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Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.
Prostate cancer (PCa) is a major urological problem associated with significant morbidity and mortality [1]. Although the majority of PCa cases are localised to the prostate, nearly one-third of newly diagnosed patients have advanced or metastatic disease [2]. Radical prostatectomy and radical radiotherapy are potentially curative treatment options for localised PCa. For those with locally advanced or metastatic disease, the initial systemic therapy is androgen deprivation therapy. Unfortunately, nearly all patients in this group eventually progress to castration resistant PCa (CRPC). For CRPC, docetaxel based chemotherapy is used as first-line. However, this only provides modest survival benefit (2.4 months) and is associated with significant side effects [3]. Insights into the regulation of immune responses in malignancies have facilitated the emergence of novel immune-based strategies. PCa is an attractive target for vaccination due to its slow growth which can allow sufficient time for immune activation [4]. Additionally, the identification of prostate tumour associated antigens (that are recognised by T cells) has created the opportunity to develop novel immune based therapeutic approaches. Several tumour associated antigens have been identified, including prostate specific antigen (PSA), prostatic acid phosphatase (PAP), prostate stem cell antigen (PSCA) and prostate specific membrane antigen (PSMA) [5]. These antigens are largely prostate specific and their expression is strongly upregulated in PCa, both locally and at metastatic sites [6,7]. This makes these antigens a viable target of active immunotherapy and can be used as DNA vaccines. Furthermore, PSA-specific cellular immune responses have been detected in some PCa patients and in normal individuals, suggesting that tolerance towards this antigen may be broken [8]. These observations led to development of a variety of vaccines for PCa in pre-clinical and clinical trials. These vaccines can be broadly classified as whole cell vaccines [9], protein/peptide based vaccines [10,11], viral vector based vaccines [12], dendritic cell vaccines [13] and naked DNA vaccines [14,15].
Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. The focus of extensive research for PCa vaccine has led to the approval of the first therapeutic vaccine (sipuleucel-T) by the FDA [16]. The sipuleucel-T is an autologous antigen presenting cell (APC) based and antigen-targeted immunotherapeutic innovation for men with CRPC [16]. The success story of the sipuleucel-T encouraged researchers to explore other agents/strategies to activate immune system against PCa. Gene therapy (including DNA vaccines) is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. A DNA vaccine consists of tumour specific/associated antigen and additional immune-stimulatory factors cloned into a bacterial plasmid downstream of an appropriate eukaryotic promoter for strong and stable expression. DNA vaccination can induce effective anti-tumour responses against various malignant cells and provides an attractive strategy for the management of PCa [17-19].
Why DNA vaccines?
DNA immunisation can efficiently stimulate humoural and cellular immune responses to protein antigens. This strategy has been used successfully for infectious diseases [20] and potentially can be applied for malignant conditions. There are several advantages associated with DNA vaccines:
Various groups have demonstrated tumour protection using DNA immunisations in several pre-clinical cancer models [21-26].
Gene sequences can be manipulated easily to provide multiple potential epitopes that stimulate both humoural and cellular immunity [22,27-29].
DNA vaccines generally skew the immune system toward the desired T-helper1 (Th1) response. This is most likely because plasmid DNA contains unmethylated CpG motifs, which have been shown to be a very potent immunological adjuvant [30,31].
DNA immunisation is safe in humans [14,32] and can induce antigen-specific immune responses [30,33].
DNA vaccines can be produced readily at a large scale [34].
Mechanisms of action
Anti-tumour immune responses
For malignant diseases, immunological therapies fall into two general categories; active and passive immunotherapy. Active immunotherapy attempts to directly elicit tumour-specific host immune responses that control or eradicate tumours. In contrast, passive immunotherapy involves the direct administration of effector molecules, such as cytokines or monoclonal antibodies. These molecules promote the development of anti-tumour responses, directly killing tumour cells, or inhibit cell invasion and angiogenesis [35]. The nature of the host immune response that can control tumour growth has been the focus of many studies. With few exceptions, the most effective anti-tumour immune responses in animal models have depended on the efficient generation of Th1 cell immunity, characterised by strong cytotoxic T lymphocyte (CTL) responses [27,28,36]. This is supported by observations in humans that progressive disease is characterised by an anti-tumour T-cell response [37] as well as by clinical evidence that Th1 T cells can control and eliminate metastatic disease [28,38]. B cell effector functions are another important component of this anti-tumour immune response (see below).
Process of DNA vaccination
A typical DNA vaccine consists of a transgene that encodes the sequence of a target protein (e.g. PSA, PSMA etc.) under the control of a eukaryotic promoter. Various modalities exist for delivering such DNA to appropriate cells (see below). After uptake of the plasmid, the target protein is produced within the cell and processed into small antigenic peptides by host proteases. The peptides then enter the lumen of the endoplasmic reticulum (E.R.) by membrane-associated transporters. In the E.R., the peptides bind to Major Histocompatability Complex I (MHC I) molecules. These peptides are presented on the cell surface in the context of MHC I. Subsequently CD8+ CTL are stimulated resulting in cell-mediated immunity. CTLs cause tumour destruction through both cytolysis of malignant cells and non-cytolysis mechanisms such as cytokines production.
The foreign protein on the plasmid can also be presented by MHC II pathway by APC which elicit CD4+ helper T cells responses. These CD4+ T cells can recognise the peptides generated from the exogenous proteins that were endocytosed or phagocytosed by APC, then degraded to peptide fragments and loaded onto MHC II molecules. Depending on the type of CD4+ T cell that binds to the complex, B cells are activated and antibody production is stimulated. This is the same manner in which traditional vaccines work [39]. Vaccine-elicited antibodies can mediate direct effects against tumour cells by fixing complement or facilitating antibody-dependent cellular cytotoxicity. Overall, stimulation of both the T and B cell arms of the immune system mediates synergies and creates a large pool of effectors cells to control tumour growth and induce generation of memory cells (Figure 1).
Figure 1. Mechanism of action of DNA vaccine after intra muscular (i.m.) plasmid delivery. Transfected muscle cells produce the antigen expressed on the plasmid. This antigen is expressed to cell surface with MHC I and presented to cytotoxic CD8+ T cells (Cell mediated Immunity). Antigen is also excreted by the muscle, which is phagocytosed by the professional Antigen Presenting Cells (APC), usually Dendritic cells. A small proportion of DNA vaccine is also taken up directly by APC and the encoded antigen can then be processed and presented endogenously (Humoural Immunity).
Methods of DNA delivery
Transfection of the host cell with the plasmid is a limiting step for a successful DNA vaccination. Most commonly, the DNA vaccines are given by intramuscular (i.m.) or intradermal (i.d) injections. To facilitate the gene delivery, various methods have been reported including viral, liposomal, bacterial, ultrasound and electroporation (EP), as well as approaches involving ex vivo transfection/transduction of cells (e.g. APC) [40]. To avoid safety issues such as immune response and cytotoxicity associated with viruses and liposomal transfection, physical methods (ultrasound, EP etc.) have been widely used for either in vivo or ex vivo gene delivery. In vivo EP has emerged as a potent method for DNA vaccine delivery and significantly improves transfection efficiency of naked plasmid DNA [41]. EP driven DNA vaccination increases antigen expression by increasing transfection efficiency (Figure 2) and is accompanied by local tissue injury and inflammation [42]. Hence, the outcomes of EP mediated vaccination are dramatic enhancement of humoural and cellular immunity [43,44].
Figure 2. Schematic representation of Electroporation mediated transfection. a) Intra-muscular plasmid injection. b) Electroporation. c) Transient increased permeability of cell membrane (yellow arrows) results in transfer of the plasmid into the cell. d) Cell membrane return to resting membrane (red arrow) and gene transfection results in production of mRNA and hence specific protein.
Preclinical studies
Numerous preclinical studies have been carried out to demonstrate the efficacy of DNA vaccines in animal models of PCa. The following vital issues regarding successful vaccines were addressed in these preclinical trials;
Induction of immune response/type of immune activation
Optimisation of vaccine dose/schedule
Mode of delivery
Breaking tolerance to self-antigen
Systemic responses /control of metastatic disease
Need for adjuvant to vaccines
Transferable immunity
Prostate-specific antigens examined
Roos et al.[45] showed for the first time that a PSA DNA vaccine can induce anti-tumour immunity in vivo. They investigated a DNA vaccination strategy to immunise mice by inducing PSA-specific cellular responses. A plasmid expressing PSA, alone or in combination with plasmids coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or IL-2, were used. It was found that the DNA vaccine induced PSA-specific cytotoxic T lymphocytes and when co-injected with GM-CSF and IL-2 it can protect mice against a PSA-expressing tumour challenge. This demonstrated that immunisation with a PSA DNA vaccine can evoke PSA-specific cellular immunity. The ability of the DNA vaccine to stimulate both humoural and cellular immune responses was demonstrated by Kim et al.[24]. They observed a strong and persistent antibody response against PSA for at least 180 days following immunisation. Additionally, significant T helper cell proliferation was also detected against PSA. Furthermore, immunisation with PSA plasmid induced CD8+ T cell-restricted cytotoxic T cell response against tumour cell expressing PSA.
PSMA is a 750 amino acid surface protein expressed primarily in prostate epithelium, Most reported antibodies to PSMA apparently recognise epitopes in the residue 43–570 region of the extra cellular domain, and upon binding are rapidly removed from the cell surface by internalisation. This would potentially limit their ability to mediate Fc-dependent cytotoxicity. Kuratsukuri et al.[46,47] used a model system to target a defined region of the extra cellular domain of PSMA. Their results suggested that vaccination with plasmid expressing extra cellular domain of PSMA induced adaptive humoural activity, which was directed against the extracellular region of human PSMA and can significantly inhibit human PCa growth in athymic mice.
Viral delivery of vaccine antigens is an active research area. However, a potential difficulty with viral-based immunisations is that immune responses elicited to the viral vector might limit the possibility of multiple immunisations. Johnson et al.[48] investigated a DNA vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. In their study, Lewis rats were immunised with either a plasmid DNA-based (pTVG-HP) or Vaccinia-based (VV-HP) vaccine each encoding human PAP (hPAP). They observed Th1-biased immune response (as indicated by proliferating PAP-specific CD4+/CD8+ cells and IFN- γ production) in rats immunised with a DNA vaccine encoding hPAP. Immunisation with Vaccinia virus (encoding hPAP) could not induce PAP-specific response, unless boosted with a heterologous vaccination scheme. Furthermore, they also established that multiple immunisations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rat PAP (rPAP) and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. In separate experiments, this DNA vaccine has not shown significant toxicities in terms of animal weights, histopathology, haematological changes, or changes in serum chemistries [49]. The vaccine was found to be effective in eliciting PAP-specific CD4+ and CD8+ T cells, predominantly Th1 in type, in all immunised animals at all doses and numbers of immunisations. PAP-specific IgG were detected in a dose-dependent fashion, with titres increasing after multiple immunisations.
