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Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth’s grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients n=28 (60.9%) were well differentiated, n=15 (32.6%) were moderately differentiated, and only n=3 (6.5%) were poorly differentiated. All n=46 cases of OSCC were positive for EP3 receptor antibody, n=14 (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, n=17 (37%) cases showed moderate intensity, and n=15 (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study.

We investigated the role that prostaglandins (PGs) and EP receptors play in facilitating the gastroprotective action of capsaicin against HCl/ethanol in rats and mice. Male Sprague-Dawley rats and C57BL/6 mice were used after 18 h of fasting. The animals were given HCl/ethanol (60% in 150 mM HCl) p.o. and killed 1 h later. Capsaicin or various EP agonists were given p.o. 30 min or i.v. 10 min before HCl/ethanol. In some cases, indomethacin or various EP agonists were given s.c. 30 min or i.v 10 min before capsaicin, respectively. Gastric lesions induced by HCl/ethanol were significantly inhibited by PGE(2) as well as capsaicin. The effect of PGE(2) was antagonized by ONO-AE-829 (EP1 antagonist), whereas the capsaicin action was mitigated by indomethacin as well as sensory deafferentation but not by ONO-AE-829. The generation of mucosal PGE(2) was not affected by either capsaicin or sensory deafferentation, but was significantly inhibited by indomethacin. Although neither butaprost (EP2), ONO-NT-012 (EP3), nor 11-deoxy PGE1 (EP4) alone had any effect on HCl/ethanol-induced gastric lesions, only butaprost restored the protective action of capsaicin in the presence of indomethacin. Capsaicin provided a protective action against HCl/ethanol-induced gastric lesions in wild-type (+/+) mice in an indomethacin-sensitive manner, and this action was similarly observed in EP1 (-/-) and EP3 (-/-) mice but not in the animals lacking IP receptors. These results suggest that capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous PGs through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin.

In a “call for leadership” panel at ISSCC, we will be seeking leaders' perspectives on the future of discontinuous innovation in the semiconductor industry. An ensemble of visionaries, experts and CEOs will discuss the opportunities and challenges for innovation in our industry. Of primary concern is the reduction in funding available for new semiconductor ventures. Are the escalating NRE costs of ASICs providing a barrier to new entrants? What advice would our distinguished panellists give to entrepreneurs thinking of starting a new semiconductor company?

To investigate the expression of four subtypes of PGE2 E-prostanoid (EP) receptors (EP1–EP4) and the effects of EP3/EP4 on bladder dysfunction in a new neurogenic bladder model induced by experimental autoimmune encephalomyelitis (EAE), the mouse model of EAE was induced using a previously established method, and bladder function in mice with different defined levels of neurological impairment was then examined, including micturition frequencies and voiding weight. Bladders were then harvested for analysis of EP receptor expression by Western blot. Activities of agonists/antagonists of EP3 and EP4 receptors as well as PGE2 were also evaluated at different stages of EAE. The results showed that EAE mice developed profound bladder dysfunction characterized by significantly increased micturition and significantly decreased urine output per micturition. EAE-induced upregulation of EP3 and EP4 receptors in the bladder was accompanied by bladder dysfunction. However, EAE had no significant effect on EP1 and EP2 receptors. Moreover, PGE2 and agonists/antagonists of EP3 and EP4 receptors significantly affected bladder dysfunction in EAE mice. Thus, we believe that EAE mice are useful for investigations of the neurogenic bladder. In addition, EP3 and EP4 receptors play a role in EAE-induced bladder dysfunction, providing us with a new target for the treatment of neurogenic bladders.

