bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Digestive Physiology
Authors: H. Karasov William , Douglas Angela E.
Published: April 2013

In vertebrates and invertebrates, morphological and functional features of gastrointestinal (GI) tracts generally reflect food chemistry, such as content of carbohydrates, proteins, fats, and material(s) refractory to rapid digestion (e.g., cellulose). The expression of digestive enzymes and nutrient transporters approximately matches the dietary load of their respective substrates, with relatively modest excess capacity. Mechanisms explaining differences in hydrolase activity between populations and species include gene copy number variations and single‐nucleotide polymorphisms. Transcriptional and posttranscriptional adjustments mediate phenotypic changes in the expression of hydrolases and transporters in response to dietary signals. Many species respond to higher food intake by flexibly increasing digestive compartment size. Fermentative processes by symbiotic microorganisms are important for cellulose degradation but are relatively slow, so animals that rely on those processes typically possess special enlarged compartment(s) to maintain a microbiota and other GI structures that slow digesta flow. The taxon richness of the gut microbiota, usually identified by 16S rRNA gene sequencing, is typically an order of magnitude greater in vertebrates than invertebrates, and the interspecific variation in microbial composition is strongly influenced by diet. Many of the nutrient transporters are orthologous across different animal phyla, though functional details may vary (e.g., glucose and amino acid transport with K+rather than Na+as a counter ion). Paracellular absorption is important in many birds. Natural toxins are ubiquitous in foods and may influence key features such as digesta transit, enzymatic breakdown, microbial fermentation, and absorption. © 2013 American Physiological Society.Compr Physiol3:741‐483, 2013.
Apoptosis and Necrosis in the Liver
Authors: Guicciardi Maria Eugenia , Malhi Harmeet , Mott Justin L. , Gores Gregory J.
Published: April 2013

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor‐mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor‐induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. © 2013 American Physiological Society.Compr Physiol3:977‐1010, 2013.
Cellular and Molecular Basis of Liver Development
Authors: Shin Donghun , Monga Satdarshan Pal Singh
Published: April 2013

Liver is a prime organ responsible for synthesis, metabolism, and detoxification. The organ is endodermal in origin and its development is regulated by temporal, complex, and finely balanced cellular and molecular interactions that dictate its origin, growth, and maturation. We discuss the relevance of endoderm patterning, which truly is the first step toward mapping of domains that will give rise to specific organs. Once foregut patterning is completed, certain cells within the foregut endoderm gain competence in the form of expression of certain transcription factors that allow them to respond to certain inductive signals. Hepatic specification is then a result of such inductive signals, which often emanate from the surrounding mesenchyme. During hepatic specification bipotential hepatic stem cells or hepatoblasts become apparent and undergo expansion, which results in a visible liver primordium during the stage of hepatic morphogenesis. Hepatoblasts next differentiate into either hepatocytes or cholangiocytes. The expansion and differentiation is regulated by cellular and molecular interactions between hepatoblasts and mesenchymal cells including sinusoidal endothelial cells, stellate cells, and also innate hematopoietic elements. Further maturation of hepatocytes and cholangiocytes continues during late hepatic development as a function of various growth factors. At this time, liver gains architectural novelty in the form of zonality and at cellular level acquires polarity. A comprehensive elucidation of such finely tuned developmental cues have been the basis of transdifferentiation of various types of stem cells to hepatocyte‐like cells for purposes of understanding health and disease and for therapeutic applications. © 2013 American Physiological Society.Compr Physiol3:799‐815, 2013.
Label‐Free Analysis of Cellular Biochemistry by Raman Spectroscopy and Microscopy
Authors: Schie Iwan W. , Huser Thomas
Published: April 2013

We review the biomedical applications of Raman spectroscopy at the single cell and tissue level. Raman scattering is the inelastic scattering of light by molecular bonds resulting in a wealth of spectral bands, which enable the identification of biological materials and the nondestructive analysis of dynamic changes in their biochemistry. We briefly review the basics behind highly sensitive Raman spectroscopy and highlight recent applications to biomedical research. We discuss advanced chemometrics methods that are utilized to analyze Raman spectral data and which permit one, for example, to distinguish between normal and diseased cells or which enable one to follow the differentiation of stem cells without perturbing the cellular biochemistry. We also discuss advanced coherent Raman scattering techniques, such as coherent anti‐Stokes Raman scattering and stimulated Raman scattering, which allow for the molecularly specific imaging of cells, tissues, and entire organismsin vitroandin vivo. © 2013 American Physiological Society.Compr Physiol3:941‐956, 2013.
Diagnostic evaluation of metastatic rhabdomyosarcoma in effusion specimens
Authors: Alderman Megan A. , Thomas Dafydd G. , Roh Michael H.
Published: April 2013