Optimisation of DNA vaccination
In preclinical trials different doses and vaccination schedules are investigated with variable results however, there is lack of consensus on these issues. Ahmad et al. have shown that the a DNA vaccine encoding human PSA significantly delayed the appearance of tumours and resulted in prolonged survival of the animals [50]. Additionally, a four-dose vaccination regimen provided optimal immunological effects and co-administration of synthetic CpG enhanced the tumour protective responses [50]. Furthermore, these immune responses were tumour specific and were transferable in adoptive T cell transfer experiments [50]. A DNA vaccination has the potential to break tolerance to self antigen [34,48,51]. A PSCA DNA vaccine when delivered by i.m. EP [51] or orally administered bacteria, [52] resulted in induction of anti-tumour immune responses against PSCA expressing subcutaneous tumours and metastatic deposits. There was activation of Th-1 type immunity against PSCA, indicating the breaking of tolerance to a self-antigen [51]. This immunity was tumour specific and was transferable by adoptive transfer of splenocytes [51].
PSMA is present in both secretary form and in prostate cells. Mincheff et al.[53] evaluated two plasmid DNA vaccines, encoding either PSMA products that are retained in the cytosol and degraded in the proteasome (tVacs; hPSMAt), or secreted proteins (sVacs; hPSMAs) for stimulation of cytotoxic cell or antibody responses. They observed that immunisation with both vectors led to generation of cell cytotoxicity, provided GM-CSF was administered with the vaccine. Spleen cells from animals immunised with hPSMAt demonstrated stronger cytotoxicity to the target cells. Interestingly, priming with a vector that encoded a xenogeneic protein (hPSMAt; 'xenogeneic' construct) and boosting with a vector that encoded an autologous protein (rPSMAt; 'autologous' construct) gave the best protection against tumour challenge. Immunisation with tVacs did not lead to formation of antibodies to the target protein, while immunisation with sVacs or with the protein did (mixed Th1-Th2 isotype). But, priming with tVacs and boosting with protein also resulted in the antibodies from the cytotoxic Th1 isotype. Hence, the best strategy to obtain a strong cellular cytotoxic response seems to be gene-based vaccinations with tVacs, priming with the 'xenogeneic' and boosting with the 'autologous' constructs.
While DNA vaccine injections, either i.m. or i.d., have been used successfully in many trials, it is still to establish which route is better. To enhance the efficacy of DNA vaccine against PCa, Roos et al.[54] have demonstrated that i.d. DNA vaccination, followed by two sets of electrical pulses of different length and voltage, can effectively induce PSA-specific T cells response. Ahmad et al. have reported successful DNA vaccination following i.m. injection coupled with EP. [50,51] These studies indicate that EP significantly enhances transfection and hence immune activation.
Clinical trials
Preclinical studies provided encouraging evidence of enhanced immune responses and tumour protection by DNA vaccine in animal models of PCa. The success achieved in these studies resulted in exploration of application of DNA vaccine in PCa patients. To our knowledge, no naked DNA vaccine has been used in a randomised clinical trial to date [55]. However, DNA vaccines have been used in phase I/II clinical trials including patients with PCa (Table 1). Some of these clinical trials are discussed below.
Table 1. Summary of prostate cancer DNA vaccination clinical trials
In a phase I trial, Pavlenko et al.[15] investigated the feasibility, safety and immunogenicity of a DNA vaccine (pVAX/PSA) in patients with CRPC. Cytokines, GM-CSF and IL-2, were also used as vaccine adjuvants. The results of this trial demonstrated that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2, is safe and can induce cellular and humoural immune responses against PSA. However, a dose–response was observed with regard to induction of a PSA-specific immune response. Interestingly, in this trial, two patients that developed cellular immune response to PSA exhibited stabilisation of disease. While only one of six that did not develop PSA-reactivity showed clinical stabilisation.
Mincheff et al.[14] performed phase I/II trials to determine the safety of the PSMA vaccine after repeated i.d. injections. Twenty-six patients with PCa were entered into this toxicity-dose escalation study. Immunisations were performed i.d. at weekly intervals. Doses of DNA between 100 and 800 μg and of recombinant virus at 5×108 PFUs per application were used. They observed no immediate or long-term side effects following immunisations. All patients who received initial inoculation with the viral vector followed by PSMA plasmid boosts showed the development of a delayed-type hypersensitivity reaction after the PSMA plasmid injection. In contrast, to the patients who received a PSMA plasmid and CD86 plasmid, only 50% showed signs of successful immunisation. Of the patients who received PSMA plasmid and soluble GM-CSF, 67% were immunised. However, all patients who received the PSMA/CD86 plasmid and sGM-CSF became immunised. The patients who did not immunise during the first round were later successfully immunised after a boost with the viral vector. Further to this study, Todorova et al.[58] characterised the humoural immune response against PSMA in PCa patients. They demonstrated that PSMA is a target for humoural immune response induced by gene-based PSMA vaccination. It is also proposed that detection of anti-PSMA antibodies by immunoblot analysis and by indirect immunofluorescence could be used to monitor the vaccination effects. These results were quite encouraging, proving evidence of immune activation with different vaccination regimens. However, the heterogeneity of the medical status and the presence of concomitant hormone therapy do not permit unequivocal interpretation of the data with respect to the effectiveness of the therapy. However, several responders, as evidenced by a change in the local disease, distant metastases, and PSA levels, were identified in this cohort.
Low et al.[56] evaluated the use of EP to deliver a novel DNA vaccine (p.DOM-PSMA(27)). This vaccine encodes a domain of fragment C of tetanus toxin to induce CD4+ T cell help, fused to a tumour-derived epitope from PSMA for use in HLA-A2+ patients with recurrent PCa. In this open label phase I/II, two-arm, dose escalation trial, the DNA vaccine was delivered either by i.m injection or by i.m. injection followed by EP. Three vaccinations were given at 0, 4, and 8 weeks, with booster doses at 24 and 48 weeks. In 20 patients with first two dose cohorts, EP did not appear to add toxicity to the vaccination apart from brief and acceptable pain at injection site. They also observed highest level of humoural responses with DNA+EP strategy and these responses persisted to 18 months of follow-up. These data favour EP as a potent method for stimulating humoural responses induced by DNA vaccination in humans.
McNeel et al.[57] conducted a phase I/IIa trial with a DNA vaccine encoding human PAP in patients with stage D0 PCa. Twenty-two patients were treated in a dose-escalation trial with 100 μg, 500 μg, or 1,500 μg plasmid DNA, co-administered i.d. with 200 μg GMC-SF as a vaccine adjuvant, six times at 14-day intervals. All of these patients were observed for one year after the treatment. They did not observe any significant adverse events. Three of 22 patients developed PAP-specific IFN-γ secreting CD8+ T-cells immediately after the treatment course. While nine (41%) out of 22 patients, developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. However, no humoural response (antibodies against PAP) was detected. Overall, the PSA doubling time was observed to increase from a median 6.5 months pre-treatment to 8.5 months on-treatment (P = 0.033), and 9.3 months in the 1-year post-treatment period (P = 0.054). This study provided 12 months follow up data and demonstrated that the DNA vaccine is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time.
Conclusions and future directions
DNA vaccination for PCa is at a crucial developmental stage. The ultimate goal of any given immunotherapy including DNA vaccination is eradication of each and every cancer cell from the patient. However, this goal may be hard to achieve. DNA vaccination is a step forward in achieving immune eradication of PCa. Induction of tumour-specific T cell activation has been demonstrated with PCa DNA vaccination in both preclinical and clinical trials. However, in clinical settings, limited success has been seen in terms of tumour regression and survival. This vaccine failure may be attributed to several potential tumour escape mechanisms such as defects in antigen presentation, production of immunosuppressive substances, T cell dysfunction, and the presence of regulatory T cells [59-61]. Additionally, there is paucity in the literature of advanced clinical trials to evaluate the role of DNA vaccination in PCa. Furthermore, in the available trials there is currently a lack of long-term follow up. Ideally, the availability of data from randomised clinical trials featuring robust end points such as biochemical response, progression free and overall survival will provide categorical evidence for DNA vaccination's potential.
In order to provoke an immune response, a tumour vaccine should not only maximise antigen-specific signals, but should also provide the necessary "co-stimulatory" environment. One approach is to include lymphokines (GM-CSF, IL-12, IL-15) or include tumour cell expression of membrane bound molecules (CD80, CD86) [62]. Furthermore, doses and schedules need optimisation; however it is clear that the immune responses depend on a primary vaccination followed by booster vaccination(s). Some studies have suggested that the best strategy for achieving an intense immune response can be priming with naked DNA followed by boosting with a viral vector [14,63]. The use of viral vectors can enhance the immunogenicity of the vaccine due to the adjuvant properties of some of the viral products. However, naked DNA immunisation offers several potential advantages over viral mediated transduction. Among these are the inexpensive production and the inherent safety of plasmid vectors, as well as the lack of immune responses against the carrier [63].
Although the current evidence suggest that the DNA vaccines can induce immune activation resulting in PCa control, certain areas still need to be explored such as selecting the ideal antigen, identifying suitable stages of PCa for vaccine therapy, optimum dosage/schedule and adjuvant agents. Evidence suggests that it is unlikely for a single therapy to achieve the goal of curing PCa especially patients with CRPC. However, better understanding of immunobiology of PCa will lead to pathways for development of novel therapies. The perceived difficulty in translating the effectiveness of DNA vaccination from small animals to human subjects appears to have been overcome by use of EP [42]. Current data are from early stage studies and further research in this field is essential to determine the place of DNA vaccination as an adjuvant to surgery, radiotherapy and chemotherapy.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SA carried out literature search, interpreted the data and drafted the manuscript. MT, PS and GCOS helped with data interpretation and drafting the manuscript. All authors read and approved the final manuscript.
This work was supported by the Cork Cancer Research Centre.
Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F: International variation in prostate cancer incidence and mortality rates.
Eur Urol 2012, 61:1079-1092. PubMed Abstract | Publisher Full Text
Miller AM, Pisa P: Tumor escape mechanisms in prostate cancer.
Cancer Immunol Immunother 2007, 56:81-87. PubMed Abstract | Publisher Full Text
Schurko B, Oh WK: Docetaxel chemotherapy remains the standard of care in castration-resistant prostate cancer.
Nat Clin Pract Oncol 2008, 5:506-507. PubMed Abstract | Publisher Full Text
Coffey DS, Isaacs JT: Control of prostate growth.
Urology 1981, 17:17-24. PubMed Abstract