We previously documented that ocular surface epithelial cells could regulate ocular surface inflammation and suggested that, while Toll-like receptor 3 upregulates, EP3, one of the prostaglandin E2 receptors, downregulates ocular surface inflammation. Others reported that rebamipide, a gastroprotective drug, could not only increase the gastric mucus production, but also suppressed gastric mucosal inflammation and that it was dominantly distributed in mucosal tissues. The eyedrop form of rebamipide, approved in Japan for use in the treatment of dry eye diseases, upregulates mucin secretion and production, thereby suppressing superficial punctate keratopathy on the ocular surface of patients with this disease. In the current study, we investigated whether rebamipide has anti- inflammatory effects on the ocular surface.To examine the effects of rebamipide on polyI:C-induced cytokine expression by primary human conjunctival epithelial cells, we used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction assay. We studied the effects of rebamipide on ocular surface inflammation in our murine experimental allergic conjunctivitis (EAC) model.Rebamipide could suppress polyI:C-induced cytokine production and the expression of mRNAs for CXCL10, CXCL11, RANTES, MCP-1, and IL-6 in human conjunctival epithelial cells. In our EAC model, the topical administration of rebamipide suppressed conjunctival allergic eosinophil infiltration.The topical application of rebamipide on the ocular surface might suppress ocular surface inflammation by suppressing the production of cytokines by ocular surface epithelial cells.

A distinguished panel of experts from global industry and academia will debate the nature of systems that will drive the killer applications of 2020. Can we really forecast these future killer applications? We have had the computing revolution, then communications, and now, the sensor revolution. Are sensors driving the future killer applications? Are there any other revolutions in sight? What circuits and system innovations can ISSCC bring forward to enable the next killer applications? What unique technology elements, device structures and memory architectures will be required? Should we continue with silicon technology and seek breakthroughs in system architecture, algorithms, SoC integration and packaging? Or, are we preparing for “beyond silicon” technologies? And if so, which beyond-silicon technologies are realisitic for the future, versus forever being technologies of the future?

A workshop devoted to a discussion of the role of prostaglandins (PGs) in bone physiology and in bone disease was held in Brussels on April 8 and 9, 1994. It was organized by the Interdisciplinary Group of Bone Physiopathology and Locomotor System Biomechanics of Brussels Free University (GIPOB). Fifteen speakers were invited to present their data regarding this subject, and there were approximately 45 participants. of cAMP (EP3). The distribution of prostanoid receptors in different tissues is variable; it conditions the intensity and the direction of the response, which can thus change with ligand concentration. PG receptors of bone cells have yet to be characterized.

The cultivation of sunflower (Helianthus annuus L.) can be conducted in various times and locations during the crop year. In state of Tocantins the culture can be explored in crop in cerrado region and in intercrop in sub-irrigated lowland. The objective of this study was to evaluate the effect of swing times in Gurupi-TO and Formoso of Araguaia-TO, with five cultivars sunflower. It was installed four times in Gurupi-TO and one in Formoso-TO. The experimental design was randomized blocks, with 25 treatments and three replications. The was five times: EP1(24/11/2008), EP2(01/12/2008), EP3(18 / 12/2008) and EP4(12/30/2008) in Gurupi-TO and Formoso (07/04/2009) in Formoso do Araguaia-TO, with five cultivars: H250, H251, H358, H360 and H884. There was significant interaction between times and cultivars for the traits: flowering, plant height, normal achene, weight of thousand achene, hectolitre weight and productivity of achenes. In Gurupi-TO, there was a negative influence for all the avaluated traits as the sowings were delayed, It accurred because of the incidence of Alternaria helianthi. Productivity close to 3000 kg ha-1 was obtained in Gurupi (EP1) and the intercrop in Formoso do Araguaia. The most productive cultivars were the H251 and H358, when cultivated in EP1 and EP5. &nbsp, O cultivo de girassol (Helianthus annuus L.) pode ser realizado em vários momentos e locais durante o ano agrícola. No estado do Tocantins, a cultura pode ser explorada em lavouras na região do cerrado e em consórcios em terras baixas sub-irrigadas. O objetivo deste estudo foi avaliar o efeito dos tempos de balanço em Gurupi-TO e Formoso de Araguaia-TO, com cinco cultivares de girassol. Foi instalado quatro vezes no Gurupi-TO e um no Formoso-TO. O delineamento experimental foi em blocos casualizados, com 25 tratamentos e três repetições. Foram cinco vezes: EP1 (24/11/2008), EP2 (12/12/2008), EP3 (18/12/2008) e EP4 (30/12/2008) em Gurupi-TO e Formoso (07/04) / 2009) no Formoso do Araguaia-TO, com cinco cultivares: H250, H251, H358, H360 e H884. Houve interação significativa entre épocas e cultivares para as características: floração, altura das plantas, aquênios normais, peso de mil aquênios, peso de hectolitros e produtividade de aquênios. Em Gurupi-TO, houve uma influência negativa para todas as características avaliadas, pois as semeaduras foram adiadas, devido à incidência de Alternaria helianthi. Produtividade próxima a 3000 kg ha-1 foi obtida em Gurupi (EP1) e o consórcio em Formoso do Araguaia. As cultivares mais produtivas foram as H251 e H358, quando cultivadas em EP1 e EP5.

