen. Only cells from mice immunized with crude timothy pollen extract (WST) or a major antigen of timothy pollen conjugated to Ascaris (antigen B-Ascaris) responded to timothy antigens in vitro. Optimum responses were obtained at 120 to 144 hr of culture with 5 to 10 mug WST per culture and ranged from three to 10 times greater than cell background. No correlations could be found between the optimum antigen concentration or the maximum response and the immune status of the spleen cell donor. Response could be inhibited by a dialyzable fraction of timothy pollen, antigen D, which is a monovalent form of a major antigen of timothy pollen.

Simulation studies of emittance growth in RMS mismatched beams

International Nuclear Information System (INIS)

Cucchetti, A.; Wangler, T.; Reiser, M.

1991-01-01

As shown in a separate paper, a charged-particle beam, whose rms size is not matched when injected into a transport channel or accelerator, has excess energy compared with that of a matched beam. If nonlinear space-charge forces are present and the mismatched beam transforms to a matched equilibrium state, rms-emittance growth will occur. The theory yields formulas for the possible rms-emittance growth, but not for the time it takes to achieve this growth. In this paper we present the results of systematic simulation studies for a mismatched 2-D round beam in an ideal transport channel with continuous linear focusing. Emittance growth rates obtained from the simulations for different amounts of mismatch and initial charge will be presented and the emittance growth will be compared with the theory. 6 refs., 7 figs

Carcinoma-associated antigens

International Nuclear Information System (INIS)

Bartorelli, A.; Accinni, R.

1981-01-01

This invention relates to novel antigens associated with breast carcinoma, anti-sera specific to said antigens, 125 I-labeled forms of said antigens and methods of detecting said antigens in serum or plasma. The invention also relates to a diagnostic kit containing standardised antigens or antisera or marked forms thereof for the detection of said antigens in human blood, serum or plasma. (author)

The effect of atom mismatch on the fragility of supercooled Lennard-Jones binary mixtures

International Nuclear Information System (INIS)

Sun Minhua; Sun Yongli; Wang Aiping; Ma Congxiao; Li Jiayun; Cheng Weidong; Liu Fang

2006-01-01

The shear viscosity of the well-known binary Lennard-Jones mixture is simulated under constant temperature and constant volume conditions (NVT) by a molecular-dynamics (MD) method. The effect of atomic size mismatch on the fragility parameter and glass-forming ability is studied. The fragility parameters calculated from shear viscosity data decrease with the increment of the atomic size mismatch. The value of the fragility changes from 168.963 to 22.976 when the mismatch changes from 0.023 to 0.25. It is shown that the fragility parameter is sensitive to the atomic size mismatch. The calculated pair distribution functions and mean square displacements indicate that the glass-forming ability increases with the atomic size mismatch

Immunity to tumour antigens.

Science.gov (United States)

Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

2005-01-01

During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

International Nuclear Information System (INIS)

Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

2014-01-01

Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

Energy Technology Data Exchange (ETDEWEB)

Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

2014-08-05

Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

Mismatch Repair Balances Leading and Lagging Strand DNA Replication Fidelity

Science.gov (United States)

2012-10-11

Rev Mol Cell Biol 7: 335–346. 7. Li GM (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18: 85–98. 8. Pavlov YI, Mian IM, Kunkel TA...11: 165–170. 41. Li F, Tian L, Gu L, Li GM (2009) Evidence that nucleosomes inhibit mismatch repair in eukaryotic cells. J Biol Chem 284: 33056–33061

A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body Size.

Science.gov (United States)

Ashby, Valarie B; Leichtman, Alan B; Rees, Michael A; Song, Peter X-K; Bray, Mathieu; Wang, Wen; Kalbfleisch, John D

2017-07-07

Outcomes for transplants from living unrelated donors are of particular interest in kidney paired donation (KPD) programs where exchanges can be arranged between incompatible donor-recipient pairs or chains created from nondirected/altruistic donors. Using Scientific Registry of Transplant Recipients data, we analyzed 232,705 recipients of kidney-alone transplants from 1998 to 2012. Graft failure rates were estimated using Cox models for recipients of kidney transplants from living unrelated, living related, and deceased donors. Models were adjusted for year of transplant and donor and recipient characteristics, with particular attention to mismatches in age, sex, human leukocyte antigens (HLA), body size, and weight. The dependence of graft failure on increasing donor age was less pronounced for living-donor than for deceased-donor transplants. Male donor-to-male recipient transplants had lower graft failure, particularly better than female to male (5%-13% lower risk). HLA mismatch was important in all donor types. Obesity of both the recipient (8%-18% higher risk) and donor (5%-11% higher risk) was associated with higher graft loss, as were donor-recipient weight ratios of transplants where both parties were of similar weight (9%-12% higher risk). These models are used to create a calculator of estimated graft survival for living donors. This calculator provides useful information to donors, candidates, and physicians of estimated outcomes and potentially in allowing candidates to choose among several living donors. It may also help inform candidates with compatible donors on the advisability of joining a KPD program. Copyright © 2017 by the American Society of Nephrology.

Significance of single ventilation/perfusion mismatches in krypton-81m/technetium-99m lung scintigraphy

International Nuclear Information System (INIS)

Rosen, J.M.; Palestro, C.J.; Markowitz, D.; Alderson, P.O.

1986-01-01

The significance of a single area of ventilation/perfusion (V/P) mismatch in lung scans performed on patients suspected of pulmonary embolism (PE) was evaluated. Ten of 20 patients with this scan finding were found to have PE. An intermediate probability of PE was found with segmental (71%) or subsegmental (45%) single V/P mismatches. Seven of 16 patients with a single V/P mismatch and without a matching radiographic opacity had PE. Three of the four patients who had a V/P mismatch and a matching radiographic opacity were found to have PE. Multiview ventilation imaging with 81mKr was found to have advantages for the evaluation of single V/P mismatches. Based on the data available at this time, a single V/P mismatch suggests an intermediate probability of PE

New Spectral Method for Halo Particle Definition in Intense Mis-matched Beams

Energy Technology Data Exchange (ETDEWEB)

Dorf, Mikhail A.; Davidson, Ronald C.; Startsev, Edward A.

2011-04-27

An advanced spectral analysis of a mis-matched charged particle beam propagating through a periodic focusing transport lattice is utilized in particle-in-cell (PIC) simulations. It is found that the betatron frequency distribution function of a mismatched space-charge-dominated beam has a bump-on-tail structure attributed to the beam halo particles. Based on this observation, a new spectral method for halo particle definition is proposed that provides the opportunity to carry out a quantitative analysis of halo particle production by a beam mismatch. In addition, it is shown that the spectral analysis of the mismatch relaxation process provides important insights into the emittance growth attributed to the halo formation and the core relaxation processes. Finally, the spectral method is applied to the problem of space-charge transport limits.

In Vitro Variant Surface Antigen Expression in Plasmodium falciparum Parasites from a Semi-Immune Individual Is Not Correlated with Var Gene Transcription

Science.gov (United States)

Tschan, Serena; Flötenmeyer, Matthias; Koch, Iris; Berger, Jürgen; Kremsner, Peter; Frank, Matthias

2016-01-01

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is considered to be the main variant surface antigen (VSA) of Plasmodium falciparum and is mainly localized on electron-dense knobs in the membrane of the infected erythrocyte. Switches in PfEMP1 expression provide the basis for antigenic variation and are thought to be critical for parasite persistence during chronic infections. Recently, strain transcending anti-PfEMP1 immunity has been shown to develop early in life, challenging the role of PfEMP1 in antigenic variation during chronic infections. In this work we investigate how P. falciparum achieves persistence during a chronic asymptomatic infection. The infected individual (MOA) was parasitemic for 42 days and multilocus var gene genotyping showed persistence of the same parasite population throughout the infection. Parasites from the beginning of the infection were adapted to tissue culture and cloned by limiting dilution. Flow cytometry using convalescent serum detected a variable surface recognition signal on isogenic clonal parasites. Quantitative real-time PCR with a field isolate specific var gene primer set showed that the surface recognition signal was not correlated with transcription of individual var genes. Strain transcending anti-PfEMP1 immunity of the convalescent serum was demonstrated with CD36 selected and PfEMP1 knock-down NF54 clones. In contrast, knock-down of PfEMP1 did not have an effect on the antibody recognition signal in MOA clones. Trypsinisation of the membrane surface proteins abolished the surface recognition signal and immune electron microscopy revealed that antibodies from the convalescent serum bound to membrane areas without knobs and with knobs. Together the data indicate that PfEMP1 is not the main variable surface antigen during a chronic infection and suggest a role for trypsin sensitive non-PfEMP1 VSAs for parasite persistence in chronic infections. PMID:27907004

SKILLS MISMATCH OF THE YOUNG PEOPLE AT THE EUROPEAN LEVEL

Directory of Open Access Journals (Sweden)

Hatos Roxana

2015-07-01

Full Text Available Transition from school to work is a main issue with many fields of study. Studies on transition from school to work, have highlight the importance of two categories of factors at the level of the individual formal proceedings which may affect how easy it is to graduate to integrate into the labor market: 1 so far as the educational systems are transmitting specific competences as compared with those general and 2 so far as there are direct links between employers and the education system. In this way, are reduced the costs of selection and allocation for employers. A poor articulation between educational institutions and the labor market produce a high level of unmatched competences of assimilated by formal education and competencies required of the labor market (skill mismatch (Parodi et al., 2012. The surveys with European employers reflect particular difficulties that they are experiencing in employment vacancies. Investigation on the European companies in the spring of 2013 found that 40% of the firms in the EU have difficulty in finding employees with suitable qualification (CEDEFOP-European Center for the Development of the Vocational Training, 2014. Skills mismatch is a generic term that refers to various types of imbalances between skills and competences offered and those required in the labor market. Concept has become one intensely discussed and submitted to measurement in international research on the background concerns the under-utilization human resource. Numerous opinion polls with employers come to the same unexpected conclusion - that despite high unemployment many posts can't find occupants satisfactorily prepared and identify the causes: most of them criticized the lack of skills of the candidates or the absence of skills specific to the workplace. Based on the latest studies on international databases have built a set of questions that, through secondary analysis, we tried to find answers. Questions that we try to give answer

Evaluation of diffusion-perfusion mismatch for determining indication for emergency endovascular revascularization

International Nuclear Information System (INIS)

Masuda, Atsushi; Miki, Takanori; Matsumoto, Hiroaki

2010-01-01

We evaluated the usefulness of assessing by diffusion-perfusion mismatch (D/P mismatch) whether there is adaptation of neuroendovascular revascularization for acute ischemic stroke out of intravenous tissue plasminogen activator (IV t-PA). We retrospectively analyzed 24 patients who underwent D/P mismatch and endovascular treatment between October 2005 and September 2008. This investigation included stroke patients with a National Institutes of Health Stroke Scale (NIHSS) score less than 4. Sixteen acute ischemic stroke patients had an NIHSS score greater than 5. Eight patients (50%) had a favorable neurological outcome (modified Rankin Scale 0 to 2). Eight acute ischemic stroke patients had an NIHSS score equal to or less than 4. Four patients who underwent emergency endovascular treatment on admission had a favorable neurological outcome, but 3 patients treated for progressive stroke after admission all had a poor prognosis. Evaluating D/P mismatch was useful for determining the adaptation of emergency neuroendovascular revascularization for acute ischemic stroke out of IV t-PA. Acute ischemic stroke patients with an NIHSS score equal to or less than 4 and diffusion/perfusion mismatch need careful observation to enable endovascular treatment immediately after progressive stroke. (author)

High fitness costs of climate change-induced camouflage mismatch.

Science.gov (United States)

Zimova, Marketa; Mills, L Scott; Nowak, J Joshua

2016-03-01

Anthropogenic climate change has created myriad stressors that threaten to cause local extinctions if wild populations fail to adapt to novel conditions. We studied individual and population-level fitness costs of a climate change-induced stressor: camouflage mismatch in seasonally colour molting species confronting decreasing snow cover duration. Based on field measurements of radiocollared snowshoe hares, we found strong selection on coat colour molt phenology, such that animals mismatched with the colour of their background experienced weekly survival decreases up to 7%. In the absence of adaptive response, we show that these mortality costs would result in strong population-level declines by the end of the century. However, natural selection acting on wide individual variation in molt phenology might enable evolutionary adaptation to camouflage mismatch. We conclude that evolutionary rescue will be critical for hares and other colour molting species to keep up with climate change. © 2016 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Antibodies to early EBV, CMV, and HHV6 antigens in systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Rasmussen, N S; Draborg, A H; Nielsen, C T

2015-01-01

OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology/biochemistry, serol......OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology...

Clinical Characteristics and Correlation Analysis of Subjects with Chronic Hepatitis B Virus (HBV) Infection and Sustained Low Levels of Hepatitis B Surface Antigen (HBsAg)

Science.gov (United States)

Cheng, Jun; Dai, Yuzhu; Yan, Li; Zhou, Huajun; Xu, Xujian

2018-01-01

Background The aim of this study was to investigate the clinical characteristics of individuals with chronic hepatitis B virus (HBV) infection with persistent low levels of hepatitis B surface antigen (HBsAg) and to undertake a correlation analysis of the clinical characteristics. Material/Methods The study included 1,204 subjects with chronic HBV infection. Serum HBsAg, HBV envelope antigen (HBeAg), and HBV core antigen (HBcAg) levels were measured using the chemiluminescent microparticle immunoassay (CMIA) and the neutralization test. HBV DNA was measured using real-time fluorescence quantitative polymerase chain reaction (RT-FQ-PCR). Results There were 1,023 subjects in the high-level HBsAg group (HBsAg level ≥10 IU/mL) and 181 subjects in the low-level HBsAg group (HBsAg level HBV-M2), and the asymptomatic carrier (ASC) status was 98.34%. The low-level HBsAg group had a lower HBV DNA-positive rate compared with the high-level HBsAg group (40.33% vs. 75.07%), with a normal distribution across all age groups (P>0.05). The low-level HBsAg group included an older age group. A low-level of HBsAg was positively correlated with a low level of replication of HBV DNA (r=0.452). Conclusions The findings of this study showed that individuals with chronic HBV infection and sustained low-levels of HBsAg were an older population and had a lower level of replicating HBV DNA when compared with individuals with high levels of HBsAg, and the majority (93.7%) were also HBsAg and HBeAg and HBcAg-positive. PMID:29593208

Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients

DEFF Research Database (Denmark)

Koefoed-Nielsen, Pernille; Weinreich, I; Bengtsson, M

2017-01-01

BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program...

ABO blood group antigens in oral mucosa. What is new?

DEFF Research Database (Denmark)

Dabelsteen, Erik

2002-01-01

which represent secondary gene products. They are synthesized in a stepwise fashion from a precursor by the action of different glycosyltransferases. In non-keratinized oral mucosa, a sequential elongation of the carbohydrates is associated with differentiation of epithelial cells, resulting...... in expression of precursors on basal cells and A/B antigens on spinous cells. Reduction or complete deletion of A/B antigen expression in oral carcinomas has been reported, a phenotypic change that is correlated with invasive and metastatic potential of the tumours and with the mortality rates of the patients....... Disappearance of the antigens is ascribed to the absence of A or B transferase gene expression. Several studies have shown that loss of A and B antigen expression is associated with increased cell motility, invasion in matrigel, and tumourigenecity in syngenic animals. In vivo studies of human oral wound...

Correlation Between Preoperative Serum Carcinoembryonic Antigen Levels and Expression on Pancreatic and Rectal Cancer Tissue

Directory of Open Access Journals (Sweden)

LSF Boogerd

2017-05-01

Full Text Available Carcinoembryonic antigen (CEA–targeted imaging and therapeutic agents are being tested in clinical trials. If CEA overexpression in malignant tissue corresponds with elevated serum CEA, serum CEA could assist in selecting patients who may benefit from CEA-targeted agents. This study aims to assess the relationship between serum CEA and CEA expression in pancreatic (n = 20 and rectal cancer tissues (n = 35 using histopathology. According to local laboratory standards, a serum CEA >3 ng/mL was considered elevated. In pancreatic cancer patients a significant correlation between serum CEA and percentage of CEA-expressing tumor cells was observed ( P  = .04, ρ = .47. All 6 patients with homogeneous CEA expression in the tumor had a serum CEA >3 ng/mL. Most rectal cancer tissues (32/35 showed homogeneous CEA expression, independent of serum CEA levels. This study suggests that selection of pancreatic cancer patients for CEA-targeted agents via serum CEA appears adequate. For selection of rectal cancer patients, serum CEA levels are not informative.

Constitutional mismatch repair deficiency in a healthy child : On the spot diagnosis?

NARCIS (Netherlands)

Suerink, Manon; Potjer, Thomas P.; Versluijs, A. B.; Ten Broeke, Sanne W.; Tops, Carli M.; Wimmer, K.; Nielsen, M.

2018-01-01

Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with that of neurofibromatosis type 1 (NF1), since many patients have

[The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haploidentical hematopoietic stem cell transplantation with a third part cord blood unit].

Science.gov (United States)

Zhu, W J; He, J; Bao, X J; Yuan, X N; Li, Y; Xue, S L; Pan, Z J; Chen, J; Wu, D P

2016-07-01

To analyze allele mismatches of HLA- A, - B, - C, - DRB1, - DQB1 and haplotype mismatch of donor- recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit. 230 pairs of donor-recipient were performed HLA-A, B, C, DRB1, DQB1 typing using SBT and SSOP methods from January 2012 to December 2014. Pairs were divided into HLA- 5/10、6/10、7/10 and ≥8/10 groups according to HLA- A, B, C and DRB1 highresolution typing and matched degrees, the 3-year probability of overall survival (OS) for each group were 48.7%, 59.3%, 71.1%, 38.3% (P=0.068) respectively. HLA-6/10 matched group associated with significant favorable effect on OS compared with HLA- 5/10 matched one (P=0.041).When the HLA class I antigen matched on the recipient and donor, improved OS and event free survival (EFS) in HLA- 6/10 matched group than in HLA-5/10 matched one (P=0.017,P=0.088), especially in single HLA-A loci allele matched one (P=0.013,P=0.013), were observed. As to the third part cord blood unit, sharing the same haplotype with the recipient-donor pairs produced better platelet recovery than the misfit one (95.3%vs 86.2%,P= 0.007), similar result was found in terms of neutrophil recovery (98.8%vs 96.1% ,P=0.022). HLA locus mismatch and haplotype mismatch of the donor and recipient should be useful for selection of the most optimum donor. Co- infused of an unrelated cord blood unit sharing the same haplotype with the recipient-donor pairs could improve hematopoietic recovery.

18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology.

Science.gov (United States)

Turkbey, Baris; Mena, Esther; Lindenberg, Liza; Adler, Stephen; Bednarova, Sandra; Berman, Rose; Ton, Anita T; McKinney, Yolanda; Eclarinal, Philip; Hill, Craig; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Jacobs, Paula M; Wood, Bradford J; Pinto, Peter A; Pomper, Martin G; Choyke, Peter L

2017-10-01

To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax. A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033). The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it

Architectural mismatch issues in identity management deployment

DEFF Research Database (Denmark)

Andersen, Mads Schaarup

2010-01-01

Integrating Commercial Off-The-Shelf products in a company's software product portfolio offers business value, but introduces challenges from a software architecture perspective. In this paper, the research challenges in relation to identity management in the Danish municipality administration...... system called Opus, are outlined. Opus BRS is the identity management part of Opus. Opus integrates SAP, legacy mainframe systems, and other third party systems of the individual municipality. Each of these systems define their own software architecture and access control model, leading to architectural...... mismatch with an impact on security, usability, and maintainability. The research project is discussed and access control and identity provisioning are recognized as the major areas of interest in relation to the mismatch challenges. The project is carried out in close cooperation with KMD, one...

Two-year-olds' sensitivity to subphonemic mismatch during online spoken word recognition.

Science.gov (United States)

Paquette-Smith, Melissa; Fecher, Natalie; Johnson, Elizabeth K

2016-11-01

Sensitivity to noncontrastive subphonemic detail plays an important role in adult speech processing, but little is known about children's use of this information during online word recognition. In two eye-tracking experiments, we investigate 2-year-olds' sensitivity to a specific type of subphonemic detail: coarticulatory mismatch. In Experiment 1, toddlers viewed images of familiar objects (e.g., a boat and a book) while hearing labels containing appropriate or inappropriate coarticulation. Inappropriate coarticulation was created by cross-splicing the coda of the target word onto the onset of another word that shared the same onset and nucleus (e.g., to create boat, the final consonant of boat was cross-spliced onto the initial CV of bone). We tested 24-month-olds and 29-month-olds in this paradigm. Both age groups behaved similarly, readily detecting the inappropriate coarticulation (i.e., showing better recognition of identity-spliced than cross-spliced items). In Experiment 2, we asked how children's sensitivity to subphonemic mismatch compared to their sensitivity to phonemic mismatch. Twenty-nine-month-olds were presented with targets that contained either a phonemic (e.g., the final consonant of boat was spliced onto the initial CV of bait) or a subphonemic mismatch (e.g., the final consonant of boat was spliced onto the initial CV of bone). Here, the subphonemic (coarticulatory) mismatch was not nearly as disruptive to children's word recognition as a phonemic mismatch. Taken together, our findings support the view that 2-year-olds, like adults, use subphonemic information to optimize online word recognition.

Constitutional mismatch repair deficiency syndrome: Do we know it?

Science.gov (United States)

Ramachandra, C; Challa, Vasu Reddy; Shetty, Rachan

2014-04-01

Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis-1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

Recommended practice for fracture toughness testing of weldments with strength mismatch

International Nuclear Information System (INIS)

Hornet, P.; Eripret, C.; Wang, Y.Y.; Kirk, M.T.; Gordon, J.R.

1997-01-01

Fracture toughness testing requires relationships between experimentally measured quantities, such as load and displacement, and J and crack tip opening displacement (CTOD).The relationships provided in the presently codified procedures (ASTM E813, E1152, E1290 et BSI 7848:Part 1) were derived under the assumption that the specimens have homogeneous mechanical properties. However, these codified procedures are frequently used for testing of weldments despite their strong mechanical properties variations. As a result, the accuracy of the toughness values (J or CCTOD) is sometimes in question. Systematic finite element studies of mismatched single-edge-notched-bend specimens (SENB) having a crack on the centerline have been conducted to resolve this question. The effect of various parameters on these relationships, such as weld size, degree of mismatch, and crack depth, is investigated. The accuracy of the codified J and CTOD testing procedures when applied to the mismatched SE(B) specimens is examined. This systematic examination is extended to several newly proposed procedures, such as those from Joch et al. and Hornet and Eripret. New J and CTOD estimations procedures are proposed. The expected error in applying the codified and the new procedures are shown are proposed. The expected error in applying the codified and the new procedures are shown in terms of mismatch level and level width. Recommendations are made on the use of those procedures for a variety of weld mismatch and crack depth conditions. (authors)

Capacitor Mismatch Error Cancellation Technique for a Successive Approximation A/D Converter

DEFF Research Database (Denmark)

Zheng, Zhiliang; Moon, Un-Ku; Steensgaard-Madsen, Jesper

1999-01-01

An error cancellation technique is described for suppressing capacitor mismatch in a successive approximation A/D converter. At the cost of a 50% increase in conversion time, the first-order capacitor mismatch error is cancelled. Methods for achieving top-plate parasitic insensitive operation...... are described, and the use of a gain- and offset-compensated opamp is explained. SWITCAP simulation results show that the proposed 16-bit SAR ADC can achieve an SNDR of over 91 dB under non-ideal conditions, including 1% 3 sigma nominal capacitor mismatch, 10-20% randomized parasitic capacitors, 66 dB opamp...

Mood As Cumulative Expectation Mismatch: A Test of Theory Based on Data from Non-verbal Cognitive Bias Tests

Directory of Open Access Journals (Sweden)

Camille M. C. Raoult

2017-12-01

Full Text Available Affective states are known to influence behavior and cognitive processes. To assess mood (moderately long-term affective states, the cognitive judgment bias test was developed and has been widely used in various animal species. However, little is known about how mood changes, how mood can be experimentally manipulated, and how mood then feeds back into cognitive judgment. A recent theory argues that mood reflects the cumulative impact of differences between obtained outcomes and expectations. Here expectations refer to an established context. Situations in which an established context fails to match an outcome are then perceived as mismatches of expectation and outcome. We take advantage of the large number of studies published on non-verbal cognitive bias tests in recent years (95 studies with a total of 162 independent tests to test whether cumulative mismatch could indeed have led to the observed mood changes. Based on a criteria list, we assessed whether mismatch had occurred with the experimental procedure used to induce mood (mood induction mismatch, or in the context of the non-verbal cognitive bias procedure (testing mismatch. For the mood induction mismatch, we scored the mismatch between the subjects’ potential expectations and the manipulations conducted for inducing mood whereas, for the testing mismatch, we scored mismatches that may have occurred during the actual testing. We then investigated whether these two types of mismatch can predict the actual outcome of the cognitive bias study. The present evaluation shows that mood induction mismatch cannot well predict the success of a cognitive bias test. On the other hand, testing mismatch can modulate or even inverse the expected outcome. We think, cognitive bias studies should more specifically aim at creating expectation mismatch while inducing mood states to test the cumulative mismatch theory more properly. Furthermore, testing mismatch should be avoided as much as possible

Environmental proxies of antigen exposure explain variation in immune investment better than indices of pace of life.

Science.gov (United States)

Horrocks, Nicholas P C; Hegemann, Arne; Ostrowski, Stéphane; Ndithia, Henry; Shobrak, Mohammed; Williams, Joseph B; Matson, Kevin D; Tieleman, B I

2015-01-01

Investment in immune defences is predicted to covary with a variety of ecologically and evolutionarily relevant axes, with pace of life and environmental antigen exposure being two examples. These axes may themselves covary directly or inversely, and such relationships can lead to conflicting predictions regarding immune investment. If pace of life shapes immune investment then, following life history theory, slow-living, arid zone and tropical species should invest more in immunity than fast-living temperate species. Alternatively, if antigen exposure drives immune investment, then species in antigen-rich tropical and temperate environments are predicted to exhibit higher immune indices than species from antigen-poor arid locations. To test these contrasting predictions we investigated how variation in pace of life and antigen exposure influence immune investment in related lark species (Alaudidae) with differing life histories and predicted risks of exposure to environmental microbes and parasites. We used clutch size and total number of eggs laid per year as indicators of pace of life, and aridity, and the climatic variables that influence aridity, as correlates of antigen abundance. We quantified immune investment by measuring four indices of innate immunity. Pace of life explained little of the variation in immune investment, and only one immune measure correlated significantly with pace of life, but not in the predicted direction. Conversely, aridity, our proxy for environmental antigen exposure, was predictive of immune investment, and larks in more mesic environments had higher immune indices than those living in arid, low-risk locations. Our study suggests that abiotic environmental variables with strong ties to environmental antigen exposure can be important correlates of immunological variation.

Kinetic characterisation of primer mismatches in allele-specific PCR: a quantitative assessment.

Science.gov (United States)

Waterfall, Christy M; Eisenthal, Robert; Cobb, Benjamin D

2002-12-20

A novel method of estimating the kinetic parameters of Taq DNA polymerase during rapid cycle PCR is presented. A model was constructed using a simplified sigmoid function to represent substrate accumulation during PCR in combination with the general equation describing high substrate inhibition for Michaelis-Menten enzymes. The PCR progress curve was viewed as a series of independent reactions where initial rates were accurately measured for each cycle. Kinetic parameters were obtained for allele-specific PCR (AS-PCR) amplification to examine the effect of mismatches on amplification. A high degree of correlation was obtained providing evidence of substrate inhibition as a major cause of the plateau phase that occurs in the later cycles of PCR.

Skill effort: A new theoretical perspective on the relation between skills, skill use, mismatches, and wages

NARCIS (Netherlands)

van der Velden, Rolf; Bijlsma, Ineke

2017-01-01

Mismatches between workers’ skills and job demands have large negative effects on productivity, job satisfaction, and other outcomes. Current approaches to measure the impact of skills and skill mismatches on wages fail to specify the mechanism through which skills and mismatches may affect

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Science.gov (United States)

Zachary, Andrea A.; Leffell, Mary S.

2016-01-01

HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor. PMID:28003816

An IQ mismatch calibration and compensation technique for wideband wireless transceivers

International Nuclear Information System (INIS)

Peng Jin; Zhou Liguo; Yao Heng; Yuan Fang; Shi Yin; Fang Zhi

2014-01-01

An IQ mismatch calibration and compensation technique based on the digital baseband for wideband wireless communication transmitters is proposed. The digital baseband transmits the signal used for IQ mismatch calibration. The signal passes through the RF transmitter path, the calibration loop (which is composed of a square power detector and a band-pass filter in the RF transceiver) and the variable gain amplifier of the receiver. The digital baseband samples the signal for IQ mismatch estimation and compensates for it. Compared with the self-calibration technique in the RF chip, the proposed technique saves area and power consumption for the wireless local area network solution. This technique has been successfully used for the 802.11n system and satisfies the requirement of the standard by achieving over 50 dB image suppression. (semiconductor integrated circuits)

Measurement of MOS current mismatch in the weak inversion region

International Nuclear Information System (INIS)

Forti, F.; Wright, M.E.

1994-01-01

The MOS transistor matching properties in the weak inversion region have not received, in the past, the attention that the mismatch in the strong inversion region has. The importance of weak inversion biased transistors in low power CMOS analog systems calls for more extensive data on the mismatch in this region of operation. The study presented in this paper was motivated by the need of controlling the threshold matching in a low power, low noise amplifier discriminator circuit used in a silicon radiation detector read-out, where both the transistor dimensions and the currents had to be kept to a minimum. The authors have measured the current matching properties of MOS transistors operated in the weak inversion region. They measured a total of about 1,400 PMOS and NMOS transistors produced in four different processes and report here the results in terms of mismatch dependence on current density, device dimensions, and substrate voltage, without using any specific model for the transistor

Method of Measuring the Mismatch of Parasitic Capacitance in MEMS Accelerometer Based on Regulating Electrostatic Stiffness

Directory of Open Access Journals (Sweden)

Xianshan Dong

2018-03-01

Full Text Available For the MEMS capacitive accelerometer, parasitic capacitance is a serious problem. Its mismatch will deteriorate the performance of accelerometer. Obtaining the mismatch of the parasitic capacitance precisely is helpful for improving the performance of bias and scale. Currently, the method of measuring the mismatch is limited in the direct measuring using the instrument. This traditional method has low accuracy for it would lead in extra parasitic capacitive and have other problems. This paper presents a novel method based on the mechanism of a closed-loop accelerometer. The strongly linear relationship between the output of electric force and the square of pre-load voltage is obtained through theoretical derivation and validated by experiment. Based on this relationship, the mismatch of parasitic capacitance can be obtained precisely through regulating electrostatic stiffness without other equipment. The results can be applied in the design of decreasing the mismatch and electrical adjusting for eliminating the influence of the mismatch.

THE SEARCH OF OPTIMAL COMBINATION OF ANTIGENS FOR SEROLOGICAL DIAGNOSTICS OF TUBERCULOSIS

Directory of Open Access Journals (Sweden)

E. V. Vasilyeva

2013-01-01

Full Text Available Abstract. The four chimeric recombinant antigens CBD-CFP10, CBD-ESAT6, ESAT6-CFP10 and CBD-P38 contained aminoacid sequences of full-size proteins ESAT6, CFP10 and matured protein P38 of M. tuberculosis, joined with aminoacid sequences of cellulose bind domain of endogluconase A (CBD from Cellumonas fimi have been obtained by gene engineering methods. Recombinant proteins were purified by affine chromatography in column with Ni-NTA-sepharose 6В-CL and as PPDN-3 were used for detection of their antigenic activity in indirect ELISA for TB serological diagnostics. The sera from patients with lung tuberculosis (n = 321, from persons who had professional contacts with TB patients (n = 42, from healthy blood donors (n = 366 and from patients with lung diseases of non-TB etiology were tested. It was detected that there was positive correlation between antibodies level for all studied antigens compared by pair. It has been demonstrated that although antigens were different by antigenic and immunobiological characteristics they add each other in the content of antigenic diagnostics compositions. Thus, all these antigens can be used in the test kits for serological diagnostics of TB. Using of these antigens will allow to detect persons infected by TB and patients with active tuberculosis. 

Work-Education Mismatch: An Endogenous Theory of Professionalization.

Science.gov (United States)

Ghaffarzadegan, Navid; Xue, Yi; Larson, Richard C

2017-09-16

We model the education-workforce pipeline and offer an endogenous theory of professionalization and ever-higher degree attainment. We introduce two mechanisms that act on the education enterprise, causing the number of educated people to increase dramatically with relatively short-term changes in the job market. Using our illustrative dynamic model, we argue that the system is susceptible to small changes and the introduced self-driving growth engines are adequate to over-incentivize degree attainment. We also show that the mechanisms magnify effects of short-term recessions or technological changes, and create long-term waves of mismatch between workforce and jobs. The implication of the theory is degree inflation, magnified pressures on those with lower degrees, underemployment, and job market mismatch and inefficiency.

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

DEFF Research Database (Denmark)

Tenzer, Stefan; Wee, Edmund; Burgevin, Anne

2009-01-01

-associated antigen proteins p17 and p24 correlated with epitope abundance, which was strongly influenced by proteasomal digestion profiles, affinity for the transporter protein TAP, and trimming mediated by the endoplasmatic reticulum aminopeptidase ERAAP, and was moderately influenced by HLA affinity. Structural...

Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

Science.gov (United States)

Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

1986-06-01

Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

Antigen-binding radioimmunoassays for human IgG antibodies to bovine ν-lactoglobulin

International Nuclear Information System (INIS)

Turner, M.W.; Paganelli, R.; Levinsky, R.J.; Williams, A.

