bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural heterogeneity of the midcrust adjacent to the central Alpine Fault, New Zealand: Inferences from seismic tomography and seismicity between Harihari and Ross
Authors: Bourguignon Sandra , Bannister Stephen , Henderson C. Mark , Townend John , Zhang Haijiang
Published: February 2015

Determining the rates and distributions of microseismicity near major faults at different points in the seismic cycle is a crucial step toward understanding plate boundary seismogenesis. We analyze data from temporary seismic arrays spanning the central section of the Alpine Fault, New Zealand, using double‐difference seismic tomography. This portion of the fault last ruptured in a large earthquake in 1717 AD and is now late in its typical 330 year cycle of Mw∼8 earthquakes. Seismicity varies systematically with distance from the Alpine Fault: (1) directly beneath the fault trace, earthquakes are sparse and largely confined to the footwall at depths of 4–11 km; (2) at distances of 0–9 km southeast of the trace, seismicity is similarly sparse and shallower than 8 km; (3) at distances of 9–20 km southeast of the fault trace, earthquakes are much more prevalent and shallower than 7 km. Hypocenter lineations here are subparallel to faults mapped near the Main Divide of the Southern Alps, confirming that those faults are active. The region of enhanced seismicity is associated with the highest topography and a high‐velocity tongue doming at 3–5 km depth. The low‐seismicity zone adjacent to the Alpine Fault trace is associated with Vp and Vs values at midcrustal depths about 8 and 6% lower than further southeast. We interpret lateral variations in seismicity rate to reflect patterns of horizontal strain rate superimposed on heterogeneous crustal structure, and the variations in seismicity cutoff depth to be controlled by temperature and permeability structure variations.
Analysis of the effectiveness of ground‐based VLF wave observations for predicting or nowcasting relativistic electron flux at geostationary orbit
Authors: Simms Laura E. , Engebretson Mark J. , Smith A. J. , Clilverd Mark , Pilipenko Viacheslav , Reeves Geoffrey D.
Published: February 2015

Poststorm relativistic electron flux enhancement at geosynchronous orbit has shown correlation with very low frequency (VLF) waves measured by satellite in situ. However, our previous study found little correlation between electron flux and VLF measured by a ground‐based instrument at Halley, Antarctica. Here we explore several possible explanations for this low correlation. Using 220 storms (1992–2002), our previous work developed a predictive model of the poststorm flux at geosynchronous orbit based on explanatory variables measured a day or two before the flux increase. In a nowcast model, we use averages of variables from the time period when flux is rising during the recovery phase of geomagnetic storms and limit the VLF (1.0 kHz) measure to the dawn period at Halley (09:00–12:00 UT). This improves the simple correlation of VLF wave intensity with flux, although the VLF effect in an overall multiple regression is still much less than that of other factors. When analyses are performed separately for season and interplanetary magnetic field (IMF) Bz orientation, VLF outweighs the influence of other factors only during winter months when IMF Bz is in an average northward orientation.
A simulation study on the impact of altitudinal dependent vertical plasma drift on the equatorial ionosphere in the evening
Authors: Qian Cheng , Lei Jiuhou , Wang Wenbin
Published: February 2015

We carry out a simulation study on the impact of altitudinal dependent plasma drift on the equatorial ionosphere in the evening, under geomagnetically quiet conditions. Our study used the vertical plasma drift velocity data measured by an incoherent scatter radar at Jicamarca (11.95°S, 76.87°W). The data covered the local sunset period on 15 and 16 November 2004. The plasma drift had significant altitudinal variations in the vertical component, which is perpendicular to the magnetic field. We employed SAMI2 (SAMI2 is another model of the ionosphere) to evaluate the effect of the altitude‐dependent ion drift on the equatorial ionosphere. Three types of plasma drift velocity inputs were used in our simulations. The first input is calculated from an empirical model, the second is a height‐averaged drift obtained from the observed drift velocity, and the third one corresponds to the observed altitudinal dependent drift data. A strong equatorial ionization anomaly occurred in the results of all numerical experiments. Additional layers (F3 layers) in electron densities over the equatorial F region and “arch” latitudinal structures extending to lower middle latitudes were seen in the simulations driven by the observed altitudinal dependent drift. We further show that neutral winds do not have a significant effect on the simulated F3 layers. The results of our numerical experiments suggest that the simulated additional ionospheric layers and arch structures are associated with the altitudinal gradients in the vertical plasma drift velocity.
Comprehensive survey of energetic electron events in Mercury's magnetosphere with data from the MESSENGER Gamma‐Ray and Neutron Spectrometer
Authors: Lawrence David J. , Anderson Brian J. , Baker Daniel N. , Feldman William C. , Ho George C. , Korth Haje , McNutt Ralph L. , Peplowski Patrick N. , Solomon Sean C. , Starr Richard D. , Vandegriff Jon D. , Winslow Reka M.
Published: February 2015

