A biphasic calcium phosphate with submicron needle-shaped surface topography combined with a novel polyethylene glycol/polylactic acid triblock copolymer binder (BCP-EP) was investigated in this ...study. This study aims to evaluate the composition, degradation mechanism and bioactivity of BCP-EP in vitro, and its in vivo performance as an autograft bone graft (ABG) extender in a rabbit Posterolateral Fusion (PLF) model. The characterization of BCP-EP and its in vitro degradation products showed that the binder hydrolyses rapidly into lactic acid, lactide oligomers and unaltered PEG (polyethylene glycol) without altering the BCP granules and their characteristic submicron needle-shaped surface topography. The bioactivity of BCP-EP after immersion in SBF revealed a progressive surface mineralization. In vivo, BCP-EP was assessed in a rabbit PLF model by radiography, manual palpation, histology and histomorphometry up to 12 weeks post-implantation. Twenty skeletally mature New Zealand (NZ) White Rabbits underwent single-level intertransverse process PLF surgery at L4/5 using (1) autologous bone graft (ABG) alone or (2) by mixing in a 1:1 ratio with BCP-EP (BCP-EP/ABG). After 3 days of implantation, histology showed the BCP granules were in direct contact with tissues and cells. After 12 weeks, material resorption and mature bone formation were observed, which resulted in solid fusion between the two transverse processes, following all assessment methods. BCP-EP/ABG showed comparable fusion rates with ABG at 12 weeks, and no graft migration or adverse reaction were noted at the implantation site nor in distant organs.
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Optimization of porous titanium alloy scaffolds designed for orthopedic implants requires balancing mechanical properties and osseointegrative performance. The tradeoff between scaffold porosity and ...the stiffness/strength must be optimized towards the goal to improve long term load sharing while simultaneously promoting osseointegration. Osseointegration into porous titanium implants covering a wide range of porosity (0%–90%) and manufactured by laser powder bed fusion (LPBF) was evaluated with an established ovine cortical and cancellous defect model. Direct apposition and remodeling of woven bone was observed at the implant surface, as well as bone formation within the interstices of the pores. A linear relationship was observed between the porosity and benchtop mechanical properties of the scaffolds, while a non-linear relationship was observed between porosity and the ex vivo cortical bone-implant interfacial shear strength. Our study supports the hypothesis of porosity dependent performance tradeoffs, and establishes generalized relationships between porosity and performance for design of topological optimized implants for osseointegration. These results are widely applicable for orthopedic implant design for arthroplasty components, arthrodesis devices such as spinal interbody fusion implants, and patient matched implants for treatment of large bone defects.
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•Macroscale undercut features present on the endplates and within the aperture of an interbody cage provide a series of anchoring points that, with new bone formation and remodelling, resulted in ...improved biomechanical integrity of the treated level.
The interface and interactions between an interbody cage, graft material, and host bone can all participate in the fusion. Shortcomings of Poly(aryl-ether-ether-ketone) interbody cages have been addressed with novel titanium surfaces. Titanium surfaces paired with macroscale topography features on the endplates and within the aperture may provide additional benefits.
To evaluate the influence of cage design parameters on interbody fusion in a large animal preclinical model.
A comparative preclinical large animal model was performed to evaluate how macroscale topography features of an interbody cage can facilitate early integration between the host bone, graft material, and interbody cage and these effects on biomechanical stability and fusion.
Forty single level interbody fusions (L4–L5) using iliac crest autograft and bilateral pedicle screw fixation were performed in adult sheep to evaluate the effect of undercut macrostructure topography features of an interbody cage on the endplates and within the aperture. Fusions were evaluated at 6 and 12 weeks (n=10 per group) using radiography, microcomputed tomography, biomechanical integrity, and histology endpoints.
The presence of the undercut macrostructures present on the endplates and within the aperture statistically improved biomechanical integrity at 6 and 12 weeks compared with controls. Microcomputed tomography and histology demonstrated bony interdigitation within the endplate and aperture features contributing to the improvement in properties.
The present study demonstrates that Poly(aryl-ether-ether-ketone) implants with titanium surfaces can be augmented by undercut macrostructures present on the endplates and within the aperture to provide opportunities for a series of anchoring points that, with new bone formation and remodelling, result in earlier and improved biomechanical integrity of the treated level.
This preclinical study showed that bone interdigitation with the undercut macrostructures present on the endplates and within the aperture resulted in improved fusion and biomechanical stability in a clinically relevant spinal fusion model. Future clinical study is warranted to evaluate such implants’ performance in humans.
