2,688 research outputs found
The dynamothermal aureole of the Donqiao ophiolite (northern Tibet)
Metamorphic rocks found at the base of the Jurassic Donqiao ophiolite of northern Tibet are interpreted as a basal dynamothermal aureole produced during obduction of the massif. The rocks form a sequence some 8 m thick, varying from high-grade amphibolites at the contact with overlying harzburgites to greenschist facies metasedimentary rocks lower down. The mineral paragenesis is similar to other such aureoles, and indicates that temperatures in excess of 750°C may have been reached during metamorphism. The lack of high-pressure minerals suggests that the rocks were produced by subcretion in a relatively shallow dipping subduction zone. Ar-Ar geochronology on amphibole separates provides dates of 175-180 Ma for the displacement of the ophiolite, significantly older than the age of emplacement estimated from stratigraphic relationships. The ophiolite was clearly obducted very soon after its formation in a suprasubduction zone environment.published_or_final_versio
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A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents
Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings
Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections
ERBB4 confers metastatic capacity in Ewing sarcoma.
Metastatic spread is the single-most powerful predictor of poor outcome in Ewing sarcoma (ES). Therefore targeting pathways that drive metastasis has tremendous potential to reduce the burden of disease in ES. We previously showed that activation of the ERBB4 tyrosine kinase suppresses anoikis, or detachment-induced cell death, and induces chemoresistance in ES cell lines in vitro. We now show that ERBB4 is transcriptionally overexpressed in ES cell lines derived from chemoresistant or metastatic ES tumours. ERBB4 activates the PI3K-Akt cascade and focal adhesion kinase (FAK), and both pathways contribute to ERBB4-mediated activation of the Rac1 GTPase in vitro and in vivo. ERBB4 augments tumour invasion and metastasis in vivo, and these effects are blocked by ERBB4 knockdown. ERBB4 expression correlates significantly with reduced disease-free survival, and increased expression is observed in metastatic compared to primary patient-matched ES biopsies. Our findings identify a novel ERBB4-PI3K-Akt-FAK-Rac1 pathway associated with aggressive disease in ES. These results predict that therapeutic targeting of ERBB4, alone or in combination with cytotoxic agents, may suppress the metastatic phenotype in ES
A Random shRNA-Encoding Library for Phenotypic Selection and Hit-Optimization
RNA interference (RNAi) is a mechanism for inhibiting gene expression through the action of small, non-coding RNAs. Most existing RNAi libraries target single genes through canonical pathways. Endogenous microRNAs (miRNAs), however, often target multiple genes and can act through non-canonical pathways, including pathways that activate gene expression. To interrogate all possible functions, we designed, synthesized, and validated the first shRNA-encoding library that is completely random at the nucleotide level. Screening in an IL3-dependent cell line, FL5.12, yielded shRNA-encoding sequences that double cell survival upon IL3 withdrawal. Using random mutagenesis and re-screening under more stringent IL3-starvation conditions, we hit-optimized one of the sequences; a specific nucleotide change and the creation of a mismatch between the two halves of the stem both contributed to the improved potency. Our library allows unbiased selection and optimization of shRNA-encoding sequences that confer phenotypes of interest, and could be used for the development of therapeutics and tools in many fields of biology
Massive stars as thermonuclear reactors and their explosions following core collapse
Nuclear reactions transform atomic nuclei inside stars. This is the process
of stellar nucleosynthesis. The basic concepts of determining nuclear reaction
rates inside stars are reviewed. How stars manage to burn their fuel so slowly
most of the time are also considered. Stellar thermonuclear reactions involving
protons in hydrostatic burning are discussed first. Then I discuss triple alpha
reactions in the helium burning stage. Carbon and oxygen survive in red giant
stars because of the nuclear structure of oxygen and neon. Further nuclear
burning of carbon, neon, oxygen and silicon in quiescent conditions are
discussed next. In the subsequent core-collapse phase, neutronization due to
electron capture from the top of the Fermi sea in a degenerate core takes
place. The expected signal of neutrinos from a nearby supernova is calculated.
The supernova often explodes inside a dense circumstellar medium, which is
established due to the progenitor star losing its outermost envelope in a
stellar wind or mass transfer in a binary system. The nature of the
circumstellar medium and the ejecta of the supernova and their dynamics are
revealed by observations in the optical, IR, radio, and X-ray bands, and I
discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry"
Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna
Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure
Temperature Affects the Tripartite Interactions between Bacteriophage WO, Wolbachia, and Cytoplasmic Incompatibility
Wolbachia infections are a model for understanding intracellular, bacterial symbioses. While the symbiosis is often studied from a binary perspective of host and bacteria, it is increasingly apparent that additional trophic levels can influence the symbiosis. For example, Wolbachia in arthropods harbor a widespread temperate bacteriophage, termed WO, that forms virions and rampantly transfers between coinfections. Here we test the hypothesis that temperatures at the extreme edges of an insect's habitable range alter bacteriophage WO inducibility and in turn, Wolbachia densities and the penetrance of cytoplasmic incompatibility. We report four key findings using the model wasp, Nasonia vitripennis: First, both cold treatment at 18 C and heat treatment at 30 C reduce Wolbachia densities by as much as 74% relative to wasps reared at 25 C. Second, in all cases where Wolbachia densities decline due to temperature changes, phage WO densities increase and inversely associate with Wolbachia densities. Heat has a marked effect on phage WO, yielding phage densities that are 552% higher than the room temperature control. Third, there is a significant affect of insect family on phage WO and endoysmbiont densities. Fourth, at extreme temperatures, there was a temperature-mediated adjustment to the density threshold at which Wolbachia cause complete cytoplasmic incompatibility. Taken together, these results demonstrate that temperature simultaneously affects phage WO densities, endosymbiont densities, and the penetrance of cytoplasmic incompatibility. While temperature shock enhances bacteriophage inducibility and the ensuing bacterial mortality in a wide range of medically and industrially-important bacteria, this is the first investigation of the associations in an obligate intracellular bacteria. Implications to a SOS global sensing feedback mechanism in Wolbachia are discussed
Induced pseudoscalar coupling of the proton weak interaction
The induced pseudoscalar coupling is the least well known of the weak
coupling constants of the proton's charged--current interaction. Its size is
dictated by chiral symmetry arguments, and its measurement represents an
important test of quantum chromodynamics at low energies. During the past
decade a large body of new data relevant to the coupling has been
accumulated. This data includes measurements of radiative and non radiative
muon capture on targets ranging from hydrogen and few--nucleon systems to
complex nuclei. Herein the authors review the theoretical underpinnings of
, the experimental studies of , and the procedures and uncertainties
in extracting the coupling from data. Current puzzles are highlighted and
future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic
Supermassive Black Holes in Galactic Nuclei: Past, Present and Future Research
This review discusses the current status of supermassive black hole research,
as seen from a purely observational standpoint. Since the early '90s, rapid
technological advances, most notably the launch of the Hubble Space Telescope,
the commissioning of the VLBA and improvements in near-infrared speckle imaging
techniques, have not only given us incontrovertible proof of the existence of
supermassive black holes, but have unveiled fundamental connections between the
mass of the central singularity and the global properties of the host galaxy.
It is thanks to these observations that we are now, for the first time, in a
position to understand the origin, evolution and cosmic relevance of these
fascinating objects.Comment: Invited Review, 114 pages. Because of space requirements, this
version contains low resolution figures. The full resolution version can be
downloaded from http://www.physics.rutgers.edu/~lff/publications.htm
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