Harada M, Noguchi M, Itoh K: Target molecules in specific immunotherapy against prostate cancer.
Int J Clin Oncol 2003, 8:193-199. PubMed Abstract | Publisher Full Text
Wright GL, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer PF, Moriarty R: Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
Urology 1996, 48:326-334. PubMed Abstract | Publisher Full Text
Kawakami M, Nakayama J: Enhanced expression of prostate-specific membrane antigen gene in prostate cancer as revealed by in situ hybridization.
Cancer Res 1997, 57:2321-2324. PubMed Abstract | Publisher Full Text
McNeel DG, Nguyen LD, Storer BE, Vessella R, Lange PH, Disis ML: Antibody immunity to prostate cancer associated antigens can be detected in the serum of patients with prostate cancer.
J Urol 2000, 164:1825-1829. PubMed Abstract | Publisher Full Text
Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M, Weber CE, Baccala AA, Goemann MA, Clift SM, et al.: Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer.
Cancer Res 1999, 59:5160-5168. PubMed Abstract | Publisher Full Text
McElrath MJ: Selection of potent immunological adjuvants for vaccine construction.
Semin Cancer Biol 1995, 6:375-385. PubMed Abstract | Publisher Full Text
Yedavelli SP, Guo L, Daou ME, Srivastava PK, Mittelman A, Tiwari RK: Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model.
Int J Mol Med 1999, 4:243-248. PubMed Abstract | Publisher Full Text
Eder JP, Kantoff PW, Roper K, Xu GX, Bubley GJ, Boyden J, Gritz L, Mazzara G, Oh WK, Arlen P, et al.: A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer.
Clin Cancer Res 2000, 6:1632-1638. PubMed Abstract | Publisher Full Text
Small EJ, Fratesi P, Reese DM, Strang G, Laus R, Peshwa MV, Valone FH: Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.
J Clin Oncol 2000, 18:3894-3903. PubMed Abstract | Publisher Full Text
Mincheff M, Tchakarov S, Zoubak S, Loukinov D, Botev C, Altankova I, Georgiev G, Petrov S, Meryman HT: Naked DNA and adenoviral immunizations for immunotherapy of prostate cancer: a phase I/II clinical trial.
Eur Urol 2000, 38:208-217. PubMed Abstract | Publisher Full Text
Pavlenko M, Roos AK, Lundqvist A, Palmborg A, Miller AM, Ozenci V, Bergman B, Egevad L, Hellstrom M, Kiessling R, et al.: A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.
Br J Cancer 2004, 91:688-694. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
N Engl J Med 2010, 363:411-422. PubMed Abstract | Publisher Full Text
Rice J, Ottensmeier CH, Stevenson FK: DNA vaccines: precision tools for activating effective immunity against cancer.
Nat Rev Cancer 2008, 8:108-120. PubMed Abstract | Publisher Full Text
Stevenson FK, Ottensmeier CH, Rice J: DNA vaccines against cancer come of age.
Curr Opin Immunol 2010, 22:264-270. PubMed Abstract | Publisher Full Text
Joniau S, Abrahamsson PA, Bellmunt J, Figdor C, Hamdy F, Verhagen P, Vogelzang NJ, Wirth M, Van Poppel H, Osanto S: Current vaccination strategies for prostate cancer.
Eur Urol 2012, 61(2):290-306. PubMed Abstract | Publisher Full Text
Ingolotti M, Kawalekar O, Shedlock DJ, Muthumani K, Weiner DB: DNA vaccines for targeting bacterial infections.
Expert Rev Vaccines 2010, 9:747-763. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Bowne WB, Srinivasan R, Wolchok JD, Hawkins WG, Blachere NE, Dyall R, Lewis JJ, Houghton AN: Coupling and uncoupling of tumor immunity and autoimmunity.
J Exp Med 1999, 190:1717-1722. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Finn OJ: Cancer vaccines: between the idea and the reality.
Nat Rev Immunol 2003, 3:630-641. PubMed Abstract | Publisher Full Text
Hawkins WG, Gold JS, Dyall R, Wolchok JD, Hoos A, Bowne WB, Srinivasan R, Houghton AN, Lewis JJ: Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity.
Surgery 2000, 128:273-280. PubMed Abstract | Publisher Full Text
Kim JJ, Trivedi NN, Wilson DM, Mahalingam S, Morrison L, Tsai A, Chattergoon MA, Dang K, Patel M, Ahn L, et al.: Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.
Oncogene 1998, 17:3125-3135. PubMed Abstract | Publisher Full Text
Kim JJ, Yang JS, Dang K, Manson KH, Weiner DB: Engineering enhancement of immune responses to DNA-based vaccines in a prostate cancer model in rhesus macaques through the use of cytokine gene adjuvants.
Clin Cancer Res 2001, 7:882s-889s. PubMed Abstract
Oliveira SC, Rosinha GM, de-Brito CF, Fonseca CT, Afonso RR, Costa MC, Goes AM, Rech EL, Azevedo V: Immunological properties of gene vaccines delivered by different routes.
Braz J Med Biol Res 1999, 32:207-214. PubMed Abstract
Moingeon P: Strategies for designing vaccines eliciting Th1 responses in humans.
J Biotechnol 2002, 98:189-198. PubMed Abstract | Publisher Full Text
Nishimura T, Nakui M, Sato M, Iwakabe K, Kitamura H, Sekimoto M, Ohta A, Koda T, Nishimura S: The critical role of Th1-dominant immunity in tumor immunology.
Cancer Chemother Pharmacol 2000, 46(Suppl):S52-S61. PubMed Abstract | Publisher Full Text
Gurunathan S, Klinman DM, Seder RA: DNA vaccines: immunology, application, and optimization*.
Annu Rev Immunol 2000, 18:927-974. PubMed Abstract | Publisher Full Text
Kongkasuriyachai D, Bartels-Andrews L, Stowers A, Collins WE, Sullivan J, Sattabongkot J, Torii M, Tsuboi T, Kumar N: Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission-blocking vaccine candidates Pvs25 and Pvs28-evaluation of homologous and heterologous antigen-delivery prime-boost strategy.
Vaccine 2004, 22:3205-3213. PubMed Abstract | Publisher Full Text
Grossfeld GD, Stier DM, Flanders SC, Henning JM, Schonfeld W, Warolin K, Carroll PR: Use of second treatment following definitive local therapy for prostate cancer: data from the caPSURE database.
J Urol 1998, 160:1398-1404. PubMed Abstract | Publisher Full Text
MacGregor RR, Boyer JD, Ugen KE, Lacy KE, Gluckman SJ, Bagarazzi ML, Chattergoon MA, Baine Y, Higgins TJ, Ciccarelli RB, et al.: First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response.
J Infect Dis 1998, 178:92-100. PubMed Abstract | Publisher Full Text
Moore AC, Hill AV: Progress in DNA-based heterologous prime-boost immunization strategies for malaria.
Immunol Rev 2004, 199:126-143. PubMed Abstract | Publisher Full Text
Marshall DJ, San Mateo LR, Rudnick KA, McCarthy SG, Harris MC, McCauley C, Schantz A, Geng D, Cawood P, Snyder LA: Induction of Th1-type immunity and tumor protection with a prostate-specific antigen DNA vaccine.
Cancer Immunol Immunother 2005, 54:1082-1094. PubMed Abstract | Publisher Full Text
Trikha M, Zhou Z, Nemeth JA, Chen Q, Sharp C, Emmell E, Giles-Komar J, Nakada MT: CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo.
Int J Cancer 2004, 110:326-335. PubMed Abstract | Publisher Full Text
Mosmann TR, Coffman RL: TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.
Annu Rev Immunol 1989, 7:145-173. PubMed Abstract | Publisher Full Text
Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Mueller-Berghaus J, Kirkwood JM, Kwok WW, Storkus WJ: Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma.
J Exp Med 2002, 196:619-628. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Tanaka M, Kaneda Y, Fujii S, Yamano T, Hashimoto K, Huang SK, Hoon DS: Induction of a systemic immune response by a polyvalent melanoma-associated antigen DNA vaccine for prevention and treatment of malignant melanoma.
Mol Ther 2002, 5:291-299. PubMed Abstract | Publisher Full Text
Schirmbeck R, Reimann J: Revealing the potential of DNA-based vaccination: lessons learned from the hepatitis B virus surface antigen.
Biol Chem 2001, 382:543-552. PubMed Abstract
Tangney M, Ahmad S, Collins SA, O'Sullivan GC: Gene therapy for prostate cancer.
Postgrad Med 2010, 122:166-180. PubMed Abstract | Publisher Full Text
Kusumanto YH, Mulder NH, Dam WA, Losen M, De Baets MH, Meijer C, Hospers GA: Improvement of in vivo transfer of plasmid DNA in muscle: comparison of electroporation versus ultrasound.
Drug Deliv 2007, 14:273-277. PubMed Abstract | Publisher Full Text
Ahlen G, Soderholm J, Tjelle T, Kjeken R, Frelin L, Hoglund U, Blomberg P, Fons M, Mathiesen I, Sallberg M: In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells.
J Immunol 2007, 179:4741-4753. PubMed Abstract | Publisher Full Text
Dupuis M, Denis-Mize K, Woo C, Goldbeck C, Selby MJ, Chen M, Otten GR, Ulmer JB, Donnelly JJ, Ott G, McDonald DM: Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice.
J Immunol 2000, 165:2850-2858. PubMed Abstract | Publisher Full Text
Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, Leung L, Otten GR, Thudium K, Selby MJ, Ulmer JB: Increased DNA vaccine delivery and immunogenicity by electroporation in vivo.
J Immunol 2000, 164:4635-4640. PubMed Abstract | Publisher Full Text
Roos AK, Pavlenko M, Charo J, Egevad L, Pisa P: Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine.
Prostate 2005, 62:217-223. PubMed Abstract | Publisher Full Text
Kuratsukuri K, Wang CY, Sone T, Nishisaka N, Jones RF, Haas GP: Induction of antibodies against prostate-specific membrane antigen (PSMA) by vaccination with a PSMA DNA vector.
Eur Urol 2002, 42:67-73. PubMed Abstract | Publisher Full Text
Kuratsukuri K, Sone T, Wang CY, Nishisaka N, Jones RF, Haas GP: Inhibition of prostate-specific membrane antigen (PSMA)-positive tumor growth by vaccination with either full-length or the C-terminal end of PSMA.
Int J Cancer 2002, 102:244-249. PubMed Abstract | Publisher Full Text
Johnson LE, Frye TP, Chinnasamy N, Chinnasamy D, McNeel DG: Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells.
Cancer Immunol Immunother 2007, 56:885-895. PubMed Abstract | Publisher Full Text
Johnson LE, Frye TP, Arnot AR, Marquette C, Couture LA, Gendron-Fitzpatrick A, McNeel DG: Safety and immunological efficacy of a prostate cancer plasmid DNA vaccine encoding prostatic acid phosphatase (PAP).
Vaccine 2006, 24:293-303. PubMed Abstract | Publisher Full Text
Ahmad S, Casey G, Sweeney P, Tangney M, O'Sullivan GC: Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.
Genet Vaccines Ther 2010, 8:1. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Ahmad S, Casey G, Sweeney P, Tangney M, O'Sullivan GC: Prostate stem cell antigen DNA vaccination breaks tolerance to self-antigen and inhibits prostate cancer growth.
Mol Ther 2009, 17:1101-1108. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Ahmad S, Casey G, Cronin M, Rajendran S, Sweeney P, Tangney M, O'Sullivan GC: Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous prostate cancer specific antigen.
J Urol 2011, 186:687-693. PubMed Abstract | Publisher Full Text
Mincheff M, Zoubak S, Makogonenko Y: Immune responses against PSMA after gene-based vaccination for immunotherapy-A: results from immunizations in animals.
Cancer Gene Ther 2006, 13:436-444. PubMed Abstract | Publisher Full Text
Roos AK, King A, Pisa P: DNA vaccination for prostate cancer.
Methods Mol Biol 2008, 423:463-472. PubMed Abstract | Publisher Full Text
Alam S, McNeel DG: DNA vaccines for the treatment of prostate cancer.
Expert Rev Vaccines 2010, 9:731-745. PubMed Abstract | Publisher Full Text
Todorova K, Ignatova I, Tchakarov S, Altankova I, Zoubak S, Kyurkchiev S, Mincheff M: Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.
Cancer Immun 2005, 5:1. PubMed Abstract | Publisher Full Text
Low L, Mander A, McCann K, Dearnaley D, Tjelle T, Mathiesen I, Stevenson F, Ottensmeier CH: DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer.
Hum Gene Ther 2009, 20:1269-1278. PubMed Abstract | Publisher Full Text
McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, et al.: Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer.
J Clin Oncol 2009, 27:4047-4054. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Kiessling R, Wasserman K, Horiguchi S, Kono K, Sjoberg J, Pisa P, Petersson M: Tumor-induced immune dysfunction.
Cancer Immunol Immunother 1999, 48:353-362. PubMed Abstract | Publisher Full Text
Pawelec G: Tumour escape: antitumour effectors too much of a good thing?
Cancer Immunol Immunother 2004, 53:262-274. PubMed Abstract | Publisher Full Text
Ahmad M, Rees RC, Ali SA: Escape from immunotherapy: possible mechanisms that influence tumor regression/progression.
Cancer Immunol Immunother 2004, 53:844-854. PubMed Abstract | Publisher Full Text
Tangney M, Casey G, Larkin JO, Collins CG, Soden D, Cashman J, Whelan MC, O'Sullivan GC: Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease.
Cancer Immunol Immunother 2006, 55:1443-1450. PubMed Abstract | Publisher Full Text
Mincheff M, Altankova I, Zoubak S, Tchakarov S, Botev C, Petrov S, Krusteva E, Kurteva G, Kurtev P, Dimitrov V, et al.: In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer–changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.
Crit Rev Oncol Hematol 2001, 39:125-132. PubMed Abstract | Publisher Full Text


