CAD Files and European Design Law

Three-dimensional printing (“3DP”) is an additive manufacturing technology that starts with a virtual 3D model of the object to be printed, the so-called Computer-Aided-Design (“CAD”) file. This file, when sent to the printer, gives instructions to the device on how to build the object layer-by-layer. This paper explores whether design protection is available under the current European regulatory framework for designs that are computer-created by means of CAD software, and, if so, under what circumstances. The key point is whether the appearance of a product, embedded in a CAD file, could be regarded as a protectable element under existing legislation. To this end, it begins with an inquiry into the concepts of “design” and “product”, set forth in Article 3 of the Community Design Regulation No. 6/2002 (“CDR”). Then, it considers the EUIPO’s practice of accepting 3D digital representations of designs. The enquiry goes on to illustrate the implications that the making of a CAD file available online might have. It suggests that the act of uploading a CAD file onto a 3D printing platform may be tantamount to a disclosure for the purposes of triggering unregistered design protection, and for appraising the state of the prior art. It also argues that, when measuring the individual character requirement, the notion of “informed user” and “the designer’s degree of freedom” may need to be reconsidered in the future. The following part touches on the exceptions to design protection, with a special focus on the repairs clause set forth in Article 110 CDR. The concluding part explores different measures that may be implemented to prohibit the unauthorised creation and sharing of CAD files embedding design-protected products.

The design and Evaluation of 'CAP Tools' - A computer aided parallelisation tool-kit

Abstract not available

Computer-aided Drug Design of Novel PLA(2) Inhibitor Candidates for Treatment of Snakebite

Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine its active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.

Global and local detection of liver steatosis from ultrasound

Liver steatosis is a common disease usually associated with social and genetic factors. Early detection and quantification is important since it can evolve to cirrhosis. Steatosis is usually a diffuse liver disease, since it is globally affected. However, steatosis can also be focal affecting only some foci difficult to discriminate. In both cases, steatosis is detected by laboratorial analysis and visual inspection of ultrasound images of the hepatic parenchyma. Liver biopsy is the most accurate diagnostic method but its invasive nature suggest the use of other non-invasive methods, while visual inspection of the ultrasound images is subjective and prone to error. In this paper a new Computer Aided Diagnosis (CAD) system for steatosis classification and analysis is presented, where the Bayes Factor, obatined from objective intensity and textural features extracted from US images of the liver, is computed in a local or global basis. The main goal is to provide the physician with an application to make it faster and accurate the diagnosis and quantification of steatosis, namely in a screening approach. The results showed an overall accuracy of 93.54% with a sensibility of 95.83% and 85.71% for normal and steatosis class, respectively. The proposed CAD system seemed suitable as a graphical display for steatosis classification and comparison with some of the most recent works in the literature is also presented.

Study of ligand-based virtual screening tools in computer-aided drug design

Virtual screening is a central technique in drug discovery today. Millions of molecules can be tested in silico with the aim to only select the most promising and test them experimentally. The topic of this thesis is ligand-based virtual screening tools which take existing active molecules as starting point for finding new drug candidates. One goal of this thesis was to build a model that gives the probability that two molecules are biologically similar as function of one or more chemical similarity scores. Another important goal was to evaluate how well different ligand-based virtual screening tools are able to distinguish active molecules from inactives. One more criterion set for the virtual screening tools was their applicability in scaffold-hopping, i.e. finding new active chemotypes. In the first part of the work, a link was defined between the abstract chemical similarity score given by a screening tool and the probability that the two molecules are biologically similar. These results help to decide objectively which virtual screening hits to test experimentally. The work also resulted in a new type of data fusion method when using two or more tools. In the second part, five ligand-based virtual screening tools were evaluated and their performance was found to be generally poor. Three reasons for this were proposed: false negatives in the benchmark sets, active molecules that do not share the binding mode, and activity cliffs. In the third part of the study, a novel visualization and quantification method is presented for evaluation of the scaffold-hopping ability of virtual screening tools.