1983-01-01

A double antibody antigen-binding assay for the detection of human IgG antibodies to the bovine milk allergen ν-lactoglobulin is described. The levels of such antibodies in patients with established cows' milk protein intolerance were significantly higher than the levels observed in a healthy control group (P<0.01). The assay showed excellent correlation with a solid phase antigen binding assay (rsub(s) = 0.8, P<0.001). (Auth.)

Ductile Crack Initiation Criterion with Mismatched Weld Joints Under Dynamic Loading Conditions.

Science.gov (United States)

An, Gyubaek; Jeong, Se-Min; Park, Jeongung

2018-03-01

Brittle failure of high toughness steel structures tends to occur after ductile crack initiation/propagation. Damages to steel structures were reported in the Hanshin Great Earthquake. Several brittle failures were observed in beam-to-column connection zones with geometrical discontinuity. It is widely known that triaxial stresses accelerate the ductile fracture of steels. The study examined the effects of geometrical heterogeneity and strength mismatches (both of which elevate plastic constraints due to heterogeneous plastic straining) and loading rate on critical conditions initiating ductile fracture. This involved applying the two-parameter criterion (involving equivalent plastic strain and stress triaxiality) to estimate ductile cracking for strength mismatched specimens under static and dynamic tensile loading conditions. Ductile crack initiation testing was conducted under static and dynamic loading conditions using circumferentially notched specimens (Charpy type) with/without strength mismatches. The results indicated that the condition for ductile crack initiation using the two parameter criterion was a transferable criterion to evaluate ductile crack initiation independent of the existence of strength mismatches and loading rates.

Significance of Serology by Multi-Antigen ELISA for Tissue Helminthiases in Korea

Science.gov (United States)

2017-01-01

It is clinically important to differentiate tissue-invading helminthiasis. The purpose of this study was to assess the specific immunoglobulin G (IgG) antibody positive rates for clonorchiasis, paragonimiasis, cysticercosis, and sparganosis 4 helminthiases from 1996 to 2006 using multi-antigen enzyme-linked immunosorbent assay (ELISA) in Korea. Results of 6,017 samples, which were referred to our institute for serodiagnosis, were analyzed. The subjects with positive serum IgG antibodies were 1,502 (25.0%) for any of the 4 helminthiases. The overall positive numbers for clonorchiasis, paragonimiasis, cysticercosis, and sparganosis were 728 (12.1%), 166 (2.8%), 729 (12.1%), and 263 (4.4%), respectively. The positive serologic reaction to multi-antigens was determined in 309 (20.6%) of the 1,502 total seropositive subjects. Those with multi-antigen positivity were regarded as positive for the antigen of strongest reaction but cross-reaction to others with weak positive reaction. Annual seropositive rates for those 4 tissue helminthiases ranged from 12.1% to 35.7%. The highest rate was observed in age from 60 to 69 years old and prevalence of men (27.4%; 1,030/3,763) was significantly higher than of women (19.1%; 332/1,741). Hospital records of 165 ELISA positive patients were reviewed to confirm correlation with their clinical diagnosis. Paragonimiasis was highly correlated as 81.8% (9/11), cysticercosis 29.9% (20/67), clonorchiasis 29.0% (20/69), and sparganosis 11.1% (2/18). In conclusion, the multi-antigen ELISA using 4 helminth antigens is useful to differentiate suspected tissue-invading helminthiases, especially ELISA diagnosis of paragonimiasis is reliable. The seropositivity is still high among suspected patients in Korea. PMID:28581268

Surface reconstruction: An effective method for the growth of mismatched materials

Energy Technology Data Exchange (ETDEWEB)

Sun, Yu; Zheng, Beining; Wu, Xiaofeng; Yuan, Long; Wu, Jie; Guo, Hongping; Huang, Keke; Feng, Shouhua, E-mail: shfeng@mail.jlu.edu.cn

2016-01-01

Graphical abstract: High quality thin film of GaSb was fabricated with molecular beam epitaxy technique on the reconstructed Si(1 1 1) surface. - Highlights: • Surface reconstruction formed by different surface treatments controls the heteroepitaxial growth. • Mismatched stress can be effectively released when the mismatched material epi-film tilts out of the epitaxial interface plane to create a coincidence-site lattice. • GaSb films grown on Si(1 1 1)-(5√3 × 5√3)-Sb surface show better crystal quality and morphology for its self-assembled 2D fishbone structure. - Abstract: The crystalline quality of epitaxial films depends on the degree of lattice match between substrates and films. Here, we report a growth strategy for large mismatched epi-films to grow GaSb films on Si(1 1 1) substrates. The epitaxial strategy can be influenced by controlling the surface reconstructions of Sb-treated Si(1 1 1). The film with the best quality was grown on Si(1 1 1)-(5√3 × 5√3)-Sb surface due to the stress release and the formation of a self-assembled 2D fishbone structure. Controlled surface engineering provides an effective pathway towards the growth of the large mismatched materials.

Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

Science.gov (United States)

Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

2017-01-01

Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

Aspects related to fracture toughness of mismatch welds

International Nuclear Information System (INIS)

Kumar, Suranjit; Khan, I.A.; Bhasin, V.; Vaze, K.K.

2011-01-01

In this work effect of weld strength mismatch and weld slenderness on plastic η factor was systematically examined. Solutions presented here are based on extensive two-dimensional finite element analysis. Results of FE analysis has shown that for homogeneous specimens plastic η -factor does not vary significantly with material strain hardening index. Plastic η -factors for non-hardening material models were in better agreement with ASTM solutions than for hardening material models. For mismatch welded specimens analyses were performed on Compact tension (CT) and three points bend (TPB) specimens. Studies were performed for both hardening as well as elastic-perfectly plastic (non-hardening) material models. Results of finite element analysis have shown that unlike homogeneous specimens there is an influence of material strain hardening on plastic η -factor. For over match welds plastic η -factor evaluated for non-hardening material model are lower while for under match welds use of non-hardening material model gives higher value as compare to that of hardening material model. However, it was observed that for over match welds use of ASTM based plastic η -factors (valid for homogeneous specimens) gives the higher values than actual plastic η -factors (evaluated for both hardening as well as non-hardening material model) of mismatch welded specimens. This in turn would lead to un-conservative estimate of fracture toughness and vice versa is true for under-matched welds. (author)

Molecular dynamics simulation of thin film interfacial strength dependency on lattice mismatch

International Nuclear Information System (INIS)

Yang, Zhou; Lian, Jie; Wang, Junlan

2013-01-01

Laser-induced thin film spallation experiments have been previously developed to characterize the intrinsic interfacial strength of thin films. In order to gain insights of atomic level thin film debonding processes and the interfacial strength dependence on film/substrate lattice structures, in this study, molecular dynamics simulations of thin film interfacial failure under laser-induced stress waves were performed. Various loading amplitudes and pulse durations were employed to identify the optimum simulation condition. Stress propagation as a function of time was revealed in conjunction with the interface structures. Parametric studies confirmed that while the interfacial strength between a thin film and a substrate does not depend on the film thickness and the duration of the laser pulse, a thicker film and a shorter duration do provide advantage to effectively load the interface to failure. With the optimized simulation condition, further studies were focused on bulk Au/Au bi-crystals with mismatched orientations, and Ni/Al, Cu/Al, Cu/Ag and Cu/Au bi-crystals with mismatched lattices. The interfacial strength was found to decrease with increasing orientation mismatch and lattice mismatch but more significantly dominated by the bonding elements' atomic structure and valence electron occupancy. - Highlights: • Molecular dynamics simulation was done on stress wave induced thin film spallation. • Atomic structure was found to be a primary strength determining factor. • Lattice mismatch was found to be a secondary strength determining factor

Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch.

Science.gov (United States)

Yuan, Yi; Zhao, Yongyun; Chen, Lianqi; Wu, Jiasi; Chen, Gangyi; Li, Sheng; Zou, Jiawei; Chen, Rong; Wang, Jian; Jiang, Fan; Tang, Zhuo

2017-09-06

Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G-T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G-T mismatch as potential drug target for tumor cells. Moreover, riboflavin is a promising leading compound for further drug design due to its inherent specific recognition of the G-T mismatch. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells

International Nuclear Information System (INIS)

Suhrbier, A.; Winger, L.A.; Castellano, E.; Sinden, R.E.

1990-01-01

Exoerythrocytic (EE) stages of Plasmodium berghei derived from irradiated sporozoites were cultured in vitro in HepG2 cells. They synthesized several antigens, predominantly but not exclusively those expressed by normal early erythrocytic schizonts. After invasion, over half the intracellular sporozoites, both normal and irradiated, appeared to die. After 24 h, in marked contrast to the normal parasites, EE parasites derived from irradiated sporozoites continued to break open, shedding their antigens into the cytoplasm of the infected host cells. Increasing radiation dosage, which has previously been shown to reduce the ability of irradiated sporozoites to protect animals, correlated with reduced de novo antigen synthesis by EE parasites derived from irradiated sporozoites

DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

OpenAIRE

Poulogiannis , George; Frayling , Ian; Arends , Mark

2009-01-01

Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

Mycobacterial r32-kDa antigen-specific T-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients.

Science.gov (United States)

Neela, Venkata Sanjeev Kumar; Devalraju, Kamakshi Prudhula; Pydi, Satya Sudheer; Sunder, Sharada Ramaseri; Adiraju, Kameswara Rao; Singh, Surya Satyanarayana; Anandaraj, M P J S; Valluri, Vijaya Lakshmi

2016-09-01

Immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro T-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. The main goal of this study was to evaluate the use of Mycobacterium bovis recombinant 32-kDa protein (r32-kDa) antigen-stimulated T-cell assay as a surrogate marker for treatment outcome and monitor vitamin D receptor (VDR)-mediated anti-microbial responses during multidrug therapy (MDT) in leprosy. Newly diagnosed tuberculoid and lepromatous leprosy patients were enrolled and followed up during their course of MDT at 6 and 12 months. IFN-γ, IL-10, IL-17 and IL-23 levels in culture supernatants and expression of VDR, TLR2, LL37 and DEFB in r32-kDa-stimulated PBMCs were measured. Controls comprised household contacts (HHCs) and healthy endemic subjects (HCs). Significant differences were observed in the levels of IFN-γ, IL-17, IL-23, VDR and anti-microbial peptides LL37 and DEFB after treatment and when compared with that of HHCs and HCs, respectively. These findings suggest that responses to r32-kDa antigen reflect an improved immunological and anti-microbial response in leprosy patients during therapy, thereby indicating its potential use as an immune correlate in the treatment of leprosy patients. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prosthesis-patient mismatch

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Philippe Pibarot

2011-04-01

Full Text Available Prosthesis-patient mismatch (PPM is present when the effective orifice area of the inserted prosthetic valve is too small in relation to body size. Its main hemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves. The purpose of this review is to present an update on the present state of knowledge with regards to diagnosis, prognosis and prevention of PPM. PPM is a frequent occurrence (20%–70% of aortic valve replacements that has been shown to be associated with worse hemodynamics, less regression of left ventricular hypertrophy, more cardiac events, and lower survival. Moreover, as opposed to most other risk factors, PPM can largely be prevented by using a prospective strategy at the time of operation.

The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis.

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Wunsch, Marie; Hohmann, Christopher; Milles, Bianca; Rostermund, Christina; Lehmann, Paul V; Schroeter, Michael; Bayas, Antonios; Ulzheimer, Jochen; Mäurer, Mathias; Ergün, Süleyman; Kuerten, Stefanie

2016-04-23

There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.

The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis

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Marie Wunsch

2016-04-01

Full Text Available There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV infection and brain inflammation in multiple sclerosis (MS. Here, we tested MS patients during relapse (n = 11 and in remission (n = 19 in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT and enzyme-linked immunosorbent assay (ELISA. Cytomegalovirus (CMV was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.

LORETA current source density for duration mismatch negativity and neuropsychological assessment in early schizophrenia.

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Tomohiro Miyanishi

Full Text Available INTRODUCTION: Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN, by using low-resolution brain electromagnetic tomography (LORETA, and neuropsychological performance in subjects with early schizophrenia. METHODS: Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J. RESULTS: Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. CONCLUSIONS: This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.

Chemiluminescence immunoassay for prostate-specific antigen

International Nuclear Information System (INIS)

Zhang Xuefeng; Liu Yibing; Jia Juanjuan; Xu Wenge; Li Ziying; Chen Yongli; Han Shiquan

2008-01-01

The chemiluminescence immunoassay (CLIA) for serum total prostate-specific antigen (T-PSA) was developed. The reaction of luminol with hydrogen peroxide was introduced into this chemiluminescence system. The detection limit is established as 0.12 μg/L (n=10, mean of zero standard + 2SD) and the analytical recovery of PSA is 83.8%-118.7%. The intra-assay and inter-assay CVs vary from 4.4%-5.0% and 6.2%-11.7%, respectively. The experimental correlation coefficient of dilution is found to be 0.999. Compared with immunoradiometric assay (IRMA) kits, the correlative equation is y=1.07x+0.68, and correlation coefficient r=0.97. The standard range for the method is 1.5-80 μg/L, and it presents good linearity. (authors)

Receiver IQ mismatch estimation in PDM CO-OFDM system using training symbol

Science.gov (United States)

Peng, Dandan; Ma, Xiurong; Yao, Xin; Zhang, Haoyuan

2017-07-01

Receiver in-phase/quadrature (IQ) mismatch is hard to mitigate at the receiver via using conventional method in polarization division multiplexed (PDM) coherent optical orthogonal frequency division multiplexing (CO-OFDM) system. In this paper, a novel training symbol structure is proposed to estimate IQ mismatch and channel distortion. Combined this structure with Gram Schmidt orthogonalization procedure (GSOP) algorithm, we can get lower bit error rate (BER). Meanwhile, based on this structure one estimation method is deduced in frequency domain which can achieve the estimation of IQ mismatch and channel distortion independently and improve the system performance obviously. Numerical simulation shows that the proposed two methods have better performance than compared method at 100 Gb/s after 480 km fiber transmission. Besides, the calculation complexity is also analyzed.

Hydrophobic mismatch in gramicidin A'/lecithin systems

International Nuclear Information System (INIS)

Watnick, P.I.; Chan, S.I.; Dea, P.

1990-01-01

Gramicidin A' (GA') has been added to three lipid systems of varying hydrophobic thickness: dimyristoyllecithin (DML), dipalmitoyllecithin (DPL), and distearoyllecithin (DSL). The similarity in length between the hydrophobic portion of GA' and the hydrocarbon chains of the lipid bilayers has been studied by using 31 P and 2 H NMR. Hydrophobic mismatch has been found to be most severe in the DML bilayer system and minimal in the case of DSL. In addition, the effects of hydrophobic mismatch on the cooperative properties of the bilayer have been obtained from 2 H NMR relaxation measurements. The results indicate that incorporation of the peptide into the bilayer disrupts the cooperative director fluctuations characteristic of pure multilamellar lipid dispersions. Finally, the GA'/lecithin ratio at which the well-known transformation from bilayer to reverse hexagonal (H II ) phase occurs is shown to depend on the acyl chain length of the phospholipid. A rationale is proposed for this chain length dependence

Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

Science.gov (United States)

Hasanzadeh, Leila; Ghaznavi-Rad, Ehsanollah; Soufian, Safieh; Farjadi, Vahideh; Abtahi, Hamid

2013-01-01

Objective(s) : Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA) is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity. Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3) pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis . PMID:23997913

Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

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Leila Hasanzadeh

2013-07-01

Full Text Available Objective(s: Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity.   Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3 pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis .

Resonance Polarization and Phase-Mismatched CARS of Pheophytin b Excited in the Qy Band

NARCIS (Netherlands)

de Boeij, W.P.; Lucassen, G.W.; Lucassen, Gerald; Otto, Cornelis; Greve, Jan

1993-01-01

Resonance polarization and phase-mismatched coherent anti-Stokes Raman scattering (CARS) measurements were performed on pheophytin b dissolved in acetone excited in the Qy absorption band, where strong broad fluorescence makes spontaneous Raman spectroscopy impossible. The phase-mismatching

Gender differences in specialty preference and mismatch with real needs in Japanese medical students

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Harada Tadanari

2010-02-01

Full Text Available Abstract Background The shortage of doctors and maldistribution among specialties are of great concern in the Japanese health care system. This study investigated specialty preference in medical students of one university, and examined gender differences and compared their preference with real needs. Methods We conducted a self-administered questionnaire including specialty preference in all students of one medical university. Preference was assessed by the five-level probability of their future choice: 1 = very low, 2 = low, 3 = moderate, 4 = high, and 5 = very high. The proportion of 4 or 5 was calculated as the preference rate. The real needs (magnitude of doctor shortage in the prefecture were drawn from two different surveys. The relationship between the sex-specific preference rate by specialty and real needs was assessed by Spearman's correlation coefficient. Results Internal medicine showed the highest preference rate, followed by general surgery, pediatrics, and emergency medicine. There was no significant correlation between the preference rates of men and women (r = 0.27, p = 0.34. The preference rates for general surgery, orthopedics, neurosurgery, and emergency medicine were significantly higher in men than in women, while those of obstetrics & gynecology, pediatrics, and dermatology were significantly higher in women. The magnitude of doctor shortage by specialty from two surveys were significantly correlated with the total preference rate and men's preference rate (r = 0.54 to 0.74, but not with women's preference rate (r = 0.06 and 0.32. Conclusions This study elucidated not only gender differences in specialty preference but also the relationship to real needs. Critical gender differences and mismatch with real needs were found in women. In addition to traditional gender roles and insufficient support for women's participation in Japan, gender differences and mismatch influence the current and future maldistribution of

Educational mismatch in the labour market: overqualification and its implications

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Marija Bečić

2013-12-01

Full Text Available Educational mismatch as a labour market disruption has lately attracted the interest of many economic experts and scholars. This interest is spurred by considerable improvements in the educational profile of the population, combined with changes in the demand for highly-qualified workers linked to technological developments. The mismatch can appear if an increase in highly-qualified workforce supply is not accom - panied by an equal growth in the demand. Overqualification is one such type of mismatch: it means that knowledge and skills acquired during formal education remain unused in the workplace. Many economies face this problem that can have negative consequences for individuals, businesses, and the government alike. This paper provides an overview of the basic concepts related to overqualification, focusing on the possible implications of this phenomenon, given that employee dissatisfaction can affect businesses and their productivity, and ultimately, the country as a whole. Systematization of previous research and analysis of the basic concepts related to overqualification can contribute to the literature in economics of education in Croatia and create a foundation for future research

Expression of cancer-associated simple mucin-type O-glycosylated antigens in parasites.

Science.gov (United States)

Osinaga, Eduardo

2007-01-01

Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens, are among of the most specific human cancer-associated structures. These antigens are involved in several types of receptor-ligand interactions, and they are potential targets for immunotherapy. In the last few years several simple mucin-type O-glycan antigens were identified in different species belonging to the main two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in Trypanosoma cruzi. These results are of interest to understand new aspects in parasite glycoimmunology and may help identify new biological characteristics of parasites as well of the host-parasite relationship. Considering that different groups reported a negative correlation between certain parasite infections and cancer development, we could hypothesize that simple mucin-type O-glycosylated antigens obtained from parasites could be good potential targets for cancer immunotherapy.

Optimizing the face Paradigm of BCI system by modified Mismatch Negative paradigm

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Siejie Zhou

2016-10-01

Full Text Available Many recent studies have focused on improving the performance of event-related potential (ERP based brain computer interfaces (BCIs. The use of a face pattern has been shown to obtain high classification accuracies and information transfer rates (ITRs by evoking discriminative ERPs (N200 and N400 in addition to P300 potentials. Recently, it has been proved that the performance of traditional P300-based BCIs could be improved through a modification of the mismatch pattern. In this paper, a mismatch inverted face pattern (MIF-pattern was presented to improve the performance of the inverted face pattern (IF-pattern, one of the state of the art patterns used in visual-based BCI systems. Ten subjects attended in this experiment. The result showed that the mismatch inverted face pattern could evoke significantly larger vertex positive potentials (p<0.05 and N400s (p<0.05 compared to the inverted face pattern. The classification accuracy (mean accuracy is 99.58% and ITRs (mean bit rate is 27.88 bit/min of the mismatch inverted face pattern was significantly higher than that of the inverted face pattern (p<0.05.

Mismatch of Cultural Dimensions in an Urban Medical Educational Environment

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Bethany Malone

2013-01-01

Full Text Available Objective. To identify cultural dimensions and their potential mismatches between attending physicians and their residents and medical students. Methods. We surveyed faculty and students, both undergraduates and postgraduate resident physicians, at the SUNY Downstate College of Medicine, using Hofstede’s VSM-08 questionnaire, and calculated cultural dimensions, including the Power-Distance Index (PDI, Individualism (IDV, Masculinity (MAS, Uncertainty Avoidance Index (UAI, and Long-term Outlook (LTO. Correlations between faculty and student demographic data and cultural dimensions were calculated (SPSS. Results. There were 237 student and resident respondents and 96 faculty respondents. Comparing all faculty and student respondents, significant differences were found in four of five cultural dimensions, with faculty scoring higher in MAS, and lower in PDI, IDV, UAI, and LTO. Conclusions. These differences may be important in the design and implementation of a medical educational curriculum, and, particularly, in the measurement and evaluation of educational outcomes.

Coevolution of female and male genital components to avoid genital size mismatches in sexually dimorphic spiders.

Science.gov (United States)

Lupše, Nik; Cheng, Ren-Chung; Kuntner, Matjaž

2016-08-17

In most animal groups, it is unclear how body size variation relates to genital size differences between the sexes. While most morphological features tend to scale with total somatic size, this does not necessarily hold for genitalia because divergent evolution in somatic size between the sexes would cause genital size mismatches. Theory predicts that the interplay of female-biased sexual size dimorphism (SSD) and sexual genital size dimorphism (SGD) should adhere to the 'positive genital divergence', the 'constant genital divergence', or the 'negative genital divergence' model, but these models remain largely untested. We test their validity in the spider family Nephilidae known for the highest degrees of SSD among terrestrial animals. Through comparative analyses of sex-specific somatic and genital sizes, we first demonstrate that 99 of the 351 pairs of traits are phylogenetically correlated. Through factor analyses we then group these traits for MCMCglmm analyses that test broader correlation patterns, and these reveal significant correlations in 10 out of the 36 pairwise comparisons. Both types of analyses agree that female somatic and internal genital sizes evolve independently. While sizes of non-intromittent male genital parts coevolve with male body size, the size of the intromittent male genital parts is independent of the male somatic size. Instead, male intromittent genital size coevolves with female (external and, in part, internal) genital size. All analyses also agree that SGD and SSD evolve independently. Internal dimensions of female genitalia evolve independently of female body size in nephilid spiders, and similarly, male intromittent genital size evolves independently of the male body size. The size of the male intromittent organ (the embolus) and the sizes of female internal and external genital components thus seem to respond to selection against genital size mismatches. In accord with these interpretations, we reject the validity of the

Numerical simulations of material mismatch and ductile crack growth

Energy Technology Data Exchange (ETDEWEB)

Oestby, Erling

2002-07-01

Both the global geometry and inhomogeneities in material properties will influence the fracture behaviour of structures in presence of cracks. In this thesis numerical simulations have been used to investigate how some aspects of both these issues affect the conditions at the crack-tip. The thesis is organised in an introduction chapter, summarising the major findings and conclusions, a review chapter, presenting the main aspects of the developments in the field of fracture mechanics, and three research papers. Paper I considers the effect of mismatch in hardening exponent on the local near-tip stress field for stationary interface cracks in bi-materials under small scale yielding conditions. It is demonstrated that the stress level in the weaker material increases compared to what is found in the homogeneous material for the same globally applied load level, with the effect being of increasing importance as the crack-tip is approached. Although a coupling between the radial and angular dependence of the stress fields exists, the evolving stress field can still be normalised with the applied J. The effect on the increase in stress level can closely be characterised by the difference in hardening exponent, {delta}n, termed the hardening mismatch, and is more or less independent of the absolute level of hardening in the two materials. Paper II and Ill deal with the effects of geometry, specimen size, hardening level and yield stress mismatch in relation to ductile crack growth. The ductile crack growth is simulated through use of the Gurson model. In Paper H the effect of specimen size on the crack growth resistance is investigated for deep cracked bend and shallow cracked tensile specimens. At small amounts of crack growth the effect of specimen size on the crack growth resistance is small, but a more significant effect is found for larger amounts of crack growth. The crack growth resistance decreases in smaller specimens loaded in tension, whereas the opposite is

Mismatch removal via coherent spatial relations

Science.gov (United States)

Chen, Jun; Ma, Jiayi; Yang, Changcai; Tian, Jinwen

2014-07-01

We propose a method for removing mismatches from the given putative point correspondences in image pairs based on "coherent spatial relations." Under the Bayesian framework, we formulate our approach as a maximum likelihood problem and solve a coherent spatial relation between the putative point correspondences using an expectation-maximization (EM) algorithm. Our approach associates each point correspondence with a latent variable indicating it as being either an inlier or an outlier, and alternatively estimates the inlier set and recovers the coherent spatial relation. It can handle not only the case of image pairs with rigid motions but also the case of image pairs with nonrigid motions. To parameterize the coherent spatial relation, we choose two-view geometry and thin-plate spline as models for rigid and nonrigid cases, respectively. The mismatches could be successfully removed via the coherent spatial relations after the EM algorithm converges. The quantitative results on various experimental data demonstrate that our method outperforms many state-of-the-art methods, it is not affected by low initial correct match percentages, and is robust to most geometric transformations including a large viewing angle, image rotation, and affine transformation.

Mapping the antigenicity of the parasites in Leishmania donovani infection by proteome serology.

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Michael Forgber

Full Text Available BACKGROUND: Leishmaniasis defines a cluster of protozoal diseases with diverse clinical manifestations. The visceral form caused by Leishmania donovani is the most severe. So far, no vaccines exist for visceral leishmaniasis despite indications of naturally developing immunity, and sensitive immunodiagnostics are still at early stages of development. METHODOLOGY/PRINCIPLE FINDINGS: Establishing a proteome-serological methodology, we mapped the antigenicity of the parasites and the specificities of the immune responses in human leishmaniasis. Using 2-dimensional Western blot analyses with sera and parasites isolated from patients in India, we detected immune responses with widely divergent specificities for up to 330 different leishmanial antigens. 68 antigens were assigned to proteins in silver- and fluorochrome-stained gels. The antigenicity of these proteins did not correlate with the expression levels of the proteins. Although some antigens are shared among different parasite isolates, there are extensive differences and no immunodominant antigens, but indications of antigenic drift in the parasites. Six antigens were identified by mass spectrometry. CONCLUSIONS/SIGNIFICANCE: Proteomics-based dissection of the serospecificities of leishmaniasis patients provides a comprehensive inventory of the complexity and interindividual heterogeneity of the host-responses to and variations in the antigenicity of the Leishmania parasites. This information can be instrumental in the development of vaccines and new immune monitoring and diagnostic devices.

The effect of sociodemographic (mis)match between interviewers and respondents on unit and item nonresponse in Belgium.

Science.gov (United States)

Vercruyssen, Anina; Wuyts, Celine; Loosveldt, Geert

2017-09-01

Interviewer characteristics affect nonresponse and measurement errors in face-to-face surveys. Some studies have shown that mismatched sociodemographic characteristics - for example gender - affect people's behavior when interacting with an interviewer at the door and during the survey interview, resulting in more nonresponse. We investigate the effect of sociodemographic (mis)matching on nonresponse in two successive rounds of the European Social Survey in Belgium. As such, we replicate the analyses of the effect of (mis)matching gender and age on unit nonresponse on the one hand, and of gender, age and education level (mis)matching on item nonresponse on the other hand. Recurring effects of sociodemographic (mis)match are found for both unit and item nonresponse. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of Schistosoma mansoni candidate antigens for diagnosis of schistosomiasis

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Gardenia Braz Figueiredo Carvalho

2011-11-01

Full Text Available The development of a more sensitive diagnostic test for schistosomiasis is needed to overcome the limitations of the use of stool examination in low endemic areas. Using parasite antigens in enzyme linked immunosorbent assay is a promising strategy, however a more rational selection of parasite antigens is necessary. In this study we performed in silico analysis of the Schistosoma mansoni genome, using SchistoDB database and bioinformatic tools for screening immunogenic antigens. Based on evidence of expression in all parasite life stage within the definitive host, extracellular or plasmatic membrane localization, low similarity to human and other helminthic proteins and presence of predicted B cell epitopes, six candidates were selected: a glycosylphosphatidylinositol-anchored 200 kDa protein, two putative cytochrome oxidase subunits, two expressed proteins and one hypothetical protein. The recognition in unidimensional and bidimensional Western blot of protein with similar molecular weight and isoelectric point to the selected antigens by sera from S. mansoni infected mice indicate a good correlation between these two approaches in selecting immunogenic proteins.

Mismatch-shaping switching for two-capacitor DAC

DEFF Research Database (Denmark)

Steensgaard-Madsen, Jesper; Moon, U.; Temes, G.C.

1998-01-01

A mismatch-shaping scheme is proposed for a two-capacitor digital-to-analogue converter (DAC). It uses a delta-sigma loop for finding the optimal switching sequence for each input word. Simulations indicate that the scheme can be used for the realisation of DACs with 16 bit linearity and SNR...

Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens.

Science.gov (United States)

Ondigo, Bartholomew N; Park, Gregory S; Gose, Severin O; Ho, Benjamin M; Ochola, Lyticia A; Ayodo, George O; Ofulla, Ayub V; John, Chandy C

2012-12-21

Multiplex cytometric bead assay (CBA) have a number of advantages over ELISA for antibody testing, but little information is available on standardization and validation of antibody CBA to multiple Plasmodium falciparum antigens. The present study was set to determine optimal parameters for multiplex testing of antibodies to P. falciparum antigens, and to compare results of multiplex CBA to ELISA. Antibodies to ten recombinant P. falciparum antigens were measured by CBA and ELISA in samples from 30 individuals from a malaria endemic area of Kenya and compared to known positive and negative control plasma samples. Optimal antigen amounts, monoplex vs multiplex testing, plasma dilution, optimal buffer, number of beads required were assessed for CBA testing, and results from CBA vs. ELISA testing were compared. Optimal amounts for CBA antibody testing differed according to antigen. Results for monoplex CBA testing correlated strongly with multiplex testing for all antigens (r = 0.88-0.99, P values from <0.0001 - 0.004), and antibodies to variants of the same antigen were accurately distinguished within a multiplex reaction. Plasma dilutions of 1:100 or 1:200 were optimal for all antigens for CBA testing. Plasma diluted in a buffer containing 0.05% sodium azide, 0.5% polyvinylalcohol, and 0.8% polyvinylpyrrolidone had the lowest background activity. CBA median fluorescence intensity (MFI) values with 1,000 antigen-conjugated beads/well did not differ significantly from MFI with 5,000 beads/well. CBA and ELISA results correlated well for all antigens except apical membrane antigen-1 (AMA-1). CBA testing produced a greater range of values in samples from malaria endemic areas and less background reactivity for blank samples than ELISA. With optimization, CBA may be the preferred method of testing for antibodies to P. falciparum antigens, as CBA can test for antibodies to multiple recombinant antigens from a single plasma sample and produces a greater range of values in

Correlation of mRNA and protein levels: Cell type-specific gene expression of cluster designation antigens in the prostate

Directory of Open Access Journals (Sweden)

Deutsch Eric W

2008-05-01

Full Text Available Abstract Background: Expression levels of mRNA and protein by cell types exhibit a range of correlations for different genes. In this study, we compared levels of mRNA abundance for several cluster designation (CD genes determined by gene arrays using magnetic sorted and laser-capture microdissected human prostate cells with levels of expression of the respective CD proteins determined by immunohistochemical staining in the major cell types of the prostate – basal epithelial, luminal epithelial, stromal fibromuscular, and endothelial – and for prostate precursor/stem cells and prostate carcinoma cells. Immunohistochemical stains of prostate tissues from more than 50 patients were scored for informative CD antigen expression and compared with cell-type specific transcriptomes. Results: Concordance between gene and protein expression findings based on 'present' vs. 'absent' calls ranged from 46 to 68%. Correlation of expression levels was poor to moderate (Pearson correlations ranged from 0 to 0.63. Divergence between the two data types was most frequently seen for genes whose array signals exceeded background (> 50 but lacked immunoreactivity by immunostaining. This could be due to multiple factors, e.g. low levels of protein expression, technological sensitivities, sample processing, probe set definition or anatomical origin of tissue and actual biological differences between transcript and protein abundance. Conclusion: Agreement between these two very different methodologies has great implications for their respective use in both molecular studies and clinical trials employing molecular biomarkers.

Performance of ARCHITECT HCV core antigen test with specimens from US plasma donors and injecting drug users.

Science.gov (United States)

Mixson-Hayden, Tonya; Dawson, George J; Teshale, Eyasu; Le, Thao; Cheng, Kevin; Drobeniuc, Jan; Ward, John; Kamili, Saleem

2015-05-01

Hepatitis C virus (HCV) core antigen is a serological marker of current HCV infection. The aim of this study was mainly to evaluate the performance characteristics of the ARCHITECT HCV core antigen assay with specimens from US plasma donors and injecting drug users. A total of 551 serum and plasma samples with known anti-HCV and HCV RNA status were tested for HCV core antigen using the Abbott ARCHITECT HCV core antigen test. HCV core antigen was detectable in 100% of US plasma donor samples collected during the pre-seroconversion phase of infection (anti-HCV negative/HCV RNA positive). Overall sensitivity of the HCV core antigen assay was 88.9-94.3% in samples collected after seroconversion. The correlation between HCV core antigen and HCV RNA titers was 0.959. HCV core antigen testing may be reliably used to identify current HCV infection. Published by Elsevier B.V.