Data from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) Gamma‐Ray and Neutron Spectrometer have been used to detect and characterize energetic electron (EE) events in Mercury's magnetosphere. This instrument detects EE events indirectly via bremsstrahlung photons that are emitted when instrument and spacecraft materials stop electrons having energies of tens to hundreds of keV. From Neutron Spectrometer data taken between 18 March 2011 and 31 December 2013 we have identified 2711 EE events. EE event amplitudes versus energy are distributed as a power law and have a dynamic range of a factor of 400. The duration of the EE events ranges from tens of seconds to nearly 20 min. EE events may be classified as bursty (large variation with time over an event) or smooth (small variation). Almost all EE events are detected inside Mercury's magnetosphere on closed field lines. The precise occurrence times of EE events are stochastic, but the events are located in well‐defined regions with clear boundaries that persist in time and form what we call “quasi‐permanent structures.” Bursty events occur closer to dawn and at higher latitudes than smooth events, which are seen near noon‐to‐dusk local times at lower latitudes. A subset of EE events shows strong periodicities that range from hundreds of seconds to tens of milliseconds. The few‐minute periodicities are consistent with the Dungey cycle timescale for the magnetosphere and the occurrence of substorm events in Mercury's magnetotail region. Shorter periods may be related to phenomena such as north‐south bounce processes for the energetic electrons.
Ionospheric loop currents and associated ULF oscillations at geosynchronous altitudes during preonset intervals of substorm aurora
Authors: Saka O. , Hayashi K. , Leonovich A. S.
Published: February 2015

A substorm aurora was observed at 04:52 UT on 27 January 1986 by an all‐sky imager installed at Shamattawa (66.3°N, 336.0° in corrected geomagnetic coordinates) and a magnetometer on board a conjugate satellite (GOES 6) at geosynchronous altitudes. In the preonset intervals lasting for approximately 50 min prior to the expansion onset, an equatorward drift of the auroras beginning from 71°N to 64°N was observed. Meanwhile, GOES 6 observed ULF oscillations in 25–200 s periods at geosynchronous altitudes after about 10 min following the start of the equatorward drift. During the equatorward drift of the arc, the flow reversal occurred, where the auroral arc propagating eastward was replaced by a westward propagation. Simultaneously, the major axes of the ULF oscillations rotated clockwise by ~90° in the equatorial plane. We conclude that the ULF oscillations are azimuthally small‐scale Alfvén waves excited in the magnetosphere by field‐aligned currents associated with ionospheric loop currents.
Approximate expressions for lightning electromagnetic fields at near and far ranges: Influence of return‐stroke speed
Authors: Chen Yazhou , Wang Xiaojia , Rakov Vladimir A.
Published: February 2015

The waveforms of lightning return‐stroke electromagnetic fields on ground are studied using the transmission line model. Approximate expressions to calculate lightning electromagnetic fields at near and far ranges are presented. It is found that the waveforms of lightning electric and magnetic fields in the time domain at both near and far ranges can be expressed approximately as the channel‐base current waveform multiplied by a factor which is a function of the return‐stroke speed v and the horizontal distance r between the return‐stroke channel and the observation point on ground. The ranges at which the approximate expressions are valid are determined. The ranges of validity increase with increasing the return‐stroke speed, and the near and far field approximate expressions converge to the exact formula as the return‐stroke speed approaches the speed of light.
Optics for Digital Imaging
Authors: Catrysse Peter B.
Published: March 2015

Digital imaging has become the predominant way to capture, process, store, and share images and photographs. The images in digital imaging systems are formed by an optical system composed of two equally important subsystems: the imaging optics and the pixel optics. In this chapter, I introduce, describe, and analyze these systems in detail since they both contribute in forming the optical images and are part of any digital imaging system, whether used for consumer, professional, industrial, and even scientific applications. By placing them on equal footing, I will illustrate the intricate interplay between them in accomplishing the goal of the optical system in digital imaging. I start by introducing the entire optical system in Section 1 by defining the imaging and pixel optics subsystems in terms of their optical components. In Section 2, I establish the optics fundamentals as they apply to digital imaging by reviewing the different languages used in the description of the imaging optics and pixel optics. This section provides the foundation for the remainder of the chapter. The concepts, therefore, apply to current and any future systems. Specifically, I describe the use of geometrical optics, radiometry, physical optics, and electromagnetic field optics. The first three are used in the analysis and design of the imaging optics subsystem, while the last is necessary to design, analyze, and optimize the pixel optics subsystem. Next, I apply these optical languages to the design and analysis of the optical system in digital imaging in Section 3. Here, I cover established practices and methods in light of the fact that the subsystems serve different purposes. The purpose of the imaging optics is to create beautiful images, while the pixel optics are engineered in an attempt to waste as little as possible of the photons incident on the pixels of the solid‐state image sensor. The design and the metrics used to assess their performance reflect these differing goals. In Section 4, I briefly touch on digital imaging system simulation and prediction, which is described in greater detail in Image Simulation on Image Simulation, before moving on to design considerations for optical systems in Section 5. Here, I discuss the role that pixel scaling has on imaging and pixel optics design, which is a very timely aspect of optical system design for digital imaging. In this context, I stress the important of capturing every photon incident on a pixel, which in turn motivates the concept of flux‐invariant or photon‐invariant scaling. This sets the stage for an analysis of the microlens performance limits, a study of optical confinement methods for light inside pixels, and a review of backside illumination technology. Finally, I highlight the emerging trends in optical systems for digital imaging in Section 6. As specific illustrations, I point to a few key developments in nanophotonics and computational imaging that have the potential for a significant impact on the future of optical systems.
Digital Versus Analog Imaging
Authors: Kriss Michael
Published: March 2015

