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1.  XUV-Exposed, Non-Hydrostatic Hydrogen-Rich Upper Atmospheres of Terrestrial Planets. Part II: Hydrogen Coronae and Ion Escape 
Astrobiology  2013;13(11):1030-1048.
We studied the interactions between the stellar wind plasma flow of a typical M star, such as GJ 436, and the hydrogen-rich upper atmosphere of an Earth-like planet and a “super-Earth” with a radius of 2 REarth and a mass of 10 MEarth, located within the habitable zone at ∼0.24 AU. We investigated the formation of extended atomic hydrogen coronae under the influences of the stellar XUV flux (soft X-rays and EUV), stellar wind density and velocity, shape of a planetary obstacle (e.g., magnetosphere, ionopause), and the loss of planetary pickup ions on the evolution of hydrogen-dominated upper atmospheres. Stellar XUV fluxes that are 1, 10, 50, and 100 times higher compared to that of the present-day Sun were considered, and the formation of high-energy neutral hydrogen clouds around the planets due to the charge-exchange reaction under various stellar conditions was modeled. Charge-exchange between stellar wind protons with planetary hydrogen atoms, and photoionization, lead to the production of initially cold ions of planetary origin. We found that the ion production rates for the studied planets can vary over a wide range, from ∼1.0×1025 s−1 to ∼5.3×1030 s−1, depending on the stellar wind conditions and the assumed XUV exposure of the upper atmosphere. Our findings indicate that most likely the majority of these planetary ions are picked up by the stellar wind and lost from the planet. Finally, we estimated the long-time nonthermal ion pickup escape for the studied planets and compared them with the thermal escape. According to our estimates, nonthermal escape of picked-up ionized hydrogen atoms over a planet's lifetime within the habitable zone of an M dwarf varies between ∼0.4 Earth ocean equivalent amounts of hydrogen (EOH) to <3 EOH and usually is several times smaller in comparison to the thermal atmospheric escape rates. Key Words: Stellar activity—Low-mass stars—Early atmospheres—Earth-like exoplanets—Energetic neutral atoms—Ion escape—Habitability. Astrobiology 13, 1030–1048.
PMCID: PMC3865724  PMID: 24283926
2.  The air-sea interface and surface stress under tropical cyclones 
Scientific Reports  2014;4:5306.
Tropical cyclone track prediction is steadily improving, while storm intensity prediction has seen little progress in the last quarter century. Important physics are not yet well understood and implemented in tropical cyclone forecast models. Missing and unresolved physics, especially at the air-sea interface, are among the factors limiting storm predictions. In a laboratory experiment and coordinated numerical simulation, conducted in this work, the microstructure of the air-water interface under hurricane force wind resembled Kelvin-Helmholtz shear instability between fluids with a large density difference. Supported by these observations, we bring forth the concept that the resulting two-phase environment suppresses short gravity-capillary waves and alters the aerodynamic properties of the sea surface. The unified wave-form and two-phase parameterization model shows the well-known increase of the drag coefficient (Cd) with wind speed, up to ~30 ms−1. Around 60 ms−1, the new parameterization predicts a local peak of Ck/Cd, under constant enthalpy exchange coefficient Ck. This peak may explain rapid intensification of some storms to major tropical cyclones and the previously reported local peak of lifetime maximum intensity (bimodal distribution) in the best-track records. The bimodal distribution of maximum lifetime intensity, however, can also be explained by environmental parameters of tropical cyclones alone.
PMCID: PMC4058872  PMID: 24930493
3.  Nanoscale observation of surface potential and carrier transport in Cu2ZnSn(S,Se)4 thin films grown by sputtering-based two-step process 
Stacked precursors of Cu-Zn-Sn-S were grown by radio frequency sputtering and annealed in a furnace with Se metals to form thin-film solar cell materials of Cu2ZnSn(S,Se)4 (CZTSSe). The samples have different absorber layer thickness of 1 to 2 μm and show conversion efficiencies up to 8.06%. Conductive atomic force microscopy and Kelvin probe force microscopy were used to explore the local electrical properties of the surface of CZTSSe thin films. The high-efficiency CZTSSe thin film exhibits significantly positive bending of surface potential around the grain boundaries. Dominant current paths along the grain boundaries are also observed. The surface electrical parameters of potential and current lead to potential solar cell applications using CZTSSe thin films, which may be an alternative choice of Cu(In,Ga)Se2.
