Impulsivity Relates to Relative Preservation of Mesolimbic Connectivity in Patients with Parkinson Disease.

IntroductionThe relationship between Parkinson Disease (PD) pathology, dopamine replacement therapy (DRT), and impulse control disorder (ICD) development is still incompletely understood. Given the sensorimotor-lateral substantia nigra (SN) selective degeneration associated with PD, we posit that a relative sparing of the limbic-medial SN in the context of DRT drives impulsive, reward-seeking behavior in PD patients with recent history of severe impulsivity.MethodsImpulsive and control participants were selected from a consecutive list of PD patients receiving pre-operative deep brain stimulation (DBS) planning scans including 3T structural MRI and 64 direction diffusion tensor imaging (DTI). Using previously identified substantia nigra (SN) subsegment network connectivity profiles to develop classification targets, split-hemisphere target-based SN segmentation with probabilistic tractography was performed. The relative subsegment volumes and strength of connectivity between the SN and the limbic, associative, and motor network targets were compared.ResultsOur results show that there is greater probability of connectivity between the SN and limbic network targets relative to motor and associative network targets in PD patients with recent history of severe impulsivity as compared to PD patients without impulsivity (P = 0.0075). We did not observe relative volumetric subsegment differences across groups.ConclusionFirstly, our results suggest that fine-grained, atlas-derived classification targets may be used in PD to parcellate and classify functionally distinct subsegments of the SN, with the apparent preservation of previously reported topographical limbic-medial SN, associative-ventral SN, and sensorimotor-lateral SN orientation. We suggest that relative, as opposed to absolute, degeneration amongst SN-associated dopaminergic networks relates to the impulsivity phenotype in PD

“A growing excitement that ‘something was happening’”: A Rhetorical History of Gay Liberation and Socialist Feminism in the New American Movement between 1970 and 1980

This project charts a rhetorical history of the New American Movement’s (NAM) organizational debates on gay liberation and socialist feminism between 1970 and 1980. NAM was a socialist feminist organization active across the 1970s in the United States that sought to create a mass movement through a conception of a particularly “American Socialism.” Through a periodization of NAM’s archival history, I highlight how NAM members were able to work in coalition with a wide range of individuals and groups both within and outside of the organization to build a socialist feminist conception of gay liberation. Drawing on original archival research performed at four archives in the United States in collections of speeches, internal memos, personal and organizational correspondence, newsletters, and discussion notes, I argue that NAM’s adoption of a socialist feminist approach to gay liberation augments “siloed” rhetorical approaches to social movements in the 1970s in as much as NAM members, as well as their theories and practice, worked out of, within, and with autonomous liberation movements. This project also intervenes in histories of gay liberation, feminism, and socialism in the 1970s by centering NAM’s, largely unaddressed in scholarship, work which challenges the seemingly stable lines between each movement

The guanine nucleotide exchanger Vav2 interacts with c-ErbB-2 and induces alveolar morphogenesis of mammary epithelial cells

