Significance The design of new antitumor agents and the search for delivery vehicles for existing drugs are two problems in cancer therapy that are often solved separately. Drug delivery vehicles are ...typically nontherapeutic, leaving antitumor effects exclusively to the encapsulated drug. However, the combination of an anticancer drug and a delivery vehicle with inherent antitumor properties could produce a synergistic effect, thus enhancing the therapy. We describe herein the synthesis and characterization of two supramolecular coordination complexes with well-defined geometries, along with their in vitro localization and in vivo assessment of antitumor effects. These complexes are stable in cell culture and nontoxic to cells, yet show substantial reduction of the tumor growth and tumor burden in mouse xenograft models.
The development of novel antitumor agents that have high efficacy in suppressing tumor growth, have low toxicity to nontumor tissues, and exhibit rapid localization in the targeted tumor sites is an ongoing avenue of research at the interface of chemistry, cancer biology, and pharmacology. Supramolecular metal-based coordination complexes (SCCs) have well-defined shapes and geometries, and upon their internalization, SCCs could affect multiple oncogenic signaling pathways in cells and tissues. We investigated the uptake, intracellular localization, and antitumor activity of two rhomboidal Pt(II)-based SCCs. Laser-scanning confocal microscopy in A549 and HeLa cells was used to determine the uptake and localization of the assemblies within cells and their effect on tumor growth was investigated in mouse s.c. tumor xenograft models. The SCCs are soluble in cell culture media within the entire range of studied concentrations (1 nM–5 µM), are nontoxic, and showed efficacy in reducing the rate of tumor growth in s.c. mouse tumor xenografts. These properties reveal the potential of Pt(II)-based SCCs for future biomedical applications as therapeutic agents.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A bright μm-sized source of hard synchrotron x-rays (critical energy Ecrit > 30 keV) based on the betatron oscillations of laser wakefield accelerated electrons has been developed. The potential of ...this source for medical imaging was demonstrated by performing micro-computed tomography of a human femoral trabecular bone sample, allowing full 3D reconstruction to a resolution below 50 μm. The use of a 1 cm long wakefield accelerator means that the length of the beamline (excluding the laser) is dominated by the x-ray imaging distances rather than the electron acceleration distances. The source possesses high peak brightness, which allows each image to be recorded with a single exposure and reduces the time required for a full tomographic scan. These properties make this an interesting laboratory source for many tomographic imaging applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
We describe the selection of galaxies targeted in eight low-redshift clusters (APMCC0917, A168, A4038, EDCC442, A3880, A2399, A119 and A85; 0.029 < z < 0.058) as part of the Sydney-AAO ...Multi-Object Integral field spectrograph Galaxy Survey (SAMI-GS). We have conducted a redshift survey of these clusters using the AAOmega multi-object spectrograph on the 3.9-m Anglo-Australian Telescope. The redshift survey is used to determine cluster membership and to characterize the dynamical properties of the clusters. In combination with existing data, the survey resulted in 21 257 reliable redshift measurements and 2899 confirmed cluster member galaxies. Our redshift catalogue has a high spectroscopic completeness (∼94 per cent) for rpetro ≤ 19.4 and cluster-centric distances R < 2R200. We use the confirmed cluster member positions and redshifts to determine cluster velocity dispersion, R200, virial and caustic masses, as well as cluster structure. The clusters have virial masses 14.25 ≤ log(M200/M⊙) ≤ 15.19. The cluster sample exhibits a range of dynamical states, from relatively relaxed-appearing systems, to clusters with strong indications of merger-related substructure. Aperture- and point spread function matched photometry are derived from Sloan Digital Sky Survey and VLT Survey Telescope/ATLAS imaging and used to estimate stellar masses. These estimates, in combination with the redshifts, are used to define the input target catalogue for the cluster portion of the SAMI-GS. The primary SAMI-GS cluster targets have R <R200, velocities |vpec| < 3.5σ200 and stellar masses $9.5 \le {\rm log({\it M}}^*_{{\rm approx}}/$M⊙)≤12. Finally, we give an update on the SAMI-GS progress for the cluster regions.
ABSTRACT
We present the first detection of mass-dependent galactic spin alignments with local cosmic filaments with >2σ confidence using IFS kinematics. The 3D network of cosmic filaments is ...reconstructed on Mpc scales across GAlaxy and Mass Assembly fields using the cosmic web extractor DisPerSe. We assign field galaxies from the SAMI survey to their nearest filament segment in 3D and estimate the degree of alignment between SAMI galaxies’ kinematic spin axis and their nearest filament in projection. Low-mass galaxies align their spin with their nearest filament while higher mass counterparts are more likely to display an orthogonal orientation. The stellar transition mass from the first trend to the second is bracketed between $10^{10.4}$ and $10^{10.9}\, \mathrm{ M}_{\odot }$, with hints of an increase with filament scale. Consistent signals are found in the Horizon-AGN cosmological hydrodynamic simulation. This supports a scenario of early angular momentum build-up in vorticity rich quadrants around filaments at low stellar mass followed by progressive flip of spins orthogonal to the cosmic filaments through mergers at high stellar mass. Conversely, we show that dark matter only simulations post-processed with a semi-analytical model treatment of galaxy formation struggles to reproduce this alignment signal. This suggests that gas physics is key in enhancing the galaxy-filament alignment.