PACS number: 08.37.-d; 61.72.Mm; 71.35.-y
PMCID: PMC3895808  PMID: 24397924
Cu2ZnSn(S,Se)4; Cu(In,Ga)Se2; Kesterite; Conductive atomic force microscopy; Kelvin probe force microscopy
4.  An NC-AFM and KPFM study of the adsorption of a triphenylene derivative on KBr(001) 
The adsorption on KBr(001) of a specially designed molecule, consisting of a flat aromatic triphenylene core equipped with six flexible propyl chains ending with polar cyano groups, is investigated by using atomic force microscopy in the noncontact mode (NC-AFM) coupled to Kelvin probe force microscopy (KPFM) in ultrahigh vacuum at room temperature. Two types of monolayers are identified, one in which the molecules lie flat on the surface (MLh) and another in which they stand approximately upright (MLv). The Kelvin voltage on these two structures is negatively shifted relative to that of the clean KBr surface, revealing the presence of surface dipoles with a component pointing along the normal to the surface. These findings are interpreted with the help of numerical simulations. It is shown that the surface–molecule interaction is dominated by the electrostatic interaction of the cyano groups with the K+ ions of the substrate. The molecule is strongly adsorbed in the MLh structure with an adsorption energy of 1.8 eV. In the MLv layer, the molecules form π-stacked rows aligned along the polar directions of the KBr surface. In these rows, the molecules are less strongly bound to the substrate, but the structure is stabilized by the strong intermolecular interaction due to π-stacking.
PMCID: PMC3323911  PMID: 22496995
atomic force microscopy; insulating surfaces; Kelvin force probe microscopy; molecular adsorption
1. It has been shown in preceding publications that the membrane potentials of protein solutions or gels are determined by differences in the concentration of a common ion (e.g. hydrogen ion) inside a protein solution or protein gel and an outside aqueous solution free from protein, and that the membrane potentials can be calculated with a good degree of accuracy from Donnan's equation for membrane equilibria. 2. On the basis of the theory of electrical double layers developed by Helmholtz, we are forced to assume that the cataphoretic potentials of protein particles are determined by a difference in the concentration of the two oppositely charged ions of the same electrolyte in the two strata of an electrical double layer surrounding the protein particle but situated entirely in the aqueous solution. 3. The membrane potentials of proteins agree with the cataphoretic potentials in that the sign of charge of the protein is negative on the alkaline side and positive on the acid side of the isoelectric point of the protein in both membrane potentials and cataphoretic potentials. The two types of potential of proteins disagree, especially in regard to the action of salts with trivalent and tetravalent ions on the sign of charge of the protein. While low concentrations of these salts bring about a reversal of the sign of the cataphoretic potentials of protein particles (at least in the neighborhood of the isoelectric point), the same salts can bring the membrane potentials of proteins only to zero, but call bring about no or practically no reversal of the sign of charge of the protein. Where salts seem to bring about a reversal in the membrane potential of protein solutions, the reversal is probably in reality always due to a change in the pH. 4. We may state, as a result of our experiments, that the cataphoretic migration and the cataphoretic P.D. of protein particles or of suspended particles coated with a protein are the result of two groups of forces; namely, first, forces inherent in the protein particles (these forces being linked with the membrane equilibrium between protein particles and the outside aqueous solution); and second, forces inherent entirely in the aqueous solution surrounding the protein particles. The forces inherent in the protein particles and linked with the membrane equilibrium prevail to such an extent over the forces inherent in the water, that the sense of the cataphoretic migration of protein particles is determined by the forces resulting from the membrane equilibrium.
PMCID: PMC2140571  PMID: 19872017
6.  Determining the mechanism of cusp proton aurora 
Scientific Reports  2013;3:1654.
Earth's cusp proton aurora occurs near the prenoon and is primarily produced by the precipitation of solar energetic (2–10 keV) protons. Cusp auroral precipitation provides a direct source of energy for the high-latitude dayside upper atmosphere, contributing to chemical composition change and global climate variability. Previous studies have indicated that magnetic reconnection allows solar energetic protons to cross the magnetopause and enter the cusp region, producing cusp auroral precipitation. However, energetic protons are easily trapped in the cusp region due to a minimum magnetic field existing there. Hence, the mechanism of cusp proton aurora has remained a significant challenge for tens of years. Based on the satellite data and calculations of diffusion equation, we demonstrate that EMIC waves can yield the trapped proton scattering that causes cusp proton aurora. This moves forward a step toward identifying the generation mechanism of cusp proton aurora.
PMCID: PMC3622916  PMID: 23575366
7.  Maxwell rheological model for lipid-shelled ultrasound microbubble contrast agents 
The present paper proposes a model that describes the encapsulation of microbubble contrast agents by the linear Maxwell constitutive equation. The model also incorporates the translational motion of contrast agent microbubbles and takes into account radiation losses due to the compressibility of the surrounding liquid. To establish physical features of the proposed model, comparative analysis is performed between this model and two existing models, one of which treats the encapsulation as a viscoelastic solid following the Kelvin-Voigt constitutive equation and the other assumes that the encapsulating layer behaves as a viscous Newtonian fluid. Resonance frequencies, damping coefficients, and scattering cross sections for the three shell models are compared in the regime of linear oscillation. Translational displacements predicted by the three shell models are examined by numerically calculating the genera1, nonlinearized equations of motion for weakly nonlinear excitation. Analogous results for free bubbles are also presented as a basis to which calculations made for encapsulated bubbles can be related. It is shown that the Maxwell shell model possesses specific physical features that are unavailable in the two other models.