Sarcomas, including rhabdomyosarcoma (RMS), are rarely encountered in effusion specimens; therefore, difficulties in the accurate diagnosis of metastatic sarcomas in effusions can occasionally arise. Immunohistochemistry for myogenin has emerged as a useful adjunct in the diagnosis of RMS, especially in small biopsy specimens. To date, there are no published series describing the utility of immunocytochemistry for myogenin in the diagnosis of RMS in effusion specimens. A total of 15 patients, for whom metastatic sarcomas were diagnosed in effusion specimens between 1998 and 2012, were identified for analysis: alveolar RMS (n = 5); embryonal RMS (n = 1); pleomorphic RMS (n = 1); angiosarcoma (n = 1); Ewing's sarcoma (n = 2); osteosarcoma (n = 1); endometrial stromal sarcoma (n = 1); unclassified spindle cell sarcoma (n = 1); unclassified/undifferentiated pleomorphic sarcoma (n = 1); and leiomyosarcoma (n = 1). Immunocytochemistry for myogenin was performed for each of these cases as well as for 102 effusions that were positive for metastatic carcinoma. Immunocytochemistry for myogenin diffusely and strongly highlighted the nuclei of the tumor cells in six (86%) of seven cases of metastatic RMS; specifically, the five alveolar RMS and one embryonal RMS cases. The one case of pleomorphic RMS, the eight remaining metastatic sarcoma cases, and all 102 cases of metastatic carcinoma were completely negative for myogenin expression. In conclusion, immunocytochemistry for myogenin is a sensitive and specific ancillary adjunct in the diagnostic evaluation of metastatic RMS in effusion specimens. Diagn. Cytopathol. 2013;41:955–959. © 2013 Wiley Periodicals, Inc.
Pathways of introduction of the invasive aquatic plant Cabomba caroliniana
Authors: McCracken Andrée , Bainard Jillian D. , Miller Michelle C. , Husband Brian C.
Published: April 2013

The pathway and frequency of species' introductions can affect the extent, impact, and management of biological invasions. Here, we examine the pathway of introduction of the aquatic plant Cabomba caroliniana (fanwort) into Canada and the northern United States using plastid DNA sequence (intergenic spacers atpF‐atpH, trnH‐psbA, and trnL‐trnF) and DNA content analyses. We test the hypothesis that the spread of fanwort is a result of commercial trade by comparing a Canadian population (Kasshabog Lake, ON) to native populations from southern U.S., introduced populations in northern U.S., and plants from commercial retailers. Thirteen plastid haplotypes were identified throughout North America, including one dominant haplotype, which was present in all C. caroliniana populations. Several rare haplotypes were used to infer shared colonization history. In particular, the Canadian population shared two rare alleles with a population from Massachusetts, suggesting range expansion of C. caroliniana from the northern U.S. However, the possibility of a commercial introduction cannot be excluded, as common alleles were shared between the Canadian population and both commercial and southern U.S. sources. Variation in C. caroliniana genome size was bimodal and populations were classified into “high” and “low” categories. The Canadian population had DNA contents similar to several northern U.S. populations (low DNA content). This may provide additional support for range expansion from these introduced populations rather than from commercial sources or populations in the southern U.S., which had high DNA content.
Alpha‐tocopherol microspheres with cross‐linked and acetylated inulin and their release profile in a hydrophilic model
Authors: García Paula , Vega Juan , Jimenez Paula , Santos José , Robert Paz
Published: April 2013

Alpha‐tocopherol (AT) was encapsulated with native (NIn), acetylated (AIn) or cross‐linked (CIn) inulin (two degrees each) by spray‐drying. A face central composite experimental design for each system (AT–NIn, AT–AIn1, AT–AIn2, AT–CIn1, and AT–CIn2) was evaluated to determine the influence of inlet air temperature and AT/coating material ratio on the AT encapsulation percentage (EP). The AT microspheres obtained under optimal conditions were characterized determining the AT EP, morphology and their release profile in a hydrophilic system. The AT encapsulating percentage reached values above 86% in all the systems studied. The acetylation and cross‐linking of inulin improved slight but significantly the AT encapsulating percentage respect to native inulin. The release profiles showed biphasic behavior, being the first and second zone attributed to uncovered and encapsulated AT, respectively. The AT release was <15% (0–540 min) from all AT‐inulin microparticles, corresponding mainly to superficial AT release, following Higuchi model consistent with a diffusional mechanism. AT release rate constant from AT–NIn microspheres was significantly lower than those of AT–AIn and AT–CIn. The AT release pattern suggest that the microparticles could be applied in the design of functional foods, preserving the nutritional role of AT.
Influence of lipids on the properties of solid lipid nanoparticles from microemulsion technique
Authors: Boonme Prapaporn , Souto Eliana B. , Wuttisantikul Norasak , Jongjit Tarntep , Pichayakorn Wiwat
Published: April 2013

Solid lipid nanoparticles (SLN) are colloidal lipid carriers widely employed as efficient drug delivery systems. In this report, SLN were produced by microemulsion technique, and the influence of lipid composition on the physical properties of SLN was evaluated. Lipids with different molecular structures in carbon number of the fatty acid residue and their polarity were selected (i.e., glyceryl trimyristate, glyceryl tripalmitate, glyceryl tristearate, stearic acid, and glyceryl monostearate). A warm oil‐in‐water microemulsion containing 7% lipid, 30% water, and 63% surfactant mixture (polysorbate 80:1‐butanol 4:1) was prepared by simple mixing at 60°C, following its dilution in cold water at various ratios at constant stirring. The obtained SLN were analyzed for appearance, particle size, zeta potential, and sedimentation rate. The chemical structure of the selected lipids affected both the microemulsion formation and the physical characteristics of SLN. From the obtained results, a dilution ratio of 1:50 was selected for the production of SLN composed of glyceryl trimyristate as solid lipid matrix. The obtained particles were of 154.9 ± 0.7 nm mean particle size, with a polydispersity index (PI) of 0.274 and zeta potential of −7.46 ± 0.68 mV.

