פרסומים

The liver is the main organ responsible for the modification, clearance, and transformational toxicity of most xenobiotics owing to its abundance in cytochrome P450 (CYP450) enzymes. However, the scarcity and variability of primary hepatocytes currently limits their utility. Human pluripotent stem cells (hPSCs) represent an excellent source of differentiated hepatocytes; however, current protocols still produce fetal-like hepatocytes with limited mature function. Interestingly, fetal hepatocytes acquire mature CYP450 expression only postpartum, suggesting that nutritional cues may drive hepatic maturation. We show that vitamin K2 and lithocholic acid, a by-product of intestinal flora, activate pregnane X receptor (PXR) and subsequent CYP3A4 and CYP2C9 expression in hPSC-derived and isolated fetal hepatocytes. Differentiated cells produce albumin and apolipoprotein B100 at levels equivalent to primary human hepatocytes, while demonstrating an 8-fold induction of CYP450 activity in response to aryl hydrocarbon receptor (AhR) agonist omeprazole and a 10-fold induction in response to PXR agonist rifampicin. Flow cytometry showed that over 83% of cells were albumin and hepatocyte nuclear factor 4 alpha (HNF4α) positive, permitting high-content screening in a 96-well plate format. Analysis of 12 compounds showed an R2 correlation of 0.94 between TC50 values obtained in stem cell-derived hepatocytes and primary cells, compared to 0.62 for HepG2 cells. Finally, stem cell-derived hepatocytes demonstrate all toxicological endpoints examined, including steatosis, apoptosis, and cholestasis, when exposed to nine known hepatotoxins. Conclusion: Our work provides fresh insights into liver development, suggesting that microbial-derived cues may drive the maturation of CYP450 enzymes postpartum. Addition of these cues results in the first functional, inducible, hPSC-derived hepatocyte for predictive toxicology. © 2015 by the American Association for the Study of Liver Diseases.

In this work we demonstrate the planar configuration on hole conductor (HTM) free perovskite based solar cells. The CH3NH3PbI3 perovskite was deposited using the spray technique to achieve micrometer size perovskite crystals. The number of spray passes changes the CH3NH3PbI3 film thickness; for example, 10 spray passes achieved a film thickness of 3.4 μm of perovskite. Surprisingly, power conversion efficiency of 6.9% was demonstrated for this novel, simple solar cell structure with thick perovskite film that has no HTM. Capacitance-voltage measurements reveal charge accumulation at the CH3NH3PbI3/Au interface while the compact TiO2/CH3NH3PbI3 junction showed a space charge region, which inhibits the recombination. Studying these interfaces is key to understanding the operation mechanism of this unique solar cell structure. This simple planar HTM free perovskite solar cell demonstrates the potential to make large-scale solar cells while maintaining a simple, low-cost architecture.

Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits. © 2015, Springer Science+Business Media New York.

The resharpening of sidescrapers is a widely discussed issue in recent Middle Paleolithic studies. However, in the Levantine record the evidence for sidescraper resharpening is meager. The Middle Paleolithic site of Nesher Ramla, Israel, represents a rare case in which sidescrapers were frequently modified by removal of longitudinal spalls from their edges. Both parent sidescrapers and spalls, 'Long Sharpening Flakes' (LSF), are abundant throughout the site's stratigraphy, providing a rare opportunity for a complementary study of both artifact groups. The aim of the present study is to reconstruct the life history of sidescrapers retrieved from Nesher Ramla. We ask how the LSF removal changed the morphology of the sidescraper edge, at which stage of the sidescraper life-history it occurred, what was the purpose of LSF removal and was it a part of a recycling system aimed at producing a new edge/tool type or the maintenance of the existing tool edge.

The studied artifacts (100 parent sidescrapers and 60 complete LSF) were sampled randomly from the most intensively occupied and richest layers of the site. Our results suggest that sidescraper edge modification was a well-mastered and skillful process that resulted in standardized and morphologically distinct products. In most cases the sidescrapers were not further retouched after the LSF removal. This leads us to propose that the major goal was to transform the sidescraper into a tool with a sharp, straight and flat edge. The LSF removal at Nesher Ramla provides an exceptional case in which a simple raw edge was deliberately manufactured at the expense of the previously retouched edge. This reinforces the previous assumptions that simple raw edges were often preferred over retouched ones.

