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Sample records for cancer clone transmission

  1. Immunologically silent cancer clone transmission from mother to offspring

    PubMed Central

    Isoda, Takeshi; Ford, Anthony M.; Tomizawa, Daisuke; van Delft, Frederik W.; De Castro, David Gonzalez; Mitsuiki, Norkio; Score, Joannah; Taki, Tomohiko; Morio, Tomohiro; Takagi, Masatoshi; Saji, Hiroh; Greaves, Mel; Mizutani, Shuki

    2009-01-01

    Rare cases of possible materno-fetal transmission of cancer have been recorded over the past 100 years but evidence for a shared cancer clone has been very limited. We provide genetic evidence for mother to offspring transmission, in utero, of a leukemic cell clone. Maternal and infant cancer clones shared the same unique BCR-ABL1 genomic fusion sequence, indicating a shared, single-cell origin. Microsatellite markers in the infant cancer were all of maternal origin. Additionally, the infant, maternally-derived cancer cells had a major deletion on one copy of chromosome 6p that included deletion of HLA alleles that were not inherited by the infant (i.e., foreign to the infant), suggesting a possible mechanism for immune evasion. PMID:19822752

  2. Flux Cloning in Josephson Transmission Lines

    SciTech Connect

    Gulevich, D.R.; Kusmartsev, F.V.

    2006-07-07

    We describe a novel effect related to the controlled birth of a single Josephson vortex. In this phenomenon, the vortex is created in a Josephson transmission line at a T-shaped junction. The 'baby' vortex arises at the moment when a 'mother' vortex propagating in the adjacent transmission line passes the T-shaped junction. In order to give birth to a new vortex, the mother vortex must have enough kinetic energy. Its motion can also be supported by an externally applied driving current. We determine the critical velocity and the critical driving current for the creation of the baby vortices and briefly discuss the potential applications of the found effect.

  3. Tumor clone dynamics in lethal prostate cancer

    PubMed Central

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; de Bono, Johann S.; Demichelis, Francesca; Attard, Gerhardt

    2015-01-01

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. PMID:25232177

  4. Transmissible Tumors: Breaking the Cancer Paradigm.

    PubMed

    Ostrander, Elaine A; Davis, Brian W; Ostrander, Gary K

    2016-01-01

    Transmissible tumors are those that have transcended the bounds of their incipient hosts by evolving the ability to infect another individual through direct transfer of cancer cells, thus becoming parasitic cancer clones. Coitus, biting, and scratching are transfer mechanisms for the two primary species studied, the domestic dog (Canis lupus familiaris) and the Tasmanian devil (Sarcophilus harrisii). Canine transmissible venereal tumors (CTVT) are likely thousands of years old, and have successfully travelled from host to host around the world, while the Tasmanian devil facial tumor disease (DFTD) is much younger and geographically localized. The dog tumor is not necessarily lethal, while the devil tumor has driven the population to near extinction. Transmissible tumors are uniform in that they have complex immunologic profiles, which allow them to escape immune detection by their hosts, sometimes for long periods of time. In this review, we explore how transmissible tumors in CTVT, DFTD, and as well as the soft-shell clam and Syrian hamster, can advance studies of tumor biology. PMID:26686413

  5. Cloning of human lung cancer cells.

    PubMed Central

    Walls, G. A.; Twentyman, P. R.

    1985-01-01

    We have carried out a comparison of two different methods for cloning human lung cancer cells. The method of Courtenay & Mills (1978) generally gave higher plating efficiencies (PE) than the method of Carney et al. (1980). The number of colonies increased with incubation time in both methods and the weekly medium replenishment in the Courtenay method was advantageous for longer incubation times of several weeks. In the Courtenay method, the use of August rat red blood cells (RBC) and low oxygen tension were both found to be necessary factors for maximum plating efficiency. The usefulness of heavily irradiated feeder cells in improving PE is less certain; each cell type may have its own requirement. PMID:3904799

  6. A second transmissible cancer in Tasmanian devils.

    PubMed

    Pye, Ruth J; Pemberton, David; Tovar, Cesar; Tubio, Jose M C; Dun, Karen A; Fox, Samantha; Darby, Jocelyn; Hayes, Dane; Knowles, Graeme W; Kreiss, Alexandre; Siddle, Hannah V T; Swift, Kate; Lyons, A Bruce; Murchison, Elizabeth P; Woods, Gregory M

    2016-01-12

    Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens. PMID:26711993

  7. A second transmissible cancer in Tasmanian devils

    PubMed Central

    Pye, Ruth J.; Pemberton, David; Tovar, Cesar; Tubio, Jose M. C.; Dun, Karen A.; Fox, Samantha; Darby, Jocelyn; Hayes, Dane; Knowles, Graeme W.; Kreiss, Alexandre; Siddle, Hannah V. T.; Swift, Kate; Lyons, A. Bruce; Murchison, Elizabeth P.; Woods, Gregory M.

    2016-01-01

    Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens. PMID:26711993

  8. The evolutionary ecology of transmissible cancers.

    PubMed

    Ujvari, Beata; Gatenby, Robert A; Thomas, Frédéric

    2016-04-01

    Transmissible tumours, while rare, present a fascinating opportunity to examine the evolutionary dynamics of cancer as both an infectious agent and an exotic, invasive species. Only three naturally-occurring transmissible cancers have been observed so far in the wild: Tasmanian devil facial tumour diseases, canine transmissible venereal tumour, and clam leukaemia. Here, we define four conditions that are necessary and sufficient for direct passage of cancer cells between either vertebrate or invertebrate hosts. Successful transmission requires environment and behaviours that facilitate transfer of tumour cells between hosts including: tumour tissue properties that promote shedding of large numbers of malignant cells, tumour cell plasticity that permits their survival during transmission and growth in a new host, and a 'permissible' host or host tissue. This rare confluence of multiple host- and tumour cell-traits both explains the rarity of tumour cell transmission and provides novel insights into the dynamics that both promote and constrain their growth. PMID:26861618

  9. Transmissible cancers in an evolutionary context.

    PubMed

    Ujvari, Beata; Papenfuss, Anthony T; Belov, Katherine

    2016-07-01

    Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for

  10. Cloning

    MedlinePlus

    Cloning describes the processes used to create an exact genetic replica of another cell, tissue or organism. ... named Dolly. There are three different types of cloning: Gene cloning, which creates copies of genes or ...

  11. Cloning

    MedlinePlus

    ... DNA Reproductive cloning, which creates copies of whole animals Therapeutic cloning, which creates embryonic stem cells. Researchers hope to use these cells to grow healthy tissue to replace injured or diseased tissues in the human body. NIH: National Human Genome Research Institute

  12. Mixed-genotype infections of malaria parasites: within-host dynamics and transmission success of competing clones.

    PubMed Central

    Taylor, L H; Walliker, D; Read, A F

    1997-01-01

    Mixed-genotype infections of microparasites are common, but almost nothing is known about how competitive interactions within hosts affect the subsequent transmission success of individual genotypes. We investigated changes in the composition of mixed-genotype infections of the rodent malaria Plasmodium chabaudi clones CR and ER by monoclonal antibody analysis of the asexual infection in mice, and by PCR amplification of clone-specific alleles in oocysts sampled from mosquitoes which had fed on these mice. Mixed-clone infections were initiated with a 9:1 ratio of the two clones, with ER as the minority in the first experiment and CR as the minority in the second experiment. When beginning as the majority, clones achieved parasite densities in mice comparable to those achieved in control (single-clone) infections. When they began as the minority, clones were suppressed to less than 10% of control parasitaemias during the early part of the infections. However, in mosquitoes, the frequency of the initially rare clone was substantially greater than it was in mice at the start of the infection or four days prior to the feed. In both experiments, the minority clone in the inocula produced as many, or more, oocysts than it did as a single-clone infection. These experiments show that asexual dominance during most of the infection is poorly correlated to transmission probability, and therefore that the assumption that within-host population size correlates to transmission probability may not be warranted. They also raise the fundamental question of why transmission rates of individual genotypes are often higher from mixed than single-clone infections. PMID:9225482

  13. Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning

    SciTech Connect

    Deymier, Martin J.; Claiborne, Daniel T.; Ende, Zachary; Ratner, Hannah K.; Kilembe, William; Hunter, Eric

    2014-11-15

    The high genetic diversity of HIV-1 impedes high throughput, large-scale sequencing and full-length genome cloning by common restriction enzyme based methods. Applying novel methods that employ a high-fidelity polymerase for amplification and an unbiased fusion-based cloning strategy, we have generated several HIV-1 full-length genome infectious molecular clones from an epidemiologically linked transmission pair. These clones represent the transmitted/founder virus and phylogenetically diverse non-transmitted variants from the chronically infected individual's diverse quasispecies near the time of transmission. We demonstrate that, using this approach, PCR-induced mutations in full-length clones derived from their cognate single genome amplicons are rare. Furthermore, all eight non-transmitted genomes tested produced functional virus with a range of infectivities, belying the previous assumption that a majority of circulating viruses in chronic HIV-1 infection are defective. Thus, these methods provide important tools to update protocols in molecular biology that can be universally applied to the study of human viral pathogens. - Highlights: • Our novel methodology demonstrates accurate amplification and cloning of full-length HIV-1 genomes. • A majority of plasma derived HIV variants from a chronically infected individual are infectious. • The transmitted/founder was more infectious than the majority of the variants from the chronically infected donor.

  14. Rates of Mutation and Host Transmission for an Escherichia coli Clone over 3 Years

    PubMed Central

    Reeves, Peter R.; Liu, Bin; Zhou, Zhemin; Li, Dan; Guo, Dan; Ren, Yan; Clabots, Connie; Lan, Ruiting; Johnson, James R.; Wang, Lei

    2011-01-01

    Although over 50 complete Escherichia coli/Shigella genome sequences are available, it is only for closely related strains, for example the O55:H7 and O157:H7 clones of E. coli, that we can assign differences to individual evolutionary events along specific lineages. Here we sequence the genomes of 14 isolates of a uropathogenic E. coli clone that persisted for 3 years within a household, including a dog, causing a urinary tract infection (UTI) in the dog after 2 years. The 20 mutations observed fit a single tree that allows us to estimate the mutation rate to be about 1.1 per genome per year, with minimal evidence for adaptive change, including in relation to the UTI episode. The host data also imply at least 6 host transfer events over the 3 years, with 2 lineages present over much of that period. To our knowledge, these are the first direct measurements for a clone in a well-defined host community that includes rates of mutation and host transmission. There is a concentration of non-synonymous mutations associated with 2 transfers to the dog, suggesting some selection pressure from the change of host. However, there are no changes to which we can attribute the UTI event in the dog, which suggests that this occurrence after 2 years of the clone being in the household may have been due to chance, or some unknown change in the host or environment. The ability of a UTI strain to persist for 2 years and also to transfer readily within a household has implications for epidemiology, diagnosis, and clinical intervention. PMID:22046404

  15. Particle infectivity of HIV-1 full-length genome infectious molecular clones in a subtype C heterosexual transmission pair following high fidelity amplification and unbiased cloning

    PubMed Central

    Deymier, Martin J.; Claiborne, Daniel T.; Ende, Zachary; Ratner, Hannah K.; Kilembe, William; Allen, Susan; Hunter, Eric

    2014-01-01

    The high genetic diversity of HIV-1 impedes high throughput, large-scale sequencing and full-length genome cloning by common restriction enzyme based methods. Applying novel methods that employ a high-fidelity polymerase for amplification and an unbiased fusion-based cloning strategy, we have generated several HIV-1 full-length genome infectious molecular clones from an epidemiologically linked transmission pair. These clones represent the transmitted/founder virus and phylogenetically diverse non-transmitted variants from the chronically infected individual's diverse quasispecies near the time of transmission. We demonstrate that, using this approach, PCR-induced mutations in full-length clones derived from their cognate single genome amplicons are rare. Furthermore, all eight non-transmitted genomes tested produced functional virus with a range of infectivities, belying the previous assumption that a majority of circulating viruses in chronic HIV-1 infection are defective. Thus, these methods provide important tools to update protocols in molecular biology that could be universally applied to the study of human viral pathogens. PMID:25243334

  16. An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors.

    PubMed

    Shan, Chao; Xie, Xuping; Muruato, Antonio E; Rossi, Shannan L; Roundy, Christopher M; Azar, Sasha R; Yang, Yujiao; Tesh, Robert B; Bourne, Nigel; Barrett, Alan D; Vasilakis, Nikos; Weaver, Scott C; Shi, Pei-Yong

    2016-06-01

    The Asian lineage of Zika virus (ZIKV) has recently caused epidemics and severe disease. Unraveling the mechanisms causing increased viral transmissibility and disease severity requires experimental systems. We report an infectious cDNA clone of ZIKV that was generated using a clinical isolate of the Asian lineage. The cDNA clone-derived RNA is infectious in cells, generating recombinant ZIKV. The recombinant virus is virulent in established ZIKV mouse models, leading to neurological signs relevant to human disease. Additionally, recombinant ZIKV is infectious for Aedes aegypti and thus provides a means to examine virus transmission. The infectious cDNA clone was further used to generate a luciferase ZIKV that exhibited sensitivity to a panflavivirus inhibitor, highlighting its potential utility for antiviral screening. This ZIKV reverse genetic system, together with mouse and mosquito infection models, may help identify viral determinants of human virulence and mosquito transmission as well as inform vaccine and therapeutic strategies. PMID:27198478

  17. Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

    PubMed

    Murchison, Elizabeth P; Schulz-Trieglaff, Ole B; Ning, Zemin; Alexandrov, Ludmil B; Bauer, Markus J; Fu, Beiyuan; Hims, Matthew; Ding, Zhihao; Ivakhno, Sergii; Stewart, Caitlin; Ng, Bee Ling; Wong, Wendy; Aken, Bronwen; White, Simon; Alsop, Amber; Becq, Jennifer; Bignell, Graham R; Cheetham, R Keira; Cheng, William; Connor, Thomas R; Cox, Anthony J; Feng, Zhi-Ping; Gu, Yong; Grocock, Russell J; Harris, Simon R; Khrebtukova, Irina; Kingsbury, Zoya; Kowarsky, Mark; Kreiss, Alexandre; Luo, Shujun; Marshall, John; McBride, David J; Murray, Lisa; Pearse, Anne-Maree; Raine, Keiran; Rasolonjatovo, Isabelle; Shaw, Richard; Tedder, Philip; Tregidgo, Carolyn; Vilella, Albert J; Wedge, David C; Woods, Gregory M; Gormley, Niall; Humphray, Sean; Schroth, Gary; Smith, Geoffrey; Hall, Kevin; Searle, Stephen M J; Carter, Nigel P; Papenfuss, Anthony T; Futreal, P Andrew; Campbell, Peter J; Yang, Fengtang; Bentley, David R; Evers, Dirk J; Stratton, Michael R

    2012-02-17

    The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations. PMID:22341448

  18. Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer

    PubMed Central

    Murchison, Elizabeth P.; Schulz-Trieglaff, Ole B.; Ning, Zemin; Alexandrov, Ludmil B.; Bauer, Markus J.; Fu, Beiyuan; Hims, Matthew; Ding, Zhihao; Ivakhno, Sergii; Stewart, Caitlin; Ng, Bee Ling; Wong, Wendy; Aken, Bronwen; White, Simon; Alsop, Amber; Becq, Jennifer; Bignell, Graham R.; Cheetham, R. Keira; Cheng, William; Connor, Thomas R.; Cox, Anthony J.; Feng, Zhi-Ping; Gu, Yong; Grocock, Russell J.; Harris, Simon R.; Khrebtukova, Irina; Kingsbury, Zoya; Kowarsky, Mark; Kreiss, Alexandre; Luo, Shujun; Marshall, John; McBride, David J.; Murray, Lisa; Pearse, Anne-Maree; Raine, Keiran; Rasolonjatovo, Isabelle; Shaw, Richard; Tedder, Philip; Tregidgo, Carolyn; Vilella, Albert J.; Wedge, David C.; Woods, Gregory M.; Gormley, Niall; Humphray, Sean; Schroth, Gary; Smith, Geoffrey; Hall, Kevin; Searle, Stephen M.J.; Carter, Nigel P.; Papenfuss, Anthony T.; Futreal, P. Andrew; Campbell, Peter J.; Yang, Fengtang; Bentley, David R.; Evers, Dirk J.; Stratton, Michael R.

    2012-01-01

    Summary The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations. PaperClip PMID:22341448

  19. PyClone: Statistical inference of clonal population structure in cancer

    PubMed Central

    Roth, Andrew; Khattra, Jaswinder; Yap, Damian; Wan, Adrian; Laks, Emma; Biele, Justina; Ha, Gavin; Aparicio, Samuel; Bouchard-Côté, Alexandre; Shah, Sohrab P.

    2016-01-01

    We introduce a novel statistical method, PyClone, for inference of clonal population structures in cancers. PyClone is a Bayesian clustering method for grouping sets of deeply sequenced somatic mutations into putative clonal clusters while estimating their cellular prevalences and accounting for allelic imbalances introduced by segmental copy number changes and normal cell contamination. Single cell sequencing validation demonstrates that PyClone infers accurate clustering of mutations that co-occur in individual cells. PMID:24633410

  20. Molecular evidence for zoonotic transmission of an emergent, highly pathogenic Campylobacter jejuni clone in the United States.

    PubMed

    Sahin, Orhan; Fitzgerald, Collette; Stroika, Steven; Zhao, Shaohua; Sippy, Rachel J; Kwan, Patrick; Plummer, Paul J; Han, Jing; Yaeger, Michael J; Zhang, Qijing

    2012-03-01

    Campylobacter jejuni is a major zoonotic pathogen. A highly virulent, tetracycline-resistant C. jejuni clone (clone SA) has recently emerged in ruminant reservoirs and has become the predominant cause of sheep abortion in the United States. To determine whether clone SA is associated with human disease, we compared the clinical isolates of clone SA from sheep abortions with the human isolates of the PulseNet National Campylobacter databases at the CDC and the FDA using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and serotyping. The combined SmaI and KpnI PFGE pattern designations of clone SA from sheep were indistinguishable from those of 123 (9.03%) human C. jejuni isolates (total, 1,361) in the CDC database, among which 56 were associated with sporadic infections and 67 were associated with outbreaks that occurred in multiple states from 2003 to 2010. Most of the outbreaks were attributed to raw milk, while the sources for most of the sporadic cases were unknown. All clone SA isolates examined, including PFGE-matched human isolates, belong to sequence type 8 (ST-8) by MLST and serotype HS:1,8, further indicating the clonality of the related isolates from different host species. Additionally, C. jejuni clone SA was identified in raw milk, cattle feces, the feces and bile of healthy sheep, and abortion cases of cattle and goats, indicating the broad distribution of this pathogenic clone in ruminants. These results provide strong molecular and epidemiological evidence for zoonotic transmission of this emergent clone from ruminants to humans and indicate that C. jejuni clone SA is an important threat to public health. PMID:22189122

  1. Widespread transmission of independent cancer lineages within multiple bivalve species.

    PubMed

    Metzger, Michael J; Villalba, Antonio; Carballal, María J; Iglesias, David; Sherry, James; Reinisch, Carol; Muttray, Annette F; Baldwin, Susan A; Goff, Stephen P

    2016-06-30

    Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils and dogs), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria) suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers are found spreading within the species of origin, cross-species transmission of cancer cells can occur. PMID:27338791

  2. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480

    PubMed Central

    Takaya, Akari; Hirohashi, Yoshihiko; Murai, Aiko; Morita, Rena; Saijo, Hiroshi; Yamamoto, Eri; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Tamura, Yasuaki; Takemasa, Ichiro; Kondo, Toru; Sato, Noriyuki; Torigoe, Toshihiko

    2016-01-01

    Human cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be isolated as side population (SP) cells, aldehyde dehydrogenase high (ALDHhigh) cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP) cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis. PMID:27415781

  3. Generation of transmissible hepatitis C virions from a molecular clone in chimpanzees.

    PubMed

    Hong, Z; Beaudet-Miller, M; Lanford, R E; Guerra, B; Wright-Minogue, J; Skelton, A; Baroudy, B M; Reyes, G R; Lau, J Y

    1999-03-30

    Multiple alignments of hepatitis C virus (HCV) polyproteins from six different genotypes identified a total of 22 nonconsensus mutations in a clone derived from the Hutchinson (H77) isolate. These mutations, collectively, may have contributed to the failure in generating a "functionally correct" or "infectious" clone in earlier attempts. A consensus clone was constructed after systematic repair of these mutations, which yielded infectious virions in a chimpanzee after direct intrahepatic inoculation of in vitro transcribed RNAs. This RNA-infected chimpanzee has developed hepatitis and remained HCV positive for more than 11 months. To further verify this RNA-derived infectivity, a second naive chimpanzee was injected intravenously with serum collected from the first chimpanzee. Infectivity analysis of the second chimpanzee demonstrated that the HCV infection was successfully transmitted, which validated unequivocally the infectivity of our repaired molecular clone. Amino acid sequence comparisons revealed that our repaired infectious clone had 4 mismatches with the isogenic clone reported by Kolykhalov et al. (1997, Science 277, 570-574) and 8 mismatches with that reported by Yanagi et al. (1997, Proc. Natl. Acad. Sci. USA 94, 8738-8743). At the RNA level, more mismatches (43 and 67, respectively) were identified; most of them were synonymous substitutions. Further comparisons with 16 isolates from different genotypes demonstrated that our repaired clone shares greater consensus than the reported isogenic clones. This approach of generating infectious HCV RNA validates the importance of amino acid sequence consensus in relation to the biology of HCV. PMID:10087224

  4. Identification of a Highly Transmissible Animal-Independent Staphylococcus aureus ST398 Clone with Distinct Genomic and Cell Adhesion Properties

    PubMed Central

    Uhlemann, Anne-Catrin; Porcella, Stephen F.; Trivedi, Sheetal; Sullivan, Sean B.; Hafer, Cory; Kennedy, Adam D.; Barbian, Kent D.; McCarthy, Alex J.; Street, Craig; Hirschberg, David L.; Lipkin, W. Ian; Lindsay, Jodi A.; DeLeo, Frank R.; Lowy, Franklin D.

    2012-01-01

    ABSTRACT A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage φ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans. PMID:22375071

  5. Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays.

    PubMed

    Chatterjee, Madhumita; Mohapatra, Saroj; Ionan, Alexei; Bawa, Gagandeep; Ali-Fehmi, Rouba; Wang, Xiaoju; Nowak, James; Ye, Bin; Nahhas, Fatimah A; Lu, Karen; Witkin, Steven S; Fishman, David; Munkarah, Adnan; Morris, Robert; Levin, Nancy K; Shirley, Natalie N; Tromp, Gerard; Abrams, Judith; Draghici, Sorin; Tainsky, Michael A

    2006-01-15

    A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations. PMID:16424057

  6. Immunology of a Transmissible Cancer Spreading among Tasmanian Devils.

    PubMed

    Woods, Gregory M; Howson, Lauren J; Brown, Gabriella K; Tovar, Cesar; Kreiss, Alexandre; Corcoran, Lynn M; Lyons, A Bruce

    2015-07-01

    Devil facial tumor disease (DFTD) is a transmissible cancer that has killed most of the Tasmanian devil (Sarcophilus harrissii) population. Since the first case appeared in the mid-1990s, it has spread relentlessly across the Tasmanian devil's geographic range. As Tasmanian devils only exist in Tasmania, Australia, DFTD has the potential to cause extinction of this species. The origin of DFTD was a Schwann cell from a female devil. The disease is transmitted when devils bite each other around the facial areas, a behavior synonymous with this species. Every devil that is 'infected' with DFTD dies from the cancer. Once the DFTD cells have been transmitted, they appear to develop into a cancer without inducing an immune response. The DFTD cancer cells avoid allogeneic recognition because they do not express MHC class I molecules on the cell surface. A reduced genetic diversity and the production of immunosuppressive cytokines may also contribute. PMID:26092814

  7. Rapid evolutionary response to a transmissible cancer in Tasmanian devils.

    PubMed

    Epstein, Brendan; Jones, Menna; Hamede, Rodrigo; Hendricks, Sarah; McCallum, Hamish; Murchison, Elizabeth P; Schönfeld, Barbara; Wiench, Cody; Hohenlohe, Paul; Storfer, Andrew

    2016-01-01

    Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species' range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease. PMID:27575253

  8. Nanoparticle analysis of cancer cells by light transmission spectroscopy.

    PubMed

    Sun, N; Johnson, J; Stack, M S; Szajko, J; Sander, C; Rebuyon, R; Deatsch, A; Easton, J; Tanner, C E; Ruggiero, S T

    2015-09-01

    We have measured the optical properties of cancer and normal whole cells and lysates using light transmission spectroscopy (LTS). LTS provides both the optical extinction coefficient in the wavelength range from 220 to 1100nm and (by spectral inversion using a Mie model) the particle distribution density in the size range from 1 to 3000nm. Our current work involves whole cells and lysates of cultured human oral cells in liquid suspension. We found systematic differences in the optical extinction between cancer and normal whole cells and lysates, which translate to different particle size distributions (PSDs) for these materials. Specifically, we found that cancer cells have distinctly lower concentrations of nanoparticles with diameters less than 100nm and have higher concentrations of particles with diameters from 100 to 1000nm-results that hold for both whole cells and lysates. We also found a power-law dependence of particle density with diameter over several orders of magnitude. PMID:25981981

  9. Generation of Novel Thyroid Cancer Stem-Like Cell Clones: Effects of Resveratrol and Valproic Acid.

    PubMed

    Hardin, Heather; Yu, Xiao-Min; Harrison, April D; Larrain, Carolina; Zhang, Ranran; Chen, Jidong; Chen, Herbert; Lloyd, Ricardo V

    2016-06-01

    Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies. PMID:27060227

  10. RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones

    PubMed Central

    2010-01-01

    Background Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides. Methods Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting Results When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 μm pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides. Conclusion Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC. PMID:20236512

  11. Clonal spread and interspecies transmission of clinically relevant ESBL-producing Escherichia coli of ST410--another successful pandemic clone?

