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We have launched a new website for Trade Express Services in Melbourne! (take a look)
Based in Bayswater, Stephen at Trade Express Services has been providing electrical test & tag services across Melbourne for more than 15 years.
The business required a new simple website with a clean and easy to use design that could promote the services and form a base for the target of marketing activities, to be expanded upon in the future. Our content writers prepared new content to detail individual services and the industries that they apply to.
Be sure to check out the website, and if you are in Melbourne looking for professional test & tag services, give Stephen a call.
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Bee (Large)
About this work of Art
Bee (large)- seven colour screen print by Andy Wilx developed from the smaller giclee print. This version is printed in rich gold and pearlised.
Edition of 20 and is sold unframed.
If bought online this will be sent to you rolled in a tube.
Sheet size: H:86cm x W:85cm
Image size: H:60cm x W:60cm
Additional information
- Size : H 80 cm x W 80 cm

subset: commoncrawl


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Summer Holidays
Melanie Roger Gallery will be closed for the Summer holidays from 21st December, reopening 28th January with a solo exhibition of new work by Grace Bader. We are happy to meet by appointment where possible within this time however. To arrange, please text gallery director Melanie Roger on 021-747-505. Emails will also be checked but somewhat more sporadically during this time.


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School of Education
School of Education Doctoral Students Incorporate Travel into Learning about Education
Two University of North Carolina at Chapel Hill School of Education doctoral students have incorporated travel opportunities into their study, benefitting from funding that has helped them explore innovations and challenges in learning communities in other parts of the world. Diana Tursi and Lucia Mock, doctoral students in the Cultural Studies and Literacies strand of… Read more »
Exchange Program Exposes Carolina, German Students to Different Education Systems
A group of students from the University of Hamburg in Germany recently spent a month learning about the American education system through a partnership with the University of North Carolina at Chapel Hill School of Education. And soon, 11 students in the school's Master of Arts in Teaching program will head to Hamburg to get… Read more »
School of Education Alumnus Trey Adcock Named Whiting Public Engagement Fellow
Trey Adcock Ph.D. '12, assistant professor of education at the University of North Carolina at Asheville, has been named a 2018-2019 Public Engagement Fellow by the Whiting Foundation. The honor recognizes scholars who work to champion the role of humanities in enriching public life. The fellowship carries a $50,000 award that is intended to support… Read more »
Kelly Ryoo Among Eight Tar Heels to Win NSF CAREER Grants
Kihyun "Kelly" Ryoo, assistant professor of learning sciences, is one of eight faculty members at the University of North Carolina at Chapel Hill who has won prestigious National Science Foundation CAREER grants this year. This is the largest number of NSF CAREER grants ever won at UNC in a single year. Ryoo's five-year grant of $674,000… Read more »
Abd-El-Khalick Named New Dean of School of Education
The University of North Carolina at Chapel Hill today announced that Fouad Abd-El-Khalick has been selected as the new dean for the School of Education, one of the oldest professional schools at Carolina. He is currently the associate dean for research and research education in the College of Education at the University of Illinois at… Read more »
Doctoral Student Alex Lowry Selected by US State Department to Teach in Nepal
The U.S. Department of State has selected University of North Carolina at Chapel Hill School of Education doctoral student Alex Lowry for a 10-month fellowship project conducting English teacher training in Nepal. Lowry is one of 165 U.S. citizens selected for the 2015-2016 English Language Fellow Program. Lowry, of Great Falls, Virginia, is pursuing a… Read more »
Juan Carrillo Named NAE/Spencer Fellow
Juan Carrillo, an assistant professor at the School of Education at the University of North Carolina at Chapel Hill, has been named a 2015 National Academy of Education/Spencer Postdoctoral Fellow. It's the second year in a row that a school of education faculty member has been awarded one of the most prestigious fellowships in the… Read more »
Collaboration Creates Multimedia Tool for Teaching About World War I
Katie Gulledge grew up wondering about a little family tale about her great-grandfather in World War I. It was a story told by a man who had seen the horrors of trench warfare, a story of a hungry soldier, asking a woman, using his little bit of French, for something to eat: simply a potato…. Read more »
Paul Cuadros, Educator and Journalist, to Give School of Education Commencement Address
Paul Cuadros, a member of the faculty at Carolina's School of Journalism and Mass Communication, will give the Commencement address at the School of Education's graduation exercises on May 9. Commencement will begin at 1 p.m. in the Dean E. Smith Center. Cuadros is an award-winning investigative journalist who wrote a book about his experience… Read more »
Knotek's Fulbright Experience in Croatia Sparks Learning Moments
During his three months working as a Fulbright Specialist, Steve Knotek learned a few things about Croatia's elementary school system. The quality of Croatian preschool is very high, with all preschool instructors having college degrees. Preschool instruction focuses on social learnings, with play and group activities making up most of the day and academic work waiting until kindergarten…. Read more »


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Newlands Court Motel
About Newlands Court Motel
Refurbished in 2016 Newlands Court Motel is located in Newlands within 15 minutes' drive from the centre of Wellington. Guests of this motel can enjoy gardens and free on-site parking.Each heated room here features a flat-screen TV and a sofa. For convenience all rooms include a microwave and a refrigerator. Select rooms include a kitchen with an oven.Fax and photocopying services are offered to guests of Newlands Court Motel.Te Papa Museum Westpac Stadium and Hutt Valley are all within 10 minutes' drive from the property. The motel is located along the main bus route to Wellington where you will find a large variety of restaurants shops and entertainment facilities. The Interisland Ferry Terminal is 11 minutes' drive away.