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Nathan Ensmenger is Associate Professor in the School of Informatics and Computing at Indiana University.
This is a book about the computer revolution of the mid-twentieth century and the people who made it possible. Unlike most histories of computing, it is not a book about machines, inventors, or entrepreneurs. Instead, it tells the story of the vast but largely anonymous legions of computer specialists--programmers, systems analysts, and other software developers--who transformed the electronic computer from a scientific curiosity into the defining technology of the modern era.

subset: commoncrawl


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Sun 24th Feb at 10:00am daily - 5:50pm except Thurs & Fri 9:00pm
Humphrey Ocean: A Handbook Of Modern Life
@ National Portrait Gallery, London
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Humphrey Ocean: A Handbook Of Modern Life
A display of 40 works by British artist Humphrey Ocean painted in gouache on paper comprising colourful portraits of visitors to his south London studio, produced since 2006. The sitters include family members and friends.
Humphrey Ocean RA has a long association with the National Portrait Gallery, which began in 1982 when he won the Gallery's annual Portrait Prize with the painting Lord Volvo and his Estate. Ocean has undertaken several commissions for the Gallery including portraits of Paul McCartney (1982), the poet Philip Larkin (1984) and Tony Benn (1996). In The Painter's Eye at the National Portrait Gallery in 1999, Humphrey Ocean and film-maker John Tchalenko, with whom he has often collaborated, exhibited work from their Wellcome Trust Art and Science project. For the final room of the exhibition Ocean borrowed portraits by Rembrandt, Warhol, Auerbach and Gwen John.
A Handbook Of Modern Life has an obsessive character that is compelling and, when seen together, the portraits are an exuberant display of the artist's love of painting, colour and people. The immediacy of the gouache medium allows Ocean to capture quickly his sitters in simple forms, yet with striking presence. The majority of portraits on display show the sitter seated, yet each has a real sense of vitality and vibrancy that extends beyond the stillness of the pose.
Although the sitters have shared the experience, the unique quality of each portrait is a reflection of the way the artist and sitter responded to each other during the short period of the sitting. Ocean has attempted to paint what he saw in the studio that day; a portrait of the moment, not based on an accumulation of knowledge of the sitter. This was particularly challenging when his sitters included his daughters and wife.
Held in rooms 41 and 41a
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Venue: National Portrait Gallery
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Lover Girl Video
"Lover Girl" Premiere with Interview Magazine
The song is worth the wait: sexy and downtempo, laced with slippery synths, it's an argument in favor of evolution.-Interview Magazine
Sarah Featured on NPR's All Things Considered
Sarah's new track "Some People Will Tell You" was featured on NPR's All Things Considered. Check it out!
Sarah Jaffe To Perform at Dallas' Majestic Theater
Sarah will celebrate the release of her new cd on Aug 23rd at Dallas' historic Majestic Theater. Tickets are on sale now at prekindle.com


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VIDEO: David Corn Talks Rand Paul on Olbermann
Sun May 23, 2010 2:15 AM EDT
On Countdown With Keith Olbermann, David Corn discusses whether Rand Paul's remarks about the Civil Rights Act and the Obama administration will hurt the GOP. Watch the video below.
Visit msnbc.com for breaking news, world news, and news about the economy
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Truth Skepticism: An Inquiry into the Value of Truth in Times of TransitionErin DalyWidener University - School of Law March 2008 The International Journal of Transitional Justice, Vol. 2, Issue 1, pp. 23-41, 2008 Abstract: Truth commissions have become so fashionable in times of transition that one can readily recognize what might be called a 'truth cascade.' The commissions, and the reports they produce, are reputed to promote many of the goals at the heart of the transitional justice project: helping victims to heal, promoting accountability, drawing a bright line between the past and the present, promoting reconciliation and so forth. And yet, a closer look at the truth-seeking enterprise suggests that it may not be able to deliver on these promises. This article explores both the intrinsic and instrumental reasons why truth commissions may not be effective in promoting the goals attributed to them. The article does not argue that transitional governments should not pursue the truth, but it does urge governments to use caution and careful planning when they do so. Date posted: May 19, 2009Suggested CitationContact Information
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Pretrial hearing help for accused S. Ind. serial killer
UPDATED 5:45 PM EDT Sep 19, 2012Attorneys discuss crucial questions about moving forward in the case of William Clyde Gibson, who is charged in three deaths.
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Inspired by Georgian architecture, this mirror's frame is made of zinc-plated pine. Just shy of seven feet high, it will give any room the illusion of more space and light.


