Incomplete Gamma Kernels: Generalizing Locally Optimal Projection Operators.

We present incomplete gamma kernels, a generalization of Locally Optimal Projection (LOP) operators. In particular, we reveal the relation of the classical localized L1 estimator, used in the LOP operator for point cloud denoising, to the common Mean Shift framework via a novel kernel. Furthermore, we generalize this result to a whole family of kernels that are built upon the incomplete gamma function and each represents a localized Lp estimator. By deriving various properties of the kernel family concerning distributional, Mean Shift induced, and other aspects such as strict positive definiteness, we obtain a deeper understanding of the operator's projection behavior. From these theoretical insights, we illustrate several applications ranging from an improved Weighted LOP (WLOP) density weighting scheme and a more accurate Continuous LOP (CLOP) kernel approximation to the definition of a novel set of robust loss functions. These incomplete gamma losses include the Gaussian and LOP loss as special cases and can be applied to various tasks including normal filtering. Furthermore, we show that the novel kernels can be included as priors into neural networks. We demonstrate the effects of each application in a range of quantitative and qualitative experiments that highlight the benefits induced by our modifications.

Inhibition of adenovirus replication by CRISPR-Cas9-mediated targeting of the viral E1A gene.

DNA-targeting CRISPR-Cas systems are able to cleave dsDNA in mammalian cells. Accordingly, they have been employed to target the genomes of dsDNA viruses, mostly when present in cells in a non-replicative state with low copy numbers. However, the sheer amount of viral DNA produced within a very short time by certain lytically replicating viruses potentially brings the capacities of CRISPR-Cas systems to their limits. The accessibility of viral DNA replication sites, short time of accessibility of the DNA before encapsidation, or its complexation with shielding proteins are further potential hurdles. Adenoviruses are fast-replicating dsDNA viruses for which no approved antiviral therapy currently exists. We evaluated the potency of CRISPR-Cas9 in inhibiting the replication of human adenovirus 5 in vitro by targeting its master regulator E1A with a set of guide RNAs and observed a decrease in infectious virus particles by up to three orders of magnitude. Target DNA cleavage also negatively impacted the amount of viral DNA accumulated during the infection cycle. This outcome was mainly caused by specific deletions, inversions, and duplications occurring between target sites, which abolished most E1A functions in most cases. Additionally, we compared two strategies for multiplex gRNA expression and obtained comparable results.

Versatile multi-constrained planning for thermal ablation of large liver tumors.

The surgical planning of large hepatic tumor ablation remains a challenging task that relies on fulfilling multiple medical constraints, especially for the ablation based on configurations of multiple electrodes. The placement of the electrodes to completely ablate the tumor as well as their insertion trajectory to their final position have to be planned to cause as little damage to healthy anatomical structures as possible to allow a fast rehabilitation. In this paper, we present a novel, versatile approach for the computer-assisted planning of multi-electrode thermal ablation of large liver tumors based on pre-operative CT data with semantic annotations. This involves both the specification of the number of required electrodes and their distribution to adequately ablate the tumor region without damaging too much healthy tissue. To determine the insertion trajectory of the electrodes to their final position, we additionally incorporate a series of medical constraints into our optimization, which allows a global analysis where obstacles such as bones are taken into account and damage to healthy tissue is mitigated. Compared with the state-of-the-art method, our method achieves compact ablation regions without relying on assumptions on a potential needle path for optimal global search and, hence, is suitable for guiding clinicians through the planning of the tumor ablation. We also demonstrate the feasibility of our approach in various experiments of clinical data and demonstrate that our approach not only allows completely ablating the tumor region but also reducing the damage of healthy tissue in comparison to the previous state-of-the-art method.

Collaborative VR-Based 3D Labeling of Live-Captured Scenes by Remote Users.

