bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel Hafnium-Based X-ray Contrast Agent
Authors: Frenzel Thomas , Bauser Marcus , Berger Markus , Hilger Christoph Stephan , Hegele-Hartung Christa , Jost Gregor , Neis Christian , Hegetschweiler Kaspar , Riefke Björn , Suelzle Detlev , Pietsch Hubertus 
Published: June 2016

Objective
Characterization of BAY-576, a new x-ray contrast agent which is not based on iodine, but rather on the heavy metal hafnium. Compared with iodine, hafnium provides better x-ray absorption in the energy range of computed tomography (CT) and allows images of comparable quality to be acquired at a significantly reduced radiation dose.

Materials and Methods
A range of standard methods were used to explore the physicochemistry of BAY-576 as well as its tolerability in in vitro assays, its pharmacokinetics and toxicology in rats, and its performance in CT imaging in rabbits.

Results
BAY-576 is an extraordinarily stable chelate with a metal content of 42% (wt/wt) and with excellent water solubility. Formulations of 300 mg Hf/mL exhibited viscosity (3.3–3.6 mPa) and osmolality (860–985 mOsm/kg) in the range of nonionic x-ray agents. No relevant effects on erythrocytes, the coagulation, or complement system or on a panel of 87 potential biological targets were observed. The compound did not bind to plasma proteins of a number of species investigated. After intravenous injection in rats, it was excreted fast and mainly via the kidneys. Its pharmacokinetics was comparable to known extracellular contrast agents. A dose of 6000 mg Hf/kg, approximately 10 to 20 times the expected diagnostic dose, was well tolerated by rats with only moderate adverse effects. Computed tomography imaging in rabbits bearing a tumor in the liver demonstrated excellent image quality when compared with iopromide at the same contrast agent dose in angiography during the arterial phase. At 70% of the radiation dose, BAY-576 provided a contrast-to-noise ratio of the tumor, which was equivalent to iopromide at 100% radiation dose.

Conclusions
The profile of BAY-576 indicates its potential as the first compound in a new class of noniodine x-ray contrast agents, which can contribute to the reduction of the radiation burden in contrast-enhanced CT imaging.
“One-Stop Shop”
Authors: Riffel Philipp , Zoellner Frank G. , Budjan Johannes , Grimm Robert , Block Tobias K. , Schoenberg Stefan O. , Hausmann Daniel 
Published: June 2016

Aims and Objectives
The purpose of the present study was to evaluate a recently introduced technique for free-breathing dynamic contrast-enhanced renal magnetic resonance imaging (MRI) applying a combination of radial k-space sampling, parallel imaging, and compressed sensing. The technique allows retrospective reconstruction of 2 motion-suppressed sets of images from the same acquisition: one with lower temporal resolution but improved image quality for subjective image analysis, and one with high temporal resolution for quantitative perfusion analysis.

Materials and Methods
In this study, 25 patients underwent a kidney examination, including a prototypical fat-suppressed, golden-angle radial stack-of-stars T1-weighted 3-dimensional spoiled gradient-echo examination (GRASP) performed after contrast agent administration during free breathing. Images were reconstructed at temporal resolutions of 55 spokes per frame (6.2 seconds) and 13 spokes per frame (1.5 seconds). The GRASP images were evaluated by 2 blinded radiologists. First, the reconstructions with low temporal resolution underwent subjective image analysis: the radiologists assessed the best arterial phase and the best renal phase and rated image quality score for each patient on a 5-point Likert-type scale.
In addition, the diagnostic confidence was rated according to a 3-point Likert-type scale. Similarly, respiratory motion artifacts and streak artifacts were rated according to a 3-point Likert-type scale.
Then, the reconstructions with high temporal resolution were analyzed with a voxel-by-voxel deconvolution approach to determine the renal plasma flow, and the results were compared with values reported in previous literature.

Results
Reader 1 and reader 2 rated the overall image quality score for the best arterial phase and the best renal phase with a median image quality score of 4 (good image quality) for both phases, respectively. A high diagnostic confidence (median score of 3) was observed. There were no respiratory motion artifacts in any of the patients. Streak artifacts were present in all of the patients, but did not compromise diagnostic image quality.
The estimated renal plasma flow was slightly higher (295 ± 78 mL/100 mL per minute) than reported in previous MRI-based studies, but also closer to the physiologically expected value.