PMCID: PMC3092912  PMID: 17552685
8.  Junction formation of Cu3BiS3 investigated by Kelvin probe force microscopy and surface photovoltage measurements 
Recently, the compound semiconductor Cu3BiS3 has been demonstrated to have a band gap of ~1.4 eV, well suited for photovoltaic energy harvesting. The preparation of polycrystalline thin films was successfully realized and now the junction formation to the n-type window needs to be developed. We present an investigation of the Cu3BiS3 absorber layer and the junction formation with CdS, ZnS and In2S3 buffer layers. Kelvin probe force microscopy shows the granular structure of the buffer layers with small grains of 20–100 nm, and a considerably smaller work-function distribution for In2S3 compared to that of CdS and ZnS. For In2S3 and CdS buffer layers the KPFM experiments indicate negatively charged Cu3BiS3 grain boundaries resulting from the deposition of the buffer layer. Macroscopic measurements of the surface photovoltage at variable excitation wavelength indicate the influence of defect states below the band gap on charge separation and a surface-defect passivation by the In2S3 buffer layer. Our findings indicate that Cu3BiS3 may become an interesting absorber material for thin-film solar cells; however, for photovoltaic application the band bending at the charge-selective contact has to be increased.
PMCID: PMC3323917  PMID: 22497001
buffer layer; Cu3BiS3; Kelvin probe force microscopy; solar cells
9.  Role of transcript and interplay between transcription and replication in triplet-repeat instability in mammalian cells 
Nucleic Acids Research  2010;39(2):526-535.
Triplet-repeat expansions cause several inherited human diseases. Expanded triplet-repeats are unstable in somatic cells, and tissue-specific somatic instability contributes to disease pathogenesis. In mammalian cells instability of triplet-repeats is dependent on the location of the origin of replication relative to the repeat tract, supporting the ‘fork-shift’ model of repeat instability. Disease-causing triplet-repeats are transcribed, but how this influences instability remains unclear. We examined instability of the expanded (GAA•TTC)n sequence in mammalian cells by analyzing individual replication events directed by the SV40 origin from five different locations, in the presence and absence of doxycycline-induced transcription. Depending on the location of the SV40 origin, either no instability was observed, instability was caused by replication with no further increase due to transcription, or instability required transcription. Whereas contractions accounted for most of the observed instability, one construct showed expansions upon induction of transcription. These expansions disappeared when transcript stability was reduced via removal or mutation of a spliceable intron. These results reveal a complex interrelationship of transcription and replication in the etiology of repeat instability. While both processes may not be sufficient for the initiation of instability, transcription and/or transcript stability seem to further modulate the fork-shift model of triplet-repeat instability.
PMCID: PMC3025579  PMID: 20843782
1. It had been shown in previous publications that when pure water is separated from a solution of an electrolyte by a collodion membrane the ion with the same sign of charge as the membrane increases and the ion with the opposite sign of charge as the membrane diminishes the rate of diffusion of water into the solution; but that the relative influence of the oppositely charged ions upon the rate of diffusion of water through the membrane is not the same for different concentrations. Beginning with the lowest concentrations of electrolytes the attractive influence of that ion which has the same sign of charge as the collodion membrane upon the oppositely charged water increases more rapidly with increasing concentration of the electrolyte than the repelling effect of the ion possessing the opposite sign of charge as the membrane. When the concentration exceeds a certain critical value the repelling influence of the latter ion upon the water increases more rapidly with a further increase in the concentration of the electrolyte than the attractive influence of the ion having the same sign of charge as the membrane. 2. It is shown in this paper that the influence of the concentration of electrolytes on the rate of transport of water through collodion membranes in electrical endosmose is similar to that in the case of free osmosis. 3. On the basis of the Helmholtz theory of electrical double layers this seems to indicate that the influence of an electrolyte on the rate of diffusion of water through a collodion membrane in the case of free osmosis is due to the fact that the ion possessing the same sign of charge as the membrane increases the density of charge of the latter while the ion with the opposite sign diminishes the density of charge of the membrane. The relative influence of the oppositely charged ions on the density of charge of the membrane is not the same in all concentrations. The influence of the ion with the same sign of charge increases in the lowest concentrations more rapidly with increasing concentration than the influence of the ion with the opposite sign of charge, while for somewhat higher concentrations the reverse is true.
PMCID: PMC2140385  PMID: 19871831
11.  Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni 
PLoS Pathogens  2014;10(5):e1004138.
The Venus Kinase Receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G Protein Coupled Receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration, these receptors control parasite reproduction and can therefore be considered as potential targets for anti-schistosome therapies.