Mechanical behaviour of cracked welded structures including mismatch effect

International Nuclear Information System (INIS)

Hornet, P.

2002-01-01

The most important parameters for predicting more precisely the fracture behaviour of welded structures have been identified. In particular, the plasticity development at the crack tip in the ligament appeared as a major parameter to evaluate the yield load of such a complex structure. In this way defect assessments procedures have been developed or modified to take into account the mismatch effect that is to say the mechanical properties of the different material constituting the weld joint. This paper is a synthesis of the work done in the past at Electricite de France on this topic in regards with other work done in France or around the World. The most important parameters which control the plasticity development at the crack tip and so mainly influence the fracture behaviour of welded structures are underlined: the mismatch ratio (weld to base metal yield strength ratio), the mismatch ratio (weld to base metal yield strength ratio), the ligament size and the weld width. Moreover, commonly used fracture toughness testing procedures developed in case of homogeneous specimens cannot be used in a straight forward manner and so has to be modified to take into account the mismatch effect. Number or defect assessment procedures taking into account the mismatch effect by considering the yield load of the welded structure are shortly described. Then, the 'Equivalent Material Method' developed at EDF which allows a good prediction of the applied J-Integral at the crack tip is more detailed. This procedure includes not only both weld and base metal yield strength, the structure geometry, the crack size and the weld dimension using the yield load of the real structures but also includes the effect of both weld and base metal strain hardening exponents. Some validations of this method are proposed. Finally, the ability of finite element modelling to predict the behaviour of such welded structures is demonstrated by modelling real experiments: crack located in the middle of

Prostate specific antigen - brief update on its clinical use | Heyns ...

African Journals Online (AJOL)

Prostate specific antigen - brief update on its clinical use. ... (45 years in those with a family history of prostate cancer and – possibly – African men); ... PSA doubling time (the period it takes for the PSA to double) correlates with the prognosis ...

Perceived match or mismatch on the Gottman conflict styles: associations with relationship outcome variables.

Science.gov (United States)

Busby, Dean M; Holman, Thomas B

2009-12-01

Gottman has proposed that there are 3 functional styles of conflict management in couple relationships, labeled Avoidant, Validating, and Volatile, and 1 dysfunctional style, labeled Hostile. Using a sample of 1,983 couples in a committed relationship, we test the association of perceived matches or mismatches on these conflict styles with relationship outcome variables. The results indicate that 32% of the participants perceive there is a mismatch with their conflict style and that of their partner. The Volatile-Avoidant mismatch was particularly problematic and was associated with more stonewalling, relationship problems, and lower levels of relationship satisfaction and stability than the Validating matched style and than other mismatched styles. The most problematic style was the Hostile style. Contrary to existing assumptions by Gottman, the 3 matched functional styles were not equivalent, as the Validating Style was associated with substantially better results on relationship outcome measures than the Volatile and Avoidant styles.

Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.

Science.gov (United States)

Leventhal, Joseph; Abecassis, Michael; Miller, Joshua; Gallon, Lorenzo; Ravindra, Kadiyala; Tollerud, David J; King, Bradley; Elliott, Mary Jane; Herzig, Geoffrey; Herzig, Roger; Ildstad, Suzanne T

2012-03-07

The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

Environmental determinants and spatial mismatch of mammal diversity measures in Colombia

Energy Technology Data Exchange (ETDEWEB)

Gonzalez-Maya, J.F.; Arias-Alzate, A.; Granados-Peña, R.; Mancera-Rodriguez, N.J.; Ceballos, G.

2016-07-01

Including complementary diversity measures into ecological and conservation studies should improve our ability to link species assemblages to ecosystems. Recent measures such as phylogenetic and functional diversity have furthered our understanding of assemblage patterns of ecosystems and species, allowing improved inference of ecosystem function and conservation. We evaluated spatial patterns of taxonomic, phylogenetic and functional diversity of mammals in Colombia and identified their main environmental determinants, as well as interrelationships and spatial mismatch between the three measures. We found significant effects of elevation and precipitation on species richness, slope and species richness on phylogenetic diversity, and slope and phylogenetic diversity on functional diversity. We also identified a spatial mismatch of the three measures in some areas of the country: 12% of the country for species richness and 14% for phylogenetic and functional diversity. Our results highlight the importance of including species relationships within environmental drivers with biogeographical and distribution analyses and could facilitate selection of priority areas for conservation, especially when mismatch occurs between measures. (Author)

Detecting mismatches of bird migration stopover and tree phenology in response to changing climate

Science.gov (United States)

Kellermann, Jherime L.; van Riper, Charles

2015-01-01

Migratory birds exploit seasonal variation in resources across latitudes, timing migration to coincide with the phenology of food at stopover sites. Differential responses to climate in phenology across trophic levels can result in phenological mismatch; however, detecting mismatch is sensitive to methodology. We examined patterns of migrant abundance and tree flowering, phenological mismatch, and the influence of climate during spring migration from 2009 to 2011 across five habitat types of the Madrean Sky Islands in southeastern Arizona, USA. We used two metrics to assess phenological mismatch: synchrony and overlap. We also examined whether phenological overlap declined with increasing difference in mean event date of phenophases. Migrant abundance and tree flowering generally increased with minimum spring temperature but depended on annual climate by habitat interactions. Migrant abundance was lowest and flowering was highest under cold, snowy conditions in high elevation montane conifer habitat while bird abundance was greatest and flowering was lowest in low elevation riparian habitat under the driest conditions. Phenological synchrony and overlap were unique and complementary metrics and should both be used when assessing mismatch. Overlap declined due to asynchronous phenologies but also due to reduced migrant abundance or flowering when synchrony was actually maintained. Overlap declined with increasing difference in event date and this trend was strongest in riparian areas. Montane habitat specialists may be at greatest risk of mismatch while riparian habitat could provide refugia during dry years for phenotypically plastic species. Interannual climate patterns that we observed match climate change projections for the arid southwest, altering stopover habitat condition.

Cervical Cord-Canal Mismatch: A New Method for Identifying Predisposition to Spinal Cord Injury.

Science.gov (United States)

Nouri, Aria; Montejo, Julio; Sun, Xin; Virojanapa, Justin; Kolb, Luis E; Abbed, Khalid M; Cheng, Joseph S

2017-12-01

The risk for spinal cord injuries (SCIs) ranging from devastating traumatic injuries, compression because of degenerative pathology, and neurapraxia is increased in patients with congenital spinal stenosis. Classical diagnostic criteria include an absolute anteroposterior diameter of spinal cord, which varies across patients, independent of canal size. Recent large magnetic resonance imaging studies of population cohorts have allowed newer methods to emerge that account for both cord and canal size by measuring a spinal cord occupation ratio (SCOR). A SCOR defined as ≥70% on midsagittal imaging or ≥80% on axial imaging appears to be an effective method of identifying cord-canal mismatch, but requires further validation. Cord-canal size mismatch predisposes patients to SCI because of 1) less space within the canal lowering the amount of degenerative changes needed for cord compression, and 2) less cerebrospinal fluid surrounding the spinal cord decreasing the ability to absorb kinetic forces directed at the spine. Patients with cord-canal mismatch have been reported to be at a substantially higher risk of traumatic SCI, and present with degenerative cervical myelopathy at a younger age than patients without cord-canal mismatch. However, neurologic outcome after SCI has occurred does not appear to be different in patients with or without a cord-canal mismatch. Recognition that canal and cord size are both factors which predispose to SCI supports that cord-canal size mismatch rather than a narrow cervical canal in isolation should be viewed as the underlying mechanism predisposing to SCI. Copyright © 2017. Published by Elsevier Inc.

The prognostic significance of preoperative serum cancer antigen 15-3 levels in endometrial carcinomas

Science.gov (United States)

Tas, Emre E.; Yavuz, Ayse F.

2017-01-01

Objectives: To determine the associations between serum cancer antigen 15-3 levels and prognostic factors in patients with endometrial carcinomas. Additionally, we investigated the clinical utility of serum cancer antigen 15-3 levels in the selection of low-risk patients with endometrioid type, tumor size <2 cm, myometrial invasion ≤50%, and histological grade 1-2. Methods: Ninety-six patients, who were surgically staged at Ankara Yildirim Beyazit University, Ankara, Turkey, between 2007 and 2016, were retrospectively analyzed. Demographic, clinical, and surgical characteristics were retrieved from the patients’ hospital records. A p<0.05 was considered significant. Results: Fifteen patients had advanced (≥Stage II) disease, 14 patients had Type 2 histology, 20 patients had Grade 3 tumors, 23 patients had lymphovascular space invasion, and 10 patients had positive lymph node involvement. Serum cancer antigen 15-3 levels were significantly higher in patients with advanced (≥Stage II) disease, Type 2 histology, Grade 3 tumors, lymp°hovascular space invasion, and positive lymph node involvement (p<0.05). Serum cancer antigen 15-3 levels were also significantly correlated with tumor size (p=0.006). Serum cancer antigen 15-3 levels were significantly lower (95% confidence interval: 0.57−0.79; p=0.03) in low-risk patients compared to other endometrial carcinoma patients. A cutoff of 25.0 IU/mL was used to identify high-risk patients with a specificity of 100%. Conclusion: Serum cancer antigen 15-3 levels significantly correlated with prognostic factors and were a useful diagnostic tool for endometrial carcinomas. PMID:29114696

The prognostic significance of preoperative serum cancer antigen 15-3 levels in endometrial carcinomas

Directory of Open Access Journals (Sweden)

Emre E. Tas

2017-11-01

Full Text Available Objectives: To determine the associations between serum cancer antigen 15-3 levels and prognostic factors in patients with endometrial carcinomas. Additionally, we investigated the clinical utility of serum cancer antigen 15-3 levels in the selection of low-risk patients with endometrioid type, tumor size less than 2 cm, myometrial invasion ≤50%, and histological grade 1-2. Methods: Ninety-six patients, who were surgically staged at Ankara Yildirim Beyazit University, Ankara, Turkey, between 2007 and 2016, were retrospectively analyzed. Demographic, clinical, and surgical characteristics were retrieved from the patients’ hospital records. A p less than 0.05 was considered significant. Results: Fifteen patients had advanced (≥Stage II disease, 14 patients had Type 2 histology, 20 patients had Grade 3 tumors, 23 patients had lymphovascular space invasion, and 10 patients had positive lymph node involvement. Serum cancer antigen 15-3 levels were significantly higher in patients with advanced (≥Stage II disease, Type 2 histology, Grade 3 tumors, lymphovascular space invasion, and positive lymph node involvement (p less than 0.05. Serum cancer antigen 15-3 levels were also significantly correlated with tumor size (p=0.006. Serum cancer antigen 15-3 levels were significantly lower (95% confidence interval: 0.57−0.79; p=0.03 in low-risk patients compared to other endometrial carcinoma patients. A cutoff of 25.0 IU/mL was used to identify high-risk patients with a specificity of 100%. Conclusion: Serum cancer antigen 15-3 levels significantly correlated with prognostic factors and were a useful diagnostic tool for endometrial carcinomas.

Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

Science.gov (United States)

Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

2001-06-14

Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

Antiviral activity of Small interfering RNAs: Specificity testing using heterologous virus reveals interferon-related effects overlooked by conventional mismatch controls

DEFF Research Database (Denmark)

Schyth, Brian Dall; Lorenzen, Niels; Pedersen, Finn Skou

2006-01-01

to the viral glycoprotein gene of the target-virus efficiently inhibited viral multiplication in infected cell cultures, while two of three corresponding mismatched siRNAs did not have this effect. This suggested specific interference, but similar results were obtained when the same siRNAs were tested against...... a heterologous virus. Further analyses revealed that the siRNAs induced a non-target-specific anti-viral effect correlating with upregulation of the interferon induced Mx gene....

Fuzzy Backstepping Sliding Mode Control for Mismatched Uncertain System

Directory of Open Access Journals (Sweden)

H. Q. Hou

2014-06-01

Full Text Available Sliding mode controllers have succeeded in many control problems that the conventional control theories have difficulties to deal with; however it is practically impossible to achieve high-speed switching control. Therefore, in this paper an adaptive fuzzy backstepping sliding mode control scheme is derived for mismatched uncertain systems. Firstly fuzzy sliding mode controller is designed using backstepping method based on the Lyapunov function approach, which is capable of handling mismatched problem. Then fuzzy sliding mode controller is designed using T-S fuzzy model method, it can improve the performance of the control systems and their robustness. Finally this method of control is applied to nonlinear system as a case study; simulation results are also provided the performance of the proposed controller.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

Directory of Open Access Journals (Sweden)

Isabel Correa

2018-03-01

Full Text Available Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1 specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells.

Science.gov (United States)

Correa, Isabel; Ilieva, Kristina M; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F; Tutt, Andrew N J; Nestle, Frank O; Karagiannis, Panagiotis; Lacy, Katie E; Karagiannis, Sophia N

2018-01-01

Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

Science.gov (United States)

Correa, Isabel; Ilieva, Kristina M.; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F.; Tutt, Andrew N. J.; Nestle, Frank O.; Karagiannis, Panagiotis; Lacy, Katie E.; Karagiannis, Sophia N.

2018-01-01

Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. PMID:29628923

Distinct mutational signatures characterize concurrent loss of polymerase proofreading and mismatch repair.

Science.gov (United States)

Haradhvala, N J; Kim, J; Maruvka, Y E; Polak, P; Rosebrock, D; Livitz, D; Hess, J M; Leshchiner, I; Kamburov, A; Mouw, K W; Lawrence, M S; Getz, G

2018-05-01

Fidelity of DNA replication is maintained using polymerase proofreading and the mismatch repair pathway. Tumors with loss of function of either mechanism have elevated mutation rates with characteristic mutational signatures. Here we report that tumors with concurrent loss of both polymerase proofreading and mismatch repair function have mutational patterns that are not a simple sum of the signatures of the individual alterations, but correspond to distinct, previously unexplained signatures: COSMIC database signatures 14 and 20. We then demonstrate that in all five cases in which the chronological order of events could be determined, polymerase epsilon proofreading alterations precede the defect in mismatch repair. Overall, we illustrate that multiple distinct mutational signatures can result from different combinations of a smaller number of mutational processes (of either damage or repair), which can influence the interpretation and discovery of mutational signatures.

The Scientist and the Educational Development Team: An Impedance Mismatch?

Science.gov (United States)

Pompea, S. M.

2001-05-01

This talk describes my experiences and those of several other scientists who have worked on teams to develop new instructional materials and programs. At each stage of the development process we try to communicate our skills and experiences to the rest of the development team. In turn, the experiences of non-scientist educators on the team must be communicated to us. However, in many cases there is an "impedance mismatch" which makes communication difficult. One primary source of this mismatch is the scientist's lack of experience with schools, students, teachers, school administrators, museums, and the public. The result of this mismatch can leave the scientist in one limited, but useful role: proofreader and critic. Unfortunately, this can hardly be described as a partnership. This talk gives some advice, based on 25 years of educational materials and program development work, on how to avoid such a limited role. The talk would be appropriate for those scientists who want to lead, inspire, or significantly contribute to educational initiatives and to share in the frustration and the rewards enjoyed by professional educators and professional educational developers. S. Pompea is an adjunct faculty member of Steward Observatory of the University of Arizona.

Magnetic source localization of early visual mismatch response

NARCIS (Netherlands)

Susac, A.; Heslenfeld, D.J.; Huonker, R.; Supek, S.

2014-01-01

Previous studies have reported a visual analogue of the auditory mismatch negativity (MMN) response that is based on sensory memory. The neural generators and attention dependence of the visual MMN (vMMN) still remain unclear. We used magnetoencephalography (MEG) and spatio-temporal source

Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions In Vivo.

Science.gov (United States)

Pei, Xiaolei; Earley, Lauriel Freya; He, Yi; Chen, Xiaojing; Hall, Nikita Elexa; Samulski, Richard Jude; Li, Chengwen

2018-01-01

Adeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an in vitro analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions. In the present study, we examined capsid antigen presentation from administration of empty virions in animal models. In wild-type mice, similar to AAV full particles, capsid antigen presentation from AAV empty virion infection was dose dependent, and the kinetics studies showed that antigen presentation was detected from 2 to 40 days after AAV empty virion administration. In the transporter associated with antigen processing 1 deficient (TAP-/-) mice, capsid antigen presentation was inhibited from both AAV full and empty virions, but higher inhibition was achieved from AAV full particle administration than that from empty virions. This indicates that the pathway of capsid antigen presentation from AAV transduction is dependent on proteasome-mediated degradation of AAV capsids (mainly for full particles) and that the endosomal pathway may also play a role in antigen presentation from empty particles but not full virions. The capsid antigen presentation efficiency from AAV preparations was positively correlated with the amount of empty virions contaminated with full particles. Collectively, the results indicate that contamination of AAV empty virions induces efficient antigen presentation in vivo and the mechanism of capsid antigen presentation from empty virions involves both endosomal and proteasomal pathways. The elucidation of capsid antigen presentation from AAV empty

Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator

Science.gov (United States)

Pierre, Valérie C.; Kaiser, Jens T.; Barton, Jacqueline K.

2007-01-01

We report the 1.1-Å resolution crystal structure of a bulky rhodium complex bound to two different DNA sites, mismatched and matched in the oligonucleotide 5′-(dCGGAAATTCCCG)2-3′. At the AC mismatch site, the structure reveals ligand insertion from the minor groove with ejection of both mismatched bases and elucidates how destabilized mispairs in DNA may be recognized. This unique binding mode contrasts with major groove intercalation, observed at a matched site, where doubling of the base pair rise accommodates stacking of the intercalator. Mass spectral analysis reveals different photocleavage products associated with the two binding modes in the crystal, with only products characteristic of mismatch binding in solution. This structure, illustrating two clearly distinct binding modes for a molecule with DNA, provides a rationale for the interrogation and detection of mismatches. PMID:17194756

Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

Science.gov (United States)

Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

2012-01-01

Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

Directory of Open Access Journals (Sweden)

Ewoud Bernardus Compeer

2012-03-01

Full Text Available The cross-presentation of endocytosed antigen as peptide/class I MHC complexes plays a central role in the elicitation of CD8+ T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells (APC capable of antigen cross-presentation, description of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC, there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlight DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, recycling and maturation including the sorting of membrane proteins, dynamic remodeling of endosomal structures and cell-surface directed endosomal trafficking. We will conclude with description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

A P300 brain-computer interface based on a modification of the mismatch negativity paradigm.

Science.gov (United States)

Jin, Jing; Sellers, Eric W; Zhou, Sijie; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2015-05-01

The P300-based brain-computer interface (BCI) is an extension of the oddball paradigm, and can facilitate communication for people with severe neuromuscular disorders. It has been shown that, in addition to the P300, other event-related potential (ERP) components have been shown to contribute to successful operation of the P300 BCI. Incorporating these components into the classification algorithm can improve the classification accuracy and information transfer rate (ITR). In this paper, a single character presentation paradigm was compared to a presentation paradigm that is based on the visual mismatch negativity. The mismatch negativity paradigm showed significantly higher classification accuracy and ITRs than a single character presentation paradigm. In addition, the mismatch paradigm elicited larger N200 and N400 components than the single character paradigm. The components elicited by the presentation method were consistent with what would be expected from a mismatch paradigm and a typical P300 was also observed. The results show that increasing the signal-to-noise ratio by increasing the amplitude of ERP components can significantly improve BCI speed and accuracy. The mismatch presentation paradigm may be considered a viable option to the traditional P300 BCI paradigm.

Imagery mismatch negativity in musicians.

Science.gov (United States)

Herholz, Sibylle C; Lappe, Claudia; Knief, Arne; Pantev, Christo

2009-07-01

The present study investigated musical imagery in musicians and nonmusicians by means of magnetoencephalography (MEG). We used a new paradigm in which subjects had to continue familiar melodies in their mind and then judged if a further presented tone was a correct continuation of the melody. Incorrect tones elicited an imagery mismatch negativity (iMMN) in musicians but not in nonmusicians. This finding suggests that the MMN component can be based on an imagined instead of a sensory memory trace and that imagery of music is modulated by musical expertise.

Minimizing the effect of process mismatch in a neuromorphic system using spike-timing-dependent adaptation.

Science.gov (United States)

Cameron, Katherine; Murray, Alan

2008-05-01

This paper investigates whether spike-timing-dependent plasticity (STDP) can minimize the effect of mismatch within the context of a depth-from-motion algorithm. To improve noise rejection, this algorithm contains a spike prediction element, whose performance is degraded by analog very large scale integration (VLSI) mismatch. The error between the actual spike arrival time and the prediction is used as the input to an STDP circuit, to improve future predictions. Before STDP adaptation, the error reflects the degree of mismatch within the prediction circuitry. After STDP adaptation, the error indicates to what extent the adaptive circuitry can minimize the effect of transistor mismatch. The circuitry is tested with static and varying prediction times and chip results are presented. The effect of noisy spikes is also investigated. Under all conditions the STDP adaptation is shown to improve performance.

Educational Mismatch and the Careers of Scientists

Science.gov (United States)

Bender, Keith A.; Heywood, John S.

2011-01-01

Previous research confirms that many employees work in jobs not well matched to their skills and education, resulting in lower pay and job satisfaction. While this literature typically uses cross-sectional data, we examine the evolution of mismatch and its consequences over a career, by using a panel data set of scientists in the USA. The results…

Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone Marrow Transplantation.

Science.gov (United States)

Imus, Philip H; Blackford, Amanda L; Bettinotti, Maria; Iglehart, Brian; Dietrich, August; Tucker, Noah; Symons, Heather; Cooke, Kenneth R; Luznik, Leo; Fuchs, Ephraim J; Brodsky, Robert A; Matsui, William H; Huff, Carol Ann; Gladstone, Douglas; Ambinder, Richard F; Borrello, Ivan M; Swinnen, Lode J; Jones, Richard J; Bolaños-Meade, Javier

2017-11-01

Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1

Conformations of MutS in DNA mismatch repair

NARCIS (Netherlands)

F.S. Groothuizen (Flora)

2015-01-01

markdownabstract__Abstract__ Prior to cell division, the DNA containing the genetic information of a cell has to be copied. During this process, errors are sometimes incorporated (so-called mismatches), which may cause genetic abnormalities in future cells. To prevent this, cells contain a DNA

Dominant phonon polarization conversion across dimensionally mismatched interfaces: Carbon-nanotube-graphene junction

Science.gov (United States)

Shi, Jingjing; Lee, Jonghoon; Dong, Yalin; Roy, Ajit; Fisher, Timothy S.; Ruan, Xiulin

2018-04-01

Dimensionally mismatched interfaces are emerging for thermal management applications, but thermal transport physics remains poorly understood. Here we consider the carbon-nanotube-graphene junction, which is a dimensionally mismatched interface between one- and two-dimensional materials and is the building block for carbon-nanotube (CNT)-graphene three-dimensional networks. We predict the transmission function of individual phonon modes using the wave packet method; surprisingly, most incident phonon modes show predominantly polarization conversion behavior. For instance, longitudinal acoustic (LA) polarizations incident from CNTs transmit mainly into flexural transverse (ZA) polarizations in graphene. The frequency stays the same as the incident mode, indicating elastic transmission. Polarization conversion is more significant as the phonon wavelength increases. We attribute such unique phonon polarization conversion behavior to the dimensional mismatch across the interface, and it opens significantly new phonon transport channels as compared to existing theories where polarization conversion is neglected.

Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

International Nuclear Information System (INIS)

Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori; Narabayashi, Masaru; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

2009-01-01

Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using one display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.

Selective alkylation of T-T mismatched DNA using vinyldiaminotriazine-acridine conjugate.

Science.gov (United States)

Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato; Nagatsugi, Fumi

2018-02-16

The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T-T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)-acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T-T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T-T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT-acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1.

Environmental determinants and spatial mismatch of mammal diversity measures in Colombia

Directory of Open Access Journals (Sweden)

González–Maya, J. F.

2016-02-01

Full Text Available Including complementary diversity measures into ecological and conservation studies should improve our ability to link species assemblages to ecosystems. Recent measures such as phylogenetic and functional diversity have furthered our understanding of assemblage patterns of ecosystems and species, allowing improved inference of ecosystem function and conservation. We evaluated spatial patterns of taxonomic, phylogenetic and functional diversity of mammals in Colombia and identified their main environmental determinants, as well as interrelationships and spatial mismatch between the three measures. We found significant effects of elevation and precipitation on species richness, slope and species richness on phylogenetic diversity, and slope and phylogenetic diversity on functional diversity. We also identified a spatial mismatch of the three measures in some areas of the country: 12% of the country for species richness and 14% for phylogenetic and functional diversity. Our results highlight the importance of including species relationships within environmental drivers with biogeographical and distribution analyses and could facilitate selection of priority areas for conservation, especially when mismatch occurs between measures.

Significance of angular mismatch between vertebral endplate and prosthetic endplate in lumbar total disc replacement.

Science.gov (United States)

Lee, Chong Suh; Chung, Sung Soo; Oh, Sung Kyun; You, Je Wook

2011-05-01

A retrospective study. To determine whether angular mismatch between the vertebral endplate and prosthetic endplate during lumbar total disc replacement (L-TDR) affects the radiological and clinical outcomes. A prosthesis anchored to the vertebral body by using a large central keel carries an inherent risk of angular mismatch between the vertebral endplate and prosthetic endplate at a segment with a greater degree of lordosis, such as L5-S1. Theoretically, this angular mismatch can cause several problems, such as segmental hyperlordosis, anterior positioning of the upper prosthesis, posterior prosthetic edge subsidence, decreased range of motion (ROM), and a poor clinical outcome. This study evaluated 64 prosthetic levels of 56 patients who were implanted with L-TDR between June 2002 and February 2006. There were 38 and 26 prosthetic levels at the L4-5 and L5-S1, respectively. The mean follow-up period was 25.6 (12 to 49) months. The angle of mismatch between the lower endplate of the upper vertebral body and the upper prosthetic plate, segmental flexion/extension ROM, segmental lordosis angle at extension, distance from the posterior wall of the vertebral body to the posterior prosthetic edge were measured by obtaining radiographs. Clinically, the Visual Analogue Scale and Oswestry Disability Index were also evaluated. The angular mismatches between the upper vertebra and prosthesis at L4-5 and L5-S1 were 1.6 degree and 5.6 degree, respectively (P body to the posterior edge of the prosthesis in L5-S1 were 6.8 degree (4 to 13), 12.8 degree (8 to 17), and 3.8 mm (1 to 6 mm) in patients with an angular mismatch of 0.05). Angular mismatch was more common in L5-S1 than in L4-5. L-TDR at the most lordotic level, L5-S1, and implantation of an upper prosthesis with a mismatched angle seem to be the causes of a reduced segmental ROM, increased segmental lordosis, and anterior malpositioning of the prosthesis. However, these changes do not affect the clinical outcomes of

Does Glycosylation as a modifier of Original Antigenic Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza?

Directory of Open Access Journals (Sweden)

Nishiura Hiroshi

2010-01-01

until the early 1940s. Later H1N1 viruses progressively added new glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes were relatively unchanged. Conclusions In this evolutionary context, Original Antigenic Sin exposure should produce an immune response increasingly mismatched to novel H1N1 in progressively younger persons. We suggest that it is this mismatch that produces both the gradation in susceptibility and the unusual toxicity. Several murine studies suggest specific cell types as a likely basis of the unusual toxicity. These studies also point to widely available pharmaceutical agents as plausible candidates for mitigating the toxic effects. The principle of Original Antigenic Sin modified by glycosylation appears to explain both the case age distribution and the unusual toxicity pattern of the novel H1N1 pandemic. In addition, it suggests pharmaceutical agents for immediate investigation for mitigation potential, and provides strategic guidance for the distribution of pandemic mitigation resources of all types.

Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage

NARCIS (Netherlands)

Schlingemann, R. O.; Hofman, P.; Vrensen, G. F.; Blaauwgeers, H. G.

1999-01-01

AIMS/HYPOTHESIS: The Pathologische Anatomie Leiden-Endothelium (PAL-E) antigen is a marker for loss of the blood-brain barrier function in brain tumours. It is endothelium specific and is associated with the endothelial plasmalemmal vesicles (caveolae) involved in transcellular transport. To test

Measuring DNA hybridization using fluorescent DNA-stabilized silver clusters to investigate mismatch effects on therapeutic oligonucleotides.

Science.gov (United States)

de Bruin, Donny; Bossert, Nelli; Aartsma-Rus, Annemieke; Bouwmeester, Dirk

2018-04-06

Short nucleic acid oligomers have found a wide range of applications in experimental physics, biology and medicine, and show potential for the treatment of acquired and genetic diseases. These applications rely heavily on the predictability of hybridization through Watson-Crick base pairing to allow positioning on a nanometer scale, as well as binding to the target transcripts, but also off-target binding to transcripts with partial homology. These effects are of particular importance in the development of therapeutic oligonucleotides, where off-target effects caused by the binding of mismatched sequences need to be avoided. We employ a novel method of probing DNA hybridization using optically active DNA-stabilized silver clusters (Ag-DNA) to measure binding efficiencies through a change in fluorescence intensity. In this way we can determine their location-specific sensitivity to individual mismatches in the sequence. The results reveal a strong dependence of the hybridization on the location of the mismatch, whereby mismatches close to the edges and center show a relatively minor impact. In parallel, we propose a simple model for calculating the annealing ratios of mismatched DNA sequences, which supports our experimental results. The primary result shown in this work is a demonstration of a novel technique to measure DNA hybridization using fluorescent Ag-DNA. With this technique, we investigated the effect of mismatches on the hybridization efficiency, and found a significant dependence on the location of individual mismatches. These effects are strongly influenced by the length of the used oligonucleotides. The novel probe method based on fluorescent Ag-DNA functions as a reliable tool in measuring this behavior. As a secondary result, we formulated a simple model that is consistent with the experimental data.

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

Studies on antigenic cross-reactivity of Trichuris ovis with host mucosal antigens in goat

Directory of Open Access Journals (Sweden)

Gautam Patra

2015-12-01

Full Text Available Objective: To ascertain whether immunodominant antigens of Trichuris ovis might share and cross react with host molecule. Methods: Two crude protein preparations from anterior and posterior parts of Trichuris ovis were characterized along with host mucosal antigen by double immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting technique. Conventional scanning electron microscopy was performed as per standard procedure. Results: Sharp and distinct bands of three antigens have been found in double immunodiffusion using hyperimmune serum raised in rabbit indicating the presence of specific antibody against each antigen. All three antigens have shown major and minor bands with molecular weight ranging from 15 to 110 kDa during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Conclusions: The antigenic cross-reactivity was thought to result from shared antigens. The existence of paracloacal papillae found in the anterior part of the male was not a unique feature for species differentiation.

Ground state energy and wave function of an off-centre donor in spherical core/shell nanostructures: Dielectric mismatch and impurity position effects

Energy Technology Data Exchange (ETDEWEB)

Ibral, Asmaa [Equipe d’Optique et Electronique du Solide, Département de Physique, Faculté des Sciences, Université Chouaïb Doukkali, B.P. 20 El Jadida Principale, El Jadida 24000 (Morocco); Laboratoire d’Instrumentation, Mesure et Contrôle, Département de Physique, Université Chouaïb Doukkali, B.P. 20 El Jadida Principale, El Jadida (Morocco); Zouitine, Asmae [Département de Physique, Ecole Nationale Supérieure d’Enseignement Technique, Université Mohammed V Souissi, B.P. 6207 Rabat-Instituts, Rabat (Morocco); Assaid, El Mahdi, E-mail: eassaid@yahoo.fr [Equipe d’Optique et Electronique du Solide, Département de Physique, Faculté des Sciences, Université Chouaïb Doukkali, B.P. 20 El Jadida Principale, El Jadida 24000 (Morocco); Laboratoire d’Instrumentation, Mesure et Contrôle, Département de Physique, Université Chouaïb Doukkali, B.P. 20 El Jadida Principale, El Jadida (Morocco); Feddi, El Mustapha [Département de Physique, Ecole Nationale Supérieure d’Enseignement Technique, Université Mohammed V Souissi, B.P. 6207 Rabat-Instituts, Rabat (Morocco); and others

2014-09-15

Ground state energy and wave function of a hydrogen-like off-centre donor impurity, confined anywhere in a ZnS/CdSe spherical core/shell nanostructure are determined in the framework of the envelope function approximation. Conduction band-edge alignment between core and shell of nanostructure is described by a finite height barrier. Dielectric constant mismatch at the surface where core and shell materials meet is taken into account. Electron effective mass mismatch at the inner surface between core and shell is considered. A trial wave function where coulomb attraction between electron and off-centre ionized donor is used to calculate ground state energy via the Ritz variational principle. The numerical approach developed enables access to the dependence of binding energy, coulomb correlation parameter, spatial extension and radial probability density with respect to core radius, shell radius and impurity position inside ZnS/CdSe core/shell nanostructure.