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This book was written for statisticians, computer scientists, geographers, researchers, and others interested in visualizing data. It presents a unique foundation for producing almost every ...quantitative graphic found in scientific journals, newspapers, statistical packages, and data visualization systems. While the tangible results of this work have been several visualization software libraries, this book focuses on the deep structures involved in producing quantitative graphics from data. What are the rules that underlie the production of pie charts, bar charts, scatterplots, function plots, maps, mosaics, and radar charts? Those less interested in the theoretical and mathematical foundations can still get a sense of the richness and structure of the system by examining the numerous and often unique color graphics it can produce. The second edition is almost twice the size of the original, with six new chapters and substantial revision. Much of the added material makes this book suitable for survey courses in visualization and statistical graphics. "This fascinating book deconstructs the process of producing graphics and in doing so raises many fascinating questions on the nature and representation of information...This second edition is almost twice the size of the original, with six new chapters and substantial revisions." Short Book Reviews of the International Statistical Institute, December 2005 "When the first edidtion of this book appeared in 2000 it was much praised. I called it a tour de force of the highest order. (Wainer, 2001), Edward Wegman (2000) argued that it was destined to become a classic. Now, six years later this very fine book has been much improved." Howard Wainer for Psychometrika
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6.
Building a Better Bridge WILLS, Dan
Civil engineering (New York, N.Y. 1983),
03/2008, Volume:
78, Issue:
3
Magazine Article
The Homestead Grays Bridge spans the Monongahela River southeast of Pittsburgh to link Homestead and West Homestead. Constructed in 1936 as the Homestead High-Level Bridge, it was renamed in 2002 to ...honor the Homestead Grays, a championship baseball team that played in the various Negro leagues from 1912 to 1950. From November 2005 to October 2007, the bridge and ramp underwent an extensive rehabilitation funded by the Federal Highway Administration, the Pennsylvania Department of Transportation, and Allegheny County. The bridge's framing system consists of girders and trusses supporting floor beams, which support longitudinal stringers supporting transverse joists. One of the greatest challenges during the rehabilitation was maintaining two lanes of traffic on the bridge at all times. The existing railing was tagged, removed, and delivered to a nearby storage site. The damaged and deteriorated pieces of the railing were repaired, the lead-based paint was removed, and three coats of an organic zinc-rich coating system were applied.
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Anterior cruciate ligament (ACL) reconstruction (ACLR) is used to treat clinical instability post ACL rupture, however, there is a high rate of incomplete return to sport and rerupture. There is ...increasing interest in posterior tibial slope as an intrinsic risk factor for ACLR failure and persistent instability. Zoobiquity describes the collaboration between the human and veterinary professions in order to advance the scientific understanding of both fields. Given the cranial cruciate ligament (CCL) in dogs is synonymous with the anterior cruciate ligament in humans, functioning to control internal rotation and anterior translation, but osteotomies, rather than ligament reconstruction, are the mainstay of treatment for CCL rupture, this editorial sort to gain insights into this form of treatment from the veterinary world.
Level of Evidence: Level V, evidence.
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The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell ...cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20
and UL24
To test whether UL21 is needed only for the A855V mutant, additional gB
derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gB
phenotype. This is the first example of a differential requirement for a viral protein across the four
loci.
UL21 is conserved among alphaherpesviruses, but its role is poorly understood. This study shows that HSV-1 can replicate without UL21, although the virus titers are greatly reduced. The null virus had greater proportions of empty (DNA-less) capsids in the cytoplasm of infected cells, suggesting that UL21 may play a role in retaining them in the nucleus. This is consistent with reports showing UL21 to be capsid associated and localized to the nuclei of infected cells. UL21 also appears to be needed for viral membrane activities. It was found to be required for virus-mediated cell fusion, but only for mutants that harbor syncytial mutations in gB (not variants of gK, UL20, or UL24). The machinery needed for syncytial formation is similar to that needed for direct spread of the virus through cell junctions, and these studies show that UL21 is required for cell-to-cell spread even in the absence of syncytial mutations.
Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this ...scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.
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The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been ...shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined.
The HSV-1-encoded tegument protein UL16 is involved in multiple events of the virus replication cycle, ranging from virus assembly to cell-cell spread of the virus, and hence it can serve as an important drug target. Unfortunately, a lack of both structural and functional information limits our understanding of this protein. The discovery of domain interactions within UL16 and the novel ability of UL16 to interact with mitochondria in HSV-infected cells lays a foundational framework for future investigations aimed at deciphering the structure and function of not just UL16 of HSV-1 but also its homologs in other herpesviruses.
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