Author Summary
Schistosomiasis is a chronic, debilitating disease affecting more than 200 million people in the world caused by parasitic flatworms of the genus Schistosoma. Pathology is mainly due to massive egg production by parasites and formation of granulomas around the eggs trapped in liver and different organs. Therefore, targeting the molecular processes responsible for gonad development or egg production in schistosomes appears as a valuable strategy to reduce pathogenesis and dissemination of schistosomiasis. In the present study, we investigated the importance of Venus Kinase Receptors (VKRs) which are unusual receptor tyrosine kinases (RTKs) with an extracellular Venus Flytrap (VFT) ligand-binding domain in the control of reproduction of schistosomes. SmVKRs are expressed in female ovaries of Schistosoma mansoni and the knock-down of their expression provoked dramatic alterations of the oocyte content in ovaries and reduction of egg formation. SmVKRs were also shown to activate different signalling pathways potentially involved in oocyte proliferation, growth and migration. Therefore our results demonstrate that VKRs are essential actors of oogenesis and egg formation in S. mansoni. Moreover, their presence in a large variety of invertebrate species including other helminth parasites and insect parasite vectors can open new perspectives in the control of various vector-borne infectious diseases.
PMCID: PMC4038586  PMID: 24875530
12.  A new non-destructive readout by using photo-recovered surface potential contrast 
Scientific Reports  2014;4:6980.
Ferroelectric random access memory is still challenging in the feature of combination of room temperature stability, non-destructive readout and high intensity storage. As a non-contact and non-destructive information readout method, surface potential has never been paid enough attention because of the unavoidable decay of the surface potential contrast between oppositely polarized domains. That is mainly due to the recombination of the surface movable charges around the domain walls. Here, by introducing a laser beam into the combination of piezoresponse force microscopy and Kelvin probe force microscopy, we demonstrate that the surface potential contrast of BiFeO3 films can be recovered under light illumination. The recovering mechanism is understood based on the redistribution of the photo-induced charges driven by the internal electric field. Furthermore, we have created a 12-cell memory pattern based on BiFeO3 films to show the feasibility of such photo-assisted non-volatile and non-destructive readout of the ferroelectric memory.
PMCID: PMC4225563  PMID: 25381929
13.  Noise performance of frequency modulation Kelvin force microscopy 
Noise performance of a phase-locked loop (PLL) based frequency modulation Kelvin force microscope (FM-KFM) is assessed. Noise propagation is modeled step by step throughout the setup using both exact closed loop noise gains and an approximation known as “noise gain” from operational amplifier (OpAmp) design that offers the advantage of decoupling the noise performance study from considerations of stability and ideal loop response. The bandwidth can be chosen depending on how much noise is acceptable and it is shown that stability is not an issue up to a limit that will be discussed. With thermal and detector noise as the only sources, both approaches yield PLL frequency noise expressions equal to the theoretical value for self-oscillating circuits and in agreement with measurement, demonstrating that the PLL components neither modify nor contribute noise. Kelvin output noise is then investigated by modeling the surrounding bias feedback loop. A design rule is proposed that allows choosing the AC modulation frequency for optimized sharing of the PLL bandwidth between Kelvin and topography loops. A crossover criterion determines as a function of bandwidth, temperature and probe parameters whether thermal or detector noise is the dominating noise source. Probe merit factors for both cases are then established, suggesting how to tackle noise performance by probe design. Typical merit factors of common probe types are compared. This comprehensive study is an encouraging step toward a more integral performance assessment and a remedy against focusing on single aspects and optimizing around randomly chosen key values.
PMCID: PMC3896264  PMID: 24455457
dynamic; frequency noise; Kelvin force microscopy; noise performance; phase noise; thermal excitation
14.  Initiation of Genome Instability and Preneoplastic Processes through Loss of Fhit Expression 
PLoS Genetics  2012;8(11):e1003077.
Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress. A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression. Because common chromosome fragile sites are exquisitely sensitive to replication stress, it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products. Here, we show in normal, transformed, and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks. Using DNA combing, we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse. The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels; notably, restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells. Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest, allowing continued cell proliferation and ongoing chromosomal instability. This finding was in accord with in vivo studies, as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci. Furthermore, cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications, including amplification of the Mdm2 gene, suggesting that Fhit loss-induced genome instability facilitates transformation. We propose that loss of Fhit expression in precancerous lesions is the first step in the initiation of genomic instability, linking alterations at common fragile sites to the origin of genome instability.