Ground state energy and wave function of an off-centre donor in spherical core/shell nanostructures: Dielectric mismatch and impurity position effects

International Nuclear Information System (INIS)

Ibral, Asmaa; Zouitine, Asmae; Assaid, El Mahdi; Feddi, El Mustapha

2014-01-01

Ground state energy and wave function of a hydrogen-like off-centre donor impurity, confined anywhere in a ZnS/CdSe spherical core/shell nanostructure are determined in the framework of the envelope function approximation. Conduction band-edge alignment between core and shell of nanostructure is described by a finite height barrier. Dielectric constant mismatch at the surface where core and shell materials meet is taken into account. Electron effective mass mismatch at the inner surface between core and shell is considered. A trial wave function where coulomb attraction between electron and off-centre ionized donor is used to calculate ground state energy via the Ritz variational principle. The numerical approach developed enables access to the dependence of binding energy, coulomb correlation parameter, spatial extension and radial probability density with respect to core radius, shell radius and impurity position inside ZnS/CdSe core/shell nanostructure

Luminescent platinum(II) complexes with functionalized N-heterocyclic carbene or diphosphine selectively probe mismatched and abasic DNA

OpenAIRE

Che, CM; Chen, T; To, WP; Zou, T; FUNG, SK; Lok, CN; YANG, C; Cao, B

2016-01-01

The selective targeting of mismatched DNA overexpressed in cancer cells is an appealing strategy in designing cancer diagnosis and therapy protocols. Few luminescent probes that specifically detect intracellular mismatched DNA have been reported. Here we used Pt(II) complexes with luminescence sensitive to subtle changes in the local environment and report several Pt(II) complexes that selectively bind to and identify DNA mismatches. We evaluated the complexes' DNA-binding characteristics by ...

Mismatch Negativity and P50 Sensory Gating in Abstinent Former Cannabis Users

Directory of Open Access Journals (Sweden)

Samantha J. Broyd

2016-01-01

Full Text Available Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50 in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence and 18 nonusers completed (1 a multifeature oddball task with duration, frequency, and intensity deviants and (2 a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation may be related to either self-medication or an accelerated aging process.

Follow-up of neurocysticercosis patients after treatment using an antigen detection ELISA

Directory of Open Access Journals (Sweden)

Nguekam

2003-03-01

Full Text Available Seven patients with active neurocysticercosis (NCC received an eight days treatment with albendazole and were followed up using computed tomography (CT-scan and a monoclonal antibody based ELISA for the detection of circulating antigen (Ag-ELISA. Only three patients were cured as was shown by CT-scan and by the disappearance of circulating antigens one month after treatment. After a second course of albendazole therapy, two other patients became seronegative. CT-scan showed the disappearance of viable cysts in all persons who became seronegative whereas patients who were not cured remained seropositive. These preliminary results show that this Ag-ELISA is a promising technique for monitoring the success of treatment of NCC patients because of the excellent correlation between the presence of circulating antigens and of viable brain cysts.

Standard Test Method for Determination of the Spectral Mismatch Parameter Between a Photovoltaic Device and a Photovoltaic Reference Cell

CERN Document Server

American Society for Testing and Materials. Philadelphia

2010-01-01

1.1 This test method covers a procedure for the determination of a spectral mismatch parameter used in performance testing of photovoltaic devices. 1.2 The spectral mismatch parameter is a measure of the error, introduced in the testing of a photovoltaic device, caused by mismatch between the spectral responses of the photovoltaic device and the photovoltaic reference cell, as well as mismatch between the test light source and the reference spectral irradiance distribution to which the photovoltaic reference cell was calibrated. Examples of reference spectral irradiance distributions are Tables E490 or G173. 1.3 The spectral mismatch parameter can be used to correct photovoltaic performance data for spectral mismatch error. 1.4 This test method is intended for use with linear photovoltaic devices. 1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.6 This standard does not purport to address all of the safety concerns, if any, a...

The role of the bacterial mismatch repair system in SOS-induced mutagenesis: a theoretical background

International Nuclear Information System (INIS)

Belov, O.V.; Kapralov, M.I.; Chuluunbaatar, O.; Sweilam, N.H.

2012-01-01

A theoretical study is performed of the possible role of the methyl-directed mismatch repair system in the ultraviolet-induced mutagenesis of Escherichia coli bacterial cells. For this purpose, a mathematical model of the bacterial mismatch repair system is developed. Within this model, the key pathways of this type of repair are simulated on the basis of modern experimental data related to its mechanisms. Here we have modelled in detail five main pathways of DNA misincorporation removal with different DNA exonucleases. Using our calculations, we have tested the hypothesis that the bacterial mismatch repair system is responsible for the removal of the nucleotides misincorporated by DNA polymerase V (the UmuD' 2 C complex) during ultraviolet-induced SOS response. For the theoretical analysis of the mutation frequency, we have combined the proposed mathematical approach with the model of SOS-induced mutagenesis in the E.coli bacterial cell developed earlier. Our calculations support the hypothesis that methyl-directed mismatch repair influences the mutagenic effect of ultraviolet radiation

Duffy blood group antigens: structure, serological properties and function

Directory of Open Access Journals (Sweden)

Ewa Łukasik

2016-03-01

Full Text Available Duffy (Fy blood group antigens are located on seven-transmembrane glycoprotein expressed on erythrocytes and endothelial cells, which acts as atypical chemokine receptor (ACKR1 and malarial receptor. The biological role of the Duffy glycoprotein has not been explained yet. It is suggested that Duffy protein modulate the intensity of the inflammatory response. The Duffy blood group system consists of two major antigens, Fya and Fyb, encoded by two codominant alleles designated FY*A and FY*B which differ by a single nucleotide polymorphism (SNP at position 125G>A of the FY gene that results in Gly42Asp amino acid change in the Fya and Fyb antigens, respectively. The presence of antigen Fya and/or Fyb on the erythrocytes determine three Duffy-positive phenotypes: Fy(a+b-, Fy(a-b+ and Fy(a+b+, identified in Caucasian population. The Duffy-negative phenotype Fy(a-b-, frequent in Africans, but very rare in Caucasians, is defined by the homozygous state of FY*B-33 alleles. The FY*B-33 allele is associated with a SNP -33T>C in the promoter region of the FY gene, which suppresses erythroid expression of this gene without affecting its expression in other tissues. The FY*X allele, found in Caucasians, is correlated with weak expression of Fyb antigen. Fyx antigen differs from the native Fyb by the Arg89Cys and Ala100Thr amino acid substitutions due to SNPs: 265C>T and 298G>A in FY*B allele. The frequency of the FY alleles shows marked geographic disparities, the FY*B-33 allele is predominant in Africans, the FY*B in Caucasians, while the FY*A allele is dominant in Asians and it is the most prevalent allele globally.

Space-charge driven emittance growth in a 3D mismatched anisotropic beam

International Nuclear Information System (INIS)

Qiang, J.; Ryne, R.D.; Hofmann, I.

2002-01-01

In this paper we present a 3D simulation study of the emittance growth in a mismatched anisotropic beam. The equipartitioning driven by a 4th order space-charge resonance can be significantly modified by the presence of mismatch oscillation and halo formation. This causes emittance growth in both the longitudinal and transverse directions which could drive the beam even further away from equipartition. The averaged emittance growth per degree freedom follows the upper bound of the 2D free energy limit plus the contributions from equipartitioning

Chlorphenesin: an antigen-associated immunosuppressant.

Science.gov (United States)

Whang, H Y; Neter, E

1970-07-01

Chlorphenesin (3-p-chlorophenoxy-1,2-propanediol), when injected intravenously together with either of two common bacterial antigens, inhibits the antibody response of the rabbit. The antigens studied are those common to Enterobacteriaceae and to gram-positive bacteria. The immunosuppression is contingent upon incubation of chlorphenesin and antigen in vitro prior to administration, since separate injection of antigen and inhibitor or of mixtures without prior incubation yields undiminished antibody response. Chlorphenesin, as shown by hemagglutination-inhibition tests, does not alter the antigenic determinants, because antibody neutralization occurs in the presence or absence of the drug. The immunosuppressive effect is reversible, since precipitation of chlorphenesin at 4 C substantially restores immunogenicity. Animals immunized with antigen-drug mixtures, which fail to respond with significant antibody production, nonetheless are immunologically primed. It is concluded that chlorphenesin represents another example of antigen-associated immunosuppressants.

Tissue polypeptide antigen activity in cerebrospinal fluid

DEFF Research Database (Denmark)

Bach, F; Söletormos, Georg; Dombernowsky, P

1991-01-01

Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis......, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPp...... metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells...

Log-layer mismatch and modeling of the fluctuating wall stress in wall-modeled large-eddy simulations

Science.gov (United States)

Yang, Xiang I. A.; Park, George Ilhwan; Moin, Parviz

2017-10-01

Log-layer mismatch refers to a chronic problem found in wall-modeled large-eddy simulation (WMLES) or detached-eddy simulation, where the modeled wall-shear stress deviates from the true one by approximately 15 % . Many efforts have been made to resolve this mismatch. The often-used fixes, which are generally ad hoc, include modifying subgrid-scale stress models, adding a stochastic forcing, and moving the LES-wall-model matching location away from the wall. An analysis motivated by the integral wall-model formalism suggests that log-layer mismatch is resolved by the built-in physics-based temporal filtering. In this work we investigate in detail the effects of local filtering on log-layer mismatch. We show that both local temporal filtering and local wall-parallel filtering resolve log-layer mismatch without moving the LES-wall-model matching location away from the wall. Additionally, we look into the momentum balance in the near-wall region to provide an alternative explanation of how LLM occurs, which does not necessarily rely on the numerical-error argument. While filtering resolves log-layer mismatch, the quality of the wall-shear stress fluctuations predicted by WMLES does not improve with our remedy. The wall-shear stress fluctuations are highly underpredicted due to the implied use of LES filtering. However, good agreement can be found when the WMLES data are compared to the direct numerical simulation data filtered at the corresponding WMLES resolutions.

Educational mismatches for second generation migrants. An analysis of applied science graduates in the Netherlands

NARCIS (Netherlands)

Falcke, Swantje; Meng, Christoph; Nollen, Romy

2016-01-01

Educational mismatches, i.e. diferences between the education attained and required for a job have been found to negatively affect earnings and job satisfaction and thus lead to a lower return to education. In this paper we aim to see whether immigrants are more prone to educational mismatches and

[Pathogens in expressed prostatic secretion and their correlation with serum prostate specific antigen: analysis of 320 cases].

Science.gov (United States)

Wang, Shu-Xia; Zhang, Jia-Ming; Wu, Kai; Chen, Juan; Shi, Jian-Feng

2014-08-01

To investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis. Three EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot. Totally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P Prostatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.

Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium.

Science.gov (United States)

Bakry, Doua; Aronson, Melyssa; Durno, Carol; Rimawi, Hala; Farah, Roula; Alharbi, Qasim Kholaif; Alharbi, Musa; Shamvil, Ashraf; Ben-Shachar, Shay; Mistry, Matthew; Constantini, Shlomi; Dvir, Rina; Qaddoumi, Ibrahim; Gallinger, Steven; Lerner-Ellis, Jordan; Pollett, Aaron; Stephens, Derek; Kelies, Steve; Chao, Elizabeth; Malkin, David; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

2014-03-01

Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (psyndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

Science.gov (United States)

Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato

2018-01-01

Abstract The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T–T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)–acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T–T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T–T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT–acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1. PMID:29309639

Position dependent mismatch discrimination on DNA microarrays – experiments and model

Directory of Open Access Journals (Sweden)

Michel Wolfgang

2008-12-01

Full Text Available Abstract Background The propensity of oligonucleotide strands to form stable duplexes with complementary sequences is fundamental to a variety of biological and biotechnological processes as various as microRNA signalling, microarray hybridization and PCR. Yet our understanding of oligonucleotide hybridization, in particular in presence of surfaces, is rather limited. Here we use oligonucleotide microarrays made in-house by optically controlled DNA synthesis to produce probe sets comprising all possible single base mismatches and base bulges for each of 20 sequence motifs under study. Results We observe that mismatch discrimination is mostly determined by the defect position (relative to the duplex ends as well as by the sequence context. We investigate the thermodynamics of the oligonucleotide duplexes on the basis of double-ended molecular zipper. Theoretical predictions of defect positional influence as well as long range sequence influence agree well with the experimental results. Conclusion Molecular zipping at thermodynamic equilibrium explains the binding affinity of mismatched DNA duplexes on microarrays well. The position dependent nearest neighbor model (PDNN can be inferred from it. Quantitative understanding of microarray experiments from first principles is in reach.

Role descriptions induce gender mismatch effects in eye movements during reading

Directory of Open Access Journals (Sweden)

Chiara eReali

2015-11-01

Full Text Available The present eye-tracking study investigates the effect of gender typicality on the resolution of anaphoric personal pronouns in English. Participants read descriptions of a person performing a typically male, typically female or gender-neutral occupational activity. The description was followed by an anaphoric reference (he or she which revealed the referent's gender. The first experiment presented roles which were highly typical for men (e.g., blacksmith or for women (e.g., beautician, the second experiment presented role descriptions with a moderate degree of gender typicality (e.g., psychologist, lawyer. Results revealed a gender mismatch effect in early and late measures in the first experiment and in an early measure in the second experiment. Moreover, eye-movement data for highly typical roles correlated with explicit typicality ratings. The results are discussed from a cross-linguistic perspective, comparing natural gender languages and grammatical gender languages. An interpretation of the cognitive representation of typicality beliefs is proposed.

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

International Nuclear Information System (INIS)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T.

1990-01-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis

Structure Transformation and Coherent Interface in Large Lattice-Mismatched Nanoscale Multilayers

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J. Y. Xie

2013-01-01

Full Text Available Nanoscale Al/W multilayers were fabricated by DC magnetron sputtering and characterized by transmission electron microscopy and high-resolution electron microscopy. Despite the large lattice mismatch and significantly different lattice structures between Al and W, a structural transition from face-centered cubic to body-centered cubic in Al layers was observed when the individual layer thickness was reduced from 5 nm to 1 nm, forming coherent Al/W interfaces. For potential mechanisms underlying the observed structure transition and forming of coherent interfaces, it was suggested that the reduction of interfacial energy and high stresses induced by large lattice-mismatch play a crucial role.

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

Energy Technology Data Exchange (ETDEWEB)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T. (Medical College of Wisconsin, Milwaukee (USA))

1990-05-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus

International Nuclear Information System (INIS)

Salfeld, J.; Pfaff, E.; Noah, M.; Schaller, H.

1989-01-01

The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis virus nucleocapsid

A Bulky Rhodium Complex Bound to an Adenosine-Adenosine DNA Mismatch: General Architecture of the Metalloinsertion Binding Mode†

Science.gov (United States)

Zeglis, Brian M.; Pierre, Valérie C.; Kaiser, Jens T.; Barton, Jacqueline K.

2009-01-01

Two crystal structures are determined for Δ-Rh(bpy)2(chrysi)3+ (chrysi = 5,6-chrysenequinone diimine) bound to the oligonucleotide duplex 5′-CGGAAATTACCG-3′ containing two adenosine-adenosine mismatches (italics) through metalloinsertion. Diffraction quality crystals with two different space groups (P3221 and P43212) were obtained under very similar crystallization conditions. In both structures, the bulky rhodium complex inserts into the two mismatched sites from the minor groove side, ejecting the mismatched bases into the major groove. The conformational changes are localized to the mismatched site; the metal complex replaces the mismatched base pair without an increase in base pair rise. The expansive metal complex is accommodated in the duplex by a slight opening in the phosphodiester backbone; all sugars retain a C2′-endo puckering, and flanking base pairs neither stretch nor shear. The structures differ, however, in that in one of the structures, an additional metal complex is bound by intercalation from the major groove at the central 5′-AT-3′ step. We conclude that this additional metal complex is intercalated into this central step because of crystal packing forces. The structures described here of Δ-Rh(bpy)2(chrysi)3+ bound to thermodynamically destabilized AA mismatches share critical features with binding by metalloinsertion in two other oligonucleotides containing different single base mismatches. These results underscore the generality of the metalloinsertion as a new mode of non-covalent binding by small molecules with a DNA duplex. PMID:19374348

Channel normalization technique for speech recognition in mismatched conditions

CSIR Research Space (South Africa)

Kleynhans, N

2008-11-01

Full Text Available , where one wishes to use any available training data for a variety of purposes. Research into a new channel normalization (CN) technique for channel mismatched speech recognition is presented. A process of inverse linear filtering is used in order...

Analytical Expressions for Harmonic Distortion at Low Frequencies due to Device Mismatch in CMOS Current Mirrors

DEFF Research Database (Denmark)

Bruun, Erik

1999-01-01

One of the origins of harmonic distortion in current mirrors is the inevitable mismatch between the mirror transistors. In this brief we examine both single current mirrors and complementary class AB current mirrors and develop analytical expressions for the mismatch induced harmonic distortion. ...

Abnormal auditory mismatch response in tinnitus sufferers with high-frequency hearing loss is associated with subjective distress level

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Berg Patrick

2004-03-01

Full Text Available Abstract Background Tinnitus is an auditory sensation frequently following hearing loss. After cochlear injury, deafferented neurons become sensitive to neighbouring intact edge-frequencies, guiding an enhanced central representation of these frequencies. As psychoacoustical data 123 indicate enhanced frequency discrimination ability for edge-frequencies that may be related to a reorganization within the auditory cortex, the aim of the present study was twofold: 1 to search for abnormal auditory mismatch responses in tinnitus sufferers and 2 relate these to subjective indicators of tinnitus. Results Using EEG-mismatch negativity, we demonstrate abnormalities (N = 15 in tinnitus sufferers that are specific to frequencies located at the audiometrically normal lesion-edge as compared to normal hearing controls (N = 15. Groups also differed with respect to the cortical locations of mismatch responsiveness. Sources in the 90–135 ms latency window were generated in more anterior brain regions in the tinnitus group. Both measures of abnormality correlated with emotional-cognitive distress related to tinnitus (r ~ .76. While these two physiological variables were uncorrelated in the control group, they were correlated in the tinnitus group (r = .72. Concerning relationships with parameters of hearing loss (depth and slope, slope turned out to be an important variable. Generally, the steeper the hearing loss is the less distress related to tinnitus was reported. The associations between slope and the relevant neurophysiological variables are in agreement with this finding. Conclusions The present study is the first to show near-to-complete separation of tinnitus sufferers from a normal hearing control group based on neurophysiological variables. The finding of lesion-edge specific effects and associations with slope of hearing loss corroborates the assumption that hearing loss is the basis for tinnitus development. It is likely that some central

Immunological correlates for protection against intranasal challenge of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits.

Science.gov (United States)

Weiss, Shay; Kobiler, David; Levy, Haim; Marcus, Hadar; Pass, Avi; Rothschild, Nili; Altboum, Zeev

2006-01-01

Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to challenge with B. anthracis spores. Immunized rabbits were challenged by intranasal spore instillation with one of two virulent strains (strains Vollum and ATCC 6605). The immune competence was estimated by measuring the level of total anti-PA antibodies, the neutralizing antibody titers, and the conferred protective immunity. The results indicate that total anti-PA antibody titers greater than 1 x 10(5) conferred protection, whereas lower titers (between 10(4) and 10(5)) provided partial protection but failed to predict protection. Neutralizing antibody titers between 500 and 800 provided partial protection, while titers higher than 1,000 conferred protection. In conclusion, this study emphasizes that regardless of the immunization regimen or the time of challenge, neutralizing antibody titers are better predictors of protection than total anti-PA titers.

Fundamental and clinical evaluation of ''SCC RIABEAD'' kit for immunoradiometric assay of squamous cell carcinoma related antigen

International Nuclear Information System (INIS)

Koizumi, Mitsuru; Endo, Keigo; Nakajima, Kotoko

1987-01-01

A commercial ''SCC RIABEAD'' kit for immunoradiometric assay of squamous cell carcinoma related antigen (SCC antigen) was fundamentally and clinically evaluated. Laboratory performance was satisfactory for intra-assay and inter-assay reproducibility, recovery, and dilution, with rapid and simple measurement techniques. Seropositivity for SCC antigen was significantly higher for squamous cell carcinoma of the liver and uterine cervix than the other histology types. In the case of cervical squamous cell carcinoma, it increased with progressing disease. Post-treatment serum levels of SCC antigen returned to negative. SCC antigen is considered to be a useful tumor marker for these diseases. There was a good correlation between the measurement values obtained from the present and conventional (SCC RIAKIT) assays. The present assay remarkably decreased false-positive cases of pulmonary benign diseases. The results showed a ''SCC RIABEAD'' to be a favorable kit for immunoradiometric assay of SSC antigen, as compared with conventional assay kit. (Namekawa, K.)

Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

Science.gov (United States)

Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam

2018-01-01

Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. PMID:29488881

Mismatch analysis of humeral nailing. Antegrade versus retrograde insertion

International Nuclear Information System (INIS)

Mahaisavariya, B.; Jiamwatthanachai, P.; Aroonjarattham, P.; Aroonjarattham, K.; Wongcumchang, M.; Sitthiseripratip, K.

2011-01-01

Closed humeral nailing is now considered an alternative treatment for humeral-shaft fracture. The nail can be inserted with either the antegrade or retrograde method. We investigated and compared the problem of geometric mismatch of the humeral nail to the humerus between the two methods of insertion. The study was performed using virtual simulation based on computed tomography (CT) data of 76 Thai cadaveric humeri and the commonly used Russell-Taylor humeral nail 8 mm in diameter and 220 mm long. Mismatch of the nail to the intact humerus was analyzed and compared between the antegrade and retrograde nailing approaches. The results showed: the diameter of the medullary canal averaged 7.9-13.8 mm; the minimal reaming diameter to accommodate virtual nail insertion averaged 8.8-14.8 mm for the antegrade and 8.8-29.3 mm for the retrograde approach; the minimal reaming thickness of the inner cortex averaged 0.1-1.5 mm for the antegrade and 0.1-9.9 mm for the retrograde approach; the percentages of cortical bone removed prior to nail insertion were 3.8-107.1% and 3.8-1,287.6% for the antegrade and retrograde approaches, respectively; the eccentricity of the nail-medullary canal center were 0.4-3.4 and 0.4-10.6 mm for the antegrade and retrograde approaches, respectively. Less mismatching occurred with antegrade nailing than with the retrograde approach. Retrograde nailing requires excessive reaming at the distal part of the humerus to accommodate nail insertion. This may create bone weakness and the risk of supracondylar fracture. (author)

Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome

NARCIS (Netherlands)

Westdorp, Harm; Kolders, Sigrid; Hoogerbrugge, Nicoline; de Vries, I Jolanda M; Jongmans, Marjolijn C.J.; Schreibelt, Gerty

2017-01-01

Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations

Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells.

Science.gov (United States)

Komada, Y; Ochiai, H; Shimizu, K; Azuma, E; Kamiya, H; Sakurai, M

1990-07-01

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

Science.gov (United States)

Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

2013-11-01

Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Design Impedance Mismatch Physical Unclonable Functions for IoT Security

Directory of Open Access Journals (Sweden)

Xiaomin Zheng

2017-01-01

Full Text Available We propose a new design, Physical Unclonable Function (PUF scheme, for the Internet of Things (IoT, which has been suffering from multiple-level security threats. As more and more objects interconnect on IoT networks, the identity of each thing is very important. To authenticate each object, we design an impedance mismatch PUF, which exploits random physical factors of the transmission line to generate a security unique private key. The characteristic impedance of the transmission line and signal transmission theory of the printed circuit board (PCB are also analyzed in detail. To improve the reliability, current feedback amplifier (CFA method is applied on the PUF. Finally, the proposed scheme is implemented and tested. The measure results show that impedance mismatch PUF provides better unpredictability and randomness.

Femoral head retroposition as a potential compensatory mechanism in patients with a severe mismatch between pelvic incidence and lumbar lordosis.

Science.gov (United States)

Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

2017-12-01

Severe mismatch between pelvic incidence (PI) and lumbar lordosis (LL) leads to extra anterior displacement of the gravity line. The objective of this study is to investigate whether femoral head retroposition is a separate compensatory mechanism responsible for the extra anterior displacement. Based on the values of PI and LL, 94 patients were divided into the PI-LL match group (PI-LL ≤ 0°), the mild PI-LL mismatch group (20°> PI-LL >0°), and the severe PI-LL mismatch group (PI-LL ≥ 20°). A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), sagittal vertical axis (SVA), S1 overhang, femoral head shift (FHS), and pelvic shift (PS) were measured and compared among the three groups. The severe PI-LL mismatch group exhibited significantly greater PI, PI-LL, PT, KFA, SVA, PS, and FHS, and less LL and TK, compared with the control and mild PI-LL mismatch group. The mild PI-LL mismatch group had significantly greater PI-LL, PT, KFA, TOA, and S1 overhang, and less LL and SS than the control group. SS, TOA, and S1 overhang in the severe PI-LL mismatch group differed significantly from that in the control group, but did not differ significantly from that in the mild PI-LL mismatch group. Femoral head retroposition is an entirely separate compensatory mechanism and, in this study, participated in the compensation for the anterior displacement of the gravity line induced by extra-sagittal spinal malalignment in patients with severe PI-LL mismatch.

Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

Directory of Open Access Journals (Sweden)

Huei-Mei Liu

Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

DNA Ploidy Measured on Archived Pretreatment Biopsy Material May Correlate With Prostate-Specific Antigen Recurrence After Prostate Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca [Radiation Oncology, Provincial Prostate Brachytherapy Program, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); MacAulay, Calum [Department of Integrative Oncology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Hayes, Malcolm [Department of Pathology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Korbelik, Jagoda [Department of Integrative Oncology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Morris, W. James [Radiation Oncology, Provincial Prostate Brachytherapy Program, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada); Palcic, Branko [Department of Integrative Oncology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia (Canada)

2013-08-01

Purpose: To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Methods and Materials: Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate {sup 125}I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used for the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. Results: The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with “excellent” dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as “nonexcellent” (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and “excellent” dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Conclusions: Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a

Antigenic evaluation of a recombinant baculovirus-expressed Sarcocystis neurona SAG1 antigen.

Science.gov (United States)

Gupta, G D; Lakritz, J; Saville, W J; Livingston, R S; Dubey, J P; Middleton, J R; Marsh, A E

2004-10-01

Sarcocystis neurona is the primary parasite associated with equine protozoal myeloencephalitis (EPM). This is a commonly diagnosed neurological disorder in the Americas that infects the central nervous system of horses. Current serologic assays utilize culture-derived parasites as antigen. This method requires large numbers of parasites to be grown in culture, which is labor intensive and time consuming. Also, a culture-derived whole-parasite preparation contains conserved antigens that could cross-react with antibodies against other Sarcocystis species and members of Sarcocystidae such as Neospora spp., Hammondia spp., and Toxoplasma gondii. Therefore, there is a need to develop an improved method for the detection of S. neurona-specific antibodies. The sera of infected horses react strongly to surface antigen 1 (SnSAG1), an approximately 29-kDa protein, in immunoblot analysis, suggesting that it is an immunodominant antigen. The SnSAG1 gene of S. neurona was cloned, and recombinant S. neurona SAG1 protein (rSnSAG1-Bac) was expressed with the use of a baculovirus system. By immunoblot analysis, the rSnSAG1-Bac antigen detected antibodies to S. neurona from naturally infected and experimentally inoculated equids, cats, rabbit, mice, and skunk. This is the first report of a baculovirus-expressed recombinant S. neurona antigen being used to detect anti-S. neurona antibodies in a variety of host species.

Prostate-specific antigen density: correlation with histological diagnosis of prostate cancer, benign prostatic hyperplasia and prostatitis

NARCIS (Netherlands)

van Iersel, M. P.; Witjes, W. P.; de la Rosette, J. J.; Oosterhof, G. O.

1995-01-01

To assess the additional value of prostate-specific antigen density in the diagnosis of prostate cancer in patients who undergo prostate biopsies. The study comprised 376 patients with symptoms of prostatism who were undergoing prostate biopsy. Digital rectal examination (DRE) and transrectal

Multiuser Random Coding Techniques for Mismatched Decoding

OpenAIRE

Scarlett, Jonathan; Martinez, Alfonso; Guillén i Fàbregas, Albert

2016-01-01

This paper studies multiuser random coding techniques for channel coding with a given (possibly suboptimal) decoding rule. For the mismatched discrete memoryless multiple-access channel, an error exponent is obtained that is tight with respect to the ensemble average, and positive within the interior of Lapidoth's achievable rate region. This exponent proves the ensemble tightness of the exponent of Liu and Hughes in the case of maximum-likelihood decoding. An equivalent dual form of Lapidoth...

Development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

International Nuclear Information System (INIS)

Knauf, S.; Urbach, G.I.

1978-01-01

Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinants as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was virtually no correlation (r 2 = 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay

Use of nitrocellulose blotting for the study of hepatitis B surface antigen electrophoresed in agarose gels

Energy Technology Data Exchange (ETDEWEB)

McMichael, J C; Greisiger, L M; Millman, I [Institute for Cancer Research, Philadelphia, PA (USA). Fox Chase Cancer Center

1981-08-28

Nitrocellulose-protein blotting of serum electrophoresed in agarose gels has been adapted for the study of hepatitis B surface antigen (HBsAg). /sup 125/I-labeled anti-HBs was used as the antigen probe, and the electrophoretic migration was monitored by autoradiography. The method required 3 ..mu..l or less of serum and could detect as little as 1 pg of purified HBsAg. Typically, the authors observed two bands of HBsAg; a moving band which migrated about one-third the distance moved by human serum albumin and a non-migratory band which remained at the loading site. Some examples of the use of the method include: (1) empirical methods for correlating HBsAg concentration in serum to film darkness; (2) observations of mobility changes in serial sera from dialysis patients with chronic HBsAg antigenemia; and (3) detection of related antigens such as antigen from the PLC/PRF/5 hepatoma tissue culture line and the cross-reacting woodchuck hepatitis virus surface antigen (WHsAg).

Source-Sink Mismatch Causing Functional Conduction Block in Re-Entrant Ventricular Tachycardia.

Science.gov (United States)

Ciaccio, Edward J; Coromilas, James; Wit, Andrew L; Peters, Nicholas S; Garan, Hasan

2018-01-01

Ventricular tachycardia (VT) caused by a re-entrant circuit is a life-threatening arrhythmia that at present cannot always be treated adequately. A realistic model of re-entry would be helpful to accurately guide catheter ablation for interruption of the circuit. In this review, models of electrical activation wavefront propagation during onset and maintenance of re-entrant VT are discussed. In particular, the relationship between activation mapping and maps of transition in infarct border zone thickness, which results in source-sink mismatch, is considered in detail and supplemented with additional data. Based on source-sink mismatch, the re-entry isthmus can be modeled from its boundary properties. Isthmus boundary segments with large transitions in infarct border zone thickness have large source-sink mismatch, and functional block forms there during VT. These alternate with segments having lesser thickness change and therefore lesser source-sink mismatch, which act as gaps, or entrance and exit points, to the isthmus during VT. Besides post-infarction substrates, the source-sink model is likely applicable to other types of volumetric changes in the myocardial conducting medium, such as when there is presence of fibrosis or dissociation of muscle fibers. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Antigens of worms and eggs showed a differentiated detection of specific IgG according to the time of Schistosoma mansoni infection in mice

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Rafaella Fortini Queiroz Grenfell

2012-08-01

Full Text Available INTRODUCTION: The correlation between the immunological assay and the antibody titer can offer a tool for the experimental analysis of different phases of the disease. METHODS: Two simple immunological assays for Schistosoma mansoni in mice sera samples based on specific IgG detection for worms soluble antigens and eggs soluble antigens were standardized and evaluated in our laboratory. Fifty mice were used in negative and positive groups and the results obtained by enzyme-linked immunosorbent assays (ELISA assays were compared with the number of worms counted and the IgG titers at different times of infection. RESULTS: Data showed that ELISA using adult worm antigens (ELISA-SWAP presented a satisfactory correlation between the absorbance value of IgG titers and the individual number of worms counted after perfusion technique (R²=0.62. In addition, ELISA-SWAP differentially detected positive samples with 30 and 60 days post infection (p=0.011 and 0.003, respectively, whereas ELISA using egg antigens (ELISA-SEA detected samples after 140 days (p=0.03. CONCLUSIONS: These data show that the use of different antigens in immunological methods can be used as potential tools for the analysis of the chronological evolution of S. mansoni infection in murine schistosomiasis. Correlations with human schistosomiasis are discussed.

Detection of HBs antigens and antibodies by immunoenzymology and radioimmunology. Comparison of the results

International Nuclear Information System (INIS)

Fauchet, R.; Genetet, B.; Phengsavath

1981-01-01

The respective sensitivity threshold of immunoenzymology and radioimmunology in HBs antigen and antibody detection were compared and the optical density (o.d.) and counts per minute (cpm) values were correlated with the concentration in ng/ml of a given sample. The sensitivity comparison between RIA and EIA appears in favour of the former technique for both HBs antigen and HBs antibody detection. However the procedure tried here to detect HBs antibodies by immunoenzymology is simple, requires only the choice of neutralising antigenic pool and sensitivity threshold and could usefully be generalized for teams not authorized to handle radioelements. Quantification of the HBs antigen content in ng/ml is a difficult operation, needing great care in the dilution of the sera tested. The reproducibility is not perfect. The semi-quantitative RIA determination expressed in R.U. (radioimmunological units) seems adequate as a mean to follow the progress of an HBs antibody in both liver disease and vaccination [fr

Porcine reproductive and respiratory syndrome virus: antigenic and molecular diversity of British isolates and implications for diagnosis.