In nature, the only continuous image is the “true” scene made up of the point‐to‐point reflectance or emission of light from the various objects in the scene or the direct capture of light from a source such as the sun or light bulb or the translucent transmission of light. There is no limit to the fineness of the detail or the amount of light present. Before the digital age, film was considered by many to be a continuous media (to the unaided eye) even though all photograph images were either made up of very small clusters of developed silver or dye clouds that ranged from one micron to several microns in size. For color films, the dye clouds were normally formed in multiple layers (as many as nine imaging layers) and the overlap of the dye clouds gave rise to a very continuous image unless observed under the microscope. Again, before the digital age, film images were scanned by high quality graphic art scanners that created separations (cyan, magenta, yellow, and black) on black‐and‐white film that would then be used to make halftone separations for printing. The resulting halftones looked continuous if the combination of viewing distance and dot pitch was such that the human eye integrated the dots into an apparent continuous image. If the eye failed to integrate the dots, then is was seen as a halftone dot pattern with some image content. When digital cameras and scanners became available at a moderate cost, the notion of a continuous, captured image gave way to the discrete, sampled image. The sampling transformed a region of the continuous image, the pixel aperture, into a well‐defined pixel of some spatial dimension and some well‐defined value (the average over the pixel aperture). The sampling of the image introduced aliasing artifacts (low frequency banding) when the sampling distance was less than the spatial frequency content of the image. The value of the data defined by each pixel is then quantized into some well‐defined number of bits and a calibration curve. Hence a transmittance or reflectance signal between zero and one would be quantized to 8 bits or more resulting in levels between 0 and 255 or higher. In the same manner, electrical signals captured by a digital camera would be quantized, compressed, and stored in the camera storage media. The impact of this discrete sampling and quantization is covered in this chapter.
Image Compression and File Formats
Authors: Kriss Michael
Published: March 2015

As long as memory storage is at a premium, compression of documents and images was a necessity. While today storage is relatively inexpensive, the role of compression still plays an important part of digital imaging. While digital cameras have significant internal memory and the various memory cards can store in as much as 64 gigabytes of data, data compression is still required for the transmission of images and graphics across networks and even from the personal computer to a printer. Transmission of “movies” would be impossible without sophisticated compression algorithms. This chapter focuses on the compression methods developed for the digital still camera, but they have found considerable use in other fields of imaging where massive data sets need to be stored and retrieved for many imaging uses including medicine, graphic arts,
HD TV
, video conferencing, and digital entertainment. Here,
JPEG
, JPEG 2000, and some of the encoding techniques are demonstrated along with their advantages and disadvantages.
Plasma Display Panel (PDP)
Authors: Mikoshiba Shigeo
Published: March 2015

A plasma display panel (PDP) is basically an assembly of a top and a bottom glass plates. The simplicity of the structure makes a large area, thin, and lightweighted display possible. The display is rugged to withstand high levels of shock and vibration. Phosphor is used for visible emission with highly saturated colors. Fabrication processes unique to plasma display panels are barrier rib fabrications and phosphor coatings, to which various methods have been proposed. Unlike the semiconductor‐like plant of TFT‐LCDs, plasma displays can be manufactured in a less clean and a less precision environment. This reduces the manufacturing cost.

Basic principles of ignition and steady‐state glow discharges in the plasma displays are identical to gas discharge devices, such as fluorescent lamps, but with a difference of a high speed control of millions of tiny discharge cells. The driving of PDPs also requires high voltages, to which various cares have to be taken. The large area plasma displays are suited for expressing high quality images of digital high definition TVs. Picture quality of the PDPs is excellent, especially for fast‐moving images and 3D displays. One of the important issues of the panel characteristics is to improve the luminous efficacy in order to reduce the power consumption.
Ink‐Jet Ink Technologies
Authors: Stoffel John L.
Published: March 2015

Inks are composed of colorant and vehicle. Colorants can be categorized as a dye or a pigment where dye is soluble in the vehicle and pigment in not soluble in the vehicle. The vehicle may be aqueous, solvent, solid, or monomer that can be cured by ultraviolet light. Digital ink‐jet inks have similar requirements to analog inks in terms of print quality and durability and also most need to recover quickly from an idle nonprinting state with minimal intervention. Ink‐jet inks are a critical part of the printing process and can be categorized as thermal ink‐jet, piezo ink‐jet, or continuous ink‐jet ink. Each printing process places requirements on the ink. Ink also must be designed for key substrates that will be needed by the customer. Uncoated free sheet paper, photographic ink‐jet paper, and vinyl are key substrates for ink‐jet printing.
Digital Halftones
Authors: Vanderhaeghe David , Ostromoukhov Victor
Published: March 2015

This chapter presents in detail how halftoning algorithms are designed and can be implemented, from the simplest and widely used to the latest improvements.

There are two main types of digital halftoning approaches. Three algorithmic classes exist to perform digital halftoning : point algorithms, neighborhood algorithms, and iterative algorithms. Point algorithms are local, parallelizable, processes that use a single original image pixel to decide whether a microdot should receive ink or not. Majority of algorithms in this class use a matrix‐based approach.

