bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrete, matched‐load, step‐up converter for 60–400 mV thermoelectric energy harvesting source
Authors: Shuttleworth R. , Simpson K.
Published: June 2013

A circuit is described that enables the output of a thermoelectric generator (TEG) to be boosted to around 5V over a TEG open circuit voltage range of 60 to 400mV. The topology has a JFET and MOSFET start‐up system which operates sequentially to charge a reservoir capacitor. When the capacitor is charged, the topology is converted to a discontinuous current mode flyback circuit which uses a BUZ11 MOSFET as the switch. The flyback circuit matches the converter input resistance to the TEG output resistance, thereby obtaining maximum power from the TEG. The circuit uses easily obtainable discrete components.
Asymmetric magnetic unit of three‐phase IPT system for achieving effective power transmission
Authors: Xia C.Y. , Zhang J. , Jia N. , Zhuang Y.H. , Wu X.J.
Published: June 2013

A new asymmetric magnetic unit is proposed, which can effectively eliminate the ‘dead spot’ in a three‐phase IPT (inductive power transfer) system, in which the spiral direction of any one of the three primary coils is opposite to that of the other two, and the pick‐up voltage can increase more effectively compared to that of the traditional symmetrical magnetic unit. The viability of the proposed magnetic unit is supported by experiments, the results of which show that the unit plays a key role in the three‐phase IPT system design.
Minimisation of power losses in source‐R‐C circuit with any (possibly nonlinear) capacitor
Authors: Gluskin E.
Published: June 2013

In power electronics circuits, the capacitor, whose charging and discharging provides the energy transfer from a source to the load is, usually, a linear one. It is interesting to consider also a nonlinear capacitor having a smooth voltage‐current characteristic, as, e.g. a ferroelectric capacitor, or a piecewise linear characteristic, as a switched unit in which linear capacitors are switched. This can give a designer an additional degree of freedom for optimisation of such a circuit, first of all for minimisation of the power losses in it. The proof of the reasonability to use a current (and not a voltage) source is provided in terms of the variation principle that is widely used in classical mechanics. The use of the variational principle not just for optimisation of some parameters (which is usual), but also for the qualitative conclusion regarding the circuit structure – the use of the current source – is another methodological point not to be missed.
Fringing capacitance in sections of circular parallel plates with variable overlapping area
Authors: García‐Moreno S. , Bandala‐Sánchez M.
Published: June 2013

A model for the fringing field in sections of circular parallel plates is derived using potential‐theoretic methods. The calculation accurately predicts fringing effects when the overlapping area is varied by one plate being slided on top of one another. This capacitance calculation can be useful to estimate torque in several micromotor configurations.
Microwave energy harvesting for satellite applications
Authors: Takacs A. , Aubert H. , Despoisse L. , Fredon S.
Published: June 2013

This reported work addresses microwave energy harvesting for powering wireless sensors onboard brodcasting geostationary satellites. The electromagnetic environment existing on such satellites is first investigated. Experimental results in K‐band demonstrate for the first time the feasibility of such energy harvesting for powering autonomous wireless sensors used to monitor the satellite health.
Class of inductive two‐ports that includes two‐winding coupled inductors
Authors: Sommariva A.M.
Published: June 2013

A rigorous and complete analysis of the inductive two‐ports that are linear lumped time‐invariant, duly‐controlled and non‐trivial, reciprocally coupled and passive is carried out. It is based on the use of the flux/current transmission matrix, which permits pursuing a straightforward unified investigation. It clarifies some important features concerning the perfect coupling mode of operation, and shows the existence of another mode of operation that in some sense is the counterpart of the perfect coupling one.
Offset error reduction using gate‐bulk‐driven error correction amplifier for low‐voltage sub‐bandgap reference
Authors: Lu Li , Li Changzhi
Published: June 2013

Presented is a gain‐boosted gate‐bulk‐driven error correction amplifier with reduced offset errors for low‐voltage sub‐bandgap reference designs. The method can be applied to sub‐bandgap circuits with BJT diodes, subthreshold MOSFETs or Schottky barrier diodes. Detailed analysis and circuit implementation are presented. Low voltage operation has been verified over − 55 to 125 °C. Simulation and measurement results demonstrate the minimised offset error and improved supply sensitivity, which indicates the effectiveness of the proposed gain boosting mechanism.
Analysis of switching network in PWM DC–DC converters in terms of averaged resistance and conductance
Authors: Ayachit A. , Kazimierczuk M.K.
Published: June 2013

Equivalent circuit modelling of pulse‐width modulated (PWM) converters requires averaging the on‐state and forward resistances of transistor (M) and diode (D) over one switching period. Their values vary between a finite number (M‐ON) and infinity (M‐OFF) during the switching instants. Analytically, it becomes impossible to calculate the equivalent average resistance over one switching period. By determining their averaged conductances, a more intuitive model is derived for continuous conduction mode. Using reflective rules, these conductances are transferred to the inductor branch and an equivalent averaged conductance is derived and analysed.
Use of first‐ and second‐order sigma–delta quantisers in context of odd‐stacked cosine modulated filter banks
Authors: Abdelkefi F. , Ayadi J.
Published: June 2013

