1,204 research outputs found
The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease
MicroRNAs (miRNAs) are implicated in the differentiation and function of many cell types. We provide genetic and in vivo evidence that the two RNaseIII enzymes, Drosha and Dicer, do indeed function in the same pathway. These have previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C. Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and V.N. Kim. 2003. Nature. 425:415â419), and genetic ablation of either within the T cell compartment, or specifically within Foxp3+ regulatory T (T reg) cells, results in identical phenotypes. We found that miRNA biogenesis is indispensable for the function of T reg cells. Specific deletion of either Drosha or Dicer phenocopies mice lacking a functional Foxp3 gene or Foxp3+ cells, whereas deletion throughout the T cell compartment also results in spontaneous inflammatory disease, but later in life. Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity
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Bioactive secondary metabolites with multiple activities from a fungal endophyte
In order to replace particularly biohazardous nematocides, there is a strong drive to finding natural product-based alternatives with the aim of containing nematode pests in agriculture. The metabolites produced by the fungal endophyte Fusarium oxysporum 162 when cultivated on rice media were isolated and their structures elucidated. Eleven compounds were obtained, of which six were isolated from a Fusarium spp. for the first time. The three most potent nematode-antagonistic compounds, 4-hydroxybenzoic acid, indole-3-acetic acid (IAA) and gibepyrone D had LC50 values of 104, 117 and 134 Όg mlâ1, respectively, after 72 h. IAA is a well-known phytohormone that plays a role in triggering plant resistance, thus suggesting a dual activity, either directly, by killing or compromising nematodes, or indirectly, by inducing defence mechanisms against pathogens (nematodes) in plants. Such compounds may serve as important leads in the development of novel, environmental friendly, nematocides
Ball on a beam: stabilization under saturated input control with large basin of attraction
This article is devoted to the stabilization of two underactuated planar
systems, the well-known straight beam-and-ball system and an original circular
beam-and-ball system. The feedback control for each system is designed, using
the Jordan form of its model, linearized near the unstable equilibrium. The
limits on the voltage, fed to the motor, are taken into account explicitly. The
straight beam-and-ball system has one unstable mode in the motion near the
equilibrium point. The proposed control law ensures that the basin of
attraction coincides with the controllability domain. The circular
beam-and-ball system has two unstable modes near the equilibrium point.
Therefore, this device, never considered in the past, is much more difficult to
control than the straight beam-and-ball system. The main contribution is to
propose a simple new control law, which ensures by adjusting its gain
parameters that the basin of attraction arbitrarily can approach the
controllability domain for the linear case. For both nonlinear systems,
simulation results are presented to illustrate the efficiency of the designed
nonlinear control laws and to determine the basin of attraction
A novel method to perform morphological measurements on three-dimensional (3D) models of the calcaneus based on computed tomography (CT)-imaging
Background: While current preoperative and postoperative assessment of the fractured and surgically reconstructed calcaneus relies on computed tomography (CT)-imaging, there are no established methods to quantify calcaneus morphology on CT-images. This study aims to develop a semi-automated method for morphological measurements of the calcaneus on three-dimensional (3D) models derived from CT-imaging. Methods: Using CT data, 3D models were created from healthy, fractured, and surgically reconstructed calcanei. Böhler's angle (BA) and Critical angle of Gissane (CAG) were measured on conventional lateral radiographs and corresponding 3D CT reconstructions using a novel point-based method with semiautomatic landmark placement by three observers. Intraobserver and interobserver reliability scores were calculated using intra-class correlation coefficient (ICC). In addition, consensus among observers was calculated for a maximal allowable discrepancy of 5 and 10 degrees for both methods. Results: Imaging data from 119 feet were obtained (40 healthy, 39 fractured, 40 reconstructed). Semiautomated measurements on 3D models of BA and CAG showed excellent reliability (ICC: 0.87-1.00). The manual measurements on conventional radiographs had a poor-to-excellent reliability (ICC: 0.22-0.96). In addition, the percentage of consensus among observers was much higher for the 3D method when compared to conventional two-dimensional (2D) measurements. Conclusions: The proposed method enables reliable and reproducible quantification of calcaneus morphology in 3D models of healthy, fractured and reconstructed calcanei.</p
A novel method to perform morphological measurements on three-dimensional (3D) models of the calcaneus based on computed tomography (CT)-imaging
Background: While current preoperative and postoperative assessment of the fractured and surgically reconstructed calcaneus relies on computed tomography (CT)-imaging, there are no established methods to quantify calcaneus morphology on CT-images. This study aims to develop a semi-automated method for morphological measurements of the calcaneus on three-dimensional (3D) models derived from CT-imaging. Methods: Using CT data, 3D models were created from healthy, fractured, and surgically reconstructed calcanei. Böhler's angle (BA) and Critical angle of Gissane (CAG) were measured on conventional lateral radiographs and corresponding 3D CT reconstructions using a novel point-based method with semiautomatic landmark placement by three observers. Intraobserver and interobserver reliability scores were calculated using intra-class correlation coefficient (ICC). In addition, consensus among observers was calculated for a maximal allowable discrepancy of 5 and 10 degrees for both methods. Results: Imaging data from 119 feet were obtained (40 healthy, 39 fractured, 40 reconstructed). Semiautomated measurements on 3D models of BA and CAG showed excellent reliability (ICC: 0.87-1.00). The manual measurements on conventional radiographs had a poor-to-excellent reliability (ICC: 0.22-0.96). In addition, the percentage of consensus among observers was much higher for the 3D method when compared to conventional two-dimensional (2D) measurements. Conclusions: The proposed method enables reliable and reproducible quantification of calcaneus morphology in 3D models of healthy, fractured and reconstructed calcanei.</p
Noise parametric identification and whitening for LIGO 40-meter interferometer data
We report the analysis we made on data taken by Caltech 40-meter prototype
interferometer to identify the noise power spectral density and to whiten the
sequence of noise. We concentrate our study on data taken in November 1994, in
particular we analyzed two frames of data: the 18nov94.2.frame and the
19nov94.2.frame.