Previous work on interactive 3D labeling focused on improving user experience based on virtual/augmented reality and, thereby, speeding-up the labeling of scenes. In this article, we present a novel interactive, collaborative VR-based 3D labeling system for live-captured scenes by multiple remotely connected users based on sparse multi-user input with automatic label propagation and completion. Hence, our system is particularly beneficial in the case of multiple users that are able to label different scene parts from the respectively adequate views in parallel. Our proposed system relies on 1) the RGB-D capture of an environment by a user, 2) a reconstruction client that integrates this stream into a 3D model, 3) a server that gets scene updates and manages the global 3D scene model as well as client requests and the integration/propagation of labels, 4) labeling clients that allow an independent VR-based scene exploration and labeling for each user, and 5) remotely connected users that provide a sparse 3D labeling used to control the label propagation over objects and the label prediction to other scene parts. Our evaluation demonstrates the intuitive collaborative 3D labeling experience as well as its capability to meet the efficiency constraints regarding reconstruction speed, data streaming, visualization, and labeling.

Towards quantitative and intuitive percutaneous tumor puncture via augmented virtual reality.

In recent years, the radiofrequency ablation (RFA) therapy has become a widely accepted minimal invasive treatment for liver tumor patients. However, it is challenging for doctors to precisely and efficiently perform the percutaneous tumor punctures under free-breathing conditions. This is because the traditional RFA is based on the 2D CT Image information, the missing spatial and dynamic information is dependent on surgeons' experience. This paper presents a novel quantitative and intuitive surgical navigation modality for percutaneous respiratory tumor puncture via augmented virtual reality, which is to achieve the augmented visualization of the pre-operative virtual planning information precisely being overlaid on intra-operative surgical scenario. In the pre-operation stage, we first combine the signed distance field of feasible structures (like liver and tumor) where the puncture path can go through and unfeasible structures (like large vessels and ribs) where the needle is not allowed to go through to quantitatively generate the 3D feasible region for percutaneous puncture. Then we design three constraints according to the RFA specialists consensus to automatically determine the optimal puncture trajectory. In the intra-operative stage, we first propose a virtual-real alignment method to precisely superimpose the virtual information on surgical scenario. Then, a user-friendly collaborative holographic interface is designed for real-time 3D respiratory tumor puncture navigation, which can effectively assist surgeons fast and accurately locating the target step-by step. The validation of our system is performed on static abdominal phantom and in vivo beagle dogs with artificial lesion. Experimental results demonstrate that the accuracy of the proposed planning strategy is better than the manual planning sketched by experienced doctors. Besides, the proposed holographic navigation modality can effectively reduce the needle adjustment for precise puncture as well. Our system shows its clinical feasibility to provide the quantitative planning of optimal needle path and intuitive in situ holographic navigation for percutaneous tumor ablation without surgeons' experience-dependence and reduce the times of needle adjustment. The proposed augmented virtual reality navigation system can effectively improve the precision and reliability in percutaneous tumor ablation and has the potential to be used for other surgical navigation tasks.

Parameter identification for the simulation of the periodontal ligament during the initial phase of orthodontic tooth movement.

The paper is concerned with simulation of the periodontal ligament response to force in the initial phase of orthodontic tooth movement. This is based on two previous investigations, a in vitro experiment with specimens of porcine mandibular premolars and a in vivo experiment on human upper first incisors. For the curve fit of the in vitro experiment a model function, assuming viscoelasticity, was introduced. The viscoelastic model function was augmented by a ramp rise time term, to account for observed dependence of the response on actuator velocity, and a previous load history term, to account for the effect of the previous tests on the current test. The correlation coefficient of a curve fit for all tests grouped together was R2=0.98. Next, a curve fit of the in vivo experiment was done. Good correlation was found for a simplified model function, without viscoelastic term (R2=0.96). For both tests, in vitro and in vivo, the ramp rise time term improved correlation. A finite element model of the specimen of the in vitro experiment was created. For the PDL a hyperelastic constitutive model for compressible material was used and model parameters were identified. The present work indicates that the macroscopic response of the periodontal ligament to an external load can be simulated with a poro-visco-hyperelastic model. The simulation showed that poroelastic behaviour will gradually cease when viscoelastic relaxation progresses. This followed also from dimensionless analysis. As a consequence, for slow loading, or if initial response to fast loading is not of interest, a visco-hyperelastic model may suffice. To identify parameters of the finite element model several optimisation problems were solved. A model function, which can be regarded as a reduced order model, allowed a full factorial experiment (analysis) at low cost, to identify initial parameters. The thus found parameters were further refined with an optimum interpolation meta-model. That is, for limited number of parameter combinations the response was simulated with the finite element model and a refined parameter study was conducted by means of optimal interpolation. The thus found optimal parameters were verified by simulation with the finite element model. Optimal interpolation is computationally cheap, which allowed full factorial experiments at low cost.