The use of sigma–delta (ΣΔ) quantisers in the context of an oversampled odd‐stacked cosine modulated filter bank (CMFB) is investigated. Shown is that the exploitation of the ΣΔ quantisers jointly with the CMFB ensures significant robustness of the transmitted signal against transmission errors. In this context, an upper bound of the minimum squares error of the reconstructed signal is derived and it is proved that it decreases as (1/r2), where r denotes the CMFB frame redundancy, for the first‐ and the second‐order ΣΔ quantisers.
Analysis of parasitic effects in triple‐well CMOS SPDT switch
Authors: Sun Pinping , Liu Peng
Published: June 2013

A comparison between a conventional body floating single pole double throw (SPDT) CMOS switch design and a proposed switched gate floating CMOS SPDT switch design based on an analysis of parasitic effects is presented. In standard CMOS technology, the switched gate floating switch is analytically proved to have higher isolation owing to the alleviation of parasitic diode and substrate coupling effects in the operation state. The proposed switch maintains a similar insertion loss as conventional swithches while achieving an average of 6 dB isolation improvement over the operating frequency, which agrees well with the presented analysis.
IT project governance at Worthington Health-Care System
Authors: Schultze Ulrike
Published: June 2013

In 2012, the Chief Information Officer (CIO) of Worthington Health-Care System (WHCS), a St. Louis company with 27 health-care facilities, is considering how to improve IT project governance. Over the previous 7 years, three approaches to developing project oversight had been attempted, including a Project Management Office, a project Portfolio Management application (PlanView), and more recently, an incremental approach to process improvement, which was meeting with increasing resistance. The CIO's challenge is to find an effective solution to IT project work and oversight at WHCS. This teaching case was prepared to support a Business Process Consulting course, but it may also be suitable in an IT Management, IS Project Management, Business Process Improvement and IT-Enabled Change, and Accounting Information Systems class.
The diffusion and relaxation of Gaussian chains in narrow rectangular slits
Authors: Bhattacharyya Pinaki , Cherayil Binny J.
Published: June 2013

The confinement of a polymer to volumes whose characteristic linear dimensions are comparable to or smaller than its bulk radius of gyration RG,bulk can produce significant changes in its static and dynamic properties, with important implications for the understanding of single-molecule processes in biology and chemistry. In this paper, we present calculations of the effects of a narrow rectangular slit of thickness d on the scaling behavior of the diffusivity D and relaxation time τr of a Gaussian chain of polymerization index N and persistence length l0. The calculations are based on the Rouse-Zimm model of chain dynamics, with the pre-averaged hydrodynamic interaction being obtained from the solutions to Stokes equations for an incompressible fluid in a parallel plate geometry in the limit of small d. They go beyond de Gennes’ purely phenomenological analysis of the problem based on blobs, which has so far been the only analytical route to the determination of chain scaling behavior for this particular geometry. The present model predicts that D ∼ dN−1ln (N/d2) and τr ∼ N2d−1[ln (N/d2)]−1 in the regime of moderate confinement, where l0 ≪ d < RG,bulk. The corresponding results for the blob model have exactly the same power law behavior, but contain no logarithmic corrections; the difference suggests that segments within a blob may actually be partially draining and not non-draining as generally assumed.
Note: One more important thermodynamic potential for solids and heterogeneous systems
Authors: Rusanov A. I.
Published: June 2013

A novel thermodynamic potential based on generalized Gibbs energy is introduced and substantiated for an arbitrarily loaded solid surrounded with a fluid. The potential is also applicable to heterogeneous fluid systems where it simplifies calculations. The wide use of the potential is illustrated with practical examples.
Autoresonant-spectrometric determination of the residual gas composition in the ALPHA experiment apparatus
Authors: Amole C. , Ashkezari M. D. , Baquero-Ruiz M. , Bertsche W. , Butler E. , Capra A. , Cesar C. L. , Chapman S. , Charlton M. , Eriksson S. , Fajans J. , Friesen T. , Fujiwara M. C. , Gill D. R. , Gutierrez A. , Hangst J. S. , Hardy W. N. , Hayden M. E. , Isaac C. A. , Jonsell S. , Kurchaninov L. , Little A. , Madsen N. , McKenna J. T. K. , Menary S. , Napoli S. C. , Nolan P. , Olchanski K. , Olin A. , Povilus A. , Pusa P. , Rasmussen C. Ø. , Robicheaux F. , Sarid E. , Silveira D. M. , Stracka S. , So C. , Thompson R. I. , Turner M. , van der Werf D. P. , Wurtele J. S. , Zhmoginov A. ,   ALPHA Collaboration
Published: June 2013