Author Summary
Normal cells have robust mechanisms to maintain the proper sequence of their DNA; in cancer cells these mechanisms are compromised, resulting in complex changes in the DNA of tumors. How this genome instability begins has not been defined, except in cases of familial cancers, which often have mutations in genes called “caretaker” genes, necessary to preserve DNA stability. We have defined a mechanism for genome instability in non-familial tumors that occur sporadically in the population. Certain fragile regions of our DNA are more difficult to duplicate during cell division and are prone to breakage. A fragile region, FRA3B, lies within the FHIT gene, and deletions within FRA3B are common in precancer cells, causing loss of Fhit protein expression. We find that loss of Fhit protein causes defective DNA replication, leading to further DNA breaks. Cells that continue DNA replication in the absence of Fhit develop numerous chromosomal aberrations. Importantly, cells established from tissues of mice that are missing Fhit undergo selection for increasing DNA alterations that can promote immortality, a cancer cell hallmark. Thus, loss of Fhit expression in precancer cells is the first step in the initiation of genomic instability and facilitates cancer development.
PMCID: PMC3510054  PMID: 23209436
15.  Meshless Method with Operator Splitting Technique for Transient Nonlinear Bioheat Transfer in Two-Dimensional Skin Tissues 
A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue.
PMCID: PMC4307345  PMID: 25603180
transient nonlinear bioheat transfer; meshless method; operator splitting; radial basis function; method of fundamental solutions
16.  Posterolateral instability of the elbow in an adolescent boy with a lateral epicondyle fracture: a case report 
Hand (New York, N.Y.)  2010;6(1):71-75.
Posterolateral rotatory instability of elbow is considered to be due to the disruption of the ulnar part of the lateral collateral ligament (LUCL). This instability pattern may also be induced by a fracture of components of the lateral column.
We present the case of a 16-year-old boy who fell on his left outstretched arm as he attempted to jump over a tennis net. On initial physical examination, the elbow had instability found on varus stress and the radial head could be felt posteriorly. With attempted valgus and supination force combined with axial loading, the elbow gapped open and the patient had a sense of increased instability. X-rays showed a fracture of the lateral humeral epicondyle and posterolateral subluxation of the elbow. In the operating room, the patient was found to have reproducible posterolateral instability of the elbow. The lateral epicondyle was found to be fractured off the humerus with the LUCL still attached to the fragment. The elbow was reduced, and the injury was stabilized with small screws and suture anchors. At 6-month follow-up, the patient was pain-free, and physical examination revealed 170° of flexion, full extension, 90° of pronation, and 65° of supination. X-rays showed healing of the fracture with concentric reduction of the elbow joint.
In lateral epicondyle fractures, the affected elbow should be assessed for any signs of associated instability. If signs of clear instability are seen that would prohibit proper postinjury rehabilitation, then surgical reduction and fixation of the epicondyle with reinforcement of the LUCL is an effective method of treatment.
PMCID: PMC3041873  PMID: 22379442
Elbow; Rotatory; Instability; Ulnar collateral ligament
17.  ERCC1/XPF Protects Short Telomeres from Homologous Recombination in Arabidopsis thaliana 
PLoS Genetics  2009;5(2):e1000380.
Many repair and recombination proteins play essential roles in telomere function and chromosome stability, notwithstanding the role of telomeres in “hiding” chromosome ends from DNA repair and recombination. Among these are XPF and ERCC1, which form a structure-specific endonuclease known for its essential role in nucleotide excision repair and is the subject of considerable interest in studies of recombination. In contrast to observations in mammalian cells, we observe no enhancement of chromosomal instability in Arabidopsis plants mutated for either XPF (AtRAD1) or ERCC1 (AtERCC1) orthologs, which develop normally and show wild-type telomere length. However, in the absence of telomerase, mutation of either of these two genes induces a significantly earlier onset of chromosomal instability. This early appearance of telomere instability is not due to a general acceleration of telomeric repeat loss, but is associated with the presence of dicentric chromosome bridges and cytologically visible extrachromosomal DNA fragments in mitotic anaphase. Such extrachromosomal fragments are not observed in later-generation single-telomerase mutant plants presenting similar frequencies of anaphase bridges. Extensive FISH analyses show that these DNAs are broken chromosomes and correspond to two specific chromosome arms. Analysis of the Arabidopsis genome sequence identified two extensive blocks of degenerate telomeric repeats, which lie at the bases of these two arms. Our data thus indicate a protective role of ERCC1/XPF against 3′ G-strand overhang invasion of interstitial telomeric repeats. The fact that the Atercc1 (and Atrad1) mutants dramatically potentiate levels of chromosome instability in Attert mutants, and the absence of such events in the presence of telomerase, have important implications for models of the roles of recombination at telomeres and is a striking illustration of the impact of genome structure on the outcomes of equivalent recombination processes in different organisms.