The second class of digital halftoning approaches uses local neighborhood knowledge to compute the output image. A typical example is error diffusion. Error diffusion is a sequential process: it processes one microdot after the other, propagating an error value to unprocessed pixels. We present both the original error diffusion methods and the improvements, with a comparative study of their pros and cons.

The last class is iterative algorithms which consider original and output images globally during the computation. The distribution of microdots becomes a global iterative process. Iterative algorithms are generally costly; but the resulting halftones show very good distribution and can take into account complex model of printers and the human visual system.
Digital Microscopy
Authors: Stuurman Nico , Thorn Kurt
Published: March 2015

Light microscopes can visualize structures down to 200 nm (or sometimes less) and are therefore the tool of choice to visualize cells, the basic unit of life. No longer do researchers peer through the microscope's eyepieces and document their findings through drawings or on film, rather, digital image acquisition and motorized control of the microscope play a key role. Modern light microscopes capture data on digital detectors and are often fully automated, providing computer control of fluorescence excitation and detection and sample positioning. This makes it possible to automatically acquire multicolor three‐dimensional time‐lapse movies. Moreover, accurate, sensitive detectors enable quantification of microscope images and are a key component of various strategies to improve the spatial and temporal resolution of the microscope. Here, we review modern biological light microscopes, discuss their components, and describe how these tools are utilized experimentally.
Phosphates: Solid‐State Chemistry
Authors: Attfield J. Paul
Published: February 2015

Phosphates contain oxyanions of phosphorus(V). The most common anion is the orthophosphate groupPO43−, which is found in many solid phosphates, including hydrated and acid phosphate salts. Oligomeric polyphosphate chains PnO3n+1(n+2)−up ton= 6 and cyclophosphate rings PnO3nn−up ton= 12 are also observed, and a unique cage ultraphosphate anion P8O236−is found in the Na3FeP8O23structure. Polymeric phosphate anions include the infinite chain catenaphosphate anion (PO3−)∞and the ultraphosphate networks found in CaP4O11and the lanthanide MP5O14structures. Many compound anions and neutral frameworks such as silicophosphates, aluminophosphates, and molybdenum phosphates also exist. Phosphate species are characterized through P–O stretching and bending vibrations in infrared and Raman spectroscopies, and by31P NMR. Phosphate structures are generally rigid, resistant to chemical attack, and (when anhydrous) insoluble and thermally stable. Some phosphate crystals have important physical properties such as ferroelectricity in KH2PO4(potassium dihydrogenphosphate,KDP). Diffusion of extra‐framework ions leads to potential uses of solid phosphates as ion exchangers and conductors, for example, NASICON based on NaZr2(PO4)3, and LiFePO4as a cathode material for lithium‐ion batteries. Vanadium phosphates are important selective oxidation catalysts. Large pore phosphates in which molecules can be adsorbed and undergo acid‐catalyzed reactions have been intensively studied. These materials are crystalline microporous solids such as aluminophosphates, or lamellar structures, typically based on α‐Zr(HPO4)2·H2O that can be pillared. This area of interest has led to the synthesis of many new organically templated metal phosphates, usually through hydrothermal reactions. Hydrated and acid orthophosphates can also be prepared in solution, and anhydrous phosphates are synthesized by direct high‐temperature reactions and from phosphate‐rich melts or fluxes. Slow cooling of melts is used to grow crystals, and quenching can result in many stable phosphate glasses. Phosphate anions do not absorb significantly in the UV–visible region and so solid phosphates also find use as optical materials such as phosphors, nonlinear crystals (e.g., KTiOPO4), and lasers. Solid phosphates constitute many minerals, notably apatites, which are also found in living organisms as rigid components such as bones and teeth. Synthetic calcium phosphate biomaterials are used for bone implants.
Sol–Gel Synthesis of Solids
Authors: Coradin Thibaud
Published: February 2015

The synthesis of glasses and ceramics via the sol–gel route is based on the inorganic polymerization of molecular precursors such as metal alkoxides. Precursor structure and reactivity can be chemically controlled via complexation or acid–base catalysis. Sol–gel chemistry allows the powderless processing of glasses and ceramics, at much lower temperatures than that at usual solid‐state reactions. It provides a convenient and flexible access to nanoparticles, films, and fibers. Moreover, precursors are mixed at the molecular level and multicomponent materials can be formed. Thus, hybrid organic–inorganic materials have been made via the sol–gel route. The organic component can be used as a network modifier during the sol–gel synthesis and then withdrawn, allowing the formation of structured porous materials. It can also remain entrapped in the mineral matrix via weak interactions. Alternatively, organoalkoxysilanes allow covalent binding of organic moieties to silica networks. Such composites fill the gap between polymers and glasses, opening new possibilities for the design of functional materials in the fast developing areas of energy, biotechnology, and medicine.
Hydrogenase Maturation Protein HypF
Authors: Cygler Miroslaw , Petkun Svetlana
Published: February 2015

