69 research outputs found
Achieving higher returns with Piotroskiâs F_Score model - An empirical study on the Swedish stock market
This thesis evaluates the success of a fundamental investing strategy on the Swedish stock market between 2004 and 2016. The main purpose is to examine if the F_Score system developed by Piotroski (2000) could be used to identify winners and losers during aforementioned time frame. A lot of research has previously been conducted on the topic of fundamental investing and some focusing on F_Score. This work should be seen as a contribution to the existing research. It contributes by examining a different region during a different time and by changing some of the systemâs characteristics. The collected data is statistically tested using a t-test with varying levels of significance. The results of the thesis imply that a investor could increase his or her risk-adjusted returns by using Piotroskiâs system to separate good firms from bad. Moreover, it implies that the investor could garner a greater risk-adjusted return than the market in general, which contradicts the efficient market hypothesis
Optimizing the anti-tumor efficacy of protein-drug conjugates by engineering the molecular size and half-life
Despite some approvals of antibody-drug conjugates for cancer therapy, their clinical success rate is unsatisfactory because of very small therapeutic windows, influenced by on-target and off-target toxicities of conjugate and liberated toxin. Additional formats with systematically investigated molecular parameters must therefore be explored to increase their therapeutic window. Here we focused on the effective molecular weight. To generate conjugates with exactly defined drug loads and tunable pharmacokinetics, we used Designed Ankyrin Repeat Proteins (DARPins), fused to unstructured polypeptides of different lengths, to produce proteins with any desired half-life, to identify those with the best efficacy. We generated an EpCAM-targeting DARPin-MMAF conjugate, fused to PAS or XTEN of different lengths, and a matched series of controls of a non-binding DARPin to account for the enhanced permeability and retention (EPR) effect, covering half-lives of minutes to 20.6 h in mice. All conjugates were produced at high purity, and demonstrated high specificity and cytotoxicity in human tumor cell cultures, with IC50 values in the low nM range, independent of the polypeptide type and length. Due to their more facile purification, the PASylated conjugates were tested in nude mice bearing HT29 tumor xenografts. Independent of their size, all PASylated conjugates were very well tolerated after repeated systemic administration of 300 nmol/kg. We found that the conjugates with intermediate size and half-life showed the strongest anti-tumor effects, and deduced that this effect is a compromise of serum half-life and diffusion within the tumor, as on-rates and affinities are essentially identical, with extravasation playing only a very minor role
Climate change and mixed forests: how do altered survival probabilities impact economically desirable species proportions of Norway spruce and European beech?
International audienceKey message Economic consequences of altered survival probabilities under climate change should be considered for regeneration planning in Southeast Germany. Findings suggest that species compositions of mixed stands obtained from continuous optimization may buffer but not completely mitigate economic consequences. Mixed stands of Norway spruce (Picea abiesL. Karst.) and European beech (Fagus sylvaticaL.) (considering biophysical interactions between tree species) were found to be more robust, against both perturbations in survival probabilities and economic input variables, compared to block mixtures (excluding biophysical interactions).ContextClimate change is expected to increase natural hazards in European forests. Uncertainty in expected tree mortality and resulting potential economic consequences complicate regeneration decisions.AimsThis study aims to analyze the economic consequences of altered survival probabilities for mixing Norway spruce (Picea abies L. Karst.) and European beech (Fagus sylvatica L.) under different climate change scenarios. We investigate whether management strategies such as species selection and type of mixture (mixed stands vs. block mixture) could mitigate adverse financial effects of climate change.MethodsThe bio-economic modelling approach combines a parametric survival model with modern portfolio theory. We estimate the economically optimal species mix under climate change, accounting for the biophysical and economic effects of tree mixtures. The approach is demonstrated using an example from Southeast Germany.ResultsThe optimal tree species mixtures under simulated climate change effects could buffer but not completely mitigate undesirable economic consequences. Even under optimally mixed forest stands, the risk-adjusted economic value decreased by 28%. Mixed stands economically outperform block mixtures for all climate scenarios.ConclusionOur results underline the importance of mixed stands to mitigate the economic consequences of climate change. Mechanistic bio-economic models help to understand consequences of uncertain input variables and to design purposeful adaptation strategies
X-ray background synthesis: the infrared connection
We present a synthesis model of the X-ray background based on the
cross-correlation between mid-infrared and X-ray surveys, where the
distribution of type 2 sources is assumed to follow that of luminous infrared
galaxies while type 1 sources are traced by the observed ROSAT distribution.