    PubMed

    Schaufler, Katharina; Semmler, Torsten; Wieler, Lothar H; Wöhrmann, Michael; Baddam, Ramani; Ahmed, Niyaz; Müller, Kerstin; Kola, Axel; Fruth, Angelika; Ewers, Christa; Guenther, Sebastian

    2016-01-01

    Clinically relevant extended-spectrum beta-lactamase (ESBL)-producing multi-resistant Escherichia coli have been on the rise for years. Initially restricted to mostly a clinical context, recent findings prove their prevalence in extraclinical settings independent of the original occurrence of antimicrobial resistance in the environment. To get further insights into the complex ecology of potentially clinically relevant ESBL-producing E. coli, 24 isolates from wild birds in Berlin, Germany, and 40 ESBL-producing human clinical E. coli isolates were comparatively analyzed. Isolates of ST410 occurred in both sample groups (six). In addition, three ESBL-producing E. coli isolates of ST410 from environmental dog feces and one clinical dog isolate were included. All 10 isolates were clonally analyzed showing almost identical macrorestriction patterns. They were chosen for whole-genome sequencing revealing that the whole-genome content of these 10 E. coli isolates showed a very high genetic similarity, differing by low numbers of single nucleotide polymorphisms only. This study gives initial evidence for a recent interspecies transmission of a new successful clone of ST410 E. coli between wildlife, humans, companion animals and the environment. The results underline the zoonotic potential of clinically relevant multi-resistant bacteria found in the environment as well as the mandatory nature of the 'One Health' approach. PMID:26656065

  12. Is tumor growth sustained by rare cancer stem cells or dominant clones?

    PubMed

    Adams, Jerry M; Strasser, Andreas

    2008-06-01

    A key issue for cancer biology and therapy is whether the relentless growth of a tumor is driven by a substantial proportion of its cells or exclusively by a rare subpopulation, commonly termed "cancer stem cells." Support for the cancer stem cell model has been stimulated by experiments in which human tumor cells were transplanted into immunodeficient mice. Most notably, in human acute myeloid leukemia, only a minute proportion of the cells, displaying a defined phenotype, could seed leukemia in mice. Xenotransplantation, however, may fail to reveal many tumor growth-sustaining cells because the foreign microenvironment precludes essential interactions with support cells. In studies that instead have transplanted mouse leukemias and lymphomas into syngeneic animals, most of the tumors seem to be maintained by the dominant cell population, and only a few types of mouse leukemia seem to be sustained by a minor tumor growth-sustaining subpopulation. The collective evidence suggests that various tumors may span the spectrum between the extremes represented by the two models. If tumor growth can indeed be sustained either by rare cancer stem cells or dominant clones or both, as current evidence suggests, curative therapy for many types of tumors will most likely require targeting all the tumor cell populations. PMID:18519656

  13. Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone

    PubMed Central

    2014-01-01

    Background Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain6B-2) clone of Streptococcus pneumoniae. Results Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. Conclusions PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans. PMID:24957517

  14. Telomere Dynamics and Homeostasis in a Transmissible Cancer

    PubMed Central

    Ujvari, Beata; Pearse, Anne-Maree; Taylor, Robyn; Pyecroft, Stephen; Flanagan, Cassandra; Gombert, Sara; Papenfuss, Anthony T.; Madsen, Thomas; Belov, Katherine

    2012-01-01

    Background Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that threatens the world's largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii) with extinction. This transmissible cancer is passed between individual devils by cell implantation during social interactions. The tumour arose in a Schwann cell of a single devil over 15 years ago and since then has expanded clonally, without showing signs of replicative senescence; in stark contrast to a somatic cell that displays a finite capacity for replication, known as the “Hayflick limit”. Methodology/Principal Findings In the present study we investigate the role of telomere length, measured as Telomere Copy Number (TCN), and telomerase and shelterin gene expression, as well as telomerase activity in maintaining hyperproliferation of Devil Facial Tumour (DFT) cells. Our results show that DFT cells have short telomeres. DFTD TCN does not differ between geographic regions or between strains. However, TCN has increased over time. Unlimited cell proliferation is likely to have been achieved through the observed up-regulation of the catalytic subunit of telomerase (TERT) and concomitant activation of telomerase. Up-regulation of the central component of shelterin, the TRF1-intercating nuclear factor 2 (TINF2) provides DFT a mechanism for telomere length homeostasis. The higher expression of both TERT and TINF2 may also protect DFT cells from genomic instability and enhance tumour proliferation. Conclusions/Significance DFT cells appear to monitor and regulate the length of individual telomeres: i.e. shorter telomeres are elongated by up-regulation of telomerase-related genes; longer telomeres are protected from further elongation by members of the shelterin complex, which may explain the lack of spatial and strain variation in DFT telomere copy number. The observed longitudinal increase in gene expression in DFT tissue samples and telomerase activity in DFT cell lines might indicate a

  15. The human tumour cloning assay in the management of breast cancer patients.

    PubMed Central

    Dittrich, C.; Jakesz, R.; Wrba, F.; Havelec, L.; Haas, O.; Spona, J.; Holzner, H.; Kolb, R.; Moser, K.

    1985-01-01

    A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01). PMID:4027163

  16. Contamination of public buses with MRSA in Lisbon, Portugal: a possible transmission route of major MRSA clones within the community.

    PubMed

    Conceição, Teresa; Diamantino, Fernanda; Coelho, Céline; de Lencastre, Hermínia; Aires-de-Sousa, Marta

    2013-01-01

    In a previous study we have shown that public buses in Oporto, the second largest city in Portugal, were highly contaminated with MRSA. Here we describe the results of a similar study performed in another urban area of Portugal-Lisbon, the capital. Between May 2011 and May 2012, hand touched surfaces of 199 public buses in Lisbon were screened for MRSA contamination. Subsequently, the hands of 575 passengers who frequently use these bus lines were also screened. All hand carriers of MRSA were further screened for nasal carriage. The isolates were characterized by PFGE, staphylococcal cassette chromosome (SCC) mec typing, spa typing, MLST and were tested for the presence of mecA, Panton-Valentine leukocidin and arginine catabolic mobile element genes. MRSA contamination was shown in 72 buses (36.2%). The majority of the isolates belonged to three major clones: Clone A was identified as EMRSA-15 defined by pattern PFGE A, spa types t2357/t747/t025/t379/t910, ST22, and SCCmec IVh (n = 21; 29%). Clone B was the New York/Japan clone characterized by PFGE B-t002/t10682-ST5-II (n = 15; 21%). Clone C included isolates with characteristics of the international community-acquired USA300 or related clones, PFGE C-t008-ST8-IVa/IVc/IVg/IVnt/VI (n = 19; 26%). The first two clones are currently the two major lineages circulating in Portuguese hospitals. The hands of 15 individuals were contaminated with MRSA belonging to the nosocomial clones A or B. Eleven of these individuals were not nasal carriers of MRSA and all but one had travelled by public transportation, namely by bus, prior to sampling. In conclusion, public buses in two major cities in Portugal are often contaminated with MRSA representing clones dominant in hospitals in the particular geographic area. MRSA contamination of public transport and the transfer of the bacteria to the hands of passengers may represent a route through which hospital-acquired MRSA clones may spread to the community. PMID:24223124

  17. Infectious clones of the crinivirus cucurbit chlorotic yellows virus are competent for plant systemic infection and vector transmission.

    PubMed

    Shi, Yan; Shi, Yajuan; Gu, Qinsheng; Yan, Fengming; Sun, Xinyan; Li, Honglian; Chen, Linlin; Sun, Bingjian; Wang, Zhenyue

    2016-06-01

    Cucurbit chlorotic yellows virus (CCYV), a recently identified bipartite crinivirus, causes economic losses in cucurbit plants. CCYV is naturally transmitted only by whitefly Bemisia tabaci. Here we constructed full-length cDNA clones of CCYV (RNA1 and RNA2) fused to the T7 RNA polymerase promoter and the cauliflower mosaic virus 35S promoter. CCYV replicated and accumulated efficiently in Cucumis sativus protoplasts transfected with in vitro transcripts. Without RNA2, RNA1 replicated efficiently in C. sativus protoplasts. Agroinoculation with the infectious cDNA clones of CCYV resulted in systemic infection in the host plants of C. sativus and Nicotiana benthamiana. Virus derived from the infectious clones could be transmitted between cucumber plants by vector whiteflies. This system will greatly enhance the reverse genetic studies of CCYV gene functions. PMID:26982585

  18. Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A

    PubMed Central

    Beall, Anne; Yount, Boyd; Lin, Chun-Ming; Hou, Yixuan; Wang, Qiuhong; Saif, Linda

    2016-01-01

    ABSTRACT Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic alphacoronavirus. In the United States, highly virulent PEDV strains cause between 80 and 100% mortality in suckling piglets and are rapidly transmitted between animals and farms. To study the genetic factors that regulate pathogenesis and transmission, we developed a molecular clone of PEDV strain PC22A. The infectious-clone-derived PEDV (icPEDV) replicated as efficiently as the parental virus in cell culture and in pigs, resulting in lethal disease in vivo. Importantly, recombinant PEDV was rapidly transmitted to uninoculated pigs via indirect contact, demonstrating virulence and efficient transmission while replicating phenotypes seen in the wild-type virus. Using reverse genetics, we removed open reading frame 3 (ORF3) and replaced this region with a red fluorescent protein (RFP) gene to generate icPEDV-ΔORF3-RFP. icPEDV-ΔORF3-RFP replicated efficiently in vitro and in vivo, was efficiently transmitted among pigs, and produced lethal disease outcomes. However, the diarrheic scores in icPEDV-ΔORF3-RFP-infected pigs were lower than those in wild-type-virus- or icPEDV-infected pigs, and the virus formed smaller plaques than those of PC22A. Together, these data describe the development of a robust reverse-genetics platform for identifying genetic factors that regulate pathogenic outcomes and transmission efficiency in vivo, providing key infrastructural developments for developing and evaluating the efficacy of live attenuated vaccines and therapeutics in a clinical setting. PMID:26733065

  19. Regional spectroscopy of paraffin-embedded breast cancer tissue using pulsed terahertz transmission imaging

    NASA Astrophysics Data System (ADS)

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas

    2016-03-01

    This work seeks to obtain the properties of paraffin-embedded breast cancer tumor tissues using transmission imaging and spectroscopy. Formalin-fixed and paraffin-embedded breast tumors are first sectioned into slices of 20 μm and 30 μm and placed between two tsurupica slides. The slides are then scanned in a pulsed terahertz system using transmission imaging. The tissue regions in adjacent pathology section are compared to the transmission imaging scan in order to define a region of points over which to average the electrical properties results from the scan.

  20. A comparative genomics approach to understanding transmissible cancer in Tasmanian devils.

    PubMed

    Deakin, Janine E; Belov, Katherine

    2012-01-01

    A fatal contagious cancer is driving an entire species to extinction. Comparative genomics will unravel the origin and evolution of devil facial tumor disease (DFTD). The DFTD allograft arose from a Schwann cell in a female Tasmanian devil more than 15 years ago; since then, the tumor has passed through at least 100,000 hosts, evolving and mutating along the way. Tumor genome sequencing and molecular cytogenetic technologies now allow direct comparisons of candidate genes involved in tumorigenesis in human cancers. As a stable transmissible cancer, DFTD provides unique insights into cancer development, progression, and immune evasion and is likely to help increase our understanding of human cancer. In addition, these studies provide hope for discoveries of drug targets or vaccine candidates that will prevent the extinction of this iconic Australian marsupial. PMID:22657390

  1. Horizontal transmission of clonal cancer cells causes leukemia in soft-shell clams

    PubMed Central

    Metzger, Michael J.; Reinisch, Carol; Sherry, James; Goff, Stephen P.

    2015-01-01

    SUMMARY Outbreaks of fatal leukemia-like cancers of marine bivalves throughout the world have led to massive population loss. The cause of the disease is unknown. We recently identified a retrotransposon, Steamer, that is highly expressed and amplified to high copy number in neoplastic cells of soft-shell clams (Mya arenaria). Through analysis of Steamer integration sites, mitochondrial DNA single nucleotide polymorphisms (SNPs), and polymorphic microsatellite alleles, we show that the genotypes of neoplastic cells do not match those of the host animal. Instead, neoplastic cells from dispersed locations in New York, Maine, and Prince Edward Island (PEI), Canada, all have nearly identical genotypes that differ from those of the host. These results indicate that the cancer is spreading between animals in the marine environment as a clonal transmissible cell derived from a single original clam. Our findings suggest that horizontal transmission of cancer cells is more widespread in nature than previously supposed. PMID:25860608

  2. Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts.

    PubMed

    Brunetti, Dario; Perota, Andrea; Lagutina, Irina; Colleoni, Silvia; Duchi, Roberto; Calabrese, Fiorella; Seveso, Michela; Cozzi, Emanuele; Lazzari, Giovanna; Lucchini, Franco; Galli, Cesare

    2008-12-01

    The pig represents the xenogeneic donor of choice for future organ transplantation in humans for anatomical and physiological reasons. However, to bypass several immunological barriers, strong and stable human genes expression must occur in the pig's organs. In this study we created transgenic pigs using in vitro transfection of cultured cells combined with somatic cell nuclear transfer (SCNT) to evaluate the ubiquitous transgene expression driven by pCAGGS vector in presence of different selectors. pCAGGS confirmed to be a very effective vector for ubiquitous transgene expression, irrespective of the selector that was used. Green fluorescent protein (GFP) expression observed in transfected fibroblasts was also maintained after nuclear transfer, through pre- and postimplantation development, at birth and during adulthood. Germ line transmission without silencing of the transgene was demonstrated. The ubiquitous expression of GFP was clearly confirmed in several tissues including endothelial cells, thus making it a suitable vector for the expression of multiple genes relevant to xenotransplantation where tissue specificity is not required. Finally cotransfection of green and red fluorescence protein transgenes was performed in fibroblasts and after nuclear transfer blastocysts expressing both fluorescent proteins were obtained. PMID:18823265

  3. Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer

    PubMed Central

    Strakova, Andrea; Ní Leathlobhair, Máire; Wang, Guo-Dong; Yin, Ting-Ting; Airikkala-Otter, Ilona; Allen, Janice L; Allum, Karen M; Bansse-Issa, Leontine; Bisson, Jocelyn L; Castillo Domracheva, Artemio; de Castro, Karina F; Corrigan, Anne M; Cran, Hugh R; Crawford, Jane T; Cutter, Stephen M; Delgadillo Keenan, Laura; Donelan, Edward M; Faramade, Ibikunle A; Flores Reynoso, Erika; Fotopoulou, Eleni; Fruean, Skye N; Gallardo-Arrieta, Fanny; Glebova, Olga; Häfelin Manrique, Rodrigo F; Henriques, Joaquim JGP; Ignatenko, Natalia; Koenig, Debbie; Lanza-Perea, Marta; Lobetti, Remo; Lopez Quintana, Adriana M; Losfelt, Thibault; Marino, Gabriele; Martincorena, Inigo; Martínez Castañeda, Simón; Martínez-López, Mayra F; Meyer, Michael; Nakanwagi, Berna; De Nardi, Andrigo B; Neunzig, Winifred; Nixon, Sally J; Onsare, Marsden M; Ortega-Pacheco, Antonio; Peleteiro, Maria C; Pye, Ruth J; Reece, John F; Rojas Gutierrez, Jose; Sadia, Haleema; Schmeling, Sheila K; Shamanova, Olga; Ssuna, Richard K; Steenland-Smit, Audrey E; Svitich, Alla; Thoya Ngoka, Ismail; Vițălaru, Bogdan A; de Vos, Anna P; de Vos, Johan P; Walkinton, Oliver; Wedge, David C; Wehrle-Martinez, Alvaro S; van der Wel, Mirjam G; Widdowson, Sophie AE; Murchison, Elizabeth P

    2016-01-01

    Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution. DOI: http://dx.doi.org/10.7554/eLife.14552.001 PMID:27185408

  4. Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

    PubMed

    Strakova, Andrea; Ní Leathlobhair, Máire; Wang, Guo-Dong; Yin, Ting-Ting; Airikkala-Otter, Ilona; Allen, Janice L; Allum, Karen M; Bansse-Issa, Leontine; Bisson, Jocelyn L; Castillo Domracheva, Artemio; de Castro, Karina F; Corrigan, Anne M; Cran, Hugh R; Crawford, Jane T; Cutter, Stephen M; Delgadillo Keenan, Laura; Donelan, Edward M; Faramade, Ibikunle A; Flores Reynoso, Erika; Fotopoulou, Eleni; Fruean, Skye N; Gallardo-Arrieta, Fanny; Glebova, Olga; Häfelin Manrique, Rodrigo F; Henriques, Joaquim Jgp; Ignatenko, Natalia; Koenig, Debbie; Lanza-Perea, Marta; Lobetti, Remo; Lopez Quintana, Adriana M; Losfelt, Thibault; Marino, Gabriele; Martincorena, Inigo; Martínez Castañeda, Simón; Martínez-López, Mayra F; Meyer, Michael; Nakanwagi, Berna; De Nardi, Andrigo B; Neunzig, Winifred; Nixon, Sally J; Onsare, Marsden M; Ortega-Pacheco, Antonio; Peleteiro, Maria C; Pye, Ruth J; Reece, John F; Rojas Gutierrez, Jose; Sadia, Haleema; Schmeling, Sheila K; Shamanova, Olga; Ssuna, Richard K; Steenland-Smit, Audrey E; Svitich, Alla; Thoya Ngoka, Ismail; Vițălaru, Bogdan A; de Vos, Anna P; de Vos, Johan P; Walkinton, Oliver; Wedge, David C; Wehrle-Martinez, Alvaro S; van der Wel, Mirjam G; Widdowson, Sophie Ae; Murchison, Elizabeth P

    2016-01-01

    Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution. PMID:27185408

  5. Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2)

    SciTech Connect

    Lee, Soojin . E-mail: leesoojin@cnu.ac.kr; Gang, Jingu; Jeon, Sun Bok; Jung, Jinyoung; Song, Si Young; Koh, Sang Seok . E-mail: sskoh@kribb.re.kr

    2007-08-31

    We examined genome-wide differences in gene expression between tumor biopsies and normal tissues in order to identify differentially regulated genes in tumors. Cancer-upregulated gene 2 (CUG2) was identified as an expressed sequence tag (EST) that exhibits significant differential expression in multiple human cancer types. CUG2 showed weak sequence homology with the down-regulator of transcription 1 (DR1) gene, a human transcription repressor. We found that EGFP-CUG2 fusion proteins were predominantly localized in the nucleus, suggesting their putative role in gene regulation. In addition, CUG2-overexpressing mouse fibroblast cells exhibited distinct cancer-specific phenotypes in vitro and developed into tumors in nude mice. Taken together, these findings suggest that CUG2 is a novel tumor-associated gene that is commonly activated in various human cancers and exhibits high transforming activities; it possibly belongs to a transcription regulator family that is involved in tumor biogenesis.

  6. Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response.

    PubMed

    Hamede, Rodrigo K; Pearse, Anne-Maree; Swift, Kate; Barmuta, Leon A; Murchison, Elizabeth P; Jones, Menna E

    2015-09-01

    Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness. PMID:26336167

  7. The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

    PubMed Central

    Booth, Laurence; Roberts, Jane L.; Tavallai, Mehrad; Webb, Timothy; Leon, Daniel; Chen, Jesse; McGuire, William P.; Poklepovic, Andrew; Dent, Paul

    2016-01-01

    We generated afatinib resistant clones of H1975 lung cancer cells by transient exposure of established tumors to the drug and collected the re-grown tumors. Afatinib resistant H1975 clones did not exhibit any additional mutations in proto-oncogenes when compared to control clones. Afatinib resistant H1975 tumor clones expressed less PTEN than control clones and in afatinib resistant clones this correlated with increased basal SRC Y416, ERBB3 Y1289, AKT T308 and mTOR S2448 phosphorylation, decreased expression of ERBB1, ERBB2 and ERBB3 and increased total expression of c-MET, c-KIT and PDGFRβ. Afatinib resistant clones were selectively killed by knock down of [ERBB3 + c-MET + c-KIT] but not by the individual or doublet knock down combinations. The combination of the ERBB1/2/4 inhibitor afatinib with the SRC family inhibitor dasatinib killed afatinib resistant H1975 cells in a greater than additive fashion; other drugs used in combination with dasatinib such as sunitinib, crizotinib and amufatinib were less effective. [Afatinib + dasatinib] treatment profoundly inactivated ERBB3, AKT and mTOR in the H1975 afatinib resistant clones and increased ATG13 S318 phosphorylation. Knock down of ATG13, Beclin1 or eIF2α strong suppressed killing by [ERBB3 + c-MET + c-KIT] knock down, but were only modestly protective against [afatinib + dasatinib] lethality. Thus afatinib resistant H1975 NSCLC cells rely on ERBB1- and SRC-dependent hyper-activation of residual ERBB3 and elevated signaling, due to elevated protein expression, from wild type c-MET and c-KIT to remain alive. Inhibition of ERBB3 signaling via both blockade of SRC and ERBB1 results in tumor cell death. PMID:26934000

  8. Concise review: transmissible animal tumors as models of the cancer stem-cell process.

    PubMed

    O'Neill, Iain D

    2011-12-01

    Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are highly unusual cancers capable of being transmitted between animals as an allograft. The concept that these tumors represent a cancer stem-cell process has never been formally evaluated. For each, evidence of self-renewal is found in the natural history of these tumors in the wild, tumor initiation in recipient animals, and serial transplantation studies. Additional data for stem-cell-specific genes and markers in DFTD also exist. Although both tumor types manifest as undifferentiated cancers, immunocytohistochemistry supports a histiocytic phenotype for CTVT and a neural crest origin, possibly a Schwann-cell phenotype, for DFTD. In these data, differential expression of lineage markers is seen which may suggest some capacity for differentiation toward a heterogeneous variety of cell types. It is proposed that DFTD and CTVT may represent and may serve as models of the cancer stem-cell process, but formal investigation is required to clarify this. Appreciation of any such role may act as a stimulus to ongoing research in the pathology of DFTD and CTVT, including further characterization of their origin and phenotype and possible therapeutic approaches. Additionally, they may provide valuable models for future studies of their analogous human cancers, including any putative CSC component. PMID:21956952

  9. High molecular weight stress proteins: Identification, cloning and utilisation in cancer immunotherapy.

    PubMed

    Wang, Xiang-Yang; Subjeck, John R

    2013-08-01

    Although the large stress/heat shock proteins (HSPs), i.e. Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent anti-tumour activity of the Hsp110/Grp170-tumour protein antigen complexes demonstrated in preclinical studies has led to a phase I clinical trial through the National Cancer Institute's rapid access to intervention development (RAID) programme that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and anti-tumour immunity induced by large HSP vaccines and other immunotherapies. PMID:23829534

  10. The High Molecular Weight Stress Proteins: Identification, Cloning, and Utilization in Cancer Immunotherapy*

    PubMed Central

    Wang, Xiang-Yang; Subjeck, John R.

    2013-01-01

    Although the large stress/heat shock proteins (HSPs), i.e., Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent antitumor activity of the Hsp110/Grp170-tumor protein antigen complexes, demonstrated in preclinical studies, has led to a phase I clinical trial through the National Cancer Institute's RAID Program that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and antitumor immunity induced by large HSP vaccines and other immunotherapies. PMID:23829534

  11. Molecular cloning of an activated human oncogene, homologous to v-raf, from primary stomach cancer.

    PubMed Central

    Shimizu, K; Nakatsu, Y; Sekiguchi, M; Hokamura, K; Tanaka, K; Terada, M; Sugimura, T

    1985-01-01

    Transfection with high molecular weight DNA from a primary stomach cancer induced foci of transformed NIH 3T3 cells, and the transformed cells were tumorigenic in nude mice. By screening with a human Alu-family probe, we isolated the human DNA sequence from the secondary transformant cells. This transforming sequence encompasses about 60 kilobase pairs and is unrelated to known human transforming genes. Examination of homologies between this sequence and retroviral oncogenes revealed that the human transforming sequence is closely related to the v-raf oncogene of murine transforming retrovirus 3611-MSV. Images PMID:3862088

  12. Why Clone?

    MedlinePlus

    ... How might cloning be used in medicine? Cloning animal models of disease Much of what researchers learn about human disease comes from studying animal models such as mice. Often, animal models are ...

  13. Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid.

    PubMed

    Hulikova, Alzbeta; Black, Nicholas; Hsia, Lin-Ting; Wilding, Jennifer; Bodmer, Walter F; Swietach, Pawel

    2016-09-01

    Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture. Expression of the acid-loading transporter anion exchanger 2 (AE2) (SLC4A2 product) was detected in myofibroblasts and fibroblasts, but not in CRC cells. Compared with CRC cells, Hs675.T and InMyoFib myofibroblasts had very high capacity to absorb extracellular acid. Acid uptake into CCD-112-CoN and NHDF-Ad cells was slower and comparable to levels in CRC cells, but increased alongside SLC4A2 expression under stimulation with transforming growth factor β1 (TGFβ1), a cytokine involved in cancer-stroma interplay. Myofibroblasts and fibroblasts are connected by gap junctions formed by proteins such as connexin-43, which allows the absorbed acid load to be transmitted across the stromal syncytium. To match the stimulatory effect on acid uptake, cell-to-cell coupling in NHDF-Ad and CCD-112-CoN cells was strengthened with TGFβ1. In contrast, acid transmission was absent between CRC cells, even after treatment with TGFβ1. Thus, stromal cells have the necessary molecular apparatus for assembling an acid-venting route that can improve the flow of metabolic acid through tumors. Importantly, the activities of stromal AE2 and connexin-43 do not place an energetic burden on cancer cells, allowing resources to be diverted for other activities. PMID:27543333

  14. Heterogeneity Underlies the Emergence of EGFR T790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third Generation EGFR Inhibitor

    PubMed Central

    Piotrowska, Zofia; Niederst, Matthew J.; Karlovich, Chris A.; Wakelee, Heather A.; Neal, Joel W.; Mino-Kenudson, Mari; Fulton, Linnea; Hata, Aaron N.; Lockerman, Elizabeth L.; Kalsy, Anuj; Digumarthy, Subba; Muzikansky, Alona; Raponi, Mitch; Garcia, Angel R.; Mulvey, Hillary E.; Parks, Melissa K.; DiCecca, Richard H.; Dias-Santagata, Dora; Iafrate, A. John; Shaw, Alice T.; Allen, Andrew R.; Engelman, Jeffrey A.; Sequist, Lecia V.