Die Familie der ErbB-Rezeptor-Tyrosinkinasen besteht aus vier Mitgliedern, dem EGF-Rezeptor (ErbB-1), ErbB-2, ErbB-3 und ErbB-4. ErbB-Rezeptoren spielen eine wichtige Rolle bei der Entwicklung des Nervensystems, des Herzens und der Brustdrüsen. Ein Teil dieser Differenzierungsvorgänge läßt sich in vitro nachvollziehen: so ist zum Beispiel die Aktivierung des ErbB-2 Rezeptors ausreichend für alveoläre Morphogenese der Brustdrüsenepithelzellinie EpH4. Intrazelluläre Moleküle, die dieses ErbB2-Signal übertragen, sind allerdings noch unbekannt. Mit Hilfe eines neuen, modifizierten Hefe-2-Hybrid-Systems wurde in der vorliegenden Arbeit Vav2 als neuer Interaktionspartner von ErbB-2 identifiziert. Vav2 assoziiert mit aktiviertem ErbB-2 über eine SH2-Domäne. Die Interaktion ist direkt und ist von zwei Phosphotyrosinen in ErbB-2 abhängig. Vav2 kann den GDP/GTP-Austausch bei GTPasen der Rho-Familie vermitteln. Dadurch kann der Umbau des Zytoskeletts und Veränderungen der Transkription sowie Zelltransformation induziert werden. In einem dreidimensionalen Zellkultursystem kann aktiviertes Vav2 in EpH4 Zellen die Bildung von alveolären Zellaggregaten induzieren. In diesen Alveolen umgibt eine Schicht polarisierter milchproduzierender Zellen ein zentrales Lumen. Diese Vav2-vermittelte Morphogenese ist abhängig von der katalytischen GDP/GTP-Austausch Aktivität von Vav2. Katalytisch-inaktives Vav2 kann die morphogenetische Aktivität von ErbB-2 in EpH4-Zellen verhindern, ohne die mitogene Aktivität von ErbB-2 zu beeinflussen. Vav2 ist mit ErbB-2 coexprimiert und interagiert mit dem Rezeptor in Brustdrüsenzellen schwangerer Mäuse. Diese Untersuchungen deuten darauf hin, dass Vav2 eine wichtige Funktion bei der durch ErbB-2 induzierten alveolären Morphogenese der Brustdrüse spielt.The ErbB receptor tyrosine kinases constitute a subfamily of four structurally related members, the EGF receptor (ErbB-1), ErbB-2, ErbB-3 and ErbB-4. ErbB receptor tyrosine kinases are critical for embryonic development of central and peripheral neural structures and heart. In addition, ErbB receptors play an important role in the postnatal development of the mammary gland. Previous studies showed that activated ErbB-2 receptor induces alveolar morphogenesis of EpH4 mammary epithelial cells that are cultured on a three-dimensional matrix (termed Matrigel). However, the downstream signaling proteins that mediate this biological activity of ErbB-2 were unknown. In this work, Vav2 was identified as a direct interaction partner of tyrosine-phosphorylated ErbB receptors using the yeast two-hybrid system. Vav2 is a member of a family of guanine nucleotide exchange factors that induce cytoskeletal rearrangements, transcriptional alterations, and have oncogenic potential when activated. To test the ability of Vav2 to mediate morphogenic signals of ErbB-2, EpH4 cells overexpressing Vav2 protein were cultured on Matrigel. Indeed, Vav2 induces alveolar morphogenesis of EpH4 cells when activated either by oncogenic mutation or tyrosine phosphorylation by ErbB-2. The morphogenic activity of Vav2 requires the Dbl homology domain, which mediates GDP/GTP exchange. Dominant-negative Vav2 specifically blocks the morphogenic signals of ErbB-2 in EpH4 cells without interfering with ErbB2-induced mitogenesis. Importantly, Vav2 is co-expressed and interacts with ErbB-2 in the mammary glands of pregnant mice. Taken together, these results point to Vav2 as a candidate to mediate ErbB-2 signals for alveolar morphogenesis in vivo, which is a relevant step in the development of the mammary gland during pregnancy

Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization

Initiation of mineralization during endochondral ossification is a multistep process and has been assumed to correlate with specific interactions of annexins A5 and A6 and collagens. However, skeletal development appears to be normal in mice deficient for either A5 or A6, and the highly conserved structures led to the assumption that A5 and A6 may fulfill redundant functions. We have now generated mice deficient of both proteins. These mice were viable and fertile and showed no obvious abnormalities. Assessment of skeletal elements using histologic, ultrastructural, and peripheral quantitative computed tomographic methods revealed that mineralization and development of the skeleton were not significantly affected in mutant mice. Otherwise, global gene expression analysis showed subtle changes at the transcriptome level of genes involved in cell growth and intermediate metabolism. These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo

A Performance Guide To Prokofiev: Romeo And Juliet For Solo Tuba

As the most recent brass instrument to be added to the standard orchestra, the tuba’s solo repertoire is relatively new compared to other orchestral instruments. Ralph Vaughan Williams composed the first major concerto for tuba in 1954, over 100 years after the tuba’s creation in 1835 by Wilhelm Friedrich Wieprecht and Johann Gottfried Moritz. Though many composers — including Bruce Broughton, Eric Ewazen, Paul Hindemith, Gunther Schuller, and John Williams — have written solos for the tuba since Vaughan Williams, performers rely on arrangements and transcriptions of existing works to fill gaps in the repertoire. In 2011, Chicago Symphony Orchestra’s bass trombonist Charles Vernon arranged ten movements of Sergei Prokofiev’s ballet Romeo and Juliet for the Chicago Symphony Orchestra’s Principal Tuba, Gene Pokorny. Sergei Prokofiev is one of the most well-known composers of the 20th century. His works include concerti, chamber music, orchestral music, operas, and ballets; one of his most popular works is the ballet Romeo and Juliet, William Shakespeare’s timeless story of star-crossed lovers. He also used material from the ballet to create three orchestral suites. This performance guide serves as a detailed resource for Prokofiev’s Romeo and Juliet Suite No. 1, Op. 64, arranged for Tuba and Piano by Charles Vernon. There are many resources that provide historical details and context on the life and works of Sergei Prokofiev, but there are few performance guides for tuba solos, let alone transcriptions of his works. Though the breadth of literature on tuba solos is limited, what is available will be referenced as best as possible. This paper fills a gap in tuba performance guides and provides a needed resource for tubists. There have been transcriptions of Romeo and Juliet movements for other instruments, including trombone, piano, and viola, but no performance guide or literature can be found for tuba. Since Romeo and Juliet was written for orchestra, there are many things to consider when performing a transcription. The player should know what instrument the original melody was written for to inform musical decisions, what character is represented by the theme they are playing, and what drama is accompanying that movement. This arrangement is for solo tuba and piano, so important orchestral lines are played by the piano. This guide helps decipher when the “solo” voice has the melody and is playing a background role. There are also technical challenges since the piece was not originally written for the tuba. In addition to the analysis of the transcription itself, the tuba player will run into technically challenging aspects of the music. The included practice guide gives the tubist a path toward working through the difficulties with various methods, techniques, and practice tools to aid in learning the piece. The first resources referenced in this paper are books, dissertations, and articles related to the composer Sergei Prokofiev and his music. These are used for historical context and biographical context. These also provide information on his ballets, including Romeo and Juliet. Performance guides for other solos are also examined to illustrate past approaches and ideas. The second methodology predominately used in this paper are musical scores of the original orchestral parts to Romeo and Juliet and the Charles Vernon tuba solo. Scores of Prokofiev’s earlier works are also cited in order to understand how he usually wrote for the tuba in an orchestral setting. Analysis of the original ballet score alongside the Vernon arrangement provides important information for the performer on the similarities and differences between the two

Synergistic qualities of form and space

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System Response Time and User Satisfaction: An Experimental Study of Browser-based Applications

With rapid advances in hardware speed and data communication bandwidth, one might not expect to have to deal with issues such as response time and system performance. But these issues remain a very real concern today. Lengthy system response times may cause lower satisfaction and poor productivity among users. Lowered user satisfaction may lead to discontinued use of an application, especially in discretionary applications such as those found on the Internet. The intent of this experimental research is to (1) substantiate that slow system response time leads to dissatisfaction; (2) assess the point at which users may become dissatisfied with system response time; (3) determine a threshold at which dissatisfaction may lead to discontinued use of the application, and (4) determine if experience influences response time tolerance. The results showed that indeed satisfaction does decrease as response time increases. However, instant response was not perceived as making the system easier to use or learn. It also showed that for discretionary applications, there appears to be a level of intolerance in the 12-second response range

Women of Discord: Female Power in Aztec Thought

This article addresses the perennial debate over the origins and nature of female power by examining the significance of ‘Women of Discord’ in Aztec (more properly, Mexica) culture. Influential, but often troublesome, these formidable figures embody the complex significance of female power, rooted in women's privileged access to the awesome earth forces through childbirth. This chaotic energy lent cosmological and dynastic significance to the mytho-historical Women of Discord, but also led to a persistent female association with disorder which had tangible (and often overlooked) consequences for the lives of ‘real’ women in Aztec culture. This article explores the ways in which beliefs about the female capacity for disruption both reflected and shaped reality, ensnaring all women in a cycle of myth and history which made femininity a source of both authority and apprehension. Importantly, in Tenochtitlan ideas about ‘disorderly women’ did not lead inevitably to their practical subordination or suppression; women held practical markers of influence and esteem in Aztec culture. Thus, the Women of Discord challenge our assumptions about gender by offering a distinctive perspective on the ways in which femininity and fertility may be seen as disruptive, without necessarily debasing women or depriving them of individual agency

Effective RFID-based object tracking for manufacturing

International audienceAbstract Automated Identification and in particular, Radio Frequency Identification (RFID) promises to assist with the automation of mass customised production processes by simplifying the retrieval, tracking and usage of highly specialised components. RFID has long been used to gather a history or trace of object movements, but its use as an integral part of the automated control process is yet to be fully exploited. Such (automated) use places stringent demands on the quality of the sensor data collected and the method used to interpret that data. In particular, this paper focuses on the issue of correctly identifying, tracking and dealing with aggregated objects in customised production with the use of RFID. In particular, this work presents approaches for making best use of RFID data in this context. The presented approach is evaluated in the context of a laboratory manufacturing system that produces customised gift boxes