The Girl Talk Dilemma: Can Copyright Law Accomodate New Forms of Sample-Based Music?

On Gregg Gillis’ laptop computer are thousands of files representing a vast slice of 20th and 21st century popular music.1 His digital music collection is similar to that of many music consumers: it spans a wide variety of genres and runs from the obscure to the mainstream. But Gillis is different from most music consumers in that he uses computer software to cut his digital music files into audio snippets, or samples, and then piece them together into song collages.2 Gregg Gillis is Girl Talk, a recording artist on the Illegal Art label whose music has made yearend best music lists in Time Magazine,3 Rolling Stone,4 Blender5 and Pitchforkmedia.com.6 Girl Talk has developed a strong following throughout the United States and has toured throughout Europe and Australia.7 A PC user, he was recently featured in one of the “I’m a PC” ads for Microsoft.8 But while Girl Talk has been successful, Gillis adds almost no original musical content to his recordings. Although he often alters the speed or pitch of his samples, or loops them in a continuous pattern, he does not sing or rap over his creations. Furthermore, Gillis has never sought licenses or authorization for any of the samples he uses.9 For instance, his latest album, “Feed the Animals,” includes over 300 unauthorized samples10 of artists ranging from Lil Wayne to Radiohead to Metallica to Kenny Loggins

Role of ERO1-α–mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress–induced apoptosis

CHOP turns on ERO1-α to release calcium via IP3R and trigger cell death in response to ER stress

Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2

Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300–1,800 working cardiomyocytes or 90–160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia

Compartmentalized Phosphodiesterase-2 Activity Blunts β-Adrenergic Cardiac Inotropy via an NO/cGMP-Dependent Pathway

β-Adrenergic signaling via cAMP generation and PKA activation mediates the positive inotropic effect of catecholamines on heart cells. Given the large diversity of protein kinase A targets within cardiac cells, a precisely regulated and confined activity of such signaling pathway is essential for specificity of response. Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus poised to regulate intracellular cAMP gradients. Their spatial confinement to discrete compartments and functional coupling to individual receptors provides an efficient way to control local [cAMP] i in a stimulus-specific manner. By performing real-time imaging of cyclic nucleotides in living ventriculocytes we identify a prominent role of PDE2 in selectively shaping the cAMP response to catecholamines via a pathway involving β 3 -adrenergic receptors, NO generation and cGMP production. In cardiac myocytes, PDE2, being tightly coupled to the pool of adenylyl cyclases activated by β-adrenergic receptor stimulation, coordinates cGMP and cAMP signaling in a novel feedback control loop of the β-adrenergic pathway. In this, activation of β 3 -adrenergic receptors counteracts cAMP generation obtained via stimulation of β 1 /β 2 -adrenoceptors. Our study illustrates the key role of compartmentalized PDE2 in the control of catecholamine-generated cAMP and furthers our understanding of localized cAMP signaling

Working memory dynamics and spontaneous activity in a flip-flop oscillations network model with a Milnor attractor

Many cognitive tasks require the ability to maintain and manipulate simultaneously several chunks of information. Numerous neurobiological observations have reported that this ability, known as the working memory, is associated with both a slow oscillation (leading to the up and down states) and the presence of the theta rhythm. Furthermore, during resting state, the spontaneous activity of the cortex exhibits exquisite spatiotemporal patterns sharing similar features with the ones observed during specific memory tasks. Here to enlighten neural implication of working memory under these complicated dynamics, we propose a phenomenological network model with biologically plausible neural dynamics and recurrent connections. Each unit embeds an internal oscillation at the theta rhythm which can be triggered during up-state of the membrane potential. As a result, the resting state of a single unit is no longer a classical fixed point attractor but rather the Milnor attractor, and multiple oscillations appear in the dynamics of a coupled system. In conclusion, the interplay between the up and down states and theta rhythm endows high potential in working memory operation associated with complexity in spontaneous activities

Electronic Transport on W-Rich Films Deposited by Focused Ion Beam

International audienc

Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice

Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30–50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50–75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor-α coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30–78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency (P = 0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function