Knowledge of the residual gas composition in the ALPHA experiment apparatus is important in our studies of antihydrogen and nonneutral plasmas. A technique based on autoresonant ion extraction from an electrostatic potential well has been developed that enables the study of the vacuum in our trap. Computer simulations allow an interpretation of our measurements and provide the residual gas composition under operating conditions typical of those used in experiments to produce, trap, and study antihydrogen. The methods developed may also be applicable in a range of atomic and molecular trap experiments where Penning-Malmberg traps are used and where access is limited.
An easy-to-implement filter for separating photo-excited signals from topography in scanning tunneling microscopy
Authors: Wang Kangkang , Rosenmann Daniel , Holt Martin , Winarski Robert , Hla Saw-Wai , Rose Volker
Published: June 2013

In order to achieve elemental and chemical sensitivity in scanning tunneling microscopy (STM), synchrotron x-rays have been applied to excite core-level electrons during tunneling. The x-ray photo-excitations result in tip currents that are superimposed onto conventional tunneling currents. While carrying important physical information, the varying x-ray induced currents can destabilize the feedback loop causing it to be unable to maintain a constant tunneling current, sometimes even causing the tip to retract fully or crash. In this paper, we report on an easy-to-implement filter circuit that can separate the x-ray induced currents from conventional tunneling currents, thereby allowing simultaneous measurements of topography and chemical contrasts. The filter and the schematic presented here can also be applied to other variants of light-assisted STM such as laser STM.
Spin states in Co-PI catalysts
Authors: Richter M. , Schmeißer D.
Published: June 2013

Cobalt based oxygen evolution catalysts (Co-PI, PI = electrodeposited from pH 7 phosphate) are studied by resonant photoemission spectroscopy at the Co L3 and O1s edge. For the individual Co3d states, we determine their configuration, their spin, and their energy level relative to the Fermi energy. We identify the Co divalent high spin state and the trivalent low spin state. In addition, we also find the corresponding oxygen-to-metal charge transfer states. We attribute the trivalent charge transfer state to be the active state for the oxygen evolution reaction.
An alternative to Wigner d-matrices for rotating real spherical harmonics
Authors: Aubert G.
Published: June 2013

Transformation of spherical harmonics under rotation is a major problem in many areas of theoretical and applied science. While elegantly and efficiently solved for complex spherical harmonics with Wigner D- and d-matrices, extending this method to real spherical harmonics (RSH) faces serious difficulties not yet overcome. This work presents novel explicit formulas and recurrence relations for building RSH rotation matrices with lesser complexity and better computational efficiency. It also gives general closed forms of Wigner d-matrix elements in terms of the rotation angle instead of half this angle as is usual.
A simple model for ion injection and transport in conducting polymers
Authors: Stavrinidou Eleni , Leleux Pierre , Rajaona Harizo , Fiocchi Michel , Sanaur Sébastien , Malliaras George G.
Published: June 2013

We present a simple analytical model that describes ion transport in a planar junction between an electrolyte and a conducting polymer film. When ions are injected in the film, holes recede, leading to partial dedoping of the film. This is modeled by two resistors in series, an ionic one for the dedoped part and an electronic one for the still-doped part. We show that analytical predictions can be made for the temporal evolution of the drift length of ions and the current, variables that could be assessed experimentally. A numerical model based on forward time iteration of drift/diffusion equations is used to validate these predictions. Using realistic materials parameters, we find that the analytical model can be used to obtain the ion drift mobility in the film, and as such, it might be useful towards the development of structure vs. ion transport properties relationships in this important class of electronic materials.
Non-polar (11-20) InGaN quantum dots with short exciton lifetimes grown by metal-organic vapor phase epitaxy
Authors: Zhu Tongtong , Oehler Fabrice , Reid Benjamin P. L. , Emery Robert M. , Taylor Robert A. , Kappers Menno J. , Oliver Rachel A.
Published: June 2013

We report on the optical characterization of non-polar a-plane InGaN quantum dots (QDs) grown by metal-organic vapor phase epitaxy using a short nitrogen anneal treatment at the growth temperature. Spatial and spectral mapping of sub-surface QDs has been achieved by cathodoluminescence at 8 K. Microphotoluminescence studies of the QDs reveal resolution limited sharp peaks with typical linewidth of 1 meV at 4.2 K. Time-resolved photoluminescence studies suggest the excitons in these QDs have a typical lifetime of 538 ps, much shorter than that of the c-plane QDs, which is strong evidence of the significant suppression of the internal electric fields.
Effects of electrode modification using calcium on the performance of alternating current field-induced polymer electroluminescent devices
Authors: Xia Yingdong , Chen Yonghua , Smith Gregory M. , Li Yuan , Huang Wenxiao , Carroll David L.
Published: June 2013

In this work, the effects of electrode modification by calcium (Ca) on the performance of AC field induced polymer electroluminescence (FIPEL) devices are studied. The FIPEL device with Ca/Al electrode exhibits 550 cd m−2, which is 27.5 times higher than that of the device with only an Al electrode (20 cd m−2). Both holes and electrons are injected from one electrode in our FIPEL device. We found that the electron injection can be significantly enhanced by a Ca modification on the Al electrode without greatly affecting the hole injection. Therefore, the electrons and holes can be effectively recombined in the emissive layer to form more excitons under the AC voltage, leading to effective light emission. The device emitted much brighter light than other AC-based organic EL devices. This result provides an easy and effective way to improve FIPEL performance.
Determination of structure tilting in magnetized plasmas—Time delay estimation in two dimensions
Authors: Guszejnov Dávid , Bencze Attila , Zoletnik Sándor , Krämer-Flecken Andreas
Published: June 2013

