Auswahl der wissenschaftlichen Literatur zum Thema „Art. 9 (3) Rome I Regulation“

ABSTRACT The purpose of this study is to investigate the protective effect of gambogenic acid (GA) in acetaminophen (APAP)-induced hepatotoxicity in rat models. GA (10 mg/kg) was administered intraperitoneal (i.p.) to rats for 7 consecutive days followed by APAP (500 mg/kg) single dose (i.p.) on the final day after GA administration. The levels of MDA, GSH, SOD, CAT, GPx, GST, ALP, AST, ALT, proinflammatory cytokines (TNF-α, IL-1β, IL-6), apoptosis markers (caspase-3 and -9, Bax, Bcl-2), 4-hydroxynonenal (4-HNE), and prostaglandin E2 (PGE2) were evaluated. Results exhibited protective effects of GA by inhibiting inflammation, preventing oxidative stress and apoptosis in APAP-induced liver. Histopathological changes caused by APAP were attenuated, protein expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were upregulated, and nuclear factor–kappa β (NF-kβ) was downregulated by GA. In summary, GA significantly exerted anti-inflammatory and antiapoptotic effects against APAP-induced hepatotoxicity potentially through regulation of PI3K/Akt and NF-kβ signaling pathways.

To what extent are Greek saving laws, resulting in payment cuts in the public sector (that is employment conditions), capable of overriding the applicable (German) law? A dispute arising from an employment relationship between the Greek Republic and an employee habitually carrying out work in Germany, gave rise to preliminary questions having regard to the temporal scope of EU Regulation No. 593/2008 (the ‘Rome I Regulation’)1 and, closely related thereto, the functional reach of Article 9(3) of that Regulation in respect of ‘foreign’ mandatory laws, in light of the principle of sincere cooperation enshrined in Article 4(3) TEU. An analysis of the Advocate General’s Opinion and the Court of Justice of the European Union’s (CJEU) ruling is followed by critical commentary and suggestions for future EU legislative amendments to the Rome I regime.

