101 research outputs found

    Remaining Silent in Indian Country: Self-Incrimination and Grants of Immunity for Tribal Court Defendants

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    A defendant in state and federal courts is entitled to a constitutional protection against self-incrimination. The Fifth Amendment establishes this privilege, which can only be overcome through a voluntary waiver or by the granting of an appropriate level of immunity. Those grants of immunity were made mutually binding on the state and federal governments in Kastigar v. United States and Murphy v. Waterfront Commission of New York Harbor. However, in Talton v. Mayes, the U.S. Supreme Court held that the Fifth and Fourteenth Amendments do not limit the conduct of the more than 560 federally recognized Indian tribes within the boundaries of the United States. In response, Congress exercised its plenary power and passed the Indian Civil Rights Act (ICRA). Under federal law, ICRA extended many, but not all, protections afforded under the Bill of Rights to tribal defendants without any required action from the tribes; many of the provisions are verbatim from the Constitution’s amendments. However, the complicated distribution of jurisdiction amongst sovereigns, as well as the tribal authority to create and implement unique constitutions and systems of justice, calls into question the standard by which to evaluate violations of the privilege against self-incrimination in tribal court. Furthermore, rare examples exist in which a court of any jurisdiction has considered or extended the mutually binding nature of grants of immunity and the use of testimony compelled by a separate jurisdiction to include tribal courts. This Comment suggests that violations of ICRA’s protections against self-incrimination be evaluated under a Fifth Amendment standard, utilizing U.S. Supreme Court precedent. This approach ensures a predictable analysis that is consistent with the legislative intent of ICRA and minimizes potential complications upon federal habeas review. This Comment further suggests that the universal application of Fifth Amendment precedent is a prerequisite for mutual and binding recognition of tribal, state, and federal grants of immunity. Mutual recognition places tribal courts on equal footing with state and federal courts. Further, a defendant facing prosecution in two or more courts exercising concurrent jurisdiction benefits when courts extend and recognize binding grants of immunity. Lastly, when grants of immunity apply in each jurisdiction, tribal courts and communities are empowered to pursue avenues of justice unique to tribal traditions and culture

    Cancer cachexia

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    In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome

    Reconstitution of Nup157 and Nup145N into the Nup84 Complex

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    About 30 different nucleoporins (Nups) constitute the nuclear pore complex. We have affinity-purified 28 of these nuclear pore proteins and identified new nucleoporin interactions by this analysis. We found that Nup157 and Nup170, two members of the large structural Nups, and the Gly-Leu-Phe-Gly nucleoporin Nup145N specifically co-purified with members of the Nup84 complex. In addition, Nup145N co-enriched during Nup157 purification. By in vitro reconstitution, we demonstrate that Nup157 and Nup145N form a nucleoporin subcomplex. Moreover, we show that Nup157 and Nup145N bind to the heptameric Nup84 complex. This assembly thus represents approximately one-third of all nucleoporins. To characterize Nup157 structurally, we purified and analyzed it by electron microscopy. Nup157 is a hollow sphere that resembles a clamp or a gripping hand. Thus, we could reconstitute an interaction between a large structural Nup, an FG repeat Nup, and a major structural module of the nuclear pore complex

    LuFo V-3 CORINNE - Schlussbericht Comfort Of Ride Improved eNgiNEering -Komfortverbesserung im niederfrequenten Bereich fĂŒr Hubschrauber

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    Hubschrauberpiloten sind auch in aktuellen Hubschraubermustern einem hohen Vibrationsniveau ausgesetzt. Diese Vibrationen können negative Auswirkungen auf die Gesundheit und die LeistungsfĂ€higkeit der Hubschrauberbesatzung und der Passagiere haben. Insbesondere Schwingungen im niederfrequenten Bereich standen dabei im Fokus des Verbundprojekts CORINNE. Diese Vibrationen werden u.a. durch Turbulenz angeregt und wirken verstĂ€rkt durch Flugregelungssysteme und Autopiloten auf die flugmechanischen Moden des Hubschraubers. Im DLR-Beitrag von CORINNE wurde hauptsĂ€chlich an drei Teilaspekten zur Reduzierung der niederfrequenten Vibrationen geforscht. Erstens wurde ein Turbulenzmodell fĂŒr den Forschungshubschrauber ACT/FHS auf Basis von Flugversuchsdaten erstellt und validiert. Dieses sog. CETI-Modell wurde auch auf andere Hubschraubermuster skaliert. ZusĂ€tzlich ist es im ACT/FHS und AVES Simulator verfĂŒgbar, um Turbulenz zu simulieren. Zweitens wurde das Simulationsverfahren UPM in das Hubschraubersimulationsmodell von Airbus Helicopters integriert und validiert. Mit diesem Simulationsverfahren können flugmechanische StabilitĂ€tseigenschaften wie die der Phygoide und des Dutch Rolls genauer vorhersagt und die SimulationsgĂŒte im Manöverflug gesteigert werden. Drittens wurde ein Beobachter fĂŒr die longitudinalen und lateralen Rotormastmomente des ACT/FHS auf Basis von Flugversuchsdaten entwickelt. Der Beobachter benötigt dabei lediglich MessgrĂ¶ĂŸen aus dem stehenden Hubschraubersystem, welche auch auf Serienhubschraubern verfĂŒgbar sind. Durch die Integration des Beobachters in die Flugregelung soll der Komfort in turbulenter Luft gesteigert werden