Practical applications: The methodology presented here describes the application of microemulsion technique on processing different lipid compositions, to develop and produce an optimal SLN formulation using pseudoternary phase diagrams. Microemulsion technique is well‐known for preparation SLN by adding a warm oil‐in‐water microemulsion, which can be spontaneously formed, when diluted in a large volume of cold water. The data presented in this paper show that the molecular structures of lipids influenced both the microemulsion formation and the physical characteristics of the resulting SLN. The optimal SLN formulation could be developed.
Screening of antioxidants as stabilisers for Jatropha curcas L. oil
Authors: Subroto Erna , Manurung Robert , Heeres Hero Jan , Broekhuis Antonius Augustinus
Published: April 2013

The effect of antioxidants on the oxidation stability of oils extracted from Jatropha curcas seeds was measured by the accelerated oxidation test specified in EN 14112 using commercial Rancimat 873 equipment. To find the appropriate antioxidant for jatropha oil, fourteen different antioxidants were screened at concentrations of 500 and 1000 ppm. Pyrogallol (PY) and propyl gallate (PG) significantly improved the oxidative stability of jatropha oil and PY was further studied at concentrations of 50–1000 ppm. Even at concentrations as low as 50 ppm, PY was found to fulfill the specifications set by the DIN 51605 norm for plant oil as biofuels. Mixtures of antioxidants were tested at concentrations varying between 100 and 1000 ppm, showing a synergistic effect for the combination of PY and N,N′‐di‐sec‐butyl‐p‐phenylenediamine at all concentrations and ratios tested. It further was found that the quality, i.e. the history of the oil in terms of processing, age and storage conditions, strongly affects the performance of PY as the antioxidant. PY in particular improved the oxidative stability of oxidized and highly acidic oils. PY was found to be a good antioxidant for both jatropha oil and the derived biodiesel.

Practical applications: Jatropha oil is one of many potential triglyceride feedstocks suitable for the production of biofuel or other consumer products. Finding the best antioxidant for this particular resource is important since the resistance to oxidative degradation depends on the chemical structure of the triglyceride. Pyrogallol was found to be the preferred antioxidant with beneficial results found for oxidized and, as a result, highly acidic oils. The results of this study are useful for companies involved in jatropha oil‐derived products such as biodiesel, lubricants or other non‐food applications.
Associations of RBP4 with lipid metabolism and renal function in diabetes mellitus
Authors: Junjun Wang , Jia Wu , Jiaxi Song , Dongmei Niu , Yonghui Shi , Fang Zheng , Xin Zhou
Published: April 2013

To investigate the plasma retinol‐binding protein 4 (RBP4), small dense low‐density lipoprotein cholesterol (sdLDL‐C), oxidized low‐density lipoprotein (ox‐LDL) levels and to evaluate the associations of RBP4 with abnormal lipid metabolism and renal dysfunction in type 2 diabetes mellitus (T2DM) patients, we determined RBP4, sdLDL‐C, ox‐LDL levels and renal parameters in 120 T2DM patients with or without nephropathy and 70 controls. The correlation analysis and multiple linear regression analysis were performed. Compared with controls, the RBP4 and sdLDL‐C levels were found significantly increased only in diabetic nephropathy (DN) patients and ox‐LDL levels were elevated in both groups of T2DM patients. The RBP4 levels were positively correlated with sdLDL‐C, ox‐LDL, and negatively with estimated glomerular filtration rate (eGFR) in all the T2DM patients. Multiple linear regression analysis showed that sdLDL‐C and eGFR were the independent predictors of RBP4 levels, and RBP4 were one of the independent determinants for sdLDL‐C and ox‐LDL levels in T2DM patients, respectively. In conclusion, plasma RBP4, sdLDL‐C, ox‐LDL levels were significantly increased in DN patients. Circulating RBP4 may be associated with abnormal lipid metabolism and renal dysfunction, and considered as a biomarker of cardiovascular disease and renal function in T2DM patients.

Practical applications: The findings in the present study support the hypothesis that circulating RBP4 not only plays an important role in lipid metabolism abnormalities of atherosclerosis, contributing to the increased risk of CVD, but also could reflect renal dysfunction and be associated with the severity of nephropathy in T2DM patients. Therefore, the clinical monitoring of plasma RBP4 level as well as its dynamic changes may possess distinctly clinical value for assessments of renal function and CVD risk in T2DM patients. These findings may contribute to the further understanding of the pathogenic role of circulating RBP4 in proatherogenic dyslipidemia and nephropathy in T2DM.
Production of lipids and docosahexasaenoic acid (DHA) by a native Thraustochytrium strain
Authors: Shene Carolina , Leyton Allison , Rubilar Mónica , Pinelo Manuel , Acevedo Francisca , Morales Eduardo
Published: April 2013