The subject of this article is to analyze the meaning of the prohibition of discrimination on grounds of nationality in the light of the provisions of primary and secondary European Union law and the case law of the Court of Justice of the European Union, which is inherent to the functioning of the internal market and EU citizenship. The prohibition of discrimination on grounds of nationality is undoubtedly one of the main goals of the European Union[1] in the social and economic context, which was reflected in the localization of the matter in question in the primary law of the European Union[2], in secondary law and in the jurisprudence of the Court of Justice of the European Union (CJEU). The Treaty on European Union (TEU)[3] and the Treaty on the Functioning of the European Union (TFEU)[4] indicate equality as one of the EU values (Article 2 TEU), require it to be promoted and combat all discrimination (Articles 8 and 10 TFEU) and prohibit discrimination due to the criteria indicated therein (Articles 18 and 19 TFEU). In secondary law, this principle was expressed primarily in the Regulation of the European Parliament and of the Council No. 492/2011 on the free movement of workers within the Union and in art. 24 of Directive 2004/38/EC 2004 on the right of citizens of the Union and their relatives to move freely[5]. A special role in this area is played by the case law of the Court of Justice of the European Union (CJEU), which stated that all authorities of the Member States are obliged to refuse to apply a provision of national law that is contrary to the prohibition of discrimination on the grounds of citizenship (Article 18 TFEU)[6]. Moreover, national measures may be examined in the light of art. 18 TFEU, but only to the extent that they apply to situations not covered by specific non-discrimination provisions included in the Treaty[7]. The author puts forward the thesis that the analysis of CJEU jurisprudence reveals a visible dissonance between the application of national regulations of the Member States and the provisions of EU law in this matter, which significantly hinders the implementation of the principle of non-discrimination in practice. Discrepancies mainly occur in domestic legal acts due to the improper drafting of national legal provisions and / or their misinterpretation by national judicial or administrative authorities. It should be emphasized that the Member States are obliged to comply with EU law, which is not tantamount only to the obligation of state authorities to respect directly applicable acts, or to implement required regulations into internal law, but also the obligation to interpret and apply internal law in a manner that does not violate the requirement resulting from EU law[8]. Judicial and administrative authorities of the Member States should therefore interpret national law as far as possible, in line with EU law, because the limits of the pro-EU interpretation will be determined by the powers conferred by domestic law[9]. The study uses the legal-comparative method, consisting in a comparative analysis of the legal systems of the Member States and the European Union in the field of non-discrimination on the basis of nationality, rights and restrictions on the freedom of movement of authorized entities. Comparative verification of EU acts with the internal standards of individual EU Member States allows to reveal the degree of advancement of the implementation process of EU law provisions under the free movement of EU citizens and their family members in the discussed area in the legal systems of European Union Member States. The purpose of this analysis is to, inter alia, diagnose areas in which these countries have not implemented or improperly implemented EU regulations, or have misinterpreted them. The second method used is the method of analyzing the jurisprudence of the Court of Justice of the European Union - the rulings of the CJEU constitute a significant part of the study. The case law in question covers the period from the establishment of the Treaties of Rome to the present day. The use of the latter obligated the author to apply the comparative method of judgments based on same or similar legal bases in similar circumstances from different stages of the evolution of the free movement of citizens of the European Union and their family members under the prohibition of discrimination on the basis of nationality. [1] Cf. Olivier De Schutter, Links between migration and discrimination. A legal analysis of the situation in EU Member States (Brussels: European Commission, 2016), 102 and next; See also Brita Sundberg-Weitman, Discrimination on Grounds of Nationality. Free Movement of Workers and Freedom of Establishment under the EEC Treaty (Amsterdam, New York, Oxford: North-Holland Publishing Co., 1977). [2] Erica Szyszczak, “Antidiscrimination Law in the European Union,” Fordham International Law Journal, no. 32 (2008): 635. [3] The Treaty on European Union (consolidated version) OJ of the EU 2012, No. C 326/01. [4] The Treaty on the Functioning of the European Union (consolidated version) OJ of the EU 2012, No. C 326/01. [5] Directive of the European Parliament and of the Council No. 2004/38 on the right of citizens of the Union and their family members to move and reside freely within the territory of the Member States amending Regulation (EEC) No. 1612/68 and repealing Directives 64/221/EEC, 68/360/EEC, 72/194/EEC, 73/148/EEC, 75/34/EEC, 75/35/EEC, 90/364/EEC, 90/365/EEC and 93/96/EEC (O.J.E.C. L 158, 30 April 2004). [6] CJEU Judgement of 7 May 1998, Clean Car Autoservice GmbH p. Landeshauptmann von Wien, Case C-350/96, ECLI:EU:C:1998:205. [7] CJEU Judgement of 18 June 2019, Republic of Austria v Federal Republic of Germany, Case C-591/17, ECLI:EU:C:2019:504, pt 41. [8] Marek Górski, “Wpływ orzecznictwa Europejskiego Trybunału Sprawiedliwości na interpretację i stosowanie przepisów o ochronie środowiska,” in Wspólnotowe prawo ochrony środowiska i jego implementacja w Polsce trzy lata po akcesji, ed. Jerzy Jendrośka and Magdalena Bar (Wrocław: Centrum Prawa Ekologicznego Press, 2008), 31. [9] Monika Niedźwiedź, “Stosowanie prawa wspólnotowego przez organy administracyjne,” Casus, no. 32 (October 2004): 6.

Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.

Caveolae are specialized cell membrane invaginations known to regulate several cancer cell functions and oncogenic signaling pathways. Among other caveolar proteins, they are characterized by the presence of proteins of the cavin family. In this study, we assessed the impact of cavin-1, cavin-2, and cavin-3 on cell migration in a human HT-1080 fibrosarcoma model. We found that all cavin-1, -2 and -3 transcripts were expressed and that treatment with phorbol 12-myristate 13-acetate (PMA), which is known to prime cell migration and proliferation, specifically upregulated cavin-3 gene and protein expression. PMA also triggered matrix metalloproteinase (MMP)-9 secretion, but reduced the global cell migration index. Overexpression of recombinant forms of the three cavins demonstrated that only cavin-3 was able to reduce basal cell migration, and this anti-migratory effect was potentiated by PMA. Interestingly, cavin-3 overexpression inhibited PMA-induced MMP-9, while cavin-3 gene silencing led to an increase in MMP-9 gene expression and secretion. Furthermore, recombinant cavin-3 significantly prevented PMA-mediated dephosphorylation of AKT, a crucial regulator in MMP-9 transcription. In conclusion, our results demonstrate that cellular cavin-3 expression may repress MMP-9 transcriptional regulation in part through AKT. We suggest that the balance in cavin-3-to-MMP-9 expression regulates the extent of extracellular matrix degradation, confirming the tumor-suppressive role of cavin-3 in controlling the invasive potential of human fibrosarcoma cells.