HypF
is an accessory protein for assembling the
NiFe
(
CN
)
2
CO
active center of [
NiFe
]‐hydrogenases.
HypF
together with
HypE
catalyzes the synthesis of the
CN
‐ ligands using carbamoylphosphate as the initial substrate.
HypF
comprises four domains: the acylphosphatase domain, the Zn finger domain, the
YrdC
‐like domain with a nucleotide‐binding site and the Kae1‐like “universal domain” with a second nucleotide‐binding site coordinated by a metal. The
YrdC
‐ and Kae1‐like domains are juxtaposed with their nucleotide‐binding sites facing each other and sequestered in an internal cavity. The distance between the two sites is approximately 14 Å. The carbamoylphosphate is hydrolyzed to carbamate within the acylphosphatase domain, which then likely migrates through a tunnel in the
YrdC
‐like domain toward the
ATP
molecule bound within this domain's nucleotide‐binding site. The end of the tunnel is near the α‐phosphate of
ATP
where the carbamate is converted to carbamoyl adenylate intermediate. This intermediate presumably diffuses across the cavity to the nucleotide‐binding site in Kae1‐like domain where the transfer of
CN
moiety to the C‐terminal cysteine of
HypE
finally occurs. While the structure discloses the architecture of the various active sites, the details of each catalytic step require further investigations.
Adaptive model predictive inventory controller for multiproduct batch plant
Authors: Yi Gyeongbeom , Reklaitis Gintaras V.
Published: February 2015

An inventory control system was developed for multiproduct batch plants with an arbitrary number of batch processes and storage units. Customer orders are received by the plant at order intervals and in order quantities that are subject to random fluctuations. The objective of the plant operation is to minimize the total cost while maintaining inventory levels within the storage or warehouse capacity by adjusting the startup times, the quantities of raw material orders, and production batch sizes. An adaptive model predictive control algorithm was developed that uses a periodic square wave model to represent the flows of the material between the processes and the storage units. The boundedness of the control output and the convergence of the estimated parameters in implementations of the proposed algorithm were mathematically proven under the assumption that disturbances in the orders are bounded. The effectiveness of this approach was demonstrated by performing simulations. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1867–1880, 2015
Model‐based analysis of a gas/vapor–liquid microchannel membrane contactor
Authors: Lautenschleger Anna , Kenig Eugeny Y. , Voigt Andreas , Sundmacher Kai
Published: February 2015

A comprehensive numerical investigation on membrane distillation of methanol and water in a microseparator was carried out. The focus was to investigate the impact of the apparatus geometry on the separation performance and to develop alternative designs for process intensification. To describe the process, a computational fluid dynamics‐based model was developed and validated against experimental data from literature. Based on this model, parametric studies were performed to gain a deeper understanding of the microchannel geometry influence. Furthermore, two geometry modifications were suggested and analyzed, a miniaturization of the channel and an implementation of baffles. The modification with baffles was chosen for a new separator design which was studied experimentally, and the obtained experimental data were used for another model validation, this time for the baffle arrangement. Subsequent comprehensive simulations were performed to investigate mass‐transfer enhancement by the modified geometry. Generally, the baffles reveal a considerable potential for the process intensification. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2240–2256, 2015
Partial monosomy of 11q22.2q22.3 including the SDHD gene in individuals with developmental delay
Authors: Yelavarthi Krishna , Cabral Huong , Wilson Golder N. , Rohena Luis , Risheg Hiba , Penton Andrea , Schleede Justin , Burnside Rachel D.
Published: March 2015

Deletions in the middle portion of 11q are not as well described in the literature as terminal 11q deletions that result in Jacobsen syndrome. One confounding factor in the older literature is that the G‐banding pattern of 11q13q21 is very similar to 11q21q23. The advent of fluorescence in situ hybridization and later microarray technologies have allowed for a better resolution of many of these deletions, but genotype‐phenotype correlations are still difficult since these deletions are rare events. We present five individuals who presented with developmental delays with de novo 11q22.2q23.3 deletions. Deletions were observed by standard G‐banded chromosome analysis with clarification of breakpoints and gene content by SNP microarray analysis. Of note, all individuals had identical distal breakpoints. All deletions include SDHD, which is implicated in hereditary paraganglioma/pheochromocytoma, for which the patients will need to be monitored in adulthood. In spite of the large deletions of 8.6 Mb (Patients 1 and 3), 13.98 Mb (Patient 2), and 12.6 Mb (Patients 4 and 5) all patients show somewhat mild intellectual disability and dysmorphism. © 2015 Wiley Periodicals, Inc.
Traumatic brain injury in later life increases risk for Parkinson disease
Authors: Gardner Raquel C. , Burke James F. , Nettiksimmons Jasmine , Goldman Sam , Tanner Caroline M. , Yaffe Kristine
Published: February 2015

Objective

Traumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We sought to address these concerns by quantifying risk of PD after TBI compared to non‐TBI trauma (NTT; defined as fractures).

Methods

Using inpatient/emergency department (ED) International Classification of Disease, Ninth Revision code data for California hospitals from 2005–2006, we identified patients aged ≥55 years with TBI (n = 52,393) or NTT (n = 113,406) and without baseline PD or dementia who survived hospitalization. Using Kaplan–Meier estimates and Cox proportional hazards models (adjusted for age, sex, race/ethnicity, income, comorbidities, health care use, and trauma severity), we estimated risk of PD after TBI during follow‐up ending in 2011. We also assessed interaction with mechanism of injury (fall vs nonfall) and effect of TBI severity (mild vs moderate/severe) and TBI frequency (1 TBI vs >1 TBI).