    ANALISIS BANJIR RANCANGAN DENGAN METODE HSS NAKAYASU PADA BENDUNGAN GINTUNG

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    Jebolnya Situ Gintung merupakan akibat dari perubahan debit banjir yang terus bertambah. Hal tersebut perlu diana/isis terhadap debit banjir rancangan yang selanjutnya dapat digunakan untuk merencanakan Bendungan Gintung yang baru. Berdasarkan permasalahan di atas, maka perlu dikembangkan perhitungan banjir rancangan dengan metode HSS Nakayasu. Perhitungan dengan menggunaan data hujan. Pada penelitian ini digunakan 18 Pos stasiun penangkar hujan yang diseleksi menurut kelayakan data menjadi 9 pos stasiun hujan dengan memasukan nilai hujan harian maksimum tahunan. Data curah hujan yang disaring memilki tingkat kepercayaan yang rendah, namun masih masuk ke dalam data aman. Dalam penentuan debit banjir rencana terlebih dahulu dilakukan ana/isa frekuensi dan penetapan sebaran data curah hujan kemudian diuji dengan chi-kuadrat. Distribusi yang sesuai adalah distribusi Log Pearson Type III. Dari hasil ana/isa debit banjir rancangan, untuk merencanakan bendungan digunakan debit banjir kala ulang Ql000 = 289,348 m3/dt

    A gene signature derived from the loss of cdkn1a (P21) is associated with CMS4 colorectal cancer

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    The epithelial–mesenchymal transition (EMT) is associated with tumor aggressiveness and increased invasion, migration, metastasis, angiogenesis, and drug resistance. Although the HCT116 p21-/- cell line is well known for its EMT-associated phenotype, with high Vimentin and low E-cadherin protein levels, the gene signature of this rather intermediate EMT-like cell line has not been determined so far. In this work, we present a robust molecular and bioinformatics analysis, to reveal the associated gene expression profile and its correlation with different types of colorectal cancer tumors. We compared the quantitative signature obtained with the NanoString platform with the expression profiles of colorectal cancer (CRC) Consensus Molecular Subtypes (CMS) as identified, and validated the results in a large independent cohort of human tumor samples. The expression signature derived from the p21-/- cells showed consistent and reliable numbers of upregulated and downregulated genes, as evaluated with two machine learning methods against the four CRC subtypes (i.e., CMS1, 2, 3, and 4). High concordance was found between the upregulated gene signature of HCT116 p21-/- cells and the signature of the CMS4 mesenchymal subtype. At the same time, the upregulated gene signature of the native HCT116 cells was similar to that of CMS1. Using a multivariate Cox regression model to analyze the survival data in the CRC tumor cohort, we selected genes that have a predictive risk power (with a significant gene risk incidence score). A set of genes of the mesenchymal signature was proven to be significantly associated with poor survival, specifically in the CMS4 CRC human cohort. We suggest that the gene signature of HCT116 p21-/- cells could be a suitable metric for mechanistic studies regarding the CMS4 signature and its functional consequences in CRC. Moreover, this model could help to discover the molecular mechanisms of intermediate EMT, which is known to be associated with extraordinarily high stemness and drug resistance.R.S.-S. was supported by the Emerging Fields Initiative ‘Cell Cycle in Disease and Regeneration’ (CYDER) of the Friedrich Alexander University (Erlangen-NĂŒrnberg, Germany). This article is partly based upon work from COST Action CA17118 TRANSCOLONCAN, supported by COST (European Cooperation in Science and Technology, www.cost.eu, last accessed 20 December 2021). The JDLR research group is supported by the Spanish Government, Instituto de Salud Carlos III (ISCiii, AES project PI18/00591) co-funded by FEDER/ERDF (European Regional Development Fund)

    An overview of DLR compound rotorcraft aerodynamics and aeroacoustics activities within the CleanSky2 NACOR Project

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    The challenge of increasing range and speed of a rotorcraft is encountered in the scope of the European CleanSky2 “Fast Rotorcraft” project by Airbus Helicopters with the compound helicopter design RACER (RapidAndCostEfficientRotorcraft) for which the box wing and the tail parts designs are respectively protected by patent. This paper presents the DLR contributions to the RACER development. This includes the aerodynamic design of the wing and tail section as well as an overall assessment of performance and noise. In a first step the aerodynamic properties of the configuration are evaluated both isolated and with consideration of the main rotor and lateral rotor interferences by the use of actuator discs. In the second step, the investigated possibilities to improve the configurations performance are described. These include airfoil design for improved high lift performance of the wing and tail section, an optimization of the box wing circulation distribution on the upper and lower wing. Additionally, the intersection fairings were improved and the efficiency of the trim flaps was evaluated. In this regard, it could be determined for which cases an isolated approach is appropriate and when the rotor interference should be considered. At the end the evaluation of the aero acoustics of the configuration is conducted. The applied configuration shows good aerodynamic characteristics with some further cruise and off design optimization potential

    Probing the nucleoporin FG repeat network defines structural and functional features of the nuclear pore complex

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    A new tool to probe the FG repeat network of the nuclear pore complex transport channel in vivo provides insight into the organization and functional features of the channel

    A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models

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    van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD
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