Constraint-Based Optimized Human Skeleton Extraction from Single-Depth Camera.

As a cutting-edge research topic in computer vision and graphics for decades, human skeleton extraction from single-depth camera remains challenging due to possibly occurring occlusions of different body parts, huge appearance variations, and sensor noise. In this paper, we propose to incorporate human skeleton length conservation and symmetry priors as well as temporal constraints to enhance the consistency and continuity for the estimated skeleton of a moving human body. Given an initial estimation of the skeleton joint positions provided per frame by the Kinect SDK or Nuitrack SDK, which do not follow the aforementioned priors and can prone to errors, our framework improves the accuracy of these pose estimates based on the length and symmetry constraints. In addition, our method is device-independent and can be integrated into skeleton extraction SDKs for refinement, allowing the detection of outliers within the initial joint location estimates and predicting new joint location estimates following the temporal observations. The experimental results demonstrate the effectiveness and robustness of our approach in several cases.

SLAMCast: Large-Scale, Real-Time 3D Reconstruction and Streaming for Immersive Multi-Client Live Telepresence.

Real-time 3D scene reconstruction from RGB-D sensor data, as well as the exploration of such data in VR/AR settings, has seen tremendous progress in recent years. The combination of both these components into telepresence systems, however, comes with significant technical challenges. All approaches proposed so far are extremely demanding on input and output devices, compute resources and transmission bandwidth, and they do not reach the level of immediacy required for applications such as remote collaboration. Here, we introduce what we believe is the first practical client-server system for real-time capture and many-user exploration of static 3D scenes. Our system is based on the observation that interactive frame rates are sufficient for capturing and reconstruction, and real-time performance is only required on the client site to achieve lag-free view updates when rendering the 3D model. Starting from this insight, we extend previous voxel block hashing frameworks by introducing a novel thread-safe GPU hash map data structure that is robust under massively concurrent retrieval, insertion and removal of entries on a thread level. We further propose a novel transmission scheme for volume data that is specifically targeted to Marching Cubes geometry reconstruction and enables a 90% reduction in bandwidth between server and exploration clients. The resulting system poses very moderate requirements on network bandwidth, latency and client-side computation, which enables it to rely entirely on consumer-grade hardware, including mobile devices. We demonstrate that our technique achieves state-of-the-art representation accuracy while providing, for any number of clients, an immersive and fluid lag-free viewing experience even during network outages.

The Viral Gene ORF79 Encodes a Repressor Regulating Induction of the Lytic Life Cycle in the Haloalkaliphilic Virus ϕCh1.

