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Supplementary Data from Skp2 Directs Myc-Mediated Suppression of p27Kip1 yet Has Modest Effects on Myc-Driven Lymphomagenesis

Abstract: Latin Gospel Harmonies have attracted comparatively little interest within broader biblical tradition. The oldest extant Latin harmony is Codex Fuldensis, and scholarship has tended to use this in conjunction with vernacular harmonies to try to reconstruct a lost Old Latin Vorlage rather than examine the surviving later manuscripts. After a brief account of the history of research, this chapter presents a gospel pericope (John 2:1–11) from fourteen Latin harmony manuscripts. This provides an impression of their textual variety, especially in later manuscripts. A comparison between earlier and later commentaries on Latin gospel harmonies show that the same traditions are utilized, which belong to the wider stream of medieval commentary tradition manifested in the Glossa ordinaria. Finally, an outline is given of the likely trajectory from the Fuldensis-type Vulgate harmony to vernacular harmonies via the glossed Latin harmony.

Highly periodic structures are often said to convey the beauty of nature. However, most material properties are strongly influenced by the defects they contain. On the mesoscopic scale, molecular self-assembly exemplifies this interplay; thermodynamic principles determine short-range order, but long-range order is mainly impeded by the kinetic history of the material and by thermal fluctuations. For the development of self-assembly technologies, it is imperative to characterise and understand the interplay between self-assembled order and defect-induced disorder. Here we used synchrotron-based hard X-ray nanotomography to reveal a pair of extended topological defects within a self-assembled single-diamond network morphology. These defects are morphologically similar to the comet and trefoil patterns of equal and opposite half-integer topological charges observed in liquid crystals and appear to maintain a constant separation across the thickness of the sample, resembling pairs of full vortices in superconductors and other hard condensed matter systems. These results are expected to open new windows to study defect formation in soft condensed matter, particularly in biological systems where most structures are formed by self-assembly.

Block copolymers are recognised as a valuable platform for creating nanostructured materials with unique properties. Morphologies formed by block copolymer self-assembly can be transferred into a wide range of inorganic materials, enabling applications including energy storage and metamaterials. However, imaging of the underlying, often complex, nanostructures in large volumes has remained a challenge, limiting progress in materials development. Taking advantage of recent advances in X-ray nanotomography, we non-invasively imaged exceptionally large volumes of nanostructured soft materials at high resolution, revealing a single diamond morphology in a triblock terpolymer composite network. This morphology, which is ubiquitous in nature, has so far remained elusive in block copolymers, despite its potential to create materials with large photonic bandgaps. The discovery was made possible by the precise analysis of distortions in a large volume of the self-assembled diamond network, which are difficult to unambiguously assess using traditional characterisation tools. We anticipate that high-resolution X-ray nanotomography, which allows imaging of much larger sample volumes than electron-based tomography, will become a powerful tool for the quantitative analysis of complex nanostructures and that structures such as the triblock terpolymer-directed single diamond will enable the generation of advanced multicomponent composites with hitherto unknown property profiles., Comment: updated reference 38; added reference 40; corrected name of one author; corrected one affiliation; corrected legend in Extended Data Fig. 3

To address the key challenges in the development of next-generation drug delivery systems (DDS) with desired physicochemical properties to overcome limitations regarding safety, in vivo efficacy, and solid tumor penetration, an ultrasmall folate receptor alpha (FRα) targeted silica nanoparticle (C'Dot) drug conjugate (CDC; or folic acid CDC) was developed. A broad array of methods was employed to screen a panel of CDCs and identify a lead folic acid CDC for clinical development. These included comparing the performance against antibody-drug conjugates (ADCs) in three-dimensional tumor spheroid penetration ability, assessing in vitro/ex vivo cytotoxic efficacy, as well as in vivo therapeutic outcome in multiple cell-line-derived and patient-derived xenograft models. An ultrasmall folic acid CDC, EC112002, was identified as the lead candidate out of500 folic acid CDC formulations evaluated. Systematic studies demonstrated that the lead formulation, EC112002, exhibited highly specific FRα targeting, multivalent binding properties that would mediate the ability to outcompete endogenous folate

