The Synthesis, Characterization, and Cell Seeding of a Collagen/Hydroxyapatite Porous Scaffold for Treatment of Osseous Defects

The need for finding a bone graft substitute stems from the fact that approximately 200,000 bone grafting procedures are performed annually in the U.S. alone. Although biological grafting options (i.e. autografts & allografts) exist, they do suffer from inherent problems. These include limited resources, costly processing, and potential for pathogen transfer. Thus, investigators have sought synthetic alternatives. The objective of this research was to utilize hydroxyapatite (HA) and collagen, both analogues to the major constituents of bone, to fabricate an optimal synthetic osteoconductive/osteoinductive bone scaffold. Current attempts by other investigators to combine the two materials have been met with some difficulties, resulting in free or loosely bound particulate HA within the collagen matrix. This may ultimately result in a foreign body response to the disseminated crystals. Yet, this study revealed that through manipulation of the collagen\u27s collodial chemistry, it could be made into a more effective carrier medium for particulate HA. It was found that treating the collagen with either IOOmM NaOH or hydrochloric acid followed by titration with 1 N NaOH to a basic pH ( approximately 11 . 8) would yield an adhesive, paste-like matrix capable of incorporating the HA, following lyophilization of the matrix. Composites made under acidic, neutral, and conditions correlating to pH values below 11 .8 were found to possess free HA particulates and loose, friable collagen fibers. The composites were also frozen at two different temperatures to study their effects on microporosity formation. Porosity is an essential characteristic given that it serves as 111 pathways by which vasculature is established, cellular elements may infiltrate; and by which nutrients are supplied to the graft. It was found that porosity of the composite could be controlled by regulating the ice crystal formation prior to lyophilization of the material. Micron size pores were achieved by freezing the composite to -l 5°C and controlling the amount of particulate HA added to the system. TGF-β 1 was also studied for its efficacy in serving as an osteoinductive catalyst with the collagen/HA composite. It was chosen due to its ability to modulate the growth and differentiation of osteoblast precursor cells. Utilizing 1125 as a tracer, release kinetics of the adsorbed polypeptide from the composite were evaluated. Elution was rapid, with approximately 56 ± 3.5% of the theoretical load release following 24 hours incubation. Improved methods by which to prolong the release of the growth factor may be needed in order to provide for optimal inductive properties. Last, the cytocompatibility of the composite was evaluated. Primary cultures of adult, rabbit and fetal bovine osteoblasts were seeded into two formulations of the collagen/HA composite. Following three days of culture, an acid-to-base titrated composite formulation grafted with fetal bovine cells was the only combination which exhibited the presence of adherent cells. The lack of fetal cells upon a base-only treated collagen/HA composite was speculated to be a result of modifications to the collagen due to processing. Seeding technique and cell donor age were also suggested as possible reasons for the absence of cells utilizing adult rabbit cells on either composite formulation. Together, the findings suggest that the composite could serve as a suitable, porous bone scaffold. Due to its compressive strength values, it would best be reserved for non-load-bearing applications, such as an osseous filler material used, for example, in IV conjunction with plated fractures. Improved TGF-β1 incorporation, in-depth in vitro studies, as well as an in vivo model will need to be assessed to determine the true effectiveness of the composite to replace existing biological sources

Multiple time scales in cataclysmic binaries. The low-field magnetic dwarf nova DO Draconis