Results

TBI patients were significantly more likely to be diagnosed with PD compared to NTT patients (1.7% vs 1.1%, p < 0.001, adjusted hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31–1.58). Risk of PD was similar for TBI sustained via falls versus nonfalls (interaction p = 0.6). Assessment by TBI severity (mild TBI: HR = 1.24, 95% CI = 1.04–1.48; moderate/severe TBI: HR = 1.50, 95% CI = 1.35–1.66) and TBI frequency (1 TBI: HR = 1.45, 95% CI = 1.30–1.60; >1 TBI: HR = 1.87, 95% CI = 1.58–2.21) revealed a dose response.

Interpretation

Among patients aged ≥55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation. Ann Neurol 2015;77:987–995
Electrical stimulation enhances sensory recovery: A randomized controlled trial
Authors: Wong Joshua N. , Olson Jaret L. , Morhart Michael J. , Chan K. Ming
Published: February 2015

Objective

Brief postsurgical electrical stimulation (ES) has been shown to enhance peripheral nerve regeneration in animal models following axotomy and crush injury. However, whether this treatment is beneficial in humans with sensory nerve injury has not been tested. The goal of this study was to test the hypothesis that ES would enhance sensory nerve regeneration following digital nerve transection compared to surgery alone.

Methods

Patients with complete digital nerve transection underwent epineurial nerve repair. After coaptation of the severed nerve ends, fine wire electrodes were implanted before skin closure. Postoperatively, patients were randomized to receiving either 1 hour of 20Hz continuous ES or sham stimulation in a double‐blinded manner. Patients were followed monthly for 6 months by a blinded evaluator to monitor physiological recovery of spatial discrimination, pressure threshold, and quantitative small fiber sensory testing. Functional disability was measured using the Disability of Arm, Shoulder, and Hand questionnaire.

Results

A total of 36 patients were recruited, with 18 in each group. Those in the ES group showed consistently greater improvements in all sensory modalities by 5 to 6 months postoperatively compared to the controls. Although there was a trend of greater functional improvements in the ES group, it was not statistically significant (p > 0.01).

Interpretation

Postsurgical ES enhanced sensory reinnervation in patients who sustained complete digital nerve transection. The conferred benefits apply to a wide range of sensory functions. Ann Neurol 2015;77:996–1006
Complement C1q‐C3–associated synaptic changes in multiple sclerosis hippocampus
Authors: Michailidou Iliana , Willems Janske G. P. , Kooi Evert‐Jan , van Eden Corbert , Gold Stefan M. , Geurts Jeroen J. G. , Baas Frank , Huitinga Inge , Ramaglia Valeria
Published: February 2015

Objective

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, leading to memory impairment in up to 65% of patients. Memory dysfunction in MS has been associated with loss of synapses in the hippocampus, but its molecular basis is unknown. Accumulating evidence suggests that components of the complement system, C1q and C3, can mediate elimination of synapses.

Methods

To investigate the involvement of complement in synaptic changes in MS, gene and protein expression and localization of C1q and C3 were analyzed in relation to neuropathological changes in myelinated and demyelinated hippocampi from postmortem MS brains. Findings were compared to hippocampi of Alzheimer disease (AD) and non‐neurological controls.

Results

C1q expression and C3 activation were increased in myelinated and demyelinated MS hippocampi, mainly in the CA3/2 and CA1 subfields, which also showed a marked decrease in synaptic density and increased neuronal staining for the mitochondrial heat shock protein 70 (mtHSP70) stress marker. Neurons were the major source of C1q mRNA. C1q protein and activated C3 localized at synapses within human leukocyte antigen–positive cell processes and lysosomes, suggesting engulfment of complement‐tagged synapses by microglia. A significant association (p < 0.0001) between the density of C1q and synaptophysin‐positive synapses or mtHSP70 was seen in myelinated MS hippocampi, further pointing toward a link between the complement pathway and synaptic changes. In contrast to AD, MS hippocampi were consistently negative for the terminal complement activation complex C5b9.

Interpretation

These data support a role for the C1q‐C3 complement axis in synaptic alterations in the MS hippocampus. Ann Neurol 2015;77:1007–1026
Flurbiprofen axetil loaded coaxial electrospun poly(vinyl pyrrolidone)–nanopoly(lactic‐co‐glycolic acid) core–shell composite nanofibers: Preparation, characterization, and anti‐adhesion activity
Authors: Zhu Tonghe , Chen Sihao , Li Wenyao , Lou Jianzhong , Wang Jihu
Published: February 2015

