Copyright Exhaustion Rationales and Used Software: A Law and Economics Approach to Oracle v. UsedSoft

This article aims to provide courts and policymakers with an analytical framework that, building upon the traditional rationales of IP exhaustion doctrine, identifies factors which advocate for a modulation or flexibilization of the role of exhaustion in copyright law. Factors include (i) the personal features of acquirers of copies of copyrighted works, distinguishing between consumers and commercial users; (ii) whether post-sale restrictions have been adequately communicated to acquirers and have been agreed in the contract or license; (iii) the degree of complexity of the acquired goods and their prospects of productive uses and interoperability; (iv) the role of other exclusive rights in providing rightholders with indirect control over uses of the copies in the aftermarket; (v) the impact of post-sale restraints in preventing opportunism in long-term contracts and in reducing deadweight losses created by IP pricing; and (vi) the temporal scope of post-sale restraints. After setting out this analytical framework, the ECJ Judgement in Oracle v. UsedSoft is discussed.

Variability in the prevalence of adult ADHD in treatment seeking substance use disorder patients: results from an international multi-center study exploring DSM-IV and DSM-5 criteria

Background: Available studies vary in their estimated prevalence of attention deficit/hyperactivity disor-der (ADHD) in substance use disorder (SUD) patients, ranging from 2 to 83%. A better understanding ofthe possible reasons for this variability and the effect of the change from DSM-IV to DSM-5 is needed.Methods: A two stage international multi-center, cross-sectional study in 10 countries, among patientsform inpatient and outpatient addiction treatment centers for alcohol and/or drug use disorder patients. Atotal of 3558 treatment seeking SUD patients were screened for adult ADHD. A subsample of 1276 subjects,both screen positive and screen negative patients, participated in a structured diagnostic interview. 5AdultsResults: Prevalence of DSM-IV and DSM-5 adult ADHD varied for DSM-IV from 5.4% (CI 95%: 2.4–8.3) forHungary to 31.3% (CI 95%:25.2–37.5) for Norway and for DSM-5 from 7.6% (CI 95%: 4.1–11.1) for Hungary to32.6% (CI 95%: 26.4–38.8) for Norway. Using the same assessment procedures in all countries and centersresulted in substantial reduction of the variability in the prevalence of adult ADHD reported in previousstudies among SUD patients (2–83% → 5.4–31.3%). The remaining variability was partly explained byprimary substance of abuse and by country (Nordic versus non-Nordic countries). Prevalence estimatesfor DSM-5 were slightly higher than for DSM-IV.Conclusions: Given the generally high prevalence of adult ADHD, all treatment seeking SUD patientsshould be screened and, after a confirmed diagnosis, treated for ADHD since the literature indicates poorprognoses of SUD in treatment seeking SUD patients with ADHD.

Amplified bioproductivity during Transition IV (332 000-342 000 yr ago): evidence from the geochemical record of Lake El'gygytgyn

Abstract. To date, terrestrial archives of long-term climatic change within the Arctic have widely been restricted to ice cores from Greenland and, more recently, sediments from Lake El’gygytgyn in northeast Arctic Russia. Sediments from this lake contain a paleoclimate record of glacialinterglacial cycles during the last three million years. Lowresolution studies at this lake have suggested that changes observed during Transition IV (the transition from marine isotope stage (MIS) 10 to MIS 9) are of greater amplitude than any observed since. In this study, geochemical parameters are used to infer past climatic conditions thus providing the first high-resolution analyses of Transition IV from a terrestrial Arctic setting. These results demonstrate that a significant shift in climate was subsequently followed by a rapid increase in biogenic silica (BSi) production. Following this sharp increase, bioproductivity remained high, but variable, for over a thousand years. This study reveals differences in the timing and magnitude of change within the ratio of silica to titanium (Si/Ti) and BSi records that would not be apparent in lower resolution studies. This has significant implications for the increasingly common use of Si/Ti data as an alternative to traditional BSi measurements.