Production of docosahexasaenoic acid (DHA) by a native Labyrinthulomycetes strain, Thraustochytriidae sp. TN5, whose growth characteristics present some differences to related strains, was scaled from shaken flask to a laboratory fermentor. The effect of the growth medium composition and growth conditions for (i) biomass production, (ii) lipid content of the biomass, and (iii) DHA content in the lipids was determined. Taguchi's design of experiments was used to study the influence of two discrete – carbon and nitrogen sources – and six continuous – concentrations of the carbon and nitrogen sources, yeast extract and artificial seawater, incubation temperature, and time‐ factors on the three mentioned variables. In the flask experiments the lipidic content in the biomass (25.2% w/w) and DHA concentration (0.48 g/L) were the highest at the following conditions: maltose 20 g/L, sodium glutamate 2.4 g/L, yeast extract 6 g/L, 72 h, 25°C, and artificial seawater 30% v/v; under these conditions biomass concentration was 5.1 g/L. Fed‐batch allowed to increase biomass concentration to 14 g/L. The lipidic fraction of Thraustochytriidae sp. TN5 biomass in the repeated batches was found between 16.2 and 34.8% w/w. Under this growth condition lipids and DHA productivities were 50 and 23 mg/(L h), respectively.

Practical applications: Consumption of long chain‐polyunsaturated fatty acids (LC‐PUFA) belonging to the omega‐3 family such as DHA has several positive effects on human and animal health. However, natural sources are restricted to cold‐water fish and their oils. Marine protists are also good candidates for the production of microbial DHA. For evaluating the potential of new strains the effect of the growth medium composition, growth conditions, and cultivation mode on DHA productivity has to be determined. In this work the production of DHA by a native Labyrinthulomycetes strain was scaled from shaken flask to a laboratory fermentor with the aid of Taguchi's methodology, process in which biomass concentration, lipid content in the biomass, and DHA content in the lipids were increased.
The Role of the Chiral cis‐1,3‐Disubstituted 2,2‐Dimethylcyclobutane Motif in the Conformational Bias of Several Types of γ‐Peptides
Authors: Aguilera Jordi , Cobos Juan A. , Gutiérrez‐Abad Raquel , Acosta Carles , Nolis Pau , Illa Ona , Ortuño Rosa M.
Published: April 2013

Three series of new γ‐peptides have been synthesized by starting from conveniently protected cis‐3‐amino‐2,2‐dimethylcyclobutane‐1‐carboxylic acid derivatives. The first series is constructed with only one enantiomer of this γ‐amino acid, whereas in the second one both enantiomeric cyclobutane residues are joined in alternating fashion. The high degrees of rigidity in these γ‐peptides induce the adoption of extended but sterically constrained conformations in both cases. The third series is the product of alternation of a cyclobutane residue with linear γ‐aminobutyric acid (GABA). Conformational bias in these three systems accounts for the cyclobutane being a major disrupting factor to the formation of strong intramolecular hydrogen bonds, leading to extended conformations. In contrast, investigation of cyclobutane/GABA hybrid γ‐peptides of a fourth series, in which the carbocyclic moiety is not a part of the polyamide skeleton but acts as a chiral polyfunctional platform, reveals that these peptides are able to produce intramolecular hydrogen bonds leading to well defined folded conformations.
Polymer‐Supported Stereoselective Synthesis of (1S,5S)‐6‐Oxa‐3,8‐diazabicyclo[3.2.1]octanes
Authors: Schütznerová Eva , Oliver Allen G. , Zajíček Jaroslav , Krchňák Viktor
Published: April 2013

We describe a polymer‐supported stereoselective synthesis of the (1S,5S)‐6‐oxa‐3,8‐diazabicyclo[3.2.1]octane‐bridged scaffold by tandem iminium ion cyclization/nucleophilic addition reactions. A series of resin‐bound acyclic intermediates bearing different substituents were prepared, and the scope and limitations of the chemical route leading to the bridged scaffold were evaluated. The Thr‐derived bridged scaffold was found to be substantially more stable in acid than the Ser‐derived scaffold, which was partially transformed into dihydropyrazinones. Substitution at the iminium‐forming nitrogen was critical for acid stability, and the N‐arylsulfonamides with electron‐withdrawing groups yielded the highest purity of the crude products prepared by acid‐mediated cleavage. The acid‐labile target compounds were synthesized by nucleophile‐mediated cleavage from the esterified Wang resin and cyclization in formic acid.
Unified Azoline and Azole Syntheses by Optimized Aza‐Wittig Chemistry
Authors: Loos Patrick , Ronco Cyril , Riedrich Matthias , Arndt Hans‐Dieter
Published: April 2013

Intramolecular aza‐Wittig ring closures were applied to synthesize thiazolines, oxazolines, and imidazolines from β‐azido thioester, ester, and amide precursors. The cyclization precursors were obtained from amino acid derivatives. Optimized conditions for diazo transfer with a fast rate and racemization suppression, (thio)esterification, and amide coupling reactions are described. The ring closure reaction can be executed with PPh3 under neutral conditions and was found to be highly chemoselective for five‐membered rings. If amide groups were activated with tosyl groups, smooth intramolecular ring closure of iminophosphoranes furnished enantiopure imidazoline products with position‐specific tosyl protection. This aza‐Wittig‐based azoline synthesis was then extended to double azoline ring closures to furnish catenated azoline building blocks common to peptide natural product building blocks and their analogues.
Stereoselective Synthesis of Benzoxepines through Tandem Alkylation/Michael Addition to Vinylogous Carbonates
Authors: Gharpure Santosh J. , Reddy S. Raja Bhushan
Published: April 2013