Porous polymer-derived membranes are useful for applications ranging from filtration and separation technologies to energy storage and conversion. Combining block copolymer (BCP) self-assembly with the industrially scalable, non-equilibrium phase inversion technique (SNIPS) yields membranes comprising periodically ordered top surface structures supported by asymmetric, hierarchical substructures that together overcome performance tradeoffs typically faced by materials derived from equilibrium approaches. This review first reports on recent advances in understanding the top surface structural evolution of a model SNIPS-derived system during standard membrane formation. Subsequently, the application of SNIPS to multicomponent systems is described, enabling pore size modulation, chemical modification, and transformation to non-polymeric materials classes without compromising the structural features that define SNIPS membranes. Perspectives on future directions of both single-component and multicomponent membrane materials are provided. This points to a rich and fertile ground for the study of fundamental as well as applied problems using non-equilibrium-derived asymmetric porous materials with tunable chemistry, composition, and structure.

We develop a pure characteristics equilibrium sorting model to recover estimates of willingness to pay (WTP) for both marginal and non-marginal changes in urban noise exposure. Using data from Vienna, Austria, we provide several new insights in the urban noise literature. First, we demonstrate the importance of considering general equilibrium feedback effects following large changes in noise levels. We document impacts to residents in policy targeted and non-targeted locations due to changes in both noise and equilibrium prices. Second, we confirm evidence of the importance of noise thresholds with significant and increasing negative impacts associated with increases in area covered by high levels of noise at 50 dB and 60 dB thresholds, respectively. Finally, we use an equilibrium sorting model to predict new price patterns and welfare implications following hypothetical policy changes that alter the distribution and intensity of nighttime noise in Vienna and are relevant to other urban settings seeking to reduce noise levels. Our work additionally provides a roadmap for conducting similar equilibrium sorting work in data limited settings outside the U.S.

The contingent valuation method is often used to estimate the willingness to pay for changes in a public good (e.g., water quality, public transport or food safety). We show how the stated willingness to pay changes when respondents to a contingent valuation survey believe their response affects not only the provision of the public good offered, but also the provision of an alternative public good in case the government cannot provide both goods. Empirical evidence suggests that at least 10 % of respondents consider alternative public goods when responding to contingent valuation surveys. Consequently, practitioners need to make sure that respondents are not influenced by the value of alternative public goods.

To conduct a randomised controlled trial (RCT) to evaluate the Common Agricultural Policy it would be necessary to exclude a random selection of farms from participation. This exclusion might limit the acceptance of RCTs. We assess the acceptance of an innovative alternative RCT called the ‘unconditional payment RCT’ (upRCT). UpRCTs allow for the evaluation of the impact of policy measures in which farmers receive a payment conditional on the adoption of farm management practices (e.g., agri-environment-climate measures). We surveyed Austrian farmers who participated in the ‘refrain from silage’ measure to compare the acceptance of a conventional RCT and an upRCT using thought experiments. The acceptance of the farmers was between 18% and 51%, and the treatment effects of both variants were of comparable size. Our survey suggests that acceptance of the up-RCT is about twice as high as the acceptance of the conventional RCT. We discuss that upRCTs are useful when a new measure is introduced or when the up-RCT is conducted for several years.

Fragrance allergy is a lifelong condition, and the probability of being affected increases with frequent exposure to fragrance. Currently, fragrance-free laundry detergents are not common in superm...

Galley proofs for the paper Carbon-Assisted Stable Silver Nanostructures

Discrepancies in certification effects on smallholder incomes have been found in scientific literature. Unobserved farmer-group heterogeneity is a likely reason. For the long-standing Robusta coffee farmer-groups in Uganda, we find no significant effect of certification on net-farm income. But, we find 20 percentage point differences in net-farm income between certified and non-certified farmers explained by membership duration. In contrast, the recently founded certified Arabica coffee farmer-groups have positive net-farm income effects of 151 per cent, partly explained by a higher degree of vertical integration. With or without certification, long-standing group membership is found to have positive income effects.

Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations.