Time delay estimation (TDE) is a well-known technique to investigate poloidal flows in fusion plasmas. The present work is an extension of the earlier works of Bencze and Zoletnik [Phys. Plasmas 12, 052323 (2005)] and Tal et al. [Phys. Plasmas 18, 122304 (2011)]. From the prospective of the comparison of theory and experiment, it seems to be important to estimate the statistical properties of the TDE based on solid mathematical groundings. This paper provides analytic derivation of the variance of the TDE using a two-dimensional model for coherent turbulent structures in the plasma edge and also gives an explicit method for determination of the tilt angle of structures. As a demonstration, this method is then applied to the results of a quasi-2D Beam Emission Spectroscopy measurement performed at the TEXTOR tokamak.
CuSbS2 and CuBiS2 as potential absorber materials for thin-film solar cells
Authors: Kumar Mukesh , Persson Clas
Published: June 2013

The current thin-film photovoltaic (PV) technologies are dominated by CdTe and Cu(In,Ga)Se2 compounds. However, due to the limited availably and toxicity of the elements in these technologies, the current research efforts are directed to search alternative earth abundant materials. Therefore, in this work, we analyze the CuSbS2 and CuBiS2 compounds as alternative absorber materials for future thin-film solar cells. Employing a first-principles approach within the density functional theory, we calculate the structural, electronic, and optical properties of CuSbS2 and CuBiS2 compounds. We show that these compounds have indirect fundamental band gap Eg ≈ 1.5–1.7 eV. The indirect gap nature is different from the previous experimental measurements. However, due to the flat bands, the direct gap Egd ≈ 1.6–1.8 eV is suitable for solar energy technologies. Furthermore, calculations reveal that these compounds have strong absorption coefficients, which are about twice as large as in other Cu-S based PV materials like CuInS2 and Cu2ZnSnS4. Therefore, CuSbS2 and CuBiS2 have the potential to be used as absorber materials in thin-film PV technologies.
Plasmon-loss imaging of polymer-methanofullerene bulk heterojunction solar cells
Authors: Mendis Budhika G. , Bishop Sarah J. , Groves Chris , Szablewski Marek , Berlie Adam , Halliday Douglas P.
Published: June 2013

The plasmon feature in an electron energy loss spectrum provides unique insight into poly(3-hexylthiophene) (P3HT)-phenyl-C61-butyric acid methyl ester (PCBM) solar cells. Analysis of the intensity, shape, and energy of the plasmon reveals information about the type of phase, distribution of P3HT semi-crystalline fibres, and PCBM packing density at high spatial resolution. Plasmon-loss imaging has also revealed nano-scale residual solvent pockets with preferentially dissolved PCBM. A robust tomography method for reconstructing the 3D morphology of the bulk heterojunction thin-film via plasmon-loss images is also presented. The analysis techniques can be used to investigate morphology evolution during thin-film processing and its effect on device performance.
Trade-off between curvature tuning and position invariance in visual area V4
Authors: Sharpee Tatyana O. , Kouh Minjoon , Reynolds John H.
Published: June 2013

Humans can rapidly recognize a multitude of objects despite differences in their appearance. The neural mechanisms that endow high-level sensory neurons with both selectivity to complex stimulus features and “tolerance” or invariance to identity-preserving transformations, such as spatial translation, remain poorly understood. Previous studies have demonstrated that both tolerance and selectivity to conjunctions of features are increased at successive stages of the ventral visual stream that mediates visual recognition. Within a given area, such as visual area V4 or the inferotemporal cortex, tolerance has been found to be inversely related to the sparseness of neural responses, which in turn was positively correlated with conjunction selectivity. However, the direct relationship between tolerance and conjunction selectivity has been difficult to establish, with different studies reporting either an inverse or no significant relationship. To resolve this, we measured V4 responses to natural scenes, and using recently developed statistical techniques, we estimated both the relevant stimulus features and the range of translation invariance for each neuron. Focusing the analysis on tuning to curvature, a tractable example of conjunction selectivity, we found that neurons that were tuned to more curved contours had smaller ranges of position invariance and produced sparser responses to natural stimuli. These trade-offs provide empirical support for recent theories of how the visual system estimates 3D shapes from shading and texture flows, as well as the tiling hypothesis of the visual space for different curvature values.
Genome of a SAR116 bacteriophage shows the prevalence of this phage type in the oceans
Authors: Kang Ilnam , Oh Hyun-Myung , Kang Dongmin , Cho Jang-Cheon
Published: June 2013