Conclusions
Dynamic, motion-suppressed contrast-enhanced renal MRI can be performed in high diagnostic quality during free breathing using a combination of golden-angle radial sampling, parallel imaging, and compressed sensing. Both morphologic and quantitative functional information can be acquired within a single acquisition.
The physics of stratum corneum lipid membranes
Authors: Das Chinmay , Olmsted Peter D. 
Published: June 2016

The stratum corneum (SC), the outermost layer of skin, comprises rigid corneocytes (keratin-filled dead cells) in a specialized lipid matrix. The continuous lipid matrix provides the main barrier against uncontrolled water loss and invasion of external pathogens. Unlike all other biological lipid membranes (such as intracellular organelles and plasma membranes), molecules in the SC lipid matrix show small hydrophilic groups and large variability in the length of the alkyl tails and in the numbers and positions of groups that are capable of forming hydrogen bonds. Molecular simulations provide a route for systematically probing the effects of each of these differences separately. In this article, we present the results from atomistic molecular dynamics of selected lipid bilayers and multi-layers to probe the effect of these polydispersities. We address the nature of the tail packing in the gel-like phase, the hydrogen bond network among head groups, the bending moduli expected for leaflets comprising SC lipids and the conformation of very long ceramide lipids in multi-bilayer lipid assemblies.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Soft electrostatic repulsion in particle monolayers at liquid interfaces: surface pressure and effect of aggregation
Authors: Kralchevsky Peter A. , Danov Krassimir D. , Petkov Plamen V. 
Published: June 2016

Non-densely packed interfacial monolayers from charged micrometre-sized colloid particles find applications for producing micropatterned surfaces. The soft electrostatic repulsion between the particles in a monolayer on an air/water (or oil/water) interface is mediated by the non-polar fluid, where Debye screening is absent and the distances between the particles are considerably greater than their diameters. Surface pressure versus area isotherms were measured at the air/water interface. The experiments show that asymptotically the surface pressure is inversely proportional to the third power of the interparticle distance. A theoretical model is developed that predicts not only the aforementioned asymptotic law but also the whole surface pressure versus area dependence. An increase in the surface pressure upon aggregation of charged particles in the interfacial monolayers is experimentally established. This effect is explained by the developed theoretical model, which predicts that the surface pressure should linearly increase with the square root of the particle mean aggregation number. The effect of added electrolyte on the aggregation is also investigated. The data lead to the conclusion that ‘limited aggregation’ exists in the monolayers of charged particles. In brief, the stronger electrostatic repulsion between the bigger aggregates leads to a higher barrier to their coalescence that, in turn, prevents any further aggregation, i.e. negative feedback is present.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
A phenomenological description of BslA assemblies across multiple length scales
Authors: Morris Ryan J. , Bromley Keith M. , Stanley-Wall Nicola , MacPhee Cait E. 
Published: June 2016

Intrinsically interfacially active proteins have garnered considerable interest recently owing to their potential use in a range of materials applications. Notably, the fungal hydrophobins are known to form robust and well-organized surface layers with high mechanical strength. Recently, it was shown that the bacterial biofilm protein BslA also forms highly elastic surface layers at interfaces. Here we describe several self-assembled structures formed by BslA, both at interfaces and in bulk solution, over a range of length scales spanning from nanometres to millimetres. First, we observe transiently stable and highly elongated air bubbles formed in agitated BslA samples. We study their behaviour in a range of solution conditions and hypothesize that their dissipation is a consequence of the slow adsorption kinetics of BslA to an air–water interface. Second, we describe elongated tubules formed by BslA interfacial films when shear stresses are applied in both a Langmuir trough and a rheometer. These structures bear a striking resemblance, although much larger in scale, to the elongated air bubbles formed during agitation. Taken together, this knowledge will better inform the conditions and applications of how BslA can be used in the stabilization of multi-phase materials.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Curvature-driven assembly in soft matter
Authors: Liu Iris B. , Sharifi-Mood Nima , Stebe Kathleen J. 
Published: June 2016