Molecular quantum similarity in QSAR: applications in computer-aided molecular design

La present tesi està centrada en l'ús de la Teoria de Semblança Quàntica per a calcular descriptors moleculars. Aquests descriptors s'utilitzen com a paràmetres estructurals per a derivar correlacions entre l'estructura i la funció o activitat experimental per a un conjunt de compostos. Els estudis de Relacions Quantitatives Estructura-Activitat són d'especial interès per al disseny racional de molècules assistit per ordinador i, en particular, per al disseny de fàrmacs. Aquesta memòria consta de quatre parts diferenciades. En els dos primers blocs es revisen els fonaments de la teoria de semblança quàntica, així com l'aproximació topològica basada en la teoria de grafs. Ambdues teories es fan servir per a calcular els descriptors moleculars. En el segon bloc, s'ha de remarcar la programació i implementació de programari per a calcular els anomenats índexs topològics de semblança quàntica. La tercera secció detalla les bases de les Relacions Quantitatives Estructura-Activitat i, finalment, el darrer apartat recull els resultats d'aplicació obtinguts per a diferents sistemes biològics.

O forjamento de ligas de alumínio : um estudo para a liga ABNT 6061

Este trabalho pretende, na visão de novas tecnologias, discutir o processo de forjamento das ligas de alumínio (ABNT 6061), buscando propor uma metodologia baseada na ciência da engenharia. Deseja-se minimizar os procedimentos de tentativa e erro no desenvolvimento de processos de conformação. Para tanto, novas tecnologias disponíveis atualmente, tais como o Projeto Assistido por Computador (CAD), a Fabricação Assistida por Computador (CAM) e a Simulação do Processo (CAE) são empregadas. Resultados experimentais mostrando o comportamento da liga ABNT 6061 através das curvas de escoamento bem como o estabelecimento da condição do atrito no processo de conformação, avaliando dois lubrificantes comerciais disponíveis (Deltaforge 31 e Oildag) para aplicações nas ligas de alumínio, são reportados neste trabalho. A comparação dos resultados obtidos de um experimento prático de forjamento com a simulação pelo “Método dos Elementos Finitos” usando o código “QForm” é apresentada para uma peça de simetria axial em liga de alumínio. Finalmente, os resultados obtidos no forjamento de um componente automotivo em liga de alumínio (ABNT 6061), desenvolvido em parceria com a empresa Dana, são analisados e comparados com as simulações computacionais realizadas usando o código “Superforge”.

Desenvolvimento de um núcleo versátil e integrado de ferramentas CAD/CAE para a modelagem e simulação de peças mecânicas

Currently there is still a high demand for quality control in manufacturing processes of mechanical parts. This keeps alive the need for the inspection activity of final products ranging from dimensional analysis to chemical composition of products. Usually this task may be done through various nondestructive and destructive methods that ensure the integrity of the parts. The result generated by these modern inspection tools ends up not being able to geometrically define the real damage and, therefore, cannot be properly displayed on a computing environment screen. Virtual 3D visualization may help identify damage that would hardly be detected by any other methods. One may find some commercial softwares that seek to address the stages of a design and simulation of mechanical parts in order to predict possible damages trying to diminish potential undesirable events. However, the challenge of developing softwares capable of integrating the various design activities, product inspection, results of non-destructive testing as well as the simulation of damage still needs the attention of researchers. This was the motivation to conduct a methodological study for implementation of a versatile CAD/CAE computer kernel capable of helping programmers in developing softwares applied to the activities of design and simulation of mechanics parts under stress. In this research it is presented interesting results obtained from the use of the developed kernel showing that it was successfully applied to case studies of design including parts presenting specific geometries, namely: mechanical prostheses, heat exchangers and piping of oil and gas. Finally, the conclusions regarding the experience of merging CAD and CAE theories to develop the kernel, so as to result in a tool adaptable to various applications of the metalworking industry are presented

Computer-aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand-binding domain contains the ligand-dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations, and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new-ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. (c) 2005 Wiley Periodicals, Inc.