A tandem SN2 alkylation/Michael addition to vinylogous carbonates based approach for the stereoselective synthesis of benzoxepines is developed. The stereoselectivity improves with an increase in the steric bulk of the substituents. The method is extended to the synthesis of benzopyranoxepines and benzoxepinopyridines with angular substituents.
Toll‐like receptor 7 stimulates production of specialized pro‐resolving lipid mediators and promotes resolution of airway inflammation
Authors: Koltsida Ourania , Karamnov Sergey , Pyrillou Katerina , Vickery Thad , Chairakaki Aikaterini‐Dimitra , Tamvakopoulos Constantin , Sideras Paschalis , Serhan Charles N. , Andreakos Evangelos
Published: April 2013

Although specialized pro‐resolving mediators (SPMs) biosynthesized from polyunsaturated fatty acids are critical for the resolution of acute inflammation, the molecules and pathways that induce their production remain elusive. Here, we show that TLR7, a receptor recognizing viral ssRNA and damaged self‐RNA, mobilizes the docosahexaenoic acid (DHA)‐derived biosynthetic pathways that lead to the generation of D‐series SPMs. In mouse macrophages and human monocytes, TLR7 activation triggered production of DHA‐derived monohydroxy metabolome markers and generation of protectin D1 (PD1) and resolvin D1 (RvD1). In mouse allergic airway inflammation, TLR7 activation enhanced production of DHA‐derived SPMs including PD1 and accelerated the catabasis of Th2‐mediated inflammation. D‐series SPMs were critical for TLR7‐mediated resolution of airway inflammation as this effect was lost in Alox15−/− mice, while resolution was enhanced after local administration of PD1 or RvD1. Together, our findings reveal a new previously unsuspected role of TLR7 in the generation of D‐series SPMs and the resolution of allergic airway inflammation. They also identify TLR stimulation as a new approach to drive SPMs and resolution of inflammatory diseases.
On the modeling and simulation of a laser‐induced cavitation bubble
Authors: Zein Ali , Hantke Maren , Warnecke Gerald
Published: April 2013

Single cavitation bubbles exhibit severe modeling and simulation difficulties. This is due to the small scales of time and space as well as due to the involvement of different phenomena in the dynamics of the bubble. For example, the compressibility, phase transition, and the existence of a noncondensable gas inside the bubble have strong effects on the dynamics of the bubble. Moreover, the collapse of the bubble involves the occurrence of critical conditions for the pressure and temperature. This adds extra difficulties to the choice of equations of state. Even though several models and simulations have been used to study the dynamics of the cavitation bubbles, many details are still not clearly accounted for.

Here, we present a numerical investigation for the collapse and rebound of a laser‐induced cavitation bubble in liquid water. The compressibility of the liquid and vapor are involved. In addition, great focus is devoted to study the effects of phase transition and the existence of a noncondensable gas on the dynamics of the collapsing bubble. If the bubble contains vapor only, we use the six‐equation model for two‐phase flows that was modified in our previous work [A. Zein, M. Hantke, and G. Warnecke,J. Comput. Phys., 229(8):2964‐2998, 2010]. This model is an extension to the six‐equation model with a single velocity of Kapilaet al.(Phys. Fluid, 13:3002‐3024, 2001) taking into account the heat and mass transfer.

To study the effect of a noncondensable gas inside the bubble, we add a third phase to the original model. In this case, the phase transition is considered only at interfaces that separate the liquid and its vapor. The stiffened gas equations of state are used as closure relations. We use our own method to determine the parameters to obtain reasonable equations of state for a wide range of temperatures and make them suitable for the phase transition effects. We compare our results with experimental ones. Also our results confirm some expected physical phenomena. Copyright © 2013 John Wiley & Sons, Ltd.
Magma flow between summit and Pu‘u ‘Ō‘ō at K̄lauea Volcano, Hawai‘i
Authors: Montagna C. P. , Gonnermann H. M.
Published: April 2013

Volcanic eruptions are often accompanied by spatiotemporal migration of ground deformation, a consequence of pressure changes within magma reservoirs and pathways. We modeled the propagation of pressure variations through the east rift zone (ERZ) of K̄lauea Volcano, Hawai‘i, caused by magma withdrawal during the early eruptive episodes (1983–1985) of the ongoing Pu‘u ‘Ō‘ō‐Kupaianaha eruption. Eruptive activity at the Pu‘u ‘Ō‘ō vent was typically accompanied by abrupt deflation that lasted for several hours and was followed by a sudden onset of gradual inflation once the eruptive episode had ended. Similar patterns of deflation and inflation were recorded at K̄lauea's summit, approximately 15 km to the northwest, albeit with time delays of hours. These delay times can be reproduced by modeling the spatiotemporal changes in magma pressure and flow rate within an elastic‐walled dike that traverses K̄lauea's ERZ. Key parameters that affect the behavior of the magma‐dike system are the dike dimensions, the elasticity of the wall rock, the magma viscosity, and to a lesser degree the magnitude and duration of the pressure variations themselves. Combinations of these parameters define a transport efficiency and a pressure diffusivity, which vary somewhat from episode to episode, resulting in variations in delay times. The observed variations in transport efficiency are most easily explained by small, localized changes to the geometry of the magma pathway.
Revisiting the controversial issue of tropical tropospheric temperature trends
Authors: Mitchell D. M. , Thorne P. W. , Stott P. A. , Gray L. J.
Published: April 2013