Control over the spatial arrangement of colloids in soft matter hosts implies control over a wide variety of properties, ranging from the system’s rheology, optics, and catalytic activity. In directed assembly, colloids are typically manipulated using external fields to form well-defined structures at given locations. We have been developing alternative strategies based on fields that arise when a colloid is placed within soft matter to form an inclusion that generates a potential field. Such potential fields allow particles to interact with each other. If the soft matter host is deformed in some way, the potential allows the particles to interact with the global system distortion. One important example is capillary assembly of colloids on curved fluid interfaces. Upon attaching, the particle distorts that interface, with an associated energy field, given by the product of its interfacial area and the surface tension. The particle’s capillary energy depends on the local interface curvature. We explore this coupling in experiment and theory. There are important analogies in liquid crystals. Colloids in liquid crystals elicit an elastic energy response. When director fields are moulded by confinement, the imposed elastic energy field can couple to that of the colloid to define particle paths and sites for assembly. By improving our understanding of these and related systems, we seek to develop new, parallelizable routes for particle assembly to form reconfigurable systems in soft matter that go far beyond the usual close-packed colloidal structures.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Non-ionic surfactant phase diagram prediction by recursive partitioning
Authors: Bell Gordon 
Published: June 2016

A model has been designed to predict the phase which forms in water for a non-ionic surfactant, at a given concentration and temperature. The full phase diagram is generated by selecting enough data points to cover the region of interest. The model estimates the probability for each one of 10 possible phases and selects the one with the highest likelihood. The probabilities are based on the recursive partitioning of a dataset of 10 000 known observations. The model covers alkyl chain length and branching, ethoxylate head length and number, and end capping of one or more of the ethoxylate chains. The relationship between chemical structure, shape and phase behaviour is discussed.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Self-assembly of small peptide amphiphiles, the structures formed and their applications. (A foods and home and personal care perspective)
Authors: Frith W. J. 
Published: June 2016

In this opinion piece, some specific challenges in the field of peptide self-assembly and gel formation are discussed. One major hurdle to finding functional small peptides is that there are a huge number of compounds to explore, which increases exponentially with the peptide size. This in itself creates a barrier to the discovery and application of materials, both through the difficulty of finding the peptides, and because protecting inventions also becomes more difficult. Recent work has shown that computer simulations may provide us a route to explore such a huge compound space; this is discussed along with the prospect for future developments. At the microscopic scale, many fibril-forming peptides form gels, apparently through a process of lateral association of primary self-assembled filaments, which leads to a relatively coarse-grained structure of rigid interconnects. However, recent data obtained on Fmoc-tyrosine gels appear to indicate that the gel microstructure is both more flexible and finer grained than previously believed. As such, it is clear that there is a considerable amount that is still not understood regarding this class of gel.
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
The origin and evolution ofHomo sapiens
Authors: Stringer Chris 
Published: June 2016

If we restrict the use ofHomo sapiensin the fossil record to specimens which share a significant number of derived features in the skeleton with extantH. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister speciesHomo neanderthalensisshared a last common ancestor in the middle Pleistocene approximately 400–700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of thesapienslineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards latersapiensmorphology, and there was chronological overlap between different ‘archaic’ and ‘modern’ morphs. Even in the late Pleistocene within and outside Africa, we findH. sapiensspecimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.This article is part of the themed issue ‘Major transitions in human evolution’.
A demographic perspective on the Middle to Later Stone Age transition from Nasera rockshelter, Tanzania
Authors: Tryon Christian A. , Faith J. Tyler 
Published: June 2016

Increased population density is among the proposed drivers of the behavioural changes culminating in the Middle to Later Stone Age (MSA–LSA) transition and human dispersals from East Africa, but reliable archaeological measures of demographic change are lacking. We use Late Pleistocene–Holocene lithic and faunal data from Nasera rockshelter (Tanzania) to show progressive declines in residential mobility—a variable linked to population density—and technological shifts, the latter associated with environmental changes. These data suggest that the MSA–LSA transition is part of a long-term pattern of changes in residential mobility and technology that reflect human responses to increased population density, with dispersals potentially marking a complementary response to larger populations.This article is part of the themed issue ‘Major transitions in human evolution’.
The transition to foraging for dense and predictable resources and its impact on the evolution of modern humans
Authors: Marean Curtis W. 
Published: June 2016

