1,702 research outputs found
A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth
We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords “immunotherapy” AND “cancer” for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5–121 mm3 in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm3 was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm3, and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm3, and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth
True 3D imaging with monocular cues using holographic stereography
A quantitative condition is derived to evaluate the monocular accommodation
in holographic stereograms. We find that the reconstruction can be viewed as
true-3D image when the whole scene is located in the monocular cues area, with
compatible monocular cues and binocular cues. In contrast, it reveals incorrect
monocular cues in the visible multi-imaging area and the lacking information
area. To demonstrate our theoretical predictions, a pupil-function integral
imaging algorithm is developed to simulate the mono-eye observation, and a
holographic printing system is set up to fabricate the full-parallax
holographic stereogram. Both simulation and experimental results match our
theoretical predictions.Comment: 16 pages, 4 figure
SPECULOOS exoplanet search and its prototype on TRAPPIST
One of the most significant goals of modern science is establishing whether
life exists around other suns. The most direct path towards its achievement is
the detection and atmospheric characterization of terrestrial exoplanets with
potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs),
i.e. very-low-mass stars and brown dwarfs with effective temperatures lower
than 2700 K, represent a unique opportunity to reach this goal within the next
decade. The potential of the transit method for detecting potentially habitable
Earth-sized planets around these objects is drastically increased compared to
Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby
UCD would be amenable for a thorough atmospheric characterization, including
the search for possible biosignatures, with near-future facilities such as the
James Webb Space Telescope. In this chapter, we first describe the physical
properties of UCDs as well as the unique potential they offer for the detection
of potentially habitable Earth-sized planets suitable for atmospheric
characterization. Then, we present the SPECULOOS ground-based transit survey,
that will search for Earth-sized planets transiting the nearest UCDs, as well
as its prototype survey on the TRAPPIST telescopes. We conclude by discussing
the prospects offered by the recent detection by this prototype survey of a
system of seven temperate Earth-sized planets transiting a nearby UCD,
TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H.
Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure
Structure and function of CutC choline lyase from human microbiota bacterium Klebsiella pneumoniae
Publisher Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.CutC choline trimethylamine-lyase is an anaerobic bacterial glycyl radical enzyme (GRE) that cleaves choline to produce trimethylamine (TMA) and acetaldehyde. In humans, TMA is produced exclusively by the intestinal microbiota, and its metabolite, trimethylamine oxide, has been associated with a higher risk of cardiovascular diseases. Therefore, information about the three-dimensional structures of TMA-producing enzymes is important for microbiota-targeted drug discovery. We have cloned, expressed, and purified the CutC GRE and the activating enzyme CutD from Klebsiella pneumoniae, a representative of the human microbiota. We have determined the first crystal structures of both the choline-bound and choline-free forms of CutC and have discovered that binding of choline at the ligand-binding site triggers conformational changes in the enzyme structure, a feature that has not been observed for any other characterized GRE.publishersversionPeer reviewe
An LRP5 Receptor with Internal Deletion in Hyperparathyroid Tumors with Implications for Deregulated WNT/β-Catenin Signaling
Gunnar Westin and colleagues report the expression of an aberrantly spliced LRP5 receptor in primary and spontaneous parathyroid tumors and implicate it in the deregulated activation of the Wnt/β-catenin signaling pathway
Planet Populations as a Function of Stellar Properties
Exoplanets around different types of stars provide a window into the diverse
environments in which planets form. This chapter describes the observed
relations between exoplanet populations and stellar properties and how they
connect to planet formation in protoplanetary disks. Giant planets occur more
frequently around more metal-rich and more massive stars. These findings
support the core accretion theory of planet formation, in which the cores of
giant planets form more rapidly in more metal-rich and more massive
protoplanetary disks. Smaller planets, those with sizes roughly between Earth
and Neptune, exhibit different scaling relations with stellar properties. These
planets are found around stars with a wide range of metallicities and occur
more frequently around lower mass stars. This indicates that planet formation
takes place in a wide range of environments, yet it is not clear why planets
form more efficiently around low mass stars. Going forward, exoplanet surveys
targeting M dwarfs will characterize the exoplanet population around the lowest
mass stars. In combination with ongoing stellar characterization, this will
help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet
The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins
TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 angstrom resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-beta promoter, as well as NF-kappa B-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation
Search for Kaluza-Klein Graviton Emission in Collisions at TeV using the Missing Energy Signature
We report on a search for direct Kaluza-Klein graviton production in a data
sample of 84 of \ppb collisions at = 1.8 TeV, recorded
by the Collider Detector at Fermilab. We investigate the final state of large
missing transverse energy and one or two high energy jets. We compare the data
with the predictions from a -dimensional Kaluza-Klein scenario in which
gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for
=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71
TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure
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