Controversy remains over a discrepancy between modeled and observed tropical upper tropospheric temperature trends. This discrepancy is reassessed using simulations from the Coupled Climate Model Inter‐comparison Project phase 5 (CMIP 5) together with radiosonde and surface observations that provide multiple realizations of possible “observed” temperatures given various methods of homogenizing the data. Over the 1979–2008 period, tropical temperature trends are not consistent with observations throughout the depth of the troposphere, and this primarily stems from a poor simulation of the surface temperature trends. This discrepancy is substantially reduced when (1) atmosphere‐only simulations are examined or (2) the trends are considered as an amplification of the surface temperature trend with height. Using these approaches, it is shown that within observational uncertainty, the 5–95 percentile range of temperature trends from both coupled‐ocean and atmosphere‐only models are consistent with the analyzed observations at all but the upper most tropospheric level (150 hPa), and models with ultra‐high horizontal resolution (≤ 0.5° × 0.5°) perform particularly well. Other than model resolution, it is hypothesized that this remaining discrepancy could be due to a poor representation of stratospheric ozone or remaining observational uncertainty.
Simultaneous observations of optical lightning and terrestrial gamma ray flash from space
Authors: Østgaard N. , Gjesteland T. , Carlson B. E. , Collier A. B. , Cummer S. A. , Lu G. , Christian H. J.
Published: April 2013

We present the very first simultaneous detection from space of a terrestrial gamma ray flash (TGF) and the optical signal from lightning. By fortuitous coincidence, two independent satellites passed less than 300 km from the thunderstorm system that produced a TGF that lasted 70  μs. Together with two independent measurements of radio emissions, we have an unprecedented coverage of the event. We find that the TGF was produced deep in the thundercloud at the initial stage of an intracloud (IC) lightning before the leader reached the cloud top and extended horizontally. A strong radio pulse was produced by the TGF itself. This is the first time the sequence of radio pulses, TGF, and optical emissions in an IC lightning flash has been identified.
Coupling of Hawaiian volcanoes only during overpressure condition
Authors: Shirzaei Manoochehr , Walter Thomas R. , Bürgmann Roland
Published: April 2013

Mauna Loa and Kilauea volcanoes, Hawaii, are thought to be coupled by pore pressure diffusion through an asthenospheric melt layer. However, abundant observations of independent activity of these volcanoes suggest a more complicated relationship. Here we analyze surface deformation data, deep seismicity and gas measurements, to reveal strong coupling of these volcanoes between 2003 and 2008. In early 2005, we find a shift from anticorrelation to correlation of magma‐chamber inflation. The shift is preceded by a seismic swarm in the mantle beneath Mauna Loa and accompanied by a large silent slip event beneath the south flank of Kilauea. This suggests that these volcanoes are coupled during mantle‐driven surges and that the 2005 silent slip event was triggered by accelerated magma supply at Kilauea.
Seismoelectric effects due to mesoscopic heterogeneities
Authors: Jougnot Damien , Rubino J. Germán , Carbajal Marina Rosas , Linde Niklas , Holliger Klaus
Published: April 2013

While the seismic effects of wave‐induced fluid flow due to mesoscopic heterogeneities have been studied for several decades, the role played by these types of heterogeneities on seismoelectric phenomena is largely unexplored. To address this issue, we have developed a novel methodological framework which allows for the coupling of wave‐induced fluid flow, as inferred through numerical oscillatory compressibility tests, with the pertinent seismoelectric conversion mechanisms. Simulating the corresponding response of a water‐saturated sandstone sample containing mesoscopic fractures, we demonstrate for the first time that these kinds of heterogeneities can produce measurable seismoelectric signals under typical laboratory conditions. Given that this phenomenon is sensitive to key hydraulic and mechanical properties, we expect that the results of this pilot study will stimulate further exploration on this topic in several domains of the Earth, environmental, and engineering sciences.
Sedimentation in the floodplains of the Mekong Delta, Vietnam Part II: deposition and erosion
Authors: Hung Nguyen Nghia , Delgado José Miguel , Güntner Andreas , Merz Bruno , Bárdossy András , Apel Heiko
Published: April 2013