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Braid, the best selling Xbox Live Arcade game of 2008, and highest rated Arcade Game on Metacritic, has given Johnathan Blow great success. Now, gamers are left wanting more. Not necessarily more Braid, but more of the ingenuity that the game has brought to the market. Read more… »
Metallica may be limiting most of their touring to Europe these days, but they have graciously decided to share the full Guitar Hero songlist with everyone. If you haven't been following the games development, the game feature about 60% Metallica songs and 40% songs by musicians they admire.
Read more… »
Len Wiseman in a recent interview with Bloody Disgusting released a few interesting tidbits relating to the Gears of War Movie he is directing.
As I'm sure any gamer will tell you, Resident Evil 5 is one of the most, if not THE most anticipated game of 2009. Set to release on Friday the 13th in March, Capcom has tremendous hype to face after its predecessor was voted game of year by Spike TV, Nintendo Power, Game Informer and even Japan's ultra-critical Famitsu, and has even landed at number one of IGN's Top 99 Games of All Time list. However, with the RE5 demo release just one mere week away, many gamers are turning off the lights, cranking the sound, and screaming like six-year-old girls in frightened preparation. And let me tell you, this little six-year-old girl needs direct injections of RE5 into his veins.
In my opinion, Criterion Games has supported Burnout Paradise better than any other company has ever supported their game. Paradise has already had two free updates, one of which included a free motorcycle pack. Hit the jump to see whats in this new free pack! Read more… »
It seems that Anime isn't the only new venue being considered in the epic struggle to dislodge Blizzard from it's MMORPG throne. It appears that Halcyon Games have hinted that the Terminator franchise is an "interesting space" to consider development of an MMO.
In Katamari Damacy, the player rolls a giant ball in order to accrue items, and become bigger than the Earth. In Noby Noby Boy, the player eats items and stretches, to become the biggest…er..worm, ever! The game was supposed to have a worldwide release of January 29th on the PSN, but is instead pushed back to February 19th. The good news? The game is $5! Read more… »
Another day, another home-brew game in development. Stick this up your exhaust pipe and smoke it: developers are brewin' up a Mario Kart game using Half Life 2′s source as a basis. The game is going to be released for free, and has exact character models and stages from various Mario Kart games. Read more… »
A demo has recently been made available for F.E.A.R. 2 Project Origin, the sequel to the critically acclaimed F.E.A.R. The demo takes you through one level with a chilling and creepy layout and features a collection of weapons which are available for both singleplayer and multiplayer game modes.
So it's finally happened. The MMO genre has gotten so godforsakenly large that every game developer/publisher and their mothers think they can produce a smash hit and rake the mounds of cash in. And its hard to argue with them. With World of Warcraft breaching the 11 million players mark just a couple weeks back and competitors such as Warhammer Online, Lord of the Rings Online, and Star Wars: The Old Republic on the horizon, its no surprise a lot of companies are trying their hand at competing with the best.
However, as time has shown, the beast that is WoW will not go down easily, if it ever does. Yet, Namco Bandai (huh?) is taking their turn with hopes that a predominant anime series cultivates enough of a following to give them an edge over Blizzard. The series? Dragonball.
If you haven't played Meat Boy yet, here's a taste of what Super Meat Boy might be like. The game is an odd-ball 2d adventure, and is set to be released as a WiiWare title. There isn't much to say about this title except that when it comes out, it will be insanely popular. Read more… »
Rockstar Games has provided RockstarWatch with achievement information and a new screen shot for "The Lost and Damned" downloadable content for Grand Theft Auto IV. The expansion is set to hit Xbox Live on February 17, 2009 Read more… »


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Sura 40 - Ayat 58 |
Transliteration: |
(Click on
Ayat to hear it recited) |
English (Yusuf Ali): (Recite) 40:58 Not equal are the blind and those who (clearly) see: Nor are (equal) those who believe and work deeds of righteousness, and those who do evil. Little do ye learn by admonition! Turkish: French: German: Spanish: Copyright ©2000-2010 IslamiCity.com |


text: Monica Carter lives in Los Angeles, California and was a PEN USA Emerging Voices Fellow 2010 and a Lambda Literary Foundation Emerging GLBT Voice 2010. Her fiction has appeared in Strange Cargo, An Emerging Voices Anthology and Black Clock 12. She is the owner and curator of her own website dedicated to international literature, Salonica World Lit. She is currently working on a novel entitled Eating the Apple. |


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total posts: 41
Spicy Radish paste cooked with coconut and chilies...An east Indian relish which is served with rice.
A spicy relish made of Bottle gourd leaves
Freshly made syrup soaked cottage cheese balls in Thickened milk
Chocolate dipped sweetened coconut balls {recipe}
Banana Blossom patties with ginger, raisins and peanuts. {recipe}
Soy and vegetable grilled sandwich with whole wheat bread. healthy and scrumptious.
Thai Fish Curry
Rui Posto-fish in spicy poppy seeds gravy.
Indian Mutton Curry
Panthar Mangsho or Indian Goat meat curry
Spicy mango chutney with green chilies {recipe}
Chicken Rezala: Chicken cooked in Yogurt gravy {recipe}
Vietnamese Iced Coffee. Step by step pictorial {recipe}
Sun dried Cherry tomatoes {recipe}
Indian cottage cheese dumplings simmered in a spicy gravy {recipe}
A special summer treat of Palm jaggery laced baked yogurt. Easy and delicious {recipe}
Eggplant in a sweet and tangy yogurt sauce {recipe}
Vegetable Tempura on a bed of steamed white rice. A perfect winter meal.
{recipe} The classic caramel pudding with a twist of coffee flavour.
Bombay duck in a hot and fiery sauce to make your tastebuds alive in Winter
Winter flavours at its best. Fresh fenugreek greens and potato curry, for a comforting and warming meal.
Roasted vegetables, Chickpeas and fresh herb salad, Refreshingly light and tasty
{recipe} Mini spicy bites of lentil papad loaded with crunchy salad.
{recipe} Nimki, Indian deep fried savory snack
{recipe} Chicken Pilaf Indian syle
{recipe} Indian fried flat bread with spicy lentil curry
Semolina Pudding
Fish in creamy yogurt sauce. A delectable fish recipe from Eastern India.
Indian style veg fritters in tangy yogurt gravy
Wagashi, Traditional Japanese Sweets
Quick and easy eggplant-chicken stir fry with fewer ingredients for a wholesome meal.
Savoury Eggplant Fritter, Batter fried thin slices of eggplant fried to golden perfection.
Spicy Coastal India style prawn curry.
Indian style spicy mashed veggies with buttered buns