The abundance, genetic diversity, and crucial ecological and evolutionary roles of marine phages have prompted a large number of metagenomic studies. However, obtaining a thorough understanding of marine phages has been hampered by the low number of phage isolates infecting major bacterial groups other than cyanophages and pelagiphages. Therefore, there is an urgent requirement for the isolation of phages that infect abundant marine bacterial groups. In this study, we isolated and characterized HMO-2011, a phage infecting a bacterium of the SAR116 clade, one of the most abundant marine bacterial lineages. HMO-2011, which infects “
Candidatus
Puniceispirillum marinum” strain IMCC1322, has an ∼55-kb dsDNA genome that harbors many genes with novel features rarely found in cultured organisms, including genes encoding a DNA polymerase with a partial DnaJ central domain and an atypical methanesulfonate monooxygenase. Furthermore, homologs of nearly all HMO-2011 genes were predominantly found in marine metagenomes rather than cultured organisms, suggesting the novelty of HMO-2011 and the prevalence of this phage type in the oceans. A significant number of the viral metagenome sequences obtained from the ocean surface were best assigned to the HMO-2011 genome. The number of reads assigned to HMO-2011 accounted for 10.3%–25.3% of the total reads assigned to viruses in seven viromes from the Pacific and Indian Oceans, making the HMO-2011 genome the most or second-most frequently assigned viral genome. Given its ability to infect the abundant SAR116 clade and its widespread distribution,
Puniceispirillum
phage HMO-2011 could be an important resource for marine virus research.
Regional variations in the health, environmental, and climate benefits of wind and solar generation
Authors: Siler-Evans Kyle , Azevedo Inês Lima , Morgan M. Granger , Apt Jay
Published: June 2013

When wind or solar energy displace conventional generation, the reduction in emissions varies dramatically across the United States. Although the Southwest has the greatest solar resource, a solar panel in New Jersey displaces significantly more sulfur dioxide, nitrogen oxides, and particulate matter than a panel in Arizona, resulting in 15 times more health and environmental benefits. A wind turbine in West Virginia displaces twice as much carbon dioxide as the same turbine in California. Depending on location, we estimate that the combined health, environmental, and climate benefits from wind or solar range from $10/MWh to $100/MWh, and the sites with the highest energy output do not yield the greatest social benefits in many cases. We estimate that the social benefits from existing wind farms are roughly 60% higher than the cost of the Production Tax Credit, an important federal subsidy for wind energy. However, that same investment could achieve greater health, environmental, and climate benefits if it were differentiated by region.
Gut bacteria facilitate adaptation to crop rotation in the western corn rootworm
Authors: Chu Chia-Ching , Spencer Joseph L. , Curzi Matías J. , Zavala Jorge A. , Seufferheld Manfredo J.
Published: June 2013

Insects are constantly adapting to human-driven landscape changes; however, the roles of their gut microbiota in these processes remain largely unknown. The western corn rootworm (WCR,
Diabrotica virgifera virgifera
LeConte) (Coleoptera: Chrysomelidae) is a major corn pest that has been controlled via annual rotation between corn (
Zea mays
) and nonhost soybean (
Glycine max
) in the United States. This practice selected for a “rotation-resistant” variant (RR-WCR) with reduced ovipositional fidelity to cornfields. When in soybean fields, RR-WCRs also exhibit an elevated tolerance of antiherbivory defenses (i.e., cysteine protease inhibitors) expressed in soybean foliage. Here we show that gut bacterial microbiota is an important factor facilitating this corn specialist’s (WCR's) physiological adaptation to brief soybean herbivory. Comparisons of gut microbiota between RR- and wild-type WCR (WT-WCR) revealed concomitant shifts in bacterial community structure with host adaptation to soybean diets. Antibiotic suppression of gut bacteria significantly reduced RR-WCR tolerance of soybean herbivory to the level of WT-WCR, whereas WT-WCR were unaffected. Our findings demonstrate that gut bacteria help to facilitate rapid adaptation of insects in managed ecosystems.
Diarylcoumarins inhibit mycolic acid biosynthesis and kill
Mycobacterium tuberculosis
by targeting FadD32
Authors: Stanley Sarah A. , Kawate Tomohiko , Iwase Noriaki , Shimizu Motohisa , Clatworthy Anne E. , Kazyanskaya Edward , Sacchettini James C. , Ioerger Thomas R. , Siddiqi Noman A. , Minami Shoko , Aquadro John A. , Grant Sarah Schmidt , Rubin Eric J. , Hung Deborah T.
Published: June 2013

Infection with the bacterial pathogen
Mycobacterium tuberculosis
imposes an enormous burden on global public health. New antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. Here, we describe the identification of a 4,6-diaryl-5,7-dimethyl coumarin series that kills
M. tuberculosis
by inhibiting fatty acid degradation protein D32 (FadD32), an enzyme that is required for biosynthesis of cell-wall mycolic acids. These substituted coumarin inhibitors directly inhibit the acyl-acyl carrier protein synthetase activity of FadD32. They effectively block bacterial replication both in vitro and in animal models of tuberculosis, validating FadD32 as a target for antibiotic development that works in the same pathway as the established antibiotic isoniazid. Targeting new steps in well-validated biosynthetic pathways in antitubercular therapy is a powerful strategy that removes much of the usual uncertainty surrounding new targets and in vivo clinical efficacy, while circumventing existing resistance to established targets.
Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site
Authors: Sigala Paul A. , Fafarman Aaron T. , Schwans Jason P. , Fried Stephen D. , Fenn Timothy D. , Caaveiro Jose M. M. , Pybus Brandon , Ringe Dagmar , Petsko Gregory A. , Boxer Steven G. , Herschlag Daniel
Published: June 2013