We study the variability of the cataclysmic variable DO Dra, on time-scales of between minutes and decades. The characteristic decay time dt/dm=0.902(3) days/mag was estimated from our 3 nights of CCD R observations. The quiescent data show a photometric wave with a cycle about 303(15)d. We analyzed the profile of the composite (or mean) outburst. We discovered however, that a variety of different outburst heights and durations had occurred, contrary to theoretical predictions. With increasing maximum brightness, we find that the decay time also increases; this is in contrast to the model predictions, which indicate that outbursts should have a constant shape. This is interpreted as representing the presence of outburst-to-outburst variability of the magnetospheric radius. A presence of a number of missed weak narrow outbursts is predicted from this statistical relationship. A new type of variability is detected, during 3 subsequent nights in 2007: periodic (during one nightly run) oscillations with rapidly-decreasing frequency from 86 to 47 cycles/day and a semi-amplitude increasing from 0.06 to 0. 10, during a monotonic brightness increase from 14. 27 to 14. 13. This phenomenon was observed only during an unusually prolonged event of about 1 mag brightening in 2007 (lasting till autumn), during which no (expected) outburst was detected. We refer to this behaviour as to the transient periodic oscillations (TPO). To study this new and interesting phenomenon, new regular photometric and spectral (in a target of opportunity mode) observations are required.Comment: 12pages, 8figures, accepted in Astronomy and Astrophysic

Wisconsin Sentence Modification: A View from the Trial Court

In Wisconsin, trial courts have discretion to modify a defendant\u27s criminal sentence if the defendant introduces a new factor. Published Wisconsin case law gives little guidance on what constitutes a new factor. The Wisconsin Supreme Court has declined to find a new factor present in every case it has published since defining new factor in 1978. Because of ambiguous and conflicting rulings, the standards for both prongs of the new factor definition remain unclear. This Comment attempts to shed light on the new factor requirement for sentence modification by examining Wisconsin trial court decisions on a limited sample of sentence modification motions. This study reveals that trial courts modified sentences in a variety of cases to effect their intent in sentencing the defendant when it has been frustrated, to respond to a change in a defendant\u27s health or family circumstances, or to reward a defendant for cooperating with the district attorney after sentencing. These grounds for sentence modification are offered in other states through statutory exceptions to the time limits governing sentence modification motions. This Comment concludes that Wisconsin\u27s sentence modification law, though frought with confusion at the appellate level, nonetheless provides defendants with a broader and more flexible form of post-con- viction relief than that provided in states where statues define the factors justifying a sentence modification

Why does the intermediate polar V405 Aurigae show a double-peaked spin pulse?

V405 Aurigae is an intermediate polar showing a double-peaked pulsation in soft X-rays and a single-peaked pulsation in harder X-rays. From XMM-Newton observations we find that the soft band is dominated by blackbody emission from the heated white-dwarf surface. Such emission is at a maximum when either magnetic pole points towards us, explaining the double-peaked pulsation. The symmetry of the pulses requires that the angle between the magnetic and spin axes be high. The single-peaked pulsation in harder X-rays is explained in the usual way, as a result of opacity in the accretion curtains. However, the high dipole inclination means that the accretion curtains are nearly in the plane. Thus the outer regions of the curtains do not cross the line of sight to the accretion footprints, explaining the absence of the deep absorption dip characteristic of many intermediate polars. The sawtooth profile of this pulsation requires that the magnetic axis be offset from the white-dwarf centre. We remark also on the double-peaked optical emission in this star. We suggest that the difference between V405 Aur's spin pulse and those of other intermediate polars is the result of its high dipole inclination.Comment: 7 pages, 6 figures, accepted for publication in MNRA

An alternative approach to field-aligned coordinates for plasma turbulence simulations

Turbulence simulation codes can exploit the flute-like nature of plasma turbulence to reduce the effective number of degrees of freedom necessary to represent fluctuations. This can be achieved by employing magnetic coordinates of which one is aligned along the magnetic field. This work presents an approach in which the position along the field lines is identified by the toroidal angle, rather than the most commonly used poloidal angle. It will be shown that this approach has several advantages. Among these, periodicity in both angles is retained. This property allows moving to an equivalent representation in Fourier space with a reduced number of toroidal components. It will be shown how this duality can be exploited to transform conventional codes that use a spectral representation on the magnetic surface into codes with a field-aligned coordinate. It is also shown that the new approach can be generalised to get rid of magnetic coordinates in the poloidal plane altogether, for a large class of models. Tests are carried out by comparing the new approach with the conventional approach employing a uniform grid, for a basic ion temperature gradient (ITG) turbulence model implemented by the two corresponding versions of the ETAI3D code. These tests uncover an unexpected property of the model, that localized large parallel gradients can intermittently appear in the turbulent regime. This leaves open the question whether this is a general property of plasma turbulence, which may lead one to reconsider some of the usual assumptions on micro-turbulence dynamics.Comment: 19 pages (once in pdf format). 1 LaTeX file and 10 eps figures in the zip folde