We previously reported that prostaglandin (PG) E2 acts as a ligand for prostaglandin E receptor 3 (EP3) in conjunctival epithelial cells, that it downregulates the progression of experimental murine allergic conjunctivitis, and that in human conjunctival epithelial cells it modulates the expression of polyI:C-induced proinflammatory genes via prostaglandin E receptor 2 (EP2) and EP3, suggesting that PGE2 might have important roles in ocular surface inflammation such as allergic conjunctivitis. Here, we investigated whether PGE2 also downregulates polyI:C-induced cytokine production in human corneal epithelial cells.We used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction to examine the effects of PGE2 on polyI:C-induced cytokine expression by immortalized human corneal-limbal epithelial cells (HCLE). Using reverse transcription-polymerase chain reaction, we examined the messenger RNA (mRNA) expression of the PGE2 receptor, EP1-4.PGE2 significantly attenuated the expression of CC chemokine ligand (CCL)5 (P0.0005), CCL20 (P0.0005), C-X-C chemokine (CXCL)10 (P0.0005), CXCL11 (P0.05), and interleukin (IL)-6 (P0.005) in human corneal-limbal epithelial cells. Human corneal epithelial cells manifested the mRNA expression of EP2, EP3, and EP4, but not EP1. The EP2 agonist significantly suppressed the polyI:C-induced expression of CCL5 (P0.005), CXCL10 (P0.0005), and CXCL11 (P0.05) but not of CCL20 and IL-6. The EP3 agonist significantly suppressed the expression of CCL5 (P0.05), CCL20 (P0.005), CXCL10 (P0.0005), CXCL11 (P0.0005), and IL-6 (P0.005). The EP4 agonist failed to suppress cytokine production induced by polyI:C stimulation.Our results show that in human corneal epithelial cells, PGE2 attenuated the mRNA expression and production of CCL5, CXCL10, and CXCL11 via both EP2 and EP3, and that the mRNA expression and production of CCL20 and IL-6 was attenuated only by EP3.

Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E2 (PGE2) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE2, but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE2 metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity. Hum Mutat 33:11751181, 2012. (c) 2012 Wiley Periodicals, Inc.

Consumption is, and has long been, synonymous with destruction. Hence, destruction is the dubious legacy of consumption. However, throughout the history of many counterstream cultures consumption was a distinctly constructive concept. We propose the EP3 Model of Cultural Evolution to explain why mainstream cultures took the low road toward conceiving of consumption as synonymous with environmental destruction, while counterstream cultures took the road less traveled toward conceiving of consumption as synonymous with environmental conservation. We also discuss important lessons to be learned about the constructive consequences of consumption from cultures far off the beaten path.

The potential for G-protein-coupled receptors (GPCRs) to show constitutive activity is emerging as one of the fundamental properties of GPCRs signal transduction. Indeed, of the four subtypes of E-type prostanoid (EP) receptors, the EP3 and EP4 subtypes show constitutive activity in addition to their innate ligand-dependent activation of signaling pathways. The constitutive activity of the EP3 and EP4 receptor subtypes was discovered during the initial characterizations of these receptors and may be important for setting the basal level of cellular tone in the given signaling pathway. This chapter introduces some of the methods that can be used to study the constitutive activity of the EP receptors.

Intracerebroventricular (icv) injection of GR 63799X (GR, 20–300 ng), an agonist for prostaglandin E2 (PGE2) receptor subtype EP3, produced a dose-related increase in the body temperature (Tb) of rats. Pretreatment with an antisense (AS), but not a missense (MS), oligodeoxyribonucleotide (oligo) against the EP3 receptor attenuated GR (20 ng)-induced fever. Icv GR (20 ng) or PGE2 (200 ng) induced a hyperalgesia in the cold water tail-flick test, but not in the AS group. These results demonstrate that central EP3 receptors play an important role in fever and hyperalgesia caused by PGE2.