The best fits to both the X-ray number counts and background spectrum require
at least some density evolution. We explore a limited range of parameter space
for the evolutionary variables of the type 2 luminosity function. Matching the
redshift distribution to that observed in deep Chandra and XMM fields, we find
weak residuals as a signature of Fe emission from sources in a relatively
peaked range of redshift. This extends the recent work of Franceschini et al.,
and emphasizes the possible correlation between obscured AGN and star-forming
activity.Comment: 9 pages, 8 figures, MNRAS accepte
Consecutive photoinduced electron transfer (conPET): The mechanism of the photocatalyst rhodamine-6G
The dye rhodamine 6G can act as a photocatalyst through photoinduced electron transfer. After electronic excitation with green light, rhodamine 6G takes an electron from an electron donor, such as N,N-diisopropylethylamine, and forms the rhodamine 6G radical. This radical has a reduction potential of around -0.90 V and can split phenyl iodide into iodine anions and phenyl radicals. Recently, it has been reported that photoexcitation of the radical at 420 nm splits aryl bromides into bromide anions and aryl radicals. This requires an increase in reduction potential, hence the electronically excited rhodamine 6G radical was proposed as the reducing agent. Here, we present a study of the mechanism of the formation and photoreactions of the rhodamine 6G radical by transient absorption spectroscopy in the time range from femtoseconds to minutes in combination with quantum chemical calculations. We conclude that one photon of 540 nm light produces two rhodamine 6G radicals. The lifetime of the photoexcited radicals of around 350 fs is too short to allow diffusion-controlled interaction with a substrate. A fraction of the excited radicals ionize spontaneously, presumably producing solvated electrons. This decay produces hot rhodamine 6G and hot rhodamine 6G radicals, which cool with a time constant of around 10 ps. In the absence of a substrate, the ejected electrons recombine with rhodamine 6G and recover the radical on a timescale of nanoseconds. Photocatalytic reactions occur only upon excitation of the rhodamine 6G radical, and due to its short excited-state lifetime, the electron transfer to the substrate probably takes place through the generation of solvated electrons as an additional step in the proposed photochemical mechanism
Membrane damage as mechanism of photodynamic inactivation using Methylene blue and TMPyP in Escherichia coli and Staphylococcus aureus
The worldwide threat of antibiotic resistance requires alternative strategies to fight bacterial infections. A promising approach to support conventional antibiotic therapy is the antimicrobial photodynamic inactivation (aPDI). The aim of this work was to show further insights into the antimicrobial photodynamic principle using two photosensitizers (PS) of different chemical classes, Methylene Blue (MB) and TMPyP, and the organisms Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive representatives. Planktonic cultures of both species were cultured under aerobic conditions for 24 h followed by treatment with MB or TMPyP at various concentrations for an incubation period of 10 min and subsequent irradiation for 10 min. Ability to replicate was evaluated by CFU assay. Accumulation of PS was measured using a spectrophotometer. The cytoplasmic membrane integrity was investigated by flow cytometry using SYBR Green and propidium iodide. In experiments on the replication ability of bacteria after photodynamic treatment with TMPyP or MB, a killing rate of 5 log10 steps of the bacteria was achieved. Concentration-dependent accumulation of both PS was shown by spectrophotometric measurements whereby a higher accumulation of TMPyP and less accumulation of MB was found for S. aureus as compared to E. coli. For the first time, a membrane-damaging effect of TMPyP and MB in both bacterial strains could be shown using flow cytometry analyses. Furthermore, we found that reduction of the replication ability occurs with lower concentrations than needed for membrane damage upon MB suggesting that membrane damage is not the only mechanism of aPDI using MB
Targeted delivery and endosomal cellular uptake of DARPin-siRNA bioconjugates: Influence of linker stability on gene silencing