Significance

Hydrogen bond networks play critical structural and functional roles in proteins but have been challenging to study within this complex environment. We incorporated spectroscopic probes into the active site of the bacterial enzyme ketosteroid isomerase to systematically dissect the proton transfer equilibrium within a key hydrogen bond network formed to bound transition state analogs. Our study provides direct insight into the physical and energetic properties of a hydrogen bond network within an enzyme and presents a simple computational model of electrostatic effects within this protein that succeeds due to detailed knowledge of ionization states and a tightly controlled experimental system.
STAT3 promotes motor neuron differentiation by collaborating with motor neuron-specific LIM complex
Authors: Lee Seunghee , Shen Rongkun , Cho Hyong-Ho , Kwon Ryuk-Jun , Seo So Yeon , Lee Jae W. , Lee Soo-Kyung
Published: June 2013

The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord.
On the mechanism of recombination hotspot scanning during double-stranded DNA break resection
Authors: Carrasco Carolina , Gilhooly Neville S. , Dillingham Mark S. , Moreno-Herrero Fernando
Published: June 2013

Significance

We report the use of the magnetic tweezers approach to monitor the dynamics of double-stranded DNA break resection at single-molecule resolution. In this work, we unveil the inner workings of the
Bacillus subtilis
AddAB complex by showing that the domain responsible for the recognition of the recombination hotspot sequence Crossover hotspot instigator (Chi) antagonizes the translocation activity, causing the complex to transiently stall at Chi and Chi-like sequences. We propose a simple model for failed and successful Chi recognition in which the battle between the translocation and sequence-specific binding activities acts as a selectivity filter for bona fide Chi sequences.
MS/MS networking guided analysis of molecule and gene cluster families
Authors: Nguyen Don Duy , Wu Cheng-Hsuan , Moree Wilna J. , Lamsa Anne , Medema Marnix H. , Zhao Xiling , Gavilan Ronnie G. , Aparicio Marystella , Atencio Librada , Jackson Chanaye , Ballesteros Javier , Sanchez Joel , Watrous Jeramie D. , Phelan Vanessa V. , van de Wiel Corine , Kersten Roland D. , Mehnaz Samina , De Mot René , Shank Elizabeth A. , Charusanti Pep , Nagarajan Harish , Duggan Brendan M. , Moore Bradley S. , Bandeira Nuno , Palsson Bernhard Ø. , Pogliano Kit , Gutiérrez Marcelino , Dorrestein Pieter C.
Published: June 2013

Significance

The paper introduces the concepts of molecular families (MFs) and gene cluster families (GCFs). We define MFs as structurally related molecules based on their mass spectral fragmentation patterns, whereas GCFs are biosynthetic gene clusters that show similar gene cluster organization with a high degree of sequence similarity. We use MS/MS networking as a tool to map the molecular network of more than 60 organisms, most of which are unsequenced, and locate their nonribosomal peptide MFs. These MFs from unsequenced organisms are then connected to GCFs of publicly available genome sequences of closely related organisms.
Interfering with Gal-1–mediated angiogenesis contributes to the pathogenesis of preeclampsia
Authors: Freitag Nancy , Tirado-González Irene , Barrientos Gabriela , Herse Florian , Thijssen Victor L. J. L. , Weedon-Fekjær Susanne M. , Schulz Herbert , Wallukat Gerd , Klapp Burghard F. , Nevers Tania , Sharma Surendra , Staff Anne Cathrine , Dechend Ralf , Blois Sandra M.
Published: June 2013

Preeclampsia (PE) is a pregnancy-specific disorder characterized by sudden onset of hypertension and proteinuria in the second half of pregnancy (>20 wk). PE is strongly associated with abnormal placentation and an excessive maternal inflammatory response. Galectin-1 (Gal-1), a member of a family of carbohydrate-binding proteins, has been shown to modulate several processes associated with placentation and to promote maternal tolerance toward fetal antigens. Here, we show that Gal-1 exhibits proangiogenic functions during early stages of pregnancy, promoting decidual vascular expansion through VEGF receptor 2 signaling. Blocking Gal-1–mediated angiogenesis or lectin, galactoside-binding, soluble, 1 deficiency results in a spontaneous PE-like syndrome in mice, mainly by deregulating processes associated with good placentation and maternal spiral artery remodeling. Consistent with these findings, we observed a down-regulation of Gal-1 in patients suffering from early onset PE. Collectively, these results strengthen the notion that Gal-1 is required for healthy gestation and highlight Gal-1 as a valuable biomarker for early PE diagnosis.
Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors
Authors: Harms Michael J. , Eick Geeta N. , Goswami Devrishi , Colucci Jennifer K. , Griffin Patrick R. , Ortlund Eric A. , Thornton Joseph W.
Published: June 2013