Discovery of a new cataclysmic variable through optical variability and X-ray emission

Aims: We present discovery observations of the new cataclysmic variable star (CV) 1RXS J092737.4-191529, as well as spectra and photometry of SY Vol. The selection technique that turned up these two CVs is described; it should be efficient for finding dwarf novae with high outburst duty cycles. Methods: Two very common observational features of CVs, namely optical variability and X-ray emission, are combined to select targets for follow-up observations. Long-slit spectra were taken to identify CVs in the sample. Results: Two out of three objects selected in this way are CVs. One of these is the known dwarf nova SY Vol, while the second system, 1RXS J092737.4-191529, is a new discovery. We present medium resolution spectra, $UBVRI$ magnitudes, and high-speed photometry for both these CVs. Rapid flickering in the light curve of 1RXS J092737.4-191529 confirms the mass transferring binary nature of this object; it is probably a dwarf nova that was in quiescence during our observations.Comment: 4 pages, 5 figures, accepted to A&

Analysis of Adverse Events in Drug Safety: A Multivariate Approach Using Stratified Quasi-least Squares

Safety assessment in drug development involves numerous statistical challenges, and yet statistical methodologies and their applications to safety data have not been fully developed, despite a recent increase of interest in this area. In practice, a conventional univariate approach for analysis of safety data involves application of the Fisher\u27s exact test to compare the proportion of subjects who experience adverse events (AEs) between treatment groups; This approach ignores several common features of safety data, including the presence of multiple endpoints, longitudinal follow-up, and a possible relationship between the AEs within body systems. In this article, we propose various regression modeling strategies to model multiple longitudinal AEs that are biologically classified into different body systems via the stratified quasi-least squares (SQLS) method. We then analyze safety data from a clinical drug development program at Wyeth Research that compared an experimental drug with a standard treatment using SQLS, which could be a superior alternative to application of the Fisher\u27s exact test

The X-ray Pulse Profile of BG CMi

We present an analysis of the X-ray data of a magnetic cataclysmic variable, BG CMi, obtained with ROSAT in March 1992 and with ASCA in April 1996. We show that four peaks clearly exist in the X-ray pulse profile, unlike a single peak found in the optical profile. The fluxes of two major pulses are $\sim 2 - 5$ times larger than those of two minor pulses. The fraction of the total pulsed flux increases from 51% to 85% with increasing energy in 0.1 $-$ 2.0 keV, whereas it decreases from 96% to 22% in 0.8 $-$ 10 keV. We discuss the implications of our findings for the origin of the pulse profile and its energy dependence.Comment: To appear in New Astronom

Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo

Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a “proof of concept” vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage

Questioning Classic Patient Classification Techniques in Gait Rehabilitation: Insights from Wearable Haptic Technology

Classifying stroke survivors based on their walking abilities is an important part of the gait rehabilitation process. It can act as powerful indicator of function and prognosis in both the early days after a stroke and long after a survivor receives rehabilitation. This classification often relies solely on walking speed; a quick and easy measure, with only a stopwatch needed. However, walking speed may not be the most accurate way of judging individual’s walking ability. Advances in technology mean we are now in a position where ubiquitous and wearable technologies can be used to elicit much richer measures to characterise gait. In this paper we present a case study from one of our studies, where within a homogenous group of stroke survivors (based on walking speed classification) important differences in individual results and the way they responded to rhythmic haptic cueing were identified during the piloting of a novel gait rehabilitation technique