Specific cell targeting and efficient intracellular delivery are major hurdles for the widespread therapeutic use of nucleic acid technologies, particularly siRNA mediated gene silencing. To enable receptor-mediated cell-specific targeting, we designed a synthesis scheme that can be generically used to engineer Designed Ankyrin Repeat Protein (DARPin)-siRNA bioconjugates. Different linkers, including labile disulfide-, and more stable thiol-maleimide- and triazole- (click chemistry) tethers were employed. Crosslinkers were first attached to a 3â-terminal aminohexyl chain on the siRNA sense strands. On the protein side thiols of a C-terminal cysteine were used as anchoring site for disulfide- and thiol-maleimide conjugate formation, while strain-promoted azido-alkyne cycloadditions were carried out at a metabolically introduced N-terminal azidohomoalanine. After establishing efficient purification methods, highly pure products were obtained. Bioconjugates of EpCAM-targeted DARPins with siRNA directed at the luciferase gene were evaluated for cell-specific binding, uptake and gene silencing. As shown by flow cytometry and fluorescence microscopy, all constructs retained the highly specific and high-affinity antigen recognition properties of the native DARPin. As expected, internalization was observed only in EpCAM-positive cell lines, and predominantly endolysosomal localization was detected. Disulfide linked conjugates showed lower serum stability against cleavage at the linker and thus lower internalization into endosomes compared to thiol-maleimide- and triazole-linked conjugates, yet induced more pronounced gene silencing. This indicates that the siRNA payload needs to be liberated from the protein in the endosome. Our data confirm the promise of DARPin-siRNA bioconjugates for tumor targeting, but also identified endosomal retention and limited cytosolic escape of the siRNA as the rate-limiting step for more efficient gene silencing
The emission by dust and stars of nearby galaxies in the Herschel KINGFISH survey
Using new far-infrared imaging from the Herschel Space Observatory with ancillary data from ultraviolet (UV) to submillimeter wavelengths, we estimate the total emission from dust and stars of 62 nearby galaxies in the KINGFISH survey in a way that is as empirical and model independent as possible. We collect and exploit these data in order to measure from the spectral energy distributions (SEDs) precisely how much stellar radiation is intercepted and re-radiated by dust, and how this quantity varies with galaxy properties. By including SPIRE data, we are more sensitive to emission from cold dust grains than previous analyses at shorter wavelengths, allowing for more accurate estimates of dust temperatures and masses. The dust/stellar flux ratio, which we measure by integrating the SEDs, has a range of nearly three decades (from 10(-2.2) to 10(0.5)). The inclusion of SPIRE data shows that estimates based on data not reaching these far-IR wavelengths are biased low by 17% on average. We find that the dust/stellar flux ratio varies with morphology and total infrared (IR) luminosity, with dwarf galaxies having faint luminosities, spirals having relatively high dust/stellar ratios and IR luminosities, and some early types having low dust/stellar ratios. We also find that dust/stellar flux ratios are related to gas-phase metallicity ((log(f(dust)/f(*)) over bar) = -0.66 +/- 0.08 and -0.22 +/- 0.12 for metal-poor and intermediate-metallicity galaxies, respectively), while the dust/stellar mass ratios are less so (differing by approximate to 0.2 dex); the more metal-rich galaxies span a much wider range of the flux ratios. In addition, the substantial scatter between dust/stellar flux and dust/stellar mass indicates that the former is a poor proxy of the latter. Comparing the dust/stellar flux ratios and dust temperatures, we also show that early types tend to have slightly warmer temperatures (by up to 5 K) than spiral galaxies, which may be due to more intense interstellar radiation fields, or possibly to different dust grain compositions. Finally, we show that early types and early-type spirals have a strong correlation between the dust/stellar flux ratio and specific star formation rate, which suggests that the relatively bright far-IR emission of some of these galaxies is due to ongoing (if limited) star formation as well as to the radiation field from older stars, which is heating the dust grains
Infrared Counterparts to Chandra X-Ray Sources in the Antennae
We use deep J and Ks images of the Antennae (NGC 4038/9) obtained with WIRC
on the Palomar 200-inch telescope, together with the Chandra X-ray source list
of Zezas et al. (2002a), to search for IR counterparts to X-ray point sources.