In this study, we describe the construction of the first genetically modified mutant of a halovirus infecting haloalkaliphilic Archaea By random choice, we targeted ORF79, a currently uncharacterized viral gene of the haloalkaliphilic virus ϕCh1. We used a polyethylene glycol (PEG)-mediated transformation method to deliver a disruption cassette into a lysogenic strain of the haloalkaliphilic archaeon Natrialba magadii bearing ϕCh1 as a provirus. This approach yielded mutant virus particles carrying a disrupted version of ORF79. Disruption of ORF79 did not influence morphology of the mature virions. The mutant virus was able to infect cured strains of N. magadii, resulting in a lysogenic, ORF79-disrupted strain. Analysis of this strain carrying the mutant virus revealed a repressor function of ORF79. In the absence of gp79, onset of lysis and expression of viral proteins occurred prematurely compared to their timing in the wild-type strain. Constitutive expression of ORF79 in a cured strain of N. magadii reduced the plating efficiency of ϕCh1 by seven orders of magnitude. Overexpression of ORF79 in a lysogenic strain of N. magadii resulted in an inhibition of lysis and total absence of viral proteins as well as viral progeny. In further experiments, gp79 directly regulated the expression of the tail fiber protein ORF34 but did not influence the methyltransferase gene ORF94. Further, we describe the establishment of an inducible promoter for in vivo studies in N. magadiiIMPORTANCE Genetic analyses of haloalkaliphilic Archaea or haloviruses are only rarely reported. Therefore, only little insight into the in vivo roles of proteins and their functions has been gained so far. We used a reverse genetics approach to identify the function of a yet undescribed gene of ϕCh1. We provide evidence that gp79, a currently unknown protein of ϕCh1, acts as a repressor protein of the viral life cycle, affecting the transition from the lysogenic to the lytic state of the virus. Thus, repressor genes in other haloviruses could be identified by sequence homologies to gp79 in the future. Moreover, we describe the use of an inducible promoter of N. magadii Our work provides valuable tools for the identification of other unknown viral genes by our approach as well as for functional studies of proteins by inducible expression.

Accurate Interactive Visualization of Large Deformations and Variability in Biomedical Image Ensembles.

Large image deformations pose a challenging problem for the visualization and statistical analysis of 3D image ensembles which have a multitude of applications in biology and medicine. Simple linear interpolation in the tangent space of the ensemble introduces artifactual anatomical structures that hamper the application of targeted visual shape analysis techniques. In this work we make use of the theory of stationary velocity fields to facilitate interactive non-linear image interpolation and plausible extrapolation for high quality rendering of large deformations and devise an efficient image warping method on the GPU. This does not only improve quality of existing visualization techniques, but opens up a field of novel interactive methods for shape ensemble analysis. Taking advantage of the efficient non-linear 3D image warping, we showcase four visualizations: 1) browsing on-the-fly computed group mean shapes to learn about shape differences between specific classes, 2) interactive reformation to investigate complex morphologies in a single view, 3) likelihood volumes to gain a concise overview of variability and 4) streamline visualization to show variation in detail, specifically uncovering its component tangential to a reference surface. Evaluation on a real world dataset shows that the presented method outperforms the state-of-the-art in terms of visual quality while retaining interactive frame rates. A case study with a domain expert was performed in which the novel analysis and visualization methods are applied on standard model structures, namely skull and mandible of different rodents, to investigate and compare influence of phylogeny, diet and geography on shape. The visualizations enable for instance to distinguish (population-)normal and pathological morphology, assist in uncovering correlation to extrinsic factors and potentially support assessment of model quality.

Genomic manipulations in alkaliphilic haloarchaea demonstrated by a gene disruption in Natrialba magadii.

Alkaliphilic haloarchaea, a distinct physiological group from the closely related neutrophilic haloarchaea, represent an underutilized resource for basic research and industrial applications. In contrast to the neutrophilic haloarchaea, no reports on genomic manipulations in haloalkaliphiles have been published until now. Genomic manipulations via homologous recombination are useful for basic research. In this study, we demonstrate the possibility for this strategy in alkaliphilic haloarchaea for the first time. In a previous study, we developed a PEG-mediated transformation technique for alkaliphilic haloarchaea that was deployed in this study to deliver a gene disruption cassette into the model organism Natrialba magadii. The gene encoding for the well-studied Natrialba extracellular protease was successfully disrupted by a recombination marker gene, demonstrating a proof of principle for the usability of homologous recombination for genomic manipulations in alkaliphilic haloarchaea. Since halo(alkali)philic Archaea are polyploid, a selection process was applied in order to obtain a mutant strain containing exclusively disrupted genes. The resulting strain exhibited no proteolytic activity measurable by an azo-casein assay. Complementation was able to restore proteolytic activity. The expression pattern of the Natrialba extracellular protease was different in the complemented strain.

Image-Based Reverse Engineering and Visual Prototyping of Woven Cloth.