A related, theoretical paper for the same conference explains why a new approach, both broader and more rigorous than that traditionally followed in ATM, is needed for the safety assessment of new operational and technology changes, and presents the theoretical basis for what is an argument-driven "systems-engineering approach" This paper builds on that approach and describes how it is being applied to preliminary work on the massive changes that are planned for introduction into European ATM over the period up to 2020 and beyond, under the SESAR Programme. This preliminary work, closely related to European Commission initiated Episode 3 (EP3) project, is aimed at validating the approach as well as beginning to identify ways to maximize ATM contribution to aviation safety under the SESAR concept of operations. (8 pages)

The EP receptor, one of the five types of prostanoid receptors, has four subtypes, EP1, EP2, EP3, and EP4. Pharmacology: Early studies …

Two different series of very potent and selective EP(3) antagonists have been reported: a novel series of ortho-substituted cinnamic acids [Belley, M., Gallant, M., Roy, B., Houde, K., Lachance, N., Labelle, M., Trimble, L., Chauret, N., Li, C., Sawyer, N., Tremblay, N., Lamontagne, S., Carriere, M.-C., Denis, D., Greig, G. M., Slipetz, D., Metters, K. M., Gordon, R., Chan, C. C., Zamboni, R. J. Bioorg. Med. Chem. Lett.2005, 15, 527] and the acylsulfonamides of ortho-(arylmethyl)cinnamates. [(a) Juteau, H., Gareau, Y., Labelle, M., Sturino, C. F., Sawyer, N., Tremblay, N., Lamontagne, S., Carriere, M.-C., Denis, D., Metters, K. M. Bioorg. Med. Chem. 2001, 9, 1977; (b) Juteau, H., Gareau, Y., Labelle, M., Lamontagne, S., Tremblay, N., Carriere, M.-C., Denis, D., Sawyer, N., Metters, K. M. Bioorg. Med. Chem. Lett.2001, 11, 747] The structural differences between the two series, along with their biological activity in vivo, in vitro, and metabolism, are analyzed. Some of those compounds, including hybrids containing the best structural features of both series, possess K(i) as low as 0.6 nM on the EP(3) receptor.

The University of Waterloo, partnered with key industry players, Photonics Research Ontario and the Ontario government, has launched Ontario’s first diploma-level photonics program to re-skill scientists and engineers. The Education Program for Photonics Professionals (EP3) offers the basics of a university level Optics education, but in a manageable timeframe and format for the working professional.

The University of Waterloo, partnered with key industry players, Photonics Research Ontario and the Ontario government, has launched Ontario’s first diploma-level photonics program to re-skill scientists and engineers. The Education Program for Photonics Professionals (EP3) offers the basics of a university level Optics education, but in a manageable timeframe and format for the working professional.

This paper presents EP3, an extensible preprocessor written in Perl. Included are directives that extend the power of Perl to the language being processed. This paper focuses on the Verilog Hardware Description language and provides a set of extended directives for Verilog in addition to the Standard EP3 directives. The EP3 engine is explained and example Verilog code is presented in both its pre and postprocessed forms.

Potent and selective ligands for the human EP3 prostanoid receptor are described. Biaryl compounds bearing a tethered ortho substituted acidic moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinity of key compounds on all eight human prostanoid receptors is reported.

There are eight types and subtypes of receptors for prostanoids including PGD receptor (DP), PGE receptors of EP1, EP2, EP3 and EP4 subtypes, PGF receptor (FP)

The EP3-agonist sulprostone, but not prostaglandin E2 potentiates platelet aggregation in human blood