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This article may be expanded with text translated from the corresponding article in the German Wikipedia. (April 2012)
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This article may be expanded with text translated from the corresponding article in the Italian Wikipedia. (March 2015)
Click [show] on the right to read important instructions before translating.
This article includes a list of references, but its sources remain unclear because it has insufficient inline citations. (March 2011) |
Carl Clauberg | |
Born | Wupperhof, German Empire |
28 September 1898
Died | 9 August 1957 West Germany |
(aged 58)
Allegiance | German Empire (to 1918) Weimar Republic (to 1933) Nazi Germany |
Service/branch | Schutzstaffel |
Carl Clauberg (28 September 1898 – 9 August 1957) was a German medical doctor who conducted medical experiments on human beings in Nazi concentration camps during World War II. He worked with Horst Schumann in X-ray sterilization experiments at Auschwitz concentration camp.
Carl Clauberg was born in 1898 in Wupperhof (now part of Solingen), Rhine Province, into a family of craftsmen. During the First World War he served as an infantryman. After the war he studied medicine and eventually reached the rank of chief doctor in the University gynaecological clinic in Kiel. He joined the Nazi party in 1933 and later on was appointed professor of gynaecology at the University of Königsberg. He carried out research on female fertility hormones (particularly progesterone) and their application as infertility treatments, obtaining a Habilitation for this work in 1937.[1] He received the rank of SS-Gruppenführer of the Reserve.
In 1942 he approached Heinrich Himmler (who knew of him through his treatment of the wife of a senior SS officer[1]) and asked him to give him an opportunity to sterilize women en masse for his experiments. Himmler agreed and Clauberg moved to Auschwitz concentration camp in December 1942. Part of the Block number 10 in the main camp became his laboratory. Clauberg looked for an easy and cheap way to sterilize women. He injected formaldehyde preparations into their uteruses - without anesthetics. All of his test subjects were Jewish women who suffered permanent damage and serious infections. Some of the subjects died because of the tests. Estimates of those who survived but were sterilized are around 700.
When the Red Army approached the camp, Clauberg moved to Ravensbrück concentration camp to continue his experiments on Romani women. Soviet troops captured him there in 1945.
After the war in 1948 Clauberg was put on trial in the Soviet Union and received 25 years. Seven years later he was released in the framework of a prisoners of war exchange between the Soviet Union and West Germany and returned to West Germany, where he was reinstated at his former clinic based on his prewar scientific output. Bizarre behavior, including openly boasting of his "achievements" in "developing a new sterilization technique at the Auschwitz concentration camp", destroyed any chance he might have had of staying unnoticed. After public outcry from groups of survivors, Clauberg was arrested in 1955 and was put on trial. He died of a heart attack in his cell before the trial could start.
Clauberg test[edit]
The Clauberg test is an obsolete bioassay to assess progestational activity based on the conversion of proliferative endometrium to secretory endometrium in immature rabbits.[2][3]
See also[edit]
- ^ a b Robert Jay Lifton, "The Nazi doctors: Medical Killing and the Psychology of Genocide", Basic Books, 2000, ISBN 978-0465049059; pp. 271-278 of the online edition and references there, http://www.holocaust-history.org/lifton/LiftonT271.shtml
- ^ Clauberg C. "Physiologie und Pathologie der Sexualhormone, im Besonderen des Hormons des Corpus luteum. I. Der biologische Test für das Luteumhormon (das spezielle Hormon des Corpus luteum) am infantilen Kaninchen.". Zentralblatt für Gynänekologie , 1930, 54:2757-2770.
- ^ "Clauberg's method, alt. Clauberg's test". Whonameit?. Retrieved July 11, 2014.
- Ernst Klee: Auschwitz, die NS-Medizin und ihre Opfer. 3. Auflage. S. Fischer Verlag, Frankfurt am Main, 1997, ISBN 3-596-14906-1.
- Alexander Mitscherlich, Fred Mielke: Medizin ohne Menschlichkeit: Dokumente des Nürnberger Ärzteprozesses, 1. Aufl., Heidelberg: Fischer 1960. ISBN 3-596-22003-3, Taschenbuch wird 2008 in der 16. Auflage vertrieben.
- Jürgen Peter: Der Nürnberger Ärzteprozeß im Spiegel seiner Aufarbeitung anhand der drei Dokumentensammlungen von Alexander Mitscherlich und Fred Mielke. Münster 1994. 2. Auflage 1998.
- Till Bastian: Furchtbare Ärzte. Medizinische Verbrechen im Dritten Reich. Originalausgabe, 3. Auflage, Verlag C. H. Beck, München 2001, Becksche Reihe; Band 1113, ISBN 3-406-44800-3.
- R. J. Lifton, The Nazi Doctors. Medical Killing and the Psychology of Genocide. New York 1986), ISBN 3-608-93121-X.
- Hermann Langbein: Menschen in Auschwitz. Frankfurt am Main, Berlin Wien, Ullstein-Verlag, 1980, ISBN 3-548-33014-2.
- Hans-Joachim Lang: Die Frauen von Block 10. Medizinische Experimente in Auschwitz. Hamburg 2011. ISBN 978-3-455-50222-0.
External links[edit]


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TCSD (Triathlon Club San Diego) released a preview of their 2008 race apparel:
For those of you coming down from your weekend runner's high, check out this article posted by Active Expert Charles Stuart Platkin, where researchers have finally demonstrated the existence of an 'endorphin driven runner's high'.
Do you get enough sleep? Check out this study released by the U.S. Centers for Disease Control and Prevention (CDC) suggesting that Americans aren't getting their Zzzz's.
Did your favorite marathon make the list? Check out the Guide to Some of the Best Marathons in North America and let us know.
"You can't keep those women down, you can't get them back in the kitchen." Read the full story to find out which major marathon event director has his foot in his mouth.
Listen to this podcast from Endurance Planet, where USAT Coach Troy Jacobson answers a question about strength training for the marathon, finishing strong in a 70.3, and full Iron-distance event.
And last and certainly not least, ActiveX: ARMaggedon
patriciagreen on "You are an Ironman"
sportshoesale on "You are an Ironman"
spicegeek on Top 10 Thoughts That Go Through Your Mind When Running The New York City Marathon
mrsphong on World Triathlon Corporation Continues Ironman 70.3 Growth
diarrhea on Branson, Missouri, To Host Newest Ironman 70.3


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The Woolmark Company Launches Online Retail Portal
Take the leg work out of finding merino wool.
Read more
woolmarkThe Woolmark Company Launches Online Retail PortalTake the leg work out of finding merino wool. Read morePublic School and M. Patmos Take Home Woolmark US Top HonorsLast night's heat and storms didn't dampen the festive mood at the Woolmark U.S. International Prize Awards, where Public School and M. Patmos took home the top honors for menswear and womenswear, respectively. Read moreWoolmark and Roland Mouret Team Up for Capsule CollectionMouret's signature style, Merino wool and Nicole Warne serve as the perfect combination. Read moreVogue L'Uomo Celebrates 'Powerful Australia'It's the second time this year Cate Blanchett has donned a suit for the cover of Vogue. Read moreIndian Designer Rahul Mishra Nabs the Spotlight with International Woolmark PrizeWith a coveted prize under his belt and the attention of Alexa Chung, Frida Giannini, Franka Sozzani, Tim Blanks — just a handful of the 11 judges — Mishra seems poised to bring traditional crafts to an increasingly wide audience. Read moreWatch Alexander Wang and Annie Leibovitz Behind-the-Scenes for WoolmarkIf you like sheep, this video is for you. Read more |


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Open a Wine Bottle Without a Corkscrew
From Wired How-To Wiki
It happens to every wine drinker at least once. After agonizing over the perfect bottle to crack open, you realize the corkscrew has gone AWOL. Luckily, there are plenty of other tools you can use to get into (and to the bottom of) your favorite bottle of wine.
Contents |
What You'll Need
- 2" (or longer) Screw
- Screwdriver
- Regular Claw Hammer
Step 1: Prep the Area
Although this method is a reliable way to uncork a bottle, it's not always the cleanest. Before getting started make sure your uncorking area has enough room for a wide, arching release when the cork finally gives. Also, a few standby towels couldn't hurt.
Step 2: Twist the Screw Into the Cork
After removing the foil from the top of the bottle, use the screwdriver to gently twist the screw into the center of the cork. The goal is to get enough in to be able to yank the cork out cleanly, so make sure to stop about 3/4ths of the way through the cork. When you're done most of the screw should be securely embedded, with just enough sticking out from the top to grip with the hammer.
Step 3: Scoot the Hammer Into Place
Grab the hammer and grip the exposed portion of the screw between the claws. Again, the goal here is getting a solid grip without loosening the screw.
Step 4: Yank The Cork
With the bottle held securely into place, it's time to apply the muscle. One long, smooth tug away from the body should be enough to free most corks. Don't get overzealous though. No bottle of private reserve is worth a hammer to the face.
This page was last modified 21:48, 5 August 2008 by trussell.


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Shepherdstown dependent on volunteersFebruary 28, 2014More people than ever want to give back to their communities. Recent studies show that volunteering can boost happiness, decrease depression, and help us live longer.... Jester01Good point. Serving does make me feel better. Hmmm. 0 Agrees | 0 Disagrees | Report Abuse » Showing 1 of 1 comments
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With the Triumph 800xc out would you still buy an F800gs?
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Kountersteering Krew
Joined: May 2002
Location: Denver, CO
Oddometer: 2,602
I was at the local RAT meeting last night. Bob and Denise were there. They own six or eight bikes between the two of them, and Denise just took delivery on a Tiger 800. She told me she loves the bike, but it recently stalled 20 times during a short ride.
Naturally, the dealer disavowed any knowledge of this problem, but Denise says it's well known on the internet forums. She says the fix is to fit an $800 Arrow pipe and have the bike remapped accordingly. Not wanting to spend the money to fix her brand-new bike, Denise had it remapped without the pipe, which solved the stalling problem, but now the bike runs like shit.
I had similar problems on both my 2000 Sprint ST, long since sold, and my 2001 Sprint RS, which I love and ride often. After I had the RS's front and rear suspension upgraded, the bike stalled 17 times on the 20-mile ride home. Basically, whenever I slowed for a stop, the bike would stall. The dealer was unable to diagnose the problem and eventually re-flashed the ECM. This solved the stalling problem, but now the bike is either on high idle whenever it's in neutral, or it will flip-flop and idle normally in neutral but high in every other gear. I have learned to live with this, as it's more of a nuisance than a real problem.
I love my Sprint RS. It was cheap as hell to buy used, and with cartridge emulators, fresh Q2s and an Ohlins shock, it's super comfy and handles beautifully. But I would never--NEVER--buy a new Triumph. Not only is the resale value deplorable, but the bikes are buggy and the dealers are clueless. Just my $.02.
2012 Speed Triple
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follow Dictionary.com
9 Grammatical Pitfalls
any type of processed meat whose source is indistinguishable, esp. that served in a cafeteria
Spam is the most famous mystery meat.
Meat not readily identifiable, esp as served in a student dining hall, fraternity house, etc: Parents must follow the rules: They are forbidden to smoke or leave the building, must show up at homeroom and eat mystery meat at lunch like the rest of their classmates
[1970s+ Students; meat loaf was called mystery loaf by the 1940s]