    2015-01-01

    Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790 wild-type rociletinib-resistant biopsies. Two T790 wild-type cancers underwent small cell lung cancer transformation; three T790M-positive cancers acquired EGFR amplification. We documented T790 wild-type and T790M-positive clones coexisting within a single pre-rociletinib biopsy. In fact, the pre-treatment fraction of T790M-positive cells impacted response to rociletinib. Longitudinal ctDNA analysis revealed an increase in plasma EGFR activating mutation and T790M heralded rociletinib resistance in some patients, while in others the activating mutation increased but T790M remained suppressed. Together, these findings demonstrate the role of tumor heterogeneity when therapies targeting a singular resistance mechanism are employed. To further improve outcomes, combination regimens that also target T790 wild-type clones are required. PMID:25934077

  15. A murine xenograft model for a transmissible cancer in Tasmanian devils.

    PubMed

    Kreiss, A; Tovar, C; Obendorf, D L; Dun, K; Woods, G M

    2011-03-01

    The number of Tasmanian devils in the wild is rapidly declining owing to a transmissible cancer, devil facial tumor disease (DFTD). Although progress has been made to understand the spread of this disease, crucial research on the pathogenesis of DFTD has been limited because of the threatened status of the host species. Here, the authors describe the development of a NOD/SCID (nonobese diabetic / severe combined immunodeficiency) mouse model that reproduces DFTD and provides a much-needed model to undertake studies into this intriguing transmissible cancer. Histologically, the DFTD produced in NOD/SCID mice (xenografted DFTD) was indistinguishable from the DFTD identified in Tasmanian devils. At the protein level, all xenografted DFTD tumors expressed periaxin, a marker that confirmed the diagnosis of DFTD. The karyotype of DFTD in NOD/SCID mice reproduced similar chromosomal alterations as seen in diseased devils. Furthermore, each NOD/SCID mouse inoculated with cultured DFTD tumor cells developed tumors, whereas DFTD did not develop in any of the inoculated immune-competent BALB/c mice. PMID:20861503

  16. Optical and Nanoparticle Analysis of Normal and Cancer Cells by Light Transmission Spectroscopy

    NASA Astrophysics Data System (ADS)

    Deatsch, Alison; Sun, Nan; Johnson, Jeffery; Stack, Sharon; Szajko, John; Sander, Christopher; Rebuyon, Roland; Easton, Judah; Tanner, Carol; Ruggiero, Steven

    2015-03-01

    We have investigated the optical properties of human oral and ovarian cancer and normal cells. Specifically, we have measured the absolute optical extinction for intra-cellular material (lysates) in aqueous suspension. Measurements were conducted over a wavelength range of 250 to 1000 nm with 1 nm resolution using Light Transmission Spectroscopy (LTS). This provides both the absolute extinction of materials under study and, with Mie inversion, the absolute number of particles of a given diameter as a function of diameter in the range of 1 to 3000 nm. Our preliminary studies show significant differences in both the extinction and particle size distributions associated with cancer versus normal cells, which appear to be correlated with differences in the particle size distribution in the range of approximately 50 to 250 nm. Especially significant is a clearly higher density of particles at about 100 nm and smaller for normal cells. Department of Physics, Harper Cancer Research Institute, and the Office of Research at the University of Notre Dame.

  17. Nanoparticle Distributions in Cancer and other Cells from Light Transmission Spectroscopy

    NASA Astrophysics Data System (ADS)

    Deatsch, Alison; Sun, Nan; Johnson, Jeffery; Stack, Sharon; Tanner, Carol; Ruggiero, Steven

    We have measured the optical properties of whole cells and lysates using light transmission spectroscopy (LTS). LTS provides both the optical extinction coefficient in the wavelength range from 220 to 1100 nm and (by spectral inversion using a Mie model) the particle distribution density in the size range from 1 to 3000 nm. Our current work involves whole cells and lysates of cultured human oral cells and other plant and animal cells. We have found systematic differences in the optical extinction between cancer and normal whole cells and lysates, which translate to different particle size distributions (PSDs) for these materials. We have also found specific power-law dependences of particle density with particle diameter for cell lysates. This suggests a universality of the packing distribution in cells that can be compared to ideal Apollonian packing, with the cell modeled as a fractal body comprised of spheres on all size scales.

  18. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

    NASA Astrophysics Data System (ADS)

    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans

    2003-01-01

    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

  19. Academic Cloning.

    ERIC Educational Resources Information Center

    Sikula, John P.; Sikula, Andrew F.

    1980-01-01

    The authors define "cloning" as an integral feature of all educational systems, citing teaching practices which reward students for closely reproducing the teacher's thoughts and/or behaviors and administrative systems which tend to promote like-minded subordinates. They insist, however, that "academic cloning" is not a totally negative practice.…

  20. Cloning analysis of ferritin and the cisplatin-subunit for cancer cell apoptosis in Aplysia juliana hepatopancreas.

    PubMed

    Zhu, Bo; Huang, Lin; Huang, He-Qing

    2012-08-01

    Ferritin, an iron storage protein, plays a key role in iron metabolism in vivo. Here, we have cloned an inducible ferritin cDNA with 519 bp within the open reading frame fragment from the hepatopancreas of Aplysia juliana (AJ). The subunit sequence of the ferritin was predicted to be a polypeptide of 172 amino acids with a molecular mass of 19.8291kDa and an isoelectric point of 5.01. The cDNA sequence of hepatopancreas ferritin in AJ was constructed into a pET-32a system for expressing its relative protein efficiently in E. coli strain BL21, under isopropyl-β-d-thiogalactoside induction. The recombinant ferritin, which was further purified on a Ni-NTA resin column and digested with enterokinase, was detected as a single subunit of approximately 20 kDa mass using both SDS-PAGE and mass spectrometry. The secondary structure and phosphorylation sites of the deduced amino acids were predicted using both ExPASy proteomic tools and the NetPhos 2.0 server, and the subunit space structure of the recombinant AJ ferritin (rAjFer) was built using a molecular operating environment software system. The result of in-gel digestion and identification using MALDI-TOF MS/MS showed that the recombinant protein was AjFer. ICP-MS results indicated that the rAjFer subunit could directly bind to cisplatin[cis-Diaminedichloroplatinum(CDDP)], giving approximately 17.6 CDDP/ferritin subunits and forming a novel CDDP-subunit. This suggests that a nanometer CDDP core-ferritin was constructed, which could be developed as a new anti-cancer drug. The flow cytometry results indicated that CDDP-rAjFer could induce Hela cell apoptosis. Results of the real-time PCR and Western blotting showed that the expression of AjFer mRNA was up-regulated in AJ under Cd(2+) stress. The recombinant AjFer protein should prove to be useful for further study of the structure and function of ferritin in Aplysia. PMID:22579997

  1. Identification and cloning in yeast artificial chromosomes of a region of elevated loss of heterozygosity on chromosome 1p31.1 in human breast cancer

    SciTech Connect

    Hoggard, N.; Hey, Y.; Brintnell, B.; James, L.

    1995-11-20

    We have mapped a region of high loss of heterozygosity in breast cancer to a 2-cM interval between the loci D1S430 and D1S465 on chromosome 1p31.1. This region shows allelic imbalance in around 60% of breast tumors. As part of a strategy to clone the target gene(s) within this interval, we have generated a yeast artificial chromosome contig spanning over 7 Mb. YACs from the CEPH and Zeneca (formerly ICI) libraries have been obtained by screening with PCR-based STSs from the region for both previously identified loci and newly isolated STSs. The YACs have been assembled into a contig by a combination of approaches, including analysis of their STS content, generation of new STSs from the ends of key YACs, and long-range restriction mapping. These YAC clones provide the basis for complete characterization of the region of high loss in breast cancer and for the ultimate identification of the target gene(s). 84 refs., 3 figs., 3 tabs.

  2. Association of Composite IS26-sul3 Elements with Highly Transmissible IncI1 Plasmids in Extended-Spectrum-β-Lactamase-Producing Escherichia coli Clones from Humans▿

    PubMed Central

    Curiao, Tânia; Cantón, Rafael; Garcillán-Barcia, M. Pilar; de la Cruz, Fernando; Baquero, Fernando; Coque, Teresa M.

    2011-01-01

    The association of an IS440-sul3 platform with Tn21 class 1 integrons carried by IncI1 plasmids encoding extended-spectrum β-lactamases (ESBLs; mainly SHV-12 and CTX-M-14) among worldwide Escherichia coli clones of phylogroups A (ST10, ST23, and ST46), B1 (ST155, ST351, and ST359), and D/B2 (ST131) is reported. An in silico comparative analysis of sul3 elements available in the GenBank database shows the evolution of sul3 platforms by hosting different transposable elements facilitating the potential genesis of IS26 composite transposons and further insertion element-mediated promoted arrangements. PMID:21343460

  3. 40 GHz RF biosensor based on microwave coplanar waveguide transmission line for cancer cells (HepG2) dielectric characterization.

    PubMed

    Chen, Yu-Fu; Wu, Hung-Wei; Hong, Yong-Han; Lee, Hsin-Ying

    2014-11-15

    This paper presents a 40-GHz RF biosensor that involves using a microwave coplanar waveguide (CPW) transmission line for the dielectric characterization of cancer cells (Hepatoma G2, HepG2). In the past, conventional resonator-based biosensors were designed to operate at a specific resonant peak; however, the dielectric sensitivity of the cells was restricted to a narrow bandwidth. To provide a very wide bandwidth (1-40 GHz), biosensors were based on a microwave CPW transmission line. The proposed biosensor can rapidly measure two frequency-dependent cell-based dielectric parameters of HepG2 cells, microwave attenuation (α(f)cell) and the dielectric constant (εr(f)cell), while removing the microwave parasitic effects (including the cultured medium and substrate materials). The proposed biosensor can be applied in postoperative cancer diagnosis. PMID:24934741

  4. Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo.

    PubMed

    Sipila, P E; Wiebe, V J; Hubbard, G B; Koester, S K; Emshoff, V D; Maenpaa, J U; Wurz, G T; Seymour, R C; DeGregorio, M W

    1993-01-01

    The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo. PMID:8297653

  5. Comparative study of primary and secondary tumors from patients with laryngeal and oropharyngeal cancer, using transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Ghetea, Ligia Gabriela; Niculescu, Ana-Maria; Motoc, Rozalia Magda; Mihaescu, Grigore; Duma, Virgil-Florin; Manu, Dorel Augustin; Gavrila, Lucian

    2008-04-01

    In modern laboratories, the study of cancer is performed using a series of cellular and molecular methods based on optical instruments measurements. Optical and electron microscopy are valuable tools for revealing morphological features of cancer cells. Our study was focused on laryngeal and oropharyngeal cancers, which have nowadays an increased incidence, especially for women, due to unhealthy habits like tobacco and alcohol consumption. We used transmission electron microscopy (TEM) for highlighting the ultrastructural features of cancer cells, both in primary and secondary tumors. The primary tumor is considered that which appears for the first time, at a certain organ; the secondary tumor is that which reappears at the same region or neighbouring regions, at a certain interval of time after the primary one has been surgically removed. The differences between the inner architecture of the cells from primary and secondary tumors where correlated with the expression of some genes (oncogenes and tumor suppressor factors), in order to establish the aggressiveness of the tumor, in different disease stages. The main stress in the study is placed upon electron microscopy, in order to achieve a more precise characterization of both these type of cancer cells. These ultrastructural data complete the image of laryngeal and pharyngeal cancer cells, along with molecular data obtained by Real-Time PCR.

  6. O-Linked β-N-Acetylglucosaminylation (O-GlcNAcylation) in Primary and Metastatic Colorectal Cancer Clones and Effect of N-Acetyl-β-d-glucosaminidase Silencing on Cell Phenotype and Transcriptome*

    PubMed Central

    Yehezkel, Galit; Cohen, Liz; Kliger, Adi; Manor, Esther; Khalaila, Isam

    2012-01-01

    O-Linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a regulatory post-translational modification occurring on the serine or threonine residues of nucleocytoplasmic proteins. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase and O-GlcNAcase (OGA), which are responsible for O-GlcNAc addition and removal, respectively. Although O-GlcNAcylation was found to play a significant role in several pathologies such as type II diabetes and neurodegenerative diseases, the role of O-GlcNAcylation in the etiology and progression of cancer remains vague. Here, we followed O-GlcNAcylation and its catalytic machinery in metastatic clones of human colorectal cancer and the effect of OGA knockdown on cellular phenotype and on the transcriptome. The colorectal cancer SW620 metastatic clone exhibited increased O-GlcNAcylation and decreased OGA expression compared with its primary clone, SW480. O-GlcNAcylation elevation in SW620 cells, through RNA interference of OGA, resulted in phenotypic alterations that included acquisition of a fibroblast-like morphology, which coincides with epithelial metastatic progression and growth retardation. Microarray analysis revealed that OGA silencing altered the expression of about 1300 genes, mostly involved in cell movement and growth, and specifically affected metabolic pathways of lipids and carbohydrates. These findings support the involvement of O-GlcNAcylation in various aspects of tumor cell physiology and suggest that this modification may serve as a link between metabolic changes and cancer. PMID:22730328

  7. Quantification of HER2 heterogeneity in breast cancer-implications for identification of sub-dominant clones for personalised treatment.

    PubMed

    Buckley, Niamh E; Forde, Claire; McArt, Darragh G; Boyle, David P; Mullan, Paul B; James, Jacqueline A; Maxwell, Perry; McQuaid, Stephen; Salto-Tellez, Manuel

    2016-01-01

    Breast cancer is a heterogeneous disease, at both an inter- and intra-tumoural level. Appreciating heterogeneity through the application of biomarkers and molecular signatures adds complexity to tumour taxonomy but is key to personalising diagnosis, treatment and prognosis. The extent to which heterogeneity exists, and its interpretation remains a challenge to pathologists. Using HER2 as an exemplar, we have developed a simple reproducible heterogeneity index. Cell-to-cell HER2 heterogeneity was extensive in a proportion of both reported 'amplified' and 'non-amplified' cases. The highest levels of heterogeneity objectively identified occurred in borderline categories and higher ratio non-amplified cases. A case with particularly striking heterogeneity was analysed further with an array of biomarkers in order to assign a molecular diagnosis. Broad biological complexity was evident. In essence, interpretation, depending on the area of tumour sampled, could have been one of three distinct phenotypes, each of which would infer different therapeutic interventions. Therefore, we recommend that heterogeneity is assessed and taken into account when determining treatment options. PMID:26996207

  8. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  9. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection.

    PubMed

    Giuliano, Anna R; Nyitray, Alan G; Kreimer, Aimée R; Pierce Campbell, Christine M; Goodman, Marc T; Sudenga, Staci L; Monsonego, Joseph; Franceschi, Silvia

    2015-06-15

    Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal and <50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often, mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet, HPV-related cancer incidence at this site is several-fold higher than at either the anal canal or the penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age-specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts. PMID:25043222

  10. The Clone Factory

    ERIC Educational Resources Information Center

    Stoddard, Beryl

    2005-01-01

    Have humans been cloned? Is it possible? Immediate interest is sparked when students are asked these questions. In response to their curiosity, the clone factory activity was developed to help them understand the process of cloning. In this activity, students reenact the cloning process, in a very simplified simulation. After completing the…

  11. Self-Cloning CRISPR.

    PubMed

    Arbab, Mandana; Sherwood, Richard I

    2016-01-01

    CRISPR/Cas9-gene editing has emerged as a revolutionary technology to easily modify specific genomic loci by designing complementary sgRNA sequences and introducing these into cells along with Cas9. Self-cloning CRISPR/Cas9 (scCRISPR) uses a self-cleaving palindromic sgRNA plasmid (sgPal) that recombines with short PCR-amplified site-specific sgRNA sequences within the target cell by homologous recombination to circumvent the process of sgRNA plasmid construction. Through this mechanism, scCRISPR enables gene editing within 2 hr once sgRNA oligos are available, with high efficiency equivalent to conventional sgRNA targeting: >90% gene knockout in both mouse and human embryonic stem cells and cancer cell lines. Furthermore, using PCR-based addition of short homology arms, we achieve efficient site-specific knock-in of transgenes such as GFP without traditional plasmid cloning or genome-integrated selection cassette (2% to 4% knock-in rate). The methods in this paper describe the most rapid and efficient means of CRISPR gene editing. © 2016 by John Wiley & Sons, Inc. PMID:27532819

  12. Evolution in a transmissible cancer: a study of the chromosomal changes in devil facial tumor (DFT) as it spreads through the wild Tasmanian devil population.

    PubMed

    Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; McCallum, Hamish; Pyecroft, Stephen; Taylor, Robyn; Eldridge, Mark D B; Belov, Katherine

    2012-03-01

    Tasmanian devils (Sarcophilus harrisii) are the largest extant marsupial carnivores. This species, now confined to Tasmania, is endangered from the emergence of a transmissible cancer, devil facial tumor disease (DFTD). In the present study, we use cytogenetic and molecular techniques to examine the stability of devil facial tumor (DFT) cell lines across time and space. This article describes disease progression from February 2004 to June 2011. We demonstrate evolutionary changes in the disease, which affects devils in different sites across Tasmania and over a period of several years, producing several chromosomal variants (strains) that are capable of transmission between devils. We describe the evolution of DFTs in the field and speculate on the possible impacts on the disease, including (1) development of less aggressive forms of the disease; (2) development of more aggressive forms of the disease; (3) development of forms capable of affecting closely related species of dasyurids (e.g., quolls); (4) extinction of the disease as it acquires additional deleterious mutations that affect either cell viability or transmissibility; and (5) co-evolution of the disease and the host. We also speculate about the future of the Tasmanian devil in the wild. We note that although DFTs are regarded as unstable by comparison with another much older transmissible cancer, canine transmissible venereal tumor (CTVT), the potential for development of less aggressive forms of DFTs or for development of resistance in devils is limited by devils' small numbers, low genetic diversity, and restricted geographical distribution. PMID:22469509

  13. Proportionally constant quantitative transmission of nucleolin and protein B23 in cycling cancer cells

    PubMed Central

    Sirri, V; Pession, A; Trerè, D; Montanaro, L; Derenzini, M

    1995-01-01

    Objective—To investigate whether and to what extent the two major AgNOR proteins, nucleolin and protein B23, are maintained after one cell division in proliferating cells. Design—Using three asynchronously growing human cancer cell lines, TG, SJNKP, and CHP 212 cells, nucleolin and protein B23 were first identified on SDS-polyacrylamide separated nucleolar proteins, transferred to nitrocellulose and silver stained for AgNOR proteins. Measurement of doubling time indicated a period very close to 24h for each of the cell lines. To quantify the percentage of nucleolin and protein B23 maintained in daughter cells after duplication, cells were labelled with [35S]-methionine and a 24h cold chase performed. Nucleolin and protein B23 labelling was evaluated by densitometric analysis on nitrocellulose autoradiograms. Results—The radioactivity relative to nucleolin and protein B23 bands maintained in the daughter cells was a constant fraction of that present before cell duplication. In the three cell lines the percentage of residual radioactivity measured in the nucleolin bands was 42·2, 40·6, and 41·2 and in protein B23 bands 48·0, 46·2, and 44·1. Conclusions—After one cell division the nucleolin and protein B23 quantity present in cells may be highly variable, depending on the amount of the two proteins present in the mother cell. This is important in relation to the correct utilisation of AgNOR protein quantity as an index for evaluating cell kinetics. Images PMID:16696019

  14. Non-transmissible Sendai virus vector encoding c-myc suppressor FBP-interacting repressor for cancer therapy

    PubMed Central

    Matsushita, Kazuyuki; Shimada, Hideaki; Ueda, Yasuji; Inoue, Makoto; Hasegawa, Mamoru; Tomonaga, Takeshi; Matsubara, Hisahiro; Nomura, Fumio

    2014-01-01

    AIM: To investigate a novel therapeutic strategy to target and suppress c-myc in human cancers using far up stream element (FUSE)-binding protein-interacting repressor (FIR). METHODS: Endogenous c-Myc suppression and apoptosis induction by a transient FIR-expressing vector was examined in vivo via a HA-tagged FIR (HA-FIR) expression vector. A fusion gene-deficient, non-transmissible, Sendai virus (SeV) vector encoding FIR cDNA, SeV/dF/FIR, was prepared. SeV/dF/FIR was examined for its gene transduction efficiency, viral dose dependency of antitumor effect and apoptosis induction in HeLa (cervical squamous cell carcinoma) cells and SW480 (colon adenocarcinoma) cells. Antitumor efficacy in a mouse xenograft model was also examined. The molecular mechanism of the anti-tumor effect and c-Myc suppression by SeV/dF/FIR was examined using Spliceostatin A (SSA), a SAP155 inhibitor, or SAP155 siRNA which induce c-Myc by increasing FIR∆exon2 in HeLa cells. RESULTS: FIR was found to repress c-myc transcription and in turn the overexpression of FIR drove apoptosis through c-myc suppression. Thus, FIR expressing vectors are potentially applicable for cancer therapy. FIR is alternatively spliced by SAP155 in cancer cells lacking the transcriptional repression domain within exon 2 (FIR∆exon2), counteracting FIR for c-Myc protein expression. Furthermore, FIR forms a complex with SAP155 and inhibits mutual well-established functions. Thus, both the valuable effects and side effects of exogenous FIR stimuli should be tested for future clinical application. SeV/dF/FIR, a cytoplasmic RNA virus, was successfully prepared and showed highly efficient gene transduction in in vivo experiments. Furthermore, in nude mouse tumor xenograft models, SeV/dF/FIR displayed high antitumor efficiency against human cancer cells. SeV/dF/FIR suppressed SSA-activated c-Myc. SAP155 siRNA, potentially produces FIR∆exon2, and led to c-Myc overexpression with phosphorylation at Ser62. HA-FIR suppressed

  15. Multipartite asymmetric quantum cloning

    SciTech Connect

    Iblisdir, S.; Gisin, N.; Acin, A.; Cerf, N.J.; Filip, R.; Fiurasek, J.

    2005-10-15

    We investigate the optimal distribution of quantum information over multipartite systems in asymmetric settings. We introduce cloning transformations that take N identical replicas of a pure state in any dimension as input and yield a collection of clones with nonidentical fidelities. As an example, if the clones are partitioned into a set of M{sub A} clones with fidelity F{sup A} and another set of M{sub B} clones with fidelity F{sup B}, the trade-off between these fidelities is analyzed, and particular cases of optimal N{yields}M{sub A}+M{sub B} cloning machines are exhibited. We also present an optimal 1{yields}1+1+1 cloning machine, which is an example of a tripartite fully asymmetric cloner. Finally, it is shown how these cloning machines can be optically realized.

  16. Aristotle and headless clones.

    PubMed

    Mosteller, Timothy

    2005-01-01

    Cloned organisms can be genetically altered so that they do not exhibit higher brain functioning. This form of therapeutic cloning allows for genetically identical organs and tissues to be harvested from the clone for the use of the organism that is cloned. "Spare parts" cloning promises many opportunities for future medical advances. What is the ontological and ethical status of spare parts, headless clones? This paper attempts to answer this question from the perspective of Aristotle's view of the soul. Aristotle's metaphysics as applied to his view of biological essences generates an ethic that can contribute to moral reasoning regarding the use of headless spare parts clones. The task of this paper is to show the implications that Aristotle's view of the soul, if it is true, would have on the ethics of headless, spare parts cloning. PMID:16180113

  17. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  18. Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer.

    PubMed

    Kato, Yuiko; Ochiai, Kazuhiko; Michishita, Masaki; Azakami, Daigo; Nakahira, Rei; Morimatsu, Masami; Ishiguro-Oonuma, Toshina; Yoshikawa, Yasunaga; Kobayashi, Masato; Bonkobara, Makoto; Kobayashi, Masanori; Takahashi, Kimimasa; Watanabe, Masami; Omi, Toshinori

    2015-11-01

    Although the morbidity of canine prostate cancer is low, the majority of cases present with resistance to androgen therapy and poor clinical outcomes. These pathological conditions are similar to the signs of the terminal stage of human androgen-independent prostate cancer. The co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) is known to be overexpressed in human androgen-independent prostate cancer. However, there is little information about the structure and function of canine SGTA. In this study, canine SGTA was cloned and analysed for its ability to suppress androgen receptor signalling. The full-length open reading frame (ORF) of the canine SGTA gene was amplified by RT-PCR using primers designed from canine-expressed sequence tags that were homologous to human SGTA. The canine SGTA ORF has high homology with the corresponding human (89%) and mouse (81%) sequences. SGTA dimerisation region and tetratricopeptide repeat (TPR) domains are conserved across the three species. The ability of canine SGTA to undergo homodimerisation was demonstrated by a mammalian two-hybrid system and a pull-down assay. The negative impact of canine SGTA on androgen receptor (AR) signalling was demonstrated using a reporter assay in androgen-independent human prostate cancer cell lines. Pathological analysis showed overexpression of SGTA in canine prostate cancer, but not in hyperplasia. A reporter assay in prostate cells demonstrated suppression of AR signalling by canine SGTA. Altogether, these results suggest that canine SGTA may play an important role in the acquisition of androgen independence by canine prostate cancer cells. PMID:26346258

  19. A 450 Kb cosmid contig on human chromosome 3p21.3 for cloning tumor suppressor genes associated with lung cancer

    SciTech Connect

    Wei, M.H.; Chen, J.Y.; Geil, L.

    1994-09-01

    Cytogenetic and molecular analysis of human tumors have strongly suggested that human chromosome 3p21.3 harbors putative tumor suppressor genes which directly contribute to tumorigenesis of small cell lung carcinoma (SCLC). We have constructed a cosmid contig of 450 Kb within 3p21.3. A conventional cosmid walking strategy coupled with Not1 linking and jumping clones and P1 phage clones from 3p21.3 was used to isolate 18 continuous overlapping cosmids. The common overlapping regions of several homozygous deletions in SCLC cell lines are included in this contig. Two approaches are being employed for characterization of this contig: (1) highly conserved expressed sequences are being indentified by utilizing cDNA libraries to identify hybridizing fragments from this contig. Hybridizing genomic fragments are then used to screen cDNA libraries. (2) CpG islands associated with genes are being mapped within each cosmid. Candidate genes obtained in these experiments are being analyzed for mutation in SCLC cell lines by SSCP. This contig also provides a detailed physical map of the region. It will be useful to cloning the putative tumor suppressor gene and systematic characterization of other genes in this region.