- Wi-Fi
- Parking on Premises
Newlands Court Motel Map
*Distances are shown as the crow flies and not necessarily the actual travelling


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R. J. Fahy Funeral Home in Norwich designs funeral and memorial services for families in Chenango County, New York. Our team provides families compassion and support during this emotional experience.
- Recently renovated
Flexible chapel space
Our chapel can be used for hosting your religious events
- Monument and inscription services
- Cremation remembrance jewelry
- Option for home delivery of ashes
- Option for mail delivery of ashes
Our Difference
We want you to feel confident planning a funeral for yourself or a loved one. Here are some of the unique benefits we offer to help relieve your family of emotional and financial burdens.
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Building relationships
As a locally operated funeral home in Norwich, we focus on providing families personal attention throughout the funeral planning process. Several staff members grew up in the area and continue to call it home. This enables our team to offer compassionate care while meeting the needs of our community. At R. J. Fahy Funeral Home, your family becomes a part of ours.
Celebrate your loved one
As we carefully guide you through the planning process, we'll discuss affordable funeral and cremation options as well as suggest innovative ways to honor life.
Whether you prefer a contemporary celebration, simple cremation or traditional burial, all of our services are fully customizable. We respect your values and traditions, and we work to design a service that showcases individuality. Tell us about your loved one, including their hobbies, achievements and personality. While planning, we'll design a service with these in mind, so friends and family can experience a true celebration of life.
Future planning
In addition to serving families who have an immediate need, our staff can also help plan ahead a funeral service. Preparing for the future keeps costs managed and ensures your wishes are met. We can arrange every detail, including casket or urn choices and final resting places in nearby cemeteries and mausoleums. Those who plan in advance also spare their loved ones from making important decisions during a difficult time.
Serving the community
We hope you allow us the privilege to serve you during your time of need. Please contact R. J. Fahy Funeral Home to learn more about burial and cremation services or to tour our Norwich funeral home.
"Thank you for your attention to details, knowledge and professionalism during our time of sorrow."
Verified Cremation & Memorial Service Customer
June 2019
"As my loved one had purchases a pre-paid cremation a number of years ago, this was the only, most local, funeral home that honored their product. They were most helpful and honest while assisting us )..."See More
Verified Cremation Customer
May 2019
"My family and i have dealt with this funeral home for over 40 years and have never had a complaint. We will be using them in the future as i have prearranged my funeral arrangements with them."
Verified Cremation & Memorial Service Customer
March 2019
"Need to drop prices - more like the bigger cities around us. This is a poor community."
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November 2018
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Currently Bidding
Please see the list below. These are projects D.A.G. is currently bidding. If you are interested in submitting a bid to us, please contact the estimator at 513.542.8597. Please check back as dates are subject to change.
Drawings are available on builders exchange website. www.bxohio.com.
Please contact our office for FTP site information.
- 01/17 - Blue Ash YMCA
- 01/23 - Wilkommen
- 01/24 - US Bank


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[Frontiers in Bioscience 4, d153-164, February 15, 1999]
John A. Lednicky and Janet S. Butel
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
1. Abstract
Polyomaviruses are small DNA viruses that typically establish persistent but inapparent infections of their natural hosts, although cytolytic disease may develop if the host becomes immunocompromised. Most polyomaviruses have the ability to induce tumor formation when introduced into certain foreign hosts and are considered oncoviruses. Some polyomaviruses, including those that infect humans, have occasionally been detected in cancerous tissue of their natural hosts. This article briefly reviews the biology of polyomaviruses and explores issues pertaining to the significance of association of polyomaviruses with human tumors.
The Papovaviridae family is comprised of two genera: Polyomavirus and Papillomavirus. Polyomaviruses are nonenveloped icosahedral DNA viruses that are relatively small, having capsids with a diameter of about 45 nm. Their genomes consist of a single copy of a double-stranded, covalently closed, circular, supercoiled DNA and average about 5 kilobases in length (1,2).
Currently, there are twelve members of the genus Polyomavirus recognized by the International Committee on Taxonomy of Viruses (ICTV). The six best-characterized members of the group are BK virus (BKV), JC virus (JCV), simian virus 40 (SV40), murine polyomavirus (PyV), hamster papovavirus (HaPV), and lymphotropic papovavirus (LPV). The most intensely studied viruses in this group are PyV and SV40 (3). The other six polyomaviruses that are recognized by the ICTV include budgerigar fledgling disease virus (BFDV), bovine polyomavirus (BPyV), another murine polyomavirus [Kilham virus (KV)], baboon polyomavirus 2 (PPV-2), rabbit kidney vacuolating virus (RKV), and simian virus agent 12 (SA12). Rat polyomavirus (RPV) has been reported but is not yet recognized by the ICTV (4).
The circular genomes of all polyomaviruses are superficially arranged in a similar manner, and three general regions can be identified based on function. These are referred to as the regulatory (noncoding) region, the early coding region, and the late coding region. The regulatory region separates the coding regions and contains nucleotide sequences that are necessary for the initiation of viral DNA replication and that govern the balance between early and late transcription. The direction of early and late transcription is divergent, with opposite DNA strands used during these processes (1,2).
Multiple strains have been identified for some but not all members of the genus Polyomavirus. For example, SV40 strains 776 (5), Baylor (6–8), and VA45-54 (5,7–9) have been widely used in laboratory studies. Each SV40 strain was derived from an independent isolate of the virus, and DNA sequence polymorphisms in genetically stable regions of the viral genome outside of the viral regulatory region were used to distinguish strains (7,8). The avian polyomavirus referred to as BFDV by the ICTV is not a single entity; three distinct viruses can be distinguished based on DNA sequence analysis and clinical studies, and these three viruses are designated BFDV 1–3 (10). In contrast, studies of polyomavirus KV have been based on a single virus isolate. It is likely that multiple strains would be identified for more polyomaviruses, such as KV, if additional isolates of a virus were characterized in detail. It should be emphasized that strain designations based on DNA polymorphisms do not necessarily suggest serological variations. The complete DNA sequences of many polyomaviruses have been deposited at GenBank. The GenBank genomic accession numbers for viruses that are considered reference strains by the ICTV are shown in table 1.
