109 research outputs found
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Event detection using roles and relationships of entities
A method, system, and computer program product for event detection using roles and relationships of entities are provided in the illustrative embodiments. A training event and a set of entities participating in the training event are identified in a training data. For a first entity in the set of entities, a first role occupied by the entity in the event is determined. A behavior attribute is assigned to the first role. A relationship of the first role with a second role corresponding to a second entity in the set of entities is determined. An event rule is constructed to detect an event corresponding to the training event in new data and comprising a plurality of roles, behavior attributes, and the relationship. The plurality of roles includes the first role and the second role, and the plurality of behavior attributes includes the behavior attribute assigned to the first role.Board of Regents, University of Texas Syste
Epidermal growth factor receptor downregulation by small heterodimeric binding proteins
No single engineered protein has been shown previously to robustly downregulate epidermal growth factor receptor (EGFR), a validated cancer target. A panel of fibronectin-based domains was engineered to bind with picomolar to nanomolar affinity to multiple epitopes of EGFR. Monovalent and homo- and hetero-bivalent dimers of these domains were tested for EGFR downregulation. Selected orientations of non-competitive heterodimers decrease EGFR levels by up to 80% in multiple cell types, without activating receptor signaling. These heterodimers inhibit autophosphorylation, proliferation and migration, and are synergistic with the monoclonal antibody cetuximab in these activities. These small (25 kDa) heterodimers represent a novel modality for modulating surface receptor levels.National Institutes of Health (U.S.) (NIH grant CA96504)National Institutes of Health (U.S.) (NIH grant CA118705)National Science Foundation (U.S.) (Graduate Research Fellowship Program
Scattering of energetic particles by anisotropic magnetohydrodynamic turbulence with a Goldreich-Sridhar power spectrum
Scattering rates for a Goldreich-Sridhar (GS) spectrum of anisotropic,
incompressible, magnetohydrodynamic turbulence are calculated in the
quasilinear approximation. Because the small-scale fluctuations are constrained
to have wave vectors nearly perpendicular to the background magnetic field,
scattering is too weak to provide either the mean free paths commonly used in
Galactic cosmic-ray propagation models or the mean free paths required for
acceleration of cosmic rays at quasi-parallel shocks. Where strong pitch-angle
scattering occurs, it is due to fluctuations not described by the GS spectrum,
such as fluctuations generated by streaming cosmic rays.Comment: 5 pages, 1 figure, to appear in Physical Review Letters. Minor
changes in wording and grammar from version 2. Like version 2, this version
discusses relevance of magnetic-moment conservation to non-resonant
scattering. All equations are the same as in version
Environmental and genetic influences on early attachment
Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief
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Persistence of Triploid Grass Carp in Devils Lake, Oregon
Grass carp Ctenopharyngodon idella are sometimes used as a biological tool for managing aquatic vegetation in reservoirs. Sterile, triploid fish were stocked in Devils Lake, Oregon, during 1986, 1987, and 1993 to control aquatic vegetation. We present a case study for using multiple measures on the same fish to determine whether illegal stocking of fertile, diploid grass carp occurred. An investigation into the estimated age of a dead grass carp found in Devils Lake suggested that it was significantly younger than would otherwise be expected, given the only stocking events occurred during 1986, 1987, and 1993. To determine whether illegal stocking or reproduction by presumed sterile grass carp had occurred in Devils Lake, we conducted a study that balanced the needs of lethally sampling grass carp for biological measures with the socially and politically sensitive sentiment of the proâgrass carp citizenry of Devils Lake. These considerations, in combination with a low catch per-unit effort, resulted in a modest sample size for grass carp. We sampled grass carp and recorded multiple measures for each fish. Ploidy testing of blood samples indicated the grass carp were all triploid. Based on gonadal histopathology, six fish were male, two were female, and two were sex-indeterminate with severe gonadal dysgenesis. Age estimates from lapillus otoliths were consistent with fish originating from the legal stocking events in Devils Lake. The grass carp were 21â30 y old, and we were unable to find published reports of grass carp anywhere else in the world that are older. The grass carp were significantly smaller than much younger fish from other regions. The small size of these grass carp relative to their age in Devils Lake suggests food limitations that stunted growth. The dead grass carp that was the impetus for this study was aged by anatomical structures that we have since found to be unreliable. This suggests that the dead grass carp was probably in fact older and originated from the legal stockings. The use of multiple biological measurements on a modest sample size of grass carp, combined with the knowledge that no juvenile grass carp have been observed since legal stocking occurred, lead us to conclude that the grass carp in Devils Lake are sterile fish that originated from legal stocking events.Keywords: maximum age, sterile, intersex, gonadal histology, Asian carpKeywords: maximum age, sterile, intersex, gonadal histology, Asian car
