The Biosimilars Act: The United States’ Entry into Regulating Biosimilars and its Implications, 12 J. Marshall Rev. Intell. Prop. L. 322 (2013)

The Patient Protection and Affordable Care Act is most well-known for creating a mandate requiring individuals to have health insurance. However, another provision of the Act, the Biologics Price Competition and Innovation Act, created a new process for companies to introduce biosimilars, products that are highly similar to licensed drugs in terms of purity, safety, and potency, but have minor differences in the inactive ingredients. This provision seeks to alleviate strain on companies introducing biosimilars by creating an abbreviated pathway for their approval by the Food and Drug Administration, similar to an Abbreviated New Drug Application under the Hatch-Waxman Act. This article provides a comprehensive overview of the Biologics Price Competition and Innovation Act and contrasts it with the Hatch-Waxman Act and European Law on Biosimilars. Strategies for patent claiming and resolving patent disputes are then discussed

Gene Expression Signature of Normal Cell-of-Origin Predicts Ovarian Tumor Outcomes

The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome

A Problem About the Morality of Some Common Forms of Prayer

Autor twierdzi, że nieśmiertelność niekoniecznie musi być aż tak zła, jak to opisuje Bernard Williams. Twierdzi on, że jeśli nieśmiertelne życie charakteryzowałoby się wystarczająco zróżnicowanym pakietem doświadczeń, odpowiednio podzielonych, nie ma powodu, by sądzić, że ktoś będzie się nudził (podobnie jak nie ma powodu, by sądzić, że ktoś będzie się nudził takimi doświadczeniami w życiu śmiertelnym). Przyznaje, że niektóre z przyjemnych doświadczeń „same ulegają wyczerpaniu”, ale mówi, że nie ma wystarczającej liczby powtarzalnych „przyjemności”, aby ulec nudzie, o której mówi Bernard Williams.The author argues that immortality need not be as bad as Bernard Williams says it would be. He argues that if an immortal life were characterized by a sufficiently diverse package of experiences, appropriately distributed, there is no reason to think that one would become bored (just as there is no reason to think that one would become bored of such experiences in a finite life). He acknowledges that some pleasurable experiences would be “self-exhausting,” but he says that there are enough “repeatable pleasures” to avoid the tedium of which Bernard Williams speaks

Which Naturalism?

Program „naturalizacji” bywa we współczesnej laickiej filozofii przedstawiany w opozycji do tradycyjnego teizmu. Biorąc jednak pod uwagę historię terminów „natura” i „naturalny”, widać brak ciągłości między tym, jak owe terminy są rozumiane obecnie, a jak rozumiano je w przeszłości. Nowożytny „naturalista”, który domaga się, by wszystkie zjawiska umieścić w dziedzinie tego, co naturalne, stawia tezę, którą wielu klasycznych, średniowiecznych i wczesnonowożytnych filozofów i teologów uznałoby za dość samooczywistą. Zmiana, która tu zaszła, nie polega na decyzji, by do dziedziny naturalnej włączyć to, co poprzednio było z niej wykluczone, lecz na zupełnie innym rozumieniu tejże dziedziny. W artykule argumentuję, że filozoficznie ciekawe jest nie tyle pytanie, czy powinniśmy być naturalistami, ile pytanie, który z dwóch naturalizmów należy przyjąć: świecki naturalizm, z jego neutralistyczną koncepcją natury w ogóle i ludzkiej natury w szczególności, czy teistyczny naturalizm, wedle którego świat naturalny i nasza własna natura noszą znamię boskości. Okazuje się, że ujęcie sekularystyczne musi zmierzyć się z poważnymi wyzwaniami epistemicznymi i moralnymi.The ‘naturalizing’ agenda in contemporary secularist philosophy is often presented in opposition to traditional theism. But looking at the history of the terms ‘nature’ and ‘natural’ reveals a discontinuity between how these terms are currently understood and how they were understood in the past. The modern ‘naturalist’, in insisting that all phenomena should be brought within the domain of the natural, is advancing a thesis that many classical, medieval and early-modern philosophers and theologians would have regarded as fairly self-evident. What has changed is not that there is a new determination to include within the natural domain what was previously excluded from it, but rather that there is a radical shift in how the natural domain is to be understood. This paper argues that the philosophically interesting question is not whether or not we should be naturalists, but which of two naturalisms we should adopt: secular naturalism, with its neutralist conception of nature in general and of human nature in particular, or theistic naturalism, according to which the natural world and our own nature bear the stamp of the divine. It turns out the former (secularist) view is vulnerable to serious difficulties, on both the epistemic and the moral fronts