We show that it is possible to whiten these data, to a good degree of
whiteness, using a high order whitening filter. Moreover we can choose to
whiten only restricted band of frequencies around the region we are interested
in, obtaining a higher level of whiteness.Comment: 11 pages, 15 figures, accepted for publication by Physical Review
A glassy contribution to the heat capacity of hcp He solids
We model the low-temperature specific heat of solid He in the hexagonal
closed packed structure by invoking two-level tunneling states in addition to
the usual phonon contribution of a Debye crystal for temperatures far below the
Debye temperature, . By introducing a cutoff energy in the
two-level tunneling density of states, we can describe the excess specific heat
observed in solid hcp He, as well as the low-temperature linear term in the
specific heat. Agreement is found with recent measurements of the temperature
behavior of both specific heat and pressure. These results suggest the presence
of a very small fraction, at the parts-per-million (ppm) level, of two-level
tunneling systems in solid He, irrespective of the existence of
supersolidity.Comment: 11 pages, 4 figure
Isolated limb perfusion for local gene delivery: efficient and targeted adenovirus-mediated gene transfer into soft tissue sarcomas
OBJECTIVE: To evaluate the potential of isolated limb perfusion (ILP) for
efficient and tumor-specific adenovirus-mediated gene transfer in
sarcoma-bearing rats. SUMMARY BACKGROUND DATA: A major concern in
adenovirus-mediated gene therapy in cancer is the transfer of genes to
organs other than the tumor, especially organs with a rapid cell turnover.
Adjustment of the vector delivery route might be an option creating tumor
specificity in therapeutic gene expression. METHODS: Rat hind limb
sarcomas (5-10 mm) were transfected with recombinant adenoviruses.
Intratumoral luciferase expression after ILP was compared with systemic
administration, regional infusion, or intratumoral injection using a
similar dose of adenoviruses carrying the luciferase marker gene.
Localization studies using lacZ as a marker gene were performed to
evaluate the intratumoral distribution of transfected cells after both ILP
and intratumoral injection. RESULTS: Intratumoral luciferase activity
after ILP or intratumoral administration was significantly higher compared
with regional infusion or systemic administration. After ILP, luciferase
gene expression was minimal in extratumoral organs, whether outside or
inside the isolated circuit. Localization studies demonstrated that
transfection was confined to tumor cells lying along the needle track
after intratumoral injection, whereas after ILP, lacZ expression was found
in viable tumor cells and in the tumor-associated vasculature.
CONCLUSIONS: Using ILP, efficient and tumor-specific gene transfection can
be achieved. The ILP technique might be useful for the delivery of
recombinant adenoviruses carrying therapeutic gene constructs to enhance
tumor control
Improved neonatal brain MRI segmentation by interpolation of motion corrupted slices
BACKGROUND AND PURPOSE: To apply and evaluate an intensityâbased interpolation technique, enabling segmentation of motionâaffected neonatal brain MRI. METHODS: Moderateâlate preterm infants were enrolled in a prospective cohort study (Brain Imaging in Moderateâlate Preterm infants âBIMPâstudyâ) between August 2017 and November 2019. T2âweighted MRI was performed around term equivalent age on a 3T MRI. Scans without motion (n = 27 [24%], control group) and with moderateâsevere motion (n = 33 [29%]) were included. Motionâaffected slices were reâestimated using intensityâbased shapeâpreserving cubic spline interpolation, and automatically segmented in eight structures. Quality of interpolation and segmentation was visually assessed for errors after interpolation. Reliability was tested using interpolated control group scans (18/54 axial slices). Structural similarity index (SSIM) was used to compare T2âweighted scans, and SĂžrensenâDice was used to compare segmentation before and after interpolation. Finally, volumes of brain structures of the control group were used assessing sensitivity (absolute mean fraction difference) and bias (confidence interval of mean difference). RESULTS: Visually, segmentation of 25 scans (22%) with motion artifacts improved with interpolation, while segmentation of eight scans (7%) with adjacent motionâaffected slices did not improve. Average SSIM was .895 and SĂžrensenâDice coefficients ranged between .87 and .97. Absolute mean fraction difference was â€0.17 for less than or equal to five interpolated slices. Confidence intervals revealed a small bias for cortical gray matter (0.14â3.07 cm(3)), cerebrospinal fluid (0.39â1.65 cm(3)), deep gray matter (0.74â1.01 cm(3)), and brainstem volumes (0.07â0.28 cm(3)) and a negative bias in white matter volumes (â4.47 to â1.65 cm(3)). CONCLUSION: According to qualitative and quantitative assessment, intensityâbased interpolation reduced the percentage of discarded scans from 29% to 7%
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