Background There are many papers on Electronic Prescribing and papers on Robotic Dispensing However, these terms are sometimes used generically, and the range of technical differences in the systems make it difficult for a reader to assess functionality in the papers. Purpose So that hospital pharmacists can identify which technological features deliver the most suitable benefits for their own pharmacy, a classification is proposed to grade the functionality in these systems. Materials and methods A structured review of the literature found many references to EP, and also to RD, but only a few where pharmacies had linked both together and expressed benefits (1) (2) (3) (4). A comparison of EP systems paper by Cantrell (5) highlighted the problems of not having a defined taxonomy of functionality. Goundry-Smith described theoretical functionality (6). Results The following taxonomy is suggested EP level 1: Basic messaging system from ward to pharmacy EP level 2 level 1 plus electronic medicines administration record EP Level 3: Level 2 plus safety alerts EP level 4: EP level 3 plus direct links to hospital patient database; EP level 5: EP level 4 plus direct linking to pharmacy stock EP level 6: EP level 5 plus linking to other relevant departments (e.g. pathology) for monitoring RD level 1 Basic ‘mechanical shelf’ (simplest machine design) or unit dose. RD level 2: RD level 1 plus means of automatic refilling (eg, a hopper) RD level 3: RD level 2 plus automatic labellers Rd level 4 RD level 3 plus direct link to EP system for automatic picking of medicines Conclusions Papers describing functionality could describe the EP-RD systems as EP3 RD 0, or EP 5 RD 4 etc., to indicate to the reader what systems are in place at the point of publishing. This would aid identification of what features deliver which benefits. References Reifsteck M, Swanson T, Dallas M. Driving out errors through tight integration between software and automation. Journal of Healthcare Information Management 2006;20:p35-39 Gonidec P, Diallo ML, Djoussa-Kambou S, Guizard M. Performance of an automated dispensing system combined with a computerised prescription order entry. Annales Pharmaceutiques Francaises 2009;67:p84-90 Beard RJ Smith P. ‘Electronic prescribing and Robotic Dispensing: A case study.’ 2013 SpringerPlus 2, 295 www.springerplus.com/content/2/1/295 Beard RJ. ‘How can Electronic Prescribing systems contribute to Clinical Governance’ 2009; M. Prof. Thesis University of Sunderland, England Cantrill JA, Abdel-Qader DH, Tully MP. Satisfaction predictors and attitudes towards electronic prescribing systems in three UK hospitals 2010 Pharmacy World & Science, 32; 581-593 http://www.springerlink.com/content/k0p6xn36124w2j30/ Goundry-Smith S. Principles of Electronic Prescribing: 2008 Springer Press ISBN 978-1-84800-234-0 No conflict of interest.

The coalescence of three levels has particular attractive features. Even though it may be difficult to realise such event in the laboratory (three additional real parameters must be adjusted), to take up the challenge seems worthwhile. In the same way as the chiral behaviour of a usual EP can give a direction on a line, the state vectors in the vicinity of an EP3 provide an orientation in the plane. The distinction between left and right handedness depends on the distribution of the widths of the three levels in the vicinity of the point of coalescence., Comment: Manuscript has been discussed in June 2007 with the experimental group under Professor Achim Richter at the TU Darmstadt. It has been presented at the 6th International Workshop on Pseudo Hermitian Hamiltonians, London, 16-18 July 2007. An expanded version is being prepared for publication. 3 Figures, 11 pages

Forty-eight-hr and 96-hr simple hypothermic preservations of the lung were studied on dogs using 4 kinds of solutions resembling extracellular electrolyte compositions (Ep1-Ep4). The pH of each solution was changed from 6.377 to 7.463 by HPO4(2-)/H2PO4- ratio. Twenty dogs were prepared as donors (12 for 48-hr preservation with Ep1, Ep2 and Ep3, and 8 for 96-hr preservation with Ep3 and Ep4, respectively). The heart-lung block was removed from the donor, and flushed with 500 ml of preservation solution via the pulmonary artery, then immersed in the same cold (4 degrees C) solution, after which it was stored in a cold (4 degrees C) room. After preservation, the left lung was separated from the heart-lung block and was transplanted into the recipient orthotopically. The function of the transplanted lung was evaluated with serial x-ray findings, contralateral pulmonary artery ligation test, and histologic findings. In the case of 48-hr preservation, all of the four recipients with Ep3 (pH: 7.225) showed good aeration of the grafted lungs on the chest x-ray in the early postoperative period. As for the 96-hr preservation cases, one with Ep3 and three with Ep4 (pH: 7.463) presented good x-ray findings. Of these successful cases, seven dogs (5 of 48-hr preservation cases, six dogs tolerated this procedure. On histopathological examination of the successful cases, the 48-hr preservation cases showed almost normal pulmonary structure, while the 96-hr preservation cases showed slight degenerative changes in the alveolar walls. From the present study, it becomes apparent that clinical application of 48-hr preservation may be possible by using a phosphate buffered extracellular solution.