Author Summary
Telomeres are the specialised nucleoprotein structures evolved to avoid progressive replicative shortening and recombinational instability of the ends of linear chromosomes. Notwithstanding this role of telomeres in “hiding” chromosome ends from DNA repair and recombination, many repair and recombination proteins play essential roles in telomere function and chromosome stability. Among these are XPF and ERCC1, which form a structure-specific endonuclease known for its essential role in nucleotide excision repair and that is the subject of considerable interest in studies of recombination. In this study, we analyse the roles of the XPF/ERCC1 in telomere function and chromosome stability in the plant Arabidopsis thaliana, which, with its remarkable tolerance to genomic instability and sequenced genome, is an excellent higher eukaryotic model for these studies. Surprisingly, and in striking contrast to observations in mammalian cells, we observe no enhancement of chromosomal instability in Arabidopsis plants lacking either of these two proteins, which develop normally and show wild-type telomere length. However, Atercc1 (and Atrad1) mutants profoundly affect the recombination of de-protected telomeres, dramatically potentiating chromosome instability. These results provide a striking illustration of the different outcomes and genomic impacts of the same recombination processes in different organisms.
PMCID: PMC2632759  PMID: 19214203
18.  Kelvin probe force microscopy of nanocrystalline TiO2 photoelectrodes 
Dye-sensitized solar cells (DSCs) provide a promising third-generation photovoltaic concept based on the spectral sensitization of a wide-bandgap metal oxide. Although the nanocrystalline TiO2 photoelectrode of a DSC consists of sintered nanoparticles, there are few studies on the nanoscale properties. We focus on the microscopic work function and surface photovoltage (SPV) determination of TiO2 photoelectrodes using Kelvin probe force microscopy in combination with a tunable illumination system. A comparison of the surface potentials for TiO2 photoelectrodes sensitized with two different dyes, i.e., the standard dye N719 and a copper(I) bis(imine) complex, reveals an inverse orientation of the surface dipole. A higher surface potential was determined for an N719 photoelectrode. The surface potential increase due to the surface dipole correlates with a higher DSC performance. Concluding from this, microscopic surface potential variations, attributed to the complex nanostructure of the photoelectrode, influence the DSC performance. For both bare and sensitized TiO2 photoelectrodes, the measurements reveal microscopic inhomogeneities of more than 100 mV in the work function and show recombination time differences at different locations. The bandgap of 3.2 eV, determined by SPV spectroscopy, remained constant throughout the TiO2 layer. The effect of the built-in potential on the DSC performance at the TiO2/SnO2:F interface, investigated on a nanometer scale by KPFM measurements under visible light illumination, has not been resolved so far.
PMCID: PMC3701424  PMID: 23844348
atomic force microscopy (AFM); dye-sensitized solar cells (DSC); Kelvin probe force microscopy (KPFM); surface photovoltage (SPV); titanium dioxide (TiO2)
19.  In-vitro mapping of E-fields induced near pacemaker leads by simulated MR gradient fields 
Magnetic resonance imaging (MRI) of patients with implanted cardiac pacemakers is generally contraindicated but some clinicians condone scanning certain patients. We assessed the risk of inducing unintended cardiac stimulation by measuring electric fields (E) induced near lead tips by a simulated MRI gradient system. The objectives of this study are to map magnetically induced E near distal tips of leads in a saline tank to determine the spatial distribution and magnitude of E and compare them with E induced by a pacemaker pulse generator (PG).
We mapped magnetically induced E with 0.1 mm resolution as close as 1 mm from lead tips. We used probes with two straight electrodes (e.g. wire diameter of 0.2 mm separated by 0.9 mm). We generated magnetic flux density (B) with a Helmholtz coil throughout 0.6% saline in a 24 cm diameter tank with (dB/dt) of 1 T/sec (1 kHz sinusoidal waveform). Separately, we measured E near the tip of leads when connected to a PG set to a unipolar mode. Measurements were non-invasive (not altering the leads or PG under study).
When scaled to 30 T/s (a clinically relevant value), magnetically-induced E exceeded the E produced by a PG. The magnetically-induced E only occurred when B was coincident with or within 15 msec of implantable pacemaker's pulse.
Potentially hazardous situations are possible during an MR scan due to gradient fields. Unintended stimulation can be induced via abandoned leads and leads connected to a pulse generator with loss of hermetic seal at the connector. Also, pacemaker-dependent patients can receive drastically altered pacing pulses.
PMCID: PMC2801670  PMID: 20003479
20.  The Global Coherence Initiative: Creating a Coherent Planetary Standing Wave 
The much anticipated year of 2012 is now here. Amidst the predictions and cosmic alignments that many are aware of, one thing is for sure: it will be an interesting and exciting year as the speed of change continues to increase, bringing both chaos and great opportunity. One benchmark of these times is a shift in many people from a paradigm of competition to one of greater cooperation. All across the planet, increasing numbers of people are practicing heart-based living, and more groups are forming activities that support positive change and creative solutions for manifesting a better world. The Global Coherence Initiative (GCI) is a science-based, co-creative project to unite people in heart-focused care and intention. GCI is working in concert with other initiatives to realize the increased power of collective intention and consciousness.