Over the past two decades, mountain biking has emerged as an increasingly popular recreational activity. However, at least in Austria official trails do not necessarily match the preferences of bikers and therefore they often ride on unofficial trails or on trails where biking is not allowed. This behavior can result in conflicts with other trail users, landowners, hunters and conservationists. With data from an online choice experiment we confirm and extend results from previous studies on mountain biking, such as riders preferring technically challenging trails with lots of singletrack and vertical climb. However, the specific preferences depend on rider characteristics, especially experience and age. Through a simulation of market shares and the calculation of compensating surplus for riders in the study area in forests close to Vienna, we demonstrate how this research can provide insights about how to adjust trails to better match the interests of bikers while still respecting regulations which are in the interests of landowners, hunters and ecological concerns. Management implications ● To avoid conflict with other trail users, we propose tailoring trails specifically to the needs of the diverse group of bikers. ● For example, trails should have large amounts of technically challenging singletrack, at least on down hill sections. ● Trails should vary in their attributes such as vertical climb or length, to fit the preferences of riders with different socio-demographic background and experience. ● Multi-use trails for bikers and hikers can be recommended, however, horses on the same trails should be avoided.

EU bioenergy policies and oil price hikes have resulted in a significant increase of installed pellet boilers for residential heating. Hence, European demand for wood pellets has been growing faster and more steadily than supply leading to rising market prices in recent years. This article presents an econometric analysis of demand and supply of wood pellets in the residential heating sector in Austria, one of the most dynamic markets for residential pellets. Annual and monthly time series data between 2000 and 2014 are used in a two-stage least-squares (2SLS) regression to estimate supply and demand elasticities of wood pellets. In all model specifications, pellets demand is found to be inelastic (from −0.66 to −0.76) and pellets supply unit-elastic (from 1.03 to 1.18). Thus, consumers are highly exposed to price changes resulting from supply shocks. Policies which support investments in pellet boilers will shift the demand of wood pellets and likely leading to higher prices for consumers.

Rotational and oscillatory shear rheometry were used to quantify the flow behavior under minimal and significant solvent evaporation conditions for polymer solutions used to fabricate isoporous asymmetric membranes by the self-assembly and non-solvent induced phase separation (SNIPS) method. Three different A-B-C triblock terpolymer chemistries of similar molar mass were evaluated: polyisoprene-^-polystyrene-6-poly(4-vinylpyridine) (ISV); polyisoprene-6- polystyrene-6-poly(V,A-dimethylacrylamide) (ISD); and polyisoprene-Z>-polystyrene-h-poly(fer/- butyl methacrylate) (ISB). Solvent evaporation resulted in the formation of a viscoelastic film typical of asymmetric membranes. Solution viscosity and film viscoelasticity were strongly dependent on the chemical structure of the triblock terpolymer molecules. A hierarchical magnitude (ISV>ISB>ISD) was observed for both properties, with ISV solutions displaying the greatest solution viscosity, fastest film strength development, and greatest strength magnitude.

Cities increasingly face the necessity to choose among possible policy measures to counter urban heat and then to justify them. The contingent valuation method (CVM) is a frequently applied...

Peptides are usually administered through subcutaneous injection. For low potency drugs, this may require high concentration formulations increasing the risk of peptide aggregation, especially for compounds without any intrinsic chargeable groups. Carbetocin was used as a model to study the behavior of uncharged peptides at high concentrations. Manipulation of the aggregation behavior of 70 mg/mL carbetocin was attempted by selecting excipients which interact with hydrophobic groups in carbetocin, and cover hydrophobic surfaces and interfaces. Peptide aggregation was induced by shaking stress and followed over time. Carbetocin solutions showed significant visible particle formation already after 4 h of shaking stress. This particle formation was not due to supersaturation or phase separation but suggested a nucleated aggregation process. None of the excipients prevented carbetocin aggregation, though altered aggregation behavior was observed, such as induction of fibril formation for most, but not all, charged excipients. Sodium dodecyl sulfate was found to accelerate peptide aggregation both below and above the critical micelle concentration in half-filled vials. However, in the absence of an air headspace, sodium dodecyl sulfate above the critical micelle concentration was capable of preventing shaking-induced carbetocin aggregation. Our study highlights the complexity in rational excipient selection to stabilize uncharged peptides at high concentration.

