A brief overview of international trends in Open Access

Definition and stakeholders Open Access can be defined as access to research-based publications that are peer reviewed, permanently and promptly accessible without payment, and re-usable on the sole condition of crediting the author(s). Achieving Open Access (OA) involves all the stakeholders of the research life cycle to begin with the authors who are the initial copyright holders of the publications and then the publishers who coordinate the peer review. Libraries build and maintain the national and institutional infrastructures that facilitate prompt and permanent access. Research funders define conditions for granting financing; mandating access to the resulting publications may be among these conditions. Service providers encourage the reuse of scientific and scholarly findings. Ultimately, legislators may set rules for access to knowledge in our knowledge-permeated democracies

HOW COULD AN OPEN ACCESS SCHOLARLY JOURNAL SYSTEM LOOK? A SCENARIO ANALYSIS

Ralf Schimmer’s blog “Making the moves for large scale transition toward Open Access” makes the case to achieve such a transition by means of offsetting deals. The urgency for such a transition is emphasized by the recently announced ambition of the EU to have “Open Access to scientific publications as the best option by default by 2020”i. This should be done “in a cost-effective way, without embargoes, or with as short as possible embargoes”. In this blog, we explore and analyse the scenario whereby this transition will be brought about by successful offsetting deals, meaning that ultimately all articles in the hybrid journals will become Open Access by changing the business models of these journals into APC-based Open Access journals. Success means also that the offsetting deals will be transformed in pay-as-you-publish pre-finance-agreements. What effect would such a success have on the scholarly journal system. How would it look like in terms of numbers and type of journals? Which preconditions and drivers would be needed to achieve such a success? And finally, we speculate about possible next steps and their cost-effectiveness

Sleeping with the enemy: experiments in Wageningen with a model for cohabitation between library and publisher

This is what libraries kept busy for the past two decades: keeping pace with rapid evolving technology that highly impacted their core functions. Mid nineties a number of libraries seemed to be drowned by the technology flood and some prophets predicted a museum type future for them. But they, the libraries that is, seemed to have adopted the motto of the Dutch province Zeeland which reads “Luctor et emergo”. That is: struggle and emerge. Happily, the storm flattened out some years ago. Today most libraries are technologically savvy; the situation is under control

HOW COULD AN OPEN ACCESS SCHOLARLY JOURNAL SYSTEM LOOK? A SCENARIO ANALYSIS

Ralf Schimmer’s blog “Making the moves for large scale transition toward Open Access” makes the case to achieve such a transition by means of offsetting deals. The urgency for such a transition is emphasized by the recently announced ambition of the EU to have “Open Access to scientific publications as the best option by default by 2020”i. This should be done “in a cost-effective way, without embargoes, or with as short as possible embargoes”. In this blog, we explore and analyse the scenario whereby this transition will be brought about by successful offsetting deals, meaning that ultimately all articles in the hybrid journals will become Open Access by changing the business models of these journals into APC-based Open Access journals. Success means also that the offsetting deals will be transformed in pay-as-you-publish pre-finance-agreements. What effect would such a success have on the scholarly journal system. How would it look like in terms of numbers and type of journals? Which preconditions and drivers would be needed to achieve such a success? And finally, we speculate about possible next steps and their cost-effectiveness

Internalization of the radioiodinated somatostatin analog [125I-Tyr3]octreotide by mouse and human pituitary tumor cells: increase by unlabeled octreotide