Scaffolding molecules exert a critical role in orchestrating cellular response through the spatiotemporal assembly of effector proteins as signalosomes. By increasing the efficiency and selectivity of intracellular signaling, these molecules can exert (anti/pro)oncogenic activities. As an archetype of scaffolding proteins with tumor suppressor property, the present review focuses on MAGI1, 2, and 3 (membrane-associated guanylate kinase inverted), a subgroup of the MAGUK protein family, that mediate networks involving receptors, junctional complexes, signaling molecules, and the cytoskeleton. MAGI1, 2, and 3 are comprised of 6 PDZ domains, 2 WW domains, and 1 GUK domain. These 9 protein binding modules allow selective interactions with a wide range of effectors, including the PTEN tumor suppressor, the β-catenin and YAP1 proto-oncogenes, and the regulation of the PI3K/AKT, the Wnt, and the Hippo signaling pathways. The frequent downmodulation of MAGIs in various human malignancies makes these scaffolding molecules and their ligands putative therapeutic targets. Interestingly, MAGI1 and MAGI2 genetic loci generate a series of long non-coding RNAs that act as a tumor promoter or suppressor in a tissue-dependent manner, by selectively sponging some miRNAs or by regulating epigenetic processes. Here, we discuss the different paths followed by the three MAGIs to control carcinogenesis.

Background/Aims: The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. Methods: We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. Results: The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. Conclusions: The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility.

Epidermal growth factor (EGF) is present in the maternal-fetal environment and has an important role in placental development. Matrix metalloproteinase-9 (MMP-9) expression/activation is a pre-requisite in extravillous trophoblast invasion. Whereas EGF up-regulates MMP-9 activity in a variety of cell types, there is no direct evidence for the stimulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion by EGF in extravillous trophoblasts. In addition, the signalling pathways involved in this regulation are not clear. In the present study, we have examined the possible involvement of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in the regulation of the MMP-9/TIMP-1 system by EGFin vitro. We used a well-established invasive extravillous trophoblast cell line (HTR8/Svneo) and measured gene and protein expression by semi-quantitative RT-PCR and western analysis respectively. MMP activity was determined by zymography. We showed for the first time that EGF activated both PI3K/Akt and MAPK/extracellular-signal regulated kinase (ERK) signalling in HTR8/SVneo, and increased both MMP-9 and TIMP-1 mRNAs and protein concentrations. Interfering with either signalling pathway via PI3K inhibitor LY294002 or MEK inhibitor U0126 in EGF-stimulated HTR8/SVneo cells blocked the induction of MMP-9 and TIMP-1. LY294002 inhibited Akt phosphorylation, but had no effect on ERK phosphorylation; U0126 suppressed ERK phosphorylation without interfering with the phosphorylation of Akt. In addition, expression of constitutively active Akt (Myr-Akt1, Myr-Akt2, Myr-Akt3) was not sufficient to induce proMMP-9 and TIMP-1 secretion. Our results suggest that the activation of both PI3K and MAPK pathways in extravillous trophoblasts is necessary for the up-regulation of MMP-9 and TIMP-1 expression by EGF.

Melatonin, a nighttime-secreted antioxidant hormone produced by the pineal gland, and AKT, a serine/threonine-specific protein kinase, have been identified as regulators for several cellular processes essential for reproduction. The current study aimed to investigate the potential interplay between melatonin and AKT in bovine oocytes in the context of embryo development. Results showed that the inclusion of SH6, a specific AKT inhibitor, during in vitro maturation (IVM) significantly reduced oocyte maturation, cumulus cell expansion, cleavage, and blastocyst development that were rescued upon addition of melatonin. Oocytes treated with SH6 in the presence of melatonin showed lower levels of reactive oxygen species (ROS) and blastocysts developed exhibited low apoptosis while the mitochondrial profile was significantly improved compared to the SH6-treated group. The RT-qPCR results showed up-regulation of the mRNA of maturation-, mitochondrial-, and cumulus expansion-related genes including GDF-9, BMP-15, MARF1, ATPase, ATP5F1E, POLG2, HAS2, TNFAIP6, and PTGS2 and down-regulation of Bcl-2 associated X apoptosis regulator (BAX), caspase 3, and p21 involved in apoptosis and cell cycle arrest in melatonin-SH6 co-treated group compared to SH6 sole treatment. The immunofluorescence showed high levels of caspase 3 and caspase 9, and low AKT phosphorylation in the SH6-treated group compared to the control and melatonin-SH6 co-treatment. Taken together, our results showed the importance of both melatonin and AKT for overall embryonic developmental processes and, for the first time, we report that melatonin could neutralize the deleterious consequences of AKT inhibition, suggesting a potential role in regulation of AKT signaling in bovine oocytes.