Table 1. Reference strains of polyomavirusesa
Notes: a Designation by the International Committee on Taxonomy of Viruses.
Mammalian polyomavirus infections are typically subclinical and persistent in their natural hosts (11). Persistence occurs in multiple organs and for indefinite periods (12–22). Unlike their mammalian counterparts, avian polyomaviruses are sometimes agents of clinically apparent diseases. The original BFDV isolate, now referred to as BFDV-1, was recovered from fledgling budgerigars and causes a multisystemic infection with high mortality rates. BFDV-2 was isolated from chickens (but has not yet been associated with disease in chickens), whereas BFDV-3 was isolated from a macaw exhibiting symptoms similar to those observed with BFDV-1 infection (10). Thus, two of the three known avian polyomaviruses are recognized as agents of acute lethal disease, unlike the usually benign infections caused by mammalian polyomaviruses.
Polyomaviruses replicate their DNA and form mature progeny virus particles in the nucleus of host cells. They are able to complete their life cycle in both permissive and semipermissive cells. Efficient viral growth occurs in permissive cells, resulting in the production of relatively large amounts of progeny virions and cell death. Viral growth in semipermissive cells is less efficient, resulting in low yields of progeny virions. The time required to complete the viral growth cycle varies according to cell type, as well as other factors. In contrast, infection of nonpermissive cells does not result in the production of infectious progeny. Such infections are believed to lead to abortive infection, with subsequent rapid loss of the viral genome from the infected cell, and only rarely, random integration of portions of the viral DNA into the host chromosomal DNA (23).
Under rare circumstances, usually associated with some form of immunosuppression of the host, polyomaviruses may elicit one of two distinctly different types of disease: (i) cytolytic disease and (ii) tumor formation. Examples of cytolytic diseases associated with polyomavirus infections in their natural hosts are listed (table 2).
Table 2. Examples of cytolytic diseases associated with polyomavirus infections in natural hosts
Notes: a Progressive multifocal leukoencephalopathy
Based on studies of BKV, JCV, PyV, and SV40, the ability of these viruses to occasionally induce tumors in their natural hosts is thought to be a consequence of a combination of rare circumstances, as tumor induction is not a part of the normal virus life cycle. These circumstances would probably include a cellular block that depresses new virus production, but not early gene expression, thereby preventing cell killing, coupled with a failure of the host immune response to kill or inhibit the outgrowth of virus-altered cells. To date, polyomaviruses BKV, HaPV, JCV, SV40 and PyV have been detected in association with tumors arising in their natural hosts (table 3). Tumor formation in natural hosts by polyomaviruses has been experimentally confirmed for the rodent viruses HaPV and PyV. Those studies have been performed using large inocula of virus, as large viral inputs can overcome some normal immune responses. Neonatal animals with immature immune systems are usually required in order to obtain a high frequency of tumor induction. The significance of detection of BKV and JCV DNA in certain human tumors is harder to assess, as it is not possible to conduct direct experiments to establish whether those viruses have oncogenic potential in humans.
Table 3. Examples of polyomaviruses detected in association with tumors in their natural hosts
It has not been established whether polyomavirus lytic disease in the natural host precedes tumor formation or whether tumor formation may occur concomitantly with cytolytic disease in the same animal. Precedence for the latter possibility has been presented for JCV, as JCV-induced PML is sometimes observed in patients with cerebral tumors, such as multiple gliomas and astrocytomas (discussed in Ref. 47). If tumor formation is a protracted event, it is conceivable that any virus-induced lytic disease is resolved before cancer becomes apparent. Alternatively, it is possible that the two disease spectra are unrelated, with the development of each dependent on distinct defects of the immune system. The type of tissue affected in lytic disease may reflect the site at which a particular polyomavirus establishes a latent or persistent infection. For example, the kidney is thought to be the target organ for both BKV and SV40, and each virus has been found in association with kidney disease (table 2).
A brief overview will be given of current concepts in polyomavirus tumor biology. Polyomaviruses are classified as small DNA tumor viruses, despite the fact that tumor formation is not a primary function of the viruses. The observation that polyomaviruses have oncogenic potential arose from studies which showed that selected viruses could induce tumors when inoculated into animal species that were unrelated to their natural host (3). BKV, for example, is oncogenic in hamsters (reviewed in Ref. 52,53), mice (54), and rats (55,56). The cross-species oncogenic capability of JCV has been demonstrated using Syrian hamsters (53,57–60), adult owl monkeys (61), and squirrel monkeys (62). PyV is oncogenic in newborn hamsters (63) and newborn rats (64). SV40 was shown to be oncogenic in newborn hamsters (9,65,66), in the African rodent Rattus natalensis (67), and in certain inbred strains of mice (68).
The rodent model systems have certain limitations that make them unable to accurately reflect the possible pathogenesis of virus-induced tumors in humans. As nonrodent polyomaviruses do not replicate well, if at all, in rodent tissues, the tissue tropisms, patterns of viral dissemination within the host, and replication-related events cannot be duplicated. Rather, large quantities of virus are injected into the animals, sometimes directly into sites such as the brain. Normal hosts would not be subjected to viral infection by such traumatic routes nor would they encounter as large an infective dose of polyomaviruses as a single exposure event. Moreover, it is not clear if all polyomaviruses have the capability to induce tumors in experimental animals. For example, inoculation of KV into experimental animals did not result in tumor formation (69–71), and LPV failed to induce tumor formation in newborn hamsters (72).
The ability of intact polyomaviruses, or the appropriate genomic DNA fragments encoding for viral oncoproteins, to transform cells has been explored using tissue culture systems (3). In general, when whole virus particles are used, nonpermissive cells are most readily transformed by polyomaviruses because progeny virus is not produced and the cells are not killed. If early gene expression can occur, polyomavirus tumor antigens will be produced and expression of those proteins past a cell-specific threshold level will lead to an alteration of the normal cell cycle, eventually resulting in cell transformation.
Using cultured cells, it has been shown that BFDV-1 transforms nonpermissive hamster embryo cells (73). BKV has the capacity to transform permissive or semipermissive human cells, nonpermissive or semipermissive monkey cells, and nonpermissive hamster, mouse, rabbit, and rat cells (reviewed in Ref. 52,53). HaPV DNA transforms primary rat embryo fibroblasts (74), which are nonpermissive for virus replication. JCV reportedly can transform cultured human and hamster cells, but inefficiently (reviewed in Ref. 53,75). LPV has the capacity to transform nonpermissive hamster embryo cells (reviewed in Ref. 52). PyV transforms hamster and rat cells that are either semipermissive or nonpermissive for the virus (76). Finally, SV40 has the capability to transform human cells, as well as nonpermissive rodent cells (76; reviewed in Ref. 77). These studies showed that in vitro there is a broad host range with respect to polyomavirus-mediated transformation potential, as transformation is not limited to certain specific cell types.
The oncogenic potential of polyomavirus subgenomic fragments encoding for viral tumor proteins has also been demonstrated using transgenic animal models. Transgenic mice expressing the large tumor antigen (T-ag) of JCV (78), LPV (79,80), or SV40 (79,80) develop tumors, and similar abnormalities are detected when the different viral oncoproteins are expressed in common cells. Thus, using these transgenic mouse models, it has been suggested that the biochemical events leading to cellular transformation by the T-ags of JCV, LPV, and SV40 are similar. Unlike what is observed in tissue culture models, the tumors that are formed tend to be cell-type specific, with the affected cell type being largely dependent on the promoter used to express the T-ags (reviewed in Ref. 81).
A common conclusion from the early rodent studies was that the viral genomic DNA associated with polyomavirus-induced tumors was always integrated into host-cell chromosomal DNA. However, more recent data show that, although viral DNA is commonly found to be integrated in rodent cells, episomal viral DNA may persist in some cells. The impression about viral integration status may have stemmed, in part, from the notion that infection of nonpermissive cells resulted in rapid clearance of the viral DNA and that viral DNA was retained in those cells if it became integrated. Sporadic reports of rescue of infectious virus from tumors were explained by one of several viral excision mechanisms that might have accounted for the release of the viral DNA from its site of integration (76); the possibility of long-term persistence of episomal copies of viral DNA was not considered. These ideas were popularized subsequent to experiments involving analysis of SV40 infections of nonpermissive mouse cells. Murine cells stably transformed by SV40 contained viral DNA that was integrated into the chromosomal DNA (82), and at least the early region of the viral genome was retained as transformation required expression of SV40 T-ag (83). Integration of the SV40 DNA was nonspecific with respect to sites on both the viral and host DNAs and usually resulted in loss of portions of the viral genome; however, the complete viral genome could be present, as integration of tandemly multimerized viral DNA sometimes occurred (84–91). It is known that polyomaviruses do not encode for integrases and that the viral DNA becomes integrated into host chromosomes at very low frequencies and at random sites. Thus, integration into the host chromosome is an incidental event and not a normal part of the polyomavirus life cycle.
The hypothesis that polyomavirus DNA is rapidly lost from nonpermissive and semipermissive environments appears to be an over-simplification. Induction of tumors by SV40 in rodents depends on the age and genetic background of the host at the time of virus exposure, with a cytotoxic T lymphocyte response mediating tumor rejection (92). However, it has been reported that tumor induction in mice by SV40 was controlled by long-term viral persistence as well as by the host's immune response (93). H-2d haplotype mice, which exhibit a low cytotoxic T lymphocyte response to SV40 tumor-specific transplantation antigen, formed tumors in response to virus exposure, whereas H-2k high-responder mice did not. In more recent studies, long-term persistence of SV40 in mice was confirmed; marker gene expression driven from the SV40 promoter was detected more than one year after infection of mice (94). Long-term persistence of JCV in hamsters has also been demonstrated, and viral gene expression has been shown to be tissue specific. Hamsters sacrificed 6 months postinfection with JCV contained virus in brain, kidney, and bladder tissue, although JCV-specific gene expression was confined primarily to brain tissue (95).
It is noteworthy that episomal polyomavirus DNA has been detected in various types of tumors and transformed tissue-culture cells. Although studies have not carefully compared the frequency of episomal versus integrated polyomavirus DNAs in tumors, numerous observations indicate that episomal copies commonly persist. Defective episomal BKV DNAs together with integrated BKV DNA was found in a human papillary urothelial bladder carcinoma; the episomal BKV DNA had apparently acquired a cellular DNA sequence, forming chimeric episomal DNA molecules that were larger than unit-length BKV DNA (96). Human fetal brain cells transformed by BKV contained episomal viral DNA (97). Infectious BKV was rescued from human brain tumors, from African Kaposi's sarcoma tissues, and from three human tumor cell lines (glioblastoma, neuroblastoma, and osteogenic sarcoma) (44), most likely reflecting the presence of nonintegrated viral DNA. Tumors induced in hamsters by BKV were found to contain predominantly integrated viral DNA, but some tumors also contained free viral sequences (98). Infectious JCV was molecularly cloned from tumor cells derived from a JCV-induced owl monkey astrocytoma that had been passaged twice in culture (99). HaPV particles (containing wild-type DNA) were associated with hair follicle epitheliomas in the Z3/BlnA Syrian hamster breed (46), whereas infection of HaP Syrian hamsters led to the formation of lymphomas containing defective episomal HaPV DNA (100). With one exception (101), the PyV genome is predominantly present in an unintegrated state in PyV-induced tumors arising in immunocompetent mice (discussed in Ref. 51); integrated PyV DNA appears to occur with high frequency, however, when athymic (nude) mice are tested (51,102–104). In contrast, in transformed rat embryo cells, the PyV genome was observed to be present in both integrated and unintegrated forms (105–107). Infectious SV40 has been isolated from tumors induced in hamsters by inoculation of SV40. Examples of tumor-derived isolates are SV40 strain A2895 (108), and D-128-15 (Lednicky, unpublished observations). Infectious viral DNA was demonstrated in SV40-transformed hamster, rat, mouse, and monkey cells (109,110). Human fibroblasts transformed by plasmids containing the early region of SV40 DNA (encoding for the viral oncoproteins) reportedly retained the plasmids in an episomal manner; eventually the plasmids were lost and the cells underwent senescence (111). Human glioblastoma cells persistently infected with SV40 acquired a more transformed phenotype yet carried nondefective episomal viral DNA (112). SV40 was cloned from a meningioma (113), isolated and cloned from a choroid plexus tumor (114), and isolated from a metastatic melanoma (115).
It is not clear at this time if episomal polyomaviral genomes alone are sufficient to maintain the transformed state or if an integrated viral DNA copy is required. The fact that polyomavirus DNA is sometimes found in an episomal manner in tumor tissue is reminiscent of the situation with human papillomavirus strain 16 (HPV-16). In HPV-16-associated cancers, the viral DNA is either integrated or episomal, whereas in HPV-18-associated cancers, the viral DNA is almost always integrated. HPV-16 predominates in squamous cell carcinomas, whereas HPV-18 predominates in adenocarcinomas and in small-cell undifferentiated carcinomas of the cervix (reviewed in Ref. 116). It is apparent, therefore, that strain differences among the papillomaviruses account for different types of diseases, as well as influence whether the viral DNA remains episomal or integrated in a tumor; the same situation may hold true for polyomaviruses.
There are accumulating reports of the association of polyomaviruses BKV, JCV, or SV40 with certain human tumors (table 4). It is striking that all three viruses have been associated with brain tumors, emphasizing a basic neurotropic character of primate polyomaviruses. Investigators studying the possible association of polyomaviruses with human tumors are faced with two difficult tasks: (i) detection of viral DNA and/or viral gene products, and (ii) evaluation of the significance of viral presence in tumor tissue.
Table 4. Reports of polyomavirus DNA in tumor and/or normal tissue from humans
Notes: a + = Detection of viral DNA; – = failure to detect viral DNA.
Older studies relied primarily on DNA hybridization methods, such as Southern blot analysis or DNA reassociation kinetics, and on immunological methods, such as indirect immunofluorescence studies using antibody against polyomavirus tumor antigens, to search for papovavirus DNA sequences or virus-encoded proteins in tumor tissue. More recent studies have depended primarily on sensitive polymerase chain reaction (PCR) methodology to detect viral sequences in human samples. The exquisite sensitivity of PCR requires confirmation of the specificity of presumed virus-specific amplified DNA products by sequence analysis or by Southern blot analysis (149,150). This is necessary as the PCR primers may amplify homologous DNA sequences from closely related viruses or from nonpolyomavirus DNAs under certain conditions, and this could lead to misleading results (151). Some studies have reported finding viral sequences present in both tumor and normal tissues or in normal tissue alone (table 4). It should be noted that not all PCR-based studies have detected polyomavirus DNAs in association with tumors, complicating the interpretation of these findings (152–154). The facts that BKV and JCV are known to commonly establish persistent infections in people and to be excreted in the urine by individuals who are asymptomatic complicate the evaluation of their potential role in the development of human tumors. These observations of the presence of polyomavirus sequences in normal tissues other than kidney, believed to be the target organ for BKV, JCV, and SV40, raise the theoretical possibility that there may be types of polyomavirus disease in humans that are currently unrecognized (155).
Numerous studies have validated the detection of viral sequences in human tumor tissues (3), establishing that polyomaviral DNAs were present (table 4). The question then becomes one of evaluating the biological significance of that presence. Rodent HaPV and PyV have been verified experimentally to possess oncogenic capability in their natural hosts (discussed above). Therefore, it is tempting to generalize that BKV and JCV are human tumor viruses as well and were important factors in the induction of the tumors in which they were detected. However, proof that they played significant etiological roles is lacking, and no conclusions can be drawn at this time about their status as human cancer viruses. The potential role of SV40 in human tumors is controversial at present, due to a widely held view that SV40 is unable to infect humans. However, it is evident from reports in the literature that SV40 does have the capacity to both infect and replicate efficiently in certain types of human cells (discussed in Refs. 3,7,114), including human fetal glial cells (156), in a variety of human fetal tissues and newborn human kidney cells (157), and in human fetal brain cultures and various human cell lines (158). The ability of human cells to support the replication of SV40 DNA has been demonstrated in vitro using human cell extracts (159–161), establishing that human proteins have the intrinsic ability to interact with SV40 T-ag to replicate SV40 DNA. It is worth noting that SV40 does not infect and replicate efficiently in all types of simian cells, so it is not unexpected that some human cells are nonpermissive. The potent ability of SV40 to induce tumors in foreign species, together with its ability to infect human cells, strengthens the hypothesis that SV40 might exhibit oncogenic capability in humans (3).
However, when the same virus is detected in normal tissues as in tumors, it must be considered that the virus is present in the neoplastic cells merely as a harmless "passenger". It should not be considered unusual to find polyomavirus DNA in normal tissue, as these agents establish long-term persistent infections. Accepted human oncogenic viruses are commonly detected in normal tissue; examples include human papillomaviruses, which are found in normal and precancerous cervical tissue (162; reviewed in Refs. 116,163), and hepatitis B virus, which can be found replicating in nontumorous liver tissue (164).
With most viruses, the mere detection of virus presence does not indicate the development of clinical disease; similarly, the presence of an oncovirus in tumor tissue cannot be assumed to be proof of causality. What parameters, then, can be used to establish whether a given polyomavirus is the causative agent for a human tumor in which the virus was detected? This is an important consideration in that there has not yet been a perfect correlation of any polyomavirus with a given tumor. One approach to establish causality is to demonstrate the presence of virus-specific tumor antigens in the tumor cells. Based on studies in rodents, the T-ag oncoprotein of BKV, JCV, and SV40 must be continually expressed to maintain the transformed phenotype. One way of detecting viral protein expression is to use indirect immunofluorescence with the primary antibody directed against a particular T-ag, an approach exemplified in the study by Martini et al. (117), who used monoclonal antibody Pab101 to detect SV40 T-ag in various human tumor cell lines. Such studies are highly indicative of the presence and expression of a viral T-ag in tumor cells, but are not definitive for virus identification purposes because the majority of available antibodies are cross-reactive with the T-ags of multiple polyomaviruses. Furthermore, lessons learned from studies of BPyV indicate that bovine serum used for tissue culture may be contaminated by this virus (165–167); it is possible that a bovine virus was present in the serum used to culture tumor cells and that BPyV-contaminated cells would react with the primary antibody used to detect T-ag. It was not clear if the cell lines studied by Martini et al. (117) were true positives, as the cells were obtained commercially and may have been contaminated prior to distribution. Contamination with bovine viruses is not an issue, however, when tumor samples are not exposed to bovine serum. In addition, there are monoclonal antibodies available which are reportedly specific for a given viral protein, such as pAb419 for SV40 T-ag and antibody BK-T.1 for BKV T-ag (168). The pAb419 reagent was used to demonstrate SV40 T-ag in mesotheliomas (139).
Immunohistochemical assays can be performed using antibodies directed against a particular T-ag, as reported by Bergsagel et al. (132). However, many antibodies that are useful in other types of assays fail to react by immunohistochemistry on paraffin-embedded tissues. Again, the limitation of such studies for virus identification purposes is the type of primary antibody used. For example, the polyclonal antibody used in the study by Bergsagel et al. (132) may have been cross-reactive with T-ags other than that of SV40. Antibody tests that employ cross-reactive reagents could be coupled with additional assays, such as reverse transcriptase PCR, to demonstrate expression of a specific T-ag RNA in a tumor; this approach was used by Martini et al. (117).
A more sophisticated approach is to demonstrate the presence of a functionally active viral T-ag in the tumor tissue. For example, a particular T-ag could be detected and confirmed, using two independent tests, and then be shown to be functional, using a test that measures a known activity of that T-ag. SV40 T-ag in mesotheliomas was shown to interact with tumor suppressor protein p53 (139) and to be able to bind the Rb family of tumor suppressor proteins (140). Unfortunately, these types of functional assays require relatively large amounts of fresh, unfixed tumor sample. Paraffin-embedded samples, needle biopsy material, or small amounts of tumor tissue are not adequate to be tested using these procedures.
An additional level of complexity is that viruses may act as cocarcinogens, i.e., cancer development may be influenced by viral infection but require other cofactors as well. This possibility is exemplified by reports of association of SV40 with human mesotheliomas (137–143). There is a significant correlation between asbestos exposure and the development of mesotheliomas; it is possible that SV40 accelerates the development of mesotheliomas in asbestos-exposed individuals or that both asbestos and SV40 together are required to induce mesothelioma development in some persons.
Polyomaviruses are small DNA viruses that are dependent upon host cellular factors for replication, requiring the involvement of a single viral product, the T-ag. These viruses target terminally differentiated cells, which are usually in a quiescent state. Because the factors required for DNA replication are not actively expressed in quiescent cells, polyomaviruses induce the synthesis of necessary factors by stimulating entry into the cell cycle. This is mediated at least in part by the binding of viral T-ags to tumor suppressor proteins Rb and p53, leading to cellular S-phase. The side effect of this replication function is that the viruses have an intrinsic ability to transform cells under certain conditions, especially in cells resistant to a permissive viral infection.
The mere association of polyomavirus DNA with cancer tissue is not proof of causality. The main difficulties in establishing a polyomavirus as an etiologically significant factor in human cancer causation are similar to those that were encountered in studies of cancer induction by HPV (reviewed in Ref. 3,116). These difficulties are: (i) The infecting viruses cause ubiquitous infections, yet only a small percentage of infected individuals develop cancer. (ii) The time periods elapsing between primary infections and cancer development may be prolonged. (iii) Other agents (such as chemicals) are frequently suspected to be causally related to the same tumors.
To date, the number of human tumors associated with polyomaviruses is small, yet infections by BKV and JCV are ubiquitous and evidence is mounting that infections by SV40 do occur (3). There is no doubt these agents can cause cancer in experimental animals. To provide convincing evidence of an etiologic role in human tumors, functional studies will need to be carried out to analyze viral expression in the implicated tumors. Useful approaches would examine properties including the status of viral DNA in tumor cells, the percentage of virus-infected tumor cells, the expression of viral oncoproteins in tumor cells and their interaction with cellular tumor suppressor proteins, the possible strain variation of tumor-associated viruses, and possible synergism due to coinfection of tumor cells by two known polyomaviruses. If polyomaviruses are contributing to the development of human neoplasia, it will be informative to determine the unique genetic, physiological, or immunological nature of those individuals who are prone to virus-mediated tumor induction.
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96. Monini, P., L. de Lellis, A. Rotola, D. Di Luca, T. Ravaiolo, B. Bigoni, and E. Cassai: Chimeric BK virus DNA episomes in a papillary urothelial bladder carcinoma. Intervirology 38, 304-308 (1995)
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From the Marble Falls Police Department:
On September 4, 2015 the Marble Falls High School hosted San Antonio John Jay High School for Friday night football. During the game, two players from John Jay High School targeted one of the game officials and blindsided him, knocking him to the ground. The incident was recorded on video from several different angles and the Marble Falls Police Department is conducting an investigating. No arrests have been made at this time. An update will be released within the week.


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By Thomas J Webster
Managerial economics is the applying of monetary thought and quantitative equipment (mathematics and data) to the managerial decision-making technique. This booklet will entice scholars with restricted past education in economics and quantitative equipment. It assumes that scholars could have had arithmetic education a minimum of via pre-calculus and they have had a path in effortless records. It additionally expects scholars to have had an undergraduate path in intermediate microeconomics. The e-book contains those beneficial properties: an internet Instructor's handbook; an internet research advisor; a problem-solving method of the learn of managerial economics that mixes the positive factors of a typical managerial economics textbook with these of a separate research consultant; a style for aiding company scholars strengthen the analytical abilities beneficial for fulfillment within the examine of managerial economics, finance, and administration; and, a extra broad overview of mathematical options than such a lot related textbooks. It features a separate bankruptcy on online game conception, together with: noncooperative, simultaneous-move, one- shot video games; cooperative, simultaneous-move, infinitely- repeated video games (including collusions, dishonest principles, and determinants of collusive agreements); cooperative, simultaneous-move, finitely- repeated video games; focal-point equilibria; multistage video games; bargaining with and with no symmetric and uneven impatience. It features a bankruptcy at the time price of cash and capital budgeting. there's the accentuation of probability, uncertainty, and the economics of knowledge all through publication. it's perform orientated, keeping off advanced theoretical motives with bulky notation. the issues are incorporated in every one part and are made critical to studying and knowing matters. Math assessment makes use of fiscal relationships rather than normal notation. there's first-class stability between motivation, concept, and examples, and transparent exposition. It emphasizes application and applicability, no longer innovation. Chapters finish with: bankruptcy evaluation, key phrases and ideas, bankruptcy questions, bankruptcy workouts, and chosen readings.
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Sample text
Corporate executives who inflate expense accounts in attempts to curry favor with potential clients and bartenders who give free drinks attest to some of the problems associated with revenue-based incentive schemes. OTHER WORKER INCENTIVES Other methods of encouraging workers to put forth their best efforts are piecework, time clocks, and spot checks. Piecework involves payment based on the number of units produced. Sweatshop operations, once common in the textile industry, are examples of this type of revenue-based incentive scheme.
THE OBJECTIVE OF THE FIRM Economists have traditionally assumed that the goal of the firm is to maximize profit p. This behavioral assumption is central to the neoclassical theory of the firm, which posits the firm as a profit-maximizing "black box" that transforms inputs into outputs for sale in the market. While the precise contents of the "black box" are unknown, it is generally assumed to contain the "secret formula" that gives the firm its competitive advantage. The appeal of the neoclassical model is its application to a wide range of profitmaximizing firms and market situations.
Economic good A good or service not available in sufficient quantity to satisfy everyone's desire for that good or service at a zero price. Factors of production Inputs that are used to product goods and services. Also called productive resources, factors of production fall into one of four broad categories: land, labor, capital, and entrepreneurial ability. Financial intermediaries Institutions that act as a link between those who have money to lend and those who want to borrow money, such as commercial banks, savings banks, and insurance companies.
Managerial Economics: Theory and Practice by Thomas J Webster
by Michael


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November 2019
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Near-record highs on the ASX 200 and Nasdaq have propelled a technology wealth boom, with Australia now home to seven billionaire individuals or couples.
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Online entrepreneurs are making their way further up the Rich Bosses List, in sharp contrast to the banking sector.
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The wealthy wage slaves climbing the Rich Bosses List
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Of the 100 people featured in this year's Rich Bosses list, published in Boss magazine on Friday, just three of them are women.
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Metallurgists and old mates Patrick Walta and John Carr took a risk on an old mine that is paying big dividends.
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A Remembrance
A playful, witty, reflective memoir of childhood by the science fiction master Stanisław Lem.
With Highcastle, Stanisław Lem offers a memoir of his childhood and youth in prewar Lvov. Reflective, artful, witty, playful—"I was a monster," he observes ruefully—this lively and charming book describes a youth spent reading voraciously (he was especially interested in medical texts and French novels), smashing toys, eating pastries, and being terrorized by insects. Often lonely, the young Lem believed that he could communicate with household objects—perhaps anticipating the sentient machines in the adult Lem's novels. Lem reveals his younger self to be a dreamer, driven by an unbridled imagination and boundless curiosity.
In the course of his reminiscing, Lem also ponders the nature of memory, innocence, and the imagination. Highcastle (the title refers to a nearby ruin) offers the portrait of a writer in his formative years.
Pre-Order Paperback$17.95 T | £14.99 ISBN: 9780262538466 152 pp. | 5.375 in x 8 in
"An entire vanished world has been lovingly and quirkily recalled in this pages."—New York Times
"Remarkably candid….interlaced with soaring reflections on art, memory, innocence, faith and myth."—Publishers Weekly
"A charming, effervescent memoir from a writer who consistently transcends genre."—Kirkus Reviews


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Relaxing massages provided take a Greece and relax
More Show. Date of experience: December Ask shaddi about Massage Point - Athens. Thank shaddi. Report response as inappropriate Thank you. We appreciate your input. See all reviews. Ways to Experience Massage Point - Athens.
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Traveler rating. Excellent Very good Well done! Beautiful pampering experience worth every cent spent! Flights Vacation Rentals Restaurants Things to.
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Log in to get trip updates and message other travelers. Profile Join. Log in Join. Review Highlights. Reviewed July 7, Reviewed January 10, Excellent massage, nice ambiance.
Maseages Show. Date of experience: August Thank serjs.
Massage Point - Athens: excellent relaxing massage in Athens - See traveler reviews, 27 candid photos, and great deals for Athens, Greece, at TripAdvisor. Log in to get trip updates and message other travelers. Profile When we arrived , we were offered some very good herbal tea and were able to relax and settle. A long weekend in Athens to relax while enjoying the outdoors and the mild tasty and healthy food provide the perfect setting for spending a few days to take a break even further with a Greek traditional relaxing massage (optional/ extra). Your eyes are closed. You are calm, relaxed, your senses have awakened and you leave yourself to be tended to by experienced hands: You.
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Relaxing massages provided take a Greece and relax
Reviews The algae and natural ingredients complex improves blood circulation, stimulates venous flow and reduces foot swelling. A wonderful mask rich in seaweed polysaccharides and green tea extract that gives the body relaxing massages provided take a Greece and relax relas feeling of positive energy and leaves the skin extremely soft, moisturised and radiant.
Luxury treatment with spirulina extract, Palmaria and Brazil Nut Butter which caresses your skin leaving it feeling silky soft and providing a complete holistic wellness experience. Mask with brown seaweed polysaccharides that moisturises the skin, girl and woman kiss redness and boasts tissue regeneration.
Anti-aging mask with spirulina which boasts collagen composition, gives a lifting effect and slows down the skin aging process.
Wellness, spa and rejuvenation in Greece | Discover Greece
Rellaxing made of green clay and algae for deep cleansing, reducing skin oiliness and improvement of elasticity. Rich in healthy ingredients this mask has a visible anti-age and lifting effect. An effective treatment that do something cute for your girlfriend relaxing massages provided take a Greece and relax results, this facial helps to restore radiance for a more youthful glow and more evenly toned skin. Enjoy traditional exfoliation with a special rellaxing in the Byzantine hammam and in the end a few minutes of massage with soap.
An intensive mineral-rich treatment mask that deeply conditions, to leave hair soft and smooth, and the scalp nourished.
Vitamin C-rich Watercress and Red Clay soothe and nourish the scalp, while Apricot Kernel Oil conditions to help promote stronger, healthy looking, manageable hair. Relaxing Spa Massages. Massage with saffron A treatment of Greek origin, which starts with a deeply relaxing massage using a precious Greek product, saffron, and special techniques that relieve the body from accumulated tension.
Swedish massage A traditional full body massage using firm pressure to promote relaxation and ease muscle tension. Mother-to-be A specially designed massage for pregnancy, aiming to offer you comfort and well-being. Antistress Special pressure, massage and stretching techniques that relieve muscles from tension and stress. Slim silhouette Massage with red grape extract focusing on problem areas, with firming and slimming properties. Relaxing massages provided take a Greece and relax massage Relaxing massage where the hands of the therapist are replaced by bamboos, releasing muscle tension and nepali sexy site a deep sense of relaxation.Ladies Looking Nsa Redrock
DETOX massage A massage aiming not only to relax but also to remove toxins using pressure and special lymphatic massage techniques. Lomi Lomi Hawaiian energy massage facilitating mental, relaxnig and spiritual healing by means of soft hand massagees throughout the entire body.
Muscle reviver ESPA A condensed massage for those who relaxing massages provided take a Greece and relax with tension-related headaches and neck strain. Shiatsu massage The perfect coordination of the mind, body and treatment.
Thai massage A year old rhythmic massage that combines stretching, yoga exercises and massaging to relieve muscle tension, enhance flexibility and balance mind, body and spirit. Balinese ESPA This unique treatment transports you to a world of peace and tranqullity where the day-to-day demands of life become a distant memory. Ayurveda massage The entire power and professionalism of the East. Indian head massage A stress relieving massage working on upper back, neck and scalp.
After sun Relaxing massages provided take a Greece and relax mask with aloe and nourishing and moisturising elements, will quench looking for a mature male single skin's thirst and nourish it after relaxing massages provided take a Greece and relax exposure. Body ritual minutes by ESPA This treatment combines a body wrap and massage to restore equilibrium, peace of mind and bring deep relaxation to body and spirit.
Body wrap by ESPA This personalised body wrap is a tailor-made experience designed to comfortably raise the temperature, nourish the skin and increase the effects and absorption of the wrap. Oxygen Oxygen therapy is ideal for the first signs of ageing. Personalised facial ESPA Discover the deeply cleansing, skin-boosting powers of this results-focused facial.
De-sensitiser orovided ESPA A comforting facial for sensitive skins prone to redness and irritation, leaving skin calmed and nourished. Welcome dinner offered in a veg Bio Greek modern restaurant. In the morning you will enjoy a guided walk in the historic center of Athens visit to the Acropolis and to the Acropolis museum are optional.
Next, you will leave for the coast, and join a Greek nutrition workshop, where you will learn hands-on how to prepare Greek healthy food. In the afternoon you will then enjoy a relaxing yoga session by the sea.Discreet Married Dating Blonde Phone Sex Australia
The day will end with a sunset tour to Cape Sounio, where to admire the majestic Temple of Poseidon, before heading back to your hotel.