The convergence of several independent lines of evidence provides strong support for the existence of a global information field that connects all living systems and consciousness. Every cell in our bodies is bathed in an external and internal environment of fluctuating invisible magnetic forces that can affect virtually every cell and circuit in biological systems. Therefore, it should not be surprising that numerous physiological rhythms in humans and global collective behaviors are not only synchronized with solar and geomagnetic activity, but disruptions in these fields can create adverse effects on human health and behavior.
The most likely mechanism for explaining how solar and geomagnetic influences affect human health and behavior are a coupling between the human nervous system and resonating geomagnetic frequencies, called Schumann resonances, which occur in the earth-ionosphere resonant cavity and Alfvén waves. It is well established that these resonant frequencies directly overlap with those of the human brain and cardiovascular system. If all living systems are indeed interconnected and communicate with each other via biological, electromagnetic, and nonlocal fields, it stands to reason that humans can work together in a co-creative relationship to consciously increase the coherence in the global field environment, which in turn distributes this information to all living systems within the field.
GCI was established to help facilitate the shift in global consciousness from instability and discord to balance, cooperation, and enduring peace. A primary goal of GCI is to test the hypothesis that large numbers of people when in a heart-coherent state and holding a shared intention can encode information on the earth's energetic and geomagnetic fields, which act as carrier waves of this physiologically patterned and relevant information. In order to conduct this research, a global network of 12 to 14 ultrasensitive magnetic field detectors specifically designed to measure the earth's magnetic resonances is being installed strategically around the planet. More important is GCI's primary goal to motivate as many people as possible to work together in a more coherent and collaborative manner to increase the collective human consciousness.
If we are persuaded that not only external fields of solar and cosmic origins but also human attention and emotion can directly affect the physical world and the mental and emotional states of others (consciousness), it broadens our view of what interconnectedness means and how it can be intentionally utilized to shape the future of the world we live in. It implies that our attitudes, emotions, and intentions matter and that coherent, cooperative intent can have positive effects.
GCI hypothesizes that when enough individuals and social groups increase their coherence baseline and utilize that increased coherence to intentionally create a more coherent standing reference wave in the global field, it will help increase global consciousness. This can be achieved when an increasing number of people move towards more balanced and self-regulated emotions and responses. This in turn can help facilitate cooperation and collaboration in innovative problem solving and intuitive discernment for addressing society's significant social, environmental, and economic problems. In time, as more individuals stabilize the global field and families, workplaces, and communities move to increased social coherence, it will lead to increased global coherence. This will be indicated by countries adopting a more coherent planetary view so that social and economic oppression, warfare, cultural intolerance, crime, and disregard for the environment can be addressed meaningfully and successfully.
PMCID: PMC3833489  PMID: 24278803
Global Coherence Initiative; geomagnetic; Schumann resonances; coherence; heart-based living; global health
21.  Role for perinuclear chromosome tethering in maintenance of genome stability 
Nature  2008;456(7222):667-670.
Repetitive DNA sequences, which constitute half the genome in some organisms, often undergo homologous recombination. This can instigate genomic instability due to gain or loss of DNA1. Assembly of DNA into silent chromatin is generally thought to serve as a mechanism ensuring repeat stability by limiting access to the recombination machinery2. Consistent with this notion, in the budding yeast Saccharomyces cerevisiae, stability of the highly repetitive ribosomal DNA (rDNA) sequences requires a Sir2-containing chromatin silencing complex that also inhibits transcription from foreign promoters and transposons inserted within the repeats by a process called rDNA silencing2-5. Here, we describe a protein network that stabilizes rDNA repeats of budding yeast via interactions between rDNA-associated silencing proteins and two inner nuclear membrane (INM) proteins. Deletion of either the INM or silencing proteins reduces perinuclear rDNA positioning, disrupts the nucleolus-nucleoplasm boundary, induces the formation of recombination foci, and destabilizes the repeats. In addition, artificial targeting of rDNA repeats to the INM suppresses the instability observed in cells lacking an rDNA-associated silencing protein typically required for peripheral tethering of the repeats. Moreover, in contrast to Sir2 and its associated nucleolar factors, the INM proteins are not required for rDNA silencing, indicating that Sir2-dependent silencing is not sufficient to inhibit recombination within the rDNA locus. These findings demonstrate a role for INM proteins in perinuclear chromosome localization and show that tethering to the nuclear periphery is required for rDNA repeat stability. The INM proteins studied here are conserved and have been implicated in chromosome organization in metazoans6,7. Our results therefore reveal an ancient mechanism in which interactions between INM and chromosomal proteins ensure genome stability.
PMCID: PMC2596277  PMID: 18997772
Nucleolus; rDNA; ribosomal RNA genes; copy number; unequal recombination; silencing; heterochromatin; chromosome; Heh1; Man1; Nur1; Ydl089w; CLIP; LEM domain; HEH fold; Emerin; Sir2; SIRT1; RENT; Net1; Cdc14; nuclear envelope; perinuclear; nuclear periphery
22.  Strong Temporal Variation Over One Saturnian Year: From Voyager to Cassini 
Scientific Reports  2013;3:2410.