Die Arbeit setzt sich mit dem neuen europäischen Anknüpfungskonzept für ausländisches Eingriffsrecht in der Rom I-VO auseinander. Im Fokus der Untersuchung steht die politisch motivierte und restriktiv ausgefallene Regelung des Art. 9 Abs. 3 Rom I-VO. Zudem widmet sich ein Teil der Untersuchung allgemein der hinter dem Eingriffsrecht – insbesondere dem Konzept des ausländischen Eingriffsrechts im IPR – stehenden Dogmatik, die aus einer dogmatisch-historischen Perspektive beleuchtet wird. Schwerpunktmäßig gilt es der Frage nachzugehen, welche Überlegungen hinter der neuen Kollisionsnorm stehen und ob die Sonderanknüpfung des Art. 9 Abs. 3 Rom I-VO einen dogmatisch geeigneten, mit der Zielsetzung der Rom I-VO vereinbaren rechtlichen Rahmen für die einheitliche kollisionsrechtliche Berufung der berücksichtigungswürdigen ausländischen Eingriffsnormen in den Mitgliedstaaten schafft.
The thesis examines the European concept of the newly defined connecting factor for foreign overriding mandatory rules in the Rome I Regulation. The central attention of the study is the analysis of the politically motivated and restrictive regulation of Art. 9 (3) of the Rome I Regulation. In addition, the first part of the study is dedicated to the examination of the general approach behind the application of foreign overriding mandatory rules in private international law from a dogmatic-historical perspective. The main focus of the thesis, however, is on the research of the considerations behind the new conflict of laws rule. The author specifically questions whether the new connecting factor defined in the Art. 9 (3) Rome I Regulation provides a worthy and sufficient legal framework for the application of foreign overriding mandatory rules.

This chapter comments on Article of the Rome Statute of the International Criminal Court. Article 91 deals with the content of a request to a State for arrest or surrender of a person wanted by the Court. It consists of four paragraphs, of which the first addresses the contents of the request and any supporting documentation. The two subsequent paragraph distinguish between a request concerning a person for whom a warrant of arrest has been issued (paragraph 2) and one for a person who has already been convicted (paragraph 3). Paragraph 4 provides for consultations between the Court and the State Party.

This chapter comments on Article 99 of the Rome Statute of the International Criminal Court. Article 99 completes articles 93 and 96 by providing for the execution of requests for assistance subject to those provisions. Paragraph 1 confirms that this will take place in accordance with applicable national law. Paragraph 2 states that when a request is urgent, the response should be sent urgently. Paragraph 3 concerns the language and form of the response. Paragraph 4 enables the Prosecutor to execute a request directly on the territory of a State Party. Paragraph confirms the application of special rules concerning national security in such situations.

This chapter comments on Article 122 of the Rome Statute of the International Criminal Court. Article 122 provides full and exhaustive list of provisions of the Statute ‘which are of an exclusively institutional nature’. These consist of the service of judges (art. 35), criteria for the section of judges (art. 36(8)), terms of judges (art. 36(9)), judicial vacancies (art. 37), the Presidency (art. 38), organization of Chambers, with the exception of the requirement that Pre-Trial and Trial Chambers be composed predominantly of judges with criminal trial experience (art. 39(1), first two sentences), composition of Chambers (art. 39(2), (4)), election of the Prosecutor and Deputy Prosecutors (art. 42(4)), independence and recusal of the Prosecutor and Deputy Prosecutors (art. 42(5)-(8)), advisers to the Prosecutor (art. 42(9)), appointment and qualifications of the Registrar (art. 43(2), (3)), Staff (art. 44), removal from office (art. 46), disciplinary measures (art. 47), and salaries, allowances, and expenses (art. 49).

This chapter examines the entitlement of a claimant to recover damages in respect of a breach of contract committed by the defendant, and is organized as follows. Section 2 discusses the different measures of damages that can be awarded, while Section 3 analyses the performance interest. Section 4 examines the circumstances in which a claimant can seek damages based on his ‘reliance’ losses rather than his performance interest, while Section 5 discusses the circumstances in which damages may be awarded to protect the claimant’s ‘restitution’ interest. Section 6 examines the entitlement of a claimant to recover damages in respect of non-pecuniary losses, particularly ‘mental distress’. Section 7 considers the general rule that damages are assessed as at the date of breach and the exceptions to that rule, while Section 8 considers the various doctrines which the courts use in order to keep liability within acceptable bounds. These include remoteness, mitigation, and contributory negligence. Section 9 examines the circumstances in which a defendant can be ordered to account to a claimant for the profits that he has made from his breach of contract. Section 10 looks at the possibility that exemplary damages might play a role in breach of contract cases. The chapter concludes, in Sections 11 and 12, with a discussion of agreed damages clauses (and related clauses) and their legal regulation.