Deposition and erosion play a key role in the determination of the sediment budget of a river basin, as well as for floodplain sedimentation. Floodplain sedimentation, in turn, is a relevant factor for the design of flood protection measures, productivity of agro‐ecosystems, and for ecological rehabilitation plans. In the Mekong Delta, erosion and deposition are important factors for geomorphological processes like the compensation of deltaic subsidence as well as for agricultural productivity. Floodplain deposition is also counteracting the increasing climate change induced hazard by sea level rise in the delta. Despite this importance, a sediment database of the Mekong Delta is lacking, and the knowledge about erosion and deposition processes is limited. In the Vietnamese part of the Delta, the annually flooded natural floodplains have been replaced by a dense system of channels, dikes, paddy fields, and aquaculture ponds, resulting in floodplain compartments protected by ring dikes. The agricultural productivity depends on the sediment and associated nutrient input to the floodplains by the annual floods. However, no quantitative information regarding their sediment trapping efficiency has been reported yet. The present study investigates deposition and erosion based on intensive field measurements in three consecutive years (2008, 2009, and 2010). Optical backscatter sensors are used in combination with sediment traps for interpreting deposition and erosion processes in different locations. In our study area, the mean calculated deposition rate is 6.86 kg/m2 (≈ 6 mm/year). The key parameters for calculating erosion and deposition are estimated, i.e. the critical bed shear stress for deposition and erosion and the surface constant erosion rate. The bulk of the floodplain sediment deposition is found to occur during the initial stage of floodplain inundation. This finding has direct implications on the operation of sluice gates in order to optimize sediment input and distribution in the floodplains. Copyright © 2013 John Wiley & Sons, Ltd.
Protein‐Protein Interaction Modeling and Inhibition: The TAU Bioinfo3D Perspective
Authors: Wolfson Haim J.
Published: April 2013

Protein‐protein interactions are central to cell function. In order to fully understand these interactions, one has to elucidate the three‐dimensional structures of the underlying complexes. While experimental methods have advanced significantly in the last decade, there are still few structures of protein complexes in the Protein Data Bank. Reliable computational techniques are required to fill in this gap. Better understanding of protein‐protein interactions has also opened a large number of potential targets for the pharmaceutical industry, which previously viewed these interactions as “undruggable”. In this review, we focus on the algorithms developed by the Tel Aviv University Structural Bioinformatics (Bioinfo3D) Lab to model protein‐protein interactions, and on a preliminary attempt to search for peptide inhibitors for these interactions. All the algorithms presented are among the fastest available today and can be accessed via the group web server.
ConSurf: Using Evolutionary Data to Raise Testable Hypotheses about Protein Function
Authors: Celniker Gershon , Nimrod Guy , Ashkenazy Haim , Glaser Fabian , Martz Eric , Mayrose Itay , Pupko Tal , Ben‐Tal Nir
Published: April 2013

Many mutations disappear from the population because they impair protein function and/or stability. Thus, amino acid positions that are essential for proper function evolve more slowly than others, or in other words, the slow evolutionary rate of a position reflects its importance. ConSurf (http://consurf.tau.ac.il), reviewed in this manuscript, exploits this to reveal key amino acid positions that are important for maintaining the native conformation(s) of the protein and its function, be it binding, catalysis, transport, etc. Given the sequence or 3D structure of the query protein as input, a search for similar sequences is conducted and the sequences are aligned. The multiple sequence alignment is subsequently used to calculate the evolutionary rates of each amino acid site, using Bayesian or maximum‐likelihood algorithms. Both algorithms take into account the evolutionary relationships between the sequences, reflected in phylogenetic trees, to alleviate problems due to uneven (biased) sampling in sequence space. This is particularly important when the number of sequences is low. The ConSurf‐DB, a new release of which is presented here, provides precalculated ConSurf conservation analysis of nearly all available structures in the Protein DataBank (PDB). The usefulness of ConSurf for the study of individual proteins and mutations, as well as a range of large‐scale, genome‐wide applications, is reviewed.
The Effects of Mutations on Protein Function: A Comparative Study of Three Databases of Mutations in Humans
Authors: Azia Ariel , Uversky Vladimir N. , Horovitz Amnon , Unger Ron
Published: April 2013

Single‐nucleotide mutations (SNPs) in protein‐coding regions of the human genome are a major factor in determining human variation in health and disease. Here, we analyze the amino acid changes and functional effects due to non‐synonymous SNPs. Three databases were used: (i) Variation – mutations found in the general human population; (ii) Cosmic – mutations found in cancer cells; and (iii) Pathogenic – a curated subset of mutations in Variation that are associated with diseases. The distributions of amino acid changes in these datasets were analyzed. It is shown that mutations in the Pathogenic dataset, in particular, tend to introduce order‐promoting residues. The effects of the mutations in these datasets were also studied using the program Polyphen‐2, which predicts the functional impact of non‐synonymous mutations. In order to evaluate the significance of these predicted effects, we compared them to those due to the same amino acid replacements introduced at other positions in the same proteins as a control. A mutation can be deleterious because the amino acid change is drastic (for example a change from hydrophobic residue to hydrophilic residue) or because of its location in the protein. We found that, on both counts, mutations in the Variation dataset tend to be less deleterious than randomly expected whereas mutations in the Pathogenic dataset tend to be more deleterious than their control mutations. The mutations in the Cosmic dataset are found to be more deleterious than those in its control set but less than those in Pathogenic.
JSmol and the Next‐Generation Web‐Based Representation of 3D Molecular Structure as Applied to Proteopedia
Authors: Hanson Robert M. , Prilusky Jaime , Renjian Zhou , Nakane Takanori , Sussman Joel L.
Published: April 2013

