Saccharomyces Cerevisiae Cdc7 Homology in Drosophila Melanogaster

Saccharomyces cerevisiae Dbf4(Dumbbell former 4) and Cdc7(Cell Division Cycle 7) form a complex that phosphorylates Mcm2 (Minichromosome maintenance 2) to initiate DNA replication. Cdc7 is a target for cancer research because there is a Cdc7 ortholog in humans that is necessary for DNA replication and cell survival. Our goal is to characterise a putative Cdc7 homolog in Drosophila melanogaster (dCdc7). We have previously shown that expression of the known Drosophila Dbf4 ortholog, Chiffon, and dCdc7 can rescue yeast cells deficient in active Cdc7. Our hypothesis is that the dCdc7 is activated by Chiffon to phosphorylate MCM2. To test this hypothesis, we will determine if Chiffon interacts with dCdc7 and if Chiffon triggers kinase activity of dCdc7. To do this we purified dCdc7, a putative kinase dead substitution mutant of dCdc7, Chiffon, and Chiffon truncations that are predicted to contain the interacting domains. To produce these proteins we performed a combination of subcloning, SLIC(sequence and ligation independent cloning), and MultiBac Baculovirus techniques. SLIC is a recently developed method of cloning that uses single strand sequence complements instead of ligation to combine vector and insert. This allows us to clone any insert without regard to enzyme restriction sites within the insert’s DNA sequence. MultiBac is a system that allows us to infect insect cells with a Baculovirus to coexpress multiple proteins. We purified our proteins through affinity chromatography using various resins that bind to tags on the proteins. These proteins will then be used for protein binding pulldowns and kinase activity assays to determine if Chiffon and dCdc7 have a physical interaction, and if dCdc7 is a kinase. The results from the protein binding pulldown and kinase assay are pending. The results from these experiments will show us whether or not this protein is the Cdc7 ortholog in Drosophila

Solar-electric-propulsion cargo vehicles for split/sprint Mars mission

In support of the proposed exploration of Mars, an unmanned cargo ferry SEMM1 (Solar Electric Mars Mission) was designed. The vehicle is based on solar electric propulsion, and required to transport a cargo of 61,000 kg. The trajectory is a combination of spirals; first, out from LEO, then around the sun, then spiral down to low Mars orbit. The spacecraft produces 3.03 MWe power using photovoltaic flexible blanket arrays. Ion thrusters using argon as a propellant were selected to drive the ship, providing about 60 Newtons of thrust in low Earth orbit. The configuration is based on two long truss beams to which the 24 individual, self-deployable, solar arrays are attached. The main body module supports the two beams and houses the computers, electrical, and control equipment. The thruster module is attached to the rear of the main body, and the cargo to the front

Civilian casualties and public support for military action: Experimental evidence

In contrast to the expansive literature on military casualties and support for war, we know very little about public reactions to foreign civilian casualties. This article, based on representative sample surveys in the US and Britain, reports four survey experiments weaving information about civilian casualties into vignettes about Western military action. These produce consistent evidence of civilian casualty aversion: where death tolls were higher, support for force was invariably and significantly lower. Casualty effects were moderate in size but robust across our two cases and across different scenarios. They were also strikingly resistant to moderation by other factors manipulated in the experiments, such as the framing of casualties or their religious affiliation. The importance of numbers over even strongly humanizing frames points towards a utilitarian rather than a social-psychological model of casualty aversion. Either way, civilian casualties deserve a more prominent place in the literature on public support for war

Transport Properties of Multiple Quantum Dots Arranged in Parallel: Results from the Bethe Ansatz

In this paper we analyze transport through a double dot system connected to two external leads. Imagining each dot possessing a single active level, we model the system through a generalization of the Anderson model. We argue that this model is exactly solvable when certain constraints are placed upon the dot Coulomb charging energy, the dot-lead hybridization, and the value of the applied gate voltage. Using this exact solvability, we access the zero temperature linear response conductance both in and out of the presence of a Zeeman field. We are also able to study the finite temperature linear response conductance. We focus on universal behaviour and identify three primary features in the transport of the dots: i) a so-called RKKY Kondo effect; ii) a standard Kondo effect; and iii) interference phenomena leading to sharp variations in the conductance including conductance zeros. We are able to use the exact solvability of the dot model to characterize these phenomena quantitatively. While here we primarily consider a double dot system, the approach adopted applies equally well to N-dot systems.Comment: 28 pages, 10 figures; references added in v

Relaxation equations for two-dimensional turbulent flows with a prior vorticity distribution