This chapter examines the entitlement of a claimant to recover damages in respect of a breach of contract committed by the defendant, and is organized as follows. Section 2 discusses the different measures of damages that can be awarded, while Section 3 analyses the performance interest. Section 4 examines the circumstances in which a claimant can seek damages based on his ‘reliance’ losses rather than his performance interest, while Section 5 discusses the circumstances in which damages may be awarded to protect the claimant’s ‘restitution’ interest. Section 6 examines the entitlement of a claimant to recover damages in respect of non-pecuniary losses, particularly ‘mental distress’. Section 7 considers the general rule that damages are assessed as at the date of breach and the exceptions to that rule, while Section 8 considers the various doctrines which the courts use in order to keep liability within acceptable bounds. These include remoteness, mitigation, and contributory negligence. Section 9 examines the circumstances in which a claimant can recover what is known as ‘negotiating damages’ or the defendant can be ordered to account to a claimant for the profits that he has made from his breach of contract. Section 10 looks at the possibility that exemplary damages might play a role in breach of contract cases. The chapter concludes, in Sections 11 and 12, with a discussion of agreed damages clauses (and related clauses) and their legal regulation.

In Chap. 9 we introduced calcium ions and alluded to their crucial role in regulating the day-to-day life of neurons. The dynamics of the free intracellular calcium is controlled by a number of physical and chemical processes, foremost among them diffusion and binding to a host of different proteins, which serve as calcium buffers and as calcium sensors or triggers. Whereas buffers simply bind Ca2+ above some critical concentration, releasing it back into the cytoplasm when [Ca2+]i has been reduced below this level, certain proteins— such as calmodulin—change their conformation when they bind with Ca2+ ions, thereby activating or modulating enzymes, ionic channels, or other proteins. The calcium concentration inside the cell not only determines the degree of activation of calcium-dependent potassium currents but—much more importantly—is relevant for determining the changes in structure expressed in synaptic plasticity. As discussed in Chap. 13, it is these changes that are thought to underlie learning. Given the relevance of second messenger molecules, such as Ca2+, IP3, cyclic AMP and others, for the processes underlying growth, sensory adaptation, and the establishment and maintenance of synaptic plasticity, it is crucial that we have some understanding of the role that diffusion and chemical kinetics play in governing the behavior of these substances. Today, we have unprecedented access to the spatio-temporal dynamics of intracellular calcium in individual neurons using fluorescent calcium dyes, such as fura-2 or fluo-3, in combination with confocal or two-photon microscopy in the visible or in the infrared spectrum (Tsien, 1988; Tank et al., 1988; Hernández-Cruz, Sala, and Adams, 1990; Ghosh and Greenberg, 1995).

While small leucine rich proteins/proteoglycans (SLRPs) are present in very low concentrations in the extracellular matrix (ECM), they have been shown to be critical determinants of the proper ECM assembly and function in connective tissues [1] including bone [2], cornea [3], and cartilage [4]. However, their direct and indirect roles in matrix biomechanics and the potential for osteoarthritis-related dysfunction of cartilage remain unclear. With the advent of new high resolution nanotechnological tools, the direct quantification of cartilage biomechanical properties using murine models can provide important insights into how secondary ECM molecules, such as SLRPs, affect the function and pathology of cartilage [5]. Previous nanoindentation studies of murine cartilage have assessed the effects of maturation and osteoarthritis-like degradation of cartilage on its biomechanical properties [6, 7]. Recently, murine models have received increased attention because of the availability of specific gene-knockout and gene alteration technologies [8]. For example, chondroadherin (CHAD) is a non-collagenous small leucine-rich proteoglycan (SLRP) with α-helix and β-sheet secondary structure, spatially localized in the territorial matrix (MW = 38 kDa) [9]. In articular cartilage, CHAD is distributed non-uniformly with depth [10], and binds to type II collagen and the α2β1 integrin and is hypothesized to function in the communication between chondrocytes and their surrounding matrix, as well as in the regulation of collagen fibril assembly [11, 12] (Fig. 1). The objective of the present study is to explore the role of CHAD and its depletion on the structure and nanomechanical properties of both superficial and middle/deep zone cartilage. The current methods thereby enabled depth-dependent analysis of cartilage nanostructure and dynamic energy-dissipative mechanisms.

