5,216 research outputs found
Multi-mesh gear dynamics program evaluation and enhancements
A multiple mesh gear dynamics computer program was continually developed and modified during the last four years. The program can handle epicyclic gear systems as well as single mesh systems with internal, buttress, or helical tooth forms. The following modifications were added under the current funding: variable contact friction, planet cage and ring gear rim flexibility options, user friendly options, dynamic side bands, a speed survey option and the combining of the single and multiple mesh options into one general program. The modified program was evaluated by comparing calculated values to published test data and to test data taken on a Hamilton Standard turboprop reduction gear-box. In general, the correlation between the test data and the analytical data is good
Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent
Pif1 Helicase Lengthens Some Okazaki Fragment Flaps Necessitating Dna2 Nuclease/Helicase Action in the Two-nuclease Processing Pathway
We have developed a system to reconstitute all of the proposed steps of Okazaki fragment processing using purified yeast proteins and model substrates. DNA polymerase Ī“ was shown to extend an upstream fragment to displace a downstream fragment into a flap. In most cases, the flap was removed by flap endonuclease 1 (FEN1), in a reaction required to remove initiator RNA in vivo. The nick left after flap removal could be sealed by DNA ligase I to complete fragment joining. An alternative pathway involving FEN1 and the nuclease/helicase Dna2 has been proposed for flaps that become long enough to bind replication protein A (RPA). RPA binding can inhibit FEN1, but Dna2 can shorten RPA-bound flaps so that RPA dissociates. Recent reconstitution results indicated that Pif1 helicase, a known component of fragment processing, accelerated flap displacement, allowing the inhibitory action of RPA. In results presented here, Pif1 promoted DNA polymerase Ī“ to displace strands that achieve a length to bind RPA, but also to be Dna2 substrates. Significantly, RPA binding to long flaps inhibited the formation of the final ligation products in the reconstituted system without Dna2. However, Dna2 reversed that inhibition to restore efficient ligation. These results suggest that the two-nuclease pathway is employed in cells to process long flap intermediates promoted by Pif1
Land-use planning, inequality and the problem of 'left-behind places' - A 'provocation' for the UK2070 Commission
The problems of so-called 'left-behind' places - typically former industrial regions have figured prominently in voting patterns over the last five years in the UK, and also the USA and Europe. This paper examines the following issues: the political economy of 'left-behind' regions; the new policy prescriptions for 'left-behind' regions; and the kinds of institutions that are required to create a new economic future in such disadvantaged places
Phase 1 Safety and Tolerability Study of BMP-7 in Symptomatic Knee Osteoarthritis
BACKGROUND: There are no proven therapies that modify the structural changes associated with osteoarthritis (OA). Preclinical data suggests that intra-articular recombinant human BMP-7 (bone morphogenetic protein-7) has reparative effects on cartilage, as well as on symptoms of joint pain. The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7. The secondary objectives were to determine the effect on symptomatic responses through 24 weeks. METHODS: This was a Phase 1, double-blind, randomized, multi-center, placebo-controlled, single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA. Each cohort was to consist of 8 treated participants, with treatment allocation in a 3:1 active (intra-articular BMP-7) to placebo ratio. Eligible participants were persons with symptomatic radiographic knee OA over the age of 40. The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessments, immunogenicity data and radiographic assessments. Secondary objectives were to determine the proportion of participants with a 20%, 50%, and 70% improvement in the WOMAC pain and function subscales at 4, 8, 12, and 24 weeks. Other secondary outcomes included the change from baseline to 4, 8, 12, and 24 weeks for the OARSI responder criteria. RESULTS: The mean age of participants was 60 years and 73% were female. All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups. The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays. By week 12, most participants in both the BMP-7 and placebo groups experienced a 20% improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement. In the participants who received 0.1 mg and 0.3 mg BMP-7, there was a trend toward greater symptomatic improvement than placebo. The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo. CONCLUSIONS: There was no dose limiting toxicity identified in this study. The suggestion of a symptom response, together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis.ARC Future Fellowship; Stryker Biotec
Low-Temperature Permittivity of Insulating Perovskite Manganites
Measurements of the low-frequency (f<=100 kHz) permittivity and conductivity
at T<= 150 K are reported for La(1-x)Ca(x)MnO(3) (0<=x<=1) and
Ca(1-y)Sr(y)MnO(3) (0<=y<=0.75) having antiferromagnetic, insulating ground
states covering a broad range of Mn valencies from Mn(3+) to Mn(4+). Static
dielectric constants are determined from the low-T limiting behavior. With
increasing T, relaxation peaks associated with charge-carrier hopping are
observed in the real part of the permittivities and analyzed to determine
dopant binding energies. The data are consistent with a simple model of
hydrogenic impurity levels and imply effective masses m*/m_e~3 for the Mn(4+)
compounds. Particularly interesting is a large dielectric constant (~100)
associated with the C-type antiferromagnetic state near the composition
La(0.2)Ca(0.8)MnO(3).Comment: 6 pages, 8 figures, PRB in pres
Allosteric regulation of epidermal growth factor (EGF) receptor ligand binding by tyrosine kinase inhibitors
Hysteresis loops of Co-Pt perpendicular magnetic multilayers
We develop a phenomenological model to study magnetic hysteresis in two
samples designed as possible perpendicular recording media. A stochastic
cellular automata model captures cooperative behavior in the nucleation of
magnetic domains. We show how this simple model turns broad hysteresis loops
into loops with sharp drops like those observed in these samples, and explains
their unusual features. We also present, and experimentally verify, predictions
of this model, and suggest how insights from this model may apply more
generally.Comment: 4.5 pages, 5 figure
Proceedings of the Spacecraft Charging Technology Conference: Executive Summary
Aerospace environments are reviewed in reference to spacecraft charging. Modelling, a theoretical scheme which can be used to describe the structure of the sheath around the spacecraft and to calculate the charging currents within, is discussed. Materials characterization is considered for experimental determination of the behavior of typical spacecraft materials when exposed to simulated geomagnetic substorm conditions. Materials development is also examined for controlling and minimizing spacecraft charging or at least for distributing the charge in an equipotential manner, using electrical conductive surfaces for materials exposed to space environment
Labour Market and Social Policy in Italy: Challenges and Changes. Bertelsmann Policy Brief #2016/02
vEight years after the outbreak of the financial crisis, Italy has still to cope with and
overcome a plethora of economic and social challenges. On top of this, it faces an
unfavourable demographic structure and severe disparities between its northern and
southern regions. Some promising reforms have recently been enacted, specifically
targeting poverty and social exclusion. However, much more remains to be done on
the way towards greater economic stability and widely shared prosperity
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