Science.gov (United States)

Frossard, Jean-Pierre; Fearnley, Catherine; Naidu, Brindha; Errington, Jane; Westcott, David G; Drew, Trevor W

2012-08-17

Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease of pigs, caused by PRRS virus, a member of the Arteriviridae family. First seen in Britain in 1991, the disease continues to be a significant economic and welfare problem for pig producers. To date, only PRRSV genotype 1 has been found in Britain. At the genetic level, a considerable increase has been reported in the diversity of PRRS viruses isolated in Britain between 2003 and 2007, versus the early 1990 s. In this study, the diversity has been shown to extend to the antigenic level too, with potential consequences for diagnostic methods. Antigenic diversity was assessed using a panel of twelve monoclonal antibodies, only one of which reacted with all isolates tested. Nine diverse viruses were compared as potential antigens in immunoperoxidase monolayer assays, where each one produced quite different results for a common panel of sera. As a single virus is used in each diagnostic assay, results must therefore be interpreted cautiously. For a real-time RT-PCR assay, published oligonucleotide primer and probe sequences were evaluated against available genetic sequences of British and European viruses, and were re-designed where considerable mismatches were found. The multiplex assay incorporating these modified primers to detect genotype 1 and 2 PRRS viruses was then validated for use with diagnostic sera and tissues. As the increasing degree of diversity exhibited by British strains is mirrored in other countries, PRRSV will continue to provide an ongoing challenge to diagnosis at a global, as well as national level. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda)

Science.gov (United States)

Choi, Min-Ho; Ryu, Jin-Sook; Lee, Mejeong; Li, Shunyu; Chung, Byung-Suk; Chai, Jong-Yil; Sithithaworn, Paiboon; Tesana, Smarn

2003-01-01

The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection. PMID:12972729

Circuit mismatch and current coupling effect influence on paralleling SiC MOSFETs in multichip power modules

DEFF Research Database (Denmark)

Li, Helong; Beczkowski, Szymon; Munk-Nielsen, Stig

2015-01-01

This paper reveals that there are circuit mismatches and a current coupling effect in the direct bonded copper (DBC) layout of a silicon carbide (SiC) MOSFET multichip power module. According to the modelling and the mathematic analysis of the DBC layout, the mismatch of the common source stray i...

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection

International Nuclear Information System (INIS)

Tsang, R.S.W.; Chau, P.Y.; Lam, S.K.

1981-01-01

Serum antibody responses to the lipopolysaccharide and protein antigens of S. typhi in typhoid patients were studied using a solid-phase radioimmunoassay technique with 125 I labelled anti-immunoglobulin antibody. Sera from 24 adult typhoid patients and 20 non-typhoid adult controls were compared. As a group, sera from typhoid patients showed increased IgA, IgG and IgM immunoglobulin levels and gave significantly higher anti-LPS and anti-protein antibody titres in all three major immunoglobulin classes than did non-typhoid controls. Levels of antibodies against LPS or protein in sera of typhoid patients were highly variable with a skew distribution. A good correlation was found between antibody titres to the LPS antigen and those to a protein antigen. No correlation, however, was found between the anti-LPS antibody titres measured by radioimmunoassay and the anti-O antibody titres measured by the Widal agglutination test. Titration of anti-LPS or anti-protein antibodies by radioimmunoassay was found to be more sensitive and specific than Widal test for the serological diagnosis of typhoid fever. The advantages of measuring antibody response by radioimmunoassay over conventional Widal test are discussed. (author)

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

Science.gov (United States)

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (Pprostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (Pprostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.

Science.gov (United States)

Kratz, C P; Holter, S; Etzler, J; Lauten, M; Pollett, A; Niemeyer, C M; Gallinger, S; Wimmer, K

2009-06-01

Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). Alluding to the underlying genetic defect, we refer to this syndrome as constitutional mismatch repair-deficiency (CMMR-D) syndrome. The tumour spectrum of CMMR-D syndrome includes haematological neoplasias, brain tumours and Lynch syndrome-associated tumours. Other tumours, such as neuroblastoma, Wilm tumour, ovarian neuroectodermal tumour or infantile myofibromatosis, have so far been found only in individual cases. We analysed two consanguineous families that had members with suspected CMMR-D syndrome who developed rhabdomyosarcoma among other neoplasias. In the first family, we identified a pathogenic PMS2 mutation for which the affected patient was homozygous. In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue. Together with the family history and microsatellite instability observed in one tumour this strongly suggests an underlying PMS2 alteration in family 2 also. Together, these two new cases show that rhabdomyosarcoma and possibly other embryonic tumours, such as neuroblastoma and Wilm tumour, belong to the tumour spectrum of CMMR-D syndrome. Given the clinical overlap of CMMR-D syndrome with NF1, we suggest careful examination of the family history in patients with embryonic tumours and signs of NF1 as well as analysis of the tumours for loss of one of the mismatch repair genes and microsatellite instability. Subsequent mutation analysis will lead to a definitive diagnosis of the underlying disorder.

Interpreting and Correcting Cross-scale Mismatches in Resilience Analysis: a Procedure and Examples from Australia's Rangelands

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John A. Ludwig

2005-12-01

Full Text Available Many rangelands around the globe are degraded because of mismatches between the goals and actions of managers operating at different spatial scales. In this paper, we focus on identifying, interpreting, and correcting cross-scale mismatches in rangeland management by building on an existing four-step resilience analysis procedure. Resilience analysis is an evaluation of the capacity of a system to persist in the face of disturbances. We provide three examples of cross-scale resilience analysis using a rangeland system located in northern Australia. The system was summarized in a diagram showing key interactions between three attributes (water quality, regional biodiversity, and beef quality, which can be used to indicate the degree of resilience of the system, and other components that affect these attributes at different scales. The strengths of cross-scale interactions were rated as strong or weak, and the likely causes of mismatches in strength were interpreted. Possible actions to correct cross-scale mismatches were suggested and evaluated. We found this four-step, cross-scale resilience analysis procedure very helpful because it reduced a complex problem down to manageable parts without losing sight of the larger-scale whole. To build rangeland resilience, many such cross-scale mismatches in management will need to be corrected, especially as the global use of rangelands increases over the coming decades.

Oncogenic cancer/testis antigens

DEFF Research Database (Denmark)

Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

2015-01-01

Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

A monofunctional platinum complex coordinated to a rhodium metalloinsertor selectively binds mismatched DNA in the minor groove.

Science.gov (United States)

Weidmann, Alyson G; Barton, Jacqueline K

2015-10-05

We report the synthesis and characterization of a bimetallic complex derived from a new family of potent and selective metalloinsertors containing an unusual Rh-O axial coordination. This complex incorporates a monofunctional platinum center containing only one labile site for coordination to DNA, rather than two, and coordinates DNA nonclassically through adduct formation in the minor groove. This conjugate displays bifunctional, interdependent binding of mismatched DNA via metalloinsertion at a mismatch as well as covalent platinum binding. DNA sequencing experiments revealed that the preferred site of platinum coordination is not the traditional N7-guanine site in the major groove, but rather N3-adenine in the minor groove. The complex also displays enhanced cytotoxicity in mismatch repair-deficient and mismatch repair-proficient human colorectal carcinoma cell lines compared to the chemotherapeutic cisplatin, and it triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors.

Radioimmunoassays of hidden viral antigens

International Nuclear Information System (INIS)

Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

1982-01-01

Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure

Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens

Directory of Open Access Journals (Sweden)

Ondigo Bartholomew N

2012-12-01

Full Text Available Abstract Background Multiplex cytometric bead assay (CBA have a number of advantages over ELISA for antibody testing, but little information is available on standardization and validation of antibody CBA to multiple Plasmodium falciparum antigens. The present study was set to determine optimal parameters for multiplex testing of antibodies to P. falciparum antigens, and to compare results of multiplex CBA to ELISA. Methods Antibodies to ten recombinant P. falciparum antigens were measured by CBA and ELISA in samples from 30 individuals from a malaria endemic area of Kenya and compared to known positive and negative control plasma samples. Optimal antigen amounts, monoplex vs multiplex testing, plasma dilution, optimal buffer, number of beads required were assessed for CBA testing, and results from CBA vs. ELISA testing were compared. Results Optimal amounts for CBA antibody testing differed according to antigen. Results for monoplex CBA testing correlated strongly with multiplex testing for all antigens (r = 0.88-0.99, P values from Conclusion With optimization, CBA may be the preferred method of testing for antibodies to P. falciparum antigens, as CBA can test for antibodies to multiple recombinant antigens from a single plasma sample and produces a greater range of values in positive samples and lower background readings for blank samples than ELISA.

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients

International Nuclear Information System (INIS)

Stamey, T.A.; Kabalin, J.N.; Ferrari, M.

1989-01-01

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 183 men after radiation therapy for adenocarcinoma of the prostate. A total of 163 men had received 7,000 rad external beam radiotherapy and 20 had been implanted with iodine-125 seeds. Only 11 per cent of these 183 patients had undetectable prostate specific antigen levels at a mean interval of 5 years since completion of radiotherapy. Prostate specific antigen levels after radiotherapy were directly related to initial clinical stage and Gleason score before treatment. Multiple prostate specific antigen determinations were performed with time in 124 of 183 patients. During year 1 after radiotherapy prostate specific antigen levels were decreasing in 82 per cent of the patients but only 8 per cent continued to decrease beyond year 1. Of 80 patients observed greater than 1 year after completion of radiotherapy 51 per cent had increasing values and 41 per cent had stable values. Increasing prostate specific antigen values after radiotherapy were correlated with progression to metastastic disease and residual cancer on prostate biopsy. Total serum acid phosphatase levels were poorly related to prostate specific antigen levels, were less effective in discriminating patients with metastatic disease and provided no additional information beyond that provided by prostate specific antigen

DNA mismatch repair, genome instability and cancer in zebrafish

NARCIS (Netherlands)

Feitsma, H.

2008-01-01

The objective of this study was to find out whether the zebrafish can be an appropriate model for studying DNA repair and cancer. For this purpose three fish lines were used that lack components of an important mechanism for the repair of small DNA damage: DNA mismatch repair. These fish are

Counting the mismatches - lung ventilation/perfusion subtraction index

International Nuclear Information System (INIS)

Anderson, T.C.; Evans, S.G.; Larcos, G.; Farlow, D.C.

1998-01-01

Full text: There is potential for interobserver variability in interpretation of ventilation/perfusion (V/Q) scans. Objective quantification of V/Q mismatch could be useful. Thus, the aim of this study is to determine the validity of image subtraction in a group of 27 patients (11 men, 8 women; mean age 59.4 years [range 21-81 years])investigated by V/Q scans for suspected pulmonary emboli. A standard 6 view V/Q scan was obtained with two cobalt markers used on the anterior and posterior surfaces for image alignment. Ventilation images were normalised to the perfusion using an area of normal ventilation and perfusion. With the use of automated, and if required, manual alignment, perfusion images were subtracted from ventilation, with a median filter applied. A summed index of mismatch for each lung scan was calculated from the difference. This index was then retrospectively compared to the result reported by one of four experienced physicians. Two patients with chronic obstructive airways disease were excluded from analysis. We conclude that high probability V/Q scans can be differentiated from low probability studies using this index; further prospective investigation in a larger cohort is warranted

A new measure of skill mismatch: theory and evidence from PIAAC

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Michele Pellizzari

2017-01-01

Full Text Available Abstract This paper proposes a new measure of skill mismatch to be applied to the recent OECD Survey of Adult Skills (PIAAC. The measure is derived from a formal theory and combines information about skill proficiency, self-reported mismatch and skill use. The theoretical foundations underling this measure allow identifying minimum and maximum skill requirements for each occupation and to classify workers into three groups: the well-matched, the under-skilled and the over-skilled. The availability of skill use data further permits the computation of the degree of under- and over-usage of skills in the economy. The empirical analysis is carried out using the first round of the PIAAC data, allowing comparisons across skill domains, labour market statuses and countries.

Exploring the relationship between educational mismatch, earnings and job satisfaction in the tourism industry

OpenAIRE

Lillo-Bañuls, Adelaida; Casado-Díaz, José M.

2015-01-01

This article analyses the interrelationship between educational mismatch, wages and job satisfaction in the Spanish tourism sector in the first years of the global economic crisis. It is shown that there is a much higher incidence of over-education among workers in the Spanish tourism sector than in the rest of the economy despite this sector recording lower educational levels. This study estimates two models to analyse the influence of the educational mismatch on wages and job satisfaction f...

Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

Science.gov (United States)

Richardson, V J; Ford, C H; Tsaltas, G; Gallant, M E

1989-04-01

An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

Leukemia-associated antigens in man.

Science.gov (United States)

Brown, G; Capellaro, D; Greaves, M

1975-12-01

Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

Anvendelse af prostataspecifikt antigen. En oversigt

DEFF Research Database (Denmark)

Brasso, K; Skaarup, P; Roosen, Jens Ulrik

1998-01-01

Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific...... antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed....

Possible roles for mismatch negativity in neuropsychiatry.

Science.gov (United States)

Gené-Cos, N; Ring, H A; Pottinger, R C; Barrett, G

1999-01-01

This article reviews research on the main characteristics of mismatch negativity (MMN) and its applications in neuropsychiatry. Event-related potentials (ERPs) have been used to study many aspects of information processing. Mismatch negativity is an early auditory ERP that has been identified as an index of an automatic (preconscious) alerting mechanism stimulating an individual to attend to unexpected environmental events. Disturbances of MMN may relate to abnormalities of auditory information processing contributing to the pathophysiology of neuropsychiatric conditions. The authors review (1) studies that have evaluated the electrophysiological aspects of MMN and (2) studies that have investigated the different applications of MMN in neuropsychiatry. The first part of this article describes the characteristics of MMN, its cerebral origins, and electrophysiological parameters. We then discuss the role of "echoic memory" as well as that of attention and vigilance. In the second part of the article, disturbances in MMN associated with schizophrenia, depressive illness, dementing processes, and other neuropsychiatric states are discussed. MMN is a preconscious cognitive ERP, the main generators and functions of which are well defined. Observations relating to the origins of MMN and its role in early auditory information processing together with its possible behavioral significance, combined with observations of MMN aberrations in psychiatric conditions, may provide novel insights into the pathophysiology of neuropsychiatric states.

3D-2D image registration for target localization in spine surgery: investigation of similarity metrics providing robustness to content mismatch

Science.gov (United States)

De Silva, T.; Uneri, A.; Ketcha, M. D.; Reaungamornrat, S.; Kleinszig, G.; Vogt, S.; Aygun, N.; Lo, S.-F.; Wolinsky, J.-P.; Siewerdsen, J. H.

2016-04-01

In image-guided spine surgery, robust three-dimensional to two-dimensional (3D-2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D-2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE  >  30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE  interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of  >14% however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE  =  5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric

Pathological assessment of mismatch repair gene variants in Lynch syndrome

DEFF Research Database (Denmark)

Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

2012-01-01

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

Toward maximum transmittance into absorption layers in solar cells: investigation of lossy-film-induced mismatches between reflectance and transmittance extrema.

Science.gov (United States)

Chang, Yin-Jung; Lai, Chi-Sheng

2013-09-01

The mismatch in film thickness and incident angle between reflectance and transmittance extrema due to the presence of lossy film(s) is investigated toward the maximum transmittance design in the active region of solar cells. Using a planar air/lossy film/silicon double-interface geometry illustrates important and quite opposite mismatch behaviors associated with TE and TM waves. In a typical thin-film CIGS solar cell, mismatches contributed by TM waves in general dominate. The angular mismatch is at least 10° in about 37%-53% of the spectrum, depending on the thickness combination of all lossy interlayers. The largest thickness mismatch of a specific interlayer generally increases with the thickness of the layer itself. Antireflection coating designs for solar cells should therefore be optimized in terms of the maximum transmittance into the active region, even if the corresponding reflectance is not at its minimum.

Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

Science.gov (United States)

Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

2014-12-01

Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1. © 2014 John Wiley & Sons Ltd.

HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

Directory of Open Access Journals (Sweden)

Andrea Pession

2011-06-01

Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

Processes influencing model-data mismatch in drought-stressed, fire-disturbed eddy flux sites

Science.gov (United States)

Mitchell, Stephen; Beven, Keith; Freer, Jim; Law, Beverly

2011-06-01

Semiarid forests are very sensitive to climatic change and among the most difficult ecosystems to accurately model. We tested the performance of the Biome-BGC model against eddy flux data taken from young (years 2004-2008), mature (years 2002-2008), and old-growth (year 2000) ponderosa pine stands at Metolius, Oregon, and subsequently examined several potential causes for model-data mismatch. We used the Generalized Likelihood Uncertainty Estimation methodology, which involved 500,000 model runs for each stand (1,500,000 total). Each simulation was run with randomly generated parameter values from a uniform distribution based on published parameter ranges, resulting in modeled estimates of net ecosystem CO2 exchange (NEE) that were compared to measured eddy flux data. Simulations for the young stand exhibited the highest level of performance, though they overestimated ecosystem C accumulation (-NEE) 99% of the time. Among the simulations for the mature and old-growth stands, 100% and 99% of the simulations underestimated ecosystem C accumulation. One obvious area of model-data mismatch is soil moisture, which was overestimated by the model in the young and old-growth stands yet underestimated in the mature stand. However, modeled estimates of soil water content and associated water deficits did not appear to be the primary cause of model-data mismatch; our analysis indicated that gross primary production can be accurately modeled even if soil moisture content is not. Instead, difficulties in adequately modeling ecosystem respiration, mainly autotrophic respiration, appeared to be the fundamental cause of model-data mismatch.

Indium arsenide-on-SOI MOSFETs with extreme lattice mismatch

Science.gov (United States)

Wu, Bin

Both molecular beam epitaxy (MBE) and metal organic chemical vapor deposition (MOCVD) have been used to explore the growth of InAs on Si. Despite 11.6% lattice mismatch, planar InAs structures have been observed by scanning electron microscopy (SEM) when nucleating using MBE on patterned submicron Si-on-insulator (SOI) islands. Planar structures of size as large as 500 x 500 nm 2 and lines of width 200 nm and length a few microns have been observed. MOCVD growth of InAs also generates single grain structures on Si islands when the size is reduced to 100 x 100 nm2. By choosing SOI as the growth template, selective growth is enabled by MOCVD. Post-growth pattern-then-anneal process, in which MOCVD InAs is deposited onto unpatterned SOI followed with patterning and annealing of InAs-on-Si structure, is found to change the relative lattice parameters of encapsulated 17/5 nm InAs/Si island. Observed from transmission electron diffraction (TED) patterns, the lattice mismatch of 17/5 nm InAs/Si island reduces from 11.2 to 4.2% after being annealed at 800°C for 30 minutes. High-k Al2O3 dielectrics have been deposited by both electron-beam-enabled physical vapor deposition (PVD) and atomic layer deposition (ALD). Films from both techniques show leakage currents on the order of 10-9A/cm2, at ˜1 MV/cm electric field, breakdown field > ˜6 MV/cm, and dielectric constant > 6, comparable to those of reported ALD prior arts by Groner. The first MOSFETs with extreme lattice mismatch InAs-on-SOI channels using PVD Al2O3 as the gate dielectric are characterized. Channel recess was used to improve the gate control of the drain current.

Correlation Between the Microstructural Defects and Residual Stress in a Single Crystal Nickel-Based Superalloy During Different Creep Stages

Science.gov (United States)

Mo, Fangjie; Wu, Erdong; Zhang, Changsheng; Wang, Hong; Zhong, Zhengye; Zhang, Jian; Chen, Bo; Hofmann, Michael; Gan, Weimin; Sun, Guangai

2018-03-01

The present work attempts to reveal the correlation between the microstructural defects and residual stress in the single crystal nickel-based superalloy, both of which play the significant role on properties and performance. Neutron diffraction was employed to investigate the microstructural defects and residual stresses in a single crystal (SC) nickel-based superalloy, which was subjected to creeping under 220 MPa and 1000 °C for different times. The measured superlattice and fundamental lattice reflections confirm that the mismatch and tetragonal distortions with c/a > 1 exist in the SC superalloy. At the initially unstrained state, there exists the angular distortion between γ and γ' phases with small triaxial compressive stresses, ensuring the structural stability of the superalloy. After creeping, the tetragonal distortion for the γ phase is larger than that for the γ' phase. With increasing the creeping time, the mismatch between γ and γ' phases increases to the maximum, then decreases gradually and finally remains unchanged. The macroscopic residual stress shows a similar behavior with the mismatch, indicating the correlation between them. Based on the model of shear and dislocations, the evolution of microstructural defects and residual stress are reasonably explained. The effect of shear is dominant at the primary creep stage, which greatly enlarges the mismatch and the residual stress. The dislocations weaken the effect of shear for the further creep stage, resulting in the decrease of the mismatch and relaxation of the residual stress. Those findings add some helpful understanding into the microstructure-performance relationship in the SC nickel-based superalloy, which might provide the insight to materials design and applications.

Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

DEFF Research Database (Denmark)

Mustafa, A S; Amoudy, H A; Wiker, H G

1998-01-01

GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

Limitations of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) for detection of filarial antigens in serum

International Nuclear Information System (INIS)

Hamilton, R.G.; Alexander, E.; Adkinson, N.F.

1984-01-01

The performance of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) was examined for quantitation of filarial antigens (Brugia malayi and Dirofilaria immitis) in serum from infected human and animal hosts and non-infected controls. Multiple PEG concentrations were employed to determine the level of non-specific binding (NSB) in non-exposed human sera (NEHS) containing no filarial antigen. The NSB observed when 3 different 125 I-labelled IgG antibodies were added to 26 NEHS varied 3-fold and was correlated significantly with total serum IgM (r = 0.80, P 2 fragment of the 125 I-labelled antibody was used, but the correlation of NSB with total serum IgM remained significant (r = 0.57, P < 0.01). The presence of rheumatoid factor in NEHS sera also significantly increased NSB by an average of 3-fold. These effects eliminated the assay's ability to detect in sera from infected hosts filarial antigen the presence of which could be readily demonstrated by an immunoradiometric assay. The RIPEGA's precision (intra-assay coefficient of variation (CV) = 21% at 35% Bsub(max)) and reproducibility (inter-assay CV = 29% at 35% Bsub(max)) are less satisfactory than many alternative immunoassays. (Auth.)

Understanding the Consequences of Property Rights Mismatches: a Case Study of New Zealand's Marine Resources

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Tracy Yandle

2007-12-01

Full Text Available Within fisheries and natural resource management literature, there is considerable discussion about the key roles that property rights can play in building biologically and socially sustainable resource management regimes. A key point of agreement is that secure long-term property rights provide an incentive for resource users to manage the resource sustainably. However, property rights mismatches create ambiguity and conflict in resource use. Though the term mismatches is usually associated with problems in matching temporal and spatial resource characteristics with institutional characteristics, I expand it here to include problems that can arise when property rights are incompletely defined or incompletely distributed. Property rights mismatches are particularly likely to occur over marine resources, for which multiple types of resource and resource user can be engaged and managed under a variety of regulatory regimes. I used New Zealand's marine resources to examine the causes and consequences of these property rights mismatches. New Zealand is particularly interesting because its property-rights-based commercial fishing regime, in the form of individual transferable quotas, has attracted considerable positive attention. However, my review of the marine natural resource management regime from a broader property rights perspective highlights a series of problems caused by property rights mismatches, including competition for resources among commercial, customary, and recreational fishers; spatial conflict among many marine resource users; and conflicting incentives and objectives for the management of resources over time. The use of a property rights perspective also highlights some potential solutions such as the layering of institutional arrangements and the improvement of how property rights are defined to encourage long-term sustainability.

COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

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Rita G SOUSA

2014-03-01

Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

Supply and Demand Mismatches in Training: Can Anything Be Done?

Science.gov (United States)

Castro, Claudio de Moura; de Andrade, Antonio Cabral

1990-01-01

Vocational training often fails to provide what employers need and students want. To correct supply/demand mismatches requires improving feedback from employers, increasing the flow of information, bringing schools closer to businesses, rewarding institutions for successful employment of graduates, and providing incentives for entrepreneurs. (SK)

Use of Novel Recombinant Antigens in the Interferon Gamma Assay for Detection of Mycobacterium Avium Subsp. Paratuberculosis Infection in Cattle

DEFF Research Database (Denmark)

Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose

2012-01-01

of the study were to evaluate immunogenicity and specificity of 14 novel recombinant antigens for use in the IFN-γ assay and to assess the consistency of IFN-γ responses. The antigens used were 4 ESAT-6 family members, 4 latency proteins, 4 secreted proteins including Ag85B, 3 other antigens and PPDj......Early stage Mycobacterium avium subsp. paratuberculosis (MAP) infection can be detected by measuring antigen specific cell mediated immune responses by the interferon gamma (IFN-γ) assay. Available IFN-γ assay use purified protein derivate of Johnin (PPDj) leading to low specificity. The objectives...... of the infected and non-infected herds were significantly (Passay using PPDj did not correlate with the results using the novel antigens since 5 of the 17 animals that were positive to PPDj were...

The conceptual mismatch: transportation stressors and experiences for low-income adults.

Science.gov (United States)

2015-10-01

Physical access to jobs has long been identified as a barrier to employment and earnings, with prior : research identifying the spatial mismatch between suburban entry-level jobs and low-income workers. : However, existing transportation resear...

Enhanced acquired antibodies to a chimeric Plasmodium falciparum antigen; UB05-09 is associated with protective immunity against malaria.

Science.gov (United States)

Dinga, J N; Gamua, S D; Titanji, V P K

2017-08-01

It has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritize such a chimera for malaria vaccine development, it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here, we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05-09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross-sectional study, recombinant UB05-09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria-endemic zone, using the enzyme-linked immunosorbent assay (ELISA). Anti-UB05-09 antibody levels doubled that of its constituent antigens, UB09 and UB05, and this correlated with protection against malaria. The presence of enhanced UB05-09-specific antibody correlated with the absence of fever and parasitaemia, which are the main symptoms of malaria infection. The chimera is more effective in detecting and distinguishing acquired protective immunity against malaria than any of its constituents taken alone. Online B-cell epitope prediction tools confirmed the presence of B-cell epitopes in the study antigens. UB05-09 chimera is a marker of protective immunity against malaria that needs to be studied further. © 2017 John Wiley & Sons Ltd.

Circumpolar analysis of the Adélie Penguin reveals the importance of environmental variability in phenological mismatch

Science.gov (United States)

Youngflesh, Casey; Jenouvrier, Stephanie; Li, Yun; Ji, Rubao; Ainley, David G.; Ballard, Grant; Barbraud, Christophe; Delord, Karine; Dugger, Catherine; Emmerson, Loiuse M.; Fraser, William R.; Hinke, Jefferson T.; Lyver, Phil O'B.; Olmastroni, Silvia; Southwell, Colin J.; Trivelpiece, Susan G.; Trivelpiece, Wayne Z.; Lynch, Heather J.

2017-01-01

Evidence of climate-change-driven shifts in plant and animal phenology have raised concerns that certain trophic interactions may be increasingly mismatched in time, resulting in declines in reproductive success. Given the constraints imposed by extreme seasonality at high latitudes and the rapid shifts in phenology seen in the Arctic, we would also expect Antarctic species to be highly vulnerable to climate-change-driven phenological mismatches with their environment. However, few studies have assessed the impacts of phenological change in Antarctica. Using the largest database of phytoplankton phenology, sea-ice phenology, and Adélie Penguin breeding phenology and breeding success assembled to date, we find that, while a temporal match between Penguin breeding phenology and optimal environmental conditions sets an upper limit on breeding success, only a weak relationship to the mean exists. Despite previous work suggesting that divergent trends in Adélie Penguin breeding phenology are apparent across the Antarctic continent, we find no such trends. Furthermore, we find no trend in the magnitude of phenological mismatch, suggesting that mismatch is driven by interannual variability in environmental conditions rather than climate-change-driven trends, as observed in other systems. We propose several criteria necessary for a species to experience a strong climate-change-driven phenological mismatch, of which several may be violated by this system.

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

Isolation and characterization of NIH 3T3 cells expressing polyomavirus small T antigen

International Nuclear Information System (INIS)

Noda, T.; Satake, M.; Robins, T.; Ito, Y.

1986-01-01

The polyomavirus small T-antigen gene, together with the polyomavirus promoter, was inserted into retrovirus vector pGV16 which contains the Moloney sarcoma virus long terminal repeat and neomycin resistance gene driven by the simian virus 40 promoter. This expression vector, pGVST, was packaged into retrovirus particles by transfection of PSI2 cells which harbor packaging-defective murine retrovirus genome. NIH 3T3 cells were infected by this replication-defective retrovirus containing pGVST. Of the 15 G418-resistant cell clones, 8 express small T antigen at various levels as revealed by immunoprecipitation. A cellular protein with an apparent molecular weight of about 32,000 coprecipitates with small T antigen. Immunofluorescent staining shows that small T antigen is mainly present in the nuclei. Morphologically, cells expressing small T antigen are indistinguishable from parental NIH 3T3 cells and have a microfilament pattern similar to that in parental NIH 3T3 cells. Cells expressing small T antigen form a flat monolayer but continue to grow beyond the saturation density observed for parental NIH 3T3 cells and eventually come off the culture plate as a result of overconfluency. There is some correlation between the level of expression of small T antigen and the growth rate of the cells. Small T-antigen-expressing cells form small colonies in soft agar. However, the proportion of cells which form these small colonies is rather small. A clone of these cells tested did not form tumors in nude mice within 3 months after inoculation of 10 6 cells per animal. Thus, present studies establish that the small T antigen of polyomavirus is a second nucleus-localized transforming gene product of the virus (the first one being large T antigen) and by itself has a function which is to stimulate the growth of NIH 3T3 cells beyond their saturation density in monolayer culture

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

Science.gov (United States)

Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

2017-05-01

Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

Characterization of Antigen-Specific B Cells Using Nominal Antigen-Coated Flow-Beads

Science.gov (United States)

Akl, Ahmed; Lepetit, Maud; Crochette, Romain; Giral, Magali; Lepourry, Julie; Pallier, Annaick; Castagnet, Stéphanie; Dugast, Emilie; Guillot-Gueguen, Cécile; Jacq-Foucher, Marylène; Saulquin, Xavier; Cesbron, Anne; Laplaud, David; Nicot, Arnaud; Brouard, Sophie; Soulillou, Jean-Paul

2013-01-01

In order to characterize the reactivity of B cells against nominal antigens, a method based on the coupling of antigens onto the surface of fluorescent core polystyrene beads was developed. We first demonstrate that murine B cells with a human MOG-specific BCR are able to interact with MOG-coated beads and do not recognize beads coated with human albumin or pp65. B cells purified from human healthy volunteer blood or immunized individuals were tested for their ability to interact with various nominal antigens, including viral, vaccine, self and alloantigens, chosen for their usefulness in studying a variety of pathological processes. A substantial amount of B cells binding self-antigen MOG-coated beads can be detected in normal blood. Furthermore, greater frequencies of B cell against anti-Tetanic Toxin or anti-EBNA1 were observed in primed individuals. This method can reveal increased frequencies of anti-HLA committed B cells in patients with circulating anti-HLA antibodies compared to unsensitized patients and normal individuals. Of interest, those specific CD19 cells were preferentially identified within CD27−IgD+ (i-e naïve) subset. These observations suggest that a broad range of medical situations could benefit from a tool that allows the detection, the quantification and the characterization of antigen-specific blood B cells. PMID:24386360

[Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

Science.gov (United States)

Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

2006-02-01

A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

NARCIS (Netherlands)

Sijmons, Rolf H.; Hofstra, Robert M. W.

Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

Carbamylated albumin is one of the target antigens of anti-carbamylated protein antibodies.

Science.gov (United States)

Nakabo, Shuichiro; Hashimoto, Motomu; Ito, Shinji; Furu, Moritoshi; Ito, Hiromu; Fujii, Takao; Yoshifuji, Hajime; Imura, Yoshitaka; Nakashima, Ran; Murakami, Kosaku; Kuramoto, Nobuo; Tanaka, Masao; Satoh, Junko; Ishigami, Akihito; Morita, Satoshi; Mimori, Tsuneyo; Ohmura, Koichiro

2017-07-01

Anti-carbamylated protein (anti-CarP) antibodies are detected in RA patients. Fetal calf serum is used as an antigen source in anti-CarP ELISA, and the precise target antigens have not been found. We aimed to identify the target antigens of anti-CarP antibodies. Western blotting of anti-CarP antibodies was conducted. Anti-carbamylated human albumin (CarALB) antibody was detected by in-house ELISA for 493 RA patients and 144 healthy controls (HCs). An inhibition ELISA of anti-CarP antibodies by CarALB and citrullinated albumin (citALB) was performed using eight RA patients' sera. Serum CarALB was detected by liquid chromatography-tandem mass spectroscopy (LC/MS/MS), and the serum MPO concentration was measured by ELISA. We focused on carbamylated albumin because it corresponded to the size of the thickest band detected by western blotting of anti-CarP antibodies. Anti-CarALB antibody was detected in 31.4% of RA patients, and the correlation of the titres between anti-CarALB and anti-CarP was much closer than that between anti-citALB and anti-CCP antibodies (ρ = 0.59 and ρ = 0.16, respectively). The inhibition ELISA showed that anti-CarP antibodies were inhibited by CarALB, but not by citALB. CarALB was detected in sera from RA patients by LC/MS/MS. The serum MPO concentration was correlated with disease activity and was higher in RA patients with anti-CarALB antibody than in those without. We found that carbamylated albumin is a novel target antigen of anti-CarP antibodies, and it is the first reported target antigen that has not been reported as the target of ACPA. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch

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Fan He

2015-01-01

Full Text Available Background. Compliance mismatch is a negative factor and it needs to be considered in arterial bypass grafting. Objective. A computational model was employed to investigate the effects of arterial compliance mismatch on blood flow, wall stress, and deformation. Methods. The unsteady blood flow was assumed to be laminar, Newtonian, viscous, and incompressible. The vessel wall was assumed to be linear elastic, isotropic, and incompressible. The fluid-wall interaction scheme was constructed using the finite element method. Results. The results show that there are identical wall shear stress waveforms, wall stress, and strain waveforms at different locations. The comparison of the results demonstrates that wall shear stresses and wall strains are higher while wall stresses are lower at the more compliant section. The differences promote the probability of intimal thickening at some locations. Conclusions. The model is effective and gives satisfactory results. It could be extended to all kinds of arteries with complicated geometrical and material factors.

