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Integration of vision and force sensors for grasping
This paper describes a set of methods that can be used to integrate real-time external vision sensing with internal force and position sensing to estimate contact forces by the fingers of a hand. Estimating these forces and contacts is essential to performing dextrous manipulation tasks. Most robotic hands are either sensorless or lack the ability to accurately and robustly report position and force information relating to contact. By adding external vision sensing, we can complement any internal sensors to more accurately estimate forces and contact positions. Experiments are described that use real-time visual trackers in conjunction with internal strain gauges and a new tactile sensor to accurately estimate finger contacts and applied forces for a three fingered robotic hand
Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.
Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically
BID mediates selective killing of APC-deficient cells in intestinal tumor suppression by nonsteroidal antiinflammatory drugs
Colorectal tumorigenesis is driven by genetic alterations in the adenomatous polyposis coli (APC) tumor suppressor pathway and effectively inhibited by nonsteroidal antiinflammatory drugs (NSAIDs). However, how NSAIDs prevent colorectal tumorigenesis has remained obscure. We found that the extrinsic apoptotic pathway and the BH3 interacting-domain death agonist (BID) are activated in adenomas from NSAID-treated patients. Loss of BID abolishes NSAID-mediated tumor suppression, survival benefit, and apoptosis in tumor-initiating stem cells in APC(Min/+) mice. BID-mediated cross-talk between the extrinsic and intrinsic apoptotic pathways is responsible for selective killing of neoplastic cells by NSAIDs. We further demonstrate that NSAIDs induce death receptor signaling in both cancer and normal cells, but only activate BID in cells with APC deficiency and ensuing c-Myc activation. Our results suggest that NSAIDs suppress intestinal tumorigenesis through BID-mediated synthetic lethality triggered by death receptor signaling and gatekeeper mutations, and provide a rationale for developing more effective cancer prevention strategies and agents
RCW 86: A Type Ia Supernova in a Wind-Blown Bubble
We report results from a multi-wavelength analysis of the Galactic SNR RCW
86, the proposed remnant of the supernova of 185 A.D. We report new infrared
observations from {\it Spitzer} and {\it WISE}, where the entire shell is
detected at 24 and 22 m. We fit the infrared flux ratios with models of
collisionally heated ambient dust, finding post-shock gas densities in the
non-radiative shocks of 2.4 and 2.0 cm in the SW and NW portions of the
remnant, respectively. The Balmer-dominated shocks around the periphery of the
shell, large amount of iron in the X-ray emitting ejecta, and lack of a compact
remnant support a Type Ia origin for this remnant. From hydrodynamic
simulations, the observed characteristics of RCW 86 are successfully reproduced
by an off-center explosion in a low-density cavity carved by the progenitor
system. This would make RCW 86 the first known case of a Type Ia supernova in a
wind-blown bubble. The fast shocks ( km s) observed in the NE
are propagating in the low-density bubble, where the shock is just beginning to
encounter the shell, while the slower shocks elsewhere have already encountered
the bubble wall. The diffuse nature of the synchrotron emission in the SW and
NW is due to electrons that were accelerated early in the lifetime of the
remnant, when the shock was still in the bubble. Electrons in a bubble could
produce gamma-rays by inverse-Compton scattering. The wind-blown bubble
scenario requires a single-degenerate progenitor, which should leave behind a
companion star.Comment: Accepted for publication in ApJ. 50 pages, 9 figure
γPNA FRET Pair Miniprobes for Quantitative Fluorescent In Situ Hybridization to Telomeric DNA in Cells and Tissue
Measurement of telomere length by fluorescent in situ hybridization is widely used for biomedical and epidemiological research, but there has been relatively little development of the technology in the 20 years since it was first reported. This report describes the use of dual gammaPNA (γPNA) probes that hybridize at alternating sites along a telomere and give rise to Förster resonance energy transfer (FRET) signals. Bright staining of telomeres is observed in nuclei, chromosome spreads and tissue samples. The use of FRET detection also allows for elimination of wash steps, normally required to remove unhybridized probes that would contribute to background signals. We found that these wash steps can diminish the signal intensity through the removal of bound, as well as unbound probes, so eliminating these steps not only accelerates the process but also enhances the quality of staining. Thus, γPNA FRET pairs allow for brighter and faster staining of telomeres in a wide range of research and clinical formats
The Detailed Optical light Curve of GRB 030329
We present densely sampled BVRI light curves of the optical transient associated with the gamma-ray burst (GRB) 030329, the result of a coordinated observing campaign conducted at five observatories. Augmented with published observations of this GRB, theY. M.