Realistic visualization of cloth has many applications in computer graphics. An ongoing research problem is how to best represent and capture cloth models, specifically when considering computer aided design of cloth. Previous methods produce highly realistic images, however, they are either difficult to edit or require the measurement of large databases to capture all variations of a cloth sample. We propose a pipeline to reverse engineer cloth and estimate a parametrized cloth model from a single image. We introduce a geometric yarn model, integrating state-of-the-art textile research. We present an automatic analysis approach to estimate yarn paths, yarn widths, their variation and a weave pattern. Several examples demonstrate that we are able to model the appearance of the original cloth sample. Properties derived from the input image give a physically plausible basis that is fully editable using a few intuitive parameters.

Identification of RISC-associated adenoviral microRNAs, a subset of their direct targets, and global changes in the targetome upon lytic adenovirus 5 infection.

UNLABELLED: Adenoviruses encode a set of highly abundant microRNAs (mivaRNAs), which are generated by Dicer-mediated cleavage of the larger noncoding virus-associated RNAs (VA RNAs) I and II. We performed deep RNA sequencing to thoroughly investigate the relative abundance of individual single strands of mivaRNA isoforms in human A549 cells lytically infected with human adenovirus 5 (Ad5) at physiologically relevant multiplicities of infection (MOIs). In addition, we investigated their relative abundance in the endogenous RNA-induced silencing complexes (RISCs). The occupation of endogenous RISCs by mivaRNAs turned out to be pronounced but not as dominant as previously inferred from experiments with AGO2-overexpressing cells infected at high MOIs. In parallel, levels of RISC-incorporated mRNAs were investigated as well. Analysis of mRNAs enriched in RISCs in Ad5-infected cells revealed that only mRNAs with complementarity to the seed sequences of mivaRNAs derived from VA RNAI but not VA RNAII were overrepresented among them, indicating that only mivaRNAs derived from VA RNAI are likely to contribute substantially to the posttranscriptional downregulation of host gene expression. Furthermore, to generate a comprehensive picture of the entire transcriptome/targetome in lytically infected cells, we determined changes in cellular miRNA levels in both total RNA and RISC RNA as well, and bioinformatical analysis of mRNAs of total RNA/RISC fractions revealed a general, genome-wide trend toward detargeting of cellular mRNAs upon infection. Lastly, we identified the direct targets of both single strands of a VA RNAI-derived mivaRNA that constituted one of the two most abundant isoforms in RISCs of lytically infected A549 cells. IMPORTANCE: Viral and cellular miRNAs have been recognized as important players in virus-host interactions. This work provides the currently most comprehensive picture of the entire mRNA/miRNA transcriptome and of the complete RISC targetome during lytic adenovirus infection and thus represents the basis for a deeper understanding of the interplay between the virus and the cellular RNA interference machinery. Our data suggest that, at least in the model system that was employed, lytic infection by Ad5 is accompanied by a measurable global net detargeting effect on cellular mRNAs, and analysis of RISC-associated viral small RNAs revealed that the VA RNAs are the only source of virus-encoded miRNAs. Moreover, this work allows to assess the power of individual viral miRNAs to regulate cellular gene expression and provides a list of proven and putative direct targets of these miRNAs, which is of importance, given the fact that information about validated targets of adenovirus-encoded miRNAs is scarce.

Design and implementation of practical bidirectional texture function measurement devices focusing on the developments at the University of Bonn.

Understanding as well as realistic reproduction of the appearance of materials play an important role in computer graphics, computer vision and industry. They enable applications such as digital material design, virtual prototyping and faithful virtual surrogates for entertainment, marketing, education or cultural heritage documentation. A particularly fruitful way to obtain the digital appearance is the acquisition of reflectance from real-world material samples. Therefore, a great variety of devices to perform this task has been proposed. In this work, we investigate their practical usefulness. We first identify a set of necessary attributes and establish a general categorization of different designs that have been realized. Subsequently, we provide an in-depth discussion of three particular implementations by our work group, demonstrating advantages and disadvantages of different system designs with respect to the previously established attributes. Finally, we survey the existing literature to compare our implementation with related approaches.

Combinatorial targeting of 2 different steps in adenoviral DNA replication by herpes simplex virus thymidine kinase and artificial microRNA expression for the inhibition of virus multiplication in the presence of ganciclovir.