To further document the involvement of external Ca2+ in the platelet induced-activation process, we have studied the arachidonate (AA) metabolism of intact washed rat platelets in the presence of different concentrations of Ca2+, Sr2+ or Ba2+. The thrombin-induced mobilization of [3H]- or [14C]-AA preincorporated into platelet phospholipids was followed as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products (CLP). Results indicate that upon thrombin (<0.1 U/ml) stimulation, AA release and CLP formation are reduced by 50 to 90% only by omission of Ca2+ as compared to 1 mM Ca2+ in the suspending medium. In higher Ca2+ concentrations (5 mM), the AA mobilization and CLP formation are inhibited and the data are close to those obtained in the absence of Ca2+. In the presence of Sr2+ or Ba2+, results indicate that these cations can substitute to Ca2+. Similarly to Ca2+, an optimum concentration is found in Sr2+ or Ba2+ (3-5 mM) and higher concentrations inhibit AA release and CLP formation.We have also studied the activity of a semi-purified preparation of phospholipase A2 (PLA2) from rat platelets. This activity was assayed (pH 9) using heat-denaturated (3H)-AA prelabeled phospholipids as substrate. The results show that this PLA2 activity was strongly Ca2+-dependent. We found that unlike Mg2+, Sr2+ and Ba2+ are able to greatly enhance this activity. Relative effiency (Vmax) are in the order Ca2+>Sr2+>Ba2+. Taken together, these findings as well as our previous results (Blache et al, BBA 1987, in press) suggest that external Ca2+ may play a major role in the regulation of rat platelet activity. Our interpretation is in line with the view that Sr2+ or Ba2+ could enter the platelet through a mechanism common to Ca2+ (a kind of Ca2+ channel). Although direct evidence await the results of further studies which are in progress, it can be considered that Sr2+ or Ba2+ might cause platelet induced-activation mimickigci a rise in the cytosolic Ca2+ and subsequent activation of Ca2+-dependent enzymes.

The importance of nanotechnology standardization is to reach the main topic in developing standards, which is “uniformity in manufacturing and facilitating the commercialization of nano-products.” According to this goal, activities on standardization in nanotechnology have been started in Iran, where development of nanotechnology is assigned to National Nanotechnology Committee of Iran. This committee is working under direct supervision of presidency office. As written in the committee’s official website [http://www.nano.ir], one of the long term goals of this movement, according to the “fourth development program of Iran” is to reach appropriate share of world trade based on nanotechnology. For this purpose standard developing and quality management system is needed for facilitating industrial and technological cooperation and decreasing costs raised from quality unawareness. So our workgroup has selected nanotechnology standardization as one of its research topics. We have studied current state of different active countries in this field and find out that one can categorize these activities into two major groups, General and Specific. The general activities refer to those looking from the regulatory and nomenclature point of view. In the other side specific activities have done according to local contracts signed between manufacturers, organizations and business start-ups. As examples of the activities started in Iran we can mention: 1. Establishing National Laboratory Network for Nanotechnology by National Nanotechnology Committee of Iran. 2. Collaboration of the Institute of Standards and Industrial Research of Iran (ISIRI) with, International Standard Organization (ISO) for starting the new Nanotechnology TC (technical committee). Today, Iran is one of the 23 active members of ISO TC 229 on Nanotechnologies. 3. Academic research on standardization of measurement procedures used for nano-scale materials. We have gathered or proposed in our research some opportunities specifically for Iran, which may also be helpful for other developing countries to enhance their market position in the upcoming era of nanotechnology. These proposals can be listed as below: 1. Establishing a national committee for managing and regulating of nanotechnology standards; 2. Starting nanotechnology technical committee in Iranian Standard and Industrial Research Organization; 3. Actively collaborating with other countries and international standard institutes, insisting on the country’s core competencies; 4. Introducing Iran’s specific needs to international standard institutes; 5. Equipping national laboratories; 6. Collaborating with international laboratory networks; 7. Developing specific standards based on casual contracts; 8. Activation of researchers to focus on measurement procedures and methods; 9. Participation in regional seminars and workshops and initiation of such activities. With paying attention to these activities, we can find the opportunity of holding a highly referenced database and information center for nanotechnology related commerce. To organize the “nanotechnology technical committee” inside the ISIRI [http://www.isiri.org/], which is responsible for all standardization activities in Iran, we decided to follow the common inter organizational disciplines of this institute, but we suggested assigning 2 or 3 members of this committee, despite others, as full time members. These members would track international standardization activities, and would be the administrators of such activities within Iran. Actively collaboration with other countries and international standard institutes, insisting on the country’s core competencies, would have lots of benefits for country. Taking into consideration that, there is no comprehensive and global accepted nano-standard in the world, through these efforts we can introduce our main interested topics of standardization to international standard institutes (e.g. during our correspondences with Dr. Hatto from UK committee for standardization in Nanotechnologies, we received an offer to notice them our priorities in Nano-standards). To do so, ISIRI has announced his full support of new ISO TC on Nanostandards. To be able to play an appropriate role in this field, having laboratories with advanced equipments is something essential. Because of the reason that these facilities are costly, we decided to take the advantages of National Laboratory Network for Nanotechnology. The laboratories within this network can support nanostandardization process through measurement at nano scale, identifying characterization of nano structures and materials, and their physical and chemical properties (for more information about this network you can visit the following website http://nanolab.nano.ir). Having a well-known and advanced national laboratory network, Iran can provide services to other countries too, and also can become a member of international laboratory networks to develop it activities. The other activity that Iran is interested in is to take part in joint works with international standard making organizations to develop specific standards (e.g. characterization of nanoparticles in ceramics industry). After developing such standards they could be certified through authority standard making organization. Universities also can play an active role in nanotechnology standardization from different aspects. For instance they can do surveys to study priorities of country in this field, and also can study on measurement at nanoscale, characterization of nanomaterilas, test method subjects and etc. Also, some activities in this field have been done in some first rated universities in the country. Participating in regional seminars and making good connections between scientists who are working at this task is another way to have a good background about nano standardization and developing special standards in nano technology. Scientists can co-work in regional universities and laboratories and they can present their research results in such kind of seminars. The goal of such program is making a new task in science and a good relationship between researchers who are working at laboratories on nano standardization and governments. Developing specific standards based on casual contracts makes our universities, laboratories and industries strong for developing standards for special cases. Being strong in such contracts give our industries and universities a powerful goal for developing standards in special cases. Equipping national laboratories and Collaborating with international laboratory networks gives our industries and universities a wide range of abilities for making precision measurements and being in touch with other institutes. The researchers and engineers can use the results of each laboratory for their researches and measurements. In this way the special contracts can be stronger and appearance of Iran in seminars, workshops and commercial relations will be more effective. One of the most important decisions can be finding a proper industry in Iran which can compete in world trade. For this kind of industry using nano materials as the primary materials or in other steps of process and developing standards will be very helpful. This kind of researches will helpful for developing a long range policy for nanotechnology in Iran.

