3,837 research outputs found
Collecting Duct Carcinoma With Cardiac Metastases: A Case Report & Literature Review
AbstractCollecting duct carcinoma (CDC), is a rare and aggressive form of renal cell carcinoma (RCC) accounting for around 1% of all renal malignancy. It affects younger patients and is associated with rapid progression, distant spread and poor prognosis. Cardiac metastases from all types of RCC, without involvement of the inferior vena cava are very rare. We present the case of a 54 year old man with a history of CDC, who presents with collapse and ventricular tachycardia secondary to multifocal cardiac metastases. We are not aware of any other reports in the literature of CDC and cardiac metastases
Redução da absorção de cobre e manganês em solução, por trigo infectado com Pseudomonas sp.
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Previous issue date: 1998-08-1
Didelphid marsupial genus Thylamys.
67 p. : ill. (1 col.), maps (some col.) ; 26 cm.
"Issued December 16, 2010."Species of the didelphid marsupial genus Thylamys, commonly known as fat-tailed mouse opossums, are broadly distributed in the open habitats of central and southern South America. In this report we examine species limits in the genus and infer phylogenetic relationships among Thylamys species using both molecular phylogenetic and morphological methods. We assessed species limits using a broad geographic sample of DNA sequences from the mitochondrial gene cytochrome b in conjunction with morphological character analysis, and we inferred phylogenetic relationships among species using the cytochrome-b dataset in addition to sequences from the mitochondrial genes cytochrome c oxidase subunit II and NADH dehydrogenase 2 for a representative subset of individuals. Based on the results of these analyses, we recognize Xerodelphys (new subgenus) for T. karimii and T. velutinus, and we recognize seven valid species in the nominotypical subgenus. The latter includes T. macrurus, T. pusillus, and two monophyletic species groups: the Elegans Group (T. elegans, T. pallidior, T. tatei) and the Venustus Group (T. sponsorius, T. venustus). Analysis of cytochrome-b sequences additionally reveals deep phylogeographic structuring in three species (T. pallidior, T. pusillus, T. venustus), each of which contains two or three robustly supported allopatric haplogroups. The existence of undescribed Peruvian forms of the Elegans Group is also plausibly indicated. We provide morphological diagnoses of all species recognized as valid in this report, summarize information about geographic distributions, comment on previous misidentifications, and briefly consider historical-biogeographic scenarios with a focus on dispersal events across the Andes
An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.
Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells
Organizational Mortality of Small Firms: The Effects of Entrepreneurial Age and Human Capital
This paper addresses the issue of internal determination of organizational outcomes. It is argued that in small and simply structured organizations a considerable proportion of the variance in organizational activities and outcomes is associated with individuals. In particular, the paper uses human capital theory to derive hypotheses about individual determinants of organizational mortality. These hypotheses are tested with event-history data of firm registrations and de-registrations in a West German region. The hypotheses are corroborated by the data, but the effects may nonetheless be due to processes linking individual characteristics with organizational performance other than those suggested by the human capital approach
Crossover from thermal hopping to quantum tunneling in Mn_{12}Ac
The crossover from thermal hopping to quantum tunneling is studied. We show
that the decay rate with dissipation can accurately be determined near
the crossover temperature. Besides considering the Wentzel-Kramers-Brillouin
(WKB) exponent, we also calculate contribution of the fluctuation modes around
the saddle point and give an extended account of a previous study of crossover
region. We deal with two dangerous fluctuation modes whose contribution can't
be calculated by the steepest descent method and show that higher order
couplings between the two dangerous modes need to be taken into considerations.
At last the crossover from thermal hopping to quantum tunneling in the
molecular magnet Mn_{12}Ac is studied.Comment: 10 pages, 3 figure
Model validation for a noninvasive arterial stenosis detection problem
Copyright @ 2013 American Institute of Mathematical SciencesA current thrust in medical research is the development of a non-invasive method for detection, localization, and characterization of an arterial stenosis (a blockage or partial blockage in an artery). A method has been proposed to detect shear waves in the chest cavity which have been generated by disturbances in the blood flow resulting from a stenosis. In order to develop this methodology further, we use both one-dimensional pressure and shear wave experimental data from novel acoustic phantoms to validate corresponding viscoelastic mathematical models, which were developed in a concept paper [8] and refined herein. We estimate model parameters which give a good fit (in a sense to be precisely defined) to the experimental data, and use asymptotic error theory to provide confidence intervals for parameter estimates. Finally, since a robust error model is necessary for accurate parameter estimates and confidence analysis, we include a comparison of absolute and relative models for measurement error.The National Institute of Allergy and Infectious Diseases, the Air Force Office of Scientific Research, the Deopartment of Education and the Engineering and Physical Sciences Research Council (EPSRC)
The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus
IntroductionMany autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.MethodsWe blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigated in vitro and in autoreactive mixed bone marrow chimeras.ResultsGC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output. In vitro, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenario in vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output.DiscussionWe identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection
Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults
Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction
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