  20. Cloning, killing, and identity.

    PubMed Central

    McMahan, J

    1999-01-01

    One potentially valuable use of cloning is to provide a source of tissues or organs for transplantation. The most important objection to this use of cloning is that a human clone would be the sort of entity that it would be seriously wrong to kill. I argue that entities of the sort that you and I essentially are do not begin to exist until around the seventh month of fetal gestation. Therefore to kill a clone prior to that would not be to kill someone like you or me but would be only to prevent one of us from existing. And even after one of us begins to exist, the objections to killing it remain comparatively weak until its psychological capacities reach a certain level of maturation. These claims support the permissibility of killing a clone during the early stages of its development in order to use its organs for transplantation. PMID:10226909

  1. Cloning of mouse telomerase reverse transcriptase gene promoter and identification of proximal core promoter sequences essential for the expression of transgenes in cancer cells.

    PubMed

    Si, Shao-Yan; Song, Shu-Jun; Zhang, Jian-Zhong; Liu, Jun-Li; Liang, Shuang; Feng, Kai; Zhao, Gang; Tan, Xiao-Qing

    2011-08-01

    Telomerase is a ribonucleoprotein complex, whose function is to add motif-specific nucleotides to the end of chromosomes. Telomerase consists of three major subunits, the telomerase RNA template (hTR), the telomerase-associated protein (TEP1) and telomerase reverse transcriptase (TERT). TERT is the most important component responsible for the catalytic activity of telomerase and a rate-limiting determinant of the activity. Telomerase activities were at high levels in approximately 90% of mouse cancers or tumor-derived cell lines through TERT transcriptional up-regulation. Unlike human telomerase, telomerase activity exists in colon, liver, ovary and testis but not in brain, heart, stomach and muscle in normal mouse tissues. In this study, we prepared 5' truncations of 1086 bp fragments upstream of the initiating ATG codon of the mTERT gene to construct luciferase reporter gene plasmids, and transfected these plasmids into a normal mouse cell line and several cancer lines to identify the core promoter region essential for transcriptional activation in cancer cells by a luciferase assay. We constructed a eukaryotic expression vector of membrane-expressing staphylococcal endotoxin A (SEA) gene driven by the core promoter region of the mTERT gene and observed if the core promoter region could express the SEA gene in these cancer cells, but not in normal cells following transfection with the construct. The results showed that the transcriptional activities of each fragment of the mTERT gene promoter in the cancer cell lines Hepa1-6, B16 and CT26 were higher than those in NIH3T3 cells, and the proximal 333-bp fragment was the core promoter of the mTERT gene in the cancer cells. The proximal 333-bp fragment was able to make the SEA express on the surface of the cancer cells, but not in NIH3T3 cells. It provides a foundation for cancer targeting gene therapy by using the mTERT gene promoter. PMID:21567104

  2. Epidemiologic study of residential proximity to transmission lines and childhood cancer in California: description of design, epidemiologic methods and study population.

    PubMed

    Kheifets, Leeka; Crespi, Catherine M; Hooper, Chris; Oksuzyan, Sona; Cockburn, Myles; Ly, Thomas; Mezei, Gabor

    2015-01-01

    We conducted a large epidemiologic case-control study in California to examine the association between childhood cancer risk and distance from the home address at birth to the nearest high-voltage overhead transmission line as a replication of the study of Draper et al. in the United Kingdom. We present a detailed description of the study design, methods of case ascertainment, control selection, exposure assessment and data analysis plan. A total of 5788 childhood leukemia cases and 3308 childhood central nervous system cancer cases (included for comparison) and matched controls were available for analysis. Birth and diagnosis addresses of cases and birth addresses of controls were geocoded. Distance from the home to nearby overhead transmission lines was ascertained on the basis of the electric power companies' geographic information system (GIS) databases, additional Google Earth aerial evaluation and site visits to selected residences. We evaluated distances to power lines up to 2000 m and included consideration of lower voltages (60-69 kV). Distance measures based on GIS and Google Earth evaluation showed close agreement (Pearson correlation >0.99). Our three-tiered approach to exposure assessment allowed us to achieve high specificity, which is crucial for studies of rare diseases with low exposure prevalence. PMID:24045429

  3. Detectability of Plasmodium falciparum clones

    PubMed Central

    2010-01-01

    Background In areas of high transmission people often harbour multiple clones of Plasmodium falciparum, but even PCR-based diagnostic methods can only detect a fraction (the detectability, q) of all clones present in a host. Accurate measurements of detectability are desirable since it affects estimates of multiplicity of infection, prevalence, and frequency of breakthrough infections in clinical drug trials. Detectability can be estimated by typing repeated samples from the same host but it has been unclear what should be the time interval between the samples and how the data should be analysed. Methods A longitudinal molecular study was conducted in the Kassena-Nankana district in northern Ghana. From each of the 80 participants, four finger prick samples were collected over a period of 8 days, and tested for presence of different Merozoite Surface Protein (msp) 2 genotypes. Implications for estimating q were derived from these data by comparing the fit of statistical models of serial dependence and over-dispersion. Results The distribution of the frequencies of detection for msp2 genotypes was close to binomial if the time span between consecutive blood samples was at least 7 days. For shorter intervals the probabilities of detection were positively correlated, i.e. the shorter the interval between two blood collections, the more likely the diagnostic results matched for a particular genotype. Estimates of q were rather insensitive to the statistical model fitted. Conclusions A simple algorithm based on analysing blood samples collected 7 days apart is justified for generating robust estimates of detectability. The finding of positive correlation of detection probabilities for short time intervals argues against imperfect detection being directly linked to the 48-hour periodicity of P. falciparum. The results suggest that the detectability of a given parasite clone changes over time, at an unknown rate, but fast enough to regard blood samples taken one week

  4. Do Managers Clone Themselves?

    ERIC Educational Resources Information Center

    Baron, Alma S.

    1981-01-01

    A recent questionnaire survey provides statistics on male managers' views of female managers. The author recommends that male managers break out of their cloning behavior and that the goal ought to be a plurality in management. (Author/WD)

  5. Statement on Human Cloning

    MedlinePlus

    ... form Search American Association for the Advancement of Science Statement on Human Cloning Print Email Tweet The American Association for the Advancement of Science (AAAS) recognizes the intense debates within our society ...

  6. Cancer

    MedlinePlus

    ... body. Cancerous cells are also called malignant cells. Causes Cancer grows out of cells in the body. Normal ... of many cancers remains unknown. The most common cause of cancer-related death is lung cancer. In the U.S., ...

  7. Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor

    PubMed Central

    Decker, Brennan; Davis, Brian W.; Rimbault, Maud; Long, Adrienne H.; Karlins, Eric; Jagannathan, Vidhya; Reiman, Rebecca; Parker, Heidi G.; Drögemüller, Cord; Corneveaux, Jason J.; Chapman, Erica S.; Trent, Jeffery M.; Leeb, Tosso; Huentelman, Matthew J.; Wayne, Robert K.; Karyadi, Danielle M.; Ostrander, Elaine A.

    2015-01-01

    Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world. PMID:26232412

  8. Occupational exposure to magnetic fields in relation to mortality from brain cancer among electricity generation and transmission workers.

    PubMed Central

    Harrington, J M; McBride, D I; Sorahan, T; Paddle, G M; van Tongeren, M

    1997-01-01

    OBJECTIVE: To investigate whether the risks of mortality from brain cancer are related to occupational exposure to magnetic fields. METHODS: A total of 112 cases of primary brain cancer (1972-91) were identified from a cohort of 84,018 male and female employees of the (then) Central Electricity Generating Board and its privatised successor companies. Individual cumulative occupational exposures to magnetic fields were estimated by linking available computerised job history data with magnetic field measurements collected over 675 person-workshifts. Estimated exposure histories of the case workers were compared with those of 654 control workers drawn from the cohort (nested case-control study), by means of conditional logistic regression. RESULTS: For exposure assessments based on arithmetic means, the risk of mortality from brain cancer for subjects with an estimated cumulative exposure to magnetic fields of 5.4-13.4 microT.y v subjects with lower exposures (0.0-5.3 microT.y) was 1.04 (95% confidence interval (95% CI) 0.60 to 1.80). The corresponding relative risk in subjects with higher exposures (> or = 13.5 microT.y) was 0.95 (95% CI 0.54 to 1.69). There was no indication of a positive trend for cumulative exposure and risk of mortality from brain cancer either when the analysis used exposure assessments based on geometric means or when the analysis was restricted to exposures received within five years of the case diagnosis (or corresponding period for controls). CONCLUSIONS: Although the exposure categorisation was based solely on recent observations, the study findings do not support the hypothesis that the risk of brain cancer is associated with occupational exposure to magnetic fields. PMID:9072027

  9. [Advances in Molecular Cloning].

    PubMed

    Ashwini, M; Murugan, S B; Balamurugan, S; Sathishkumar, R

    2016-01-01

    "Molecular cloning" meaning creation of recombinant DNA molecules has impelled advancement throughout life sciences. DNA manipulation has become easy due to powerful tools showing exponential growth in applications and sophistication of recombinant DNA technology. Cloning genes has become simple what led to an explosion in the understanding of gene function by seamlessly stitching together multiple DNA fragments or by the use of swappable gene cassettes, maximizing swiftness and litheness. A novel archetype might materialize in the near future with synthetic biology techniques that will facilitate quicker assembly and iteration of DNA clones, accelerating the progress of gene therapy vectors, recombinant protein production processes and new vaccines by in vitro chemical synthesis of any in silico-specified DNA construct. The advent of innovative cloning techniques has opened the door to more refined applications such as identification and mapping of epigenetic modifications and high-throughput assembly of combinatorial libraries. In this review, we will examine the major breakthroughs in cloning techniques and their applications in various areas of biological research that have evolved mainly due to easy construction of novel expression systems. PMID:27028806

  10. Extremal quantum cloning machines

    SciTech Connect

    Chiribella, G.; D'Ariano, G. M.; Perinotti, P.; Cerf, N.J.

    2005-10-15

    We investigate the problem of cloning a set of states that is invariant under the action of an irreducible group representation. We then characterize the cloners that are extremal in the convex set of group covariant cloning machines, among which one can restrict the search for optimal cloners. For a set of states that is invariant under the discrete Weyl-Heisenberg group, we show that all extremal cloners can be unitarily realized using the so-called double-Bell states, whence providing a general proof of the popular ansatz used in the literature for finding optimal cloners in a variety of settings. Our result can also be generalized to continuous-variable optimal cloning in infinite dimensions, where the covariance group is the customary Weyl-Heisenberg group of displacement000.

  11. Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer

    PubMed Central

    Scorilas, A; Kyriakopoulou, L; Katsaros, D; Diamandis, E P

    2001-01-01

    By using the positional cloning gene approach, we were able to identify a novel gene encoding for a serine/arginine-rich protein, which appears to be the human homologue of the rat A1 gene. We named this new gene SR-A1. Members of the SR family of proteins have been shown to interact with the C-terminal domain (CTD) of the large subunit of RNA polymerase II and participate in pre-mRNA splicing. We have localized the SR-A1 gene between the known genes IRF3 and RRAS on chromosome 19q13.3. The novel gene spans 16.7 kb of genomic sequence and it is formed of 11 exons and 10 intervening introns. The SR-A1 protein is composed of 1312 amino acids, with a molecular mass of 139.3 kDa and a theoretical isoelectric point of 9.31. The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins. Through interactions with the pre-mRNA and the CTD domain of the Polymerase II, SR proteins have been shown to regulate alternative splicing. The SR-A1 gene is expressed in all tissues tested, with highest levels found in fetal brain and fetal liver. Our data suggest that this gene is overexpressed in a subset of ovarian cancers which are clinically more aggressive. Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed. Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461075

  12. Secure the Clones

    NASA Astrophysics Data System (ADS)

    Jensen, Thomas; Kirchner, Florent; Pichardie, David

    Exchanging mutable data objects with untrusted code is a delicate matter because of the risk of creating a data space that is accessible by an attacker. Consequently, secure programming guidelines for Java stress the importance of using defensive copying before accepting or handing out references to an internal mutable object. However, implementation of a copy method (like clone()) is entirely left to the programmer. It may not provide a sufficiently deep copy of an object and is subject to overriding by a malicious sub-class. Currently no language-based mechanism supports secure object cloning. This paper proposes a type-based annotation system for defining modular copy policies for class-based object-oriented programs. A copy policy specifies the maximally allowed sharing between an object and its clone. We present a static enforcement mechanism that will guarantee that all classes fulfill their copy policy, even in the presence of overriding of copy methods, and establish the semantic correctness of the overall approach in Coq. The mechanism has been implemented and experimentally evaluated on clone methods from several Java libraries.

  13. Applications of quantum cloning

    NASA Astrophysics Data System (ADS)

    Pomarico, E.; Sanguinetti, B.; Sekatski, P.; Zbinden, H.; Gisin, N.

    2011-10-01

    Quantum Cloning Machines (QCMs) allow for the copying of information, within the limits imposed by quantum mechanics. These devices are particularly interesting in the high-gain regime, i.e., when one input qubit generates a state of many output qubits. In this regime, they allow for the study of certain aspects of the quantum to classical transition. The understanding of these aspects is the root of the two recent applications that we will review in this paper: the first one is the Quantum Cloning Radiometer, a device which is able to produce an absolute measure of spectral radiance. This device exploits the fact that in the quantum regime information can be copied with only finite fidelity, whereas when a state becomes macroscopic, this fidelity gradually increases to 1. Measuring the fidelity of the cloning operation then allows to precisely determine the absolute spectral radiance of the input optical source. We will then discuss whether a Quantum Cloning Machine could be used to produce a state visible by the naked human eye, and the possibility of a Bell Experiment with humans playing the role of detectors.

  14. The Cloning of America.

    ERIC Educational Resources Information Center

    Dobson, Judith E.; Dobson, Russell L.

    1981-01-01

    Proposes that the U.S. school system purports to prize human variability, but many educators are engaged in activities that seek to homogenize students. Describes these activities, including diagnosis, labeling, ability grouping, and positive reinforcement. Presents suggestions for counselors to combat sources of cloning and self-validation. (RC)

  15. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  16. Shingles Transmission

    MedlinePlus

    ... on Shingles Immunization Action Coalition Chickenpox Q&As Transmission Language: English Español (Spanish) Recommend on Facebook Tweet ... Prevention & Treatment Related Pages Preventing Varicella Zoster Virus Transmission in Healthcare Settings Related Links Medline Plus NIH ...

  17. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer

    PubMed Central

    Hu, Bo; Elinav, Eran; Huber, Samuel; Strowig, Till; Hao, Liming; Hafemann, Anja; Jin, Chengcheng; Wunderlich, Claudia; Wunderlich, Thomas; Eisenbarth, Stephanie C.; Flavell, Richard A.

    2013-01-01

    The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals. PMID:23696660

  18. The First Human Cloned Embryo.

    ERIC Educational Resources Information Center

    Cibelli, Jose B.; Lanza, Robert P.; West, Michael D.; Ezzell, Carol

    2002-01-01

    Describes a process known as parthenogenesis which produces cloned, early-stage embryos and human embryos generated only from eggs. Speculates that this technology puts therapeutic cloning within reach. (DDR)

  19. Introduction to cloning by nuclear transplantation.

    PubMed

    Galli, Cesare; Lagutina, Irina; Lazzari, Giovanna

    2003-01-01

    Despite its long history, the cloning of animals by nuclear transplantation is going through a "renaissance" after the birth of Dolly. The amount of work and achievements obtained in the last seven years are probably greater than those obtained in half a century of research. However, the principal obstacles outlined years ago with the work on somatic cell cloning in amphybia, are all still there in mammals. The importance of somatic cell nuclear transfer is, without any doubt, beyond the scope of replicating superior animal genotypes. It is an invaluable experimental tool to address fundamental scientific issues such as nuclear potency, cell de-differentiation, chromatin structure and function, epigenetics, and genome manipulation. For these reasons the importance of cloning is not for what it can achieve but for the technical support it can provide to biomedical research and in particular to the study of epigenetics, cancer and stem cell biology, cell therapy and regenerative medicine. In this introductory paper we will summarize the intellectual and technical framework of cloning animals by nuclear transfer that still remains the only absolute way of judging the success of the procedure. Together with the achievements of the recent past we will mention the very last developments and the many questions that still remain open. Current research efforts are expected to provide some answers and certainly new questions. PMID:14733742

  20. Probabilistic Cloning and Quantum Computation

    NASA Astrophysics Data System (ADS)

    Gao, Ting; Yan, Feng-Li; Wang, Zhi-Xi

    2004-06-01

    We discuss the usefulness of quantum cloning and present examples of quantum computation tasks for which the cloning offers an advantage which cannot be matched by any approach that does not resort to quantum cloning. In these quantum computations, we need to distribute quantum information contained in the states about which we have some partial information. To perform quantum computations, we use a state-dependent probabilistic quantum cloning procedure to distribute quantum information in the middle of a quantum computation.

  1. Recombinational Cloning Using Gateway and In-Fusion Cloning Schemes

    PubMed Central

    Throop, Andrea L.; LaBaer, Joshua

    2015-01-01

    The comprehensive study of protein structure and function, or proteomics, depends on the obtainability of full-length cDNAs in species-specific expression vectors and subsequent functional analysis of the expressed protein. Recombinational cloning is a universal cloning technique based on site-specific recombination that is independent of the insert DNA sequence of interest, which differentiates this method from the classical restriction enzyme-based cloning methods. Recombinational cloning enables rapid and efficient parallel transfer of DNA inserts into multiple expression systems. This unit summarizes strategies for generating expression-ready clones using the most popular recombinational cloning technologies, including the commercially available Gateway® (Life Technologies) and In-Fusion® (Clontech) cloning technologies. PMID:25827088

  2. Overlap extension PCR cloning.

    PubMed

    Bryksin, Anton; Matsumura, Ichiro

    2013-01-01

    Rising demand for recombinant proteins has motivated the development of efficient and reliable cloning methods. Here we show how a beginner can clone virtually any DNA insert into a plasmid of choice without the use of restriction endonucleases or T4 DNA ligase. Chimeric primers encoding plasmid sequence at the 5' ends and insert sequence at the 3' ends are designed and synthesized. Phusion(®) DNA polymerase is utilized to amplify the desired insert by PCR. The double-stranded product is subsequently employed as a pair of mega-primers in a PCR-like reaction with circular plasmids. The original plasmids are then destroyed in restriction digests with Dpn I. The product of the overlap extension PCR is used to transform competent Escherichia coli cells. Phusion(®) DNA polymerase is used for both the amplification and fusion reactions, so both steps can be monitored and optimized in the same way. PMID:23996437

  3. Cloning of murine ferrochelatase.

    PubMed Central

    Brenner, D A; Frasier, F

    1991-01-01

    Ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) catalyzes the last step in the heme biosynthetic pathway, the chelation of ferrous iron and protoporphyrin to form heme. The activity of ferrochelatase is deficient in the inherited disease protoporphyria. In this study, murine ferrochelatase cDNAs were obtained by screening cDNA libraries with an oligonucleotide probe. The derived amino acid sequence of murine ferrochelatase has 47% identity with the recently cloned Saccharomyces cerevisiae ferrochelatase, but it is not significantly similar to other published sequences. Results of Southern blotting are consistent with a single murine ferrochelatase gene, while Northern blotting demonstrates two ferrochelatase transcripts in all tissues examined. The ferrochelatase protein and mRNAs have different relative concentrations in different tissues. The cloning of murine ferrochelatase cDNAs provides the basis for future studies on ferrochelatase gene expression and on the identification of the molecular defect in protoporphyria. Images PMID:1704134

  4. Cloning-free CRISPR

    PubMed Central

    Arbab, Mandana; Srinivasan, Sharanya; Hashimoto, Tatsunori; Geijsen, Niels; Sherwood, Richard I.

    2015-01-01

    Summary We present self-cloning CRISPR/Cas9 (scCRISPR), a technology that allows for CRISPR/Cas9-mediated genomic mutation and site-specific knockin transgene creation within several hours by circumventing the need to clone a site-specific single-guide RNA (sgRNA) or knockin homology construct for each target locus. We introduce a self-cleaving palindromic sgRNA plasmid and a short double-stranded DNA sequence encoding the desired locus-specific sgRNA into target cells, allowing them to produce a locus-specific sgRNA plasmid through homologous recombination. scCRISPR enables efficient generation of gene knockouts (∼88% mutation rate) at approximately one-sixth the cost of plasmid-based sgRNA construction with only 2 hr of preparation for each targeted site. Additionally, we demonstrate efficient site-specific knockin of GFP transgenes without any plasmid cloning or genome-integrated selection cassette in mouse and human embryonic stem cells (2%–4% knockin rate) through PCR-based addition of short homology arms. scCRISPR substantially lowers the bar on mouse and human transgenesis. PMID:26527385

  5. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  6. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  7. Probabilistic cloning of equidistant states

    SciTech Connect

    Jimenez, O.; Roa, Luis; Delgado, A.

    2010-08-15

    We study the probabilistic cloning of equidistant states. These states are such that the inner product between them is a complex constant or its conjugate. Thereby, it is possible to study their cloning in a simple way. In particular, we are interested in the behavior of the cloning probability as a function of the phase of the overlap among the involved states. We show that for certain families of equidistant states Duan and Guo's cloning machine leads to cloning probabilities lower than the optimal unambiguous discrimination probability of equidistant states. We propose an alternative cloning machine whose cloning probability is higher than or equal to the optimal unambiguous discrimination probability for any family of equidistant states. Both machines achieve the same probability for equidistant states whose inner product is a positive real number.

  8. Ethical issues in livestock cloning.

    PubMed

    Thompson, P B

    1999-01-01

    Although cloning may eventually become an important technology for livestock production, four ethical issues must be addressed before the practice becomes widespread. First, researchers must establish that the procedure is not detrimental to the health or well-being of affected animals. Second, animal research institutions should evaluate the net social benefits to livestock producers by weighing the benefits to producers against the opportunity cost of research capacity lost to biomedical projects. Third, scientists should consider the indirect effects of cloning research on the larger ethical issues surrounding human cloning. Finally, the market structure for products of cloned animals should protect individual choice, and should recognize that many individuals find the prospect of cloning (or consuming cloned animals) repugnant. Analysis of these four issues is complicated by spurious arguments alleging that cloning will have a negative impact on environment and genetic diversity. PMID:15719505

  9. Cancer

    MedlinePlus

    ... your life Being exposed to chemicals that can cause cancer Being at risk for skin cancer Depending on ... than nonsmokers. Other forms of tobacco can also cause cancer, such as cigars, chewing tobacco and snuff. If ...

  10. To clone or not to clone--a Jewish perspective.

    PubMed Central

    Lipschutz, J H

    1999-01-01

    Many new reproductive methods such as artificial insemination, in vitro fertilisation, freezing of human embryos, and surrogate motherhood were at first widely condemned but are now seen in Western society as not just ethically and morally acceptable, but beneficial in that they allow otherwise infertile couples to have children. The idea of human cloning was also quickly condemned but debate is now emerging. This article examines cloning from a Jewish perspective and finds evidence to support the view that there is nothing inherently wrong with the idea of human cloning. A hypothesis is also advanced suggesting that even if a body was cloned, the brain, which is the essence of humanity, would remain unique. This author suggests that the debate should be changed from "Is cloning wrong?" to "When is cloning wrong?". PMID:10226913

  11. Cloning humans? Biological, ethical, and social considerations

    PubMed Central

    Ayala, Francisco J.

    2015-01-01

    There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits. PMID:26195738

  12. Cloning humans? Biological, ethical, and social considerations.

    PubMed

    Ayala, Francisco J

    2015-07-21

    There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits. PMID:26195738

  13. Transmission eigenvalues

    NASA Astrophysics Data System (ADS)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  14. Implementing a quantum cloning machine in separate cavities via the optical coherent pulse as a quantum communication bus

    NASA Astrophysics Data System (ADS)

    Zhu, Meng-Zheng; Ye, Liu

    2015-04-01

    An efficient scheme is proposed to implement a quantum cloning machine in separate cavities based on a hybrid interaction between electron-spin systems placed in the cavities and an optical coherent pulse. The coefficient of the output state for the present cloning machine is just the direct product of two trigonometric functions, which ensures that different types of quantum cloning machine can be achieved readily in the same framework by appropriately adjusting the rotated angles. The present scheme can implement optimal one-to-two symmetric (asymmetric) universal quantum cloning, optimal symmetric (asymmetric) phase-covariant cloning, optimal symmetric (asymmetric) real-state cloning, optimal one-to-three symmetric economical real-state cloning, and optimal symmetric cloning of qubits given by an arbitrary axisymmetric distribution. In addition, photon loss of the qubus beams during the transmission and decoherence effects caused by such a photon loss are investigated.

  15. Transmission eigenvalues

    NASA Astrophysics Data System (ADS)

    Cakoni, Fioralba; Haddar, Houssem

    2013-10-01

    In inverse scattering theory, transmission eigenvalues can be seen as the extension of the notion of resonant frequencies for impenetrable objects to the case of penetrable dielectrics. The transmission eigenvalue problem is a relatively late arrival to the spectral theory of partial differential equations. Its first appearance was in 1986 in a paper by Kirsch who was investigating the denseness of far-field patterns for scattering solutions of the Helmholtz equation or, in more modern terminology, the injectivity of the far-field operator [1]. The paper of Kirsch was soon followed by a more systematic study by Colton and Monk in the context of developing the dual space method for solving the inverse scattering problem for acoustic waves in an inhomogeneous medium [2]. In this paper they showed that for a spherically stratified media transmission eigenvalues existed and formed a discrete set. Numerical examples were also given showing that in principle transmission eigenvalues could be determined from the far-field data. This first period of interest in transmission eigenvalues was concluded with papers by Colton et al in 1989 [3] and Rynne and Sleeman in 1991 [4] showing that for an inhomogeneous medium (not necessarily spherically stratified) transmission eigenvalues, if they existed, formed a discrete set. For the next seventeen years transmission eigenvalues were ignored. This was mainly due to the fact that, with the introduction of various sampling methods to determine the shape of an inhomogeneous medium from far-field data, transmission eigenvalues were something to be avoided and hence the fact that transmission eigenvalues formed at most a discrete set was deemed to be sufficient. In addition, questions related to the existence of transmission eigenvalues or the structure of associated eigenvectors were recognized as being particularly difficult due to the nonlinearity of the eigenvalue problem and the special structure of the associated transmission

  16. AQUIFER TRANSMISSIVITY

    EPA Science Inventory

    Evaluation of groundwater resources requires the knowledge of the capacity of aquifers to store and transmit ground water. This requires estimates of key hydraulic parameters, such as the transmissivity, among others. The transmissivity T (m2/sec) is a hydrauli...