Lewis antigen mediated adhesion of freshly removed human bladder tumors to E-selectin

DEFF Research Database (Denmark)

Skorsteensgaard, Karna; Vestergaard, Else Marie; Langkilde, Niels

1999-01-01

PURPOSE: Twenty fresh surgical specimens of human bladder tumors were tested for their ability to adhere to recombinant P and E-selectin. The adhesion was correlated to immunological detection of carbohydrate structures. MATERIALS AND METHODS: A static titertray assay with immobilized selectins.......003), whereas no correlation was found to secretor and Lewis genotypes. CONCLUSIONS: These data on clinical specimens indicate that Lewis antigen mediated E-selectin adhesion may play a role in the human bladder cancer disease....

Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

DEFF Research Database (Denmark)

Werdelin, O; Mouritsen, S; Petersen, B L

1988-01-01

The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic...... fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC...... molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has...

Immunodetection of Fasciola gigantica circulating antigen in sera of infected individuals for laboratory diagnosis of human fascioliasis.

Science.gov (United States)

Attallah, Abdelfattah M; Bughdadi, Faisal A; El-Shazly, Atef M; Ismail, Hisham

2013-10-01

Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P 93%), and a significant correlation (r = 0.715, P fascioliasis.

A retrospective study: correlation of histologic inflammation in biopsy specimens of Chinese men undergoing surgery for benign prostatic hyperplasia with serum prostate-specific antigen.

Science.gov (United States)

Song, Lingmin; Zhu, Yuchun; Han, Ping; Chen, Ni; Lin, Dao; Lai, Jianyu; Wei, Qiang

2011-03-01

To reveal the correlation between benign prostatic hyperplasia (BPH) histologic inflammation and serum prostate-specific antigen (sPSA) concentrations, and the possible mechanism. Patients underwent surgery at the Urology Department of West China Hospital of Sichuan University were retrospectively studied. Preoperative sPSA and transrectal ultrasonography were measured. According to the histopathological classification system for chronic prostatic inflammation proposed by the Chronic Prostatitis Collaborative Research Network (CPCRN) and the International Prostatitis Collaborative Network (IPCN), we classified the histologic sections of prostatic biopsy into glandular, periglandular, and stromal inflammation by the anatomical location of inflammatory infiltration. The glandular inflammation was graded according to the inflammatory aggressiveness. The periglandular and stromal inflammation were graded according to the inflammatory density. The correlation between histologic inflammation and sPSA was studied by a multiple regression model in conjunction with age and total prostatic volume. A total of 454 patients with exclusively BPH were analyzed. The periglandular inflammatory infiltration was the most common pattern (95.6%). Single regression analysis revealed that total prostatic volume, the aggressiveness of glandular inflammation, and the intensity of periglandular and stromal inflammation were correlated with sPSA. However, the multiple regression analysis revealed that only the total prostatic volume and the aggressiveness of glandular inflammation were correlated significantly with sPSA (R = .389, 0.289; P = .000). The aggressiveness of glandular inflammatory infiltration in BPH is a significant contributor to elevated sPSA levels. The theory of leakage may be the most reasonable mechanism to reveal the correlation morphologically. We should take inflammation into consideration when interpreting the abnormal elevating of sPSA levels. Copyright © 2011

Scale Mismatches in Management of Urban Landscapes

Directory of Open Access Journals (Sweden)

Sara T. Borgström

2006-12-01

Full Text Available Urban landscapes constitute the future environment for most of the world's human population. An increased understanding of the urbanization process and of the effects of urbanization at multiple scales is, therefore, key to ensuring human well-being. In many conventional natural resource management regimes, incomplete knowledge of ecosystem dynamics and institutional constraints often leads to institutional management frameworks that do not match the scale of ecological patterns and processes. In this paper, we argue that scale mismatches are particularly pronounced in urban landscapes. Urban green spaces provide numerous important ecosystem services to urban citizens, and the management of these urban green spaces, including recognition of scales, is crucial to the well-being of the citizens. From a qualitative study of the current management practices in five urban green spaces within the Greater Stockholm Metropolitan Area, Sweden, we found that 1 several spatial, temporal, and functional scales are recognized, but the cross-scale interactions are often neglected, and 2 spatial and temporal meso-scales are seldom given priority. One potential effect of the neglect of ecological cross-scale interactions in these highly fragmented landscapes is a gradual reduction in the capacity of the ecosystems to provide ecosystem services. Two important strategies for overcoming urban scale mismatches are suggested: 1 development of an integrative view of the whole urban social-ecological landscape, and 2 creation of adaptive governance systems to support practical management.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Jianzhong Chen

2017-01-01

Full Text Available Objective. We aimed to explore whether squamous cell carcinoma antigen (SCC, cytokeratin 19 fragment (Cyfra21-1, neuron-specific enolase (NSE, and carcinoembryonic antigen (CEA are elevated in diabetic nephropathy (DN and the association between urinary albumin-to-creatinine ratio (UACR and tumor markers in diabetic patients. Methods. Nondialysis patients with diabetes (n=261 and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results. Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001. In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05. Conclusions. Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies.

A comparative study between matched and mis-matched projection/back projection pairs used with ASIRT reconstruction method

International Nuclear Information System (INIS)

Guedouar, R.; Zarrad, B.

2010-01-01

For algebraic reconstruction techniques both forward and back projection operators are needed. The ability to perform accurate reconstruction relies fundamentally on the forward projection and back projection methods which are usually, the transpose of each other. Even though the mis-matched pairs may introduce additional errors during the iterative process, the usefulness of mis-matched projector/back projector pairs has been proved in image reconstruction. This work investigates the performance of matched and mis-matched reconstruction pairs using popular forward projectors and their transposes when used in reconstruction tasks with additive simultaneous iterative reconstruction techniques (ASIRT) in a parallel beam approach. Simulated noiseless phantoms are used to compare the performance of the investigated pairs in terms of the root mean squared errors (RMSE) which are calculated between reconstructed slices and the reference in different regions. Results show that mis-matched projection/back projection pairs can promise more accuracy of reconstructed images than matched ones. The forward projection operator performance seems independent of the choice of the back projection operator and vice versa.

A comparative study between matched and mis-matched projection/back projection pairs used with ASIRT reconstruction method

Energy Technology Data Exchange (ETDEWEB)

Guedouar, R., E-mail: raja_guedouar@yahoo.f [Higher School of Health Sciences and Techniques of Monastir, Av. Avicenne, 5060 Monastir, B.P. 128 (Tunisia); Zarrad, B., E-mail: boubakerzarrad@yahoo.f [Higher School of Health Sciences and Techniques of Monastir, Av. Avicenne, 5060 Monastir, B.P. 128 (Tunisia)

2010-07-21

For algebraic reconstruction techniques both forward and back projection operators are needed. The ability to perform accurate reconstruction relies fundamentally on the forward projection and back projection methods which are usually, the transpose of each other. Even though the mis-matched pairs may introduce additional errors during the iterative process, the usefulness of mis-matched projector/back projector pairs has been proved in image reconstruction. This work investigates the performance of matched and mis-matched reconstruction pairs using popular forward projectors and their transposes when used in reconstruction tasks with additive simultaneous iterative reconstruction techniques (ASIRT) in a parallel beam approach. Simulated noiseless phantoms are used to compare the performance of the investigated pairs in terms of the root mean squared errors (RMSE) which are calculated between reconstructed slices and the reference in different regions. Results show that mis-matched projection/back projection pairs can promise more accuracy of reconstructed images than matched ones. The forward projection operator performance seems independent of the choice of the back projection operator and vice versa.

Phenological mismatch in coastal western Alaska may increase summer season greenhouse gas uptake

Science.gov (United States)

Kelsey, Katharine C.; Leffler, A. Joshua; Beard, Karen H.; Choi, Ryan T.; Schmutz, Joel A.; Welker, Jeffery M.

2018-04-01

High latitude ecosystems are prone to phenological mismatches due to climate change- driven advances in the growing season and changing arrival times of migratory herbivores. These changes have the potential to alter biogeochemical cycling and contribute to feedbacks on climate change by altering greenhouse gas (GHG) emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) through large regions of the Arctic. Yet the effects of phenological mismatches on gas fluxes are currently unexplored. We used a three-year field experiment that altered the start of the growing season and timing of grazing to investigate how phenological mismatch affects GHG exchange. We found early grazing increased mean GHG emission to the atmosphere despite lower CH4 emissions due to grazing-induced changes in vegetation structure that increased uptake of CO2. In contrast, late grazing reduced GHG emissions because greater plant productivity led to an increase in CO2 uptake that overcame the increase in CH4 emission. Timing of grazing was an important control on both CO2 and CH4 emissions, and net GHG exchange was the result of opposing fluxes of CO2 and CH4. N2O played a negligible role in GHG flux. Advancing the growing season had a smaller effect on GHG emissions than changes to timing of grazing in this study. Our results suggest that a phenological mismatch that delays timing of grazing relative to the growing season, a change which is already developing along in western coastal Alaska, will reduce GHG emissions to the atmosphere through increased CO2 uptake despite greater CH4 emissions.

Phenological mismatch in coastal western Alaska may increase summer season greenhouse gas uptake

Science.gov (United States)

Kelsey, Katharine C.; Leffler, A. Joshua; Beard, Karen H.; Choi, Ryan T.; Schmutz, Joel A.; Welker, Jeffery M.

2018-01-01

High latitude ecosystems are prone to phenological mismatches due to climate change- driven advances in the growing season and changing arrival times of migratory herbivores. These changes have the potential to alter biogeochemical cycling and contribute to feedbacks on climate change by altering greenhouse gas (GHG) emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) through large regions of the Arctic. Yet the effects of phenological mismatches on gas fluxes are currently unexplored. We used a three-year field experiment that altered the start of the growing season and timing of grazing to investigate how phenological mismatch affects GHG exchange. We found early grazing increased mean GHG emission to the atmosphere despite lower CH4 emissions due to grazing-induced changes in vegetation structure that increased uptake of CO2. In contrast, late grazing reduced GHG emissions because greater plant productivity led to an increase in CO2 uptake that overcame the increase in CH4 emission. Timing of grazing was an important control on both CO2 and CH4 emissions, and net GHG exchange was the result of opposing fluxes of CO2 and CH4. N2O played a negligible role in GHG flux. Advancing the growing season had a smaller effect on GHG emissions than changes to timing of grazing in this study. Our results suggest that a phenological mismatch that delays timing of grazing relative to the growing season, a change which is already developing along in western coastal Alaska, will reduce GHG emissions to the atmosphere through increased CO2 uptake despite greater CH4 emissions.

Addressing private sector currency mismatches in emerging Europe

OpenAIRE

Jeromin Zettelmeyer; Piroska M. Nagy; Stephen Jeffrey

2010-01-01

This paper provides a survey of the theoretical and empirical literature on the dollarisation of corporate and household liabilities; presents evidence on the causes of FX lending specifically in transition economies; and proposes a set of criteria to help decide on the right policy response based on country characteristics. These criteria particularly affect the extent to which regulation should be part of the policy response. Regulation to contain FX mismatches is useful in relatively advan...

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

International Nuclear Information System (INIS)

Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

Performance evaluation of new automated hepatitis B viral markers in the clinical laboratory: two quantitative hepatitis B surface antigen assays and an HBV core-related antigen assay.

Science.gov (United States)

Park, Yongjung; Hong, Duck Jin; Shin, Saeam; Cho, Yonggeun; Kim, Hyon-Suk

2012-05-01

We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays.

Natural selection promotes antigenic evolvability.

Science.gov (United States)

Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

2013-01-01

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

Natural selection promotes antigenic evolvability.

Directory of Open Access Journals (Sweden)

Christopher J Graves

Full Text Available The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish

Concepts and applications for influenza antigenic cartography

Science.gov (United States)

Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

2011-01-01

Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

Occupational stratification, job-mismatches, and child poverty: understanding the disadvantage of Black immigrants in the US.

Science.gov (United States)

Thomas, Kevin J A

2015-03-01

This study examines the implications of occupational stratification and job mismatches for the welfare of children, using data from the 2005-2009 American Community Survey. The results show that Black children of immigrants have household heads that are more likely to have occupations with low SEI scores than children in US-born households. More importantly, they demonstrate that intersections between parental job-mismatches and employment in the bottom rather than upper levels of the occupational distribution have important implications for understanding poverty differences among children. Job mismatches within occupations with low SEI scores are associated with greater poverty risks among Black than White, Asian, or Hispanic children of immigrants. However, racial poverty disparities are considerably lower among children with household heads in the highest occupational strata. Copyright © 2014 Elsevier Inc. All rights reserved.

Understanding the Transfer Deficit: Contextual Mismatch, Proactive Interference, and Working Memory Affect Toddlers' Video-Based Transfer.

Science.gov (United States)

Choi, Koeun; Kirkorian, Heather L; Pempek, Tiffany A

2017-04-17

Researchers tested the impact of contextual mismatch, proactive interference, and working memory (WM) on toddlers' transfer across contexts. Forty-two toddlers (27-34 months) completed four object-retrieval trials, requiring memory updating on Trials 2-4. Participants watched hiding events on a tablet computer. Search performance was tested using another tablet (match) or a felt board (mismatch). WM was assessed. On earlier search trials, WM predicted transfer in both conditions, and toddlers in the match condition outperformed those in the mismatch condition; however, the benefit of contextual match and WM decreased over trials. Contextual match apparently increased proactive interference on later trials. Findings are interpreted within existing accounts of the transfer deficit, and a combined account is proposed. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Emotional Intelligence and Mismatching Expressive and Verbal Messages: A Contribution to Detection of Deception

Science.gov (United States)

Wojciechowski, Jerzy; Stolarski, Maciej; Matthews, Gerald

2014-01-01

Processing facial emotion, especially mismatches between facial and verbal messages, is believed to be important in the detection of deception. For example, emotional leakage may accompany lying. Individuals with superior emotion perception abilities may then be more adept in detecting deception by identifying mismatch between facial and verbal messages. Two personal factors that may predict such abilities are female gender and high emotional intelligence (EI). However, evidence on the role of gender and EI in detection of deception is mixed. A key issue is that the facial processing skills required to detect deception may not be the same as those required to identify facial emotion. To test this possibility, we developed a novel facial processing task, the FDT (Face Decoding Test) that requires detection of inconsistencies between facial and verbal cues to emotion. We hypothesized that gender and ability EI would be related to performance when cues were inconsistent. We also hypothesized that gender effects would be mediated by EI, because women tend to score as more emotionally intelligent on ability tests. Data were collected from 210 participants. Analyses of the FDT suggested that EI was correlated with superior face decoding in all conditions. We also confirmed the expected gender difference, the superiority of high EI individuals, and the mediation hypothesis. Also, EI was more strongly associated with facial decoding performance in women than in men, implying there may be gender differences in strategies for processing affective cues. It is concluded that integration of emotional and cognitive cues may be a core attribute of EI that contributes to the detection of deception. PMID:24658500

Emotional intelligence and mismatching expressive and verbal messages: a contribution to detection of deception.

Directory of Open Access Journals (Sweden)

Jerzy Wojciechowski

Full Text Available Processing facial emotion, especially mismatches between facial and verbal messages, is believed to be important in the detection of deception. For example, emotional leakage may accompany lying. Individuals with superior emotion perception abilities may then be more adept in detecting deception by identifying mismatch between facial and verbal messages. Two personal factors that may predict such abilities are female gender and high emotional intelligence (EI. However, evidence on the role of gender and EI in detection of deception is mixed. A key issue is that the facial processing skills required to detect deception may not be the same as those required to identify facial emotion. To test this possibility, we developed a novel facial processing task, the FDT (Face Decoding Test that requires detection of inconsistencies between facial and verbal cues to emotion. We hypothesized that gender and ability EI would be related to performance when cues were inconsistent. We also hypothesized that gender effects would be mediated by EI, because women tend to score as more emotionally intelligent on ability tests. Data were collected from 210 participants. Analyses of the FDT suggested that EI was correlated with superior face decoding in all conditions. We also confirmed the expected gender difference, the superiority of high EI individuals, and the mediation hypothesis. Also, EI was more strongly associated with facial decoding performance in women than in men, implying there may be gender differences in strategies for processing affective cues. It is concluded that integration of emotional and cognitive cues may be a core attribute of EI that contributes to the detection of deception.

The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch.

Directory of Open Access Journals (Sweden)

Elaine Ann Moore

Full Text Available The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with S-substitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening.

Changing of expression level of fas-antigen (CD95), cytokines synthesis and production after irradiation in low doses

International Nuclear Information System (INIS)

Kalinina, N.M.; Solntceva, O.S.; Bytchkova, N.V.; Nikiforov, A.M.

1997-01-01

It is known that bone marrow progenitor (CD34+), tymocytes and peripheral blood lymphocytes (PBL) are most radiosensitive than other cell types. Even low doses of radiation induce apoptosis. The investigators suggest that it is possible relationship between synthesis and production of cytokines and apoptotic process. With the purpose to determine correlation between expression of Fas-antigen and synthesis of cytokines after low doses irradiation the experiments by irradiation PBL of healthy persons in vitro were held. Cells were X-irradiated by 12,5, 25 and 50 cGy. In consequence of the experiments increasing of Fas-antigen was revealed. This increasing correlated with changing in synthesis and production of cytokines. Also the Chernobyl's accident liquidators (CAL) were investigated. After comparison data in the group CAL (I) with data in the control group (II) increasing of Fas-antigen expression was revealed. Also in I group was discovered increasing of the cell number sinthesied interleukine-4 (IL-4) and interleukine-6 (IL-6). Interleukine-lβ (IL-1 β) producing pell were decreased. These changes have been correlated with degree of immunodeficiency at CAL. These data allow to consider the apoptosis as cell mechanism included in pathogenesis of diseases, which can be showed later long time after irradiation. (author)

Mismatch or cumulative stress : Toward an integrated hypothesis of programming effects

NARCIS (Netherlands)

Nederhof, Esther; Schmidt, Mathias V.

2012-01-01

This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the

BEPS Action 2: Neutralizing the Effects on Hybrid Mismatch Arrangements

NARCIS (Netherlands)

de Boer, R.; Marres, O.

2015-01-01

Curbing tax arbitrage is one of the main priorities of the Organization for Economic Cooperation and Development (OECD) (endorsed by the G20 and the G8) ever since the public debate on base erosion fully erupted. Neutralizing the effect of hybrid mismatch arrangements has become Action No. 2 of the

Using a multi-feature paradigm to measure mismatch responses to minimal sound contrasts in children with cochlear implants and hearing aids.

Science.gov (United States)

Uhlén, Inger; Engström, Elisabet; Kallioinen, Petter; Nakeva von Mentzer, Cecilia; Lyxell, Björn; Sahlén, Birgitta; Lindgren, Magnus; Ors, Marianne

2017-10-01

Our aim was to explore whether a multi-feature paradigm (Optimum-1) for eliciting mismatch negativity (MMN) would objectively capture difficulties in perceiving small sound contrasts in children with hearing impairment (HI) listening through their hearing aids (HAs) and/or cochlear implants (CIs). Children aged 5-7 years with HAs, CIs and children with normal hearing (NH) were tested in a free-field setting using a multi-feature paradigm with deviations in pitch, intensity, gap, duration, and location. There were significant mismatch responses across all subjects that were positive (p-MMR) for the gap and pitch deviants (F(1,43) = 5.17, p = 0.028 and F(1,43) = 6.56, p = 0.014, respectively) and negative (MMN) for the duration deviant (F(1,43) = 4.74, p = 0.035). Only the intensity deviant showed a significant group interaction with MMN in the HA group and p-MMR in the CI group (F(2,43) = 3.40, p = 0.043). The p-MMR correlated negatively with age, with the strongest correlation in the NH subjects. In the CI group, the late discriminative negativity (LDN) was replaced by a late positivity with a significant group interaction for the location deviant. Children with severe HI can be assessed through their hearing device with a fast multi-feature paradigm. For further studies a multi-feature paradigm including more complex speech sounds may better capture variation in auditory processing in these children. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

Directory of Open Access Journals (Sweden)

Marcela V Maus

2016-01-01

Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

Science.gov (United States)

Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

2017-07-03

The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

Ultraviolet light-induced suppression of antigen presentation

International Nuclear Information System (INIS)

Spellman, C.W.; Tomasi, T.B.

1983-01-01

Ultraviolet (UV) light irradiation of animals results in the development of specific T suppressor cells that inhibit antitumor immune responses. It is thought that suppression may arise as a consequence of altered antigen presentation by UV-irradiated epidermal cells. This hypothesis is based on evidence demonstrating that specific lymphoid tissues from UV-irradiated hosts exhibit impaired antigen-presenting function and that animals cannot be contact sensitized when antigens are applied to a UV-irradiated skin site. Langerhans cells of the skin are likely candidates as targets of UV-induced defects in antigen presentation as they bear Fc and C3b receptors, express Ia antigens, are of bone marrow origin, and are capable of presenting antigen in vitro. We speculate on the possible clinical usefulness of UV-induced tolerance to specific antigens such as those encountered in monoclonal antibody therapy and tissue transplantation

Characterization of antigen association with accessory cells: specific removal of processed antigens from the cell surface by phospholipases

International Nuclear Information System (INIS)

Falo, L.D. Jr.; Haber, S.I.; Herrmann, S.; Benacerraf, B.; Rock, K.L.

1987-01-01

To characterize the basis for the cell surface association of processed antigen with the antigen-presenting cell (APC) the authors analyzed its sensitivity to enzymatic digestion. Antigen-exposed APC that are treated with phospholipase and then immediately fixed lose their ability to stimulate antigen-plus-Ia-specific T-T hybridomas. This effect is seen with highly purified phospholipase A 2 and phospholipase C. In addition it is observed with three distinct antigens - ovalbumin, bovine insulin, and poly(LGlu 56 LLys 35 LPhe 9 )[(GluLysPhe)/sub n/]. The effect of phospholipases is highly specific. Identically treated APC are equivalent to control in their ability to stimulate alloreactive hybridomas specific for precisely the same Ia molecule that is corecognized by antigen-plus-Ia-specific hybrids. Furthermore, the antigen-presenting function of enzyme-treated, fixed APC can be reconstituted by the addition of exogenous in vitro processed or processing independent antigens. In parallel studies 125 I-labeled avidin was shown to specifically bind to APC that were previously exposed and allowed to process biotin-insulin. Biotin-insulin-exposed APC that are pretreated with phospholipase bind significantly less 125 I-labeled avidin than do untreated, exposed APC. Identical enzyme treatment does not reduce the binding of avidin to a biotinylated antibody already bound to class II major histocompatibility complex molecules of APC. These studies demonstrate that phospholipase effectively removes processed cell surface antigen

Binding of hydrophobic antigens to surfaces

DEFF Research Database (Denmark)

2017-01-01

A first aspect of the present invention is a method of detecting antibodies comprising the steps of: i) providing a first group of beads comprising a surface modified with C1-C10 alkyl groups comprising amine, ammonium, ether and/or hydroxyl groups, ii) contacting said first group of beads......-antigen-antibody conjugates, and v) detecting said bead-antigen-antibody conjugates. Further aspects include an antibody detection kit, a bead-antigen conjugate and a composition comprising at least two different groups of bead-antigen-conjugates....

Genetic diversity of K-antigen gene clusters of Escherichia coli and their molecular typing using a suspension array.

Science.gov (United States)

Yang, Shuang; Xi, Daoyi; Jing, Fuyi; Kong, Deju; Wu, Junli; Feng, Lu; Cao, Boyang; Wang, Lei

2018-04-01

Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of Escherichia coli. More than 80 serologically unique K-antigens are classified into 4 groups (Groups 1-4) of capsules. Groups 1 and 4 contain the Wzy-dependent polymerization pathway and the gene clusters are in the order galF to gnd; Groups 2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters consist of 3 regions, regions 1, 2 and 3. Little is known about the variations among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated with their CPS chemical structures. On the basis of sequence data, a K-antigen-specific suspension array that detects 10 distinct CPSs, including the above 9 CPSs plus K30, was developed. This is the first report to catalog the genetic features of E. coli K-antigen variations and to develop a suspension array for their molecular typing. The method has a number of advantages over traditional bacteriophage and serum agglutination methods and lays the foundation for straightforward identification and detection of additional K-antigens in the future.

Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.

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Basanta K Dahal

2017-10-01

Full Text Available Heterochromatin contains a significant part of nuclear DNA. Little is known about the mechanisms that govern heterochromatic DNA stability. We show here that in the yeast Saccharomyces cerevisiae (i DNA mismatch repair (MMR is required for the maintenance of heterochromatic DNA stability, (ii MutLα (Mlh1-Pms1 heterodimer, MutSα (Msh2-Msh6 heterodimer, MutSβ (Msh2-Msh3 heterodimer, and Exo1 are involved in MMR at heterochromatin, (iii Exo1-independent MMR at heterochromatin frequently leads to the formation of Pol ζ-dependent mutations, (iv MMR cooperates with the proofreading activity of Pol ε and the histone acetyltransferase Rtt109 in the maintenance of heterochromatic DNA stability, (v repair of base-base mismatches at heterochromatin is less efficient than repair of base-base mismatches at euchromatin, and (vi the efficiency of repair of 1-nt insertion/deletion loops at heterochromatin is similar to the efficiency of repair of 1-nt insertion/deletion loops at euchromatin.

The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β

Science.gov (United States)

Koag, Myong-Chul; Nam, Kwangho; Lee, Seongmin

2014-01-01

To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an ‘intermediate’ protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound ‘pre-chemistry-state’ structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson–Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson–Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson–Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ. PMID:25200079

Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens

International Nuclear Information System (INIS)

Szala, S.; Kasai, Yasushi; Steplewski, Z.; Rodeck, U.; Koprowski, H.; Linnenbach, A.J.

1990-01-01

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins

Semantic processing in deaf and hard-of-hearing children: Large N400 mismatch effects in brain responses, despite poor semantic ability

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Petter Kallioinen

2016-08-01

Full Text Available Difficulties in auditory and phonological processing affect semantic processing in speech comprehension of deaf and hard-of-hearing (DHH children. However, little is known about brain responses of semantic processing in this group. We investigated event-related potentials (ERPs in DHH children with cochlear implants (CI and/or hearing aids (HA, and in normally hearing controls (NH. We used a semantic priming task with spoken word primes followed by picture targets. In both DHH children and controls, response differences between matching and mismatching targets revealed a typical N400-effect associated with semantic processing. Children with CI had the largest mismatch response despite poor semantic abilities overall, children with CI also had the largest ERP differentiation between mismatch types, with small effects of within-category mismatches (target from same category as prime and large effects between-category mismatches (were target is from a different category than prime. NH and HA children had similar responses to both mismatch types. While the large and differentiated ERP responses in the CI group were unexpected and should be interpreted with caution, the results could reflect less precision in semantic processing among children with CI, or a stronger reliance on predictive processing.

Presentation of lipid antigens to T cells.

Science.gov (United States)

Mori, Lucia; De Libero, Gennaro

2008-04-15

T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

Mismatch of Vocational Graduates: What Penalty on French Labour Market?

Science.gov (United States)

Beduwe, Catherine; Giret, Jean-Francois

2011-01-01

This study explores individual effects of educational mismatch on wages, job satisfaction and on-the-job-search on French labour market. We distinguish between horizontal matches (job matches with field of studies) and vertical matches (job matches the level of qualification) on the one hand and skills matches (worker's assessment) on the other…

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

Science.gov (United States)

Tran Vu Thieu, Nga; Trinh Van, Tan; Tran Tuan, Anh; Klemm, Elizabeth J; Nguyen Ngoc Minh, Chau; Voong Vinh, Phat; Pham Thanh, Duy; Ho Ngoc Dan, Thanh; Pham Duc, Trung; Langat, Pinky; Martin, Laura B; Galan, Jorge; Liang, Li; Felgner, Philip L; Davies, D Huw; de Jong, Hanna K; Maude, Rapeephan R; Fukushima, Masako; Wijedoru, Lalith; Ghose, Aniruddha; Samad, Rasheda; Dondorp, Arjen M; Faiz, Abul; Darton, Thomas C; Pollard, Andrew J; Thwaites, Guy E; Dougan, Gordon; Parry, Christopher M; Baker, Stephen

2017-08-01

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Antigenic and anticorpal diagnosis of invasive aspergillosis and candidosis in immunocompromised host

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Marco Machetti

2009-03-01

Full Text Available Invasive aspergillosis (IA and candidemia are an increasing cause of morbidity and mortality in immunocompromised patients, but diagnostic procedures are often hampered by critical patients conditions. In recent years, non-culture methods have reached a standardization level suitable to be marketed and widely employed. A method for a panfungal antigenic diagnosis, is the detection in serum of (1→3-ß-D-Glucan (BDG, a polisaccaridic component of fungal cell wall. Best results can be obtained in Aspergillus, Candida and Fusarium infections, while the test performs poorly with Cryptococcus and in zygomycosis. The use of this method are limited by the high costs and by the need of disposable materials certified as glucan-free, in order to avoid false positive results. Galactomannan (GM antigen detection is a method for non-invasive diagnosis of IA. The assay, in latex agglutination (LA and enzymeimmunoassay (EIA format, detect GM in serum, whose presence correlates with IA. Sensitivity and specificity strongly fluctuate (50-100% and 81-98% respectively depending on the time of sampling, the positivity cut-off employed, the concomitant administration of antifungal drugs and of some antibiotics. Nevertheless the method is a very useful and widely employed tool for the diagnosis of IA. For the diagnosis of candidemia, two Candida antigens may be detected in serum: the 56°C heat-labile antigen in LA format, and the mannan antigen, in LA and EIA format. Both the methods perform quite well, but sensitivities and specificities are not so good to allow a routinely and useful use in clinical practice.

Effects of frequency mismatch on a self-consistent arbitrary amplitude cyclotron resonance laser accelerator

International Nuclear Information System (INIS)

Pakter, R.; Schneider, R.S.; Rizzato, F.B.

1993-01-01

The cyclotron-resonance laser accelerator (CRLA), where a coherent electromagnetic wave may transfer a large amount of energy to a beam of electrons gravitating in a guide magnetic field is studied. This large amount of transferred energy takes place due to the autoresonance mechanism where, under some ideal conditions, an initial wave-particle synchronism is self-sustained throughout the accelerating period. An improved analysis of the mentioned self-consistent wave-particle interaction, taking into account a possible frequency mismatch between wave and particles. It is also shown how the frequency mismatch can compensate the dispersion effects. (L.C.J.A.)

Positive cooperativity of the specific binding between Hg2+ ion and T:T mismatched base pairs in duplex DNA

International Nuclear Information System (INIS)

Torigoe, Hidetaka; Miyakawa, Yukako; Ono, Akira; Kozasa, Tetsuo

2012-01-01

Highlights: ► Hg 2+ specifically bound with the T:T mismatched base pair at 1:1 molar ratio. ► The binding constant between Hg 2+ and the T:T mismatched base pair was 10 6 M −1 . ► The binding constant was larger than those for nonspecific metal–DNA interactions. ► The binding constant for the second Hg 2+ was larger than that for the first Hg 2+ . ► The positive cooperative binding was observed between Hg 2+ and multiple T:T. - Abstract: Metal-mediated base pairs by the interaction between metal ions and artificial bases in oligonucleotides have been developed for their potential applications in nanotechnology. We recently found that a natural T:T mismatched base pair bound with Hg 2+ ion to form a novel T–Hg–T base pair. Here, we examined the thermodynamic properties of the binding between Hg 2+ and each of the single and double T:T mismatched base pair duplex DNAs by isothermal titration calorimetry. Hg 2+ specifically bound with the T:T mismatched base pair at 1:1 molar ratio with 10 6 M −1 binding constant, which was significantly larger than those for nonspecific metal ion–DNA interactions. In the Hg 2+ –double T:T mismatched base pair interaction, the affinity for the second Hg 2+ binding was significantly larger than that for the first Hg 2+ binding. The positively cooperative binding may be favorable to align multiple Hg 2+ in duplex DNA for the application of the metal-mediated base pairs in nanotechnology.

Development of a radioimmunoassay for a high molecular mass tubular antigen in urine - its application for early detection of tubular damage

International Nuclear Information System (INIS)

Sachse, H.J.; Falkenberg, F.W.; Scherberich, J.E.; Stefanescu, T.; Fassbinder, W.; Mondorf, A.W.; Schoeppe, W.

1981-01-01

In order to isolate urinary kidney antigens, the gammaglobulin fraction of an antiserum against human kidney cortex plasma membranes was coupled to Sepharose 4B. By immunospecific affinity chromatography an antigen fraction was obtained from the urine of a patient suffering from severe kidney disease. After gel filtration, the main fraction, eluted with the exclusion volume of a Sephadex G-200 column and enriched 16000-fold, was labelled with 131 I and used in a radioimmunoassay system. Soluble kidney antigens, presumably of proximal tubular origin, could be detected and quantified by the assay system in urine samples of patients with various diseases. The samples did not need to be treated, either concentrated or dialyzed, before application. The results of the experiments show a correlation between antigen excretion and kidney damage. Rejection episodes in patients with kidney transplants could be recognized early by enhanced antigen excretion. Potentially nephrotoxic drugs caused antigen excretion as well. In normal, healthy subjects output of the antigen was very low. The assay system might be of value for monitoring renal diseases. (Auth.)

Immune markers and correlates of protection for vaccine induced immune responses

DEFF Research Database (Denmark)

Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

2012-01-01

of an appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against......-specific production of interferon-gamma (IFN-γ) has been promoted as a quantitative marker of protective cell-mediated immune responses over the past couple of decades. More recently, however, evidence from several infections has pointed towards the quality of the immune response, measured through increased levels...... of antigen-specific polyfunctional T cells capable of producing a triad of relevant cytokines, as a better correlate of sustained protective immunity against this type of infections. Also the possibilities to measure antigen-specific cytotoxic T cells (CTL) during infection or in response to vaccination...