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This LifeSmart 1500W Infrared Quartz Heater drops from $108.95 to $99.99 via exclusive code BRADSMART at VM Innovations. With free shipping, this is the best deal we could find by $24. It features a wireless remote control and it can heat up to 1500 sq ft of space. Plus, it comes with a 2 year warranty. There is no sales tax (except PA, NV and NE).
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Type: | Sport, 2 pitches, 150' |
Consensus: | YDS: 5.11 French: 6c+ Ewbanks: 23 UIAA: VIII- ZA: 23 British: E4 5c [details] |
FA: | Tim Kuss and Chris French? |
Page Views: | 771 |
Submitted By: | eDixon on Aug 20, 2008 |
Comments on Flat Track | Add Comment |
Show which comments —
By Cpt. E Sep 25, 2008 |
So, is this named Flat-track or Soul-Kitchen? |
By sssss Nov 28, 2008 |
I'm pretty sure Tim Kuss and Chris French bolted this one. |
By manuel rangel From: Tempe, Arizona Jan 12, 2009 |
I did Soul Kitchen, and it's not in the photo. It is to the right, goes up slab to dihedral. Jimmy S. told me the dihedral (at the finish) had been done as a TR and I just added the beginning pitch. There were no bolts on the route I did. |
By Tim Kuss From: Durango, CO Mar 31, 2010 |
The 5.8 first pitch of this route is called Dirt Track. I mean to go back and add a bolt to Flat Track where there is a nasty fall potential after the third bolt. |
By Ben Griffin From: Durango, CO Jun 26, 2011 rating: 5.11 6c+ 23 VIII- 23 E4 5c |
Did this route in one pitch with a 70m. I had to belay the second from a ledge where the first belay anchor is at. The rope got really heavy up there. |


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The Washington Times | October 19, 1999 |
If parents dont teach values, others fill void
By Michael Farris One of the most treasured opportunities for parents is to transmit our core values to our children. Our views about love of God, love of country, the need for honesty, and the value of loyalty to our family are just a few of these key beliefs. I was recently given a book, The Bridger Generation: Americas Second Largest Generation, What They Believe, How to Reach Them, by Thom Rainer, published by Broadman & Holman. Mr. Rainer provides statistics that should give every parent a chill. He examines the transmission of religious beliefs from one generation to the next. Specifically, he looks at this issue in the context of four generations of those who profess to be born-again Christians: builders (born before 1946), boomers (1946-64), busters (1965-76), and bridgers (1977-94). He found that the following percentages of the generations professed a personal relationship with Christ: builders, 65 percent; boomers, 35 percent; busters, 15 percent; and bridgers, 4 percent. The generational fall-off is astounding to me. This failure to transmit a core value arises among a religious group whose professes to believe that they have a duty to evangelize the whole world for Christ. What is apparent is that at least half of those growing up in the homes of evangelicals haven't adopted the religious convictions of their parents. The most important lesson I learn from this as an evangelical Christian is that I should not assume that my children will adopt my faith simply by osmosis. I need to take daily affirmative steps to ensure that my children learn to love God and His Word in a personal daily relationship. This lesson has other applications as well. If I want my children to have the values I hold dear about liberty and love of America, I dare not ignore my duty to transmit those convictions to my children. There is no substitute for both time and instruction. If I want my children to share my core beliefs, I must spend time with my children, and I must directly teach and live those beliefs in front of them. Parents may think they are doing this, but perhaps we should think again. I can guarantee you that network TV programming does not share the beliefs of any person who has managed to read this far in this column. Your childs mind is like an election. You cast ballots. The TV casts ballots. Your childs school casts ballots. Their friends cast ballots. Video games cast ballots. Movies cast ballots. Who cast the most ballots in your childs mind last week? If you believe that the others who affect your childs mind exert a benign influence, think again. Take the arena that is most pertinent to this columneducation. Multicultural education is not about celebrating all cultures. I handled one of the first lawsuits in the nation that concerned multicultural education and diversity. It was called Mozert v. Hawkins County Schools. My liberal opponents called it the Scopes II Trial. The issue was whether children could be assigned an alternative book if the designated text offended their religious faith. All manner of religions were represented in the book, but the only appearances of Christianity were for the purpose of exposing it to insinuated or explicit ridicule. Witchcraft, Eastern mystic religions, and others were presented positively. That is multiculturalism. Women were presented in careers of all types, but women who want to choose the role of wife and mother were demeaned either directly or by lack of an appropriate role models. That is the feminist version of diversity. Children who refused to read this book were expelled from school. The school and People for the American Way (which sponsored the law firm who defended the school) justified expulsions for refusing to read diversitytexts as promoting tolerance. It appeared to me that the tacticians of tolerance werent tolerant. The philosophy I challenged in court in the late 1980s in the elementary schools of Hawkins County, Tenn., is the overwhelmingly dominant philosophy of educationespecially at the high school and college levels. When a childs life is filled with television, coercive lessons on tolerance, the raunchy reeducation of MTV and diversity lessons that never reinforce the traditional beliefs of their families, it is little wonder that their belief systems differ so radically from those of their parents. If your children end up rejecting your beliefs and values, even something as important to you as your faith in God, you wont be alone. Thom Rainers statistics prove that the same thing has happened to millions of others. But the feeling of lonely anguish that comes from a childs rejection of things you hold dear is never truly assuaged. Teach your children what you believe. The coercive partisans of tolerance will teach them if you dont. Michael Farris is the father of 10 home-schooled children and chairman of the Copyright 2000 News World Communications, Inc. Reprinted with permission of The Washington Times. Visit our web site at http://www.washtimes.com.
The Washington Times
October 19, 1999
Home School Legal Defense Association


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Exploring Advanced Insurance Contract Fundamentals
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Standard liability coverage may not be enough. Special needs call for specialized policies. -
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Permanent Life Policies: Whole Vs. Universal
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Dragon Ball Z Kai: Part 8(TV) (2011)The last descendants of an evil race of warriors known as the Saiyans are on a collision course with Earth, and Goku - the strongest fighter on the planet - is all that stands between humanity and extinction. To save his friends and the world he loves, Goku must travel to a realm from which few return, but should he survive, he'll discover the power to face the villainous Saiyan warlord - Prince Vegeta. For more about Dragon Ball Z Kai: Part 8 and the Dragon Ball Z Kai: Part 8 Blu-ray release, see Dragon Ball Z Kai: Part 8 Blu-ray Review published by Jeffrey Kauffman on June 9, 2012 where this Blu-ray release scored 4.0 out of 5. Director: Yasuhiro Nowatari Starring: Masako Nozawa, Ryō Horikawa, Toshio Furukawa, Mayumi Tanaka, Hiromi Tsuru, Tōru Furuya » See full cast & crew Dragon Ball Z Kai: Part 8 Blu-ray, Video QualityThere's not a lot I can add to the assessment that Dustin Somner and I have already given to the previous seven volumes of Dragon Ball Z Kai's AVC encoded 1080p transfers in 1.33:1. As Dustin and I have discussed in our reviews of the previous releases of Dragon Ball Z Kai, FUNimation's efforts with regard to this series have been largely commendable, restoring, reediting and crafting new bridging segments to remake the original Dragon Ball Z into a supposedly "no filler", to the point piece. The video quality here is very much in line with the previous releases. A lot of this presentation looks a bit on the soft side, as all the previous volumes have, but colors are incredibly robust and beautifully saturated. As with Volume Seven especially, Volume Eight once again shows notable sharpness differences between the older and newer elements, which may simply reflect this particular set of episodes' increased usage of newer bridging elements. There are once again some minor stability issues that are akin to telecine wobble that are quite noticeable in several episodes. Dragon Ball Z Kai: Part 8 Blu-ray, Audio QualityContinuing the pace set by the first seven volumes, Dragon Ball Z Kai Part Eight offers two great lossless tracks, a Japanese language track delivered via Dolby TrueHD 2.0 and an English dub delivered via Dolby TrueHD 5.1. As has been the case in the previous volumes, the Japanese track sounds just a tad clipped at the extreme upper and lower registers, making it not only narrower but also slightly more compressed sounding. The English dub is incredibly boisterous and offers a surprising amount of really good surround activity (this volume has some especially good sound effects which zing through the surround channels, notably in the final battle arc that makes up a central part of this volume's episodes). It also has good, consistent use of LFE throughout the many battle sequences. Dragon Ball Z Kai: Other Seasons
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About Alexander Mitchell
Garry Mitchell, known as Alex Mitchell is a singer, songwriter, poet and writer, best known for being the frontman for Circus of Power (COP). Musical career: Born in Toronto but raised in Florida Mitchell began founding and performing in several bands before achieving notoriety, which included Saint Mary's Children of Salvation and Crucial Truth. In 1986, Mitchell turned his focus toward founding a more grounded rock and roll band; the Circus of Power, the most successful venture of his musical career. After they disbanded, Mitchell has been a member of Absolutely Free, Uncle Max, Second Ring of Power, Plastic Gator Machine, and Fat Nancy. Author and writer: Mitchell is now writing short stories for Far West Almanac. He collaborated with the Los Angeles band, Rusty Eye, providing spoken word and vocals on the song "The Serial Kind" for the album Possessor". Has also written a novel, Working Class Superstar.
Text from this biography licensed under
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Rhodes College, Political Economy
Assistant Professor, Contemporary United States Domestic Policy
Institution Type: | College / University |
Location: | Tennessee, United States |
Position: | Assistant Professor, Tenure Track Faculty |
Rhodes College invites applications for a tenure-track position at the Assistant Professor level focusing on contemporary United States domestic policy. The position is open to applicants from any relevant discipline and specializing in any policy area. Candidates specializing in environmental, health, education, or energy policy are particularly welcomed. The person filling this position will be a member of the appropriate Rhodes academic department and will contribute to the interdisciplinary Program in Political Economy. The successful candidate will teach introductory and upper level public policy courses, in addition to other courses in the relevant department's curriculum. The teaching load is 3-2. A Ph.D. is expected by August, 2013. Applicants must be able to demonstrate their commitment to undergraduate teaching as well as their promise for scholarly work in their discipline.
Founded in 1848, Rhodes College is a highly selective, private, residential, undergraduate college, located in Memphis, Tennessee. We aspire to graduate students with a lifelong passion for learning, a compassion for others, and the ability to translate academic study and personal concern into effective leadership and action in their communities and the world. We encourage applications from candidates interested in helping us achieve this vision.
Rhodes College values an inclusive and welcoming environment. We are an equal opportunity employer committed to diversity in the workforce.
Memphis has a metropolitan population of over one million and is the nation's 19th largest city. The city provides multiple opportunities for research and for cultural and recreational activities. Read more about Memphis at http://www.rhodes.edu/about/22775.asp.
The program uses an electronic submission process for all applications and only electronic submissions will be considered. Interested applicants can apply online at jobs.rhodes.edu. Applicants should submit a letter of application, curriculum vitae, transcript, three letters of recommendation, evidence of teaching performance, and samples of written work. Review of completed applications will begin October 22, 2012, and continue until the position is filled.
Contact: |
Teresa Gramm, Director of the Political Economy Program (firstname.lastname@example.com). |
Website: | http://www.rhodes.edu/politicaleconomy/default.asp |
Primary Category: | Public Policy |
Secondary Categories: | None |
Posting Date: | 09/28/2012 |
Closing Date | 12/26/2012 |