We establish an X-ray/IR astrometric frame tie with 0.5" rms residuals over a
\~4.3' field. We find 13 ``strong'' IR counterparts brighter than Ks = 17.8 mag
and < 1.0" from X-ray sources, and an additional 6 ``possible'' IR counterparts
between 1.0" and 1.5" from X-ray sources. The surface density of IR sources
near the X-ray sources suggests only ~2 of the ``strong'' counterparts and ~3
of the ``possible'' counterparts are chance superpositions of unrelated
objects.
Comparing both strong and possible IR counterparts to our photometric study
of ~220 Antennae, IR clusters, we find the IR counterparts to X-ray sources are
\~1.2 mag more luminous in Ks than average non-X-ray clusters. We also note
that the X-ray/IR matches are concentrated in the spiral arms and ``overlap''
regions of the Antennae. This implies that these X-ray sources lie in the most
``super'' of the Antennae's Super Star Clusters, and thus trace the recent
massive star formation history here. Based on the N_H inferred from the X-ray
sources without IR counterparts, we determine that the absence of most of the
``missing'' IR counterparts is because they are intrinsically less luminous in
the IR, implying that they trace a different (possibly older) stellar
population.Comment: 27 pages, 10 Poscript figures, accepted by Ap
Searching for Compton-thick active galactic nuclei at z~0.1
Using a suite of X-ray, mid-IR and optical active galactic nuclei (AGN)
luminosity indicators, we search for Compton-thick (CT) AGNs with intrinsic
L_X>10^42erg/s at z~0.03-0.2, a region of parameter space which is currently
poorly constrained by deep narrow-field and high-energy (E>10keV) all-sky X-ray
surveys. We have used the widest XMM-Newton survey (the serendipitous source
catalogue) to select a representative sub-sample (14; ~10%) of the 147 X-ray
undetected candidate CT AGNs in the Sloan Digital Sky Survey (SDSS) with
f_X/f_[OIII]<1; the 147 sources account for ~50% of the overall Type-2 AGN
population in the SDSS-XMM overlap region. We use mid-IR spectral decomposition
analyses and emission-line diagnostics, determined from pointed Spitzer-IRS
spectroscopic observations of these candidate CT AGNs, to estimate the
intrinsic AGN emission (predicted L_X,2-10keV (0.2-30)x10^42erg/s). On the
basis of the optical [OIII], mid-IR [OIV] and 6um AGN continuum luminosities we
conservatively find that the X-ray emission in at least 6/14 (>43%) of our
sample appear to be obscured by CT material with N_H>1.5x10^24cm^-2. Under the
reasonable assumption that our 14 AGNs are representative of the overall X-ray
undetected AGN population in the SDSS-XMM parent sample, we find that >20% of
the optical Type-2 AGN population are likely to be obscured by CT material.
This implies a space-density of log(Phi) >-4.9Mpc^-3 for CT AGNs with
L_X>10^42erg/s at z~0.1, which we suggest may be consistent with that predicted
by X-ray background synthesis models. Furthermore, using the 6um continuum
luminosity to infer the intrinsic AGN luminosity and the stellar velocity
dispersion to estimate M_BH, we find that the most conservatively identified CT
AGNs in this sample may harbour some of the most rapidly growing black holes
(median M_BH~3x10^7M_o) in the nearby Universe, with a median Eddington ratio
of ~0.2.Comment: 16 pages, 2 tables, 6 figures. Accepted for publication in MNRA
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