Degree of Predicted Minor Histocompatibility Antigen Mismatch Correlates with Poorer Clinical Outcomes of Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

DEFF Research Database (Denmark)

Larsen, Malene Erup; Kornblit, B; Larsen, Mette Voldby

2010-01-01

In fully HLA-matched allogeneic hematopoietic cell transplantations (HCT), the main mechanism of the beneficial graft-versus-tumor (GVT) effect and of the detrimental graft-versus-host disease (GVHD) is believed to be caused by donor cytotoxic T cells directed against disparate recipient minor hi...

Somatosensory mismatch response in young and elderly adults

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Juho M. Strömmer

2014-10-01

Full Text Available Aging is associated with cognitive decline and alterations in early perceptual processes. Studies in the auditory and visual modalities have shown that the mismatch negativity (or the mismatch response, MMR, an event-related potential (ERP elicited by a deviant stimulus in a background of homogenous events, diminishes with aging and cognitive decline. However, the effects of aging on the somatosensory MMR are not known. In the current study, we recorded ERPs to electrical pulses to different fingers of the left hand in a passive oddball experiment in young (22–36 years and elderly (66–95 years adults engaged in a visual task. The MMR was found to deviants as compared to standards at two latency ranges: 180–220 ms and 250–290 ms post-stimulus onset. At 180–220 ms, within the young, the MMR was found at medial electrode sites, whereas aged did not show any amplitude difference between the stimulus types at the same latency range. At 250–290 ms, the MMR was evident with attenuated amplitude and narrowed scalp distribution among aged (Fz compared to young (fronto-centrally and lateral parietal sites. Hence, the results reveal that the somatosensory change detection mechanism is altered in aging. The somatosensory MMR can be used as a reliable measure of age-related changes in sensory-cognitive functions.

Prostate-Specific Antigen Mass and Free Prostate-Specific Antigen Mass for Predicting the Prostate Volume of Korean Men With Biopsy-Proven Benign Prostatic Hyperplasia

OpenAIRE

Park, Tae Yong; Chae, Ji Yun; Kim, Jong Wook; Kim, Jin Wook; Oh, Mi Mi; Yoon, Cheol Yong; Moon, Du Geon

2013-01-01

Purpose It has been reported that prostate-specific antigen (PSA) correlates with prostate volume. Recently, some studies have reported that PSA mass (PSA adjusted for plasma volume) is more accurate than PSA at predicting prostate volume. In this study, we analyzed the accuracy of PSA and the related parameters of PSA mass, free PSA (fPSA), and fPSA mass in predicting prostate volume. Materials and Methods We retrospectively investigated 658 patients who underwent prostate biopsy from 2006 t...

Collective pedagogical teacher culture, teacher-student ethno-racial mismatch, and teacher job satisfaction.

Science.gov (United States)

Stearns, Elizabeth; Banerjee, Neena; Mickelson, Roslyn; Moller, Stephanie

2014-05-01

Teacher job satisfaction is critical to schools' successful functioning. Using a representative sample of kindergarten teachers from the Early Childhood Longitudinal Study, we investigate the association among professional learning community and teacher collaboration, teacher ethno-racial group, teacher-student ethno-racial mismatch, and teacher job satisfaction. We find that White teachers are significantly less satisfied than African-American and Latino teachers, especially when they teach in majority non-White classrooms. However, the existence of a professional community moderates the negative influence of teacher-student ethno-racial mismatch on White teachers' job satisfaction. In effect, strong professional communities serve as a cushion to bolster teacher job satisfaction. Copyright © 2014 Elsevier Inc. All rights reserved.

Allosensibilisation to erythrocyte antigens (literature review

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N. V. Mineeva

2015-01-01

Full Text Available In this article literature review of the causes of allosensibilisation to erythrocyte antigens are presented. It is shown that the ability to produce antierythrocyte antibodies is affected by many factors, principal of whom it is difficult to identify. For the allosensibilisation development requires genetically determined differences in erythrocyte antigens phenotypes of donor and recipient, mother and fetus, which can lead to immune response and antibodies production. The biochemical nature of erythrocyte antigens, antigen dose (the amount of transfused doses, the number of antigens determinants on donor and fetus erythrocytes, the number of pregnancies are important. Individual patient characteristics: age, gender, diseases, the use of immunosuppressive therapy and the presence of inflammatory processes, are also relevant. Note that antibody to one erythrocyte antigens have clinical value, and to the other – have no. The actual data about frequency of clinically significant antibodies contribute to the development of post-transfusion hemolytic complications prophylaxis as well as the improvement of laboratory diagnosis of hemolytic disease of the newborn in the presence of maternal antierythrocyte antibodies.

Doublethink and scale mismatch polarize policies for an invasive tree

Science.gov (United States)

Roberts, Caleb P.; Uden, Daniel R.; Allen, Craig R.; Twidwell, Dirac

2018-01-01

Mismatches between invasive species management policies and ecological knowledge can lead to profound societal consequences. For this reason, natural resource agencies have adopted the scientifically-based density-impact invasive species curve to guide invasive species management. We use the density-impact model to evaluate how well management policies for a native invader (Juniperus virginiana) match scientific guidelines. Juniperus virginiana invasion is causing a sub-continental regime shift from grasslands to woodlands in central North America, and its impacts span collapses in endemic diversity, heightened wildfire risk, and crashes in grazing land profitability. We (1) use land cover data to identify the stage of Juniperus virginiana invasion for three ecoregions within Nebraska, USA, (2) determine the range of invasion stages at individual land parcel extents within each ecoregion based on the density-impact model, and (3) determine policy alignment and mismatches relative to the density-impact model in order to assess their potential to meet sustainability targets and avoid societal impacts as Juniperus virginiana abundance increases. We found that nearly all policies evidenced doublethink and policy-ecology mismatches, for instance, promoting spread of Juniperus virginiana regardless of invasion stage while simultaneously managing it as a native invader in the same ecoregion. Like other invasive species, theory and literature for this native invader indicate that the consequences of invasion are unlikely to be prevented if policies fail to prioritize management at incipient invasion stages. Theory suggests a more realistic approach would be to align policy with the stage of invasion at local and ecoregion management scales. There is a need for scientists, policy makers, and ecosystem managers to move past ideologies governing native versus non-native invader classification and toward a framework that accounts for the uniqueness of native species invasions

Doublethink and scale mismatch polarize policies for an invasive tree

Science.gov (United States)

Roberts, Caleb P.; Uden, Daniel R.; Allen, Craig R.; Twidwell, Dirac

2018-01-01

Mismatches between invasive species management policies and ecological knowledge can lead to profound societal consequences. For this reason, natural resource agencies have adopted the scientifically-based density-impact invasive species curve to guide invasive species management. We use the density-impact model to evaluate how well management policies for a native invader (Juniperus virginiana) match scientific guidelines. Juniperus virginiana invasion is causing a sub-continental regime shift from grasslands to woodlands in central North America, and its impacts span collapses in endemic diversity, heightened wildfire risk, and crashes in grazing land profitability. We (1) use land cover data to identify the stage of Juniperus virginiana invasion for three ecoregions within Nebraska, USA, (2) determine the range of invasion stages at individual land parcel extents within each ecoregion based on the density-impact model, and (3) determine policy alignment and mismatches relative to the density-impact model in order to assess their potential to meet sustainability targets and avoid societal impacts as Juniperus virginiana abundance increases. We found that nearly all policies evidenced doublethink and policy-ecology mismatches, for instance, promoting spread of Juniperus virginiana regardless of invasion stage while simultaneously managing it as a native invader in the same ecoregion. Like other invasive species, theory and literature for this native invader indicate that the consequences of invasion are unlikely to be prevented if policies fail to prioritize management at incipient invasion stages. Theory suggests a more realistic approach would be to align policy with the stage of invasion at local and ecoregion management scales. There is a need for scientists, policy makers, and ecosystem managers to move past ideologies governing native versus non-native invader classification and toward a framework that accounts for the uniqueness of native species

Immunodetection of Fasciola gigantica Circulating Antigen in Sera of Infected Individuals for Laboratory Diagnosis of Human Fascioliasis

Science.gov (United States)

Attallah, Abdelfattah M.; Bughdadi, Faisal A.; El-Shazly, Atef M.

2013-01-01

Currently, the laboratory diagnosis of human fascioliasis is based on the parasitological examination of parasite eggs in stool specimens and serological detection of specific antibodies in serum samples, which are often unreliable diagnostic approaches. Ideally, a sensitive and specific diagnostic test for Fasciola infection should be based on the detection of circulating Fasciola antigen, which implies active infection. Here, a 27-kDa-molecular-mass antigen was identified in a Fasciola gigantica adult worm antigen preparation, excretory-secretory products, and sera from F. gigantica-infected individuals, and it was not detected in antigenic extracts of other parasites and sera from noninfected individuals. The target antigen was isolated and partially characterized as a protein. Immunoperoxidase staining located the target epitope within teguments and guts of F. gigantica adult worms. The performance characteristics of a newly developed enzyme-linked immunosorbent assay (ELISA) based on F. gigantica circulating antigen detection in serum (FgCA-27 ELISA) were investigated using sera of 120 parasitologically diagnosed F. gigantica-infected individuals and 80 noninfected individuals. The area under the receiving operating characteristic (ROC) curve (AUC) for ELISA was significantly high (AUC = 0.961, P 93%), and a significant correlation (r = 0.715, P fascioliasis. PMID:23945158

Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

DEFF Research Database (Denmark)

Dominguez-Valentin, Mev; Joost, Patrick; Therkildsen, Christina

2016-01-01

were high-grade tumors with Gleason scores 8-10. Prostate cancer was associated with mutations in MSH2, MLH1 and MSH6 with loss of the respective mismatch repair protein in 69 % of the tumors, though a MSI-high phenotype was restricted to 13 % of the tumors. The cumulative risk of prostate cancer...

Robust MOE Detector for DS-CDMA Systems with Signature Waveform Mismatch

Science.gov (United States)

Lin, Tsui-Tsai

In this letter, a decision-directed MOE detector with excellent robustness against signature waveform mismatch is proposed for DS-CDMA systems. Both the theoretic analysis and computer simulation results demonstrate that the proposed detector can provide better SINR performance than that of conventional detectors.

Self-organization and mismatch tolerance in protein folding: General theory and an application

Science.gov (United States)

Fernández, Ariel; Berry, R. Stephen

2000-03-01

The folding of a protein is a process both expeditious and robust. The analysis of this process presented here uses a coarse, discretized representation of the evolving form of the backbone chain, based on its torsional states. This coarse description consists of discretizing the torsional coordinates modulo the Ramachandran basins in the local softmode dynamics. Whenever the representation exhibits "contact patterns" that correspond to topological compatibilities with particular structural forms, secondary and then tertiary, the elements constituting the pattern are effectively entrained by a reduction of their rates of exploration of their discretized configuration space. The properties "expeditious and robust" imply that the folding protein must have some tolerance to both torsional "frustrated" and side-chain contact mismatches which may occur during the folding process. The energy-entropy consequences of the staircase or funnel topography of the potential surface should allow the folding protein to correct these mismatches, eventually. This tolerance lends itself to an iterative pattern-recognition-and-feedback description of the folding process that reflects mismatched local torsional states and hydrophobic/polar contacts. The predictive potential of our algorithm is tested by application to the folding of bovine pancreatic trypsin inhibitor (BPTI), a protein whose ability to form its active structure is contingent upon its frustration tolerance.

3D–2D image registration for target localization in spine surgery: investigation of similarity metrics providing robustness to content mismatch

International Nuclear Information System (INIS)

De Silva, T; Ketcha, M D; Siewerdsen, J H; Uneri, A; Reaungamornrat, S; Kleinszig, G; Vogt, S; Aygun, N; Lo, S-F; Wolinsky, J-P

2016-01-01

In image-guided spine surgery, robust three-dimensional to two-dimensional (3D–2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D–2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE  >  30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE  <  6.4 mm (±4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1–2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of  >14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE  =  5.5 mm, 2.6 mm IQR) without manual masking and with an improved

Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.

Directory of Open Access Journals (Sweden)

Shivali Gupta

Full Text Available Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd-phase for antibody response to the recombinant antigens (individually or mixed by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175. The IgG antibodies to TcG1, TcG2, and TcG4 (individually and TcG(mix were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%, TcG2- (96%, TcG4- (94.6% and TcG(mix- (98% based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8% in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

Correlation of antigen-specific IFN-γ responses of fresh blood samples from Mycobacterium avium subsp. paratuberculosis infected heifers with responses of day-old samples co-cultured with IL-12 or anti-IL-10 antibodies

DEFF Research Database (Denmark)

Mikkelsen, Heidi; Aagaard, Claus; Nielsen, Søren Saxmose

2012-01-01

Paratuberculosis is a chronic infection of the intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Early stage MAP infection can be detected by measuring cell-mediated immune responses using the interferon gamma (IFN-γ) assay. Whole blood samples are cultured...... to enhance IFN-γ responses of cultures stimulated with Johnin purified protein derivative (PPDj). Here we examined the correlation of IFN-γ production in response to PPDj and 15 recombinant antigens in day-old blood samples from heifers 10–21 months of age from a MAP infected herd with addition of either...... overnight with specific MAP antigens followed by quantification of IFN-γ by ELISA. It is recommended that the time interval from sampling to culture does not exceed eight hours but addition of the co-stimulating cytokine interleukin 12 (IL-12) or anti-IL-10 antibodies to culture have been demonstrated...

Tissue distribution of histo-blood group antigens

DEFF Research Database (Denmark)

Ravn, V; Dabelsteen, Erik

2000-01-01

carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histoblood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell- and tissue......The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data...... concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain...

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

Science.gov (United States)

Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Mis-Match Limit Load Analyses and Fracture Mechanics Assessment for Welded Pipe with Circumferential Crack at the Center of Weldment

Energy Technology Data Exchange (ETDEWEB)

Song, Tae Kwang; Jeon, Jun Young; Shim, Kwang Bo; Kim, Yun Jae [Korea University, Seoul (Korea, Republic of); Kim, Jong Sung [Sunchon University, Suncheon (Korea, Republic of); Jin, Tae Eun [Korea Power Engineering Company, Daejeon (Korea, Republic of)

2010-01-15

In this paper, limit load analyses and fracture mechanics analyses were conducted via finite element analyses for the welded pipe with circumferential crack at the center of the weldment. Systematic changes for strength mismatch ratio, width of weldment, crack shape and thickness ratio of the pipe were considered to provide strength mismatch limit load. And J-integral calculations based on reference stress method were conducted for two materials, stainless steel and ferritic steel. Reference stress defined by provided strength mis-match limit load gives much more accurate J-integral.

Kinetics of human T-cell expression of LFA-1, IL-2 receptor, and ICAM-1 following antigenic stimulation in vitro

DEFF Research Database (Denmark)

Hviid, L; Felsing, A; Theander, T G

1993-01-01

-specific stimulation is available. In the present study we have examined phenotypic T-cell changes after in vitro stimulation by the antigens purified derivative of tuberculin (PPD) and tetanus toxoid (TT). We show that the well-established differences in kinetics of mitogen- and antigen-induced T-cell proliferation...... of all 3 surface antigens showed similar kinetics, and correlated with the magnitude of the lymphoproliferative response. By day 8 (PHA-stimulation) or day 12 (PPD or TT stimulation), the lymphoproliferative response was essentially completed, the expression of CD11a and CD54 had approached...

Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

Directory of Open Access Journals (Sweden)

Stephen J. Proctor

2010-01-01

, supported by six mismatched cord blood units (one unit per 10 kg recipient weight. No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.

Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Tage-Jensen, Ulrik Viggo; Bahnsen, M

1981-01-01

Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA...... had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients....... With increasing titres of ANA the concentration of testosterone fell. Serum concentration of testosterone correlated inversely (P less than 0.05) with plasma immunoglobulin G and A. It is concluded that both genetic and hormonal factors may influence the humoral immune response in these patients....

Mismatch repair deficiency in colorectal cancer patients in a low ...

African Journals Online (AJOL)

2013-02-06

Feb 6, 2013 ... This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. Objectives. The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the. Northern Cape.

Educational Mismatch and Spatial Flexibility in Italian Local Labour Markets

Science.gov (United States)

Croce, Giuseppe; Ghignoni, Emanuela

2015-01-01

According to recent literature, this paper highlights the relevance of spatial mobility as an explanatory factor of the individual risk of job-education mismatch. To investigate this causal link, we use individual information about daily home-to-work commuting time and choices to relocate in a different local area to get a job. Our model takes…

Investigation of the antigenic evolution of field isolates using the reverse genetics system of infectious bursal disease virus (IBDV).

Science.gov (United States)

Durairaj, Vijay; Sellers, Holly S; Linnemann, Erich G; Icard, Alan H; Mundt, Egbert

2011-10-01

The antigenic profiles of over 300 infectious bursal disease virus (IBDV) isolates were analyzed using a panel of monoclonal antibodies in a reverse genetics system. In addition, the sequences of a large portion of the neutralizing-antibody-inducing VP2 of IBDV were determined. Phylogenetic analysis of nucleotide and amino acid sequences in combination with the antigenic profiles obtained using the monoclonal antibody panel, revealed a lack of correlation between antigenicity and isolate's placement within the phylogenetic tree. In-depth analysis of amino acid exchanges revealed that changes within a certain region of the VP2 molecule resulted in differences in the antigenicity of the virus. This comprehensive analysis of VP2 sequences indicated a high selective pressure in the field that was likely due to vaccination programs, which increase the rate of evolution of the virus.

Diffusion Tensor Imaging for the Differentiation of Microangiopathy, Infarction and Perfusion-Diffusion Mismatch Lesions

International Nuclear Information System (INIS)

Ha, Dong Ho; Choi, Sun Seob; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyung Jin

2009-01-01

This study was designed to evaluate the usefulness of diffusion tensor imaging (DTI) and the DTI indices for differentiating between microangiopathy lesions, acute infarction lesions and perfusion-diffusion mismatch areas. DTI was performed in 35 patients with the use of a 1.5 Tesla MRI system. The MRI parameters were as follows: a spin echo EPI sequence with a bvalue = 1000 s/mm 2 , 25 diffusion directions, a repetition time of 8400 msec, an echo time of 75 msec, a matrix size of 128 x 128, a FOV of 22 cm and a 4 mm slice thickness. From the diffusion tensor images, the apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume ratio (VR), relative anisotropy (RA), anisotropy index (AI), exponential ADC (eADC) and magnitude diffusion coefficient (MDC) were measured for the contra-lateral normal area (28 cases), the microangiopathy lesions (10 cases), the infarction lesions (17 cases) and the perfusion-diffusion mismatch area (8 cases). As compared to the normal area, the microangiopathy lesions showed increased ADC and MDC values and decreased FA, VR, RA, AI and eADC values. The infarction lesions showed increased VR, RA and eADC values, a normal FA, a decreased AI and decreased ADC and MDC values. The mismatch area showed a similar pattern as that for the microangiopathy lesions; however, the differences were not prominent, with an increase of the ADC and MDC values and a decrease of FA, VR, RA, AI and eADC values. The DTI indices could have a role in making the differential diagnosis of microangiopathy, acute infarction and perfusion-diffusion mismatch lesions

HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma.

Science.gov (United States)

Thuring, Camilla; Follin, Elna; Geironson, Linda; Freyhult, Eva; Junghans, Victoria; Harndahl, Mikkel; Buus, Søren; Paulsson, Kajsa M

2015-09-15

Tumour cells can evade the immune system by dysregulation of human leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell surface expression is the result of either HLA-I alterations or dysregulations of proteins of the antigen-processing machinery (APM). Tapasin is an APM protein dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked to higher malignancy in several different tumours. We studied the expression of APM components and HLA-I, as well as HLA-I tapasin-dependency profiles in glioblastoma tissues and corresponding cell lines. Tapasin displayed the strongest correlation to HLA-I heavy chain but also clustered with β2-microglobulin, transporter associated with antigen processing (TAP) and LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin dependence of HLA-I allomorphs in glioblastoma patients. Expression of APM proteins is highly variable between glioblastomas. Tapasin stands out as the APM component strongest correlated to HLA-I expression and we proved that HLA-I profiles in glioblastoma patients include tapasin-dependent allomorphs. The level of tapasin was also correlated with patient survival time. Our results support the need for individualisation of immunotherapy protocols.

Tunable band structures of polycrystalline graphene by external and mismatch strains

Institute of Scientific and Technical Information of China (English)

Jiang-Tao Wu; Xing-Hua Shi; Yu-Jie Wei

2012-01-01

Lacking a band gap largely limits the application of graphene in electronic devices.Previous study shows that grain boundaries (GBs) in polycrystalline graphene can dramatically alter the electrical properties of graphene.Here,we investigate the band structure of polycrystalline graphene tuned by externally imposed strains and intrinsic mismatch strains at the GB by density functional theory (DFT) calculations.We found that graphene with symmetrical GBs typically has zero band gap even with large uniaxial and biaxial strain.However,some particular asymmetrical GBs can open a band gap in graphene and their band structures can be substantially tuned by external strains.A maximum band gap about 0.19 eV was observed in matched-armchair GB (5,5) | (3,7) with a misorientation of θ =13° when the applied uniaxial strain increases to 9％.Although mismatch strain is inevitable in asymmetrical GBs,it has a small influence on the band gap of polycrystalline graphene.

Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

DEFF Research Database (Denmark)

Mustafa, A S; Amoudy, H A; Wiker, H G

1998-01-01

We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r......GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

Correlation between 'H' blood group antigen and Plasmodium falciparum invasion.

Science.gov (United States)

Pathak, Vrushali; Colah, Roshan; Ghosh, Kanjaksha

2016-06-01

The ABO blood group system is the most important blood group system in clinical practice. The relationship between Plasmodium falciparum and ABO blood groups has been studied for many years. This study was undertaken to investigate the abilities of different blood group erythrocytes to support in vitro growth of P. falciparum parasites. P. falciparum parasites of four different strains (3D7, 7G8, Dd2 and RKL9) were co-cultured with erythrocytes of blood group 'A', 'B', 'O' (n = 10 for each) and 'O(h)' (Bombay group) (n = 7) for 5 days. Statistically significant differences were observed on the fourth day among the mean percent parasitemias of 'O', non-'O' ('A' and 'B') and 'O(h)' group cultures. The parasitemias of four strains ranged from 12.23 to 14.66, 11.68 to 13.24, 16.89 to 22.3, and 7.37 to 11.27 % in 'A', 'B', 'O' and Bombay group cultures, respectively. As the expression of H antigen decreased from 'O' blood group to 'A' and 'B' and then to Bombay blood group, parasite invasion (percent parasitemia) also decreased significantly (p Ulex europaeus seeds. Mean percent parasitemia of lectin-treated cultures on the fourth day was significantly lower (p < 0.05) than that of non-treated cultures and was found to be similar with the mean percent parasitemia demonstrated by the Bombay group erythrocyte cultures, thus further strengthening the hypothesis.

Protamine-based nanoparticles as new antigen delivery systems.

Science.gov (United States)

González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

2015-11-01

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Generalized synchronization induced by noise and parameter mismatching in Hindmarsh-Rose neurons

International Nuclear Information System (INIS)

Wu Ying; Xu Jianxue; He Daihai; Earn, David J.D.

2005-01-01

Synchronization of two simple neuron models has been investigated in many studies. Thresholds for complete synchronization (CS) and phase synchronization (PS) have been obtained for coupling by diffusion or noise. In addition, it has been shown that it is possible for directional diffusion to induce generalized synchronization (GS) in a pair of neuron models even if the neurons are not identical (and differ in a single parameter). We study a system of two uncoupled, nonidentical Hindmarsh-Rose (HR) neurons and show that GS can be achieved by a combination of noise and changing the value of a second parameter in one of the neurons (the second parameter mismatch cancels the first). The significance of this approach will be the greatest in situations where the parameter that is originally mismatched cannot be controlled, but a suitable controllable parameter can be identified

An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

Science.gov (United States)

Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

2013-01-01

The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

Strategy to avoid patient-prosthesis mismatch: aortic root enlargement.

Science.gov (United States)

Srivastava, Dharmendra Kumar; Sanki, Prokash; Bhattacharya, Subhankar; Siddique, Javed Veqar

2014-02-01

The choice of a valve with an effective orifice area matching the body surface area and providing efficient hemodynamics is an important factor affecting mortality and morbidity in patients undergoing aortic valve replacement. Our preventative strategy was to implant a larger prosthetic valve by aortic root enlargement using the Nunez procedure in 17 patients between February 2010 and January 2011. The decision to enlarge the aortic root was taken when the 19-mm sizer could not be negotiated easily through the aortic root, or on the basis of body surface area of the patient or type of prosthesis available. Postoperative reductions in peak and mean pressure gradients across aortic valve of 12.8-16.5 and 10.2-12.6 mm Hg, respectively, were observed. Postoperative effective orifice areas of the aortic valves were 1.1-1.5 cm(2). By upsizing the aortic valve, we were able to eliminate patient-prosthesis mismatch in 5 patients, and reduce severe patient-prosthesis mismatch to moderate in 11. Aortic root enlargement is a safe procedure. Therefore, cardiac surgeons should not be reluctant to enlarge the aortic root with an autologous pericardial patch to permit implantation of an adequate size of aortic valve prosthesis, with minimal additional aortic crossclamp time and no added cost.

Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.

Directory of Open Access Journals (Sweden)

Nadia Musimbi Chanzu

Full Text Available The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors' while 20% do not (termed 'non-secretors'. Furthermore, there are disease conditions that are associated with secretor status.To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya.This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis.Out of the 280 participants, 212 (75.7% were secretors and 68 (24.3% were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7% versus HIV un-infected secretors (71.8% (p = 0.029 Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%, in comparison to B (12/39 = 33.3%: p = 0.066, AB (3/9 = 33.3%: p = 0.355, and O secretors (36/112 = 32.1%: p = 0.028.This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population

Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

NARCIS (Netherlands)

A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

1994-01-01

textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

The Role of Education Pathways in the Relationship between Job Mismatch, Wages and Job Satisfaction: A Panel Estimation Approach

Science.gov (United States)

Mavromaras, Kostas; Sloane, Peter; Wei, Zhang

2012-01-01

This paper examines the outcome of over-skilling and over-education on wages and job satisfaction of full-time employees in Australia between 2001 and 2008. We employ a random effects probit model with Mundlak corrections. We find differences by type of mismatch, education pathway, and gender. We categorise reported mismatches as genuine…

On the trade-off between mainlobe width and peak sidelobe level of mismatched pulse compression filters for linear chirp waveforms

CSIR Research Space (South Africa)

Cilliers, Jacques E

2009-09-01

Full Text Available that constant, extremely low sidelobe levels better than 60 dB can be achieved for minimal mismatch loss but with some broadening of the compression peak. This paper investigates the tradeoff between the sidelobe level and the mainlobe width for mismatched...

Immunogenetic mechanisms driving norovirus GII.4 antigenic variation.

Directory of Open Access Journals (Sweden)

Lisa C Lindesmith

Full Text Available Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs. Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987-1997, contemporary (2004-2009, and broad (1987-2009. NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294-298 and 368-372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393-395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing

The prevalence of hepatitis B antigen among hepatitis patients and residents of Peru.

Science.gov (United States)

Madalengoitia, J; Ishida, N; Umenay, T; Miyamoto, T; Mejía, J; Flores, W; Sánchez, S; Méndez, R

1975-01-01

Single radial immune diffusion and counterelectrophoresis tests were used to examine 2,593 serum speciments from apparently healthy men, women, and children of Peru for the presence of hepatitis B antigen (Australia antigen). The object was to estimate the prevalence of the antigen in two contrasting geographic regions and to investigate the relationship between presence of the antigen and jungle hepatitis in eastern Peru. In connection with the latter goal, both single and serial serum samples collected from hepatitis cases during an epidemic in the northeast were also examined. Of the 2,593 apparently healthy subjects, the tests showed 1.4 per cent were carrying the antigen. However, when the data were broken down by geographic region it was found that 1.8 per cent of the subjects from eastern Peru were carriers, as compared to only 0.5 per cent of those from the northern coast. Moreover, incidences as high as 5 and 6.4 per cent were found in selected eastern areas, and a peak figure of 14.3 per cent was found in sera from children living in some of these areas. Comparison of the proportions of male and female sera positive for the antigen indicated that the proportion of males with HB Ag was nearly twice as high. However, sera collected from Indians of 20 different eastern tribes and from mestizos in the eastern region showed roughly the same proportion of samples positive for HB Ag in each ethnic group. The study also showed a close correlation between presence of the antigen and hepatitis infection during a 1972-1973 epidemic in eastern Peru. Testing of sera taken from hepatitis patients at that time showed many patients to be carrying HB Ag, specially in cases where serial blood samples were available. In all, positive test results were obtained for 81.2 per cent of the patients from whom two or more samples had been obtained.

A skill mismatch for migrant workers? Evidence from WageIndicator survey data

NARCIS (Netherlands)

Tijdens, K.; van Klaveren, M.; Galgóczi, B.; Leschke, J.; Watt, A.

2012-01-01

Are overeducation and undereducation more common among migrants compared to domestic workers? If so, are overeducation and undereducation similar across migrants from various home countries and across various host countries? This chapter is aimed at unravelling the incidence of skill mismatch,

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

Science.gov (United States)

Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

2014-01-01

Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion1

Science.gov (United States)

Turner, Michael S.; Kane, Lawrence P.; Morel, Penelope A.

2009-01-01

The definitions of tolerogenic vs. immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allo-antigens. However, we have previously reported that mature DC (G4DC) prevented the onset of autoimmune diabetes whereas immature DC (GMDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR Tg mice were stimulated, in the absence of exogenous cytokine, with GMDC or G4DC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both GMDC and G4DC presenting low peptide doses induced weak TCR signaling via the Akt/mTOR pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed G4DC, but not GMDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-Tg T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with antigen dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low antigen doses. These studies indicate that strength of Akt/mTOR signaling, a critical T cell intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production. PMID:19801514

Mismatch negativity is a stronger indicator of functional outcomes than neurocognition or theory of mind in patients with schizophrenia.

Science.gov (United States)

Lee, Seung-Hwan; Sung, Kyongae; Lee, Kyong-Sang; Moon, Eunok; Kim, Chang-Gyu

2014-01-03

Mismatch negativity (MMN) is known to be associated with neurocognition, social cognition, and functional outcomes. The present study explored the relationships of MMN with neurocognition, theory of mind, and functional outcomes in patients with schizophrenia, first-degree relatives of patients with schizophrenia, and healthy controls. Twenty-five patients with schizophrenia, 21 first-degree relatives of patients with schizophrenia, and 29 healthy controls were recruited. We examined symptom severity, neurocognition, theory of mind, functional outcomes, and MMN. MMN amplitudes decreased in order of patients with schizophrenia, then first-degree relatives, then healthy controls. MMN amplitude was significantly correlated with measures of neurocognition, theory of mind, and functional outcome measurements in patients with schizophrenia. However, the most powerful correlations were those between MMN in the frontal region and measures of functional outcomes. The power and frequency of the correlations were weaker in first-degree relatives and healthy controls than in patients with schizophrenia. Hierarchical regression analysis revealed that functional outcomes (relative to measures of neurocognition and theory of mind) constituted the most powerful predictor of MMN. Our results suggest that MMN reflects functional outcomes more efficiently than do measures of neurocognition and theory of mind in patients with schizophrenia. © 2013.

Chemoselective ligation and antigen vectorization.

Science.gov (United States)

Gras-Masse, H

2001-01-01

The interest in cocktail-lipopeptide vaccines has now been confirmed by phase I clinical trials: highly diversified B-, T-helper or cytotoxic T-cell epitopes can be combined with a lipophilic vector for the induction of B- and T-cell responses of predetermined specificity. With the goal of producing an improved vaccine that should ideally induce a multispecific response in non-selected populations, increasing the diversity of the immunizing mixture represents one of the most obvious strategies.The selective delivery of antigens to professional antigen-presenting cells represents another promising approach for the improvement of vaccine efficacy. In this context, the mannose-receptor represents an attractive entry point for the targeting to dendritic cells of antigens linked to clustered glycosides or glycomimetics. In all cases, highly complex but fully characterized molecules must be produced. To develop a modular and flexible strategy which could be generally applicable to a large set of peptide antigens, we elected to explore the potentialities of chemoselective ligation methods. The hydrazone bond was found particularly reliable and fully compatible with sulphide ligation. Hydrazone/thioether orthogonal ligation systems could be developed to account for the nature of the antigens and the solubility of the vector systems. Copyright 2001 The International Association for Biologicals.

Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

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Martin Kreutz

Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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Tilahun Alelign

2018-01-01

Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

Science.gov (United States)

Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

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Madzo Jozef

2005-04-01

Full Text Available Abstract Background Aberrant expression of myeloid antigens (MyAgs on acute lymphoblastic leukemia (ALL cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases. Methods In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. Results We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p Conclusion In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

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Blanc, Pascal; Moro-Sibilot, Ludovic; Barthly, Lucas; Jagot, Ferdinand; This, Sébastien; de Bernard, Simon; Buffat, Laurent; Dussurgey, Sébastien; Colisson, Renaud; Hobeika, Elias; Fest, Thierry; Taillardet, Morgan; Thaunat, Olivier; Sicard, Antoine; Mondière, Paul; Genestier, Laurent; Nutt, Stephen L.; Defrance, Thierry

2016-01-01

Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge. PMID:27924814

Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides

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Serkan Yazıcı

2015-01-01

Full Text Available We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF. 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3+, CD4+, CD8+, TCRαβ+, TCRγδ+, CD7+, CD4+CD7+, CD4+CD7−, and CD71+, B cells (HLA-DR+, CD19+, and HLA-DR+CD19+, NKT cells (CD3+CD16+CD56+, and NK cells (CD3−CD16+CD56+. The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

Science.gov (United States)

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

Science.gov (United States)

Martinez-Selles, Manuel; Almenar, Luis; Paniagua-Martin, Maria J; Segovia, Javier; Delgado, Juan F; Arizón, Jose M; Ayesta, Ana; Lage, Ernesto; Brossa, Vicens; Manito, Nicolás; Pérez-Villa, Félix; Diaz-Molina, Beatriz; Rábago, Gregorio; Blasco-Peiró, Teresa; De La Fuente Galán, Luis; Pascual-Figal, Domingo; Gonzalez-Vilchez, Francisco

2015-03-01

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women. © 2014 Steunstichting ESOT.