This report maps the African landscape of Open Science – with a focus on Open Data as a sub-set of Open Science. Data to inform the landscape study were collected through a variety of methods, including surveys, desk research, engagement with a community of practice, networking with stakeholders, participation in conferences, case study presentations, and workshops hosted. Although the majority of African countries (35 of 54) demonstrates commitment to science through its investment in research and development (R&D), academies of science, ministries of science and technology, policies, recognition of research, and participation in the Science Granting Councils Initiative (SGCI), the following countries demonstrate the highest commitment and political willingness to invest in science: Botswana, Ethiopia, Kenya, Senegal, South Africa, Tanzania, and Uganda. In addition to existing policies in Science, Technology and Innovation (STI), the following countries have made progress towards Open Data policies: Botswana, Kenya, Madagascar, Mauritius, South Africa and Uganda. Only two African countries (Kenya and South Africa) at this stage contribute 0.8% of its GDP (Gross Domestic Product) to R&D (Research and Development), which is the closest to the AU’s (African Union’s) suggested 1%. Countries such as Lesotho and Madagascar ranked as 0%, while the R&D expenditure for 24 African countries is unknown. In addition to this, science globally has become fully dependent on stable ICT (Information and Communication Technologies) infrastructure, which includes connectivity/bandwidth, high performance computing facilities and data services. This is especially applicable since countries globally are finding themselves in the midst of the 4th Industrial Revolution (4IR), which is not only “about” data, but which “is” data. According to an article1 by Alan Marcus (2015) (Senior Director, Head of Information Technology and Telecommunications Industries, World Economic Forum), “At its core, data represents a post-industrial opportunity. Its uses have unprecedented complexity, velocity and global reach. As digital communications become ubiquitous, data will rule in a world where nearly everyone and everything is connected in real time. That will require a highly reliable, secure and available infrastructure at its core, and innovation at the edge.” Every industry is affected as part of this revolution – also science. An important component of the digital transformation is “trust” – people must be able to trust that governments and all other industries (including the science sector), adequately handle and protect their data. This requires accountability on a global level, and digital industries must embrace the change and go for a higher standard of protection. “This will reassure consumers and citizens, benefitting the whole digital economy”, says Marcus. A stable and secure information and communication technologies (ICT) infrastructure – currently provided by the National Research and Education Networks (NRENs) – is key to advance collaboration in science. The AfricaConnect2 project (AfricaConnect (2012–2014) and AfricaConnect2 (2016–2018)) through establishing connectivity between National Research and Education Networks (NRENs), is planning to roll out AfricaConnect3 by the end of 2019. The concern however is that selected African governments (with the exception of a few countries such as South Africa, Mozambique, Ethiopia and others) have low awareness of the impact the Internet has today on all societal levels, how much ICT (and the 4th Industrial Revolution) have affected research, and the added value an NREN can bring to higher education and research in addressing the respective needs, which is far more complex than simply providing connectivity. Apart from more commitment and investment in R&D, African governments – to become and remain part of the 4th Industrial Revolution – have no option other than to acknowledge and commit to the role NRENs play in advancing science towards addressing the SDG (Sustainable Development Goals). For successful collaboration and direction, it is fundamental that policies within one country are aligned with one another. Alignment on continental level is crucial for the future Pan-African African Open Science Platform to be successful. Both the HIPSSA ((Harmonization of ICT Policies in Sub-Saharan Africa)3 project and WATRA (the West Africa Telecommunications Regulators Assembly)4, have made progress towards the regulation of the telecom sector, and in particular of bottlenecks which curb the development of competition among ISPs. A study under HIPSSA identified potential bottlenecks in access at an affordable price to the international capacity of submarine cables and suggested means and tools used by regulators to remedy them. Work on the recommended