Laser cooling is a fundamental technique used in primary atomic frequency standards, quantum computers, quantum condensed matter physics and tests of fundamental physics, among other areas. It has been known since the early 1990s that laser cooling can, in principle, be improved by using squeezed light as an electromagnetic reservoir; while quantum feedback control using a squeezed light probe is also predicted to allow improved cooling. Here we show the implementation of quantum feedback control of a micro-mechanical oscillator using squeezed probe light. This allows quantum-enhanced feedback cooling with a measurement rate greater than it is possible with classical light, and a consequent reduction in the final oscillator temperature. Our results have significance for future applications in areas ranging from quantum information networks, to quantum-enhanced force and displacement measurements and fundamental tests of macroscopic quantum mechanics.

33rd European Photovoltaic Solar Energy Conference and Exhibition; 2747-2752, While many research projects mention or simulate using electric cars as moveable batteries, practical tests and measurements are rare. To better understand the current state of art and to measure the round-trip efficiency, the authors built a test system and performed various measurements. This paper describes the challenges, the performed measurements, the results and the potential for the technology.

Several energy and agricultural commodities have experienced higher price volatility in recent years. Management of price risks usually leads to additional costs that are often shared and transmitted along the supply chain to the final consumers. Only little information is currently available on how price volatility of woody biomass commodities has developed compared to energy and agricultural commodities in recent years. We compute the historic price volatility of woody biomass commodities using the standard deviation of log returns as well as univariate GARCH models. The results show that the price volatility of several woody biomass commodities has increased in recent years. However, the price volatility of woody biomass is still lower compared to the price volatility of agricultural commodities and fossil fuels. The analysis of factors and linkages provides insights of the current biomass market developments.

The book of Revelation is a prophetic work written by an author who understands himself as similar to those Christian prophets about whom the apostle Paul writes in 1 Cor 14. Besides this fact John uses prophetic idioms which call to mind Old Testament prophecy (for example Rev 2:22-23; 2:10; 3:9).

We determine the theoretical limits to squeezing-enhanced measurement sensitivity of mechanical motion in a cavity optomechanical system. The motion of a mechanical resonator is transduced onto quadrature fluctuations of a cavity optical field and a measurement is performed on the optical field exiting the cavity. We compare measurement sensitivities obtained with coherent probing and quantum-enhanced probing of the mechanical motion, i.e. the coherent probe field carries vacuum states and quadrature squeezed vacuum states at sideband frequencies, respectively. We find that quantum-enhanced probing provides little to no improvement in motion sensing for resonators in the unresolved sideband regime but may significantly increase measurement sensitivities for resonators in the resolved sideband regime.

International audience; Propensity score matching (PSM) is an increasingly popular method for evaluation studies in agricultural and development economics. However, statisticians and econometricians have stressed that results rely on untestable assumptions, and therefore, guidelines for researchers on how to improve credibility have been developed. We follow one of these guidelines with a data set analysed by other authors to evaluate the impact of Fair Trade certification on the income of coffee producers. We provide thereby a best practice example of how to evaluate the credibility of PSM estimates. We find that a thorough assessment of the assumptions made renders the data we use not suitable for a credible PSM estimation of the effects of treatment. We conclude that the debate about the impact of Fair Trade certification would greatly benefit from a detailed reporting of credibility checking.

In order to evaluate potential therapeutic targets for treatment of amyloidoses such as Alzheimer's disease (AD), it is essential to determine the structures of toxic amyloid oligomers. However, for the amyloid β-protein peptide (Aβ), thought to be the seminal neuropathogenetic agent in AD, its fast aggregation kinetics and the rapid equilibrium dynamics among oligomers of different size pose significant experimental challenges. Here we use ion-mobility mass spectrometry, in combination with electron microscopy, atomic force microscopy, and computational modeling, to test the hypothesis that Aβ peptides can form oligomeric structures resembling cylindrins and β-barrels. These structures are hypothesized to cause neuronal injury and death through perturbation of plasma membrane integrity. We show that hexamers of C-terminal Aβ fragments, including Aβ(24-34), Aβ(25-35) and Aβ(26-36), have collision cross sections similar to those of cylindrins. We also show that linking two identical fragments head-to-tail using diglycine increases the proportion of cylindrin-sized oligomers. In addition, we find that larger oligomers of these fragments may adopt β-barrel structures and that β-barrels can be formed by folding an out-of-register β-sheet, a common type of structure found in amyloid proteins.