Flurbiprofen axetil (FA)‐loaded coaxial electrospun poly(vinyl pyrrolidone) (PVP)–nanopoly(lactic‐co‐glycolic acid) core–shell composite nanofibers were successfully fabricated by a facile coaxial electrospinning, and an electrospun drug‐loaded system was formed for anti‐adhesion applications. The FA, which is a kind of lipid microsphere nonsteroidal anti‐inflammatory drug, was shown to be successfully adsorbed in the PVP, and the formed poly(lactic‐co‐glycolic acid) (PLGA)/PVP/FA composite nanofibers exhibited a uniform and smooth morphology. The cell viability assay and cell morphology observation revealed that the formed PLGA/PVP/FA composite nanofibers were cytocompatible. Importantly, the loaded FA within the PLGA/PVP coaxial nanofibers showed a sustained‐release profile and anti‐adhesion activity to inhibit the growth of the IEC‐6 and NIH3T3 model cells. With the significantly reduced burst‐release profile, good cytocompatibility, and anti‐adhesion activity, the developed PLGA/PVP/FA composite nanofibers were proposed to be a promising material in the fields of tissue engineering and pharmaceutical science. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41982.
Selective retinol production by modulating the composition of retinoids from metabolically engineered E. coli
Authors: Jang Hui‐Jeong , Ha Bo‐Kyung , Zhou Jia , Ahn Jiyoon , Yoon Sang‐Hwal , Kim Seon‐Won
Published: February 2015

Retinoids can be produced from E. coli when introduced with the β‐carotene biosynthesis pathway and the BCMO gene. E. coli has no inherent metabolic pathways related to retinoids, therefore only retinal should be produced from the cleavage of β‐carotene by BCMO. However, retinol and retinyl acetate were also produced in significant amounts, by the non‐specific activity of inherent promiscuous enzymes or the antibiotic resistance marker of the retinal‐producing plasmids. Retinol was produced by the ybbO gene of E. coli which encodes oxidoreductase and retinyl acetate was produced by the chloramphenicol resistance gene, called cat gene which encodes chloramphenicol acetyltransferase, present within the pS‐NA plasmid that also contains the mevalonate pathway. The composition of retinoids could be modulated by manipulating the relevant genes. The composition of retinol, a commercially important retinoid, was significantly increased by the overexpression of ybbO gene and the removal of cat gene in the recombinant E. coli, which suggests the possibility of selective retinoid production in the future. Biotechnol. Bioeng. 2015;112: 1604–1612. © 2015 Wiley Periodicals, Inc.
Robust kinetics of an RNA virus: Transcription rates are set by genome levels
Authors: Timm Collin , Gupta Ankur , Yin John
Published: February 2015

In order to persist in nature, RNA viruses have evolved strategies to grow in diverse host environments. To better understand how such strategies might work, we used qRT‐PCR to measure viral RNA species during cellular infections by a model RNA virus, vesicular stomatitis virus (VSV). Absolute levels of the VSV major transcript and genome were measured for infections in BHK and PC3 cells, across different multiplicities of infection (MOI 1, 10, 100), in the absence or presence of protein synthesis, as well as in cells in an interferon‐activated anti‐viral state. While viral genome replication was delayed in more resistant host cells, kinetic modeling of these data revealed a simple linear relationship between the mRNA production rate and genome levels under all tested conditions. These results indicate that while viral transcription and genome replication both depend on the availability of the viral RNA‐dependent RNA polymerase and host cellular resources, transcription proceeds without apparent limits on these resources. Biotechnol. Bioeng. 2015;112: 1655–1662. © 2015 Wiley Periodicals, Inc.
Fluid and cell behaviors along a 3D printed alginate/gelatin/fibrin channel
Authors: Xu Yufan , Wang Xiaohong
Published: February 2015

Three‐dimensional (3D) cell manipulation is available with the integration of microfluidic technology and rapid prototyping techniques. High‐Fidelity (Hi‐Fi) constructs hold enormous therapeutic potential for organ manufacturing and regenerative medicine. In the present paper we introduced a quasi‐three‐dimensional (Q3D) model with parallel biocompatible alginate/gelatin/fibrin hurdles. The behaviors of fluids and cells along the microfluidic channels with various widths were studied. Cells inside the newly designed microfluidic channels attached and grew well. Morphological changes of adipose‐derived stem cells (ADSCs) in both two‐dimensional (2D) and 3D milieu were found on the printed constructs. Endothelialization occurred with the co‐cultures of ADSCs and hepatocytes. This study provides insights into the interactions among fluids, cells and biomaterials, the behaviors of fluids and cells along the microfluidic channels, and the applications of Q3D techniques. Biotechnol. Bioeng. 2015;112: 1683–1695. © 2015 Wiley Periodicals, Inc.
High throughput screening of particle conditioning operations: II. Evaluation of scale‐up heuristics with prokaryotically expressed polysaccharide vaccines
Authors: Noyes Aaron , Huffman Ben , Berrill Alex , Merchant Nick , Godavarti Ranga , Titchener‐Hooker Nigel , Coffman Jonathan , Sunasara Khurram , Mukhopadhyay Tarit
Published: February 2015