Recently, we developed a technique that allows the in vivo visualization in man of somatostatin receptor-positive neuroendocrine tumors after i.v. injection of [125I-Tyr3]octreotide or [111In-DTPA-D-Phe1]octreotide. Radiotherapy of such tumors using somatostatin analogs coupled to alpha- or beta-emitting radionuclides has been proposed as an application for radiolabeled somatostatin analogs. To develop this concept further, it is of importance to know whether the above-mentioned radiolabeled somatostatin analogs are internalized by the tumor cells, and whether it might be possible to manipulate the degree of internalization. In the present study we investigated the internalization of a stable somatostatin analog, [125I-Tyr3]octreotide, by mouse AtT20/D16V pituitary tumor cells and primary cultures of human GH-secreting pituitary tumor cells. Treatment of the cells with low pH was used to distinguish between membrane-bound (acid-releasable) and internalize (acid-resistant) radioligand. [125I-Tyr3]octreotide showed a time-dependent increasing accumulation in AtT20 cells; after 4 h of incubation, values up to 6-8% of the dose of radioligand added were obtained. Binding and internalization of [125I-Tyr3]octreotide were temperature dependent and inhibited by pertussis toxin. Inhibitors of lysosomal degradation did not increase the amount of internalized radioligand. After 4 h of incubation, 88% of the radioactivity present in the cells was still peptide bound, suggesting a low intracellular breakdown of this radioligand. Six of seven human GH-secreting adenoma cell cultures also internalized [125I-Tyr3]octreotide (variation between 0.24-4.98% of the dose radioligand added). Displacement of binding and internalization of [125I-Tyr3]octreotide by unlabeled octreotide showed a bell-shaped curve in AtT20 cells. At low concentrations (0.1 and 1 nM), binding and internalization were increased, whereas at higher concentrations, saturation occurred. In contrast to this, binding of [125I-Tyr3]octreotide to a broken cell preparation of AtT20 cells was displaced in a dose-dependent manner by unlabeled octreotide, with an IC50 of 0.1 nM. Similar observations were made in the human GH-secreting adenoma cell cultures. In conclusion, a high amount of [125I-Tyr3]octreotide is internalized in a specific-, time-, temperature-, and pertussis toxin-sensitive GTP-binding protein-dependent manner by mouse AtT20 and human GH-secreting pituitary tumor cells. In the presence of a low concentration of unlabeled octreotide, a rapid increase in the amount of [125I-Tyr3]octreotide internalized by AtT20 cells and by the majority of the human GH-secreting adenoma cell cultures was found.(ABSTRACT TRUNCATED AT 400 WORDS

Interferon-alpha-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas

Interferon-alpha (IFN alpha) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFN alpha on hormone production by 15 GH-secreting pituitary adenomas, 4 clinically nonfunctioning or gonadotroph pituitary adenomas, and 4 prolactinomas in vitro. In the GH-secreting pituitary adenoma cultures, a short term (72-h) incubation with IFN alpha (50-100 U/mL) significantly inhibited GH secretion in 3 of 7 cases and PRL secretion in 6 of 7 cultures. During prolonged incubation (14 days) with IFN alpha, GH and/or PRL secretion was significantly inhibited in 7 of 8 cultures (GH, 17-78% inhibition; PRL, 39-88% inhibition). In the clinically nonfunctioning or gonadotroph cultures

Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

The effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7 prolactinomas, and 2 insulinomas were investigated. In the pituitary adenoma cultures, a comparison was made with the effects of the dopamine (DA) agonists bromocriptine and/or quinagolide. In 5 NFAs, 2 prolactinomas and 1 insulinoma somatostatin receptor (subtype) expression was determined by ligand binding studies and by in situ hybridization to detect sst1, sst2, and sst3 messenger RNAs (mRNAs). Four NFA cultures did not secrete detectable amounts of alpha-subunit, FSH, and/or LH. In the other cultures, hormone and/or subunit release was inhibited by DA-agonists (10 nM) in 9 of 11, by SS (10 nM) in 7 of 11, and by octapeptide SS-analogs (10 nM) in 3 of 10 cultures. In three NFA cultures, hormone release was sensitive to SS but not to SS-analogs. In all cultures, except for one, DA-agonists were the most effective in inhibiting hormone release. In the prolactinoma cultures, PRL release was inhibited by DA-agonists (10 nM) in 7 of 7, by SS in 4 of 4, and by octapeptide SS-analogs in 3 of 7 cultures. A dissociation between the effects of SS and SS-analogs was found in 3 cases. In the cultures sensitive to both bromocriptine and SS-28, bromocriptine was the most potent compound in 2 out of 4 cultures. In the 2 other cultures, both compounds were equally effective. In 2 insulinoma cultures, insulin release was inhibited by SS, and by octapeptide SS-analogs in only one. The presence or absence of an inhibitory effect by octreotide was in all cases in parallel with the presence or absence of the inhibitory effect by BIM-23014 and RC-160. Autoradiographic studies using [125I-Tyr0]SS28 showed specific binding in 4 of 5 NFAs, 1 of 2 prolactinomas, and 1 of 1 insulinoma. Specific [125I-Tyr3]octreotide binding was found in 2 of 5 NFAs, in 1 of 2 prolactinomas, and in the insulinoma. Two NFAs showed binding of SS28, but not of the sst2.5 specific ligand octreotide. The tumors showed variable sst1 and/or sst3 mRNA expression, whereas no sst2 expression was found. In conclusion, a dissociation between the inhibitory effects of SS on the one hand and of the octapeptide SS-analogs octreotide, BIM-23014 and RC-160 on the other hand, is observed in a small subgroup of NFAs, prolactinomas, and insulinomas, suggesting that novel sst subtype specific SS-analogs might be of benefit in the treatment of selected patients with somatostatin receptor positive secreting tumors not resp