Computer-aided operation planning and 3-dimensional osteotomy guidance for alveolar distraction

Objectives: In alveolar distraction, in cases of severe atrophy in particular, it is often difficult to perform osteotomies in order to make a transport segment in optimal size and shape. Moreover care must be taken, not to damage the closely locating anato- mical structures such as the maxillary sinus, the inferior alveolar nerve, and the roots of the neighboring teeth. For setting ideal osteotomy lines exactly, we have developed a CT-based preoperative planning tool. Methods: 3-dimensional visual reconstruction of the jaw is created from the preoperative CT scans (1.0-mm slice thick- ness). Using the image-processing software Mimics (Materialise, Yokohama, Japan), various procedures of virtual cutting are simulated first to determine optimal osteotomy lines and to design an ideal transport segment. After the computer planning, data from the virtual solid model are transferred to a rapid prototype model, and a guiding splint is made to transfer the planned surgical simulation to the actual surgery. Results: The method was used in a case of severe atrophy of the anterior maxilla. The patient had a large maxillary sinus requir- ing a precise osteotomy in this critical area. Using the splint allowing a 3-dimensional guidance, alveolar osteotomies were easily done to achieve a transport segment in sufficient dimen- sion as planned, and any perforation of the maxillary sinus could be avoided. Finally the alveolar distraction of 10mm has suc- cessfully been performed. Conclusion: The preoperative planning method and the guiding splint described here are useful in problematic cases requiring an extremely precise osteotomy due to lack of bony space.

Surface Roughness and Microhardness of Two Recent CAD/CAM-Materials After Storage

Objectives: To investigate surface roughness and microhardness of two recent resin-ceramic materials for computer-aided design/computer-aided manufacturing (CAD/CAM) after polishing with three polishing systems. Surface roughness and microhardness were measured immediately after polishing and after six months storage including monthly artificial toothbrushing. Methods: Sixty specimens of Lava Ultimate (3M ESPE) and 60 specimens of VITA ENAMIC (VITA Zahnfabrik) were roughened in a standardized manner and polished with one of three polishing systems (n=20/group): Sof-Lex XT discs (SOFLEX; three-step (medium-superfine); 3M ESPE), VITA Polishing Set Clinical (VITA; two-step; VITA Zahnfabrik), or KENDA Unicus (KENDA; one-step; KENDA Dental). Surface roughness (Ra; μm) was measured with a profilometer and microhardness (Vickers; VHN) with a surface hardness indentation device. Ra and VHN were measured immediately after polishing and after six months storage (tap water, 37°C) including monthly artificial toothbrushing (500 cycles/month, toothpaste RDA ~70). Ra- and VHN-values were analysed with nonparametric ANOVA followed by Wilcoxon rank sum tests (α=0.05). Results: For Lava Ultimate, Ra (mean [standard deviation] before/after storage) remained the same when polished with SOFLEX (0.18 [0.09]/0.19 [0.10]; p=0.18), increased significantly with VITA (1.10 [0.44]/1.27 [0.39]; p=0.0001), and decreased significantly with KENDA (0.35 [0.07]/0.33 [0.08]; p=0.03). VHN (mean [standard deviation] before/after storage) decreased significantly regardless of polishing system (SOFLEX: 134.1 [5.6]/116.4 [3.6], VITA: 138.2 [10.5]/115.4 [5.9], KENDA: 135.1 [6.2]/116.7 [6.3]; all p<0.0001). For VITA ENAMIC, Ra (mean [standard deviation] before/after storage) increased significantly when polished with SOFLEX (0.37 [0.18]/0.41 [0.14]; p=0.01) and remained the same with VITA (1.32 [0.37]/1.31 [0.40]; p=0.58) and with KENDA (0.81 [0.35]/0.78 [0.32]; p=0.21). VHN (mean [standard deviation] before/after storage) remained the same regardless of polishing system (SOFLEX: 284.9 [24.6]/282.4 [31.8], VITA: 284.6 [28.5]/276.4 [25.8], KENDA: 292.6 [26.9]/282.9 [24.3]; p=0.42-1.00). Conclusion: Surface roughness and microhardness of Lava Ultimate was more affected by storage and artificial toothbrushing than was VITA ENAMIC.

Influence of Abutment Design on Stiffness, Strength, and Failure of Implant-Supported Monolithic Resin Nano Ceramic (RNC) Crowns