Multivalent polysaccharide conjugate vaccines are typically comprised of several different polysaccharides produced with distinct and complex production processes. Particle conditioning steps, such as precipitation and flocculation, may be used to aid the recovery and purification of such microbial vaccine products. An ultra scale‐down approach to purify vaccine polysaccharides at the micro‐scale would greatly enhance productivity, robustness, and speed the development of novel conjugate vaccines. In part one of this series, we described a modular and high throughput approach to develop particle conditioning processes (HTPC) for biologicals that combines flocculation, solids removal, and streamlined analytics. In this second part of the series, we applied HTPC to industrially relevant feedstreams comprised of capsular polysaccharides (CPS) from several bacterial species. The scalability of HTPC was evaluated between 0.8 mL and 13 L scales, with several different scaling methodologies examined. Clarification, polysaccharide yield, impurity clearance, and product quality achieved with HTPC were reproducible and comparable with larger scales. Particle sizing was the response with greatest sensitivity to differences in processing scale and enabled the identification of useful scaling rules. Scaling with constant impeller tip speed or power per volume in the impeller swept zone offered the most accurate scale up, with evidence that time integration of these values provided the optimal basis for scaling. The capability to develop a process at the micro‐scale combined with evidence‐based scaling metrics provide a significant advance for purification process development of vaccine processes. The USD system offers similar opportunities for HTPC of proteins and other complex biological molecules. Biotechnol. Bioeng. 2015;112: 1568–1582. © 2015 Wiley Periodicals, Inc.
Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum‐free microcarrier process
Authors: Heathman Thomas R. J. , Glyn Veronica A. M. , Picken Andrew , Rafiq Qasim A. , Coopman Karen , Nienow Alvin W. , Kara Bo , Hewitt Christopher J.
Published: February 2015

Human mesenchymal stem cell (hMSC) therapies are currently progressing through clinical development, driving the need for consistent, and cost effective manufacturing processes to meet the lot‐sizes required for commercial production. The use of animal‐derived serum is common in hMSC culture but has many drawbacks such as limited supply, lot‐to‐lot variability, increased regulatory burden, possibility of pathogen transmission, and reduced scope for process optimization. These constraints may impact the development of a consistent large‐scale process and therefore must be addressed. The aim of this work was therefore to run a pilot study in the systematic development of serum‐free hMSC manufacturing process. Human bone‐marrow derived hMSCs were expanded on fibronectin‐coated, non‐porous plastic microcarriers in 100 mL stirred spinner flasks at a density of 3 × 105 cells.mL−1 in serum‐free medium. The hMSCs were successfully harvested by our recently‐developed technique using animal‐free enzymatic cell detachment accompanied by agitation followed by filtration to separate the hMSCs from microcarriers, with a post‐harvest viability of 99.63 ± 0.03%. The hMSCs were found to be in accordance with the ISCT characterization criteria and maintained hMSC outgrowth and colony‐forming potential. The hMSCs were held in suspension post‐harvest to simulate a typical pooling time for a scaled expansion process and cryopreserved in a serum‐free vehicle solution using a controlled‐rate freezing process. Post‐thaw viability was 75.8 ± 1.4% with a similar 3 h attachment efficiency also observed, indicating successful hMSC recovery, and attachment. This approach therefore demonstrates that once an hMSC line and appropriate medium have been selected for production, multiple unit operations can be integrated to generate an animal component‐free hMSC production process from expansion through to cryopreservation. Biotechnol. Bioeng. 2015;112: 1696–1707. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Cost implications of intraprocedural thrombotic events during PCI
Authors: Plent Stephanie , Fan Weihong , Kirtane Ajay , Brener Sorin J. , Genereux Philippe , Mehran Roxana , Pinto Duane S. , McEntegart Margaret , Cohen David J. , Stone Gregg W.
Published: February 2015

Objectives

We sought to estimate the direct costs (in‐hospital and 30‐day) associated with an intraprocedural thrombotic event (IPTE) among patients with non‐ST‐segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI).

Background

Patients with IPTE have higher rates of in‐hospital and 30‐day major adverse cardiac events than patients without IPTE. The extent to which IPTE also add to medical costs is unknown.

Methods

Hospital costs for patients in the ACUITY Trial were compared between patients with and without IPTE. Adjusted comparisons were performed using generalized linear models (GLMs). All costs are reported in 2012 US dollars.

Results

A total of 1,307 patients with both core laboratory‐based angiographic assessment and detailed economic data were included in the final study population. IPTE occurred in 52 patients (4.0%). Median in‐hospital costs were higher in patients with IPTE than in those without IPTE ($23,719 vs. $18,419, P = 0.01). Thirty‐day median costs were also higher for IPTE patients ($23,719 vs. $19,556, P = 0.05). After adjusting for baseline differences, IPTE was associated with 19.5% (95% CI: [2.8–38.8%], P = 0.02) and 18.9% (95% CI: [1.2–39.7%], P = 0.04) increases in in‐hospital and 30‐day costs, respectively. These relative differences represent median increases of $3,592 in initial hospital costs and $3,696 in 30‐day costs.

Conclusions

The occurrence of IPTE during the index PCI in patients with NSTEACS is associated with substantial increases in‐hospital and 30‐day costs. These findings suggest that strategies to prevent IPTE may be associated with important cost offsets as well as improved clinical outcomes. © 2015 Wiley Periodicals, Inc.
Natural ear rings
Authors: Sabaretnam Mayilvaganan , Virupakshaiah Akash , Baruah Rishiraj
Published: February 2015

Key Clinical Message

Ear lobe keloids are common following ear piercing and these lesions are conspicuous and cosmetically unappealing. Multiple methods including surgery, radiotherapy, anti mitotic agents, silicone sheet, pressure clips, and cryotherapy have been used. The Challenge is to have a good cosmetic outcome with minimal recurrence.