Lipkin and E. O. Ofek are grateful to the Dan-David prize
foundation for financial support. A. Gal-Yam acknowledges
a Colton Fellowship. Y. M. Lipkin, E. O. Ofek, A. Gal-Yam,
D. Poznanski, and D. Polishook were supported in part
by grants from the Israel Science Foundation
Review: A critical evaluation of arguments opposing male circumcision for HIV prevention in developed countries
A potential impediment to evidence-based policy development on medical male circumcision (MC) for HIV prevention in all countries worldwide is the uncritical acceptance by some of arguments used by opponents of this procedure. Here we evaluate recent opinion-pieces of 13 individuals opposed to MC. We find that these statements misrepresent good studies, selectively cite references, some containing fallacious information, and draw erroneous conclusions. In marked contrast, the scientific evidence shows MC to be a simple, low-risk procedure with very little or no adverse long-term effect on sexual function, sensitivity, sensation during arousal or overall satisfaction. Unscientific arguments have been recently used to drive ballot measures aimed at banning MC of minors in the USA, eliminate insurance coverage for medical MC for low-income families, and threaten large fines and incarceration for health care providers. Medical MC is a preventative health measure akin to immunisation, given its protective effect against HIV infection, genital cancers and various other conditions. Protection afforded by neonatal MC against a diversity of common medical conditions starts in infancy with urinary tract infections and extends throughout life. Besides protection in adulthood against acquiring HIV, MC also reduces morbidity and mortality from multiple other sexually transmitted infections (STIs) and genital cancers in men and their female sexual partners. It is estimated that over their lifetime one-third of uncircumcised males will suffer at least one foreskin-related medical condition. The scientific evidence indicates that medical MC is safe and effective. Its favourable risk/benefit ratio and cost/benefit support the advantages of medical MC
Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker
BACKGROUND:The mass of pancreatic beta-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous beta-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of beta-cells and investigated their physiological relevance in increased insulin demand conditions in rats. METHODS:Two rat beta-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. beta(high) and beta(low)-cells. Insulin release, Ca(2+) movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, beta(high) and beta(low)-cell distribution and functionality were investigated in animal models with decreased or increased beta-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. RESULTS:We show that beta-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike beta(low)-cells, beta(high)-cells express functional beta-cell markers and are highly responsive to various insulin secretagogues. Whereas beta(low)-cells represent the main population in diabetic pancreas, an increase in beta(high)-cells is associated with gain of function that follows sustained glucose overload. CONCLUSION:Our data show that a functional heterogeneity of beta-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in beta-cell defects in type 2 diabetes
Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X
The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI
From Sacred to Scientific: Epic Religion, Spectacular Science, and Charlton Heston’s Science Fiction Cinema
This paper analyses how long-1960s cinema responded to and framed public discourses surrounding religion and science. This approach allows for a discussion that extends beyond a critical study of the scholarly debates that surround the place of religion in science during a transitional period. Charlton Heston was an epic actor who went from literally playing God in The Ten Commandments (1956) to playing “god” as a messianic scientist in The Omega Man (1971). Best known for playing Moses, Heston became an unlikely science-based cinema star during the early 1970s. He was re-imagined as a scientist, but the religiosity of his established persona was inescapable. Heston and the science-based films he starred in capitalized upon the utopian promises of real science, and also the fears of the vocal activist counterculture. Planet of the Apes (1968), Omega Man (1971), Soylent Green (1973), and other science-based films made between 1968-1977 were bleak countercultural warnings about excessive consumerism, uncontrolled science, nuclear armament, irreversible environmental damage, and eventual human extinction. In this paper I argue that Heston’s transition from biblical epic star to science-fiction anti-hero represents the way in which the role and interpretation of science changed in post-classical cinema. Despite the shift from religious epic to science-based spectacle, religion remained a faithful component of Hollywood output indicating the ongoing connection between science and religion in US culture. I will consider the transition from sacred to science-based narratives and how religion was utilised across the production process of films that commented upon scientific advances
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