The genetic and biophysical mechanisms by which new protein functions evolve is a central question in evolutionary biology, biochemistry, and biophysics. Of particular interest is whether major shifts in protein function are caused by a few mutations of large effect and, if they are, the mechanisms that mediate these changes. Here we combine ancestral protein reconstruction with genetic manipulation and explicit studies of protein structure and dynamics to dissect an ancient and discrete shift in ligand specificity in the steroid receptors, a family of biologically essential hormone-controlled transcription factors. We previously found that the ancestor of the entire steroid receptor family was highly specific for estrogens, but its immediate phylogenetic descendant was sensitive only to androgens, progestogens, and corticosteroids. Here we show that this shift in function was driven primarily by two historical amino acid changes, which caused a ∼70,000-fold change in the ancestral protein’s specificity. These replacements subtly changed the chemistry of two amino acids, but they dramatically reduced estrogen sensitivity by introducing an excess of interaction partners into the receptor/estrogen complex, inducing a frustrated ensemble of suboptimal hydrogen bond networks unique to estrogens. This work shows how the protein’s architecture and dynamics shaped its evolution, amplifying a few biochemically subtle mutations into major shifts in the energetics and function of the protein.
Tailored fatty acid synthesis via dynamic control of fatty acid elongation
Authors: Torella Joseph P. , Ford Tyler J. , Kim Scott N. , Chen Amanda M. , Way Jeffrey C. , Silver Pamela A.
Published: June 2013

Medium-chain fatty acids (MCFAs, 4–12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even- and odd-chain–length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired.
Evolutionary lag times and recent origin of the biota of an ancient desert (Atacama–Sechura)
Authors: Guerrero Pablo C. , Rosas Marcelo , Arroyo Mary T. K. , Wiens John J.
Published: June 2013

The assembly of regional biotas and organismal responses to anthropogenic climate change both depend on the capacity of organisms to adapt to novel ecological conditions. Here we demonstrate the concept of evolutionary lag time, the time between when a climatic regime or habitat develops in a region and when it is colonized by a given clade. We analyzed the time of colonization of four clades (three plant genera and one lizard genus) into the Atacama–Sechura Desert of South America, one of Earth’s driest and oldest deserts. We reconstructed time-calibrated phylogenies for each clade and analyzed the timing of shifts in climatic distributions and biogeography and compared these estimates to independent geological estimates of the time of origin of these deserts.ChaetantheraandMalesherbia(plants) andLiolaemus(animal) invaded arid regions of the Atacama–Sechura Desert in the last 10 million years, some 20 million years after the initial onset of aridity in the region. There are also major lag times between when these clades colonized the region and when they invaded arid habitats within the region (typically 4–14 million years). Similarly, hyperarid climates developed ∼8 million years ago, but the most diverse plant clade in these habitats (Nolana) only colonized them ∼2 million years ago. Similar evolutionary lag times may occur in other organisms and habitats, but these results are important in suggesting that many lineages may require very long time scales to adapt to modern desertification and climatic change.
Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function
Authors: Sommese Ruth F. , Sung Jongmin , Nag Suman , Sutton Shirley , Deacon John C. , Choe Elizabeth , Leinwand Leslie A. , Ruppel Kathleen , Spudich James A.
Published: June 2013

Cardiovascular disorders are the leading cause of morbidity and mortality in the developed world, and hypertrophic cardiomyopathy (HCM) is among the most frequently occurring inherited cardiac disorders. HCM is caused by mutations in the genes encoding the fundamental force-generating machinery of the cardiac muscle, including β-cardiac myosin. Here, we present a biomechanical analysis of the HCM-causing mutation, R453C, in the context of human β-cardiac myosin. We found that this mutation causes a ∼30% decrease in the maximum ATPase of the human β-cardiac subfragment 1, the motor domain of myosin, and a similar percent decrease in the in vitro velocity. The major change in the R453C human β-cardiac subfragment 1 is a 50% increase in the intrinsic force of the motor compared with wild type, with no appreciable change in the stroke size, as observed with a dual-beam optical trap. These results predict that the overall force of the ensemble of myosin molecules in the muscle should be higher in the R453C mutant compared with wild type. Loaded in vitro motility assay confirms that the net force in the ensemble is indeed increased. Overall, this study suggests that the R453C mutation should result in a hypercontractile state in the heart muscle.
miR-9 is an essential oncogenic microRNA specifically overexpressed in
mixed lineage leukemia
–rearranged leukemia
Authors: Chen Ping , Price Colles , Li Zejuan , Li Yuanyuan , Cao Donglin , Wiley Anissa , He Chunjiang , Gurbuxani Sandeep , Kunjamma Rejani B. , Huang Hao , Jiang Xi , Arnovitz Stephen , Xu Mengyi , Hong Gia-Ming , Elkahloun Abdel G. , Neilly Mary Beth , Wunderlich Mark , Larson Richard A. , Le Beau Michelle M. , Mulloy James C. , Liu Paul P. , Rowley Janet D. , Chen Jianjun
Published: June 2013