BACKGROUND: Human adenoviruses are a frequent threat to immunocompromised patients, and disseminated disease is associated with severe morbidity and mortality. Current drugs are not capable of preventing all fatalities, thus indicating the need for alternative treatment strategies. Adenoviruses can be rendered susceptible to antiherpetic prodrugs such as ganciclovir (GCV), upon expression of the herpes simplex virus thymidine kinase (HSV-TK) gene in adenovirus-infected cells. Furthermore, adenoviruses are amenable to post-transcriptional gene silencing via small interfering RNAs (siRNAs) or artificial micro RNAs (amiRNAs). RESULTS: In this study, we combined these 2 approaches by constructing a combinatorial gene expression cassette that comprises the HSV-TK gene and multiple copies of an amiRNA directed against the mRNA encoding the adenoviral preterminal protein (pTP). HSV-TK gene expression was controlled by the adenoviral E4 promoter, which is activated in the presence of the adenoviral E1 gene products (i.e., when adenovirus is present in the cell). When inserted into a replication-deficient (E1-, E3-deleted) adenoviral vector, this cassette effectively inhibited the replication of wild-type adenovirus in vitro. The reduction rate mediated by the combinatorial approach was higher compared to that achieved by either of the 2 approaches alone, and these obvious additive effects became most pronounced when the GCV concentration was low. CONCLUSIONS: The concept presented here has the potential to aid in the inhibition of wild-type adenovirus replication. Furthermore, the combinatorial expression cassette may constitute a safeguard to potentially control unintended replication of adenoviral vectors and to prevent immune responses provoked by them.

An adenoviral vector-based expression and delivery system for the inhibition of wild-type adenovirus replication by artificial microRNAs.

Human adenoviruses are rarely associated with life-threatening infections in healthy individuals. However, immunocompromised patients, and particularly allogeneic hematopoietic stem cell transplant recipients, are at high risk of developing disseminated and potentially fatal disease. The efficacy of commonly used drugs to treat adenovirus infections (i.e., cidofovir in most cases) is limited, and alternative treatment options are needed. Artificial microRNAs (amiRNAs) are a class of synthetic RNAs resembling cellular miRNAs, and, similar to their natural relatives, can mediate the knockdown of endogenous gene expression. This process, termed RNA interference, can be harnessed to target and potentially silence both cellular and viral genes. In this study, we designed amiRNAs directed against adenoviral E1A, DNA polymerase, and preterminal protein (pTP) mRNAs in order to inhibit adenoviral replication in vitro. For the expression of amiRNA-encoding sequences, we utilized replication-deficient adenoviral vectors. In cells transduced with the recombinant vectors and infected with the wild-type (wt) adenovirus, one particular amiRNA that was directed against the pTP mRNA was capable of decreasing the output of infectious wt virus progeny by 2.6 orders of magnitude. This inhibition rate could be achieved by concatemerizing amiRNA-encoding sequences to allow for high intracellular amiRNA concentrations. Because superinfecting wt virus induces the replication and amplification of the recombinant adenoviral vector, amiRNA concentrations were increased in cells infected with wt adenovirus. Furthermore, a combination of amiRNA expression and treatment of infected cells with cidofovir resulted in additive effects that manifested as a total reduction of infectious virus progeny by greater than 3 orders of magnitude.

Inhibition of adenovirus multiplication by short interfering RNAs directly or indirectly targeting the viral DNA replication machinery.