Here we report the combined spacecraft observations of Saturn acquired over one Saturnian year (~29.5 Earth years), from the Voyager encounters (1980–81) to the new Cassini reconnaissance (2009–10). The combined observations reveal a strong temporal increase of tropic temperature (~10 Kelvins) around the tropopause of Saturn (i.e., 50 mbar), which is stronger than the seasonal variability (~a few Kelvins). We also provide the first estimate of the zonal winds at 750 mbar, which is close to the zonal winds at 2000 mbar. The quasi-consistency of zonal winds between these two levels provides observational support to a numerical suggestion inferring that the zonal winds at pressures greater than 500 mbar do not vary significantly with depth. Furthermore, the temporal variation of zonal winds decreases its magnitude with depth, implying that the relatively deep zonal winds are stable with time.
PMCID: PMC3740281  PMID: 23934437
23.  Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation 
BMC Biotechnology  2010;10:57.
Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically) of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state.
First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT) under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH). Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution). To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa)). The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size.
Water sorption leads to aggregation, inactivation, and structural changes of α-CT as has been similarly shown to occur for many other proteins. These instabilities correlate with an increase in protein structural dynamics as a result of moisture exposure. In this work, we present a novel methodology to stabilize proteins against structural perturbations in the solid-state since chemical glycosylation was effective in decreasing and/or preventing the traditionally observed moisture-induced aggregation and inactivation. It is suggested that the stabilization provided by these chemically attached glycans comes from the steric hindrance that the sugars conveys on the protein surface therefore preventing the interaction of the protein internal electrostatics with that of the water molecules and thus reducing the protein structural dynamics upon moisture exposure.
PMCID: PMC2924255  PMID: 20696067
24.  Load-Relaxation Properties of the Human Trunk in Response to Prolonged Flexion: Measuring and Modeling the Effect of Flexion Angle 
PLoS ONE  2012;7(11):e48625.
Experimental studies suggest that prolonged trunk flexion reduces passive support of the spine. To understand alterations of the synergy between active and passive tissues following such loadings, several studies have assessed the time-dependent behavior of passive tissues including those within spinal motion segments and muscles. Yet, there remain limitations regarding load-relaxation of the lumbar spine in response to flexion exposures and the influence of different flexion angles. Ten healthy participants were exposed for 16 min to each of five magnitudes of lumbar flexion specified relative to individual flexion-relaxation angles (i.e., 30, 40, 60, 80, and 100%), during which lumbar flexion angle and trunk moment were recorded. Outcome measures were initial trunk moment, moment drop, parameters of four viscoelastic models (i.e., Standard Linear Solid model, the Prony Series, Schapery's Theory, and the Modified Superposition Method), and changes in neutral zone and viscoelastic state following exposure. There were significant effects of flexion angle on initial moment, moment drop, changes in normalized neutral zone, and some parameters of the Standard Linear Solid model. Initial moment, moment drop, and changes in normalized neutral zone increased exponentially with flexion angle. Kelvin-solid models produced better predictions of temporal behaviors. Observed responses to trunk flexion suggest nonlinearity in viscoelastic properties, and which likely reflected viscoelastic behaviors of spinal (lumbar) motion segments. Flexion-induced changes in viscous properties and neutral zone imply an increase in internal loads and perhaps increased risk of low back disorders. Kelvin-solid models, especially the Prony Series model appeared to be more effective at modeling load-relaxation of the trunk.
PMCID: PMC3489838  PMID: 23144913
25.  Routes to rupture and folding of graphene on rough 6H-SiC(0001) and their identification 
Twisted few layer graphene (FLG) is highly attractive from an application point of view, due to its extraordinary electronic properties. In order to study its properties, we demonstrate and discuss three different routes to in situ create and identify (twisted) FLG. Single layer graphene (SLG) sheets mechanically exfoliated under ambient conditions on 6H-SiC(0001) are modified by (i) swift heavy ion (SHI) irradiation, (ii) by a force microscope tip and (iii) by severe heating. The resulting surface topography and the surface potential are investigated with non-contact atomic force microscopy (NC-AFM) and Kelvin probe force microscopy (KPFM). SHI irradiation results in rupture of the SLG sheets, thereby creating foldings and bilayer graphene (BLG). Applying the other modification methods creates enlarged (twisted) graphene foldings that show rupture along preferential edges of zigzag and armchair type. Peeling at a folding over an edge different from a low index crystallographic direction can result in twisted BLG, showing a similar height as Bernal (or AA-stacked) BLG in NC-AFM images. The rotational stacking can be identified by a significant contrast in the local contact potential difference (LCPD) measured by KPFM.
PMCID: PMC3817683  PMID: 24205456
graphene; Kelvin probe force microscopy (KPFM), local contact potential difference (LCPD); non-contact atomic force microscopy (NC-AFM); SiC

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