Heat-Labile Enterotoxin: Beyond GM1 Binding
Enterotoxigenic Escherichia coli (ETEC) is a significant source of morbidity and mortality worldwide. One major virulence factor released by ETEC is the heat-labile enterotoxin LT, which is structurally and functionally similar to cholera toxin. LT consists of five B subunits carrying a single catalytically active A subunit. LTB binds the monosialoganglioside GM1, the toxinâs host receptor, but interactions with A-type blood sugars and E. coli lipopolysaccharide have also been identified within the past decade. Here, we review the regulation, assembly, and binding properties of the LT B-subunit pentamer and discuss the possible roles of its numerous molecular interactions
Conjuring cognition : A review of educational magic-based interventions
For hundreds of years, magic tricks have been employed within a variety of pedagogic contexts, including promoting science and mathematics, delivering educational messaging, enhancing scepticism about the paranormal, and boosting creative thinking for product design. This review examines this diverse body of work, focusing on studies that have assessed the impact of such interventions. Although the studies tended to yield positive outcomes, much of the work suffered from methodological shortcomings, including measuring the impact of interventions over a relatively short period of time, focusing on self-report measures and failing to employ control groups. The paper makes several recommendations for future study in the area, including assessing the longer-term impact of magic-based interventions, comparing these interventions to other types of pedagogic techniques, focussing on knowledge retention and behavioural outcomes, and collaborating with magicians to develop more impactful interventions.Peer reviewedFinal Published versio
Discovery of very-high-energy gamma-ray emission from the vicinity of PSR J1913+1011 with H.E.S.S
The H.E.S.S. experiment, an array of four Imaging Atmospheric Cherenkov
Telescopes with high sensitivity and large field-of-view, has been used to
search for emitters of very-high-energy (VHE, >100 GeV) gamma-rays along the
Galactic plane, covering the region 30 deg < l < 60 deg, 280 deg < l < 330 deg,
and -3 deg < b < 3 deg. In this continuation of the H.E.S.S. Galactic Plane
Scan, a new extended VHE gamma-ray source was discovered at
alpha(2000)=19h12m49s, delta(2000)=+10d09'06'' (HESS J1912+101). Its integral
flux between 1-10 TeV is ~10% of the Crab Nebula flux in the same energy range.
The measured energy spectrum can be described by a power law with a photon
index Gamma = 2.7+-0.2(stat)+-0.3(sys). HESS J1912+101 is plausibly associated
with the high spin-down luminosity pulsar PSR J1913+1011. We also discuss
associations with an as yet unconfirmed SNR candidate proposed from low
frequency radio observation and/or with molecular clouds found in 13CO data.Comment: 6 pages, 2 figures; Accepted for publication in A&A on February 20,
200
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Exploring the Dysregulation of Iron Metabolism in Cancer: Leveraging Fenton Chemistry for Selective Drug Delivery
Most cancer chemotherapeutics are administered at or near their maximum tolerated dose, yet poor efficacy and insufficient therapeutic index remain major causes of attrition in oncology drug development. New pharmacological approaches that selectively target tumor cells are therefore of significant interest. Emerging evidence suggests that an augmented pool of intracellular labile Fe(II) is a metabolic signature of many cancers and thus may represent a targetable chemical environment. We have leveraged Fe(II)-dependent, Fenton-type reactivity of the 1,2,4-trioxolane ring to develop highly selective, reactivity-based probes of the ferrous iron pool and a prototypical scaffold for Fe(II)-dependent drug delivery of chemotherapeutics. These probes reveal higher reactive Fe(II)-pools in cancer cells as compared to non-tumorigenic cells, changes that can be linked to alteration of iron metabolism. Our findings suggest that many cancers alter iron metabolism to increase intracellular Fe(II)-pools and these changes can be exploited for cell-selective drug delivery. By using this scaffold to mask a highly potent DNA-alkylator we illustrate that this prodrug system is capable of stabilizing and selectively delivering such potent cytotoxins in vivo. Overall our results establish that Fe(II)-dependent prodrug/delivery strategies can be used to enhance the therapeutic index of cancer chemotherapeutics. Encouraged by these results further efforts were made to apply trioxolane-based systems as novel, tumor-selective cleavable linkers for antibody-drug conjugate strategies. Preliminary results indicate trioxolane-based linkers are capable of efficiently releasing drugs from ADCâs in cancer cells but optimization will be required before further development
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