ACC/AHA Task Force Members Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair¶ Sana M. Al-Khatib, MD, ...MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA¶ Ralph G. Brindis, MD, MPH, MACC¶ Joaquin E. Cigarroa, MD, FACC Anita Deswal, MD, MPH, FACC, FAHA Lesley H. Curtis, PhD, FAHA¶ Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA¶ Zachary D. Goldberger, MD, MS, FACC, FAHA Mark A. Hlatky, MD, FACC, FAHA John Ikonomidis, MD, PhD, FAHA José A. Joglar, MD, FACC, FAHA Laura Mauri, MD, MSc, FAHA Barbara Riegel, PhD, RN, FAHA Susan J. Pressler, PhD, RN, FAHA¶ Duminda N. Wijeysundera, MD, PhD¶Former Task Force member; current member during the writing effort.Table of Contents Preamble1679 Introduction1681 1.1.Methodology and Evidence Review1681 1.2.Organization of the Writing Committee1682 1.3.Document Review and Approval1682 1.4.Scope of the Guideline1682 1.5.Abbreviations1684 2. Evidence Gaps and Future Research Needs1725 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)1742 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)1744 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. Adherence to recommendations can be enhanced by shared decision-making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.Methodology and Modernization The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (P-1,P-2) and on the basis of internal reevaluation. Publication of new, potentially practice-changing study results that are relevant to an existing or new medication, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Increasing the areal capacity or electrode thickness in lithium ion batteries is one possible means to increase pack level energy density while simultaneously lowering cost. The physics that limit ...use of high areal capacity as a function of battery power to energy ratio are poorly understood and thus most currently produced automotive lithium ion cells utilize modest loadings to ensure long life over the vehicle battery operation. Here we show electrolyte transport limits the utilization of the positive electrode at critical C-rates during discharge; whereas, a combination of electrolyte transport and polarization lead to lithium plating in the graphite electrode during charge. Experimental measurements are compared with theoretical predictions based on concentrated solution and porous electrode theories. An analytical expression is derived to provide design criteria for long lived operation based on the physical properties of the electrode and electrolyte. Finally, a guideline is proposed that graphite cells should avoid charge current densities near or above 4 mA/cm2 unless additional precautions have been made to avoid deleterious side reaction.
Working memory (WM) involves a dynamic interplay between temporary maintenance and updating of goal-relevant information. The balance between maintenance and updating is regulated by an input-gating ...mechanism that determines which information should enter WM (gate opening) and which should be kept out (gate closing). We investigated whether updating and gate opening/closing are differentially sensitive to the kind of information to be encoded and maintained in WM. Specifically, since the social salience of a stimulus is known to affect cognitive performance, we investigated if self-relevant information differentially impacts maintenance, updating, or gate opening/closing. Participants first learned to associate two neutral shapes with two social labels (i.e., "you" vs. "stranger"), respectively. Subsequently they performed the reference-back paradigm, a well-established WM task that disentangles WM updating, gate opening, and gate closing. Crucially, the shapes previously associated with the self or a stranger served as target stimuli in the reference-back task. We replicated the typical finding of a repetition benefit when consecutive trials require opening the gate to WM. In Study 1 (N = 45) this advantage disappeared when self-associated stimuli were recently gated into WM and immediately needed to be replaced by stranger-associated stimuli. However, this was not replicated in a larger sample (Study 2; N = 90), where a repetition benefit always occurred on consecutive gate-opening trials. Overall, our results do not provide evidence that the self-relevance of stimuli modulates component processes of WM. We discuss possible reasons for this null finding, including the importance of continuous reinstatement and task-relevance of the shape-label associations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
We analyse the velocity dispersion properties of 472 z ∼ 0.9 star-forming galaxies observed as part of the KMOS Redshift One Spectroscopic Survey (KROSS). The majority of this sample is ...rotationally dominated (83 ± 5 per cent with vC/σ0 > 1) but also dynamically hot and highly turbulent. After correcting for beam smearing effects, the median intrinsic velocity dispersion for the final sample is σ0 = 43.2 ± 0.8 km s−1 with a rotational velocity to dispersion ratio of vC/σ0 = 2.6 ± 0.1. To explore the relationship between velocity dispersion, stellar mass, star formation rate, and redshift, we combine KROSS with data from the SAMI survey (z ∼ 0.05) and an intermediate redshift MUSE sample (z ∼ 0.5). Whilst there is, at most, a weak trend between velocity dispersion and stellar mass, at fixed mass there is a strong increase with redshift. At all redshifts, galaxies appear to follow the same weak trend of increasing velocity dispersion with star formation rate. Our results are consistent with an evolution of galaxy dynamics driven by discs that are more gas rich, and increasingly gravitationally unstable, as a function of increasing redshift. Finally, we test two analytic models that predict turbulence is driven by either gravitational instabilities or stellar feedback. Both provide an adequate description of the data, and further observations are required to rule out either model.
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