Using a Maximum Entropy Production Principle (MEPP), we derive a new type of relaxation equations for two-dimensional turbulent flows in the case where a prior vorticity distribution is prescribed instead of the Casimir constraints [Ellis, Haven, Turkington, Nonlin., 15, 239 (2002)]. The particular case of a Gaussian prior is specifically treated in connection to minimum enstrophy states and Fofonoff flows. These relaxation equations are compared with other relaxation equations proposed by Robert and Sommeria [Phys. Rev. Lett. 69, 2776 (1992)] and Chavanis [Physica D, 237, 1998 (2008)]. They can provide a small-scale parametrization of 2D turbulence or serve as numerical algorithms to compute maximum entropy states with appropriate constraints. We perform numerical simulations of these relaxation equations in order to illustrate geometry induced phase transitions in geophysical flows.Comment: 21 pages, 9 figure

AGN accretion disks as spatially resolved by polarimetry

A crucial difficulty in understanding the nature of the putative accretion disk in AGNs is that some of its key intrinsic spectral signatures cannot be observed directly. The strong emissions from the broad-line region (BLR) and the obscuring torus, which are generally yet to be spatially resolved, essentially 'bury' such signatures. Here we argue that we can actually isolate the disk emission spectrum by using optical and near-infrared polarization of quasars and uncover the important spectral signatures. In these quasars, the polarization is considered to originate from electron scattering interior to the BLR, so that the polarized flux shows the disk spectrum with all the emissions from the BLR and torus eliminated. The polarized flux observations have now revealed a Balmer edge feature in absorption and a blue near-infrared spectral shape consistent with a specific and robust theoretical prediction. These results critically verify the long-standing picture of an optically thick and locally heated disk in AGNs.Comment: Proceedings for "The Universe under the Microscope" (AHAR 2008), held in Bad Honnef (Germany) in April 2008, to be published in Journal of Physics: Conference Series by Institute of Physics Publishing, R. Schoedel, A. Eckart, S. Pfalzner, and E. Ros (eds.

Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes:insights from the EXSCEL trial

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes. Methods In the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses. Results In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m(2)/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m(2)/year). Conclusions This post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010

Concordance and diagnostic accuracy of vasodilator stress cardiac MRI and 320-detector row coronary CTA

Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study was to determine concordance and accuracy of vasodilator stress CMR and coronary CTA in the same subjects. We studied 151 consecutive subjects referred to detect or exclude suspected obstructive coronary artery disease (CAD) in patients without known disease or recurrent stenosis or ischemia in patients with previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner. CTA was performed on a 320-detector row system. Subjects were followed for cardiovascular events and downstream diagnostic testing. Subjects averaged 56 ± 12 years (60 % male), and 62 % had intermediate pre-test probability for obstructive CAD. Follow-up averaged 450 ± 115 days and was 100 % complete. CMR and CTA agreed in 92 % of cases (κ 0.81, p < 0.001). The event-free survival was 97 % for non-ischemic and 39 % for ischemic CMR (p < 0.0001). The event-free survival was 99 % for non-obstructive and 36 % for obstructive CTA (p < 0.0001). Using a reference standard including quantitative invasive angiography or major cardiovascular events, CMR and CTA had respective sensitivities of 93 and 98 %; specificities of 96 and 96 %; positive predictive values of 91 and 91 %; negative predictive values of 97 and 99 %; and accuracies of 95 and 97 %. Non-ischemic vasodilator stress CMR or non-obstructive coronary CTA were highly concordant and each confer an excellent prognosis. CMR and CTA are both accurate for assessment of obstructive CAD in a predominantly intermediate risk population

A Delphi study to strengthen research-methods training in undergraduate psychology programs

Psychology programs often emphasize inferential statistical tests over a solid understanding of data and research design. This imbalance may leave graduates underequipped to effectively interpret research and employ data to answer questions. We conducted a two-round modified Delphi to identify the research-methods skills that the UK psychology community deems essential for undergraduates to learn. Participants included 103 research-methods instructors, academics, students, and nonacademic psychologists. Of 78 items included in the consensus process, 34 reached consensus. We coupled these results with a qualitative analysis of 707 open-ended text responses to develop nine recommendations for organizations that accredit undergraduate psychology programs—such as the British Psychological Society. We recommend that accreditation standards emphasize (1) data skills, (2) research design, (3) descriptive statistics, (4) critical analysis, (5) qualitative methods, and (6) both parameter estimation and significance testing; as well as (7) give precedence to foundational skills, (8) promote transferable skills, and (9) create space in curricula to enable these recommendations. Our data and findings can inform modernized accreditation standards to include clearly defined, assessable, and widely encouraged skills that foster a competent graduate body for the contemporary world