  17. Therapeutic cloning and reproductive liberty.

    PubMed

    Sparrow, Robert

    2009-04-01

    Concern for "reproductive liberty" suggests that decisions about embryos should normally be made by the persons who would be the genetic parents of the child that would be brought into existence if the embryo were brought to term. Therapeutic cloning would involve creating and destroying an embryo, which, if brought to term, would be the offspring of the genetic parents of the person undergoing therapy. I argue that central arguments in debates about parenthood and genetics therefore suggest that therapeutic cloning would be prima facie unethical unless it occurred with the consent of the parents of the person being cloned. Alternatively, if therapeutic cloning is thought to be legitimate, this undermines the case for some uses of reproductive cloning by implying that the genetic relation it establishes between clones and DNA donors does not carry the same moral weight as it does in cases of normal reproduction. PMID:19240247

  18. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  19. Human cloning and child welfare.

    PubMed Central

    Burley, J; Harris, J

    1999-01-01

    In this paper we discuss an objection to human cloning which appeals to the welfare of the child. This objection varies according to the sort of harm it is expected the clone will suffer. The three formulations of it that we will consider are: 1. Clones will be harmed by the fearful or prejudicial attitudes people may have about or towards them (H1); 2. Clones will be harmed by the demands and expectations of parents or genotype donors (H2); 3. Clones will be harmed by their own awareness of their origins, for example the knowledge that the genetic donor is a stranger (H3). We will show why these three versions of the child welfare objection do not necessarily supply compelling reasons to ban human reproductive cloning. The claim that we will develop and defend in the course of our discussion is that even if it is the case that a cloned child will suffer harms of the type H1-H3, it is none the less permissible to conceive by cloning so long as these cloning-induced welfare deficits are not such as to blight the existence of the resultant child, whoever this may be. PMID:10226914

  20. Identifying more epidemic clones during a hospital outbreak of multidrug-resistant Acinetobacter baumannii.

    PubMed

    Domenech de Cellès, Matthieu; Salomon, Jérôme; Marinier, Anne; Lawrence, Christine; Gaillard, Jean-Louis; Herrmann, Jean-Louis; Guillemot, Didier

    2012-01-01

    Infections caused by multidrug-resistant bacteria are a major concern in hospitals. Current infection-control practices legitimately focus on hygiene and appropriate use of antibiotics. However, little is known about the intrinsic abilities of some bacterial strains to cause outbreaks. They can be measured at a population level by the pathogen's transmission rate, i.e. the rate at which the pathogen is transmitted from colonized hosts to susceptible hosts, or its reproduction number, counting the number of secondary cases per infected/colonized host. We collected data covering a 20-month surveillance period for carriage of multidrug-resistant Acinetobacter baumannii (MDRAB) in a surgery ward. All isolates were subjected to molecular fingerprinting, and a cluster analysis of profiles was performed to identify clonal groups. We then applied stochastic transmission models to infer transmission rates of MDRAB and each MDRAB clone. Molecular fingerprinting indicated that 3 clonal complexes spread in the ward. A first model, not accounting for different clones, quantified the level of in-ward cross-transmission, with an estimated transmission rate of 0.03/day (95% credible interval [0.012-0.049]) and a single-admission reproduction number of 0.61 [0.30-1.02]. The second model, accounting for different clones, suggested an enhanced transmissibility of clone 3 (transmission rate 0.047/day [0.018-0.091], with a single-admission reproduction number of 0.81 [0.30-1.56]). Clones 1 and 2 had comparable transmission rates (respectively, 0.016 [0.001-0.045], 0.014 [0.001-0.045]). The method used is broadly applicable to other nosocomial pathogens, as long as surveillance data and genotyping information are available. Building on these results, more epidemic clones could be identified, and could lead to follow-up studies dissecting the functional basis for variation in transmissibility of MDRAB lineages. PMID:23029226

  1. Thymosin alpha1. SciClone Pharmaceuticals.

    PubMed

    Billich, Andreas

    2002-05-01

    Thymosin alpha1 (Talpha1), a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement, was originally developed by Alpha 1 Biomedicals for the treatment of hepatitis B virus (HBV) infection. SciClone developed and launched Talpha1, under the trade name Zadaxin, for the treatment of HBV and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of non-small cell lung cancer (NSCLC), hepatocellular carcinoma, AIDS and malignant melanoma. Talpha1 is able to potentiate the action of cytokines and also reduce the hematological toxicity of cytotoxic drug therapy (cyclophosphamide-, 5-fluorouracil-, dacarbazine- or ifosfamide-based regimens). These studies also demonstrated the mechanism of action of Talpha1 and its role as an immune system enhancer. By July 2001, it was in phase III trials in the US in combination with PEGylated interferon-alpha, and later the same month it was approved in the Philippines. SciClone received expanded approval for HBV and HCV infection in Mexico in July 2001. Talpha1 has been launched in Argentina, China, Peru, the Philippines and Singapore for the treatment of chronic HBV infection. The product subsequently received expanded approval for the treatment of both HBV and HCV infection in Argentina. Marketing approval was granted in India for HBV infection in February 2001. The company was working to expand this approval to include HCV infection. In March 2000, approval for treatment of HBV infection was granted in Thailand, Laos and Malta. Approval was also granted in Sri Lanka and Brunei in August 1999. In September 2000, SciClone announced that approval had been expanded to include the treatment of HCV infection as well as the previously approved HBV indication in both Peru and Sri Lanka. In January 1999, SciClone received approval for Talpha1 in Venezuela for the treatment of HBV and HCV infection. The company also filed a marketing

  2. [The discrete horror of cloning].

    PubMed

    Guibourg, Ricardo A

    2009-01-01

    The author raises the topic of cloning after the decision of the Argentine government, which concerned for the "dignity of the human person", passed a decree of need and urgency, No. 200/97 (Annex), prohibiting cloning experiments with human beings. Therefore, considering that the topic is so terribly urgent and necessary, the author feels it is timely to consider it. PMID:19860340

  3. Animal Cloning and Food Safety

    MedlinePlus

    ... from clones and their offspring out of the food chain until CVM could further evaluate the issue. back to top FDA Studies Cloning For more than five years, CVM ... evaluate the safety of food from these animals. The resulting report, called a ...

  4. CATO: The Clone Alignment Tool.

    PubMed

    Henstock, Peter V; LaPan, Peter

    2016-01-01

    High-throughput cloning efforts produce large numbers of sequences that need to be aligned, edited, compared with reference sequences, and organized as files and selected clones. Different pieces of software are typically required to perform each of these tasks. We have designed a single piece of software, CATO, the Clone Alignment Tool, that allows a user to align, evaluate, edit, and select clone sequences based on comparisons to reference sequences. The input and output are designed to be compatible with standard data formats, and thus suitable for integration into a clone processing pipeline. CATO provides both sequence alignment and visualizations to facilitate the analysis of cloning experiments. The alignment algorithm matches each of the relevant candidate sequences against each reference sequence. The visualization portion displays three levels of matching: 1) a top-level summary of the top candidate sequences aligned to each reference sequence, 2) a focused alignment view with the nucleotides of matched sequences displayed against one reference sequence, and 3) a pair-wise alignment of a single reference and candidate sequence pair. Users can select the minimum matching criteria for valid clones, edit or swap reference sequences, and export the results to a summary file as part of the high-throughput cloning workflow. PMID:27459605

  5. CATO: The Clone Alignment Tool

    PubMed Central

    Henstock, Peter V.; LaPan, Peter

    2016-01-01

    High-throughput cloning efforts produce large numbers of sequences that need to be aligned, edited, compared with reference sequences, and organized as files and selected clones. Different pieces of software are typically required to perform each of these tasks. We have designed a single piece of software, CATO, the Clone Alignment Tool, that allows a user to align, evaluate, edit, and select clone sequences based on comparisons to reference sequences. The input and output are designed to be compatible with standard data formats, and thus suitable for integration into a clone processing pipeline. CATO provides both sequence alignment and visualizations to facilitate the analysis of cloning experiments. The alignment algorithm matches each of the relevant candidate sequences against each reference sequence. The visualization portion displays three levels of matching: 1) a top-level summary of the top candidate sequences aligned to each reference sequence, 2) a focused alignment view with the nucleotides of matched sequences displayed against one reference sequence, and 3) a pair-wise alignment of a single reference and candidate sequence pair. Users can select the minimum matching criteria for valid clones, edit or swap reference sequences, and export the results to a summary file as part of the high-throughput cloning workflow. PMID:27459605

  6. Therapeutic cloning: promises and issues

    PubMed Central

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment of Parkinson’s disease, Duchenne muscular dystrophy, and diabetes mellitus as shown by in vivo studies. Scientific roadblocks impeding advancement in therapeutic cloning are tumorigenicity, epigenetic reprogramming, mitochondrial heteroplasmy, interspecies pathogen transfer, low oocyte availability. Therapeutic cloning is also often tied to ethical considerations concerning the source, destruction and moral status of IVF embryos based on the argument of potential. Legislative and funding issues are also addressed. Future considerations would include a distinction between therapeutic and reproductive cloning in legislative formulations. PMID:18523539

  7. Cancer

    MedlinePlus

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  8. Human cloning: can it be made safe?

    PubMed

    Rhind, Susan M; Taylor, Jane E; De Sousa, Paul A; King, Tim J; McGarry, Michelle; Wilmut, Ian

    2003-11-01

    There are continued claims of attempts to clone humans using nuclear transfer, despite the serious problems that have been encountered in cloning other mammals. It is known that epigenetic and genetic mechanisms are involved in clone failure, but we still do not know exactly how. Human reproductive cloning is unethical, but the production of cells from cloned embryos could offer many potential benefits. So, can human cloning be made safe? PMID:14634633

  9. Transmissible amyloid.

    PubMed

    Tjernberg, L O; Rising, A; Johansson, J; Jaudzems, K; Westermark, P

    2016-08-01

    There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. PMID:27002185

  10. Rotorcraft transmissions

    NASA Technical Reports Server (NTRS)

    Coy, John J.

    1990-01-01

    Highlighted here is that portion of the Lewis Research Center's helicopter propulsion systems program that deals with drive train technology and the related mechanical components. The major goals of the program are to increase life, reliability, and maintainability, to reduce weight, noise, and vibration, and to maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development, followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for transmission research in the future is presented.

  11. Seamless Ligation Cloning Extract (SLiCE) cloning method.

    PubMed

    Zhang, Yongwei; Werling, Uwe; Edelmann, Winfried

    2014-01-01

    SLiCE (Seamless Ligation Cloning Extract) is a novel cloning method that utilizes easy to generate bacterial cell extracts to assemble multiple DNA fragments into recombinant DNA molecules in a single in vitro recombination reaction. SLiCE overcomes the sequence limitations of traditional cloning methods, facilitates seamless cloning by recombining short end homologies (15-52 bp) with or without flanking heterologous sequences and provides an effective strategy for directional subcloning of DNA fragments from bacterial artificial chromosomes or other sources. SLiCE is highly cost-effective and demonstrates the versatility as a number of standard laboratory bacterial strains can serve as sources for SLiCE extract. We established a DH10B-derived E. coli strain expressing an optimized λ prophage Red recombination system, termed PPY, which facilitates SLiCE with very high efficiencies. PMID:24395368

  12. Methylotroph cloning vehicle

    DOEpatents

    Hanson, Richard S.; Allen, Larry N.

    1989-04-25

    A cloning vehicle comprising: a replication determinant effective for replicating the vehicle in a non-C.sub.1 -utilizing host and in a C.sub.1 -utilizing host; DNA effective to allow the vehicle to be mobilized from the non-C.sub.1 -utilizing host to the C.sub.1 -utilizing host; DNA providing resistance to two antibiotics to which the wild-type C.sub.1 -utilizing host is susceptible, each of the antibiotic resistance markers having a recognition site for a restriction endonuclease; a cos site; and a means for preventing replication in the C.sub.1 -utilizing host. The vehicle is used for complementation mapping as follows. DNA comprising a gene from the C.sub.1 -utilizing organism is inserted at the restriction nuclease recognition site, inactivating the antibiotic resistance marker at that site. The vehicle can then be used to form a cosmid structure to infect the non-C.sub.1 -utilizing (e.g., E. coli) host, and then conjugated with a selected C.sub.1 -utilizing mutant. Resistance to the other antibiotic by the mutant is a marker of the conjugation. Other phenotypical changes in the mutant, e.g., loss of an auxotrophic trait, is attributed to the C.sub.1 gene. The vector is also used to inactivate genes whose protein products catalyze side reactions that divert compounds from a biosynthetic pathway to a desired product, thereby producing an organism that makes the desired product in higher yields.

  13. Cloning of a quantum measurement

    SciTech Connect

    Bisio, Alessandro; D'Ariano, Giacomo Mauro; Perinotti, Paolo; Sedlak, Michal

    2011-10-15

    We analyze quantum algorithms for cloning of a quantum measurement. Our aim is to mimic two uses of a device performing an unknown von Neumann measurement with a single use of the device. When the unknown device has to be used before the bipartite state to be measured is available we talk about 1{yields}2 learning of the measurement, otherwise the task is called 1{yields}2 cloning of a measurement. We perform the optimization for both learning and cloning for arbitrary dimension d of the Hilbert space. For 1{yields}2 cloning we also propose a simple quantum network that achieves the optimal fidelity. The optimal fidelity for 1{yields}2 learning just slightly outperforms the estimate and prepare strategy in which one first estimates the unknown measurement and depending on the result suitably prepares the duplicate.

  14. A Clone of Your Own.

    ERIC Educational Resources Information Center

    Bilodeau, Kirsten

    1997-01-01

    Describes an activity used at the Washington Park Arboretum that helps students understand cloning through plant propagation. Students also learn how to make a pot from recycled newspapers and how to make soil that is appropriate for the plants. (DDR)

  15. Human Cloning: Let's Discuss It.

    ERIC Educational Resources Information Center

    Taras, Loretta; Stavroulakis, Anthea M.; Ortiz, Mary T.

    1999-01-01

    Describes experiences with holding discussions on cloning at a variety of levels in undergraduate biology courses. Discusses teaching methods used and student reactions to the discussions. Contains 12 references. (WRM)

  16. [Cancer].

    PubMed

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  17. Methylotroph cloning vehicle

    DOEpatents

    Hanson, R.S.; Allen, L.N.

    1989-04-25

    A cloning vehicle comprising: a replication determinant effective for replicating the vehicle in a non-C[sub 1]-utilizing host and in a C[sub 1]-utilizing host; DNA effective to allow the vehicle to be mobilized from the non-C[sub 1]-utilizing host to the C[sub 1]-utilizing host; DNA providing resistance to two antibiotics to which the wild-type C[sub 1]-utilizing host is susceptible, each of the antibiotic resistance markers having a recognition site for a restriction endonuclease; a cos site; and a means for preventing replication in the C[sub 1]-utilizing host. The vehicle is used for complementation mapping as follows. DNA comprising a gene from the C[sub 1]-utilizing organism is inserted at the restriction nuclease recognition site, inactivating the antibiotic resistance marker at that site. The vehicle can then be used to form a cosmid structure to infect the non-C[sub 1]-utilizing (e.g., E. coli) host, and then conjugated with a selected C[sub 1]-utilizing mutant. Resistance to the other antibiotic by the mutant is a marker of the conjugation. Other phenotypical changes in the mutant, e.g., loss of an auxotrophic trait, is attributed to the C[sub 1] gene. The vector is also used to inactivate genes whose protein products catalyze side reactions that divert compounds from a biosynthetic pathway to a desired product, thereby producing an organism that makes the desired product in higher yields. 3 figs.

  18. Local cloning of entangled qubits

    SciTech Connect

    Choudhary, Sujit K.; Kunkri, Samir; Rahaman, Ramij; Roy, Anirban

    2007-11-15

    We discuss the exact cloning of orthogonal but entangled qubits under local operations and classical communication. The amount of entanglement necessary in a blank copy is obtained for various cases. Surprisingly, this amount is more than 1 ebit for certain sets of two nonmaximal but equally entangled states of two qubits. To clone any three Bell states, at least log{sub 2} 3 ebit is necessary.

  19. Artificial cloning of domestic animals.

    PubMed

    Keefer, Carol L

    2015-07-21

    Domestic animals can be cloned using techniques such as embryo splitting and nuclear transfer to produce genetically identical individuals. Although embryo splitting is limited to the production of only a few identical individuals, nuclear transfer of donor nuclei into recipient oocytes, whose own nuclear DNA has been removed, can result in large numbers of identical individuals. Moreover, clones can be produced using donor cells from sterile animals, such as steers and geldings, and, unlike their genetic source, these clones are fertile. In reality, due to low efficiencies and the high costs of cloning domestic species, only a limited number of identical individuals are generally produced, and these clones are primarily used as breed stock. In addition to providing a means of rescuing and propagating valuable genetics, somatic cell nuclear transfer (SCNT) research has contributed knowledge that has led to the direct reprogramming of cells (e.g., to induce pluripotent stem cells) and a better understanding of epigenetic regulation during embryonic development. In this review, I provide a broad overview of the historical development of cloning in domestic animals, of its application to the propagation of livestock and transgenic animal production, and of its scientific promise for advancing basic research. PMID:26195770

  20. Artificial cloning of domestic animals

    PubMed Central

    Keefer, Carol L.

    2015-01-01

    Domestic animals can be cloned using techniques such as embryo splitting and nuclear transfer to produce genetically identical individuals. Although embryo splitting is limited to the production of only a few identical individuals, nuclear transfer of donor nuclei into recipient oocytes, whose own nuclear DNA has been removed, can result in large numbers of identical individuals. Moreover, clones can be produced using donor cells from sterile animals, such as steers and geldings, and, unlike their genetic source, these clones are fertile. In reality, due to low efficiencies and the high costs of cloning domestic species, only a limited number of identical individuals are generally produced, and these clones are primarily used as breed stock. In addition to providing a means of rescuing and propagating valuable genetics, somatic cell nuclear transfer (SCNT) research has contributed knowledge that has led to the direct reprogramming of cells (e.g., to induce pluripotent stem cells) and a better understanding of epigenetic regulation during embryonic development. In this review, I provide a broad overview of the historical development of cloning in domestic animals, of its application to the propagation of livestock and transgenic animal production, and of its scientific promise for advancing basic research. PMID:26195770

  1. Islamic perspectives on human cloning.

    PubMed

    Sadeghi, Mahmoud

    2007-01-01

    The present paper seeks to assess various views from Islamic jurists relating to human cloning, which is one of the controversial topics in the recent past. Taking Islamic jurisprudence principles, such as the rule of necessity for self preservation and respect for human beings, the rule of la darar wa la dirar ('the necessity to refrain from causing harm to oneself and others') and the rule of usr wa haraj, one may indicate that if human cloning could not be prohibited, as such, it could still be opposed because it gives way to various harmful consequences, which include family disorder, chaos in the clone's family relationships, physical and mental diseases for clones and suffering of egg donors and surrogate mothers. However with due attention to the fact that the reasons behind the prohibition of abortion only restrict the destruction of human embryos in their post-implantation stages, human cloning for biomedical research and exploitation of stem cells from cloned embryos at the blastocyst stage for therapeutic purposes would be acceptable. PMID:17966502

  2. Cloning goes to the movies.

    PubMed

    Cormick, Craig

    2006-10-01

    Public attitude research conducted by Biotechnology Australia shows that one of the major sources of information on human reproductive cloning is movies. Traditionally, understanding of new and emerging technologies has come through the mass media but human cloning, being so widely addressed through the popular culture of movies, is more effectively defined by Hollywood than the news media or science media. But how well are the science and social issues of cloning portrayed in box office hits such as The Island, Multiplicity, Star Wars: Attack of the Clones and Jurassic Park? These movies have enormous reach and undoubted influence, and are therefore worth analyzing in some detail. This study looks at 33 movies made between 1971 and 2005 that address human reproductive cloning, and it categorizes the films based on their genre and potential influence. Yet rather than simply rating the quality of the science portrayed, the study compares the key messages in these movies with public attitudes towards cloning, to examine the correlations. PMID:17214211

  3. Characterization of sphere-forming HCT116 clones by whole RNA sequencing

    PubMed Central

    Chung, Eunkyung; Oh, Inkyung

    2016-01-01

    Purpose To determine CD133+ cells defined as cancer stem cells (CSCs) in colon cancer, we examined whether CD133+ clones in HCT116 demonstrate known features of CSCs like sphere-forming ability, chemodrug-resistance, and metastatic potential. Methods Magnetic cell isolation and cell separation demonstrated that <1% of HCT116 cells expressed CD133, with the remaining cells being CD133- clones. In colon cancer cells, radioresistance is also considered a CSC characteristic. We performed clonogenic assay using 0.4 Gy γ-irradiation. Results Interestingly, there were no differences between HCT116 parental and HCT116 CD133+ clones when the cells comprised 0.5% of the total cells, and CD133- clone demonstrated radiosensitive changes compared with parental and CD133+ clones. Comparing gene expression profiles between sphere-forming and nonforming culture conditions of HCT116 subclones by whole RNA sequencing failed to obtain specific genes expressed in CD133+ clones. Conclusion Despite no differences of gene expression profiles in monolayer attached culture conditions of each clone, sphere-forming conditions of whole HCT116 subclones, parental, CD133+, and CD133- increased 1,761 coding genes and downregulated 1,384 genes related to CSCs self-renewal and survival. Thus, spheroid cultures of HCT116 cells could be useful to expand colorectal CSCs rather than clonal expansion depending on CD133 expressions. PMID:27073788

  4. Rotorcraft transmission

    NASA Technical Reports Server (NTRS)

    Coy, John J.

    1987-01-01

    The NASA Lewis Research Center and the U.S. Army Aviation Systems Command share an interest in advancing the technology for helicopter propulsion systems. In particular, this presentation outlines that portion of the program that applies to the drive train and its various mechanical components. The major goals of the program are to increase the life, reliability, and maintainability; reduce the weight, noise, and vibration; and maintain the relatively high mechanical efficiency of the gear train. The current activity emphasizes noise reduction technology and analytical code development followed by experimental verification. Selected significant advances in technology for transmissions are reviewed, including advanced configurations and new analytical tools. Finally, the plan for transmission research in the future is presented.

  5. Imperfect Cloning Operations in Algebraic Quantum Theory

    NASA Astrophysics Data System (ADS)

    Kitajima, Yuichiro

    2015-01-01

    No-cloning theorem says that there is no unitary operation that makes perfect clones of non-orthogonal quantum states. The objective of the present paper is to examine whether an imperfect cloning operation exists or not in a C*-algebraic framework. We define a universal -imperfect cloning operation which tolerates a finite loss of fidelity in the cloned state, and show that an individual system's algebra of observables is abelian if and only if there is a universal -imperfect cloning operation in the case where the loss of fidelity is less than . Therefore in this case no universal -imperfect cloning operation is possible in algebraic quantum theory.

  6. Loss of genomic imprinting in Drosophila clones.

    PubMed

    Haigh, Andrew J; Lloyd, Vett K

    2006-08-01

    Genomic imprinting is a process that genetically distinguishes maternal and paternal genomes, and can result in parent-of-origin-dependent monoallelic expression of a gene that is dependent on the parent of origin. As such, an otherwise functional maternally inherited allele may be silenced so that the gene is expressed exclusively from the paternal allele, or vice versa. Once thought to be restricted to mammals, genomic imprinting has been documented in angiosperm plants (J.L. Kermicle. 1970. Genetics, 66: 69-85), zebrafish (C.C. Martin and R. McGowan. 1995. Genet. Res. 65: 21-28), insects, and C. elegans (C.J. Bean, C.E. Schaner, and W.G. Kelly. 2004. Nat. Genet. 36: 100-105.). In each case, it appears to rely on differential chromatin structure. Aberrant imprinting has been implicated in various human cancers and has been detected in a number of cloned mammals, potentially limiting the usefulness of somatic nuclear transfer. Here we show that genomic imprinting associated with a mini-X chromosome is lost in Drosophila melanogaster clones. PMID:17036079

  7. Local cloning of entangled states

    SciTech Connect

    Gheorghiu, Vlad; Yu Li; Cohen, Scott M.

    2010-08-15

    We investigate the conditions under which a set S of pure bipartite quantum states on a DxD system can be locally cloned deterministically by separable operations, when at least one of the states is full Schmidt rank. We allow for the possibility of cloning using a resource state that is less than maximally entangled. Our results include that: (i) all states in S must be full Schmidt rank and equally entangled under the G-concurrence measure, and (ii) the set S can be extended to a larger clonable set generated by a finite group G of order |G|=N, the number of states in the larger set. It is then shown that any local cloning apparatus is capable of cloning a number of states that divides D exactly. We provide a complete solution for two central problems in local cloning, giving necessary and sufficient conditions for (i) when a set of maximally entangled states can be locally cloned, valid for all D; and (ii) local cloning of entangled qubit states with nonvanishing entanglement. In both of these cases, we show that a maximally entangled resource is necessary and sufficient, and the states must be related to each other by local unitary 'shift' operations. These shifts are determined by the group structure, so need not be simple cyclic permutations. Assuming this shifted form and partially entangled states, then in D=3 we show that a maximally entangled resource is again necessary and sufficient, while for higher-dimensional systems, we find that the resource state must be strictly more entangled than the states in S. All of our necessary conditions for separable operations are also necessary conditions for local operations and classical communication (LOCC), since the latter is a proper subset of the former. In fact, all our results hold for LOCC, as our sufficient conditions are demonstrated for LOCC, directly.

  8. Local cloning of two product states

    SciTech Connect

    Ji Zhengfeng; Feng Yuan; Ying Mingsheng

    2005-09-15

    Local quantum operations and classical communication (LOCC) put considerable constraints on many quantum information processing tasks such as cloning and discrimination. Surprisingly, however, discrimination of any two pure states survives such constraints in some sense. We show that cloning is not that lucky; namely, probabilistic LOCC cloning of two product states is strictly less efficient than global cloning. We prove our result by giving explicitly the efficiency formula of local cloning of any two product states.

  9. [Cloning and law in Hungary].