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Copyright / Legal Information
The name "Paragon Graphics" is an individual trademark in the state of Massachusetts. The use of the name Paragon Graphics when pertaining to a graphic design company/agency is strictly prohibited and protected under Massachusetts laws governing trademark infrigement. The use of "Manny" as an avatar to a graphic design company is also trademarked and prohibited in the state of Massachusetts. Any unauthorized use of this trademarked name, logo or avatar will result in legal action.


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This past week was an exciting one for the Cloudscaling team. While we already have customers deployed on our Essex-based OCS 1.x releases, we began our first Folsom-based OCS 2.0 customer deployments last month. As a refresher, Cloudscaling announced OCS 2.0 at the OpenStack Design Summit in San Diego and there were two big pillars for that release:
Let's chat about these two major updates.
OCS Block Storage
This commercially licensed product is an optional add-on to OCS. It is our scale-out network attached disk solution that provides persistent and expandable block level storage volumes served up by independent loosely-coupled block storage nodes. If you are familiar with Amazon Web Service (AWS), OCS Block Storage provides the same benefits as AWS Elastic Block Storage (EBS). It can be thought of as a virtualized Just a Bunch Of Disks (JBOD) service. Most current demand we are seeing for block storage are customers that have a need for:
Consuming OCS Block Storage is trivial – user volumes are ordered via the OpenStack APIs (EC2, Nova, or GCE), can be attached to a running instance, and appear as block devices like any hard drive. With OCS Block Storage complementing our built-in ephemeral storage, an instance can be booted, volumes attached, data processed, instance terminated, and the data would remain to be used again later.
We developed a storage scheduler for OCS Block Storage that maximizes volume dispersion on a per-tenant basis to reduce the impact of infrastructure failures on volume availability. This is a classic "scale-out" or "sharding" approach and is exactly how OpenStack Compute manages and allocates virtual servers to hypervisors. Here is an example of how the scheduler works.
Tenants can request and allocate a number of block volumes and aggregate them into a single software RAID set, knowing that individual volume failures will simply look like failed disk drives in the RAID array, which can be easily replaced using the same process. Simple yet effective.
OpenStack Folsom – "Awesome"
Folsom, in a word, is awesome. There has been incredible and steady progress in code base, stability, bug fixes, and an incredibly number of new developers. Just look at the trend lines in this Ohloh chart showing contributors over time vs. other similar projects. This particular picture shows far more than a thousand words ever could.
As you know, we've been building OpenStack-based solutions since Cactus so we've seen our fair share of "rough around the edges" code and integration challenges in OpenStack. While many vendors gravitate towards the new projects introduced in Folsom, we are most excited about improvements to existing projects like Nova (and offshoots such as Cinder). This is because, at Cloudscaling, we focus on supporting production workloads that run on top of OCS.
One example of a major improvement in Folsom (and there are many), is Nova's VM state management, which has been massively improved. Prior to Folsom, it was common to find a VM permanently stuck in a pending state, from which there was no way to recover using Nova API calls. The only way to get rid of a VM in this state was to manually update Nova's MySQL database to wipe out any trace of that VM – a potentially tricky and risky maneuver. In Folsom, it is less likely for VMs to become stuck and if they do, there is also a "reset-state" API call that can be used to safely reset the VM state.
Deliver On OCS 2.0
At Cloudscaling, we strive to make OCS the best OpenStack-based system on the planet and delivering OCS 2.0 materially moves the needle for us towards that goal. Our OCS 1.x customers are already planning their upgrades to OCS 2.0 to take advantage of these new capabilities. I think it's an understatement to say we will have more exciting weeks ahead of us.
This entry was posted in Cloud Computing, Uncategorized and tagged Block Storage, Folsom, OCS, Open Cloud System, OpenStack. Bookmark the permalink.
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Tap Here to view the Mobile Optimized TFLN
he could've at least fucked me twice. that's just common courtesy.
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I'm guessing he didn't like it all that much the first time.
Common courtesy? Common sense.
Maybe he didn't like it the first time around..
He did. He didn't wear a condom. Now you're really fucked.
Common quick squirt!
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(wide places, i.e. streets).
+ The third of the series of wells dug by Isaac, (Genesis 26:22) in the Philistines' territory, lately identified as er-Ruheibeh, 16 miles south of Beersheba.
+ One of the four cities built by Asshur, or by Nimrod in Asshur, according as this difficult passage is translated. (Genesis 10:11) Nothing certain is known of its position.
+ The city of a certain Saul or Shaul, one of the early kings of the Edomites. (Genesis 36:37; 1 Chronicles 1:48) The affix "by the river" fixes the situation of Rehoboth as on the Euphrates.


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Summer not so hot for networks in primetime |
(Posted August 3, 2005 by Leah Yoakum) LOS ANGELES (Hollywood Reporter) - Despite all of the original series on the schedule, the Big Four networks' summer slump continued during the week ended July 31. CBS won the week in viewers, with a mere 7 million average, and tied Fox for the No. 1 ranking in the adults 18-49 demographic with an equally lackluster 2.2 rating/7 share, according to Nielsen Media Research. As usual, CBS was powered by the strength of its regular schedule, even in repeats. Fox was buoyed at opposite ends of the week by Monday's 9 p.m. "Hell's Kitchen" (7.4 million, 3.6/10) and Sunday's combo of the 8:30-9:30 p.m. "The Simpsons" (6.7 million, 3.3/10) and "Family Guy" (6.6 million, 3.2/9). Fox's Wednesday 8:00-9:30 p.m. dance competition series "So You Think You Can Dance" (8 million, 3.3/11) cooled considerably in its second airing. NBC was No. 2 to CBS for the week in viewers (5.8 million), followed by ABC (5.2 million), Fox (5.1 million), UPN (2.8 million) and WB Network (1.7 million). In the key demo, NBC trailed CBS and Fox at a 1.8/6, while ABC pulled a 1.7/6. Although the Big Four are offering a fair number of original series in the off-season this year, the numbers compared with summer 2004 are down or flat. For the period stretching from May 30-July 31, CBS is down 11% in viewers compared with the comparable period last year and down 8% in adults 18-49. NBC is off 20% in the demo and down 11% in viewers. Both CBS and NBC have had uphill climbs with their summer originals. Even CBS' "Big Brother" franchise is off its game this year, while the heavily promoted "Rock Star: INXS" has shown little spark. NBC has been in the same boat, with its "Average Joe" matchmaking series delivering unimpressive numbers, while new offerings like "I Want to Be a Hilton" were barely sampled. ABC and Fox are up 8% and 3%, respectively, in viewers for the summer-to-date; both nets are flat in the adults 18-49 column despite Fox's traction with "Hell's Kitchen" and ABC's sleeper success with "Dancing With the Stars." By Cynthia Littleton and Andrew Wallenstein |
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One Tree Hill: Season 7, Episode 19Every Picture Tells a Story (26 Apr. 2010) 7.9
Quinn's gallery opens with Clay very supportive unaware that he is being stalked by Sara lookalike Katie until she makes her presence known and Clay shows Quinn how alike Katie is to Sara. ... See full summary » Director:Chad Graves |
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Bee Deaths
5:48 pm
Fri December 20, 2013
Penalties In For Wilsonville Bee Deaths
Penalties are in for a company implicated in the deaths of bumblebees in Oregon earlier this year. The Oregon Department of Agriculture has issued civil penalties to the pesticide company and its employees.
Pesticide company Collier Arbor Care and four of its employees will pay $2,886 for bumblebee kills.
The most notable incident killed 50,000 bumblebees in Wilsonville, Ore. Collier employees incorrectly applied a pesticide to blooming linden trees.
The fine also includes a smaller incident in downtown Portland.
Bruce Pokarney is with the Oregon Department of Agriculture. He says the state is working to better educate commercial pesticide companies. To get recertified:
"There'll be some test questions that they'll have to answer that are very directly related to their knowledge of pollinator protection," Pokarney says.
Collier Arbor Care says the company is appealing the penalties.
Copyright Northwest Public Radio 2013.
Pesticide Restriction
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