A novel multi-planar radiography method for three dimensional pose reconstruction of the patellofemoral and tibiofemoral joints after arthroplasty

Determining the 3D pose of the patella after total knee arthroplasty is challenging. The commonly used single-plane fluoroscopy is prone to large errors in the clinically relevant mediolateral direction. A conventional fixed bi-planar setup is limited in the minimum angular distance between the imaging planes necessary for visualizing the patellar component, and requires a highly flexible setup to adjust for the subject-specific geometries. As an alternative solution, this study investigated the use of a novel multi-planar imaging setup that consists of a C-arm tracked by an external optoelectric tracking system, to acquire calibrated radiographs from multiple orientations. To determine the accuracies, a knee prosthesis was implanted on artificial bones and imaged in simulated 'Supine' and 'Weightbearing' configurations. The results were compared with measures from a coordinate measuring machine as the ground-truth reference. The weightbearing configuration was the preferred imaging direction with RMS errors of 0.48 mm and 1.32 ° for mediolateral shift and tilt of the patella, respectively, the two most clinically relevant measures. The 'imaging accuracies' of the system, defined as the accuracies in 3D reconstruction of a cylindrical ball bearing phantom (so as to avoid the influence of the shape and orientation of the imaging object), showed an order of magnitude (11.5 times) reduction in the out-of-plane RMS errors in comparison to single-plane fluoroscopy. With this new method, complete 3D pose of the patellofemoral and tibiofemoral joints during quasi-static activities can be determined with a many-fold (up to 8 times) (3.4mm) improvement in the out-of-plane accuracies compared to a conventional single-plane fluoroscopy setup.     

Stress chaperone mortalin regulates human melanogenesis

In order to identify the cellular factors involved in human melanogenesis, we carried out shRNA-mediated loss-of-function screening in conjunction with induction of melanogenesis by 1-oleoyl-2-acetyl-glycerol (OAG) in human melanoma cells using biochemical and visual assays. Gene targets of the shRNAs (that caused loss of OAG-induced melanogenesis) and their pathways, as determined by bioinformatics, revealed involvement of proteins that regulate cell stress response, mitochondrial functions, proliferation, and apoptosis. We demonstrate, for the first time, that the mitochondrial stress chaperone mortalin is crucial for melanogenesis. Upregulation of mortalin was closely associated with melanogenesis in in vitro cell-based assays and clinical samples of keloids with hyperpigmentation. Furthermore, its knockdown resulted in compromised melanogenesis. The data proposed mortalin as an important protein that may be targeted to manipulate pigmentation for cosmetic and related disease therapeutics.     

Histidine availability is decisive in ROS-mediated cytotoxicity of copper complexes of Aβ1–16 peptide

The binding of metal ions to Aβ peptide plays an important role in the etiology of AD. Copper coordinates chiefly to His residues and produces reactive oxygen species (ROS) upon redox cycling. ROS builds enormous burden on the normal functioning of neuronal cells and results into deleterious effects. Recently, two structurally distinct copper binding sites with contrasting redox properties were characterized. Here, we demonstrate for the first time the effect of binding of two equivalents of Cu²⁺ on redox properties and cytotoxicity of Aβ peptide. Our electrochemical data and ascorbate consumption assay suggest that in the presence of two equivalents of copper; Aβ peptide has higher propensity of H₂O₂ generation. The oxidation of Aβ1–16 peptide due to both gamma radiolysis and metal catalyzed oxidation in the presence of two equivalents of copper is inhibited confirming the binding of both equivalents of copper to peptide. The electrochemical and cytotoxicity study shows that negative shift in the reduction potential is reflected as slightly higher cytotoxicity in SH-SY5Y cell lines for Aβ1–16–Cu²⁺ (1:2) complex.     

Modeling FMS with decision Petri nets

Decision point extended timed Petri nets or decision Petri nets (DPN) are introduced as an extended modeling framework for FMS performance evaluation. The decision point extension allows the explicit modeling of the control of the flow of tokens in timed Petri nets and hence represents the control of the flow of material, resources, and information in FMS. Further, the concept of a bounded transition is proposed to conveniently model the blocking logic in an FMS with limited buffer capacities. The motivation to present these conventions is to develop a user-friendly graphic model to represent FMS designs for analysis by discrete event simulation. DPN affords concise models that can be conveniently developed and easily transformed into discrete event simulation models. With the help of a simple FMS example, which includes a number of part types, loading rules, dispatching rules, and probabilistic branching (at an inspection station), we illustrate the DPN model development. As an illustration of the ease with which it can be tranformed into a simulation model, we have developed a generalized simulator called ROBSIM and outline here its methodological basis. The proposed concepts should be of interest to users of discrete event simulation in FMS design or elsewhere to tap the potential of basic Petri net concepts for graphic representation and specification purposes. In particular, our work should encourage other researchers to develop extensions relevant to their own areas of interest.     

Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues,cell lines and conditioned medium

Background

Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.

Results

We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).

Conclusions

Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users.