    PubMed

    Julesz, Máté

    2015-03-01

    Reproductive human cloning is prohibited in Hungary, as in many other countries. Therapeutic human cloning is not prohibited, just like in many other countries. Stem cell therapy is also allowed. Article III, paragraph (3) of the Hungarian basic law (constitution) strictly forbids total human cloning. Article 1 of the Additional Protocol to the Oviedo Convention, on the Prohibition of Cloning Human Beings (1998) stipulates that any intervention seeking to create a human being genetically identical to another human being, whether living or dead, is prohibited. In Hungary, according to Article 174 of the Criminal Code, total human cloning constitutes a crime. Article 180, paragraph (3) of the Hungarian Act on Health declares that embryos shall not be brought about for research purposes; research shall be conducted only on embryos brought about for reproductive purposes when this is authorized by the persons entitled to decide upon its disposal, or when the embryo is damaged. Article 180, paragraph (5) of the Hungarian Act on Health stipulates that multiple individuals who genetically conform to one another shall not be brought about. According to Article 181, paragraph (1) of the Hungarian Act on Health, an embryo used for research shall be kept alive for not longer than 14 days, not counting the time it was frozen for storage and the time period of research. PMID:25749537

  10. Cell cloning-on-the-spot by using an attachable silicone cylinder.

    PubMed

    Park, Hong Bum; Son, Wonseok; Chae, Dong Han; Lee, Jisu; Kim, Il-Woung; Yang, Woomi; Sung, Jae Kyu; Lim, Kyu; Lee, Jun Hee; Kim, Kyung-Hee; Park, Jong-Il

    2016-06-10

    Cell cloning is a laboratory routine to isolate and keep particular properties of cultured cells. Transfected or other genetically modified cells can be selected by the traditional microbiological cloning. In addition, common laboratory cell lines are prone to genotypic drift during their continual culture, so that supplementary cloning steps are often required to maintain correct lineage phenotypes. Here, we designed a silicone-made attachable cloning cylinder, which facilitated an easy and bona fide cloning of interested cells. This silicone cylinder was easy to make, showed competent stickiness to laboratory plastics including culture dishes, and hence enabled secure isolation and culture for days of selected single cells, especially, on the spots of preceding cell-plating dishes under microscopic examination of visible cellular phenotypes. We tested the silicone cylinder in the monoclonal subcloning from a heterogeneous population of a breast cancer cell line, MDA-MB-231, and readily established independent MDA-MB-231 subclones showing different sublineage phenotypes. PMID:27169766

  11. Vented transmission

    SciTech Connect

    Nguyen, T.H.

    1990-01-29

    This patent describes a vented transmission. It comprises: a housing; a rotary input to the housing; a rotary output from the housing; transmission means within the housing interconnecting the input and the output and including a hollow, rotary shaft journaled within the housing; a vent tube having a first end extending into one end of the hollow shaft and a second end in fluid communication with the exterior of the housing; a shoulder within the hollow shaft and intermediate the ends of the vent tube and defining of relatively smaller diameter section near the first end of the vent tube that is within the hollow shaft and a relatively large diameter section nearer the second end of the vent tube; at least one aperture extending through the hollow shaft from the large diameter section immediately adjacent the shoulder; and a labyrinth seal at the interface of the vent tube and the large diameter section at a location between the aperture (s) and the second end of the vent tube.

  12. Quantum cloning machines and the applications

    NASA Astrophysics Data System (ADS)

    Fan, Heng; Wang, Yi-Nan; Jing, Li; Yue, Jie-Dong; Shi, Han-Duo; Zhang, Yong-Liang; Mu, Liang-Zhu

    2014-11-01

    No-cloning theorem is fundamental for quantum mechanics and for quantum information science that states an unknown quantum state cannot be cloned perfectly. However, we can try to clone a quantum state approximately with the optimal fidelity, or instead, we can try to clone it perfectly with the largest probability. Thus various quantum cloning machines have been designed for different quantum information protocols. Specifically, quantum cloning machines can be designed to analyze the security of quantum key distribution protocols such as BB84 protocol, six-state protocol, B92 protocol and their generalizations. Some well-known quantum cloning machines include universal quantum cloning machine, phase-covariant cloning machine, the asymmetric quantum cloning machine and the probabilistic quantum cloning machine. In the past years, much progress has been made in studying quantum cloning machines and their applications and implementations, both theoretically and experimentally. In this review, we will give a complete description of those important developments about quantum cloning and some related topics. On the other hand, this review is self-consistent, and in particular, we try to present some detailed formulations so that further study can be taken based on those results.

  13. Healthy ageing of cloned sheep

    PubMed Central

    Sinclair, K. D.; Corr, S. A.; Gutierrez, C. G.; Fisher, P. A.; Lee, J.-H.; Rathbone, A. J.; Choi, I.; Campbell, K. H. S.; Gardner, D. S.

    2016-01-01

    The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental long-term health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7–9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5-and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals. PMID:27459299

  14. Clone Poems and the Microcomputer.

    ERIC Educational Resources Information Center

    Irizarry, Estelle

    1989-01-01

    Describes how students can use the computer to study and create clone poems (altering original Spanish-language poems by substituting words and expressions), and how students can gain a deeper appreciation of the original poem's poetic structure and semantics. (CB)

  15. PlasmID: a centralized repository for plasmid clone information and distribution

    PubMed Central

    Zuo, Dongmei; Mohr, Stephanie E.; Hu, Yanhui; Taycher, Elena; Rolfs, Andreas; Kramer, Jason; Williamson, Janice; LaBaer, Joshua

    2007-01-01

    The Plasmid Information Database (PlasmID; ) was developed as a community-based resource portal to facilitate search and request of plasmid clones shared with the Dana-Farber/Harvard Cancer Center (DF/HCC) DNA Resource Core. PlasmID serves as a central data repository and enables researchers to search the collection online using common gene names and identifiers, keywords, vector features, author names and PubMed IDs. As of October 2006, the repository contains >46 000 plasmids in 98 different vectors, including cloned cDNA and genomic fragments from 26 different species. Moreover, the clones include plasmid vectors useful for routine and cutting-edge techniques; functionally related sets of human cDNA clones; and genome-scale gene collections for Saccharomyces cerevisiae, Pseudomonas aeruginosa, Yersinia pestis, Francisella tularensis, Bacillus anthracis and Vibrio cholerae. Information about the plasmids has been fully annotated in adherence with a high-quality standard, and clone samples are stored as glycerol stocks in a state-of-the-art automated −80°C freezer storage system. Clone replication and distribution is highly automated to minimize human error. Infor-mation about vectors and plasmid clones, including downloadable maps and sequence data, is freely available online. Researchers interested in requesting clone samples or sharing their own plasmids with the repository can visit the PlasmID website for more information. PMID:17132831

  16. Contagious cancer.

    PubMed

    Welsh, James S

    2011-01-01

    Although cancer can on occasion be caused by infectious agents such as specific bacteria, parasites, and viruses, it is not generally considered a transmissible disease. In rare circumstances, however, direct communication from one host to another has been documented. The Tasmanian devil is now threatened with extinction in the wild because of a fatal transmissible cancer, devil facial tumor disease (DFTD). Another example is canine transmissible venereal tumor (CTVT or Sticker's sarcoma) in dogs. There is a vast difference in prognosis between these two conditions. DFTD is often fatal within 6 months, whereas most cases of CTVT are eventually rejected by the host dog, who then is conferred lifelong immunity. In man, only scattered case reports exist about such communicable cancers, most often in the setting of organ or hematopoietic stem cell transplants and cancers arising during pregnancy that are transmitted to the fetus. In about one third of cases, transplant recipients develop cancers from donor organs from individuals who were found to harbor malignancies after the transplantation. The fact that two thirds of the time cancer does not develop, along with the fact that cancer very rarely is transmitted from person to person, supports the notion that natural immunity prevents such cancers from taking hold in man. These observations might hold invaluable clues to the immunobiology and possible immunotherapy of cancer. PMID:21212437

  17. Hydromechanical transmission

    DOEpatents

    Orshansky, Jr. deceased, Elias; Weseloh, William E.

    1978-01-01

    A power transmission having three planetary assemblies, each having its own carrier and its own planet, sun, and ring gears. A speed-varying module is connected in driving relation to the input shaft and in driving relationship to the three sun gears, all of which are connected together. The speed-varying means may comprise a pair of hydraulic units hydraulically interconnected so that one serves as a pump while the other serves as a motor and vice versa, one of the units having a variable stroke and being connected in driving relation to the input shaft, the other unit, which may have a fixed stroke, being connected in driving relation to the sun gears. The input shaft also drives the carrier of the third planetary assembly. A brake grounds the first carrier in the first range and in reverse and causes drive to be delivered to the output through the first ring gear in a hydrostatic mode. The carrier of the third planetary assembly drives the ring gear of the second planetary assembly, and a first clutching means connects the second carrier with the output in a second range, the brake for grounding the first carrier then being released. A second clutching means enables the third ring gear to drive the output shaft in a third range.

  18. Phase-covariant quantum cloning of qudits

    SciTech Connect

    Fan Heng; Imai, Hiroshi; Matsumoto, Keiji; Wang, Xiang-Bin

    2003-02-01

    We study the phase-covariant quantum cloning machine for qudits, i.e., the input states in a d-level quantum system have complex coefficients with arbitrary phase but constant module. A cloning unitary transformation is proposed. After optimizing the fidelity between input state and single qudit reduced density operator of output state, we obtain the optimal fidelity for 1 to 2 phase-covariant quantum cloning of qudits and the corresponding cloning transformation.

  19. Probabilistic cloning of three symmetric states

    SciTech Connect

    Jimenez, O.; Bergou, J.; Delgado, A.

    2010-12-15

    We study the probabilistic cloning of three symmetric states. These states are defined by a single complex quantity, the inner product among them. We show that three different probabilistic cloning machines are necessary to optimally clone all possible families of three symmetric states. We also show that the optimal cloning probability of generating M copies out of one original can be cast as the quotient between the success probability of unambiguously discriminating one and M copies of symmetric states.

  20. Economical phase-covariant cloning of qudits

    SciTech Connect

    Buscemi, Francesco; D'Ariano, Giacomo Mauro; Macchiavello, Chiara

    2005-04-01

    We derive the optimal N{yields}M phase-covariant quantum cloning for equatorial states in dimension d with M=kd+N, k integer. The cloning maps are optimal for both global and single-qudit fidelity. The map is achieved by an 'economical' cloning machine, which works without ancilla.

  1. Local cloning of arbitrarily entangled multipartite states

    SciTech Connect

    Kay, Alastair; Ericsson, Marie

    2006-01-15

    We examine the perfect cloning of nonlocal, orthogonal states using only local operations and classical communication. We provide a complete characterisation of the states that can be cloned under these restrictions, and their relation to distinguishability. We also consider the case of catalytic cloning, which we show provides no enhancement to the set of clonable states.

  2. Cloning of the human DNA methyltransferase gene

    SciTech Connect

    Ramchanani, S.K.; Rouleau, J.; Szyf, M.

    1994-09-01

    During the process of carcinogenesis it has been observed that DNA methylation is deregulated. At least two levels of regulation of the mouse DNA MeTase have been shown: at the transcriptional level, via its promoter, and at the post transcriptional level in a cell cycle dependent fashion. The sequence of the complete DNA MeTase gene and identification of the promoter has not yet been reported. Using a probe generated by PCR of the human DNA MeTase cDNA, a human genomic library was screened and a clone of approximately 22 kilobases (kb) was isolated. It was found that this clone contains the complete coding sequence of the DNA MeTase enzyme. Sequence analysis along with restriction enzyme digests have allowed us to construct a partial map of the physical structure of the human DNA MeTase gene. This partial structure has already revealed some interesting aspects related to the genetic evolution of the human DNA MeTase. First, the proposed catalytic domain of the human DNA MeTase is extremely homologous to all other cytosine DNA MeTases, even to those that are found in bacteria, and this catalytic domain is conserved within one complete exon in the human gene. This is very different from the structure of the 5{prime} region of the gene, which is fragmented into numerous little introns and exons. Within one of the small introns that have been identified, a trinucleotide repeat of ATG occurs (9 times in a row), and this repeat is upstream of the proposed start site of translation. Trinucleotide repeat expansion has been shown to be a genetic hot spot for mutation, but even more interesting is the nature of the repeat, ATG, which is the translation start codon; this repeat appears to be in frame with the {open_quotes}normal{close_quotes} coding sequence, the implications being that possible alternative methyltransferases may be translated under certain conditions such as cancer.

  3. Automatic transmission

    SciTech Connect

    Miura, M.; Inuzuka, T.

    1986-08-26

    1. An automatic transmission with four forward speeds and one reverse position, is described which consists of: an input shaft; an output member; first and second planetary gear sets each having a sun gear, a ring gear and a carrier supporting a pinion in mesh with the sun gear and ring gear; the carrier of the first gear set, the ring gear of the second gear set and the output member all being connected; the ring gear of the first gear set connected to the carrier of the second gear set; a first clutch means for selectively connecting the input shaft to the sun gear of the first gear set, including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a second clutch means for selectively connecting the input shaft to the sun gear of the second gear set a third clutch means for selectively connecting the input shaft to the carrier of the second gear set including friction elements, a piston selectively engaging the friction elements and a fluid servo in which hydraulic fluid is selectively supplied to the piston; a first drive-establishing means for selectively preventing rotation of the ring gear of the first gear set and the carrier of the second gear set in only one direction and, alternatively, in any direction; a second drive-establishing means for selectively preventing rotation of the sun gear of the second gear set; and a drum being open to the first planetary gear set, with a cylindrical intermediate wall, an inner peripheral wall and outer peripheral wall and forming the hydraulic servos of the first and third clutch means between the intermediate wall and the inner peripheral wall and between the intermediate wall and the outer peripheral wall respectively.

  4. Therapeutic cloning and tissue engineering.

    PubMed

    Koh, Chester J; Atala, Anthony

    2004-01-01

    A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. PMID:15094294

  5. Antioncogenes and human cancer.

    PubMed Central

    Knudson, A G

    1993-01-01

    The antioncogenes, or tumor suppressor genes, as negative regulators of cell division, stand in contrast to oncogenes. For most human cancers, the more frequently mutated genes are the antioncogenes, the principal exception being the leukemias and lymphomas. Persons heterozygous for germ-line mutations in antioncogenes are strongly predisposed to one or more kinds of cancer, and most dominantly inherited cancer is attributable to such heterozygosity. Seven antioncogenes have been cloned through the study of these persons, and several others have been mapped. An eighth one was mapped and cloned through the investigation of tumors and is not yet known in hereditary form. Three dominantly inherited forms of cancer are not attributable to mutations in antioncogenes. The corresponding nonhereditary forms of most cancers generally reveal abnormalities of the same antioncogenes that are found in the hereditary forms but may also show additional ones. Some cancers, especially the embryonal tumors of children, have a small number of antioncogene mutations; some others, such as most sarcomas, have more, and the common carcinomas have the most, reflecting a hierarchy of controls over growth of stem cell populations. Still more members of this gene category remain to be mapped and cloned through the study of cancer families and of tumors. The genes that have been cloned act at diverse points in the signal transduction pathway in cells, from the outer cell membranes to sites of gene transcription, in some cases as negative regulators of oncogene expression. PMID:7902574

  6. Optimal quantum cloning via spin networks

    SciTech Connect

    Chen Qing; Cheng Jianhua; Wang Kelin; Du Jiangfeng

    2006-09-15

    In this paper we demonstrate that optimal 1{yields}M phase-covariant cloning quantum cloning is available via free dynamical evolution of spin networks. By properly designing the network and the couplings between spins, we show that optimal 1{yields}M phase-covariant cloning can be achieved if the initial state is prepared as a specific symmetric state. Especially, when M is an odd number, the optimal phase-covariant cloning can be achieved without ancillas. Moreover, we demonstrate that the same framework is capable for optimal 1{yields}2 universal cloning.

  7. No-cloning theorem on quantum logics

    SciTech Connect

    Miyadera, Takayuki; Imai, Hideki

    2009-10-15

    This paper discusses the no-cloning theorem in a logicoalgebraic approach. In this approach, an orthoalgebra is considered as a general structure for propositions in a physical theory. We proved that an orthoalgebra admits cloning operation if and only if it is a Boolean algebra. That is, only classical theory admits the cloning of states. If unsharp propositions are to be included in the theory, then a notion of effect algebra is considered. We proved that an atomic Archimedean effect algebra admitting cloning operation is a Boolean algebra. This paper also presents a partial result, indicating a relation between the cloning on effect algebras and hidden variables.

  8. Probabilistic cloning of three nonorthogonal states

    NASA Astrophysics Data System (ADS)

    Zhang, Wen; Rui, Pinshu; Yang, Qun; Zhao, Yan; Zhang, Ziyun

    2015-04-01

    We study the probabilistic cloning of three nonorthogonal states with equal success probabilities. For simplicity, we assume that the three states belong to a special set. Analytical form of the maximal success probability for probabilistic cloning is calculated. With the maximal success probability, we deduce the explicit form of probabilistic quantum cloning machine. In the case of cloning, we get the unambiguous form of the unitary operation. It is demonstrated that the upper bound for probabilistic quantum cloning machine in (Qiu in J Phys A 35:6931, 2002) can be reached only if the three states are equidistant.

  9. [The identification of mouse cloned SFA DNA].

    PubMed

    Yi, Ning; Wu, Weng Qing; Ni, Zu Mei; Shi, Lu Ji

    2002-12-01

    For some basic investigation and the construction of artificial chromosomes, cloned centromeric DNAs identified on a firm ground are required. Thus, in the present work a preliminary screened clone of 13.5 kb DNA, 6# clone, form a mouse centromeric library contructed previously in our library was futher investigated by FISH and PCR. It was found that mouse 6# cloned SFA DNA, as shown by FISH is a fragment of mouse centromeric DNA. Evidence was also observed that 6# cloned SFA DNA consists of mouse minor satellite DNA and other DNA sequences. PMID:15346991

  10. Dielectrophoretic separation of mouse melanoma clones

    PubMed Central

    Sabuncu, Ahmet C.; Liu, Jie A.; Beebe, Stephen J.; Beskok, Ali

    2010-01-01

    Dielectrophoresis (DEP) is employed to differentiate clones of mouse melanoma B16F10 cells. Five clones were tested on microelectrodes. At a specific excitation frequency, clone 1 showed a different DEP response than the other four. Growth rate, melanin content, recovery from cryopreservation, and in vitro invasive studies were performed. Clone 1 is shown to have significantly different melanin content and recovery rate from cryopreservation. This paper reports the ability of DEP to differentiate between two malignant cells of the same origin. Different DEP responses of the two clones could be linked to their melanin content. PMID:20697600

  11. No-cloning theorem on quantum logics

    NASA Astrophysics Data System (ADS)

    Miyadera, Takayuki; Imai, Hideki

    2009-10-01

    This paper discusses the no-cloning theorem in a logicoalgebraic approach. In this approach, an orthoalgebra is considered as a general structure for propositions in a physical theory. We proved that an orthoalgebra admits cloning operation if and only if it is a Boolean algebra. That is, only classical theory admits the cloning of states. If unsharp propositions are to be included in the theory, then a notion of effect algebra is considered. We proved that an atomic Archimedean effect algebra admitting cloning operation is a Boolean algebra. This paper also presents a partial result, indicating a relation between the cloning on effect algebras and hidden variables.

  12. Clone DB: an integrated NCBI resource for clone-associated data.

    PubMed

    Schneider, Valerie A; Chen, Hsiu-Chuan; Clausen, Cliff; Meric, Peter A; Zhou, Zhigang; Bouk, Nathan; Husain, Nora; Maglott, Donna R; Church, Deanna M

    2013-01-01

    The National Center for Biotechnology Information (NCBI) Clone DB (http://www.ncbi.nlm.nih.gov/clone/) is an integrated resource providing information about and facilitating access to clones, which serve as valuable research reagents in many fields, including genome sequencing and variation analysis. Clone DB represents an expansion and replacement of the former NCBI Clone Registry and has records for genomic and cell-based libraries and clones representing more than 100 different eukaryotic taxa. Records provide details of library construction, associated sequences, map positions and information about resource distribution. Clone DB is indexed in the NCBI Entrez system and can be queried by fields that include organism, clone name, gene name and sequence identifier. Whenever possible, genomic clones are mapped to reference assemblies and their map positions provided in clone records. Clones mapping to specific genomic regions can also be searched for using the NCBI Clone Finder tool, which accepts queries based on sequence coordinates or features such as gene or transcript names. Clone DB makes reports of library, clone and placement data on its FTP site available for download. With Clone DB, users now have available to them a centralized resource that provides them with the tools they will need to make use of these important research reagents. PMID:23193260

  13. Cloning

    MedlinePlus

    ... mammals. These twins are produced when a fertilized egg splits, creating two or more embryos that carry ... of the donor animal's somatic cell into an egg cell, or oocyte, that has had its own ...

  14. Zika and Sexual Transmission

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button Zika and Sexual Transmission Language: English Español Português ... Healthcare Providers: Sexual Transmission of Zika Basics of Zika Virus and Sex Transmission Zika can be passed ...

  15. Hybrid Sequencing Approach Applied to Human Fecal Metagenomic Clone Libraries Revealed Clones with Potential Biotechnological Applications

    PubMed Central

    Džunková, Mária; D’Auria, Giuseppe; Pérez-Villarroya, David; Moya, Andrés

    2012-01-01

    Natural environments represent an incredible source of microbial genetic diversity. Discovery of novel biomolecules involves biotechnological methods that often require the design and implementation of biochemical assays to screen clone libraries. However, when an assay is applied to thousands of clones, one may eventually end up with very few positive clones which, in most of the cases, have to be “domesticated” for downstream characterization and application, and this makes screening both laborious and expensive. The negative clones, which are not considered by the selected assay, may also have biotechnological potential; however, unfortunately they would remain unexplored. Knowledge of the clone sequences provides important clues about potential biotechnological application of the clones in the library; however, the sequencing of clones one-by-one would be very time-consuming and expensive. In this study, we characterized the first metagenomic clone library from the feces of a healthy human volunteer, using a method based on 454 pyrosequencing coupled with a clone-by-clone Sanger end-sequencing. Instead of whole individual clone sequencing, we sequenced 358 clones in a pool. The medium-large insert (7–15 kb) cloning strategy allowed us to assemble these clones correctly, and to assign the clone ends to maintain the link between the position of a living clone in the library and the annotated contig from the 454 assembly. Finally, we found several open reading frames (ORFs) with previously described potential medical application. The proposed approach allows planning ad-hoc biochemical assays for the clones of interest, and the appropriate sub-cloning strategy for gene expression in suitable vectors/hosts. PMID:23082187

  16. Survey of Transmission Cost Allocation Methodologies for Regional Transmission Organizations

    SciTech Connect

    Fink, S.; Porter, K.; Mudd, C.; Rogers, J.

    2011-02-01

    The report presents transmission cost allocation methodologies for reliability transmission projects, generation interconnection, and economic transmission projects for all Regional Transmission Organizations.

  17. Unified universal quantum cloning machine and fidelities

    SciTech Connect

    Wang Yinan; Shi Handuo; Xiong Zhaoxi; Jing Li; Mu Liangzhu; Ren Xijun; Fan Heng

    2011-09-15

    We present a unified universal quantum cloning machine, which combines several different existing universal cloning machines together, including the asymmetric case. In this unified framework, the identical pure states are projected equally into each copy initially constituted by input and one half of the maximally entangled states. We show explicitly that the output states of those universal cloning machines are the same. One importance of this unified cloning machine is that the cloning procession is always the symmetric projection, which reduces dramatically the difficulties for implementation. Also, it is found that this unified cloning machine can be directly modified to the general asymmetric case. Besides the global fidelity and the single-copy fidelity, we also present all possible arbitrary-copy fidelities.

  18. Quantum cloning disturbed by thermal Davies environment

    NASA Astrophysics Data System (ADS)

    Dajka, Jerzy; Łuczka, Jerzy

    2016-06-01

    A network of quantum gates designed to implement universal quantum cloning machine is studied. We analyze how thermal environment coupled to auxiliary qubits, `blank paper' and `toner' required at the preparation stage of copying, modifies an output fidelity of the cloner. Thermal environment is described in terms of the Markovian Davies theory. We show that such a cloning machine is not universal any more but its output is independent of at least a part of parameters of the environment. As a case study, we consider cloning of states in a six-state cryptography's protocol. We also briefly discuss cloning of arbitrary input states.

  19. Quantum cloning disturbed by thermal Davies environment

    NASA Astrophysics Data System (ADS)

    Dajka, Jerzy; Łuczka, Jerzy

    2016-03-01

    A network of quantum gates designed to implement universal quantum cloning machine is studied. We analyze how thermal environment coupled to auxiliary qubits, `blank paper' and `toner' required at the preparation stage of copying, modifies an output fidelity of the cloner. Thermal environment is described in terms of the Markovian Davies theory. We show that such a cloning machine is not universal any more but its output is independent of at least a part of parameters of the environment. As a case study, we consider cloning of states in a six-state cryptography's protocol. We also briefly discuss cloning of arbitrary input states.

  20. STRU-cloning: a fast, inexpensive and efficient cloning procedure applicable to both small scale and structural genomics size cloning.

    PubMed

    Bellini, Dom; Fordham-Skelton, Anthony P; Papiz, Miroslav Z

    2011-05-01

    We have developed a Single-Tube Restriction-based Ultrafiltration (STRU) cloning procedure that updates traditional ligation-dependent cloning to challenge the newer, faster and more efficient ligation-free techniques and could make it the method of choice. STRU-cloning employs centrifugal filter units with membrane of suitable cut off to remove small unwanted DNA fragments created during restriction of plasmids or PCR products. Heat inactivation, of restriction enzymes, followed by DNA ligation is then performed on the filtrate. By removing the agarose gel electrophoresis DNA purification step from the traditional protocol, which is time consuming and is known to be the cause of ligation problems, STRU-cloning becomes fast, very efficient, inexpensive and offers the highest degree of cloning flexibility by using restriction sites and can be performed in a single tube. This novel agarose gel-free cloning procedure provides benefits for both small and large scale cloning projects. Unlike traditional cloning it can be easily implemented as a fully automated process at very low costs. PMID:21052867

  1. Positional Cloning by Linkage Disequilibrium

    PubMed Central

    Maniatis, Nikolas; Collins, Andrew; Gibson, Jane; Zhang, Weihua; Tapper, William; Morton, Newton E.