6002 Study on Community Development Utilizing Agriculture and Culture around Tomatu Shrine in Amagasaki City : Focus on Annual Event and Community

textabstractAdrenocortical carcinoma (ACC) is an aggressive tumor with very poor prognosis. Novel medical treatment opportunities are required. We investigated the effects of interferon-β (IFN-β), alone or in combination with mitotane, on cell growth and cortisol secretion in primary cultures of 13 human ACCs, three adrenal hyperplasias, three adrenal adenomas, and in two ACC cell lines. Moreover, the interrelationship between the effects of IGF2 and IFN-β was evaluated. Mitotane inhibited cell total DNA content/well (representing cell number) in 7/11 (IC50: 38±9.2 μM) and cortisol secretion in 5/5 ACC cultures (IC50: 4.5±0.1 μM). IFN-β reduced cell number in 10/11 (IC50: 83±18 IU/ml) and cortisol secretion in 5/5 ACC cultures (IC50: 7.3±1.5 IU/ml). The effect of IFN-β on cell number included the induction of apoptosis. IFN-β strongly inhibited mRNA expression of STAR, CYP11A1, CYP17A1, and CYP11B1. Mitotane and IFN-β induced an additive inhibitory effect on cell number and cortisol secretion. IGF2 (10 nM) inhibited apoptosis and increased cell number and cortisol secretion. These effects were counteracted by IFN-β treatment. Finally, IFN-β inhibited IGF2 secretion and mRNA expression. In conclusion, IFN-β is a potent inhibitor of ACC cell growth in human primary ACC cultures, partially mediated by an inhibition of the effects of IGF2, as well as its production. The increased sensitivity of ACC cells to mitotane induced by treatment with IFN-β may open the opportunity for combined treatment regimens with lower mitotane doses. The inhibition of the expression of steroidogenic enzymes by IFN-β is a novel mechanism that may explain its inhibitory effect on cortisol production. Copyrigh

The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5.

Objective: Currently, there is no effective medical treatment for patients with pituitary-dependent Cushing’s disease. A novel somatostatin (SS) analogue, named SOM230, with high binding affinity to SS receptor subtypes sst1, sst2, sst3 and sst5 was recently introduced. We compared the in vitro effects of the sst2-preferring SS analogue octreotide (OCT) and the multi-ligand SOM230 on ACTH release by human and mouse corticotroph tumour cells. Methods: By quantitative RT-PCR the sst subtype expression level was determined in human corticotroph adenomas. In vitro, the inhibitory effect of OCT and SOM230 on ACTH release by dispersed human corticotroph adenoma cells and mouse AtT20 corticotroph adenoma cells was determined. In addition, the influence of dexamethasone on the responsiveness to OCT and SOM230 was studied. Results: Corticotroph adenomas expressed predominantly sst5 mRNA (six out of six adenomas), whereas sst2 mRNA expression was detected at significantly lower levels. In a 72 h incubation with 10 nmol/l SOM230, ACTH release was inhibited in three out of five cultures (range –30 to –40%). Ten nmol/l OCT slightly inhibited ACTH release in only one of five cultures (– 28%). In AtT20 cells, expressing sst2, sst3 and sst5, SOM230 inhibited ACTH secretion with high potency (IC50 0.2 nmol/l). Dexamethasone (10 nmol/l) pre-treatment did not influence the sensitivity of the cells to the inhibitory effect of SOM230, suggesting that sst5 is relatively resistant to negative control by glucocorticoids. Conclusions: The selective expression of sst5 receptors in corticotroph adenomas and the preferential inhibition of ACTH release by human corticotroph adenoma cells by SOM230 in vitro, suggest that SOM230 may have potential in the treatment of patients with pituitary-dependent Cushing’s disease