Human adenoviruses are a common threat to immunocompromised patients, e.g., HIV-positive individuals or solid-organ and, in particular, allogeneic stem cell transplant recipients. Antiviral drugs have a limited effect on adenoviruses, and existing treatment modalities often fail to prevent fatal outcome. Silencing of viral genes by short interfering RNAs (siRNAs) holds a great promise in the treatment of viral infections. The aim of the present study was to identify adenoviral candidate targets for RNA interference-mediated inhibition of adenoviral replication. We investigated the impact of silencing of a set of early, middle, and late viral genes on the replication of adenovirus 5 in vitro. Adenovirus replication was inhibited by siRNAs directed against the adenoviral E1A, DNA polymerase, preterminal protein (pTP), IVa2, hexon, and protease genes. Silencing of early and middle genes was more effective in inhibiting adenovirus multiplication than was silencing of late genes. A siRNA directed against the viral DNA polymerase mRNA decreased viral genome copy numbers and infectious virus progeny by several orders of magnitude. Since silencing of any of the early genes directly or indirectly affected viral DNA synthesis, our data suggest that reducing viral genome copy numbers is a more promising strategy for the treatment of adenoviral infections than is reducing the numbers of proteins necessary for capsid generation. Thus, adenoviral DNA replication was identified as a key target for RNAi-mediated inhibition of adenovirus multiplication. In addition, the E1A transcripts emerged as a second important target, because its knockdown markedly improved the viability of cells at late stages of infection.

Targeted expression of herpes simplex virus thymidine kinase in adenovirus-infected cells reduces virus titers upon treatment with ganciclovir in vitro.

BACKGROUND: Adenoviruses are a frequent cause of life-threatening infections in immunocompromised patients. Available therapeutics still cannot completely prevent fatal outcomes. By contrast, herpes viruses are well treatable with prodrugs such as ganciclovir (GCV), which are selectively activated in virus-infected cells by virus-encoded thymidine kinases. This effective group of prodrugs is not applicable to adenoviruses and other DNA viruses because they lack those kinases. METHODS: To render adenoviruses amenable to GCV treatment, we generated an adenoviral vector-based delivery system for targeted expression of herpes simplex virus thymidine kinase (HSV-TK) in wild-type adenovirus 5 (wt Ad5)-infected cells. HSV-TK expression was largely restricted to wt virus-infected cells by transcription of the gene from the Ad5 E4 promoter. Its activity is dependent on the adenoviral E1A gene product which is not produced by the vector but is only provided in cells infected with wt adenovirus. The anti-adenoviral effect of HSV-TK expression and concomitant treatment with GCV was assessed in vitro in four different cell lines or primary cells. RESULTS: E4 promoter-mediated HSV-TK background expression was sufficiently low to prevent cytotoxicity in the presence of low-levels GCV in cells not infected with wt Ad5. However, expression was several-fold increased in wt Ad5-infected cells and treatment with low levels of GCV efficiently inhibited wt Ad5 DNA replication. Genome copy numbers and output of infectious particles were reduced by up to > 99.99% and cell viability was greatly increased. CONCLUSIONS: We extended the concept of enzyme/prodrug therapy to adenovirus infections by selectively sensitizing adenovirus-infected cells to treatment with GCV.

Development and design of a novel loading device for the investigation of bone adaptation around immediately loaded dental implants using the reindeer antler as implant bed.

The assessment of the behavior of immediately loaded dental implants using biomechanical methods is of particular importance. The primary goal of this investigation is to optimize the function of the implants to serve for immediate loading. Animal experiments on reindeer antlers as a novel animal model will serve for investigation of the bone remodeling processes in the implant bed. The main interest is directed towards the time and loading-dependant behavior of the antler tissue around the implants. The aim and scope of this work was to design an autonomous loading device that has the ability to load an inserted implant in the antler with predefined occlusal forces for predetermined time protocols. The mechanical part of the device can be attached to the antler and is capable of cyclically loading the implant with forces of up to 100 N. For the calibration and testing of the loading device a biomechanical measuring system has been used. The calibration curve shows a logarithmic relationship between force and motor current and is used to control the force on the implant. A first test on a cast reindeer antler was performed successfully.

Effective visualization of short routes.

In this work we develop a new alternative to conventional maps for visualization of relatively short paths as they are frequently encountered in hotels, resorts or museums. Our approach is based on a warped rendering of a 3D model of the environment such that the visualized path appears to be straight even though it may contain several junctions. This has the advantage that the beholder of the image gains a realistic impression of the surroundings along the way which makes it easy to retrace the route in practice. We give an intuitive method for generation of such images and present results from user studies undertaken to evaluate the benefit of the warped images for orientation in unknown environments.