Analyzing the Role of αvβ8 Integrin in Glioma-Induced Angiogenesis

In this study we aimed to determine the functional roles for αvβ8 integrin in astrocytoma-induced angiogenesis. These studies originate from our analyses of αvβ8 integrin in developmental brain angiogenesis. αv and β8 knockout (KO) mice develop brain-specific vascular phenotypes that resemble vascular pathologies observed in the malignant astrocytoma, glioblastoma multiforme (GBM). Indeed, a murine xenograft model of astrocytoma suggested a role for the integrin in glioma-induced angiogenesis. Primary mouse astroglia were cultured from wild type (WT) and β8 KO neonates and were immortalized (HPV:E6/E7) and transformed (HRas:G12V). WT and β8 KO transformed astroglia were intracranially injected into athymic mice. WT tumors displayed pathological features of grade III astrocytomas, whereas β8 KO tumors resembled grade IV GBMs. KO tumors contained widespread edema and hemorrhage as well as pathological angiogenesis, as assessed by quantitation of microvascular density and blood vessel morphology. Additionally, exogenous expression of β8 integrin in β8 KO transformed astroglia resolved the pathologies observed in KO tumors giving further credence to the idea that loss of αvβ8 integrin expression correlates with tumorigenic potential of oncogene-transformed astroglia. To compliment our mouse model, several established human glioma cell lines were characterized for expression of αvβ8 integrin protein. Some of the cell lines displayed low expression of αvβ8 integrin, whereas others showed high levels, as compared to non-malignant human astrocytes. Intracranial implantation of high and low β8 integrin-expressing human glioma cell lines resulted in tumors exhibiting similar phenotypes to those observed in the mouse model; low expressers were marked by vascular pathologies indicative of β8 KO mouse tumors. Upon overexpression of β8 integrin in a low β8 integrin-expressing human glioma cell line, angiogenic pathologies were largely resolved. Moreover, intracranially injected αvHI- and αvLO-sorted GBM stem cells (GSCs) resulted in significantly different tumor sizes, where those GSCs endogenously expressing low levels of αv integrin formed two to three fold larger tumors. Furthermore, lentiviral knockdown of β8 integrin in transformed human astrocytes formed tumors that strikingly recapitulated the characteristics of the murine β8-/- tumors, exhibiting a significant increase in microvascular density leading to decreased overall survival. A paracrine mechanism was discovered involving endothelial cell homeostatic control governed by canonical TGFβ signaling initiated by αvβ8 integrin’s role in the latent cytokine’s activation. Diminished TGFβ signaling in tumor-associated endothelial cells promoted increased angiogenesis and decreased overall survival as a result of αvβ8 integrin’s loss on the tumor cell. Collectively, these data suggest an important functional role for αvβ8 integrin in glioma angiogenesis.

The functional and structural interactions between v-{\it mos\/} proteins and cell cycle control elements

The v-mos gene of Moloney murine sarcoma virus (Mo-MuSv) encodes a serine/threonine protein kinase capable of inducing cellular transformation. The c-mos protein is an important cell cycle regulator that functions during meiotic cell division cycles in germ cells. The overall function of c-mos in controlling meiosis is becoming better understood but the role of v-mos in malignant transformation of cells is largely unknown.^ In this study, v-mos protein was shown to be phosphorylated by M phase kinase in vitro and in vivo. The kinase activity and neoplastic transforming ability of v-mos is positively regulated by the phosphorylation. Together with the earlier finding of activation of M phase kinase by c-mos, these results raise the possibility of mutual regulation between M phase kinase and mos kinases.^ In addition to its functional interaction with the M phase kinase, the v-mos protein was shown to be present in the same protein complex with a cyclin-dependent kinase (cdk). In addition, an antibody that recognizes the cdk proteins was shown to co-precipitate the v-mos proteins in the interphase and mitotic cells transformed by p85$\sp{\rm gag-mos}$. Cdk proteins have been shown to be associated with nonmitotic cyclins which are potential oncogenes. The perturbation of cdk kinase or the activation of non-mitotic cyclins as oncogenes by v-mos could contribute directly to v-mos induced cellular transformation. v-mos proteins were also shown to interact with tubulin and vimentin, the essential components of microtubules and type IV intermediate filaments, respectively. The organizations of both microtubules and intermediate filaments are cell cycle-regulated. These results suggest that the v-mos kinase could be directly involved in inducing morphological changes typically seen in transformed cells.^ The interactions between the v-mos protein and these cell cycle control elements in regards to v-mos induced neoplastic transformation are discussed in detail in the text. ^

Die Judenfrage am Ende des XIX. Jahrhunderts : nach den Verhandlungen des V. allgemeinen Parteitages der Deutsch-Sozialen Reformpartei zu Hamburg am 11. September 1899

dargest. von W. Giese

Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV

PURPOSE Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.

Frankfurt, Sonntag den 19. November: Bassermanns Bericht über seine Sendung nach Berlin: In der Sitzung der Reichsversammlung vom 17. November stellte der Abgeordnete v. Rappard nachstehenden Antrag ...

Welsch (Projektbearbeiter): Bericht Bassermanns über seine Reise nach Berlin (worin sich auch die inkriminierte Wendung von den die Straßen bevölkernden und nicht näher zu schildernden Gestalten (die sprichwörtlich gewordenen 'Bassermannschen Gestalten') findet): nach dem persönlichen Eindruck des Reichskommissars war die Arbeit der Preußischen Nationalversammlung dem Druck der Straße ausgesetzt und wurde so zusehends unmöglich gemacht. Vorsichtig positive Bewertung des Befehls Friedrich Wilhelms IV. zur Vertagung der Preußischen Nationalversammlung (9. November 1848) sowie des Einmarschs preußischen Militärs unter General von Wrangel nach Berlin (10. November 1848). Als ablehnende Replik auf den Antrag des Abgeordneten von Rappard, die preußische Regierung zur Aufhebung ihres Beschlusses über die Vertagung und Verlegung der Berliner Nationalversammlung zu bewegen