6,300 research outputs found

    Comradely Greetings: The Prison Letters of Nadya and Slavoj

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    In October 2012, Nadezhda (Nadya) Tolokonnikova and Maria Alyokhina, both members of the punk-protest group Pussy Riot, were sent to separate Russian penal colonies, charged in relation to an anti-Putin performance in Moscow’s Cathedral of Christ the Saviour the previous February. During her time in the Mordovian Penal Colony No. 14— and briefly afterwards—Tolokonnikova engaged in the exchange of letters with philosopher Slavoj Žižek collected in Comradely Greetings, alongside Tolokonnikova’s open letter that details her harrowing experience in the camp and announced her hunger strike, just under a year into her sentence. The richness of Žižek and Tolokonnikova’s correspondences—and the nuance of the flow of their back-and-forth debate—cannot be adequately summarised in the few words here. Instead, this review seeks to provide a brief overview of the key debates and disagreements between the two regarding the central questions of global capitalism and resistance to it—in particular Pussy Riot’s resistance

    Transcription activator like effector (TALE)-directed piggyBac transposition in human cells.

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    Insertional therapies have shown great potential for combating genetic disease and safer methods would undoubtedly broaden the variety of possible illness that can be treated. A major challenge that remains is reducing the risk of insertional mutagenesis due to random insertion by both viral and non-viral vectors. Targetable nucleases are capable of inducing double-stranded breaks to enhance homologous recombination for the introduction of transgenes at specific sequences. However, off-target DNA cleavages at unknown sites can lead to mutations that are difficult to detect. Alternatively, the piggyBac transposase is able perform all of the steps required for integration; therefore, cells confirmed to contain a single copy of a targeted transposon, for which its location is known, are likely to be devoid of aberrant genomic modifications. We aimed to retarget transposon insertions by comparing a series of novel hyperactive piggyBac constructs tethered to a custom transcription activator like effector DNA-binding domain designed to bind the first intron of the human CCR5 gene. Multiple targeting strategies were evaluated using combinations of both plasmid-DNA and transposase-protein relocalization to the target sequence. We demonstrated user-defined directed transposition to the CCR5 genomic safe harbor and isolated single-copy clones harboring targeted integrations

    Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms

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    Aim: Skeletal muscle nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. Results: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1−/− muscle. Functional analyses of GC1−/− muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA–IIX fiber balance. Force deficits in GC1−/− muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. Innovation: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. Conclusions: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency

    Three very young HgMn stars in the Orion OB1 Association

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    We report the detection of three mercury-manganese stars in the Orion OB1 association. HD 37886 and BD-0 984 are in the approximately 1.7 million year old Orion OB1b. HD 37492 is in the approximately 4.6 million year old Orion OB1c. Orion OB1b is now the youngest cluster with known HgMn star members. This places an observational upper limit on the time scale needed to produce the chemical peculiarities seen in mercury-manganese stars, which should help in the search for the cause or causes of the peculiar abundances in HgMn and other chemically peculiar upper main sequence stars.Comment: 8 pages including 1 figure. To appear in Astrophysical Journal Letter

    Concussion-reporting behavior in rugby: A national survey of rugby union players in the United States

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    Background: Rugby is the fastest growing team sport in the United States for male and female athletes. It is a contact/collision sport with an injury risk profile that includes concussions. Purpose: To examine the prevalence of concussions in male and female rugby players in the United States and to characterize behaviors around reporting concussions that could be a target for prevention and treatment efforts. Study Design: Cross-sectional study; Level of evidence, 3. Methods: An online survey distributed to active members on the USA Rugby membership list was used to examine self-reported concussions in male and female athletes. Concussion-reporting behaviors and return to play after a concussion were also explored. Statistical analysis was used to compare male with female athletes and report differences, with years of experience as a dependent variable. Results: The proportion of athletes with a history of at least 1 concussion was 61.9% in all respondents. Of those who reported a concussion, 50.8% reported the concussion during the game or practice in which it occurred, and 57.6% reported at least 1 concussion to a qualified medical provider. Overall, 27.7% of participants who reported ≥1 rugby-related concussion in our survey noted that at least 1 of these concussions was not formally reported. The most commonly cited reasons for not reporting a concussion included not thinking that it was a serious injury, not knowing that it was a concussion at the time, and not wanting to be pulled out of the game or practice. Additionally, 61.0% of athletes did not engage in recommended return-to-play protocols after their most recent rugby-related concussion. Conclusion: US rugby union athletes may not report concussions to medical personnel or follow return-to-play protocols guided by medical advice. This could result from a lack of education on concussion recognition and the risks associated with continued play after a concussion as well as limited access to health care. Further education efforts focusing on the identification of concussions, removal from play, and return-to-play protocols are necessary in the US rugby union population

    Electron-Spin Filters Based on the Rashba Effect

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    Semiconductor electron-spin filters of a proposed type would be based on the Rashba effect, which is described briefly below. Electron-spin filters more precisely, sources of spin-polarized electron currents have been sought for research on, and development of, the emerging technological discipline of spintronics (spin-based electronics). There have been a number of successful demonstrations of injection of spin-polarized electrons from diluted magnetic semiconductors and from ferromagnetic metals into nonmagnetic semiconductors. In contrast, a device according to the proposal would be made from nonmagnetic semiconductor materials and would function without an applied magnetic field. The Rashba effect, named after one of its discoverers, is an energy splitting, of what would otherwise be degenerate quantum states, caused by a spin-orbit interaction in conjunction with a structural-inversion asymmetry in the presence of interfacial electric fields in a semiconductor heterostructure. The magnitude of the energy split is proportional to the electron wave number. The present proposal evolved from recent theoretical studies that suggested the possibility of devices in which electron energy states would be split by the Rashba effect and spin-polarized currents would be extracted by resonant quantum-mechanical tunneling. Accordingly, a device according to the proposal would be denoted an asymmetric resonant interband tunneling diode [a-RITD]. An a-RITD could be implemented in a variety of forms, the form favored in the proposal being a double-barrier heterostructure containing an asymmetric quantum well. It is envisioned that a-RITDs would be designed and fabricated in the InAs/GaSb/AlSb material system for several reasons: Heterostructures in this material system are strong candidates for pronounced Rashba spin splitting because InAs and GaSb exhibit large spin-orbit interactions and because both InAs and GaSb would be available for the construction of highly asymmetric quantum wells. This mate-rial system affords a variety of energy-band alignments that can be exploited to obtain resonant tunneling and other desired effects. The no-common-atom InAs/GaSb and InAs/AlSb interfaces would present opportunities for engineering interface potentials for optimizing Rashba spin splitting
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