Although Java does not run on some handheld devices, e.g., iPads and iPhones, JavaScript does. The development of JSmol, a JavaScript‐only version of Jmol, is described, and its use in Proteopedia is demonstrated. A key aspect of JSmol is that it includes the full implementation of the entire set of Jmol functionalities, including file reading and writing, scripting, and rendering. The relative performances of Java‐based Jmol and JavaScript‐only JSmol are discussed. We can now confirm that the guiding principles of Java programming can be completely and relatively straightforwardly transformed directly into JavaScript, requiring no Java applet, and producing identical graphical results. JSmol is thus the first full‐featured molecular viewer, and the first ever viewer for proteins, which can be utilized with an internet browser on handheld devices lacking Java. Since the MediaWiki features of Proteopedia have been modified to optionally use JSmol, the wealth of crowd‐sourced content in Proteopedia is now directly available on such devices, without the need to download any additional applet.
Time‐Dependent Inhibition and Induction of Human Cytochrome P4503A4/5 by an Oral IAP Antagonist, LCL161, In Vitro and In Vivo in Healthy Subjects
Authors: Dhuria Shyeilla , Einolf Heidi , Mangold James , Sen Suman , Gu Helen , Wang Lai , Cameron Scott
Published: April 2013

Tumor cells can evade programmed cell death via up‐regulation of inhibitor of apoptosis proteins (IAPs). LCL161 is a small molecule oral IAP antagonist in development for use in combination with cytotoxic agents. The effect of LCL161 on CYP3A4/5 (CYP3A) activity was investigated in vitro and in a clinical study. Results in human liver microsomes indicated LCL161 inhibited CYP3A in a concentration‐ and time‐dependent manner (KI of 0.797 µM and kinact of 0.0803 min−1). LCL161 activated human PXR in a reporter gene assay and induced CYP3A4 mRNA up to ∼5‐fold in human hepatocytes. In healthy subjects, the dual inhibitor and inductive effects of a single dose of LCL161 were characterized using single midazolam doses, given before and at three time points after the LCL161 dose. Midazolam Cmax increased 3.22‐fold and AUC(0‐inf) increased 9.32‐fold when administered four hours after LCL161. Three days later, midazolam Cmax decreased by 27% and AUC(0‐inf) decreased by 30%. No drug interaction remained one week later. The strong CYP3A inhibition by LCL161 was accurately predicted using dynamic physiologically‐based pharmacokinetic (PBPK) modeling approaches in Simcyp. However, the observed induction effect after the LCL161 dose could not be modeled; suggesting direct enzyme induction by LCL161 was not the underlying mechanism.
Effect of silanization of titanium dioxide on photocatalytic decomposition of 2,4‐dinitropheonol under irradiation with artificial UV light and sunlight
Authors: Shiraishi Fumihide , Ueno Mariko , Chand Rumi , Shibata Yuichiro , Luitel Hom Nath
Published: April 2013

BACKGROUND

TiO2‐based heterogeneous photocatalysis is an effective way to degrade harmful refractory organic compounds. However, the rate of photocatalytic reaction is significantly decreased by film diffusion resistance and several other factors. To overcome this problem, TiO2 immobilized on a stainless steel screen is hydrophobically treated using a (γ‐aminopropyl) triethoxysilane–toluene solution and the performance of the silanized TiO2 for the photocatalytic decomposition of 2,4‐dinitrophenol (2,4‐DNP) is investigated.

RESULTS

The reactant 2,4‐DNP is slowly decomposed when its aqueous solution is treated using an unsilanized TiO2 screen without mixing the solution, whereas the rate of decomposition is certainly increased by use of a silanized TiO2 screen, and further increased by mixing the solution. The use of sunlight as a UV light source provides a higher rate of decomposition than does the use of an artificial UV lamp. The rate of decomposition in a well‐mixed solution is less affected up to 1.5 cm in solution depth.

CONCLUSIONS

The use of the TiO2 screen silanized with a 2% silane–toluene solution under liquid mixing decreases film diffusion resistance and facilitates rapid decomposition of 2,4‐DNP. The simultaneous use of sunlight as a UV light source and a wind‐powered propeller for liquid mixing is effective. © 2013 Society of Chemical Industry
Dynamics of ice stream temporal variability: Modes, scales, and hysteresis
Authors: Robel A. A. , DeGiuli E. , Schoof C. , Tziperman E.
Published: April 2013

Understanding the mechanisms governing temporal variability of ice stream flow remains one of the major barriers to developing accurate models of ice sheet dynamics and ice‒climate interactions. Here we analyze a simple model of ice stream hydrology coupled to ice flow dynamics and including drainage and basal cooling processes. Analytic and numerical results from this model indicate that there are two major modes of ice stream behavior: steady‒streaming and binge‒purge variability. The steady‒streaming mode arises from friction‒stabilized subglacial meltwater production, which may also activate and interact with subglacial drainage. The binge‒purge mode arises from a sufficiently cold environment sustaining successive cycles of thinning‒induced basal cooling and stagnation. Low prescribed temperature at the ice surface and weak geothermal heating typically lead to binge‒purge behavior, while warm ice surface temperature and strong geothermal heating will tend to produce steady‒streaming behavior. Model results indicate that modern Siple Coast ice streams reside in the binge‒purge parameter regime near a subcritical Hopf bifurcation to the steady‒streaming mode. Numerical experiments exhibit hysteresis in ice stream variability as the surface temperature is varied by several degrees. Our simple model simulates Heinrich event‒like variability in a hypothetical Hudson Strait ice stream including dynamically determined purge time scale, till freezing and basal cooling during the binge phase. These findings are an improvement on studies of both modern and paleo‒ice stream variability and provide a framework for interpreting complex ice flow models.