474 research outputs found
Neither Reasonable nor Remedial: The Hopeless Contradictions of the Legal Ethics Measures to Prevent Perjury
Analyzing the inherent conflict posed by the use of an undefined mandate-âreasonable remedial measuresâ-leads to analysis of the even deeper, unresolvable conflicts in the primary steps prescribed by commentary: the client\u27s narration of his own story, the lawyer\u27s withdrawal from representation, and the lawyer\u27s disclosure of the client\u27s false evidence. Not all of the reasonable remedial measures protect both the client\u27s confidentiality and the court\u27s insistence on honesty, and none of them protects the lawyer from charges of impropriety. In the face of the utter failure of the Model Rules to accomplish their conflicting goals, the ABA\u27s rules drafters should start over from the beginning with a clear-eyed view of which one goal is most important to them. They do not have to stay with the current failed regime. They could, instead, provide direct and defined rules that people of reasonable intelligence can understand and fulfill. Doing so is, at this point, the only way by which the ABA can maintain any credibility in its leadership position in the realm of legal ethics
A note on the existence of relative maxima and minima on phase velocity curves
Phase and group velocity dispersion curves for fundamental Rayleigh waves have been computed with more precision than previously attempted. The new curves show a relative minimum in phase velocity at periods near 50 sec for four perturbed Gutenberg continental models
Racial Dynamics in Counselor Training: The Racial Identity Social Interaction Model
Counselors frequently receive their initial training about the dynamics of race and culture in the counseling process in didactic group settings, such as multicultural courses and experiential skills-building labs. Whereas multicultural and diversity courses reportedly have been growth promoting for students, counselor educators describe several difficulties that arise as they attempt to teach these courses. Yet virtually no research has focused on examination of instructorsâ difficulties from a theoretical perspective. To examine the complex, intersecting dynamics that occur when teaching groups of counselor trainees about race and culture, we used Directed Content Analysis with theoretical guidance from the Racial Identity Social Interaction Model. We analyzed interviews obtained from instructors (n = 8) who had led small-group counseling skills labs with a multicultural and social justice perspective. Problematic dynamics occurred in three major domains, group, leader, and institutional dynamics. Implications for teaching about race and culture in group settings are discussed
Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium
Author Posting. © American Society for Clinical Investigation, 2006. This article is posted here by permission of American Society for Clinical Investigation for personal use, not for redistribution. The definitive version was published in Journal of Clinical Investigation 116 (2006): 1668-1674, doi:10.1172/JCI22466.Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP3R type 1 (InsP3R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.This work was supported by a grant from the NIH (GM63496 to B.E. Ehrlich), German National Merit Foundation scholarships (C. Schlecker and W. Boehmerle), and a National Kidney Foundation Fellowship (A. Varshney)
Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4
The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer
Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application
Background
The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A).
Results
The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yieldedâââ10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection.
Conclusions
E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin
Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium
Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al
Metastable Frenkel pair defect in graphite: source of Wigner energy?
The atomic processes associated with energy storage and release in irradiated graphite have long been subject to untested speculation. We examine structures and recombination routes for interstitial-vacancy (I-V) pairs in graphite. Interaction results in the formation of a new metastable defect (an intimate I-V pair) or a Stone-Wales defect. The intimate I-V pair, although 2.9 eV more stable than its isolated constituents, still has a formation energy of 10.8 eV. The barrier to recombination to perfect graphite is calculated to be 1.3 eV, consistent with the experimental first Wigner energy release peak at 1.38 eV. We expect similar defects to form in carbon nanostructures such as nanotubes, nested fullerenes, and onions under irradiation
Religious Education, Big Ideas and the study of religion(s) and worldview(s)
This is the author accepted manuscript. The final version is available from Taylor & Francis (Routledge) via the DOI in this record.This article outlines the âBig Ideasâ approach to curriculum reform, as applied in the âPrinciples and Big Ideas of Science Educationâ project (Harlen 2010). A critical analysis follows of the outcomes of the University of Exeterâs âIdentifying Principles and Big Ideas for Religious Educationâ project, which sought to apply the same approach to Religious Education (RE) in English schools (Wintersgill 2017). This project made great headway in generating âBig Ideasâ to inform and improve the selection and sequencing of RE curriculum content. However, its primary focus on subject content knowledge mean that âBig Ideasâ about epistemology and methodology are lacking. The article recommends an additional focus on multi-disciplinary, multi-methodological, inquiry-based, reflexive learning, which would ask why, how, where and by whom our âknowledgeâ of religion(s) and worldview(s) is generated. In this regard, the article posits four âBig Ideas about the study of religion(s) and worldview(s)â to highlight the symbiotic relationship between knowledge and knower, and to reject the false dichotomy between the object of study and method of study. In so doing, it draws upon the theoretical framework underpinning the âRE-searchers approachâ to primary school RE, which correspondingly exemplifies how such ideas can be taught in practice.The âIdentifying Principles and Big Ideas for Religious Educationâ project was supported by the St Lukeâs College Foundation (016J-086). The âRE-searchers: A critical dialogic approach to Religious Education in primary schoolsâ project was supported by the Culham St. Gabrielâs Trust and Hockerill Education Foundation
Photodesorption of ices I: CO, N2 and CO2
A longstanding problem in astrochemistry is how molecules can be maintained
in the gas phase in dense inter- and circumstellar regions. Photodesorption is
a non-thermal desorption mechanism, which may explain the small amounts of
observed cold gas in cloud cores and disk mid-planes. This paper aims to
determine the UV photodesorption yields and to constrain the photodesorption
mechanisms of three astrochemically relevant ices: CO, N2 and CO2. In addition,
the possibility of co-desorption in mixed and layered CO:N2 ices is explored.
The ice photodesorption is studied experimentally under ultra high vacuum
conditions and at 15-60 K using a hydrogen discharge lamp (7-10.5 eV). The ice
desorption during irradiation is monitored by reflection absorption infrared
spectroscopy of the ice and simultaneous mass spectrometry of the desorbed
molecules. Both the UV photodesorption yields per incident photon and the
photodesorption mechanisms are molecule specific. CO photodesorbs without
dissociation from the surface layer of the ice. N2, which lacks an electronic
transition in this wavelength range, has a photodesorption yield that is more
than an order of magnitude lower. This yield increases significantly due to
co-desorption when N2 is mixed in with or layered on top of CO ice. CO2
photodesorbs through dissociation and subsequent recombination from the top 10
layers of the ice. At low temperatures (15-18 K) the derived photodesorption
yields are 2.7x10^-3 and <2x10^-4 molecules photon-1 for pure CO and N2,
respectively. The CO2 photodesorption yield is 1.2x10^-3x(1-e^(-X/2.9)) +
1.1x10^-3x(1-e^(-X/4.6)) molecules photon-1, where X is the ice thickness in
monolayers and the two parts of the expression represent a CO2 and CO
photodesorption pathway.Comment: Accepted by A&A; the new version contains additional figures and text
at the referee's reques
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