657 research outputs found
Photochemical Conjugation and One-Pot Radiolabelling of Antibodies for Immuno-PET
Monoclonal antibodies (mAbs), immunoglobulin fragments, and other proteins are important scaffolds in the development of radiopharmaceuticals for diagnostic immunoâpositron emission tomography (immunoâPET) and targeted radioimmunotherapy (RIT). Conventional methods for radiolabelling proteins with metal ions such as 68Ga, 64Cu, 89Zr, and 90Y require multiâstep procedures involving preâpurification, functionalisation with a chelate, and subsequent radiolabelling. Standard coupling chemistries are timeâconsuming, difficult to automate, and involve synthesis, isolation, and storage of an intermediate, new molecular entity (the conjugated mAb) whose biochemical properties can differ from those of the parent protein. To circumvent these issues, we developed a photoradiochemical approach that uses fast, chemoselective, lightâinduced protein modification under mild conditions with novel metalâionâbinding chelates derivatised with aryl azide (ArN3) groups. Experiments show that oneâpot photochemical conjugation and radiolabelling of formulated mAbs can be achieved in <20â
min
New Debris Disks Around Nearby Main Sequence Stars: Impact on The Direct Detection of Planets
Using the MIPS instrument on the Spitzer telescope, we have searched for
infrared excesses around a sample of 82 stars, mostly F, G, and K main-sequence
field stars, along with a small number of nearby M stars. These stars were
selected for their suitability for future observations by a variety of
planet-finding techniques. These observations provide information on the
asteroidal and cometary material orbiting these stars - data that can be
correlated with any planets that may eventually be found. We have found
significant excess 70um emission toward 12 stars. Combined with an earlier
study, we find an overall 70um excess detection rate of % for mature
cool stars. Unlike the trend for planets to be found preferentially toward
stars with high metallicity, the incidence of debris disks is uncorrelated with
metallicity. By newly identifying 4 of these stars as having weak 24um excesses
(fluxes 10% above the stellar photosphere), we confirm a trend found in
earlier studies wherein a weak 24um excess is associated with a strong 70um
excess. Interestingly, we find no evidence for debris disks around 23 stars
cooler than K1, a result that is bolstered by a lack of excess around any of
the 38 K1-M6 stars in 2 companion surveys. One motivation for this study is the
fact that strong zodiacal emission can make it hard or impossible to detect
planets directly with future observatories like the {\it Terrestrial Planet
Finder (TPF)}. The observations reported here exclude a few stars with very
high levels of emission, 1,000 times the emission of our zodiacal cloud,
from direct planet searches. For the remainder of the sample, we set relatively
high limits on dust emission from asteroid belt counterparts
Light emission from a scanning tunneling microscope: Fully retarded calculation
The light emission rate from a scanning tunneling microscope (STM) scanning a
noble metal surface is calculated taking retardation effects into account. As
in our previous, non-retarded theory [Johansson, Monreal, and Apell, Phys. Rev.
B 42, 9210 (1990)], the STM tip is modeled by a sphere, and the dielectric
properties of tip and sample are described by experimentally measured
dielectric functions. The calculations are based on exact diffraction theory
through the vector equivalent of the Kirchoff integral. The present results are
qualitatively similar to those of the non-retarded calculations. The light
emission spectra have pronounced resonance peaks due to the formation of a
tip-induced plasmon mode localized to the cavity between the tip and the
sample. At a quantitative level, the effects of retardation are rather small as
long as the sample material is Au or Cu, and the tip consists of W or Ir.
However, for Ag samples, in which the resistive losses are smaller, the
inclusion of retardation effects in the calculation leads to larger changes:
the resonance energy decreases by 0.2-0.3 eV, and the resonance broadens. These
changes improve the agreement with experiment. For a Ag sample and an Ir tip,
the quantum efficiency is 10 emitted photons in the visible
frequency range per tunneling electron. A study of the energy dissipation into
the tip and sample shows that in total about 1 % of the electrons undergo
inelastic processes while tunneling.Comment: 16 pages, 10 figures (1 ps, 9 tex, automatically included); To appear
in Phys. Rev. B (15 October 1998
Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol
Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978
Dusty Planetary Systems
Extensive photometric stellar surveys show that many main sequence stars show
emission at infrared and longer wavelengths that is in excess of the stellar
photosphere; this emission is thought to arise from circumstellar dust. The
presence of dust disks is confirmed by spatially resolved imaging at infrared
to millimeter wavelengths (tracing the dust thermal emission), and at optical
to near infrared wavelengths (tracing the dust scattered light). Because the
expected lifetime of these dust particles is much shorter than the age of the
stars (>10 Myr), it is inferred that this solid material not primordial, i.e.
the remaining from the placental cloud of gas and dust where the star was born,
but instead is replenished by dust-producing planetesimals. These planetesimals
are analogous to the asteroids, comets and Kuiper Belt objects (KBOs) in our
Solar system that produce the interplanetary dust that gives rise to the
zodiacal light (tracing the inner component of the Solar system debris disk).