    2004-01-01

    Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for positional cloning by LD within a composite likelihood framework and investigate the operating characteristics of maps in physical units (kb) and LDU for two bodies of data (Daly et al. 2001; Jeffreys et al. 2001) on which current ideas of blocks are based. False-negative indications of a disease locus (type II error) were examined by selecting one single-nucleotide polymorphism (SNP) at a time as causal and taking its allelic count (0, 1, or 2, for the three genotypes) as a pseudophenotype, Y. By use of regression and correlation, association between every pseudophenotype and the allelic count of each SNP locus (X) was based on an adaptation of the Malecot model, which includes a parameter for location of the putative gene. By expressing locations in kb or LDU, greater power for localization was observed when the LDU map was fitted. The efficiency of the kb map, relative to the LDU map, to describe LD varied from a maximum of 0.87 to a minimum of 0.36, with a mean of 0.62. False-positive indications of a disease locus (type I error) were examined by simulating an unlinked causal SNP and the allele count was used as a pseudophenotype. The type I error was in good agreement with Wald’s likelihood theorem for both metrics and all models that were tested. Unlike tests that select only the most significant marker, haplotype, or haploset, these methods are robust to large numbers of markers in a candidate region. Contrary to predictions from tagging SNPs that retain haplotype diversity, the sample with smaller size but greater SNP density gave less error. The locations of causal SNPs were estimated with the same precision in blocks and steps, suggesting that block definition may be less useful than anticipated for mapping a causal SNP. These results provide a guide to

  2. Cloning genes for non-syndromal hearing impairment.

    PubMed

    Smith, R J; Van Camp, G

    1999-10-01

    Over 45 genes that cause autosomal non-syndromic hearing impairment (NSHI) have been localized and many more are predicted to exist. To clone these genes, a number of different strategies can be used. This paper focuses on four general approaches: functional cloning, positional cloning, position-dependent candidate gene cloning, and position-independent candidate gene cloning. PMID:10890140

  3. Linking the human cytogenetic map with nucleotide sequence: the CCAP clone set.

    PubMed

    Jang, Wonhee; Yonescu, Raluca; Knutsen, Turid; Brown, Theresa; Reppert, Tricia; Sirotkin, Karl; Schuler, Gregory D; Ried, Thomas; Kirsch, Ilan R

    2006-07-15

    We present the completed dataset and clone repository of the Cancer Chromosome Aberration Project (CCAP), an initiative developed and funded through the intramural program of the U.S. National Cancer Institute, to provide seamless linkage of human cytogenetic markers with the primary nucleotide sequence of the human genome. Spaced at 1-2 Mb intervals across the human genome, 1,339 bacterial artificial chromosome (BAC) clones have been localized to chromosomal bands through high-resolution fluorescence in situ hybridization (FISH) mapping. Of these clones, 99.8% can be positioned on the primary human genome sequence and 95% are placed at or close to their precise nucleotide starts and stops. This dataset can be studied and manipulated within generally available public Web sites. The clones are available from a commercial repository. The CCAP BAC clone set provides anchors for the interrogation of gene and sequence involvement in oncogenic and developmental disorders when the starting point is the recognition of a structural, numerical, or interstitial chromosomal aberration. This dataset also provides a current view of the quality and coherence of the available genome sequence and insight into the nucleotide and three-dimensional structures that manifest as Giemsa light and dark chromosomal banding patterns. PMID:16843097

  4. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  5. Immunology of naturally transmissible tumours.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  6. Reversibility of continuous-variable quantum cloning

    SciTech Connect

    Filip, Radim; Marek, Petr; Fiurasek, Jaromir

    2004-01-01

    We analyze a reversibility of optimal Gaussian 1{yields}2 quantum cloning of a coherent state using only local operations on the clones and classical communication between them and propose a feasible experimental test of this feature. Performing Bell-type homodyne measurement on one clone and anticlone, an arbitrary unknown input state (not only a coherent state) can be restored in the other clone by applying appropriate local unitary displacement operation. We generalize this concept to a partial reversal of the cloning using only local operations and classical communication (LOCC) and we show that this procedure converts the symmetric cloner to an asymmetric cloner. Further, we discuss a distributed LOCC reversal in optimal 1{yields}M Gaussian cloning of coherent states which transforms it to optimal 1{yields}M{sup '} cloning for M{sup '}cloning as a possible eavesdropping attack on quantum communication link, the reversibility can be utilized to improve the security of the link even after the attack.

  7. Cloning of endangered mammalian species: any progress?

    PubMed

    Loi, Pasqualino; Galli, Cesare; Ptak, Grazyna

    2007-05-01

    Attempts through somatic cell nuclear transfer to expand wild populations that have shrunk to critical numbers is a logical extension of the successful cloning of mammals. However, although the first mammal was cloned 10 years ago, nuclear reprogramming remains phenomenological, with abnormal gene expression and epigenetic deregulation being associated with the cloning process. In addition, although cloning of wild animals using host oocytes from different species has been successful, little is known about the implication of partial or total mitochondrial DNA heteroplasmy in cloned embryos, fetuses and offspring. Finally, there is a need for suitable foster mothers for inter-intra specific cloned embryos. Considering these issues, the limited success achieved in cloning endangered animals is not surprising. However, optimism comes from the rapid gain in the understanding of the molecular clues underlying nuclear reprogramming. If it is possible to achieve a controlled reversal of the differentiated state of a cell then it is probable that other issues that impair the cloning of endangered animals, such as the inter-intra species oocyte or womb donor, will be overcome in the medium term. PMID:17379340

  8. CLONING AND EXPRESSION OF RABBIT INTERLEUKIN-15

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to understand the inflammatory mechanisms related to rabbit interleukin-15 (RIL-15), we cloned and expressed RIL-15 cDNA gene. A cDNA encoding RIL-15 was cloned from heart mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) amplification using hIL-15 primers. The RIL-15 cDNA co...

  9. Final progress report, Construction of a genome-wide highly characterized clone resource for genome sequencing

    SciTech Connect

    Nierman, William C.

    2000-02-14

    At TIGR, the human Bacterial Artificial Chromosome (BAC) end sequencing and trimming were with an overall sequencing success rate of 65%. CalTech human BAC libraries A, B, C and D as well as Roswell Park Cancer Institute's library RPCI-11 were used. To date, we have generated >300,000 end sequences from >186,000 human BAC clones with an average read length {approx}460 bp for a total of 141 Mb covering {approx}4.7% of the genome. Over sixty percent of the clones have BAC end sequences (BESs) from both ends representing over five-fold coverage of the genome by the paired-end clones. The average phred Q20 length is {approx}400 bp. This high accuracy makes our BESs match the human finished sequences with an average identity of 99% and a match length of 450 bp, and a frequency of one match per 12.8 kb contig sequence. Our sample tracking has ensured a clone tracking accuracy of >90%, which gives researchers a high confidence in (1) retrieving the right clone from the BA C libraries based on the sequence matches; and (2) building a minimum tiling path of sequence-ready clones across the genome and genome assembly scaffolds.

  10. "Goodbye Dolly?" The ethics of human cloning.

    PubMed Central

    Harris, J

    1997-01-01

    The ethical implications of human clones have been much alluded to, but have seldom been examined with any rigour. This paper examines the possible uses and abuses of human cloning and draws out the principal ethical dimensions, both of what might be done and its meaning. The paper examines some of the major public and official responses to cloning by authorities such as President Clinton, the World Health Organisation, the European parliament, UNESCO, and others and reveals their inadequacies as foundations for a coherent public policy on human cloning. The paper ends by defending a conception of reproductive rights of "procreative autonomy" which shows human cloning to be not inconsistent with human rights and dignity. PMID:9451604

  11. Chorioallantoic placenta defects in cloned mice

    SciTech Connect

    Wakisaka-Saito, Noriko; Kohda, Takashi . E-mail: tkhoda.epgn@tmd.ac.jp; Inoue, Kimiko; Ogonuki, Narumi; Miki, Hiromi; Hikichi, Takafusa; Mizutani, Eiji; Wakayama, Teruhiko; Kaneko-Ishino, Tomoko; Ogura, Atsuo; Ishino, Fumitoshi

    2006-10-13

    Somatic cell nuclear transfer technology has been applied to produce live clones successfully in several mammalian species, but the success rates are very low. In mice, about half of the nuclear transfer embryos undergo implantation, but very few survive to term. We undertook detailed histological analyses of placentas from cloned mouse embryos generated from cumulus cells at 10.5 dpc of pregnancy, by which stage most clones have terminated their development. At 10.5 dpc, the extraembryonic tissues displayed several defined histological patterns, each reflecting their stage of developmental arrest. The most notable abnormality was the poor development of the spongiotrophoblast layer of diploid cells. This is in contrast to the placental hyperplasia frequently observed in somatic clones at 12.5 dpc or later stages. A variety of structural abnormalities were also observed in the embryos. Both placental and embryonic defects likely contribute to the low success rate of the mouse clones.

  12. AQUA Cloning: A Versatile and Simple Enzyme-Free Cloning Approach

    PubMed Central

    Beyer, Hannes M.; Gonschorek, Patrick; Samodelov, Sophia L.; Meier, Matthias; Weber, Wilfried; Zurbriggen, Matias D.

    2015-01-01

    Assembly cloning is increasingly replacing conventional restriction enzyme and DNA-ligase-dependent cloning methods for reasons of efficiency and performance. Here, we describe AQUA (advanced quick assembly), a simple and versatile seamless assembly cloning approach. We demonstrate the applicability and versatility of AQUA Cloning in selected proof-of-principle applications including targeted insertion-, deletion- and site-directed point-mutagenesis, and combinatorial cloning. Furthermore, we show the one pot de novo assembly of multiple DNA fragments into a single circular plasmid encoding a complex light- and chemically-regulated Boolean A NIMPLY B logic operation. AQUA Cloning harnesses intrinsic in vivo processing of linear DNA fragments with short regions of homology of 16 to 32 bp mediated by Escherichia coli. It does not require any kits, enzymes or preparations of reagents and is the simplest assembly cloning protocol to date. PMID:26360249

  13. AQUA Cloning: A Versatile and Simple Enzyme-Free Cloning Approach.

    PubMed

    Beyer, Hannes M; Gonschorek, Patrick; Samodelov, Sophia L; Meier, Matthias; Weber, Wilfried; Zurbriggen, Matias D

    2015-01-01

    Assembly cloning is increasingly replacing conventional restriction enzyme and DNA-ligase-dependent cloning methods for reasons of efficiency and performance. Here, we describe AQUA (advanced quick assembly), a simple and versatile seamless assembly cloning approach. We demonstrate the applicability and versatility of AQUA Cloning in selected proof-of-principle applications including targeted insertion-, deletion- and site-directed point-mutagenesis, and combinatorial cloning. Furthermore, we show the one pot de novo assembly of multiple DNA fragments into a single circular plasmid encoding a complex light- and chemically-regulated Boolean A NIMPLY B logic operation. AQUA Cloning harnesses intrinsic in vivo processing of linear DNA fragments with short regions of homology of 16 to 32 bp mediated by Escherichia coli. It does not require any kits, enzymes or preparations of reagents and is the simplest assembly cloning protocol to date. PMID:26360249

  14. Cancer Basics

    MedlinePlus

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  15. Fluorescence in situ hybridization of 16S rRNA gene clones (Clone-FISH) for probe validation and screening of clone libraries.

    PubMed

    Schramm, Andreas; Fuchs, Bernhard M; Nielsen, Jeppe L; Tonolla, Mauro; Stahl, David A

    2002-11-01

    A method is presented for fluorescence in situ hybridization (FISH) of 16S rRNA gene clones targeting in vivo transcribed plasmid inserts (Clone-FISH). Several different cloning approaches and treatments to generate target-rRNA in the clones were compared. Highest signal intensities of Clone-FISH were obtained using plasmids with a T7 RNA polymerase promoter and host cells with an IPTG-inducible T7 RNA polymerase. Combined IPTG-induction and chloramphenicol treatment of those clones resulted in FISH signals up to 2.8-fold higher than signals of FISH with probe EUB338 to cells of Escherichia coli. Probe dissociation curves for three oligonucleotide probes were compared for reference cells containing native (FISH) or cloned (Clone-FISH) target sequences. Melting behaviour and calculated T(d) values were virtually identical for clones and cells, providing a format to use 16S rRNA gene clones instead of pure cultures for probe validation and optimization of hybridization conditions. The optimized Clone-FISH protocol was also used to screen an environmental clone library for insert sequences of interest. In this application format, 13 out of 82 clones examined were identified to contain sulphate-reducing bacterial rRNA genes. In summary, Clone-FISH is a simple and fast technique, compatible with a wide variety of cloning vectors and hosts, that should have general utility for probe validation and screening of clone libraries. PMID:12460279

  16. Transmission of Mumps

    MedlinePlus

    ... Articles Related Links World Health Organization Medline Plus Transmission of Mumps Language: English Español (Spanish) Recommend on ... Answers for Patients . Top of Page Related Pages Transmission for Healthcare Providers Cover Your Cough Clean Hands ...

  17. Chickenpox (Varicella): Transmission

    MedlinePlus

    ... Multimedia Related Links Medline Plus Healthfinder.gov Shingles Transmission Language: English Español (Spanish) Recommend on Facebook Tweet ... not shingles. For more information about shingles, see Transmission . When Is a Person Contagious? A person with ...

  18. Economical quantum cloning in any dimension

    SciTech Connect

    Durt, Thomas; Fiurasek, Jaromir; Cerf, Nicolas J.

    2005-11-15

    The possibility of cloning a d-dimensional quantum system without an ancilla is explored, extending on the economical phase-covariant cloning machine for qubits found in Phys. Rev. A 60, 2764 (1999). We prove the impossibility of constructing an economical version of the optimal universal 1{yields}2 cloning machine in any dimension. We also show, using an ansatz on the generic form of cloning machines, that the d-dimensional 1{yields}2 phase-covariant cloner, which optimally clones all balanced superpositions with arbitrary phases, can be realized economically only in dimension d=2. The used ansatz is supported by numerical evidence up to d=7. An economical phase-covariant cloner can nevertheless be constructed for d>2, albeit with a slightly lower fidelity than that of the optimal cloner requiring an ancilla. Finally, using again an ansatz on cloning machines, we show that an economical version of the 1{yields}2 Fourier-covariant cloner, which optimally clones the computational basis and its Fourier transform, is also possible only in dimension d=2.

  19. Who is the parent in cloning?

    PubMed

    Elster, N

    1999-01-01

    In July 1996, a sheep named Dolly was born in Scotland. What makes Dolly's birth noteworthy is that she is the result of the first successful cloning attempt using the nucleus of an adult cell. The technique that led to Dolly's birth involved transferring the nucleus of a mammary cell from an adult sheep to the enucleated egg cell of an unrelated sheep with gestation occurring in a third sheep. The possibility of applying this technique to human reproduction raised concerns worldwide with several countries moving for an immediate bans on human cloning. In the United States, President Clinton requested that the National Bioethics Advisory Commission ("NBAC"), a multidisciplinary group composed of scientists, lawyers, educators, theologians, and ethicists study the implications of cloning and issue recommendations. The Commission consulted other scientists, ethicists, theologians, lawyers, and citizens with interests in this advancing technology and concluded that, "at this time it is morally unacceptable for anyone in the public or private sector, whether in a research or clinical setting, to attempt to create a child using somatic cell nuclear transfer cloning." This Article was included in a larger work prepared at the request of, and submitted to the Commission by, law professor Lori B. Andrews. Cloning through nuclear transfer will change the way we create and define families. This Article explores how existing law relating to parentage, surrogacy, egg donation, and artificial insemination may apply in the cloning context to clarify the parent-child relationship established through cloning. PMID:12650149

  20. Controlled secret sharing protocol using a quantum cloning circuit

    NASA Astrophysics Data System (ADS)

    Adhikari, Satyabrata; Roy, Sovik; Chakraborty, Shantanav; Jagadish, Vinayak; Haris, M. K.; Kumar, Atul

    2014-09-01

    We demonstrate the possibility of controlling the success probability of a secret sharing protocol using a quantum cloning circuit. The cloning circuit is used to clone the qubits containing the encoded information and en route to the intended recipients. The success probability of the protocol depends on the cloning parameters used to clone the qubits. We also establish a relation between the concurrence of initially prepared state, entanglement of the mixed state received by the receivers after cloning scheme and the cloning parameters of cloning machine.

  1. (New hosts and vectors for genome cloning)

    SciTech Connect

    Not Available

    1991-01-01

    The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

  2. Cloning of urease gene sequences from Providencia stuartii.

    PubMed Central

    Mobley, H L; Jones, B D; Jerse, A E

    1986-01-01

    Providencia stuartii was the most prevalent isolate recovered from urine specimens taken weekly over a 1-year period from 51 nursing home patients with urinary catheters in place. Thirty percent of the isolates were urease positive. Urease, which is implicated in renal stone formation, was shown to be transmissible on an 82-kilobase conjugative plasmid in one isolate. Plasmid DNA isolated from this strain was digested with EcoRI, ligated into the EcoRI site of pBR322, and used to transform Escherichia coli HB101. Ampicillin-resistant clones were replica plated onto urea segregation agar, and a urease-positive clone, designated pMID101, was isolated. Recombinant and native urease from cell lysates had identical electrophoretic mobilities on nondenaturing polyacrylamide urease activity gels. The native enzyme was induced fourfold when cells were grown in the presence of 0.1% urea and had a km of 9.4 mM and a Vmax of 3.2 mumol of NH3 per min per mg of protein. Its molecular weight was estimated to be 375,000 +/- 35,000 by Sephacryl S-300 chromatography. The enzyme was cytoplasmic in P. stuartii, was inhibited in vitro by hydroxyurea, acetohydroxamic acid, and EDTA, and appears to have a complex subunit structure and a unique molecular size within genera of the Proteeae tribe. Images PMID:3759233

  3. Automated manual transmission controller

    DOEpatents

    Lawrie, Robert E.; Reed, Jr., Richard G.; Bernier, David R.

    1999-12-28

    A powertrain system for a hybrid vehicle. The hybrid vehicle includes a heat engine, such as a diesel engine, and an electric machine, which operates as both an electric motor and an alternator, to power the vehicle. The hybrid vehicle also includes a manual-style transmission configured to operate as an automatic transmission from the perspective of the driver. The engine and the electric machine drive an input shaft which in turn drives an output shaft of the transmission. In addition to driving the transmission, the electric machine regulates the speed of the input shaft in order to synchronize the input shaft during either an upshift or downshift of the transmission by either decreasing or increasing the speed of the input shaft. When decreasing the speed of the input shaft, the electric motor functions as an alternator to produce electrical energy which may be stored by a storage device. Operation of the transmission is controlled by a transmission controller which receives input signals and generates output signals to control shift and clutch motors to effect smooth launch, upshift shifts, and downshifts of the transmission, so that the transmission functions substantially as an automatic transmission from the perspective of the driver, while internally substantially functioning as a manual transmission.

  4. Cloning and characterization of new bioluminescent proteins

    NASA Astrophysics Data System (ADS)

    Szent-Gyorgyi, Christopher; Ballou, Byron T.; Dagnal, Erich; Bryan, Bruce

    1999-07-01

    Over the past two years Prolume has undertaken a comprehensive program to clone luciferases and associated 'green fluorescent proteins' (GFPs) from marine animals that use coelenterazine as the luciferin. To data we have cloned several bioluminescent proteins, including two novel copepod luciferases and two anthozoan GFPs. These four proteins have sequences that differ greatly form previously cloned analogous proteins; the sequence diversity apparently is due to independent evolutionary origins and unusual evolutionary constraints. Thus coelenterazine-based bioluminescent systems may also manifest a variety of useful properties. We discuss form this taxonomic perspective the initial biochemical and spectral characterization of our cloned proteins. Emphasis is placed on the anthozoan luciferase-GFP systems, whose efficient resonance energy transfer has elicited much current interest.

  5. Optimal cloning of mixed Gaussian states

    SciTech Connect

    Guta, Madalin; Matsumoto, Keiji

    2006-09-15

    We construct the optimal one to two cloning transformation for the family of displaced thermal equilibrium states of a harmonic oscillator, with a fixed and known temperature. The transformation is Gaussian and it is optimal with respect to the figure of merit based on the joint output state and norm distance. The proof of the result is based on the equivalence between the optimal cloning problem and that of optimal amplification of Gaussian states which is then reduced to an optimization problem for diagonal states of a quantum oscillator. A key concept in finding the optimum is that of stochastic ordering which plays a similar role in the purely classical problem of Gaussian cloning. The result is then extended to the case of n to m cloning of mixed Gaussian states.

  6. Generation of phase-covariant quantum cloning

    SciTech Connect

    Karimipour, V.; Rezakhani, A.T.

    2002-11-01

    It is known that in phase-covariant quantum cloning, the equatorial states on the Bloch sphere can be cloned with a fidelity higher than the optimal bound established for universal quantum cloning. We generalize this concept to include other states on the Bloch sphere with a definite z component of spin. It is shown that once we know the z component, we can always clone a state with a fidelity higher than the universal value and that of equatorial states. We also make a detailed study of the entanglement properties of the output copies and show that the equatorial states are the only states that give rise to a separable density matrix for the outputs.

  7. Economical phase-covariant cloning with multiclones

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Hai; Ye, Liu

    2009-09-01

    This paper presents a very simple method to derive the explicit transformations of the optimal economical 1 to M phase-covariant cloning. The fidelity of clones reaches the theoretic bound [D'Ariano G M and Macchiavello C 2003 Phys. Rev. A 67 042306]. The derived transformations cover the previous contributions [Delgado Y, Lamata L et al., 2007 Phys. Rev. Lett. 98 150502] in which M must be odd.

  8. Nonrandom Germline Transmission of Mouse Spermatogonial Stem Cells.

    PubMed

    Kanatsu-Shinohara, Mito; Naoki, Honda; Shinohara, Takashi

    2016-08-01

    Genes are thought to be transmitted to offspring by random fertilization of a small number of oocytes with numerous spermatozoa. Here we analyzed the dynamics of male germline transmission by genetic marking and transplantation of spermatogonial stem cells (SSCs). We found that offspring deriving from a small number of specific SSCs appear within a limited time. Interestingly, the same SSC clones reappear later with an average functional lifespan of ∼124.4 days. Cyclic offspring production from SSCs was not caused by changes in SSC self-renewal activity because lineage-tracing analyses suggested that all SSCs actively proliferated. Selection appears to occur during the differentiating spermatogonia stage, when extensive apoptosis was observed. The pattern of germline transmission could be predicted using a mathematical model in which SSCs repeat cycles of transient spermatogenic burst and refractory periods. Thus, spermatogenesis is a regulated process whereby specific SSC clones are repeatedly recruited for fertilization with long-term cycles. PMID:27505415

  9. Human T-cell clones with reactivity to Mycobacterium leprae as tools for the characterization of potential vaccines against leprosy.

    PubMed Central

    Emmrich, F; Kaufmann, S H

    1986-01-01

    T-cell clones with the T4 phenotype were established from patients with tuberculoid leprosy. The antigen reactivity of these clones ranged from stringent specificity for Mycobacterium leprae to broad cross-reactivity with other mycobacteria. Killed M. leprae had a weak stimulatory capacity which could be enhanced by ultrasonication. Among the three candidate antileprosy vaccines, M. leprae, M. bovis BCG, and the ICRC (Indian Cancer Research Center) strain, the last was superior in stimulating cross-reactive T4 clones. This finding argues for a differential masking of similar or identical membrane antigens in various mycobacterial species. T-cell clones with defined reactivity patterns for mycobacterial antigens could be helpful tools for the characterization of an antileprosy vaccine. PMID:3081446

  10. Cloning: Past, Present, and the Exciting Future. Breakthroughs in Bioscience.

    ERIC Educational Resources Information Center

    Di Berardino, Marie A.

    This document explores the history of cloning by focusing on Dolly the Sheep, one of the first large animal clonings. The disadvantages and advantages of transgenic clones are discussed as well as the future implications of cloning from the perspective of human health. (Contains 10 resources.) (YDS)

  11. Cloning the entanglement of a pair of quantum bits

    SciTech Connect

    Lamoureux, Louis-Philippe; Navez, Patrick; Cerf, Nicolas J.; Fiurasek, Jaromir

    2004-04-01

    It is shown that any quantum operation that perfectly clones the entanglement of all maximally entangled qubit pairs cannot preserve separability. This 'entanglement no-cloning' principle naturally suggests that some approximate cloning of entanglement is nevertheless allowed by quantum mechanics. We investigate a separability-preserving optimal cloning machine that duplicates all maximally entangled states of two qubits, resulting in 0.285 bits of entanglement per clone, while a local cloning machine only yields 0.060 bits of entanglement per clone.

  12. Transmission Planning Analysis Tool

    SciTech Connect

    2015-06-23

    Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identify weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysis and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.

  13. Transmission Planning Analysis Tool

    Energy Science and Technology Software Center (ESTSC)

    2015-06-23

    Developed to solve specific problem: Assist transmission planning for regional transfers in interconnected power systems. This work was originated in a study for the U.S. Department of State, to recommend transmission reinforcements for the Central American regional system that interconnects 6 countries. Transmission planning analysis is currently performed by engineers with domainspecific and systemspecific knowledge without a unique methodology. The software codes of this disclosure assists engineers by defining systematic analysis procedures to help identifymore » weak points and make decisions on transmission planning of regional interconnected power systems. Transmission Planning Analysis Tool groups PSS/E results of multiple AC contingency analysis and voltage stability analysis and QV analysis of many scenarios of study and arrange them in a systematic way to aid power system planning engineers or transmission operators in effective decision]making process or in the off]line study environment.« less

  14. Chimerism in piglets developed from aggregated cloned embryos.

    PubMed

    Huang, Yongye; Li, Zhanjun; Wang, Anfeng; Han, Xiaolei; Song, Yuning; Yuan, Lin; Li, Tianye; Wang, Bing; Lai, Liangxue; Ouyang, Hongsheng; Pang, Daxin

    2016-04-01

    Porcine chimeras are valuable in the study of pluripotency, embryogenesis and development. It would be meaningful to generate chimeric piglets from somatic cell nuclear transfer embryos. In this study, two cell lines expressing the fluorescent markers enhanced green fluorescent protein (EGFP) and tdTomato were used as donor cells to produce reconstructed embryos. Chimeric embryos were generated by aggregating two EGFP-cell derived embryos with two tdTomato-cell derived embryos at the 4-cell stage, and embryo transfer was performed when the aggregated embryos developed into blastocysts. Live porcine chimeras were successfully born and chimerism was observed by their skin color, gene integration, microsatellite loci composition and fluorescent protein expression. The chimeric piglets were largely composed of EGFP-expressing cells, and this phenomenon was possibly due to the hyper-methylation of the promoter of the tdTomato gene. In addition, the expression levels of tumorigenicity-related genes were altered after tdTomato transfection in bladder cancer cells. The results show that chimeric pigs can be produced by aggregating cloned embryos and that the developmental capability of the cloned embryo in the subsequent chimeric development could be affected by the growth characteristics of its donor cell. PMID:27239442

  15. Prospective clinical trial of a human tumor cloning system.

    PubMed

    Von Hoff, D D; Clark, G M; Stogdill, B J; Sarosdy, M F; O'Brien, M T; Casper, J T; Mattox, D E; Page, C P; Cruz, A B; Sandbach, J F

    1983-04-01

    A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use. PMID:6339044

  16. Vaginal cancer

    MedlinePlus

    Vaginal cancer; Cancer - vagina; Tumor - vaginal ... Most vaginal cancers occur when another cancer, such as cervical or endometrial cancer , spreads. This is called secondary vaginal cancer. Cancer ...