Sharks, rays and other elasmobranch fishes are characterized by a skeletal type that is unique among living vertebrates, comprised predominantly of an unmineralized cartilage, covered by a thin outer layer of sub-millimeter, mineralized tiles called tesserae. The mineralized portion of the skeleton appears to grow only by apposition, adding material at the edges of each tessera; maintenance of non-mineralized joints between tesserae is therefore vital, with precise control of mineral deposition and inhibition at the many thousands of growth fronts in the skeleton. Yet, we have only scattered evidence as to how the elasmobranchs mineralize and grow their skeletons. In this review, we take an “environment to skeleton” approach, drawing together research from a vast range of perspectives to track calcium and phosphate from the typical elasmobranch habitats into and through the body, to their deposition at tesseral growth fronts. In the process, we discuss the available evidence for skeletal resorption capability, mineral homeostasis hormones, and nucleation inhibition mechanisms. We also outline relevant theories in crystal nucleation and typical errors in measurements of serum calcium and phosphate in the study of vertebrate biology. We assemble research that suggests consensus in some concepts in elasmobranch skeletal development, but also highlight the very large gaps in our knowledge, particularly in regards to endocrine functional networks and biomineralization mechanisms. In this way, we lay out frameworks for future directions in the study of elasmobranch skeletal biology with stronger and more comparative links to research in other disciplines and into other taxa.

We demonstrate tunable electro-optic guiding, shaping, and switching of beams in the near infrared spectrum ( 980 nm), typical of VCSEL technology, using biomimetic 3D funnel waveguides miniaturized into a sample of potassium–lithium–tantalate–niobate. The switchable waveguides are written using the slow photorefractive build-up of a 3D volume space-charge field caused by a diffracting continuous wave low intensity λ = 532 nm beam, and electro-optic functionality is supported by the quadratic electro-optic effect of the high-symmetry paraelectric phase. [ABSTRACT FROM AUTHOR]Copyright of Journal of Optics is the property of IOP Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Modes of Uncertainty: Anthropological Cases argues that today it is vital to distinguish danger, risk, and uncertainty analytically and anthropologically. In order to do so, it presents a series of concepts and cases that clarify emergent problem spaces as well as to the way these domains are currently addressed—or not addressed—by relevant scholarship. It argues that the scholarly fields previously understood as covering risk are inadequate in part because the world is increasingly being populated by forms, practices and events of uncertainty that cannot be reduced to risk. It makes the case that the study of uncertainty should not focus solely on the appearance of new risks and dangers in the world which no doubt abound, but also on how uncertainty itself should be defined as a problem; and the forms of governing and experience that are emerging in relation to it. The studies in this book, with contributions from various anthropological domains (economics and entrepreneurialism, security and humanitarianism, health and environment), enable consideration of the forms of knowledge and technologies applied to the problem of managing uncertainty, as well as differing modes of subjectivity appropriate to forms of action currently developing beyond risk assessment. The volume brings together recent thinkers whose work, while not ignoring previous scholarship on risk, nevertheless provides ground-breaking attention to the domain of uncertainty providing analytic tools and case studies necessary for understanding that domain.

Potassium (K) is an essential macronutrient shown to play a fundamental role in photosynthetic processes and may facilitate photoinhibition resistance. In some plant species, sodium (Na) can partially substitute for K. Although photosynthetic enhancement has been well established, the mechanisms by which K or Na affects photosynthesis are not fully understood. Olive (Olea europaea L.) trees were previously shown to benefit from Na nutrition when K is limiting. In order to study the effect of K and Na on photosynthetic performance, we measured gas exchange and chlorophyll fluorescence in young olive trees supplied with either K, Na or no fertilizer, and subjected to manipulated levels of CO2, O2 and radiation. Light and CO2 response curves indicate substantially superior photosynthetic capacity of K-sufficient trees, while Na substitution generated intermediate results. The enhanced performance of K, and to a lesser extent, Na-supplied trees was found to be related mainly to modification of non-stomatal limitation. This indicates that K deficiency promotes inhibition of enzymatic-photochemical processes. Results indicate lower chlorophyll content and altered Rubisco activity as probable causes of photosynthetic impairment. Potassium deficiency was found to diminish photoprotection mechanisms due to reduced photosynthetic and photorespiratory capacity. The lower CO2 and O2 assimilation rate in K-deficient trees caused elevated levels of exited energy. Consequently, non-photochemical quenching, an alternative energy dispersion pathway, was increased. Nonetheless, K-deficient trees were shown to suffer from photodamage to photosystem-II. Sodium replacement considerably diminished the negative effect of K deficiency on photoprotection mechanisms. The overall impact of K and Na nutrition plays down any indirect effect on stomatal limitation and rather demonstrates the centrality of these elements in photochemical processes of photosynthesis and photoprotection. © 2015 Elsevier GmbH.