The Frankfurt Cases: The Moral of the Stories

Autor argumentuje, że morał przykładów frankfurtowskich jest następujący: jeśli determinizm przyczynowy wyklucza odpowiedzialność moralną, to nie na mocy eliminacji alternatywnych możliwości, a następnie odpowiada na najważniejsze wyzwanie dla tej tezy, mianowicie argument nazywany „obroną przez dylemat”.The author argues that the moral of the Frankfurt stories is this: if causal determinism rules out moral responsibility, it is not in virtue of eliminating alternative possibilities, and replies the most important challenge to this claim, namely an argument called “The Dilemma Defense.

Responsiveness and Moral Responsibility

Autor przedstawia model odpowiedzialności moralnej oparty na faktycznej sekwencji i pojęciu zdolności reagowania na racje, a następnie przeprowadza analogię między tym modelem a opracowanym przez Roberta Nozicka modelem wiedzy opartej na faktycznej sekwencji, oraz wprowadza pojęcie semikompatybilizmu.The author presents a model of moral responsibility based on the actual sequence and the notion of reason-responsiveness, and draws an analogy between this model and Robert Nozick’s model of knowledge based on the actual sequence. In addition, the concept of semicompatibilism is introduced and explained

Philosophical Models of Immortality in Science Fiction

Fantastyka naukowa (ang. science fiction, w skrócie – SF) jest często przedstawiana jako gatunek literacki dobrze przystosowany do spekulacji filozoficznej. SF i filozofia dzielą zainteresowanie kwestią nieśmiertelności, a ich ujęcia tego tematu można zestawić i porównać. Proponujemy tutaj zarys taksonomii różnych modeli czy wizji nieśmiertelności oferowanych przez filozofów i autorów fantastyki naukowej. Po wskazaniu istotnych rozbieżności między tymi modelami przedstawiamy sugestię, że pewne problemy oraz wątpliwości wysuwane przez pisarzy SF i filozofów wynikają z pomieszania różnych modeli. Mamy nadzieję, że te porównania pokażą wstępnie, w jakim sensie można powiedzieć, że fantastyka naukowa funkcjonuje jako dyskurs filozoficzny.Science fiction is often described as a literary genre well suited to philosophical speculation. SF and philosophy share a common interest in the question of immortality, and comparisons and contrasts can be made regarding their respective treatments of the theme. We propose here a sketch of a taxonomy of different models or pictures of immortality offered by philosophers and SF writers. After noting important difference in these models, we suggest that some problems and concerns expressed by philosophers and SF writers alike are the result of conflating different models. It is our hope that these comparisons provide a preliminary sense of the way SF can be said to function as philosophical discourse

Parallel Opsin Switches in Multiple Cone Types of the Starry Flounder Retina: Tuning Visual Pigment Composition for a Demersal Life Style

Variable expression of visual pigment proteins (opsins) in cone photoreceptors of the vertebrate retina is a primary determinant of vision plasticity. Switches in opsin expression or variable co-expression of opsins within differentiated cones have been documented for a few rodents and fishes, but the extent of photoreceptor types affected and potential functional significance are largely unknown. Here, we show that both single and double cones in the retina of a flatfish, the starry flounder (Platichthys stellatus), undergo visual pigment changes through opsin switches or variable opsin co-expression. As the post-metamorphic juvenile (i.e., the young asymmetric flatfish with both eyes on one side of the body) grows from ~5 g to ~196 g, some single cones and one member of unequal double cones switched from a visual pigment with maximum wavelength of absorbance, λmax, at shorter wavelengths (437 nm and 527 nm) to one with longer λmax (456 nm and 545 nm, respectively) whereas other cones had intermediate visual pigments (λmax at 445 nm or 536 nm) suggesting co-expression of two opsins. The shift toward longer wavelength absorbing visual pigments was in line with maximizing sensitivity to the restricted light spectrum at greater depths and achromatic detection of overhead targets

Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer

The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC

Tumor formation, tumor burden and ascites in the OCLER and FNLER xenograft model.

a<p>Values shown are means ± s.d. across all mice injected with each cell type that had any evaluable tumor mass (the sum of 1× intraperitoneal and 2× subcutaneous sites per mouse).</p>b<p>Formation of ascites was only evaluated among mice that developed tumors.</p>c<p><i>P</i>-values were calculated using the Mann-Whitney test.</p