MicroRNAs (miRNAs), small noncoding RNAs that regulate target gene mRNAs, are known to contribute to pathogenesis of cancers. Acute myeloid leukemia (AML) is a group of heterogeneous hematopoietic malignancies with various chromosomal and/or molecular abnormalities. AML with chromosomal translocations involving the
mixed lineage leukemia
(
MLL
) gene are usually associated with poor survival. In the present study, through a large-scale, genomewide miRNA expression assay, we show that microRNA-9 (miR-9) is the most specifically up-regulated miRNA in
MLL-
rearranged AML compared with both normal control and non–
MLL
-rearranged AML. We demonstrate that miR-9 is a direct target of MLL fusion proteins and can be significantly up-regulated in expression by the latter in human and mouse hematopoietic stem/progenitor cells. Depletion of endogenous miR-9 expression by an appropriate antagomiR can significantly inhibit cell growth/viability and promote apoptosis in human
MLL
-rearranged AML cells, and the opposite is true when expression of miR-9 is forced. Blocking endogenous miR-9 function by anti-miRNA sponge can significantly inhibit, whereas forced expression of miR-9 can significantly promote, MLL fusion–induced immortalization/transformation of normal mouse bone marrow progenitor cells in vitro. Furthermore, forced expression of miR-9 can significantly promote MLL fusion–mediated leukemogenesis in vivo. In addition, a group of putative target genes of miR-9 exhibited a significant inverse correlation of expression with miR-9 in a series of leukemia sample sets, suggesting that they are potential targets of miR-9 in
MLL
-rearranged AML. Collectively, our data demonstrate that miR-9 is a critical oncomiR in
MLL
-rearranged AML and can serve as a potential therapeutic target to treat this dismal disease.
Molecular basis for chromatin binding and regulation of MLL5
Authors: Ali Muzaffar , Rincón-Arano Héctor , Zhao Wei , Rothbart Scott B. , Tong Qiong , Parkhurst Susan M. , Strahl Brian D. , Deng Lih-Wen , Groudine Mark , Kutateladze Tatiana G.
Published: June 2013

The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-Å resolution crystal structure of MLL5 plant homeodomain in complex with the H3K4me3 peptide reveals a noncanonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a unique His–Asp swapping rearrangement mediated by a C-terminal α-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is conserved in the
Drosophila
ortholog of MLL5, UpSET, and suggests the developmental control for targeting of H3K4me3. Together, our findings provide first insights into the molecular basis for the recruitment, exclusion, and regulation of MLL5 at chromatin.
Impact of Psychiatric Comorbidity on the In-Treatment Outcomes of Cocaine-Dependent Patients in Therapeutic Communities
Authors: González-Saiz Francisco , Vergara-Moragues Esperanza , Verdejo-García Antonio , Fernández-Calderón Fermín , Lozano Oscar M.
Published: June 2013

Background

This study aimed to explore the association between psychiatric comorbidity and treatment outcomes in therapeutic communities (TCs).

Methods

A prospective longitudinal descriptive design was used. A baseline psychopathological assessment was performed within the first 15 to 20 days of treatment in the TCs. The length of treatment stay was computed for each individual. The study was conducted in the region of Andalusia (Spain). The participants were 218 cocaine-dependent individuals. Psychopathological assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). The outcome measures were retention, defined as the time in TC treatment (number of days), and the patient's assessment upon leaving the TC.

Results

The number of psychopathological comorbidities present in the last year among the patients was high (57.8%) and was associated with a worse response to treatment ( P =.004). The patients with co-occurring psychiatric disorders had a decreased probability of remaining in the TCs compared with patients who only presented with substance use disorders (hazards ratio = 1.61).

Conclusions

Psychiatric comorbidity predicts cocaine-dependent individuals’ likelihood of remaining in residential treatment.
Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study
Authors: Kiblawi Zeina N. , Smith Lynne M. , Diaz Sabrina D. , LaGasse Linda L. , Derauf Chris , Newman Elana , Shah Rizwan , Arria Amelia , Huestis Marilyn , Haning William , Strauss Arthur , DellaGrotta Sheri , Dansereau Lynne M. , Neal Charles , Lester Barry
Published: June 2013

Background

Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown. Methods: The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. Of the subjects, 17,961 were eligible and 3705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or gas chromatography/mass spectroscopy (GC/MS) confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at 1 month to 380 enrollees (185 exposed, 195 comparison). Analysis of variance (ANOVA) tested exposure effects on NNNS summary scores at birth and 1 month. General linear model (GLM) repeated-measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates.

Results

By 1 month of age, both groups demonstrated higher quality of movement ( P = .029), less lethargy ( P = .001), and fewer asymmetric reflexes ( P = .012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants ( P = .031) and total stress was decreased in exposed infants, with no change in comparison infants ( P = .026).

Conclusions

Improvement in total stress and arousal were observed in MA-exposed newborns by 1 month of age relative to the newborn period.