  17. Series Transmission Line Transformer

    DOEpatents

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  18. Semi-automatic transmission

    SciTech Connect

    Morscheck, T.J.; Davis, A.R.; Huggins, M.J.

    1987-06-30

    This patent describes a semi-automatic mechanical change gear transmission system of the type comprising: a mechanical change gear transmission of the type comprising a transmission housing, an input shaft rotatably supported in the housing and driven by an engine through a nonpositive coupling, an output shaft rotatably supported in the housing and a plurality of selectable ratio gears selectively engageable one at a time to a first transmission element by means of positive, nonsynchronized jaw clutch assemblies for providing a plurality of manually selectable drive ratios between the input and output shafts, each of the jaw clutch assemblies comprising a first jaw clutch member rotatably associated with the first transmission element and a second jaw clutch member rotatably associated with a second transmission element, each of the first jaw clutch members axially moveable relative to the first transmission element; manually operated means for engaging and disengaging the nonpositive coupling; manually operated shifting means for engaging selected ratio gears to and disengaging selected ratio gears from the first transmission element; selection for sensing the identity of the particular ratio gear selected for manual engagement or disengagement from the first transmission element and for providing a signal; first and second rotational speed sensors for sensing the rotational speed of the first and second transmission elements and providing signals; a power synchronizer assembly selectively actuable for selectively varying the rotational speed of the second transmission element and the second jaw clutch members rotatably associated therewith; and a central processing unit semi-automatic mechanical change gear transmission system.

  19. Benefits and problems with cloning animals.

    PubMed Central

    Smith, L C; Bordignon, V; Babkine, M; Fecteau, G; Keefer, C

    2000-01-01

    Animal cloning is becoming a useful technique for producing transgenic farm animals and is likely to be used to produce clones from valuable adults. Other applications will also undoubtedly be discovered in the near future, such as for preserving endangered breeds and species. Although cloning promises great advantages for commerce and research alike, its outcome is not always certain due to high pregnancy losses and high morbidity and mortality during the neonatal period. Research into the mechanisms involved in the reprogramming of the nucleus is being conducted throughout the world in an attempt to better understand the molecular and cellular mechanisms involved in correcting these problems. Although the cause of these anomalies remains mostly unknown, similar phenotypes have been observed in calves derived through in vitro fertilization, suggesting that culture conditions are involved in these phenomena. In the meantime, veterinarians and theriogenologists have an important role to play in improving the efficiency of cloning by finding treatments to assure normal gestation to term and to develop preventative and curative care for cloned neonates. Images Figure 1. PMID:11143925

  20. Geotemporal Analysis of Neisseria meningitidis Clones in the United States: 2000–2005

    PubMed Central

    Wiringa, Ann E.; Shutt, Kathleen A.; Marsh, Jane W.; Cohn, Amanda C.; Messonnier, Nancy E.; Zansky, Shelley M.; Petit, Susan; Farley, Monica M.; Gershman, Ken; Lynfield, Ruth; Reingold, Arthur; Schaffner, William; Thompson, Jamie; Brown, Shawn T.; Lee, Bruce Y.; Harrison, Lee H.

    2013-01-01

    clones and patterns of transmission in populations. PMID:24349182

  1. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity | Office of Cancer Genomics

    Cancer.gov

    Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect clones that are present at a ≥10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P < 0.001).

  2. Transmission Line Security Monitor

    SciTech Connect

    2011-01-01

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  3. Passenger car transmissions

    SciTech Connect

    Not Available

    1990-01-01

    This book is organized under the following headings. The Mercedes-Benz 5-speed automatic transmission targets and comparison of concepts. 1991 model year Chrysler mini-van all wheel drive vehicle. Mesh stiffness and transmission error of spur and helical gears. High precision cutting tool system for the manufacture of world class powertrain components.

  4. Data Transmission Concepts.

    ERIC Educational Resources Information Center

    Christenson, Chris

    1995-01-01

    Introduces some basic concepts related to the transmission of data from a computer to its peripherals to help distance educators make decisions regarding computer equipment purchases for their institutions. The following data transmission concepts are described: cables, serial and parallel, synchronous and asynchronous, bandwidth, and analog and…

  5. Transmission Line Security Monitor

    ScienceCinema

    None

    2013-05-28

    The Transmission Line Security Monitor is a multi-sensor monitor that mounts directly on high-voltage transmission lines to detect, characterize and communicate terrorist activity, human tampering and threatening conditions around support towers. For more information about INL's critical infrastructure protection research, visit http://www.facebook.com/idahonationallaboratory.

  6. Bac clones generated from sheared dna

    SciTech Connect

    Osoegawa, Kazutoyo; Vessere, Gery M.; Shu, Chung Li; Hoskins,Roger A.; Abad, Jose P.; de Pablos, Beatriz; Villasante, Alfredo; deJong, Pieter J.

    2006-08-09

    BAC libraries generated from restriction-digested genomic DNA display representational bias and lack some sequences. To facilitate completion of genome projects, procedures have been developed to create BACs from DNA physically sheared to create fragments extending up to 200kb. The DNA fragments were repaired to create blunt ends and ligated to a new BAC vector. This approach has been tested by generating BAC libraries from Drosophila DNA, with insert lengths of 50 kb to 150 kb. The libraries lack chimeric clone problems as determined by mapping paired BAC-end sequences of one library to the D. melanogaster genome sequence. The utility of ''sheared'' libraries was demonstrated by closure of a previous clone gap and by isolation of clones from telomeric regions, which were notably absent from previous Drosophila BAC libraries.

  7. Bounds for state-dependent quantum cloning

    SciTech Connect

    Han Yongjian; Zhang Yongsheng; Guo Guangcan

    2002-11-01

    Due to the no-cloning theorem, the unknown quantum state can only be cloned approximately or exactly with some probability. There are two types of cloners: universal and state-dependent cloner. The optimal universal cloner has been found and can be viewed as a special state-dependent quantum cloner that has no information about the states. In this paper, we investigate the state-dependent cloning when the state set contains more than two states. We get some bounds of the global fidelity for these processes. This method is not dependent on the number of the states contained in the state set. It is also independent of the numbers of copying.

  8. Cloning quantum entanglement in arbitrary dimensions

    SciTech Connect

    Karpov, E.; Navez, P.; Cerf, N.J.

    2005-10-15

    We have found a quantum cloning machine that optimally duplicates the entanglement of a pair of d-dimensional quantum systems prepared in an arbitrary isotropic state. It maximizes the entanglement of formation contained in the two copies of any maximally entangled input state, while preserving the separability of unentangled input states. Moreover, it cannot increase the entanglement of formation of isotropic states. For large d, the entanglement of formation of each clone tends to one-half the entanglement of the input state, which corresponds to a classical behavior. Finally, we investigate a local entanglement cloner, which yields entangled clones with one-fourth the input entanglement in the large-d limit.

  9. Methods in molecular cardiology: in silico cloning

    PubMed Central

    Passier, R.; Doevendans, P.A.

    2004-01-01

    Advancements in sequencing technology have made it possible to obtain more information about the DNA sequence, structure and the transcript products of the genome from different species. This information is collected in DNA databases. These databases contain many genes of which the functions have not yet been discovered. By using online biotechnology tools novel genes and their transcripts can be identified. The identification of novel genes using DNA database analysis is referred to as in silico cloning. In silico cloning may not only provide new information on genes and their biological function, it may also lead to identification of molecular targets for drug discovery activities. In this review we describe the process of in silico cloning and its application in biomedical research. ImagesFigure 1Figure 3 PMID:25696371

  10. Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells.

    PubMed

    Okon, Imoh S; Coughlan, Kathleen A; Zhang, Miao; Wang, Qiongxin; Zou, Ming-Hui

    2015-04-01

    Therapeutic benefits offered by tyrosine kinase inhibitors (TKIs), such as gefitinib (Iressa) and erlotinib (Tarceva), are limited due to the development of resistance, which contributes to treatment failure and cancer-related mortality. The aim of this study was to elucidate mechanistic insight into cellular perturbations that accompany acquired gefitinib resistance in lung cancer cells. Several lung adenocarcinoma (LAD) cell lines were screened to characterize epidermal growth factor receptor (EGFR) expression and mutation profile. To circumvent intrinsic variations between cell lines with respect to response to drug treatments, we generated gefitinib-resistant H1650 clone by long-term, chronic culture under gefitinib selection of parental cell line. Isogenic cells were analyzed by microarray, Western blot, flow cytometry, and confocal and transmission electron microscope. We observed that although chronic gefitinib treatment provided effective action against its primary target (aberrant EGFR activity), secondary effects resulted in increased cellular reactive oxygen species (ROS). Gefitinib-mediated ROS correlated with epithelial-mesenchymal transition, as well as striking perturbation of mitochondrial morphology and function. However, gefitinib treatment in the presence of ROS scavenger provided a partial rescue of mitochondrial aberrations. Furthermore, withdrawal of gefitinib from previously resistant clones correlated with normalized expression of epithelial-mesenchymal transition genes. These findings demonstrate that chronic gefitinib treatment promotes ROS and mitochondrial dysfunction in lung cancer cells. Antioxidants may alleviate ROS-mediated resistance. PMID:25681445

  11. [MRSA clones identified in outpatient dermatology clinics].

    PubMed

    Hosoya, Shino; Ito, Teruyo; Misawa, Shigeki; Yoshiike, Takashi; Oguri, Toyoko; Hiramatsu, Keiichi

    2014-11-01

    To know the characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains disseminating through the Japanese community, we have determined types of Staphylococcal cassette chromosome mec (SCCmec) elements, Multi-Locus Sequence Typing (MLST), and carriages of four exotoxin genes (toxic-shock syndrome toxin, Panton-Valentine Leukocidine, and exfoliative toxins a and b) using 54 MRSA strains isolated from outpatients attending dermatology clinics at the four university hospitals of Juntendo University. Ten clonal complexes and 12 SCCmec types have been identified. As a result, more than 15 MRSA clones that were defined by the combination of genotype and SCCmec type, were identified. Among them, Clonal Complex (CC) 5-type IIa SCCmec strains were the most major (16 strains). In contrast to the fact that CC5- type IIa SCCmec strains known as a hospital-associated MRSA clone in Japan carried toxic-shock syndrome toxin gene (tst), only 2 of 16 strains have been shown to carry tst. Thirty-eight (70.4%) of isolates belonged to the clones distinct from the CC5-type IIa SCCmec strains. Among them, CC8 strains were major (12 strains), which contained 9 tst-positive CC8-type IVl SCCmec clones and a CC8-type IVa SCCmec strain carrying the Panton Valentine Leukocidin gene (lukS, F-PV). Clones related to impetigo were also identified: 7 exfoliative toxin b (etb) -positive clones, CC89-type IIa SCCmec and CC89-type V SCCmec strains; and 2 exfoliative toxin a (eta) -positive CC121-type V SCCmec strains. Other clones were as follows: CC1-type IVa SCCmec, CC8-type I SCCmec, CC81-type IVg SCCmec, CC97-type IVc SCCmec, CC91-type IVa SCCmec, CC59-type IVg SCCmec, CC45-type IIn SCCmec, CC89-SCCmec nontypeable, and CC8-type IVm, novel subtype of type IV SCCmec were identified in this study. Our data showed that many novel MRSA clones have emerged in the community. PMID:25764806

  12. Photonic Programmable Tele-Cloning Network.

    PubMed

    Li, Wei; Chen, Ming-Cheng

    2016-01-01

    The concept of quantum teleportation allows an unknown quantum states to be broadcasted and processed in a distributed quantum network. The quantum information injected into the network can be diluted to distant multi-copies by quantum cloning and processed by arbitrary quantum logic gates which were programed in advance in the network quantum state. A quantum network combines simultaneously these fundamental quantum functions could lead to new intriguing applications. Here we propose a photonic programmable telecloning network based on a four-photon interferometer. The photonic network serves as quantum gate, quantum cloning and quantum teleportation and features experimental advantage of high brightness by photon recycling. PMID:27353838

  13. Cloning of Gaussian states by linear optics

    SciTech Connect

    Olivares, Stefano; Paris, Matteo G. A.; Andersen, Ulrik L.

    2006-06-15

    We analyze in details a scheme for cloning of Gaussian states based on linear optical components and homodyne detection recently demonstrated by Andersen et al. [Phys. Rev. Lett. 94, 240503 (2005)]. The input-output fidelity is evaluated for a generic (pure or mixed) Gaussian state taking into account the effect of nonunit quantum efficiency and unbalanced mode mixing. In addition, since in most quantum information protocols the covariance matrix of the set of input states is not perfectly known, we evaluate the average cloning fidelity for classes of Gaussian states with the degree of squeezing and the number of thermal photons being only partially known.

  14. Photonic Programmable Tele-Cloning Network

    PubMed Central

    Li, Wei; Chen, Ming-Cheng

    2016-01-01

    The concept of quantum teleportation allows an unknown quantum states to be broadcasted and processed in a distributed quantum network. The quantum information injected into the network can be diluted to distant multi-copies by quantum cloning and processed by arbitrary quantum logic gates which were programed in advance in the network quantum state. A quantum network combines simultaneously these fundamental quantum functions could lead to new intriguing applications. Here we propose a photonic programmable telecloning network based on a four-photon interferometer. The photonic network serves as quantum gate, quantum cloning and quantum teleportation and features experimental advantage of high brightness by photon recycling. PMID:27353838

  15. Photonic Programmable Tele-Cloning Network

    NASA Astrophysics Data System (ADS)

    Li, Wei; Chen, Ming-Cheng

    2016-06-01

    The concept of quantum teleportation allows an unknown quantum states to be broadcasted and processed in a distributed quantum network. The quantum information injected into the network can be diluted to distant multi-copies by quantum cloning and processed by arbitrary quantum logic gates which were programed in advance in the network quantum state. A quantum network combines simultaneously these fundamental quantum functions could lead to new intriguing applications. Here we propose a photonic programmable telecloning network based on a four-photon interferometer. The photonic network serves as quantum gate, quantum cloning and quantum teleportation and features experimental advantage of high brightness by photon recycling.

  16. Hepatitis C Transmission after Prostate Biopsy

    PubMed Central

    Ferhi, Karim; Rouprêt, Morgan; Mozer, Pierre; Ploussard, Guillaume; Haertig, Alain; de La Taille, Alexandre

    2013-01-01

    Prostate biopsy is a current and well-codified procedure; antibiotic prophylaxis and rectal enema limit the risk of infection. To date, there has been no reported viral transmission between patients due to a contaminated ultrasound probe. In this study, we report the case of a patient who contracted the hepatitis C virus after transrectal prostate biopsy as part of an individual screening for prostate cancer. PMID:23533934

  17. Whole genome comparison of donor and cloned dogs

    PubMed Central

    Kim, Hak-Min; Cho, Yun Sung; Kim, Hyunmin; Jho, Sungwoong; Son, Bongjun; Choi, Joung Yoon; Kim, Sangsoo; Lee, Byeong Chun; Bhak, Jong; Jang, Goo

    2013-01-01

    Cloning is a process that produces genetically identical organisms. However, the genomic degree of genetic resemblance in clones needs to be determined. In this report, the genomes of a cloned dog and its donor were compared. Compared with a human monozygotic twin, the genome of the cloned dog showed little difference from the genome of the nuclear donor dog in terms of single nucleotide variations, chromosomal instability, and telomere lengths. These findings suggest that cloning by somatic cell nuclear transfer produced an almost identical genome. The whole genome sequence data of donor and cloned dogs can provide a resource for further investigations on epigenetic contributions in phenotypic differences. PMID:24141358

  18. The roles of quantum correlations in quantum cloning

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; xiong Wu, Shao-; Yu, Chang-shui

    2014-12-01

    In this paper, we study the entanglement and quantum discord of the output modes in the unified 1 → 2 state-dependent cloning and probabilistic quantum cloning. The tripartite entanglement among the output modes and the quantum cloning machine is also considered. We find that the roles of the quantum correlations including the bipartite and tripartite entanglement and quantum discord strongly depend on the quantum cloning machines as well as the cloned state. In particular, it is found that this quantum cloning scheme can be realizable even without any quantum correlation.

  19. Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: gut microbiota during development of obesity in cloned pigs

    PubMed Central

    2013-01-01

    Background Obesity induced by a high-caloric diet has previously been associated with changes in the gut microbiota in mice and in humans. In this study, pigs were cloned to minimize genetic and biological variation among the animals with the aim of developing a controlled metabolomic model suitable for a diet-intervention study. Cloning of pigs may be an attractive way to reduce genetic influences when investigating the effect of diet and obesity on different physiological sites. The aim of this study was to assess and compare the changes in the composition of the gut microbiota of cloned vs. non-cloned pigs during development of obesity by a high-fat/high-caloric diet. Furthermore, we investigated the association between diet-induced obesity and the relative abundance of the phyla Firmicutes and Bacteroidetes in the fecal-microbiota. The fecal microbiota from obese cloned (n = 5) and non-cloned control pigs (n= 6) was investigated biweekly over a period of 136 days, by terminal restriction fragment length polymorphism (T-RFLP) and quantitative real time PCR (qPCR). Results A positive correlation was observed between body-weight at endpoint and percent body-fat in cloned (r=0.9, P<0.0001) and in non-cloned control pigs (r=0.9, P<0.0001). Shannon Weaver and principal component analysis (PCA) of the terminal restriction fragments (T-RFs) revealed no differences in the bacterial composition or variability of the fecal microbiota between the cloned pigs or between cloned and non-cloned control pigs. Body-weight correlated positively with the relative abundance of Firmicutes in both cloned (r=0.37; P<0.02) and non cloned-control pigs (r=0.45; P<0.006), and negatively with the abundance of Bacteroidetes in cloned pigs (r=−0.33, P<0.04), but not in the non-cloned control pigs. Conclusion The cloned pigs did not have reduced inter-individual variation as compared to non-cloned pigs in regard to their gut microbiota in neither the obese nor the lean state. Diet

  20. Tractor Transmissions. A Teaching Reference.

    ERIC Educational Resources Information Center

    American Association for Agricultural Engineering and Vocational Agriculture, Athens, GA.

    The manual was developed as a reference for teaching students about transmissions in farm tractors. The manual is divided into five sections: (1) transmission history, (2) gears and bearings in transmission, (3) sliding-gear transmissions, (4) planetary gearing, and (5) glossary. The working principles of the sliding-gear transmission, the most…

  1. Transmission Cost Allocation Methodologies for Regional Transmission Organizations

    SciTech Connect

    Fink, S.; Rogers, J.; Porter, K.

    2010-07-01

    This report describes transmission cost allocation methodologies for transmission projects developed to maintain or enhance reliability, to interconnect new generators, or to access new resources and enhance competitive bulk power markets, otherwise known as economic transmission projects.

  2. Cloning, characterization and targeting of the mouse HEXA gene

    SciTech Connect

    Wakamatsu, N.; Trasler, J.M.; Gravel, R.A.

    1994-09-01

    The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.

  3. Comparing quantum cloning: A Fisher-information perspective

    NASA Astrophysics Data System (ADS)

    Song, Hongting; Luo, Shunlong; Li, Nan; Chang, Lina

    2013-10-01

    Perfect cloning of an unknown quantum state is impossible. Approximate cloning, which is optimal in various senses, has been found in many cases. Paradigmatic examples are Wootters-Zurek cloning and universal cloning. These cloning machines aim at optimal cloning of the full quantum states. However, in practice, what is important and relevant may only involve partial information in quantum states, rather than quantum states themselves. For example, signals are often encoded as parameters in quantum states, whose information content is well synthesized by quantum Fisher information. This raises the basic issue of evaluating the information transferring capability (e.g., distributing quantum Fisher information) of quantum cloning. We assess and compare Wootters-Zurek cloning and universal cloning from this perspective and show that, on average, Wootters-Zurek cloning performs better than universal cloning for the phase (as well as amplitude) parameter, although they are incomparable individually, and universal cloning has many advantages over Wootters-Zurek cloning in other contexts. Physical insights and related issues are further discussed.

  4. [Placental developmental defects in cloned mammalian animals].

    PubMed

    Ao, Zheng; Liu, Dewu; Cai, Gengyuan; Wu, Zhenfang; Li, Zicong

    2016-05-01

    The cloning technique, also called somatic cell nuclear transfer (SCNT), has been successfully established and gradually applied to various mammalian species. However, the developmental rate of SCNT mammalian embryos is very low, usually at 1% to 5%, which limits the application of SCNT. Placental developmental defects are considered as the main cause of SCNT embryo development inhibition. Almost all of SCNT-derived mammalian placentas exhibit various abnormalities, such as placental hyperplasia, vascular defects and umbilical cord malformation. Mechanistically, these abnormalities result from failure of establishment of correct epigenetic modification in the trophectoderm genome, which leads to erroneous expression of important genes for placenta development-related, particularly imprinted genes. Consequently, aberrant imprinted gene expression gives rise to placental morphologic abnormalities and functional defects, therefore decreases developmental competence of cloned embryos. Currently, although numerous methods that can improve the developmental ability of SCNT-derived embryos have been reported, most of them are unable to substantially enhance the success rate of SCNT due to failure to eliminate the placental development defects. In this review, we summarize placental abnormalities and imprinted gene expression in mammalian cloning, and propose directions for the future research aiming to improve the cloning efficiency. PMID:27232488

  5. Cloning: Learning to Replay the Genetic Tape.

    ERIC Educational Resources Information Center

    Holden, David J.

    1979-01-01

    Describes how plants can be produced by cloning by using tissue culture methods to mass-produce rare native prairie plants and trying to transfer some of the genetic characteristics of native grasses into cultivated cereals. The experiment was conducted at South Dakota State University. (HM)

  6. Computerized Adaptive Testing with Item Cloning.

    ERIC Educational Resources Information Center

    Glas, Cees A. W.; van der Linden, Wim J.

    2003-01-01

    Developed a multilevel item response (IRT) model that allows for differences between the distributions of item parameters of families of item clones. Results from simulation studies based on an item pool from the Law School Admission Test illustrate the accuracy of the item pool calibration and adaptive testing procedures based on the model. (SLD)

  7. Genetic Crossing vs Cloning by Computer Simulation

    NASA Astrophysics Data System (ADS)

    Dasgupta, Subinay

    We perform Monte Carlo simulation using Penna's bit string model, and compare the process of asexual reproduction by cloning with that by genetic crossover. We find them to be comparable as regards survival of a species, and also if a natural disaster is simulated.

  8. Genetic crossing vs cloning by computer simulation

    SciTech Connect

    Dasgupta, S.

    1997-06-01

    We perform Monte Carlo simulation using Penna`s bit string model, and compare the process of asexual reproduction by cloning with that by genetic crossover. We find them to be comparable as regards survival of a species, and also if a natural disaster is simulated.

  9. Increasing efficiency in production of cloned piglets.

    PubMed

    Callesen, Henrik; Liu, Ying; Pedersen, Hanne S; Li, Rong; Schmidt, Mette

    2014-12-01

    The low efficiency in obtaining piglets after production of cloned embryos was challenged in two steps-first by performing in vitro culture for 5-6 days after cloning to obtain later-stage embryos for more precise selection for transfer, and second by reducing the number of embryos transferred per recipient sow. The data set consisted of combined results from a 4-year period where cloning was performed to produce piglets that were transgenic for important human diseases. For this, different transgenes and cell types were used, and the cloning work was performed by several persons using oocytes from different pig breeds, but following a standardized and optimized protocol. Results showed that in vitro culture is possible with a relatively stable rate of transferable embryos around 41% and a pregnancy rate around 90%. Furthermore, a reduction from around 80 embryos to 40 embryos transferred per recipient was possible without changing the efficiency of around 14% (piglets born out of embryos transferred). It was concluded that this approach can increase the efficiency in obtaining piglets by means of in vitro culture and selection of high-quality embryos with subsequent transfer into more recipients. Such changes can also reduce the need for personnel, time, and material when working with this technology. PMID:25333333

  10. Transmission of Hepatitis C Virus in a Gynecological Surgery Setting

    PubMed Central

    Massari, Marco; Petrosillo, Nicola; Ippolito, Giuseppe; Solforosi, Laura; Bonazzi, Lucio; Clementi, Massimo; Manzin, Aldo

    2001-01-01

    A cluster of hepatitis C virus (HCV) infections among gynecological patients who underwent surgical intervention in the same setting is described. An epidemiological investigation was conducted to identify the cases, the likely source of infection, and the route of transmission. Four recent HCV infections were identified. Based on molecular fingerprinting analysis and epidemiological investigation, transmission between the putative source patient (an HCV-positive woman who was the first patient of the surgical session) and outbreak patients was highly suggestive. All patients, including the source patient, were infected with HCV type 1b. Molecular characterization of HCV clones by sequence analysis of both structural envelope regions (20 clones from the source patient and 58 from the outbreak patients) and the nonstructural NS5 region of the viral genome (12 clones from the source patient and 32 from the outbreak patients) showed close homology between the viral isolates from the source and those from the outbreak patients that was higher than that observed between the viral isolates from the source and those from four unrelated, HCV type 1b-infected patients from the same geographical area (in the latter case, 33 clones were sequenced for the envelope regions and 30 were sequenced for the NS5 region). The mean percent divergence between clones was 4.69 for the envelope and 3.71 for the NS5 region in the source patient and the outbreak patients compared with 6.76 (P = 0.001) and 5.22 (P = 0.01) in the source patient and control patients, respectively. Among the risk factors investigated, only that of having undergone surgery in the morning session of the same day reached statistical significance (P = 0.003). The investigation showed that the source patient and outbreak patients shared only the administration of propofol in multidose vials. The study documents the risk of nosocomial transmission of HCV and the importance of infection control procedures in the