Scientists have identified a series of milestones in the evolution of the human food quest that are anticipated to have had far-reaching impacts on biological, behavioural and cultural evolution: the inclusion of substantial portions of meat, the broad spectrum revolution and the transition to food production. The foraging shift to dense and predictable resources is another key milestone that had consequential impacts on the later part of human evolution. The theory of economic defendability predicts that this shift had an important consequence—elevated levels of intergroup territoriality and conflict. In this paper, this theory is integrated with a well-established general theory of hunter–gatherer adaptations and is used to make predictions for the sequence of appearance of several evolved traits of modern humans. The distribution of dense and predictable resources in Africa is reviewed and found to occur only in aquatic contexts (coasts, rivers and lakes). The palaeoanthropological empirical record contains recurrent evidence for a shift to the exploitation of dense and predictable resources by 110 000 years ago, and the first known occurrence is in a marine coastal context in South Africa. Some theory predicts that this elevated conflict would have provided the conditions for selection for the hyperprosocial behaviours unique to modern humans.This article is part of the themed issue ‘Major transitions in human evolution’.
The empirical case against the ‘demographic turn’ in Palaeolithic archaeology
Authors: Collard Mark , Vaesen Krist , Cosgrove Richard , Roebroeks Wil 
Published: June 2016

Recently, it has become commonplace to interpret major transitions and other patterns in the Palaeolithic archaeological record in terms of population size. Increases in cultural complexity are claimed to result from increases in population size; decreases in cultural complexity are suggested to be due to decreases in population size; and periods of no change are attributed to low numbers or frequent extirpation. In this paper, we argue that this approach is not defensible. We show that the available empirical evidence does not support the idea that cultural complexity in hunter–gatherers is governed by population size. Instead, ethnographic and archaeological data suggest that hunter–gatherer cultural complexity is most strongly influenced by environmental factors. Because all hominins were hunter–gatherers until the Holocene, this means using population size to interpret patterns in the Palaeolithic archaeological record is problematic. In future, the population size hypothesis should be viewed as one of several competing hypotheses and its predictions formally tested alongside those of its competitors.This article is part of the themed issue ‘Major transitions in human evolution’.
Sacral agenesis: A pilot whole exome sequencing and copy number study
Authors: Porsch Robert M. , Merello Elisa , De Marco Patrizia , Cheng Guo , Rodriguez Laura , So Manting , Sham Pak C. , Tam Paul K. , Carpa Valeria , Cherny Stacey S. , Garcia-Barcelo Maria-Mercè , Campbell Desmond D. 
Published: June 2016

BackgroundCaudal regression syndrome (CRS) or sacral agenesis is a rare congenital disorder characterized by a constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. CRS is a complex condition, attributed to an abnormal development of the caudal mesoderm, likely caused by the effect of interacting genetic and environmental factors. A well-known risk factor is maternal type 1 diabetes.ResultsIn this pilot study, exome sequencing and copy number variation (CNV) analyses of 4 CRS trios implicate a number of candidate genes, includingMORN1,ZNF330,CLTCL1andPDZD2.De novomutations were found inSPTBN5,MORN1andZNF330and inherited predicted damaging mutations inPDZD2(homozygous) andCLTCL1(compound heterozygous) as well as in CRS-related genesPTEN(heterozygous) andVANGL1(heterozygous). In addition, a compound heterozygous mutation inGLTSCR2, a direct regulator ofPTENwas identified.Two CNV deletions, onede novo(chr3q13.13) and one homozygous (chr8p23.2), were detected in one of our CRS patients. These deletions overlapped with CNVs previously reported in patients with similar phenotype.ConclusionDespite the genetic diversity and the complexity of the phenotype, this pilot study identified genetic features common across CRS patients.
Maintaining proton homeostasis is an essential role of glucose metabolism in cell survival
Authors: Cui Yanfen , Wang Yuanyuan , Xing Pan , Qiu Li , Liu Miao , Wang Xin , Ying Guoguang , Li Binghui 
Published: June 2016

AbstractAerobic glycolysis, termed “the Warburg Effect”, supports cell proliferation, and glucose deprivation directly elicits necrosis or shifts stimuli-induced apoptosis to necrosis. However, how glucose metabolism regulates cell survival or death choice remains largely unclear. Here we use our recently developed method to monitor in real-time cellular apoptosis and necrosis, and uncover a metabolic homeostasis linked to cell death control. We show that glucose metabolism is the major source to maintain both intracellular and extracellular proton homeostasis. Glucose deficiency leads to lack of proton provision, which provokes a compensatory lysosomal proton efflux and resultant increased lysosomal pH. This lysosomal alkalinization can trigger necrosis. Furthermore, artificial proton supplement enables cells to survive glucose deprivation. Taken together, our results reveal a critical role of glucose metabolism in maintaining cellular microenvironment, and provide a better understanding of the essential requirement of aerobic glycolysis for proliferating cells whose active anabolism consumes a great many protons.