Overview of Plant-Made Vaccine Antigens against Malaria

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Marina Clemente

2012-01-01

Full Text Available This paper is an overview of vaccine antigens against malaria produced in plants. Plant-based expression systems represent an interesting production platform due to their reduced manufacturing costs and high scalability. At present, different Plasmodium antigens and expression strategies have been optimized in plants. Furthermore, malaria antigens are one of the few examples of eukaryotic proteins with vaccine value expressed in plants, making plant-derived malaria antigens an interesting model to analyze. Up to now, malaria antigen expression in plants has allowed the complete synthesis of these vaccine antigens, which have been able to induce an active immune response in mice. Therefore, plant production platforms offer wonderful prospects for improving the access to malaria vaccines.

Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

DEFF Research Database (Denmark)

Tuxen, Malgorzata K.; Sölétormos, G; Petersen, P H

2001-01-01

The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer patie...

Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis

International Nuclear Information System (INIS)

Massa, P.T.; ter Meulen, V.; Fontana, A.

1987-01-01

In search of a phenotypic marker determining genetically controlled susceptibility to delayed-type hypersensitivity (DTH) reactions in the brain-in particular, experimental autoimmune encephalomyelitis (EAE)- the authors have compared the γ-interferon (IFN-γ) induction of Ia molecules on astrocytes and macrophages from rat and mouse strains that are susceptible or resistant to this disease. They focused on Ia expression because DTH reactions to self or foreign antigens are largely mediated by lymphocytes restricted by class II (Ia) antigens of the major histocompatibility complex (MHC). The data demonstrate that Lewis (fully susceptible) and Brown Norway (BN) (fully resistant) rats are very different in that Lewis astrocytes express much higher levels of Ia than BN astrocytes. Similar data were obtained from an analysis of EAE-susceptible and -resistant mouse strains (SJL and BALB/c, respectively), which suggest that this phenomenon may be universal and not limited to only one mammalian species. At least one gene responsible for Ia hyperinduction is located outside the rat RT-1 or the mouse MHC locus. Animals congenic at the RT-1 or MHC locus of the resistant strain but with background genes of the susceptible strain exhibit intermediate levels of Ia compared to fully resistant and susceptible rodents, which fits well with the reduced EAE susceptibility of these congenic animals. Furthermore, hyperinduction of Ia is astrocyte specific, since peritoneal macrophages of susceptible and resistant strains exhibit identical profiles of Ia induction. Thus, astrocyte Ia hyperinducibility may be a major strain- and tissue-specific factor that contributes to Ia-restricted DTH reactions in the brain

Effects of aging on neuromagnetic mismatch responses to pitch changes.

Science.gov (United States)

Cheng, Chia-Hsiung; Baillet, Sylvain; Hsiao, Fu-Jung; Lin, Yung-Yang

2013-06-07

Although aging-related alterations in the auditory sensory memory and involuntary change discrimination have been widely studied, it remains controversial whether the mismatch negativity (MMN) or its magnetic counterpart (MMNm) is modulated by physiological aging. This study aimed to examine the effects of aging on mismatch activity to pitch deviants by using a whole-head magnetoencephalography (MEG) together with distributed source modeling analysis. The neuromagnetic responses to oddball paradigms consisting of standards (1000 Hz, p=0.85) and deviants (1100 Hz, p=0.15) were recorded in healthy young (n=20) and aged (n=18) male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal neural dynamics of MMNm responses. Distributed activations to MMNm were identified in the bilateral fronto-temporo-parietal areas. Compared to younger participants, the elderly exhibited a significant reduction of cortical activation in bilateral superior temporal guri, superior temporal sulci, inferior fontal gyri, orbitofrontal cortices and right inferior parietal lobules. In conclusion, our results suggest an aging-related decline in auditory sensory memory and automatic change detection as indexed by MMNm. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Correction for spectral mismatch effects on the calibration of a solar cell when using a solar simulator

Energy Technology Data Exchange (ETDEWEB)

Seaman, C.H.

1981-01-15

A general expression has been derived to enable calculation of the calibration error resulting from simulator-solar AMX spectral mismatch and from reference cell-test cell spectral mismatch. The information required includes the relative spectral response of the reference cell, the relative spectral response of the cell under test, and the relative spectral irradiance of the simulator (over the spectral range defined by cell response). The spectral irradiance of the solar AMX is assumed to be known.

Alteration of cellular radiation response as a consequence of defective DNA mismatch repair

International Nuclear Information System (INIS)

Weese, Theodore L. de; Bucci, Jennifer M.; Larrier, Nicole A.; Cutler, Richard G.; Riele, Hein te; Nelson, William G.

1997-01-01

Purpose/Objective: A number of genes have been implicated in the response of mammalian cells to ionizing radiation. Among these include the genes P53 and P21. Disruption of these genes can alter the predicted cellular behavior following radiation-induced DNA damage. Similarly, cells defective in mismatch repair are known to be tolerant to the lethal effects of alkylating agents. We hypothesized that mammalian cells which are defective in mismatch repair and tolerant to alkylating DNA damage might also be tolerant to the effects of oxidative DNA damage inflicted by ionizing radiation. Materials and Methods: Mouse embryonic stem cells homozygous for disrupted Msh2 alleles (Msh2-/-), heterozygous for a disrupted Msh2 allele (Msh2+/-) or intact cells (Msh2+/+) were exposed to both acute dose (1 Gy/min) and low dose rate (LDR) radiation (0.004 Gy/min) and cell survival was determined by clonogenic assay. Apoptosis induced by LDR was assessed by a terminal transferase assay. Immunoblot analysis was performed in order to evaluate induction of the polypeptides p53 and p21. Another measure of radiation damage tolerance may be accumulation of oxidative DNA species. Therefore, we monitored levels of 8-hydroxyguanine (8-OHG) and 8-hydroxyadenine (8-OHA) by gas chromatography - mass spectrometry with selected ion monitoring (GC-MS/SIM). Results: Cells containing either one or two disrupted Msh2 alleles (Msh2+/-, Msh2-/-) were found to be less sensitive to LDR than cells containing a complete complement of Msh2 alleles (Msh2+/+). Interestingly, all three cell lines had a nearly identical radiosensitivity to acute dose ionizing radiation despite differences in mismatch repair capacity. Apoptosis after LDR also varied between cells, with the Msh2+/+ cells exhibiting higher levels of apoptosis as compared to either the Msh2+/- or Msh2-/- cell lines. In addition, GC-MS/SIM revealed the Msh2+/- and Msh2-/- cell lines to have an approximately ten fold greater accumulation of the

Chaos synchronization in time-delayed systems with parameter mismatches and variable delay times

International Nuclear Information System (INIS)

Shahverdiev, E.M.; Nuriev, R.A.; Hashimov, R.H.; Shore, K.A.

2004-06-01

We investigate synchronization between two undirectionally linearly coupled chaotic nonidentical time-delayed systems and show that parameter mismatches are of crucial importance to achieve synchronization. We establish that independent of the relation between the delay time in the coupled systems and the coupling delay time, only retarded synchronization with the coupling delay time is obtained. We show that with parameter mismatch or without it neither complete nor anticipating synchronization occurs. We derive existence and stability conditions for the retarded synchronization manifold. We demonstrate our approach using examples of the Ikeda and Mackey Glass models. Also for the first time we investigate chaos synchronization in time-delayed systems with variable delay time and find both existence and sufficient stability conditions for the retarded synchronization manifold with the coupling-delay lag time. (author)

Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA.

OpenAIRE

Nilsson, O.; Peter, A.; Andersson, I.; Nilsson, K.; Grundstr?m, B.; Karlsson, B.

1997-01-01

Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both...

Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats.

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Timo Ruusuvirta

Full Text Available Any change in the invariant aspects of the auditory environment is of potential importance. The human brain preattentively or automatically detects such changes. The mismatch negativity (MMN of event-related potentials (ERPs reflects this initial stage of auditory change detection. The origin of MMN is held to be cortical. The hippocampus is associated with a later generated P3a of ERPs reflecting involuntarily attention switches towards auditory changes that are high in magnitude. The evidence for this cortico-hippocampal dichotomy is scarce, however. To shed further light on this issue, auditory cortical and hippocampal-system (CA1, dentate gyrus, subiculum local-field potentials were recorded in urethane-anesthetized rats. A rare tone in duration (deviant was interspersed with a repeated tone (standard. Two standard-to-standard (SSI and standard-to-deviant (SDI intervals (200 ms vs. 500 ms were applied in different combinations to vary the observability of responses resembling MMN (mismatch responses. Mismatch responses were observed at 51.5-89 ms with the 500-ms SSI coupled with the 200-ms SDI but not with the three remaining combinations. Most importantly, the responses appeared in both the auditory-cortical and hippocampal locations. The findings suggest that the hippocampus may play a role in (cortical manifestation of MMN.

Mismatch Negativity in Patients with Schizophrenia

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Aleš Urban

2007-01-01

Full Text Available Cognitive deficit is considered to be a part of core dysfuncions in schizophrenia. It is associated with social impairment and influences the long-term course of the disorder. In addition to neuropsychological methods, event-related potentials can be used to study cognitive functions. In patients with schizophrenia an association was found between amplitude changes in slow negative component of evoked responses and infrequent deviations in a series of uniform stimuli. This amplitude change is known as „mismatch negativity“ (MMN. It is supposed to be independent of the focused attention and effort that otherwise interfere with neuropsychological testing. Recently accumulated knowledge on MMN as a possible preattentive measure of cognition supports its potential significance for neuropsychological assessment. It may be helpful in more precise diagnosis and functional evaluation of schizophrenia.

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

Science.gov (United States)

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Mismatch repair protein deficient endometrioid adenocarcinomas, metastasizing to adrenal gland and lymph nodes: Unusual cases with diagnostic implications

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Bharat Rekhi

2015-01-01

Full Text Available Recently, certain endometrial carcinomas have been found to be associated with mismatch repair (MMR protein defects/deficiency. A 39-year-old female presented with cough, decreased appetite and significant weight loss since 2 months. Earlier, she had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO for endometrioid adenocarcinoma. Imaging disclosed an 8 cm-sized adrenal mass that was surgically excised. Histopathology of the adrenal tumor, endocervical tumor, and endometrial biopsy revealed Federation of Gynecology and Obstetrics (FIGO Grade II to III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were positive for cytokeratin 7, epithelial membrane antigen, PAX8, MLH1 and PMS2 while negative for estrogen receptor (ER, progesterone receptor (PR, MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. A 34-year-old lady presented with vaginal bleeding since 9 months. She underwent TAH-BSO, reported as FIGO Grade III endometrioid adenocarcinoma. By immunohistochemistry, tumor cells were negative for ER, PR, MLH1, and PMS2 while positive for MSH2 and MSH6. She underwent adjuvant radiotherapy and chemotherapy. However, she developed multiple nodal and pericardial metastases and succumbed to the disease within a year post-diagnosis. Certain high-grade endometrioid adenocarcinomas occurring in younger women are MMR protein deficient and display an aggressive clinical course. Adrenal metastasis in endometrial carcinomas is rare.

A Database to Support the Interpretation of Human Mismatch Repair Gene Variants

NARCIS (Netherlands)

Ou, Jianghua; Niessen, Renee C.; Vonk, Jan; Westers, Helga; Hofstra, Robert M. W.; Sijmons, Rolf H.

Germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 can cause Lynch syndrome. This syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominantly-inherited disorder predominantly characterized by colorectal and endometrial cancer.

An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

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Wei Wang

2017-06-01

Full Text Available Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs has been developed by co-coupling peptide–major histocompatibility complex (pMHC multimer and anti-Fas monoclonal antibody (mAb onto the polymeric microparticles (MPs to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism. In this study, polyethylenimine (PEI-coated poly lactic-co-glycolic acid microparticle (PLGA MP was fabricated as a cell-sized scaffold to covalently co-couple H-2Kb-Ig dimer and anti-Fas mAb for the generation of alloantigen-presenting and apoptosis-inducing MPs. Intravenous infusions of the biodegradable KaAPCs prolonged the alloskin graft survival for 43 days in a single MHC-mismatched murine model, depleted the most of H-2Kb-alloreactive CD8+ T cells in peripheral blood, spleen, and alloskin graft in an antigen-specific manner and anti-Fas-dependent fashion. The cell-sized KaAPCs circulated throughout vasculature into liver, kidney, spleen, lymph nodes, lung, and heart, but few ones into local allograft at early stage, with a retention time up to 36 h in vivo. They colocalized with CD8+ T cells in secondary lymphoid organs while few ones contacted with CD4+ T cells, B cells, macrophage, and dendritic cells, or internalized by phagocytes. Importantly, the KaAPC treatment did not significantly impair the native T cell repertoire or non-pathogenic immune cells, did not obviously suppress the overall immune function of host, and did not lead to visible organ toxicity. Our results strongly document the high potential of PLGA MP-based KaAPCs as a novel antigen-specific immunotherapy for allograft rejection and autoimmune disorder. The in vivo mechanism of alloinhibition, tissue

Comparison of a stool antigen detection kit and PCR for diagnosis of Entamoeba histolytica and Entamoeba dispar infections in asymptomatic cyst passers in Iran.

Science.gov (United States)

Solaymani-Mohammadi, Shahram; Rezaian, Mostafa; Babaei, Zahra; Rajabpour, Azam; Meamar, Ahmad R; Pourbabai, Ahmad A; Petri, William A

2006-06-01

The present study was conducted to compare stool antigen detection with PCR for the diagnosis of Entamoeba sp. infection in asymptomatic cyst passers from Iran. Entamoeba dispar and, in one case, E. moshkovskii were the Entamoeba spp. found in the amebic cyst passers. There was a 100% correlation between the results from the TechLab E. histolytica II stool antigen kit and those from nested PCR. We concluded that E. dispar is much more common in asymptomatic cyst passers in Iran and that antigen detection and PCR are comparable diagnostic modalities.

Increasing donor-recipient weight mismatch in pediatric orthotopic heart transplantation does not adversely affect outcome.

Science.gov (United States)

Kanani, Mazyar; Hoskote, Aparna; Carter, Catherine; Burch, Michael; Tsang, Victor; Kostolny, Martin

2012-02-01

The aim of the study was to show the effect of heart transplant donor-recipient weight mismatch on mortality, right-ventricular (RV) failure, and medium-term control of systemic blood pressure. From 2000 to 2008 inclusive, 161 patients undergoing orthotopic heart transplantation at our unit were retrospectively analyzed. The cohort was divided into three groups of similar size depending on the tertile ranges of the donor-recipient weight ratio. Median follow-up was 4.81 years. Donor-recipient body weight ratio was analyzed with respect to intubation time, time in intensive care unit (ITU), development of RV failure, medium-term survival, and freedom from medium-term hypertension. The median age was 115 months (23 days to 18 years), at a median weight of 26.9 kg (3-88 kg) at transplant. Median donor-recipient weight ratio was 1.61 (0.62-3.25). Mean intubation time was 448 h (SD 749.2), mean time in the ITU 302.7 h (SD 617.8). On linear regression, these were not related to donor-recipient weight ratio. A total of 38 patients (23.6%) developed postoperative RV failure. Nearly one-fifth (18.9) of patients in the lowest tertile group developed RV failure. In the middle tertile group, 24.5% developed RV failure and 28.8% in the upper tertile of weight mismatch, although this was not statistically significant (p = 0.48). On survival analysis, there was a higher mortality among those with the lowest tertile of mismatch (log-rank p = 0.04), but there was no difference in midterm survival on condition of survival to discharge (log-rank p = 0.14). There was also no association between weight ratio and freedom from medium-term hypertension as measured on serial 24-h ambulatory blood pressure monitoring (log-rank p = 0.39). There were nine patients in whom the weight mismatch was 3 or greater. There was no association between this 'extreme' mismatch group and either midterm mortality (p = 0.76) or freedom from hypertension (p = 0.62), but this was associated with the need for

Detection of proliferating cell nuclear antigens and interleukin-2 beta receptor molecules on mitogen- and antigen-stimulated lymphocytes.

Science.gov (United States)

Hesketh, J; Dobbelaere, D; Griffin, J F; Buchan, G

1993-01-01

The expression of interleukin-2 receptors (IL-2R) and proliferating cell nuclear antigens (PCNA) were compared for their usefulness as markers of lymphocyte activation. Heterologous polyclonal (anti-bovine IL-2R) and monoclonal (anti-human PCNA) antibodies were used to detect the expression of these molecules on activated deer lymphocytes. Both molecules were co-expressed on blast cells which had been activated with mitogen [concanavalin A (Con A)]. There was detectable up-regulation of IL-2R expression in response to antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] stimulation while PCNA expression mimicked lymphocyte transformation (LT) reactivity. PCNA expression was found to more accurately reflect both antigen- and mitogen-activated lymphocyte activation, as estimated by LT activity. The expression of PCNA was used to identify antigen reactive cells from animals exposed to M. bovis. A very low percentage (1.1 +/- 0.4%) of peripheral blood lymphocytes from non-infected animals could be stimulated to express PCNA by in vitro culture with antigen (PPD). Within the infected group both diseased and healthy, 'in-contact', animals expressed significantly higher levels of PCNA upon antigen stimulation. PMID:8104884

Studies on antigenic cross-reactivity of Trichuris ovis with host mucosal antigens in goat

OpenAIRE

Gautam Patra; Seikh Sahanawaz Alam; Sonjoy Kumar Borthakur; Hridayesh Prasad

2015-01-01

Objective: To ascertain whether immunodominant antigens of Trichuris ovis might share and cross react with host molecule. Methods: Two crude protein preparations from anterior and posterior parts of Trichuris ovis were characterized along with host mucosal antigen by double immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting technique. Conventional scanning electron microscopy was performed as per standard procedure. Results: Sharp...

Vaccine adjuvant MF59 promotes the intranodal differentiation of antigen-loaded and activated monocyte-derived dendritic cells.

Directory of Open Access Journals (Sweden)

Rossella Cioncada

Full Text Available MF59 is an oil-in-water emulsion adjuvant approved for human influenza vaccination in European Union. The mode of action of MF59 is not fully elucidated yet, but results from several years of investigation indicate that MF59 establishes an immunocompetent environment at injection site which promotes recruitment of immune cells, including antigen presenting cells (APCs, that are facilitated to engulf antigen and transport it to draining lymph node (dLN where the antigen is accumulated. In vitro studies showed that MF59 promotes the differentiation of monocytes to dendritic cells (Mo-DCs. Since after immunization with MF59, monocytes are rapidly recruited both at the injection site and in dLN and appear to have a morphological change toward a DC-like phenotype, we asked whether MF59 could play a role in inducing differentiation of Mo-DC in vivo. To address this question we immunized mice with the auto-fluorescent protein Phycoerythrin (PE as model antigen, in presence or absence of MF59. We measured the APC phenotype and their antigen uptake within dLNs, the antigen distribution within the dLN compartments and the humoral response to PE. In addition, using Ovalbumin as model antigen, we measured the capacity of dLN APCs to induce antigen-specific CD4 T cell proliferation. Here, we show, for the first time, that MF59 promotes differentiation of Mo-DCs within dLNs from intranodal recruited monocytes and we suggest that this differentiation could take place in the medullary compartment of the LN. In addition we show that the Mo-DC subset represents the major source of antigen-loaded and activated APCs within the dLN when immunizing with MF59. Interestingly, this finding correlates with the enhanced triggering of antigen-specific CD4 T cell response induced by LN APCs. This study therefore demonstrates that MF59 is able to promote an immunocompetent environment also directly within the dLN, offering a novel insight on the mechanism of action of

Characterization of cell mismatch in a multi-crystalline silicon photovoltaic module

International Nuclear Information System (INIS)

Crozier, J.L.; Dyk, E.E. van; Vorster, F.J.

2012-01-01

In this study the causes and effects of cell mismatch were identified in a multi-crystalline silicon photovoltaic module. Different techniques were used to identify the causes of the mismatch, including Electroluminescence (EL) imaging, Infrared (IR) imaging, current–voltage (I–V) characteristics, worst-case cell determination and Large Area Laser Beam Induced Current (LA-LBIC) scans. In EL images the cracked cells, broken fingers and material defects are visible. The presence of poorly contacted cells results in the formation of hot-spots. LA-LBIC line scans give the relative photoresponse of the cells in the module. However, this technique is limited due to the penetration depth of the laser beam. The worst case cell determination compares the I–V curves of the whole module with the I–V curve of the module with one cell covered, allowing the evaluation of the performance of each cell in a series-connected string. These methods allowed detection of the poorly performing cells in the module. Using all these techniques an overall view of the photoresponse in the cells and their performance is obtained.

Characterization of cell mismatch in a multi-crystalline silicon photovoltaic module

Energy Technology Data Exchange (ETDEWEB)

Crozier, J.L., E-mail: s207094248@live.nmmu.ac.za [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Dyk, E.E. van; Vorster, F.J. [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

2012-05-15

In this study the causes and effects of cell mismatch were identified in a multi-crystalline silicon photovoltaic module. Different techniques were used to identify the causes of the mismatch, including Electroluminescence (EL) imaging, Infrared (IR) imaging, current-voltage (I-V) characteristics, worst-case cell determination and Large Area Laser Beam Induced Current (LA-LBIC) scans. In EL images the cracked cells, broken fingers and material defects are visible. The presence of poorly contacted cells results in the formation of hot-spots. LA-LBIC line scans give the relative photoresponse of the cells in the module. However, this technique is limited due to the penetration depth of the laser beam. The worst case cell determination compares the I-V curves of the whole module with the I-V curve of the module with one cell covered, allowing the evaluation of the performance of each cell in a series-connected string. These methods allowed detection of the poorly performing cells in the module. Using all these techniques an overall view of the photoresponse in the cells and their performance is obtained.

Practical impulsive synchronization of chaotic systems with parametric uncertainty and mismatch

International Nuclear Information System (INIS)

Wen, C.Y.; Ji, Y.; Li, Z.G.

2007-01-01

Recently, there has been increasing interest in the synchronization of two chaotic systems and some significant results have been reported. In these results, a strong assumption that the two chaotic systems should be identical, i.e., without any mismatch, is imposed. Furthermore, system parameters are also assumed known exactly. Clearly, these are impractical. In this Letter, pure impulsive synchronization is considered. We quantitatively establish a relationship between a pre-specified bound of the synchronization error and the length of impulsive intervals in the presence of both parametric uncertainties and mismatch between the two systems. This is the first available result in the area, to the knowledge of the authors. With such a relationship as a guideline to choose impulsive intervals, a practical impulsive synchronization scheme is obtained. With the proposed scheme, the magnitude of the synchronization error is theoretically ensured to approach to and stay within the pre-specified bound which can be arbitrarily small. Simulation studies on the Lorenz system also verify the effectiveness of the proposed scheme

Visual mismatch negativity indicates automatic, task-independent detection of artistic image composition in abstract artworks.

Science.gov (United States)

Menzel, Claudia; Kovács, Gyula; Amado, Catarina; Hayn-Leichsenring, Gregor U; Redies, Christoph

2018-05-06

In complex abstract art, image composition (i.e., the artist's deliberate arrangement of pictorial elements) is an important aesthetic feature. We investigated whether the human brain detects image composition in abstract artworks automatically (i.e., independently of the experimental task). To this aim, we studied whether a group of 20 original artworks elicited a visual mismatch negativity when contrasted with a group of 20 images that were composed of the same pictorial elements as the originals, but in shuffled arrangements, which destroy artistic composition. We used a passive oddball paradigm with parallel electroencephalogram recordings to investigate the detection of image type-specific properties. We observed significant deviant-standard differences for the shuffled and original images, respectively. Furthermore, for both types of images, differences in amplitudes correlated with the behavioral ratings of the images. In conclusion, we show that the human brain can detect composition-related image properties in visual artworks in an automatic fashion. Copyright © 2018 Elsevier B.V. All rights reserved.

Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

Science.gov (United States)

Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

2016-01-01

The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

Abnormal antigens in breast cancer tissues and production of monoclonal antibodies against one of these antigens

Energy Technology Data Exchange (ETDEWEB)

Mohammed, M E. A. [University of Khartoum, Khartoum (Sudan)

2010-02-15

Breast cancer is associated with up regulation, down regulation of normal antigens or abnormal antigens. These antigens are very useful candidates as targets for the different breast cancer therapies and for vaccination trials. This study was done to characterize abnormal antigens, extract one of them and to produce monoclonal antibodies against the extracted antigen. One hundred and twenty Sudanese female patients were included in this study after informed consent. The mean age was 47. 2 years (16-80). Two tissue samples were obtained from each patient and they were confirmed as normal and cancerous breast tissues microscopically. 2D PAGE was used to analyze the protein content of samples. LC/MS and nr. fast a database search were used for separation and indentification of the abnormal proteins. Three different patterns of 2D Page results were obtained, the first pattern involved detection of four abnormal proteins in 26.7% of the patient cancerous tissues while they were undetected in the normal tissues of the same patients. In the second 2D PAGE result pattern the cancerous and the normal tissues of 67.5% patients were identical and they did not contain the four abnormal proteins while the third 2D PAGE pattern involved the presence of two abnormal antigens (from the four) in the cancerous tissues of 5.8% of the patients and they were absent from the normal tissues of the same patients. The four abnormal proteins were identified as, human Thioredoxin (D60nmutant), x-ray crystal structure of human galectin-1, retrocopy of tropomyosin 3(rc TPM3) and beta-tropomyosin (isoform 2). The primary and the secondary structures were obtained from the SWISSPROT and the PDB databases. Beta tropomyosin spot was extracted and used as antigen for monoclonal antibody production. Monoclonal antibody against beta- tropomyosin with a concentration of 0.35 mg/ml and a G11 anti beta-tropomyosin hybridoma cell line were produced. The monoclonal antibody was with single bad and

Abnormal antigens in breast cancer tissues and production of monoclonal antibodies against one of these antigens

International Nuclear Information System (INIS)

Mohammed, M. E. A.

2010-02-01

Breast cancer is associated with up regulation, down regulation of normal antigens or abnormal antigens. These antigens are very useful candidates as targets for the different breast cancer therapies and for vaccination trials. This study was done to characterize abnormal antigens, extract one of them and to produce monoclonal antibodies against the extracted antigen. One hundred and twenty Sudanese female patients were included in this study after informed consent. The mean age was 47. 2 years (16-80). Two tissue samples were obtained from each patient and they were confirmed as normal and cancerous breast tissues microscopically. 2D PAGE was used to analyze the protein content of samples. LC/MS and nr. fast a database search were used for separation and indentification of the abnormal proteins. Three different patterns of 2D Page results were obtained, the first pattern involved detection of four abnormal proteins in 26.7% of the patient cancerous tissues while they were undetected in the normal tissues of the same patients. In the second 2D PAGE result pattern the cancerous and the normal tissues of 67.5% patients were identical and they did not contain the four abnormal proteins while the third 2D PAGE pattern involved the presence of two abnormal antigens (from the four) in the cancerous tissues of 5.8% of the patients and they were absent from the normal tissues of the same patients. The four abnormal proteins were identified as, human Thioredoxin (D60nmutant), x-ray crystal structure of human galectin-1, retrocopy of tropomyosin 3(rc TPM3) and beta-tropomyosin (isoform 2). The primary and the secondary structures were obtained from the SWISSPROT and the PDB databases. Beta tropomyosin spot was extracted and used as antigen for monoclonal antibody production. Monoclonal antibody against beta- tropomyosin with a concentration of 0.35 mg/ml and a G11 anti beta-tropomyosin hybridoma cell line were produced. The monoclonal antibody was with single bad and

Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

Science.gov (United States)

Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

2012-04-01

Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Specificity of antigens on UV radiation-induced antigenic tumor cell variants measured in vitro and in vivo

International Nuclear Information System (INIS)

Hostetler, L.W.; Romerdahl, C.A.; Kripke, M.L.

1989-01-01

The purpose of this study was to determine whether antigenic variants cross-react immunologically with the parental tumor and whether the UVR-associated antigen unique to UVR-induced tumors is also present on the variants. Antigenic (regressor) variants and nonimmunogenic (progressor) clones derived from UV-irradiated cultures of the C3H K1735 melanoma and SF19 spontaneous fibrosarcoma cell lines were used to address these questions. In an in vivo immunization and challenge assay, the antigenic variants did not induce cross-protection among themselves, but each induced immunity against the immunizing variant, the parent tumor cells, and nonimmunogenic clones derived from UV-irradiated parent cultures. Therefore, the variants can be used to induce in mice a protective immunity that prevents the growth of the parent tumor and nonimmunogenic clones, but not other antigenic variants. In contrast, immunization with cells of the parental tumor or the nonimmunogenic clones induced no protective immunity against challenge with any of the cell lines. Utilizing the K1735 melanoma-derived cell lines in vitro, T-helper (Th) cells isolated from tumor-immunized mice were tested for cross-reactivity by their ability to collaborate with trinitrophenyl-primed B-cells in the presence of trinitrophenyl-conjugated tumor cells. Also, the cross-reactivity of cytotoxic T-lymphocytes from tumor-immunized mice was assessed by a 4-h 51Cr-release assay. Antigenic variants induced cytotoxic T-lymphocytes and Th activity that was higher than that induced by the parent tumor and nonimmunogenic clones from the UVR-exposed parent tumor and cross-reacted with the parental tumor cells and nonimmunogenic clones, but not with other antigenic variants

Fast and quantitative differentiation of single-base mismatched DNA by initial reaction rate of catalytic hairpin assembly.

Science.gov (United States)

Li, Chenxi; Li, Yixin; Xu, Xiao; Wang, Xinyi; Chen, Yang; Yang, Xiaoda; Liu, Feng; Li, Na

2014-10-15

The widely used catalytic hairpin assembly (CHA) amplification strategy generally needs several hours to accomplish one measurement based on the prevailingly used maximum intensity detection mode, making it less practical for assays where high throughput or speed is desired. To make the best use of the kinetic specificity of toehold domain for circuit reaction initiation, we developed a mathematical model and proposed an initial reaction rate detection mode to quantitatively differentiate the single-base mismatch. Using the kinetic mode, assay time can be reduced substantially to 10 min for one measurement with the comparable sensitivity and single-base mismatch differentiating ability as were obtained by the maximum intensity detection mode. This initial reaction rate based approach not only provided a fast and quantitative differentiation of single-base mismatch, but also helped in-depth understanding of the CHA system, which will be beneficial to the design of highly sensitive and specific toehold-mediated hybridization reactions. Copyright © 2014 Elsevier B.V. All rights reserved.

Labour Market Mismatch among UK Graduates: An Analysis Using REFLEX Data

Science.gov (United States)

McGuinness, Seamus; Sloane, Peter J.

2011-01-01

There is much disagreement in the literature over the extent to which graduates are mismatched in the labour market and the reasons for this. In this paper we utilise the Flexible Professional in the Knowledge Society (REFLEX) data set to cast light on these issues, based on data for UK graduates. We find substantial pay penalties for…

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

International Nuclear Information System (INIS)

Wun, T.C.; Capuano, A.

1987-01-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

Energy Technology Data Exchange (ETDEWEB)

Wun, T.C.; Capuano, A.

1987-05-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above.

Analytical model of mismatched photovoltaic fields by means of Lambert W-function

Energy Technology Data Exchange (ETDEWEB)

Petrone, G.; Spagnuolo, G. [DIIIE, Universita di Salerno, Via Ponte Don Melillo, Fisciano (SA) (Italy); Vitelli, M. [DII, Seconda Universita di Napoli, Real Casa dell' Annunziata, Aversa (CE) (Italy)

2007-11-06

A new model of photovoltaic (PV) fields is introduced in this paper. It allows the simulation of a PV generator whose subsections, e.g. cells, groups of cells, panels or group of panels, work under different solar irradiation values and/or at different temperatures. Moreover, different nominal characteristics, rated power, production technology, shape and area can be settled for different subsections. Consequently, the proposed model is able to describe the behaviour of matched as well as mismatched PV fields. It results into a non linear system of equations, which includes bypass and blocking diodes models and is characterized by a sparse Jacobian matrix. The numerical model is reliable and requires a moderate computational burdensome, both in terms of memory use and processor speed. Numeric simulations confirm the accuracy and cheapness of the approach. The proposed model is used to simulate the drawbacks associated to mismatching during maximum power point tracking (MPPT) of the PV generator. (author)

Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study.

Science.gov (United States)

Ismael, Nour El Hoda S; El Sheikh, Samar A; Talaat, Suzan M; Salem, Eman M

2017-03-15

Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters. There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status. Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

Reduced response to Epstein–Barr virus antigens by T-cells in systemic lupus erythematosus patients

Science.gov (United States)

Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie; Mortensen, Shila; Larsen, Janni Lisander; Houen, Gunnar; Duus, Karen

2014-01-01

Objective Epstein–Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. Methods T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay. Results SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients. Conclusions These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed. PMID:25396062

Antigen Loss Variants: Catching Hold of Escaping Foes.

Science.gov (United States)

Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke