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Genital Warts (HPV Infection) Causes, Symptoms, Treatment
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Condylomata acuminata
Condylomata acuminata are caused by human papillomaviruses (HPV). They are usually present as genital warts, but other locations (oral) are known to be involved. HIV-infected patients have a higher risk of acquiring genital warts. The typical pathogens, human papillomavirus type 6 or type 11, are not normally considered to be cancerogenic. Although, in both male and female HIV-infected patients, epithelial atypia is seen more often than in uninfected persons. Besides sexual transmission, infection with papillomavirus may be possible via smear infection and perhaps through contaminated objects. But the primary risk factor remains the number of sexual partners (Karlsson 1995).
Laryngeal papilloma
The juvenile form is believed to be acquired during birth from maternal vaginal warts. The condition does not manifest, however, until months or years later when significant papillomata develop. In general, those who present early usually present with airway obstruction, while older children usually present with progressive hoarseness. Treatment is extremely difficult and frequent recurrence is a rule rather than exception. At laryngoscopy, there is usually extensive involvement of the whole larynx simultaneous tracheal and pharyngeal involvement by the papillomata is not uncommon. Repeated CO2 laser therapy offers the best control of the disease. In severe cases, antiviral therapy including interferon therapy may be tried. Although the effectiveness of treatment is unpredictable, spontaneous regression of the papilloma may occur at any age. The adult form typically presents with progressive hoarseness and laryngoscopy, and reveals either a solitary papilloma or multiple but discrete...
Lucky Day For Two Neuropathologists And More Luck On A Sabbatical
And we could not believe our luck and kidded about the influence of the Bacardi. After Dr. Chou developed the first photographic plates that also revealed scattered virions and filamentous forms, we hugged in the dark room what an exciting day in our lives it was. Whereas the tissue in general showed moderate autolysis, the virions were so well preserved that their images compared favorably with those in the literature. The virions belonged to an identifiable group, with oncogenic potential, perhaps explaining the bizarre shapes of as-trocytes, and this virus had penetrated deep into the brain, unlike papilloma viruses. Yet no human polyoma virus was known at that time. When we showed the plates to Dr. Angevine, his dry comment was This is the way discoveries are being made.''
The Selling Of The Apples Acceptance Collaborations And Invitations
Well, our ''apples'' sold fast and widely. Science published our first paper (Zu Rhein and Chou, 1965). Dr. Zimmerman had agreed that we should not wait for the publication of the ARNMD volume, which indeed became delayed for 4 years. A neighbor in the Bronx was Dr. Ludwik Gross, Director of the Cancer Research Unit of the VA Medical Center. A pioneer in virus research, he had stood at the cradle of the polyoma virus. Some of his work had also been met with disbelief early on. He was a virologist well versed in viral morphology. When he reviewed our PML electron micrographs, he shared our interpretation with enthusiasm. He invited me subsequently to join him in a research seminar on ''Viruses in Disease.'' We stayed in close contact for the later editions of the Oncogenic Viruses. Dr. Richard Shope (Rockefeller University), discoverer of the rabbit papilloma virus, also became an immediate supporter during a laboratory visit. ''You are in business'' he told me with confidence and true...
Regulation of p53 function
It was demonstrated some years ago that human papilloma viruses (HPV), especially HPV 16, 18 and also some other types, are associated with high-grade cervical intraepithelial neoplasia (CIN) and invasive cervical squamous carcinomas. The integration of these viruses in the genome results in increased expression of the proteins known as E6 and E7, and these proteins have the ability to transform cells into the neoplastic state. Immunohistochemical studies have shown co-localisation of p53 phosphoprotein and E6, suggesting an association between them (Liang et al., 1993). It would appear that the E6 protein binds the p53 phosphoprotein (Werness et al, 1990). This requires another cellular factor called the E6-associated protein (E6-AP). This event leads to a rapid degradation of p53 protein, mediated by ubiquitin-dependent proteolysis (Huibregtse etal., 1993). The introduction of a single HPV16-E6 gene causes the immortalisation of cells and sharply reduces p53 protein levels (Band et...
Kenneth Lundstrom PhD Contents
Alphavirus vectors can infect a broad range of mammalian cells both in cell cultures and in vivo. The presence of the RNA replicon generates extreme RNA levels in infected cells, which is the basis for the very high levels of heterologous gene expression. Application of replication-deficient vectors leads to short-term expression, which makes these vectors highly attractive for cancer gene therapy. Alphaviruses can be used as vaccine vectors for both prophylactic and therapeutic applications. In this context, the P185 tumor antigen and human papilloma virus gene E7, when administered in mice, resulted in protection against tumor challenge and tumor regression in animals with pre-existing tumors. Alphavirus vectors carrying therapeutic or toxic genes used for intratumoral injections have demonstrated efficient tumor regression. For systemic delivery, expression targeting has been obtained by the introduction of targeting sequences in the envelope structure of the virus. Alternatively,...
Alphavirus Used In Cancer Vaccines
Alphavirus vectors have frequently been applied for vaccine production. In this context, recombinant particles as well as naked nucleic acids have been applied. The proof of concept was originally demonstrated for viral surface proteins known for their potential immunogenicity and capability to induce cytotoxic T-cell (CTL) responses and protection against challenges with lethal viruses (20). Moreover, immunization against tumor challenges has resulted in some promising observations (Table 1). For instance, injection of RNA from an SFV vector expressing bacterial -galactosidase into mice provided protection against tumor challenges (21). Administration of recombinant SFV particles expressing the P1A gene resulted in protection against P185 tumor challenges in mice (22). The human papilloma virus (HPV) E6 and E7 oncoproteins have been
VSV Gene Therapy and Vaccines
Designed to protect against respiratory syncytial virus (RSV), human papillomavirus (HPV), and viruses associated with acquired immunodeficiency syndrome (AIDS), amongst others (88-91,93-96). In addition, new generations of attenuated, nonpropagat-ing viruses are being developed where the VSV G protein has been deleted. These non-propagating viruses (AG) lacking G, which is essential for infectivity, are generated via helper-cells that supply the VSV G glycoprotein in trans (29,88,97). Budding viruses incorporate the G protein on their surface and are released. Such viruses can infect cells through the highly tropic G protein and commence replication. However, AG progeny viruses, when released from their primary targets, cannot infect other cells because they lack the G protein gene product. In vaccine studies, such viruses have been shown to retain their protective efficacy compared with their wild-type, replication competent counterparts, yet are considerably attenuated (88,97)....
Retinoblastoma susceptibility gene rb abnormalities in cancer
Consistent with these thoughts is the observation by Wrede et al. (1991) that no abnormalities of rb or p53 are detectable in human papilloma virus (HPV positive cervical carcinoma cell lines. The rb protein expressed in these cell lines was of the wild-type (Scheffner et al., 1991), but evidence of abnormalities are found in HPV-negative cell lines. Riou et al. (1992) found that early-stage invasive cervical cancers which over-express the myc oncogene in the absence of HPV show a high risk of distant metastases, thus myc gene over-expression may be deemed as an independent prognostic indicator of metastasis.
Regulation of cell cycle progression by retinoblastomasusceptibilitygene product
The sequestration of unphosphorylated rb protein will allow the cells to transit into the S-phase. It is known that functional rb protein forms stable complexes with transforming oncoproteins such as those encoded by the simian virus 40 (SV40) and human papilloma viruses (Templeton et al, 1991). HPV E7 binds to rb protein and such binding is necessary for E7 protein to immortalise and transform cells (Dyson et al., 1989 Munger et al, 1989 Gage et al, 1990). The SV40 T-antigen is known to bind preferentially to the underphosphorylated rb protein (Ludlow et al., 1989). Although these studies suggest a close correlation between phosphorylation and the transition of cells from G, into the S-phase of the cell cycle, phosphorylation might be a progressive event and this may be reflected in the molecular heterogeneity found in rb proteins (Xu et al., 1989). The process of rb phosphorylation may be an incremental process beginning in late G,, several hours before transition into the S-phase
Identification Of A New Virus
On October 7, 1970, a midstream urine sample, collected a day earlier, arrived in the laboratory from a Sudanese patient who had received a renal transplant from his brother on June 24, 1970. A phone call the same day from St. Mary's Hospital informed us that this urine contained many inclusion-bearing cells, and so electron microscopy examination would be well worthwhile. Two days later, Anne Field saw very large numbers of papovavirus particles in the high-speed urine pellet and suggested that they were particles of common wart virus (the only human papovavirus known at the time). It was queried whether the patient had genital warts a report earlier that year (Spencer and Andersen, 1970) had described a high incidence of warts after renal transplantation. Ultrathin sectioning of the cells in a subsequent urine sample collected on October 12 from the same patient showed many virus particles within enlarged cell nuclei. Measurement of the virus particles (45 nm diameter) showed the...
Strategies Using Nonviral Vectors In Cancer Gene Therapy
Electroporation (66,67), resulting in significantly induced cytokine levels or specific antigen expression. Electroporation has also been used to introduce plasmids that encode antisense RNA against E6 and E7 mRNA to human papilloma virus (HPV) expressing cancer cells, which resulted in a significant inhibition of tumor growth (68). Another approach involved gene gun-mediated delivery of heat-shock protein 70 (Hsp70) linked to the HPV16 E7 tumor antigen gene into antigen presenting cells (APCs). It led to an enhanced E7-specific immune response of lymphocytes after exposure to these transfected APCs (69).
Screening and Cancer Control
This chapter focuses on the use of screening for cancer. Cancer is a leading cause of death worldwide, and in 2007 accounted for 7.9 million deaths (around 13 of all deaths), a figure that is predicted to rise to 12 million by 2030 (WHO, 2009). Screening represents a major part of the cancer control effort, particularly in developed countries. The Papanicolaou (Pap) test for the detection of pre-cancerous cervical lesions is the most widely used cancer screening test. It was developed in 1928 and is now available to women across the globe albeit with different technologies and test frequencies. Some cervical cancer screening programs now also incorporate DNA testing for human papillomavirus (HPV), the viral precursor to cervical cancer. Mammography screening was developed in the 1950s for early diagnosis of breast cancer and involves taking a low-energy X-ray of the breast which is then examined for signs of calcification or soft tissue masses. More recently, colorectal cancer (CRC or...
Provision of Cancer Screening Services
Cervical screening is currently offered to women in most developed countries. This is usually by Pap testing, but there has recently been a move to using liquid-based cytology in some countries. The USA and Canada offer cervical screening opportunistically, but organized programs are offered in Australia, the UK, and some other European countries. In a survey of 25 European screening centers (from 18 countries), organized screening was offered by 15 and opportunistic screening by 10 centers (Anttila et al, 2004). The age that cervical screening starts ranges from 18 to 30 years, and screening usually finishes between 60 and 69 years. Recommended screening intervals vary widely across countries (from 1 to 10 years) and in some countries depend on the age of the woman and whether she has had a previous abnormal result. Across Europe, the number of Pap tests a woman has in her life time therefore ranges from 7 to 50 (Anttila et al, 2004).
Optimizing Screening Uptake
In most developed countries, uptake of cervical screening is good. The most recent figures in the UK show that 79 of women aged 25-64 years have been screened within the last 5 years (2008-2009 figures NHSCSP, 2009), and in Australia the equivalent figure for women aged 20-69 years is 86 2006-2007 figures Australian Institute of Health and Welfare (AIHW), 2009b . Across Europe, uptake of cervical screening at the recommended intervals ranges from 30 to 93 and is greater than 75 for six countries Finland, Sweden, UK, Denmark, Iceland, and the Netherlands (Anttila et al, 2004). In the US National Health Interview Survey, 83 of American women aged 18 or older reported having had a Pap test in the preceding 3 years (2000 data Solomon et al, 2007). Similarly in the Canadian National Population Health Survey, 79 of women aged 20-69 said they had had a Pap test within the previous 3 years (data from 1998-1999).
Impact of Abnormal Results
The introduction of HPV testing into cervical cancer screening brings with it the negative psychological consequences that are more often associated with testing for sexually transmitted infections, including feelings of stigma and shame as well as concerns about transmission, and questions about where the virus has come from, with the associated issues of trust and fidelity (McCaffery et al, 2006). In addition, poor understanding of the meaning of an HPV result can lead to heightened anxiety, at least in the short term (Maissi et al, 2004).
Shift of Boundary Between Risk and Disease
For a disease that is as much feared as cancer, this is a powerful motive for the public too. However expansion of screening programs may also increase people's sense of risk or to put it the other way, undermine the illusion of health. With some screening programs identifying precursor risks (e.g. HPV infection) in a much higher proportion of the population than would ever have been likely to develop cancer, then the barriers between health and disease are blurred further. This is striking in the metabolic field where huge proportions of the population are identified with hypertension, insulin resistance, or hyperlipidemia, potentially creating an almost population-wide perception of compromised health status. The growth in personalized genetic testing - which will increasingly offer quantitative risk feedback rather than just testing for the presence or absence of highly penetrant mutations, will also add to the blurring of boundaries between health, disease risk, and disease....
Tumor Induced Changes In Mhc Class I Presentation Of Hostderived Peptides
Additionally, tumors display classical or universal stress responses that are easily identifiable with other disease states, such as viral infection. Indeed, a number of cancers are induced by viral infection by such agents as Epstein Barr Virus and Human Papilloma Viruses. Universal stress induced responses identified in tumor cells include up-regulation of MHC class I, Hsp72, and the NK cell ligands MHC-like MICA and MICB. Interestingly, these common stress induced genes are located within the MHC class I loci of chromosome 6 (Collins, 2004). In addition, many transcriptional regulators and translational regulators are over-expressed by both tumors and virally infected cells, including Stat-1, p68 and eIF4G (Abbas et al., 2000 Bates et al., 2005 Clemens, 2004).
Nora A Janjan John M Skibber Miguel A Rodriguez Bigas Christopher Crane Marc E Delclos Edward H Lin and Jaffer A Ajani
Anal cancer is a rare neoplasm, accounting for less than 2 of all cancers of the digestive tract. Despite its rarity, specific risk factors for anal cancer development have been identified. High rates of human papillomavirus (HPV) infection have been observed in anal cancer, and an increased risk of anal HPV infection has been demonstrated in HIV-seropositive patients. An inverse relationship has been shown between the CD4 count and HPV infection. Immunosuppression from other causes, like organ transplantation, increases the risk of anal cancer by a factor of 100. Smoking increases the risk of anal cancer by a factor of 2 to 5 conversely, a prior diagnosis of anal cancer increases the risk of lung cancer by a factor of 2.5.
Extending the Life Span of Muscle Cells
Since the moderate proliferative capacity of primary human skeletal muscle cells is a limiting factor in studies for which large numbers of myoblasts are required, several groups have tried to immortalize human myoblasts, or at least to extend their life span 123-128 . Transfection of human myoblasts with constructs that carry the gene encoding the SV40 large T antigen resulted in an extended life span of these cells while their capacity to differentiate in a nearly physiological manner was more or less well preserved. Expression of the T antigen has been used to immortalize several cell types of human origin 129 . This immortalization depends on the inactivation of tumor suppressor proteins p53, retinoblastoma gene product (RB), and the RB-related proteins p107 andp130 130 . RB, in turn, seems to bind and inactivate MyoD and myogenin, thus inhibiting dedifferentiation of myotubes 131, 132 . Therefore, in myoblasts the expression of the T antigen has to be switched off in order to...
Biological Functions of Rb and E2F
E2F can also be released from E2F Rb complexes by viral oncogenes such as the SV40 large T antigen or by the human papilloma virus E7 protein. The strains of HPV that are associated with cervical cancer encode E7 proteins with the highest affinity and the ability to degrade Rb (Munger, 2002).
Mutations In The Ube3a Gene
The UBE3A gene had been known to encode the E6-associated protein, a protein interacting with the human papilloma virus, to promote the nonlysosomal degradation of the p53 protein (Huibregtse et al., 1991 Scheffner et al., 1990). The gene encodes an E3 ubiquitin protein ligase that is probably involved in the ubiquitination of a diverse range of proteins (Scheffner et al., 1993 Huibregtse et al., 1993). The UBE3A gene encodes a member of a family of functionally related proteins defined by a conserved C-terminal 350- amino acid ''hect'' domain. Hect E3 proteins appear to be important in substrate recognition and in ubiquitin transfer. RT-PCR experiments provided evidence for several isoforms differing at their N termini. Each of the mRNAs was expressed in all cell lines tested. Additional 5' untranslated exons were also identified (Kishino and Wagstaff, 1998). In fact, at least 16 exons were identified, including six exons that encode the 5' UTR. The gene spans approximately 120 kb,...
Preclinical Vaccine Development
Fortunately, vaccine developers did not wait for the conclusions of the prospective epidemiology studies before initiating work on prophylactic HPV vaccines. Perhaps because these investigators were primarily laboratory-based researchers, and even, as in our case, involved in the studies of the HPV oncogenes, they were not unduly inhibited by the weak correlation between HPV infection and cervical disease seen in the early epidemiologic studies. In any event, considerable activity aimed toward developing HPV vaccines was underway by 1990. A vaccine based on a live attenuated HPV strain was not considered a viable option for two reasons. First, HPVs could not be propagated in replicating cells in culture, so there was no reasonable means of virus production. Second, the virus was known to contain at least three oncogenes, E5, E6, and E7, and a vaccine that delivered oncogenes might not be considered safe for general use as a prophylactic vaccine. Therefore, most efforts involved...
Posttranslational Modifications
P53 was first shown to be ubiquitinated by a cellular factor that associated with the viral E6 protein in papilloma-virus-infected cells (Scheffner et al., 1993). It was later determined to be predominantly degraded through the ubiquitin-proteosomal pathway (Chowdary et al., 1994 Maki et al., 1996). However, in normal cells Mdm2 (Hdm2 in humans hereafter referred to as Mdm2) acts as the predominant regulator of p53 protein levels by implementing its E3 ligase activity on p53 (Haupt et al., 1997 Honda et al., 1997 Kubbutat et al., 1997). Additionally, Mdm2 can inhibit the transactivation ability of p53 (Momand et al., 1992). Maintaining p53 at low levels is critical for cellular homeostasis in unstressed conditions. p53 assists in its
Antioncogenic Properties Of
The antitumor effects of AAV had been initially reported within a few years of identification of the virus itself when it was identified that infection of herpes simplex virus (HSV)-transformed hamster tumor cells with AAV delayed the appearance of palpable tumors and increased the survival time of the animals (70). Since then, several reports have confirmed the inhibition of viral oncogenesis by a variety of DNA viruses, including bovine papillomavirus-1 (71), human papillomavirus (HPV)-16 (72-74), and Epstein-Barr virus (75). Evidence from several reports also suggested that AAV infection might protect against human cervical cancer, in part, by interfering with HPV-induced tumori-genesis (76) although studies of Stickler et al. reported a lack of correlation of between AAV infection and cervical tumorigenesis in a Jamaican population (77).
Arrival Of Pml Cases And An Electron Microscope
Another interdisciplinary contact, which became of considerable importance later on, developed with Veterinary Science. In this Department, Dr. Carl Olson had created a research unit for the study of papilloma viruses, especially of bovine and canine types. A viral oncologist who appreciated the contributions of morphology, he early had acquired an electron microscope. My affiliation with Veterinary Science began in 1957. All such students had to do course work in pathology, and I became their instructor in neuropathology. Over the years I served on at least nine examination committees for M.S. or Ph.D. In May 1964, another of Dr. Olson's students took his Ph.D. examination, and I was a thesis reader. Among the illustrations for ''The Cytology of Canine Oral Papilloma'' were electron micrographs of cell nuclei with dispersed or aggregated virions. Listed among the references was Dr. Melnick's paper in Science (1962) entitled ''Papova Virus Group.'' In it, he combined the papil-loma...
The Start Of A Collaboration
Gabriele Zu Rhein clearly wanted to see this virus cultivated and characterized. She had demonstrated its presence in oligodendrocytes in PML brain tissue. The logical next step was to cultivate and identify it in order to study its role in nervous system disease. She wanted to have a part in that process, but she did not have the virology laboratory or virology background to do this, so she began prodding me to take it on in a collaborative project. I had a virology laboratory in the Department of Medical Microbiology in the same building but one floor below the Department of Pathology and Gabriele's electron microscope suite. Gabriele and I had co-authored a paper in 1956 concerned with a virus infection, but had not worked together in the interim. I had been studying persistent, chronic viral infections in cell cultures and animals and also was in the middle of a study of myxoma and fibroma virus infections. I had no experience with polyomaviruses, but I had some experience with...
The Association of HPV and Cancer
It has been known for many decades that filterable transmissible agents, i.e. viruses, cause cutaneous and mucosal papillomas (warts) in animal models and in humans 1 . The oncogenic potential of papillomaviruses was first demonstrated by Payton Rous and J.W. Beard in the 1930s. They observed that epidermal papillomas induced in domestic rabbits by Shope cottontail rabbit papillomavirus (CRPV) could progress to squamous cell carcinomas, and that viral oncogenicity was enhanced by chemical cocarcinogens. However, the progression of human common and genital warts to cancer was virtually never observed, and so a link between HPV infection and human carcinogenesis was largely discounted. However, there were indications, first noted in the mid-1800s by the Italian physician, Rigoni-Stern, that cervical cancer had the epidemiological characteristics of a sexually transmitted infection. He astutely noted that cervical cancer was common among prostitutes, but rare in virgins or nuns 2 . Much...
The Driving Force
Latent viruses associated with certain forms of cancer can also drive CD8+ T cells to senescence, as illustrated by the accumulation of CD8+CD28 T cells with reactivity to the human papilloma virus E7 antigen in cervical cancer patients (Pilch et al., 2002). Other viruses associated with chronic infection, such as Hepatitis C, also seem to elicit expanded populations of CD8+ T cells that lack CD28 expression (Kurokohchi et al., 2003). The common thread in all of these situations is chronic antigenic stimulation, which seems to result in massive cell division of antigen-reactive CD8+ T cells, ultimately causing them to reach what might be considered the endstage of their differentiation pathway, namely replicative senescence. Clearly, most memory T cells encounter their nominal antigen only once or twice over an individual's lifespan, and it is only those CD8+ T cells with reactivity to antigens that are never cleared from the body that have the potential to continue dividing...
Epithelial Membranes
The constant loss and renewal of cells is characteristic of epithelial membranes. The entire epidermis is completely replaced every 2 weeks the stomach lining is renewed every 2 to 3 days. Examination of the cells that are lost, or exfoliated, from the outer layer of epithelium lining the female reproductive tract is a common procedure in gynecology (as in the Pap smear).
DNA viruses
A number of groups, the hepadana viruses (hepatitis B), papilloma viruses (HPV) and herpes viruses (EBV) are associated with hepatocellular carcinoma, uterine cervical cancer, Burkitt's lymphoma and nasopharyngeal carcinoma, respectively. HPV have small double-stranded circular genomes of DNA which cause benign infective skin warts. They infect basal cells during their proliferative phase which on full differentiation complete the life cycle of the virus. Genital warts, the third commonest form of sexually transmitted disease, are also due to infection by HPV, and are associated with carcinoma of the cervix. Some 30 of all women are infected with HPV and DNA sequences from this have been identified in the majority of cervical carcinomas. Over 70 types of HPV are known to infect genital sites but only a few (predominately types 16 and 18) are associated with neoplasia. Cofactors are smoking, infection by herpes simplex virus and, possibly, oral...
Anal Cancer
Anal cancer is rare, accounting for less 5 of large-bowel tumours. Over 80 of anal cancers are squamous cell in origin, however, malignant melanoma may occur in the anal canal. The recognition of a high incidence of squamous cell carcinoma of the anus amongst some homosexual men led to the search for an infective aetiological agent. Risk factors for anal cancer include a history of genital warts and evidence now suggests an association between human papilloma virus types 16, 18, 30, 31 and 33, and anal cancer. It is believed that anal cancer may occur due to progression of anal intraepithelial neoplasia in a manner analogous to intraepithelial carcinoma of the cervix, vulva or vagina.
Nipple discharge
After clinical examination of the breast various investigations are undertaken. The discharge should be tested for the presence of blood (e.g. Labstix testing) and examined microscopically for the presence of malignant cells. All patients over the age of 35 years should also have mammography ultrasound examination of the breast may reveal the presence of dilated lactiferous ducts, particularly those close to the nipple and areola. In some patients, if there is discharge from a single duct, a ductogram (injection of contrast material into the duct) may demonstrate an intraduct papilloma, carcinoma or duct ectasia. In many women in whom no underlying cause for the discharge has been found, the discharge may resolve, be intermittent and or of small amount which does not concern the patient (see Fig. 17.16 for management). However, if there is a large amount of discharge, if it comes from a single duct or
The Food and Drug Administration (FDA) has recently approved the use of interferons to treat a number of diseases. Alpha interferon, for example, is now being used to treat hepatitis C, hairy-cell leukemia, virally induced genital warts, and Kaposi's sarcoma. The FDA has also approved the use of beta interferon to treat relapsing-remitting multiple sclerosis and the
Clinical Trials
In 2002, the results of the first proof of concept efficacy trial of an HPV VLP vaccine were published. Three 40 mg doses of Merck's HPV16 VLP in an aluminum adjuvant were administered over a 6-month period. Over the course of 1.5 years of follow up, 41 of the approximately 1,000 placebo controls developed persistent HPV16 infection, while none of the 1,000 VLP vaccines became persistently infected. Laura Koutsky's unannounced presentation of these results at the 2002 International Papillomavirus conference is etched in our memories. It was electrifying to hear that simple intramuscular injection of a VLP vaccine could induce 100 protection against persistent cervical infection, even in the short term. Two important decisions needed to be made before proceeding to large-scale phase III studies aimed at generating the data required for licensure. The first was the composition of the vaccine. In this instance, the development paths diverged for Merck and GSK, which, as noted above, had...
It is interesting to speculate why the efficacy of this vaccine has proven to be so high, while that of other STI vaccines have not. First, the vaccine is based on the production of neutralizing antibodies, not T cell effector responses, and antibody-mediated protection is a well-established principle on which to base a prophylactic viral vaccine. Second, strong neutralizing antibody responses are induced in greater than 99 of vaccinees. The mammalian immune system has clearly evolved to induce exceptionally strong antibody responses against the highly ordered and repetitive epitopes characteristically displayed on the surface of a VLP, presumably because virion neutralizing antibodies are so critical for defense against most viral infections. Third, papillomaviruses have a unique lifecycle that involves limited exposure of the virions to the systemic immune system. Therefore, there has been limited pressure on the virus to evolve mechanisms to escape systemic antibody responses...
Of keratinocyte and mammary epithelial cells (Neyns et al, 1999 Li et al, 2000). Although c-Jun overexpression in transgenic mice does not result in the development of tumors, c-Jun ablation or its inhibition suppresses tumor progression (Grigoriadis et al, 1993). c-Jun knockout mice have drastically reduced number and size of hepatic tumors (Eferl et al, 2003). c-Jun ablation in the skin of the tumor-prone K5-SOS-F transgenic mice results in less EGF receptor expression in basal keratinocytes and smaller papillomas, and transgenic mice expressing c-Jun TAM67 in the basal keratinocytes escape chemically induced papilloma development (Zenz et al, 2003 Young et al, 1999).
AAV vectors are also being examined as potential vehicles for tumor vaccines. In one study, an AAV-based tumor vaccine was developed by constructing a chimeric gene containing a human papillomavirus (HPV) type 16 E7 CTL epitope fused to a heat shock protein. When administered intramuscularly, this vaccine was able to eliminate tumor cells in synge-neic animals in a manner that was dependent on CD4+ and CD8+ cells. This suggests that vaccination with this gene could be a therapeutic treatment for cervical cancer containing HPV-16 E7 (295)
Although neoplasms are not a cause of acute or chronic pharyngitis, tumors arising in the oropharynx often present with signs and symptoms that most commonly indicate an infectious etiology. Patients treated for infectious pharyngitis, who do not improve, warrant further investigation to identify a possible neoplasm. Common presenting symptoms of oropharyngeal cancer include unilateral sore throat, dysphagia, odynophagia, weight loss, and otalgia. On physical exam, an asymmetric pharyngeal mass is the hallmark clinical finding and warrants further investigation (Fig. 4). The mass may be ulcerative, fungating, or mucosal covered and detectable only by palpation. Cervical adenopathy is present with advanced disease that has metastasized to the locoregional lymph nodes. Risk factors for oropharyngeal cancer include tobacco and alcohol abuse. The human papilloma virus has a role in a subset of oropharyngeal tumors.


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It's surprising how much about income taxes can be packed into a few web pages. Obviously nobody can review the whole tax law - point by point simply. But it's possible to signal a few warnings, and to single out some special pitfalls.
One point at the outset: There is no single, magic formula for smart tax work. There is no "inside" way to cut way down on what a man must inevitably pay to the Internal Revenue. There is no secret gimmick that a few informed tax solicitors and Accountants know about. What there is, though, is the possibility of reducing your taxes to a minimum level in a given situation.
And one warning: The tax man - Accountant, solicitor, or self-styled "expert" - who promises you a windfall in taxes saved, and who suggests that he has all kinds of methods for tax reduction that you never heard of - may be a man to avoid.
True, there are gray areas in the tax law, and it's possible to color them pure white and make them work to your advantage, if you use some sharp techniques. But the sharp techniques can bite back, and every year a few thousand otherwise honest people find themselves in a local courtroom. And thousands and thousands more though they stay out of court - end up paying stiff pound penalties for paying too little, too late to the UK. Treasury.
The idea is expressed by the tax solicitors this way: It's perfectly proper to avoid taxes - that is, to pay just as little as you can within the bounds of the law; it's not proper, or even legal, to evade taxes - which is what the sharpies and know-it-alls attempt to do. With this much tucked away, it's possible to review some sensible, pound-saving pointers.
You're hitting a rough market these days if you are putting a house up for sale. Finding a buyer who can pay the price - and swing the needed mortgage deal - may not be easy. Keep in mind that to help your house sell, you might:
Hire an independent appraiser (whose fee will be somewhere in the £100-£150 range). Check his appraisal against what two or three real estate men say the house is worth. This will help you price it right - and not scare away buyers by reaching for an unrealistically high price that an agent might suggest. Rule of thumb: If it's a £50,000 to £75,000 house, allow maybe 10% for "horse-trading." Ask, say £60,000 - if you're willing to go... see: On The Selling Side: How To Move A House

subset: commoncrawl


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Thanks for subscribing to Axios Science. Please consider inviting your friends and colleagues to sign up. I appreciate any tips or feedback — simply reply to this email or send me a message at [email protected].
Situational awareness: Hurricane Florence is spinning in the Atlantic, and computer model projections show it is a growing threat to the East Coast next week. Here are key messages from the National Hurricane Center.
1 big thing: Deeper corals aren't refuges after all
Deep-water coral reefs may not offer adequate protection to corals being degraded by heatwaves at the surface of the ocean, according to new research.
Why it matters: Those reefs, at between 100–500 feet underwater, are frequently viewed as conservationists' best hope in saving vulnerable corals.
- The widespread degradation of coral reefs — which nurture creatures that provide critical food supplies for millions of people — is one of the clearest impacts from climate change affecting humanity.
The details: The study, published Tuesday in Nature Communications, examines the extent to which coral bleaching penetrated to deeper waters during the Great Barrier Reef's devastating mass bleaching event in 2016.
- During this event, 30% of the Barrier Reef's shallow water corals died.
How they did it: Using temperature measurements at various depths at nine sites on the Great Barrier Reef and in the western Coral Sea, plus surveys conducted by divers down to 130 feet, the researchers concluded that deeper depths offered some protection from intense bleaching. However, this protection came with caveats:
- Initially, cooler waters moving up from deeper waters kept the deep-water corals from bleaching. But once these currents shut down as the austral summer ended, the water temperatures skyrocketed in these zones, too.
- The researchers characterized the impacts on the deep reefs as "severe" — 40% of the coral colonies studied were bleached, and 6% died.
- The toll closer to the surface: 69% of coral colonies bleached at a depth of just 16 feet.
- Researchers also found the species of corals change with water depth. That hints at the difficulty of a leading conservation strategy involving relocating vulnerable corals from the surface to deeper waters.
The context: Several studies published in the past few years raise doubt that deep-water corals can serve as refuges for coral species deemed vulnerable at the surface.
- For example, a study published in the journal Science in July, found that deep-water reefs are "distinct, impacted, and in as much need of protection as shallow coral reefs."
- Another recent paper reported reefs on the island nation of Palau have seen an uptick in bleaching events, though at different intervals and with varying severity compared to surface reefs.
Yes, but: One limitation of the new study, according to study author Pedro Rodrigues Frade from the University of Algarve, is that it does not indicate what ultimately happened to the deep coral reefs after the bleaching event.
- The research team hopes to return to their monitoring sites to see if these corals bounced back or suffered longer-term damage, like many of the surface reefs did.
Thomas Frölicher, a climate researcher at the University of Bern who was not affiliated with the study, tells Axios the new research also shows that scientists need to better understand local ocean currents, which can control the fate of deeper reefs.
2. Immunotherapy target brain cancers
An international team of scientists says it's developed a molecule that can target the two most common brain cancers, successfully slowing down tumor growth in a pre-clinical study on animals published in Nature Wednesday, Eileen Drage O'Reilly reports.
Why it matters: The targeted brain cancers — adults' glioblastoma and children's medulloblastoma — are aggressive cancers often fatal within 2 years (as seen when glioblastoma claimed the life of Sen. John McCain). The team hopes this new method, which successfully breaches the blood-brain barrier, can be an important step forward in finding an effective treatment.
What they did: The team first determined the best way to breach the brain barrier by studying the mechanism used by another disease, multiple sclerosis, to get around the barrier.
- Then, "using lessons learned from MS," they developed a molecule that can get around the barrier by attaching to certain cells of the barrier (known as ALCAM), study co-author Nabil Ahmed tells Axios.
- The T-cells are engineered to bind to an antigen produced by the cancer (called HER2), allowing it to locate and attack the tumors.
What they found: In testing in mice, the molecule, known as HS-CD6, "robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumor activity," the study states.
- The therapy did not appear to be toxic, which is a common failing of immunotherapies, and appeared to only attack the tumor sites, the authors said.
"The HS molecule that can overcome this [blood-brain] obstacle is a first-in-class; no similar molecules have been previously described. ... I am quite excited about the possible advantage of this to patients with incurable brain cancers that could hopefully benefit from using this in the clinic."— Nabil Ahmed, Baylor College of Medicine
What they're saying:
- Stanford University's Michelle Monje-Deisseroth says it's a "major leap forward" in understanding the trafficking of T-cells to brain tumors.
- Heidelberg University's Michael Platten writes in Nature that it "lays out a viable strategy for immunotherapy in glioblastoma" but faces key challenges including concerns about toxicity and targeting the wrong cells.
Go deeper: Read Eileen's full piece here.
3. How to cost-effectively decarbonize power
Renewables are just part of the answer to how we can best transition to a zero carbon power sector by midcentury, Ben Geman writes. It will also take other low-carbon tech options, and policymakers should not close the door on any of them, a new paper by MIT researchers finds.
Why it matters: So-called "deep decarbonization" of electricity systems by mid-century is an important part of preventing runaway global warming.
What they did: The study in the peer-reviewed journal Joule offers a new taxonomy for how to think about a decarbonized power mix. The study explored almost 1,000 power sector scenarios based on various emissions limits, regional differences, technology uncertainties and more.
It's the latest entry on the "no" side of a debate among some academics and activists over whether renewables and storage alone can decarbonize energy systems.
The details: The study breaks down climate-friendly energy technologies into three basic categories:
- Variable renewable resources, like wind and solar.
- "Fast-burst" resources, including batteries and pricing changes, that can provide quick adjustments to supply or demand.
- "Firm" low-carbon resources including nuclear, natural gas with carbon capture and hydro-dams with large reservoirs.
What they found: We're going to need to rely on that last category — "firm" low-carbon resources, in order to affordably get power sector emissions down to zero.
"It's not about specific technologies. It's about those key roles that we need filled on the low-carbon team," study co-author Jesse Jenkins tells Axios.
The big picture: The study arrives as California is on the cusp of enacting legislation that requires a zero carbon power mix by 2045.
What they're saying: Energy experts who were not involved in the study tell Axios it makes valuable contributions.
Costa Samaras of Carnegie Mellon University says it helps to show that even steep cost declines in renewables and batteries aren't enough.
- "What the authors have shown in this paper, is that getting to a zero carbon energy system is considerably more costly without firm low-carbon resources even when considering that variable renewables and fast-burst balancing resources could get really cheap," he said.
4. Axios stories worthy of your time
Education and family choices: American women with an advanced degree are having more kids on average than those with only bachelor's degrees, Stef W. Kight writes.
Ebola: The outbreak in the DRC has spread to a new city of about 1 million people, complicating containment efforts, Eileen reports.
Lower carbon oil: Saudi Arabia is promoting their vast oil supplies as having a lower carbon intensity than other major producers, per Ben Geman.
Anti-aging drug boom looms: As the average age in developed economies rises in coming years, the anti-aging drug market may expand, Steve LeVine writes.
Cancer: Driver, a new health startup, hopes to connect cancer patients and survivors to treatments, according to Bob Herman.
Coming epidemics: Peter Hotez writes for Axios Expert Voices about the factors that are making the U.S. increasingly vulnerable to epidemics.
5. What we're reading elsewhere
Data searching: Google launched a new service that will allow people to search scientific and other datasets, reports The Verge's James Vincent.
Huge push for open-access publishing: 11 major European research funders announced a plan to mandate, starting in 2020, that scientists they fund make resulting studies free to read upon publication, per Nature's Holly Else.
Meet NASA's newest spacecraft: NASA is set to launch a new satellite, ICESat-2, on Sept. 15. It will track Earth's melting ice sheets with greater precision than ever before, writes Maddie Stone for Earther.
Ultima Thule comes into view: NASA's intrepid New Horizons spacecraft, which flew by Pluto in 2015, caught site of its next target, writes Miriam Kramer for Mashable.
6. Something wondrous
The Cassini spacecraft, which ended its mission in September 2017, has led scientists to another new discovery about Saturn: A warming, towering polar vortex sits hundreds of miles above the clouds at its northern pole when it nears its summer season.
- This vortex isn't like Earth's now-infamous polar one, which is a ring of high winds at upper levels of the atmosphere above the North Pole during the winter.
- Instead, it takes the shape of a hexagon both in the lower and upper altitudes of the polar region, and NASA researchers now say the two circulations may be connected.
- It's not yet known exactly how the vortex maintains the hexagonal shape for such great heights, according to a new study published Sept. 3 in Nature Communications.
"While we did expect to see a vortex of some kind at Saturn's north pole as it grew warmer, its shape is really surprising," Leigh Fletcher of the University of Leicester said in a statement. "Either a hexagon has spawned spontaneously and identically at two different altitudes, one lower in the clouds and one high in the stratosphere, or the hexagon is in fact a towering structure spanning a vertical range of several hundred kilometres."
Thanks for reading! See you next Thursday.


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Section IB: Pruning
The information below, is an excerpt from the "Recommendations for Coffee Berry Borer Integrated Pest Management in Hawai'i 2016" document. The complete document can be found here.
Stump pruning by block is currently the only pruning method for establishing a large area without food or shelter for CBB. Pruning can help to make other activities easier or more effective (e.g., ease of harvest, achieving better spray coverage and penetration into the interior of the tree, etc.)
- Prune trees AFTER strip-picking all (green, ripe, over-ripe, and raisin) cherry.
- Stump pruning in blocks or areas may control CBB infestations within an orchard during the first year of production.
- Avoid stump pruning during drought. Trees need rainfall or irrigation and proper nutrition to recover.
- If you must stump prune during a drought, retain a "nurse vertical" to reduce tree shock and losses from stumping. The nurse vertical can be removed after new shoots emerge and new shoots should be thinned to 3 or 4 main verticals [2].
This is an example of field that was stump pruned following the end of harvest and after strip-picking. No berries developed until the following season, leaving about one year for CBB to find other homes and to emigrate from this field. Traps can be set up in the field to capture and kill residual beetles.
One of the smallest known stumped blocks is an area with about 250 trees.
Depiction of a nurse vertical
Remember that strip-picking, the removal of ALL berries and raisins from the tree, must be done BEFORE pruning.
Additional publications and information related to coffee pruning:
- Coffee Cultural Practices in the Kona District of Hawaii
- Growing Coffee in Hawaii - pruning information starts on page 26
- Economic Evaluation of Mechanized Pruning of Coffee in Hawaii
- Pruning section of the 2016 CBB IPM Recommendations document
- General coffee presentation with pruning, pests, etc. by Skip Bittenbender
- Factors Affecting the Growth and Yield of Coffee in Kona, Hawaii - Coffee pruning Extension publication by Beaumont and Fukunaga
- Banana Moth as a Pest of Coffee
- Additional information and photos of Banana Moth - Extension publication by Zarders et al.
- Black Twig Borer informational webpage
- Coffee root-knot nematode informational webpage
- How to sample for coffee root-knot nematode
- How to take coffee leaf and soil samples
Further reading:
[2] Beaumont, J.H., and E.T. Fukunaga. 1958. Factors affecting the growth and yield of coffee in Kona, Hawaii. Hawaii Agricultural Experiment Station Bulletin 113. http://www.ctahr.hawaii.edu/oc/freepubs/pdf/B-113.pdf.
[2] Beaumont, J.H., and E.T. Fukunaga. 1958. Factors affecting the growth and yield of coffee in Kona, Hawaii. Hawaii Agricultural Experiment Station Bulletin 113. http://www.ctahr.hawaii.edu/oc/freepubs/pdf/B-113.pdf.
Contact website management if you require any assistance with the site or information provided.


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Be with You
Woo Jin takes care of his son Ji Ho alone after his wife Soo A passed away. Before she passed away, she promised she would be back on a rainy…
Santa's Boots
A Stone Cold Christmas
A holiday encounter with a forsaken boyfriend forces money-grubbing Mia Stone to re-examine her past, present and future.
Christmas at Grand Valley
Vanilla Sky
A self-indulgent and vain publishing magnate finds his privileged life upended after a vehicular accident with a resentful lover.
Risky Business
Jerry Maguire
Far and Away
Days of Thunder
All the Right Moves
The Mask
I Love You Phillip Morris
Eternal Sunshine of the Spotless Mind
hen their relationship turns sour, a couple undergoes a medical procedure to have each other erased from their memories.
Memories of Christmas
A Snow White Christmas
Christmas with a Prince
No Sleep 'Til Christmas
A Boy. A Girl. A Dream
On the night of the 2016 Presidential election, Cass, an L.A. club promoter, takes a thrilling and emotional journey with Frida, a Midwestern visitor. She challenges him to revisit his…
A Girl Walks Home Alone at Night
Boys (Jonas)
The Guernsey Literary & Potato Peel Pie Society
In the aftermath of World War II, a writer forms an unexpected bond with the residents of Guernsey Island when she decides to write a book about their experiences during…
Book Club
To All the Boys I've Loved Before
The Little Mermaid
Southside with You
La La Land
Fifty Shades Darker
Destination Wedding
Sierra Burgess Is a Loser
Nappily Ever After
Mamma Mia! Here We Go Again
Crazy Rich Asians
A Star Is Born
The Princess Switch
Arthur Curry learns that he is the heir to the underwater kingdom of Atlantis, and must step forward to lead his people and be a hero to the world.


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Painted Photographs
The notion of the body is a complicated and elusive one (read more on this topic in our article Calligraphy on Girls). However, there is something which can be said about the body in the postmodern era – with a degree of certainty – it is a construct which bears significant meaning and conveys important aspects of our existence. Artist Ashley Oubré understands the notion of the body and utilizes this concept in order to show melancholic and intriguing, yet beautiful imagery…
Exciting Exhibitions and a Successful Year
Robert Fontaine Gallery has been a home for a number of exciting exhibitions during the year behind us. Throughout its history, the gallery has been focusing on emerging artists as well as established ones and been devoted to a various set of mediums, from digital media to conceptual installations and urban interventions. During spring, we were able to see an interesting body of work by David Walker and his take on portraiture (read more in Swapping Souls With Strangers). In October, the gallery space was a place where one could witness the play between reality and illusion by Nick Gentry (read more in Synthetic Daydreams). Robert Fountaine Gallery ended the year with a successful appearance at CONTEXT Art Fair, where, among other artwork, they exhibited pieces by Ashley Oubré…
The Art of Ashley Oubré
There are certain artists whose work is such a powerful mixture of excellence in technique and intriguing subject matter. In these cases, one can only stand in awe in front of such pieces. Work of self-taught artist Ashley Oubré are drawings created by the power of graphite powder, india ink and carbon pencil. What is even more inspiring and intriguing, the final result is a photo-realistic piece, or, as Oubré would put it, "hyper realist." Ashley Oubré had started drawing at the age of 20, but after a long break she started again just couple of years ago, quitting her office job in order to focus entirely on the art. Despite the fact that she suffers from hand cramps, the artist has said once that she will be keeping up with the meticulous exploration of shape and form…
Work of Ashley Oubré at Robert Fontaine Gallery
The drawings of the talented Oubré evoke a state of melancholy and echoes a certain darkness. More importantly, we can see how much she achieves with the use of grey tones. The achievement of this kind of aesthetics is, then, combined with the realization of how Oubré managed to capture emotion and/or the state of the object which is being depicted. In this regard, the viewer is faced with a practically perfect execution of light, shadow and texture within the piece. And finally, the realism of the work serves as a vessel for the realism of social discourses (especially those which can be seen through the concept of the body) which the artist finds significant. Be sure to visit the solo exhibition of new works by Ashley Oubré in the period between January 10th and January 31st 2015, at Robert Fontaine Gallery.
There are so many exciting exhibitions in the upcoming period – in order to be informed on time, create a profile via My Widewalls! Find out what your favorite as well as some young and emerging artists are doing by signing up for My Widewalls!
Featured images: Ashley Oubre – Saville, 2014 – graphite powder, carbon pencil and india ink on paper (unique) – segment; Ashley Oubre – The Soliloquy, 2014 – graphite powder, carbon pencil and india ink on paper (unique). All images courtesy of robertfontainegallery.com


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As the garage door closed behind me, I was about to turn off the ignition when something Anele said on 94.7 tweaked my interest. I spent the next ten minutes intently listening to a brief chat between Anele and philanthropist Carolyn Steyn. Carolyn enthusiastically elaborated on "67 Blankets", an initiative that started in December 2013, when Zelda la Grange, Nelson Mandela's trusted assistant, presented Carolyn with a challenge to knit or crochet 67 blankets to be distributed to those in need on Nelson Mandela Day.
This year it was Carolyn's vision to see 21 thousand blankets knitted or crocheted before the 21st April to celebrate the 21st anniversary of our democracy on the 27th April. It was her intention to see these 21 thousand blankets laid out at the feet of Nelson Mandela's statue on the front lawns of the Union Buildings. It was when Anele joked about sponsoring a helicopter to film this spectacle from the air that the light bulb in my head went off… MCC Aviation steps in!
After weeks of organisation, collaborating with Carolyn, The Nelson Mandela Foundation, Peter Morey (The official photographer for the event) and Richard Noseworthy (The videographer assigned to the task), there was a buzz amongst MCC Aviation staff and crew on the morning of 21st as we prepared for the "big shoot". Mike Barnes himself elected to be the pilot for the special flight. Along with Claude Oberholzer, our in house helicopter pilot and new business developer and myself, we flew our signature Bell 407 ZS-RZG to Little Company of Mary Hospital who kindly agreed to allow us to use their helipad as a pick-up and drop-off zone close to the Union Buildings to collect Peter and Richard.
What awaited us at the Union Buildings was breathtaking!! It was more than simply a visual spectacle, as 21 thousand blankets sown together, strewn across the terraced lawns of The Union Buildings at Nelson Mandela's feet evoked an incredible sense of emotion and gratitude. Gratitude for all those hands that contributed to the making of the blankets, gratitude to those citizens of South Africa who care, gratitude for Madiba himself who inspired such goodwill and gratitude for being a part of this beautiful Nation. I took a moment to recognise the privilege of witnessing this scene from our unique aerial vantage point and for the opportunity to facilitate in ensuring these images were captured.
MCC Aviation once again followed their convictions as proud South Africans and are proud to have contributed in however small a way to making a positive difference. We challenge all contemporaries in the aviation fraternity to participate by giving 67 minutes of their time on Nelson Mandela Day on the 18th July 2015 to contribute to making South Africa a better country for all.


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As a dietary supplement company we are not allowed to make any claims regarding treatment or cure of a disease, regardless of supporting scientific research. We encourage you to be an informed consumer and do your own research. Alternatively, you can contact us directly and we may be able to assist you make the most appropiate product choice to meet your individual health requirements. Here is what we can say... It takes 100 pounds of bilberries (European blueberries) to yield one pound of this superior extract. Standardized to contain 25% anthocyanidin flavonoids , the key compounds in bilberry extract, these natural antioxidants can disarm damaging free radicals that are associated with ageing and an important factor for protecting eye health. Use: 1-2 UltraCaps™ twice a day with food.
Hadley Wood Healthcare Vision Essentials60 VCaps £15.30
Lamberts Healthcare Eyewise® High Strength Lutein 20mg 60 Tabs £19.95


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there is a major probability that your existing data could be anywhere between 6 months or 2 years stale and the people within your database might have changed their jobs or their roles. You will never be able to run a focused campaign though such a database. Additionally, you might know your target audience and companies, but you don't have the desired data to run your campaigns. Here is when MillionwattsDATA plays a dominant and vital role.
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AshGold coach Hayford not disappointed after Aduana defeat
Ashanti Gold coach Bashiru Hayford insists he was not disappointed with his team's performance following a 1-0 defeat to Aduana Stars in the Ghana Premier League on Sunday.
After a resolute defending by the visitors in first half, Derrick Sassraku's struck in the winner to give the hosts their first triumph of the campaign.
"My boys did very well despite the defeat because playing against Aduana in the first away match was not easy at all and we all saw it" Hayford said.
Editors' Picks
"Winning in Dormaa Ahenkro or even taking a point has always been very difficult, so we are happy we did not disgrace ourselves. We played very well but after every football game, there must be a result either in your favour or against you. Aduana were able to utilise the only chance they had when their striker scored through the corner-kick.
"It was a fantastic display from my boys because they played to my instructions so I'm not disappointed. I know the team will be very strong as the season progresses," he added.
Ashanti Gold will host Great Olympics next weekend at the Len Clay Sports Stadium before travelling to Tema to lock horns with GPL returnees Tema Youth.


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Fairlawn Primary School celebrates successful first Ofsted inspection
Fairlawn Primary School has received a resounding Good judgement in its first Ofsted inspection. The school, which opened nearly three years ago in Fairlawn Road, Montpelier, Bristol, was rated Good in all areas by the education watchdog. Parents, staff, leaders and governors were all praised for their contribution to Fairlawn's success. "Good relationships between adults and pupils are evident across the school," the inspector, Paul Smith, wrote in his report. "Teachers and support staff are very committed to pupils' care and


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1 Corinthians 13:1 – "If I speak in the tongues of men and of angels, but have not love, I am a noisy gong or a clanging cymbal." Do you know how annoying gongs and cymbals can be if they are played over, and over, and over…!! Well, God says that's how our words can sound to people, if they are not spoken kindly, in love.
- A kind tongue makes things better at home. Respond with kind words. 2 Chronicles 10:7 – "If you are kind to these people, and please them, and speak good words to them, they will be your servants forever." It is easy to serve someone who is kind. Kind words resolve arguments, and make peace. (Romans 14:19)
- A kind tongue overcomes speech problems – not like a speech impediment, but a fear of speaking to people. This goes hand in hand with a truthful tongue. Ephesians 4:15 – "Rather, speaking the truth in love…" Even if the truth isn't good, it can be spoken in kindness and love.
- A kind tongue causes peace. 1 Peter 3:9-10 – "Do not repay evil for evil or reviling for reviling, but on the contrary, bless, for to this you were called, that you may obtain a blessing. 10 For 'Whoever desires to love life and see good days, let him keep his tongue from evil and his lips from speaking deceit." When people are mean, they usually have been hurt. If we show love to them, their thoughts may change!
- A kind tongue is a GREAT witness of Jesus' changing power! If they see something different in us, they will want to know what is different. 1 Peter 2:23 – "When he was reviled, he did not revile in return; when he suffered, he did not threaten, but continued entrusting himself to him who judges justly."
1) Choose a person who irritates you, and speak kindly to them in every situation – and not only to them, but also about them.
2) Hold your tongue next time someone is unkind to you. Try to understand why they are being unkind.
Verses for today: Colossians 4:6 – "Let your speech always be gracious, seasoned with salt, so that you may know how you ought to answer each person." Ephesians 4:32 – "Be kind to one another, tenderhearted, forgiving one another, as God in Christ forgave you."


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Welcome to Essentia, the personalized protocol for building your decentralized life. By creating an account, you can start producing Essences - containing your info, identities, communications and more - with such control of data, you can generate new, powerful interactions between centralized & decentralized resources, dapps & third party apps.
Validation (22 votes)


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Whether you are male or female reading this, when it comes to sexually pleasuring a woman you need to know the vagina. The vagina is one of the worlds most complicated topics. Every woman is different and so is every vagina different. Whoever claims that a vagina is the same ..Continue Reading
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The MMT board appointed Peter Forhaug as acting CEO while the recruitment of a new permanent CEO is ongoing. Forhaug has a background in finance and has acted as a senior advisor to the board. He is currently representing MMT at the board of the of the Smart Mobility Architecture (SMARC) research project.
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{Festival de la Gastronomie}
There are only a few spaces left for the Cooking Class scheduled for 27 September 2014 at Novotel. This event will be the Grand Finale of the Festival de la Gastronomie.
The Festival de la Gastronomie continues! Enhance cookery skills and taste some of the French's finest cuisine with a French chef!
Benefit from his experience and creativity and let him guide you through the finest French cuisine in the relaxed and welcoming atmosphere of the prestigious Novotel. 50 GHC. Register at email@example.com.
Places are limited so register now!
Mrs Hania Accad, spouse of the Mexican Consul in Accra recently hosted the AccraPremium Gourmet Cooking Club. Recipes were taught by Chef Andre Dandaba of Chase El Paso Restaurant. This event was generously sponsored by Koala Shopping Centre and French dairy company Elle & Vire.
Join us at the 2014 AccraPremium Food & Wine Festival at the Alliance Francaise d'Accra on September 21, 2014 and for the Festival de la Gastronomie September 26-27 at Novotel Accra. For Tickets and information call 0240 94 66 55
Video by Fashionista GH
{Bread & Wine Thursdays}
Since the 1800's, Ghanaians have distinguished themselves internationally as a gifted in the arts, sciences, sports, music, dance, academia, and retention of cultural traditions. Anyone who has sat in a classroom with a Ghanaian can attest to their excellence when pursuing a professional or academic goal.
AccraPremium celebrates 12 Ghanaian individuals and brands that are projecting "Brand Ghana" positively on the international scene. Who is YOUR favorite Ghanaian on the international scene? Tell us in the comments.
Proudly Ghanaian - Melissa
Enjoy the video recap of the AccraPremium Gourmet Cooking Club event hosted in the Micaletto family residence.
Delicious sights, tastes and smells, made this event extra special.
Thank you to our sponsors, Koala Shopping Centres and Elle & Vire. Images by FashionistaGH
XOXO - Melissa
AccraPremium Melissa
My 2 favorites


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Secondly, I enjoy the connection it gives me to others. In a way, it's social. Some people have suggested that maybe I'm too open laying my life out there that way. That I'm letting people intrude too far. (If they only knew the stuff I edit out before I publish a post!) Others have said that it helps them feel not so alone with their experiences. The part of me that likes to be the center of attention LOVES that other people read my blog and can identify but in the end I'm really doing it for me. I do it as a way of reaching out my hand and hoping that someone else will feel the same way and reach back for me.
Another reason I blog is for a creative outlet. I love words.... I love to play with words. I like how they feel sliding over my tongue and out of my mouth. I like how they feel skittering around in my brain and when I sit down to type them out I am often surprised at just what I have to say. Sometimes it's one of those "Oh dear... did I just put that in writing?" kind of things but other times I can fall in love with the story my words tell.
So maybe it's a way to show off, too. To present my ideas or interpretation of someone else's ideas in hopes that they will be accepted. Perhaps, even my accomplishments will be praised. As much as we all want to think we are humble beings, somewhere inside we all crave the acceptance and praise of other people because it makes us feel loved. This is very much why I want, and keep asking, you to comment here.
Finally, I blog to create a record that I was here and that my life has meaning. One thing I've learned about myself is that I need to feel relevant. I need to matter. We live in a world that tells us we are special and unique... just like everybody else. I don't fool myself that I can or need to change the world; I just need to make my little corner of it a better place.


text:
Make sure you are lucky enough to come up and stay at Sarangkot.
Sarangkot is an awesome view point for Nepal visitors to come and stay with good weather views approaching those that climbers climb to see and experience. Sarangkot is the highest point on the rim above Pokhara Valley. It is a geographically unique and a special place to stay.
Sarangkot is not hard to access from Pokhara city but it is well worthwhile.
Sarangkot also has world-class Paragliding and a Zip-Line down to Pokhara City 800 Meters below.
No Trekking Permit is required to enter trek or stay here.
PC. John O'neil


text:
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Look Up Quick Results Now! Find Related Search and Trending Suggestions Here.. Previous versions of FSFlyingSchool for X-Plane 9 and X-Plane 10 were created . Boeing 777-200 (Supplied with X-Plane . Screen of FSFlyingSchool for X-Plane 10.. Boeing 777 Worldliner Professional vs PMDG 777 Sign in to . They're limited by the core X-Plane 10 .. The FlightFactor Boeing 777 was my first payware purchase for X-plane. It is an officially licensed Boeing product and is avalible . Flying the Boeing 777 In X .. Boeing 777; Boeing 777-200ER of . X-Plane 10 nest pas un jeu mais un outil dingnierie pouvant tre utilis pour prdire avec une prcision incroyable .. I have X-Plane 10 with Boeing 777 Worldliner Pro- Extended Pack, which is designed to model the real-world operation of the 777. Why does the AP never go to the .. Hello guys, I will get my X-Plane 10 tomorrow and in preparation of the PMDG 777 Release for FSX I would like to ask, if I should buy the 777 Worldliner A.. Downloads for X-Plane.. FOLLOW US ON FACEBOOK- Website-drps4.simdif.com Youtube-subscribe above The folllowing video was made using x-plane 10 .. Review: VMAX 777 - Boeing 777 Worldliner Extended. The VMAS Boeing 777 Worldliner Extended is certainly one of the pricier add-ons for X-Plane, but offers .. Boeing 777 Cold And Dark Tutorial X Plane 10 is popular Free Mp3. You can download or play Boeing 777 Cold And Dark Tutorial X Plane 10 with best mp3 quality online .. The most advanced and complex simulation of an aircraft for X-Plane. Built with technical input from engineers, pilots and Boeing, this Boeing 777 is as close as you .. Your Perfect Beach Holiday or Weekend Getaway. Flights, Hotels & Packages.. Hey people, Does anyone know where i can find a B777 that is "FREE", x-plane 10 doesnt recognize files on x-planefreewear.net, and i dont want to pay money .. Find Our Lowest Possible Price! Cheapest X Plane 10 For Sale.. Is there a freeware Boeing 777 which is compatible with X-Plane 10? . Open her up in Plane-Maker for X-Plane 9 (before using X-Plane 10) and then: Menu, .. Look Up Quick Results Now! Find Related Search and Trending Suggestions Here.. Look Up Quick Results Now! Find Related Search and Trending Suggestions Here.. IT'S FINALLY HERE!The 767-400ER!This release of this plane marks the final release in the Boeing 767 . This Boeing 767-400ER is . seen in X-Plane! Thanks .. Your Perfect Beach Holiday or Weekend Getaway. Flights, Hotels & Packages.. PMDG quality on X-Plane 10? (self.flightsim) submitted 3 years ago by . but the X-Plane Boeing 777 Worldliner Professional is on par with the PMDG 777/737.. There is no doubt the Boeing 777 philosophy in this being a great aircraft for simulation in X-Plane. FlightFactor/VMax have been very good in the updates and keeping .. Current location: x737 website > Aircraft > x737 for X-Plane 8 .. The Boeing 777, a superlative of a . Product information "B777 Worldliner Professional" The Boeing 777, . XPlane 11 / X-Plane 10.30 (or higher) (32 or 64bit). X plane crack download. Boeing 777 worldliner professional. X plane 10 flight simulator v10.1.6 unlocked apk for android. Aircraft Review : Boeing 7.. Aircraft Update : Boeing 777 Worldliner Pro/Extended v1.8 by . Boeing 777 Worldliner . put the above notice in the X-Plane.Org threads Boeing 777 .. A friend and I have recently purchased XPlane 10 but we're struggling to get the autopilot FMC working on the 777. Would anyone be willing to hang with us on a flight .. Your Perfect Beach Holiday or Weekend Getaway. Flights, Hotels & Packages.. [X-PLANE]Req for PC. Boeing. Last . Can anyone pass me the DHC-6 Twin Otter 300 Series of RWDesigns for X Plane 10. . [X-plane] FlightFactor Boeing 777 v 1.9.9:. VMAX 777 - Boeing 777 Worldliner Professional - FSPilotShop. Download X-Plane . FSX Addons & hardware, yokes, pedals, scenery, aircraft.. Boeing 777 worldliner . [X-Plane 10] v1 cage code 81205 777-200lr . launch customer Role Wide-body jet airliner National origin States Manufacturer safe boeing .. Look Up Quick Results Now! Find Related Search and Trending Suggestions Here.. Where to Buy. Boeing Professional Models for X-Plane 10 & 11. The models are sold on x-plane.org. . Boeing 777 Worldliner Professional .. Boeing 777. Welcome to XP Jets Boeing 777! This aircraft is the result of almost a years worth of development by XP . Hope the 777 3D works in X-Plane 10 . 7b042e0984
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Gola "GRAVITY" Trainer
The Gola Active Gravity is a new addition to the juniors trainer collection. This striking lace-up style that is exceptionally lightweight features a breathable mesh upper, a moulded skeleton lacing frame for a supportive fit and a no-sew toe guard for added comfort.
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- Lightweight phylon sole unit provides comfort, durability and shock absorption
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Spicy Green Beans
The variety of produce at the market increases each week, this time of the year. This week the focus is on string beans and garlic. If you do not care for spicy, do not use sambal oelek (or chili flakes)
Throw a fried egg on top,
serve with rice, and you have a delicious meal.
f o r t w o
1 tsp vegetable oil
½ lb green beans, ends trimmed, chopped into bite-size pieces
2 cloves garlic, finely chopped
1 tsp soy sauce
1 tsp sambal oelek (or 2 tsp chili flakes, optional)
a d d i t i o n s
1 tsp ginger, grated
1 tsp lemon juice
Add the vegetable oil to a frying pan on
medium heat. Once it's hot, add the green beans.
Let them cook undisturbed for about 1 minute.
Mix the garlic, soy sauce, and sambal oelek in a
bowl (and the ginger and lemon juice, if using).
The beans should have turned bright green. Add
about ¼ cup of water to the pan. Cook another
2 minutes, until the water is mostly gone. Pour
the sauce into the pan and toss gently to coat.
Cook another 2 minutes, until everything is
fragrant and most of the liquid is gone. Poke
the beans with a fork: if it goes through easily,
they're done. They should take about 5 minutes.
Taste and add more chili sauce or soy sauce if
you want the beans hotter or saltier.
Recipe from Cheap and Good, Leanne Brown


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When you read stories about near misses between airplanes and drones, it's easy to get the impression they are almost daily events. Especially when articles are being published detailing estimates of drone incursions into restricted airspace. However, the Academy of Model Aeronautics (AMA) found that many of the "reported to FAA were vague, mistaken or involved remotely piloted aircraft that were following the rules." In a study completed by the AMA, they found that just 27 cases or 3.5% of the reported 764 close-call incidents were accurately reported. 764 vs. 27, seems like a big discrepancy to me.
Hobbyists who scrutinized reports to the FAA of alleged close calls with drones found that pilots reported near misses in only a small fraction of the cases, according to a study obtained by USA TODAY.
The study found that of the 764 close-call incidents between drones and other aircraft, only 27 were actually described by pilots as a "near miss."
But the Academy of Model Aeronautics found that many drone sightings reported to FAA were vague, mistaken or involved remotely piloted aircraft that were following the rules.
The study found 27 cases, 3.5%, where the pilot reported a "near miss" or "near collision" or "NMAC," for near mid-air collision. The study also found several reports where the pilot "isn't reporting a near mid-air" or "did not consider it as a NMAC."
"I think it should be better defined where the problem lies," Hanson said.
Drone hobbyists find flaws in "close call" reports to FAA from other aircraft
Thank you to Bart Jansen of USA Today for breaking this story.
About the Academy of Model Aeronautics (AMA)
Contact AMA today to learn how you can join one of the world's most thrilling and high tech sports, model aviation. Whether you want to hear the whine of a turbine-powered jet, learn to fly a helicopter, pilot your own giant-scale aircraft, or enjoy a quiet afternoon soaring your sailplane with friends, the AMA can show you where to find instructors, how to become involved, and help answer almost any question.
- World's largest model aviation association, representing a membership of more than 175,000 from every walk of life, income level and age group.
- Self-supporting, non-profit organization whose purpose is to promote development of model aviation as a recognized sport and worthwhile recreation activity.
- Organization open to anyone interested in model aviation.
- Official national body for model aviation in the United States. AMA sanctions more than 2,000 model competitions throughout the country each year, and certifies official model flying records on a national and international level.
- Organizer of the annual National Aeromodeling Championships, the world's largest model airplane competition.
- Chartering organization for more than 2,500 model airplane clubs across the country. AMA offers its chartered clubs official contest sanction, insurance, and assistance in getting and keeping flying sites.
- The voice of its membership, providing liaison with the Federal Aviation Administration, the Federal Communications Commission, and other government agencies through our national headquarters in Muncie, Indiana. AMA also works with local governments, zoning boards, and parks departments to promote the interests of local chartered clubs.


text:
I'm a photo architect and documenter of life. I love capturing moments in time and showing the emotion of those moments.
I specialize in event, fine art, portraiture, and boudoir photography. You can find me at a lot of bellydance events and concerts.
Boudoir, Events, Fashion & Glamour, Photojournalism, Portraits
Black & White, Candid, Glamour , Grunge, High Fashion, Natural Light, Photojournalistic, Retro, Vintage, Whimsical


text:
Letter to UN Security Council on Justice and Accountability
International Federation for East Timor (IFET), February 18, 2009
Security Council
The United Nations
1 United Nations Plaza
New York, New York 10017
February 18, 2009
Your Excellency
We are writing on behalf of organizations long concerned with the justice process in Timor-Leste.
As you meet this week to discuss renewing the UN mission in Timor-Leste, we urge you to look at the unfulfilled UN pledges concerning human rights and accountability for serious human rights crimes committed in Timor-Leste between 1975 and 1999. We urge the Security Council to seriously examine the recommendations of the 2005 Commission of Experts (CoE) report and Chega! (Enough!), the final report of the Timor-Leste's Reception, Truth and Reconciliation Commission (CAVR), as guides to establishing a process that can contribute to genuine justice and reconciliation. Such a process will support democracy and accountability in both Indonesia and Timor-Leste.
These, as well as reports from independent bodies, all concluded that the right of the people of Timor-Leste and the international community to achieve justice for war crimes and crimes against humanity committed between 1975 and 1999 was not served by the serious crimes process in Timor-Leste and Indonesia's Ad Hoc Human Rights Court, which in the end convicted no one.


text:
Glen F. Williams
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text:
Introduction to the Langtang Paper
The paper, Mass balance and runoff of the partially debris-covered Langtang Glacier, Nepal, is being revised and the records of daily precipitation and temperature at Kathmandu used for calculating the mass balance will be extended from 1987-97 to 1987-2012.
This paper is noteworthy since it represents the first time that the mass balance and runoff from a Himalayan glacier has been successfully modeled.
Verification of the results is made by comparing simulated ablation for the glacier with measured ablation on the nearby Lirung Glacier during the same time period and at nearly the same elevation.
In addition to the longer data record, the revision will also demonstrate the model's calibration process and provide an explanation of how the glacier's area-altitude distribution is instrumental for producing accurate glacier balances from routine weather observations.
The effect of the glacier's debris cover on the mass balance and runoff will also be examined.
A detailed mass balance report for Langtang glacier, with a similar format to existing reports, will be added to the PTAAGMB Project website.
The mass balance of Himalayan glaciers is especially important now due to the critical link these high elevation glaciers provide to the earth's changing climate.
Recently there has been a significant controversy regarding whether these glaciers have been shrinking for the past ten years, while glaciers in other parts of the world obviously are. The revised Langtang paper will address the possible cause for this discrepancy.
The Langtang Glacier project is the result of a collaboration between the Nepal Department of Hydrology and Meteorology, Kathmandu, Nepal and HyMet Inc., Vashon Island, Washington. Further collaboration is planned.
The Langtang Paper can be downloaded here:


text:
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text:
Improving Students' Writing Skill in Descriptive Text by Using Outdoor Activity
Register Journal. 2015;8(2):210-225 DOI 10.18326/rgt.v8i2.210-225
Journal Title: Register Journal
ISSN: 1979-8903 (Print); 2503-040X (Online)
Publisher: IAIN Salatiga
Society/Institution: ELITE Association Indonesia
LCC Subject Category: Language and Literature: Philology. Linguistics: Language. Linguistic theory. Comparative grammar
Country of publisher: Indonesia
Language of fulltext: English
Full-text formats available: PDF
Sri Suharmi
(State Institute for Islamic Studies of Salatiga)
Time From Submission to Publication: 28 weeks
Abstract | Full Text
This study is a classroom action research. The general objective of this study is improving students' writing skill through outdoor activity. While the specific objective of this research are (1) whether or not outdoor activity can increase the students' writing content of descriptive text of the second year of Mts Sudirman Kopeng Getasan. (2) it describe whether the outdoor activity can improve the students' writing skill in developing paragraph. This classroom action research was conducted at MTs Sudirman Getasan. The procedure of the research consisted of planning, action, observing, and reflection. The observation during the process of English teaching and learning was helped by the collaborator. In this research, the writer acted as a practitioner. The test was in the form of pre-test and post –test conducted in cycle 1, cycle 2, and cycle 3. The research result were: (1) using outdoor activity as a method can improve students' writing skill, its proved with the student's improvement score. The mean score of the pre-test of the students was 57 (very poor) and the mean score of the post- test 70 (good). The mean of the post-Test is higher than the mean of the pre-Test ( 64.53>56.56), the mean of the post-test in cycle 2 is higher than mean of cycle 1 (70.59>64.53) and the mean of the post –Test cycle 3 is higher than cycle 2 (74.56>70.59). the proven result of the implementation was 75%. (2) The effectiveness of using outdoor activity in improving students' writing skill is proved from the t-test and t-table in cycle 1 (9.67>2.042) which the score of t-test was higher than the score of t-table and the result of t-test and t-table in cycle 3 (15.11>2.042) also showed that the score of t-table.