BACKGROUND Recent technical development allows the digital manufacturing of monolithic reconstructions with high-performance materials. For implant-supported crowns, the fixation requires an abutment design onto which the reconstruction can be bonded. PURPOSE The aim of this laboratory investigation was to analyze stiffness, strength, and failure modes of implant-supported, computer-assisted design and computer-aided manufacturing (CAD/CAM)-generated resin nano ceramic (RNC) crowns bonded to three different titanium abutments. MATERIALS AND METHODS Eighteen monolithic RNC crowns were produced and loaded in a universal testing machine under quasi-static condition according to DIN ISO 14801. With regard to the type of titanium abutment, three groups were defined: (1) prefabricated cementable standard; (2) CAD/CAM-constructed individualized; and (3) novel prefabricated bonding base. Stiffness and strength were measured and analyzed statistically with Wilcoxon rank sum test. Sections of the specimens were examined microscopically. RESULTS Stiffness demonstrated high stability for all specimens loaded in the physiological loading range with means and standard deviations of 1,579 ± 120 N/mm (group A), 1,733 ± 89 N/mm (group B), and 1,704 ± 162 N/mm (group C). Mean strength of the novel prefabricated bonding base (group C) was 17% lower than of the two other groups. Plastic deformations were detectable for all implant-abutment crown connections. CONCLUSIONS Monolithic implant crowns made of RNC seem to represent a feasible and stable prosthetic construction under laboratory testing conditions with strength higher than the average occlusal force, independent of the different abutment designs used in this investigation.

Complications with computer-aided designed/computer-assisted manufactured titanium and soldered gold bars for mandibular implant-overdentures: short-term observations

BACKGROUND Implant-overdentures supported by rigid bars provide stability in the edentulous atrophic mandible. However, fractures of solder joints and matrices, and loosening of screws and matrices were observed with soldered gold bars (G-bars). Computer-aided designed/computer-assisted manufactured (CAD/CAM) titanium bars (Ti-bars) may reduce technical complications due to enhanced material quality. PURPOSE To compare prosthetic-technical maintenance service of mandibular implant-overdentures supported by CAD/CAM Ti-bar and soldered G-bar. MATERIALS AND METHODS Edentulous patients were consecutively admitted for implant-prosthodontic treatment with a maxillary complete denture and a mandibular implant-overdenture connected to a rigid G-bar or Ti-bar. Maintenance service and problems with the implant-retention device complex and the prosthesis were recorded during minimally 3-4 years. Annual peri-implant crestal bone level changes (ΔBIC) were radiographically assessed. RESULTS Data of 213 edentulous patients (mean age 68 ± 10 years), who had received a total of 477 tapered implants, were available. Ti-bar and G-bar comprised 101 and 112 patients with 231 and 246 implants, respectively. Ti-bar mostly exhibited distal bar extensions (96%) compared to 34% of G-bar (p < .001). Fracture rate of bars extensions (4.7% vs 14.8%, p < .001) and matrices (1% vs 13%, p < .001) was lower for Ti-bar. Matrices activation was required 2.4× less often in Ti-bar. ΔBIC remained stable for both groups. CONCLUSIONS Implant overdentures supported by soldered gold bars or milled CAD/CAM Ti-bars are a successful treatment modality but require regular maintenance service. These short-term observations support the hypothesis that CAD/CAM Ti-bars reduce technical complications. Fracture location indicated that the titanium thickness around the screw-access hole should be increased.

Advanced Protein Modeling Method: Benchmarking and Applications in Computer-Aided Drug Discovery

Development of homology modeling methods will remain an area of active research. These methods aim to develop and model increasingly accurate three-dimensional structures of yet uncrystallized therapeutically relevant proteins e.g. Class A G-Protein Coupled Receptors. Incorporating protein flexibility is one way to achieve this goal. Here, I will discuss the enhancement and validation of the ligand-steered modeling, originally developed by Dr. Claudio Cavasotto, via cross modeling of the newly crystallized GPCR structures. This method uses known ligands and known experimental information to optimize relevant protein binding sites by incorporating protein flexibility. The ligand-steered models were able to model, reasonably reproduce binding sites and the co-crystallized native ligand poses of the β2 adrenergic and Adenosine 2A receptors using a single template structure. They also performed better than the choice of template, and crude models in a small scale high-throughput docking experiments and compound selectivity studies. Next, the application of this method to develop high-quality homology models of Cannabinoid Receptor 2, an emerging non-psychotic pain management target, is discussed. These models were validated by their ability to rationalize structure activity relationship data of two, inverse agonist and agonist, series of compounds. The method was also applied to improve the virtual screening performance of the β2 adrenergic crystal structure by optimizing the binding site using β2 specific compounds. These results show the feasibility of optimizing only the pharmacologically relevant protein binding sites and applicability to structure-based drug design projects.