measures and making them operational continues in collaboration with WATRA. In addition to sufficient bandwidth and connectivity, high-performance computing facilities and services in support of data sharing are also required. The South African National Integrated Cyberinfrastructure System5 (NICIS) has made great progress in planning and setting up a cyberinfrastructure ecosystem in support of collaborative science and data sharing. The regional Southern African Development Community6 (SADC) Cyber-infrastructure Framework provides a valuable roadmap towards high-speed Internet, developing human capacity and skills in ICT technologies, high- performance computing and more. The following countries have been identified as having high-performance computing facilities, some as a result of the Square Kilometre Array7 (SKA) partnership: Botswana, Ghana, Kenya, Madagascar, Mozambique, Mauritius, Namibia, South Africa, Tunisia, and Zambia. More and more NRENs – especially the Level 6 NRENs 8 (Algeria, Egypt, Kenya, South Africa, and recently Zambia) – are exploring offering additional services; also in support of data sharing and transfer. The following NRENs already allow for running data-intensive applications and sharing of high-end computing assets, bio-modelling and computation on high-performance/ supercomputers: KENET (Kenya), TENET (South Africa), RENU (Uganda), ZAMREN (Zambia), EUN (Egypt) and ARN (Algeria). Fifteen higher education training institutions from eight African countries (Botswana, Benin, Kenya, Nigeria, Rwanda, South Africa, Sudan, and Tanzania) have been identified as offering formal courses on data science. In addition to formal degrees, a number of international short courses have been developed and free international online courses are also available as an option to build capacity and integrate as part of curricula. The small number of higher education or research intensive institutions offering data science is however insufficient, and there is a desperate need for more training in data science. The CODATA-RDA Schools of Research Data Science aim at addressing the continental need for foundational data skills across all disciplines, along with training conducted by The Carpentries 9 programme (specifically Data Carpentry 10 ). Thus far, CODATA-RDA schools in collaboration with AOSP, integrating content from Data Carpentry, were presented in Rwanda (in 2018), and during17-29 June 2019, in Ethiopia. Awareness regarding Open Science (including Open Data) is evident through the 12 Open Science-related Open Access/Open Data/Open Science declarations and agreements endorsed or signed by African governments; 200 Open Access journals from Africa registered on the Directory of Open Access Journals (DOAJ); 174 Open Access institutional research repositories registered on openDOAR (Directory of Open Access Repositories); 33 Open Access/Open Science policies registered on ROARMAP (Registry of Open Access Repository Mandates and Policies); 24 data repositories registered with the Registry of Data Repositories (re3data.org) (although the pilot project identified 66 research data repositories); and one data repository assigned the CoreTrustSeal. Although this is a start, far more needs to be done to align African data curation and research practices with global standards. Funding to conduct research remains a challenge. African researchers mostly fund their own research, and there are little incentives for them to make their research and accompanying data sets openly accessible. Funding and peer recognition, along with an enabling research environment conducive for research, are regarded as major incentives. The landscape report concludes with a number of concerns towards sharing research data openly, as well as challenges in terms of Open Data policy, ICT infrastructure supportive of data sharing, capacity building, lack of skills, and the need for incentives. Although great progress has been made in terms of Open Science and Open Data practices, more awareness needs to be created and further advocacy efforts are required for buy-in from African governments. A federated African Open Science Platform (AOSP) will not only encourage more collaboration among researchers in addressing the SDGs, but it will also benefit the many stakeholders identified as part of the pilot phase. The time is now, for governments in Africa, to acknowledge the important role of science in general, but specifically Open Science and Open Data, through developing and aligning the relevant policies, investing in an ICT infrastructure conducive for data sharing through committing funding to making NRENs financially sustainable, incentivising open research practices by scientists, and creating opportunities for more scientists and stakeholders across all disciplines to be trained in data management.