The presence of these "debris disks" around stars with a wide range of masses,
luminosities, and metallicities, with and without binary companions, is
evidence that planetesimal formation is a robust process that can take place
under a wide range of conditions. This chapter is divided in two parts. Part I
discusses how the study of the Solar system debris disk and the study of debris
disks around other stars can help us learn about the formation, evolution and
diversity of planetary systems by shedding light on the frequency and timing of
planetesimal formation, the location and physical properties of the
planetesimals, the presence of long-period planets, and the dynamical and
collisional evolution of the system. Part II reviews the physical processes
that affect dust particles in the gas-free environment of a debris disk and
their effect on the dust particle size and spatial distribution.Comment: 68 pages, 25 figures. To be published in "Solar and Planetary
Systems" (P. Kalas and L. French, Eds.), Volume 3 of the series "Planets,
Stars and Stellar Systems" (T.D. Oswalt, Editor-in-chief), Springer 201
Genoviz Software Development Kit: Java tool kit for building genomics visualization applications
<p>Abstract</p> <p>Background</p> <p>Visualization software can expose previously undiscovered patterns in genomic data and advance biological science.</p> <p>Results</p> <p>The Genoviz Software Development Kit (SDK) is an open source, Java-based framework designed for rapid assembly of visualization software applications for genomics. The Genoviz SDK framework provides a mechanism for incorporating adaptive, dynamic zooming into applications, a desirable feature of genome viewers. Visualization capabilities of the Genoviz SDK include automated layout of features along genetic or genomic axes; support for user interactions with graphical elements (Glyphs) in a map; a variety of Glyph sub-classes that promote experimentation with new ways of representing data in graphical formats; and support for adaptive, semantic zooming, whereby objects change their appearance depending on zoom level and zooming rate adapts to the current scale. Freely available demonstration and production quality applications, including the Integrated Genome Browser, illustrate Genoviz SDK capabilities.</p> <p>Conclusion</p> <p>Separation between graphics components and genomic data models makes it easy for developers to add visualization capability to pre-existing applications or build new applications using third-party data models. Source code, documentation, sample applications, and tutorials are available at <url>http://genoviz.sourceforge.net/</url>.</p
Distances and ages of globular clusters using Hipparcos parallaxes of local subdwarfs
We discuss the impact of Population II and Globular Cluster (GCs) stars on
the derivation of the age of the Universe, and on the study of the formation
and early evolution of galaxies, our own in particular. The long-standing
problem of the actual distance scale to Population II stars and GCs is
addressed, and a variety of different methods commonly used to derive distances
to Population II stars are briefly reviewed. Emphasis is given to the
discussion of distances and ages for GCs derived using Hipparcos parallaxes of
local subdwarfs. Results obtained by different authors are slightly different,
depending on different assumptions about metallicity scale, reddenings, and
corrections for undetected binaries. These and other uncertainties present in
the method are discussed. Finally, we outline progress expected in the near
future.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22
pages including 3 tables and 2 postscript figures, uses Kluwer's crckapb.sty
LaTeX style file, enclose
The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure
BACKGROUND & AIMS: Cirrhotic patients with acute decompensation frequently develop acute-on-chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD), but without ACLF, and to compare this with the Child-Pugh, MELD, and MELD-Na scores. METHODS: The derivation set included 1016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk were used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use. RESULTS: Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Child-Pugh, MELD, and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7, and 8-15 (C-index: 0.72, 0.75, and 0.77 respectively). CONCLUSIONS: The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early
Juvenile Songbirds Compensate for Displacement to Oceanic Islands during Autumn Migration
To what degree juvenile migrant birds are able to correct for orientation errors
or wind drift is still largely unknown. We studied the orientation of passerines
on the Faroe Islands far off the normal migration routes of European migrants.
The ability to compensate for displacement was tested in naturally occurring
vagrants presumably displaced by wind and in birds experimentally displaced 1100
km from Denmark to the Faroes. The orientation was studied in orientation cages
as well as in the free-flying birds after release by tracking departures using
small radio transmitters. Both the naturally displaced and the experimentally
displaced birds oriented in more easterly directions on the Faroes than was
observed in Denmark prior to displacement. This pattern was even more pronounced
in departure directions, perhaps because of wind influence. The clear
directional compensation found even in experimentally displaced birds indicates
that first-year birds can also possess the ability to correct for displacement
in some circumstances, possibly involving either some primitive form of true
navigation, or âsign postsâ, but the cues used for this are highly
speculative. We also found some indications of differences between species in
the reaction to displacement. Such differences might be involved in the
diversity of results reported in displacement studies so far
Geobiology of the late Paleoproterozoic Duck Creek Formation, Western Australia
The ca. 1.8 Ga Duck Creek Formation, Western Australia, preserves 1000 m of carbonates and minor iron formation that accumulated along a late Paleoproterozoic ocean margin. Two upward-deepening stratigraphic packages are preserved, each characterized by peritidal precipitates at the base and iron formation and carbonate turbidites in its upper part. Consistent with recent studies of Neoarchean basins, carbon isotope ratios of Duck Creek carbonates show no evidence for a strong isotopic depth gradient, but carbonate minerals in iron formations can be markedly depleted in C-13. In contrast, oxygen isotopes covary strongly with depth; delta O-18 values as positive as 2%. VPDB in peritidal facies systematically decline to values of 6 to 16% in basinal rocks, reflecting, we posit, the timing of diagenetic closure. The Duck Creek Formation contains microfossils similar to those of the Gunflint Formation, Canada; they are restricted to early diagenetic cherts developed in basinal facies, strengthening the hypothesis that such fossils capture communities driven by iron metabolism. Indeed, X-ray diffraction data indicate that the Duck Creek basin was ferruginous throughout its history. The persistence of ferruginous waters and iron formation deposition in Western Australia for at least several tens of millions of years after the transition to sulfidic conditions in Laurentia suggests that the late Paleoproterozoic expansion of sulfidic subsurface waters was globally asynchronous
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