Novel 3D manufacturing method combining microelectrial discharge machining and electrochemical polishing

This paper reports on the potential of microelectrical discharge machining (μEDM) as an innovative method for the fabrication of 3D microdevices. To demonstrate the wide capabilities of μEDM two different microsystems—a microfluidic device for the dispersion of nanoparticles and a star probe for microcoordinate metrology—are presented. To gain optimized process conditions as well as a high surface quality an adequate adaption of the single erosion parameters such as energy, pulse frequency and spark gap has to be carried out and is discussed below. Thus, a surface roughness of R_a?=?80?nm is achieved at the channel bottom. The fabricated stylus elements for the star probe have sphere diameters of 40–200?μm. For further surface quality enhancement a subsequent electrochemical polishing step is investigated. In case of the dispersion micromodule a combined process chain of μEDM-milling and electropolishing has reached a surface improvement above 70%.     

Cantilever probes for high speed AFM

Since the invention in 1986 atomic force microscopy (AFM) has become the most widely used scanning probe microscopy (Binnig et al. in Phys Rev Lett 56:930–933, 1986). The microscope images the interaction of forces like Van der Waals or Coulomb forces between a sample and the apex of a small tip integrated near the free end of a flexible cantilever. But as all other scanning probe techniques the AFM requires serial data acquisition and suffers therefore from a low temporal resolution. Enhancing the speed to video rate imaging makes high demands on scanner technology, control electronics and on the key feature the cantilever with integrated sharp stylus. For the cantilever probes, fundamental resonance frequencies in the MHz regime are envisaged while the force constant of a few nN/nm shall be maintained. We present different novel AFM probes with ultrashort cantilevers and integrated sharp tips for high speed AFM while focusing on widely dispersed applications and on aspects of mass fabrication.     

Electronically controllable microvalves based on smart hydrogels: magnitudes and potential applications

Electronically controllable microvalves based on temperature sensitive hydrogels as actuators are described. A thermal-electronic interface was used for electronic control of the liquid flow. The hydrogel actuators were directly placed in a flow channel. They used the process medium as the swelling agent. Because of the direct placement into the channel the elastic properties of the hydrogel actuator were utilized to improve the pressure insensitivity, to achieve high particle tolerance and to avoid a leakage flow. The microvalves show an extremely simple structure. They can be fabricated using conventional micro technology within a few technical steps. The microvalves can also be miniaturized to a currently unrivalled extent of about 4 /spl mu/m/spl times/4 /spl mu/m/spl times/1/spl mu/m. Valves for "laboratory on chip" applications can already be obtained. The switching times of the electronically controllable microvalves based on hydrogels are 0.3 s to 10 s.     

Stability of discrete-time systems with quantized input and state measurements

This note focuses on linear discrete-time systems controlled using a quantized input computed from quantized measurements. Nominally stabilizing, but otherwise arbitrary, state feedback gains could result in limit cycling or nonzero equilibrium points. Although a single quantizer is a sector nonlinearity, the presence of a quantizer at each state measurement channel makes traditional absolute stability theory not applicable in a direct way. A global asymptotic stability condition is obtained by means of a result which allows us to apply discrete positive real theory to systems with a sector nonlinearity which is multiplicatively perturbed by a bounded function of the state. The stability result is readily applicable by evaluating the location of the polar plot of a system transfer function relative to a vertical line whose abcissa depends on the one-norm of the feedback gain. A graphical method is also described that can be used to determine the equilibrium points of the closed-loop system for any given feedback gain.     

Design of a Medical Non‐Linear Drilling Device: The Influence of Twist and Wear on the Fatigue Behaviour of NiTi Wires Subjected to Bending Rotation

This paper considers fundamental and experimental aspects associated with the engineering design of a medical, non‐linear drilling device which exploits shape memory pseudoelasticity of NiTi wires. For this application it is important that the NiTi wires have a good fatigue resistance. This is why the present authors have previously determined the influence of various parameters on cyclic life, crack growth and stress state of pseudoelastic wires subjected to bending rotation fatigue. The actual drilling device has to withstand twist in addition to bending rotation because the free rotation is constrained by friction between the drill head and the bone material. In addition, friction between the wire and a NiTi guiding tube results in wear and this may well promote fatigue crack nucleation. In this paper, we explain the function of the medical drill. We then report results on the effect of the additional parameters (1) twist and (2) wear on the fatigue life of thin pseudoelastic NiTi wires. We finally discuss the implications of our experimental results for the design process of the medical drilling device.     

Cardiac autonomic nerve function and insulin sensitivity in obese subjects

OBJECTIVE: To investigate whether obesity influences cardiac autonomic nerve function. DESIGN: Comparing two groups of subjects with different degrees of obesity to normal weight controls. SUBJECTS: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2). MEASUREMENTS: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position). RESULTS: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001). CONCLUSION: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.     

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease—Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40–75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40–74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7–33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14–32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2–26.4%), smell assessment (12.4%, 95% CI 6.6–20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7–19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0–43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD.     

Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization,Multiplex RNA Hybridization,Sequencing and Subtyping

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.     

Temporomandibular Joint Osteoarthritis: Pathogenic Mechanisms Involving the Cartilage and Subchondral Bone,and Potential Therapeutic Strategies for Joint Regeneration

The temporomandibular joint (TMJ) is a specialized synovial joint that is crucial for the movement and function of the jaw. TMJ osteoarthritis (TMJ OA) is the result of disc dislocation, trauma, functional overburden, and developmental anomalies. TMJ OA affects all joint structures, including the articular cartilage, synovium, subchondral bone, capsule, ligaments, periarticular muscles, and sensory nerves that innervate the tissues. The present review aimed to illustrate the main pathomechanisms involving cartilage and bone changes in TMJ OA and some therapeutic options that have shown potential restorative properties regarding these joint structures in vivo. Chondrocyte loss, extracellular matrix (ECM) degradation, and subchondral bone remodeling are important factors in TMJ OA. The subchondral bone actively participates in TMJ OA through an abnormal bone remodeling initially characterized by a loss of bone mass, followed by reparative mechanisms that lead to stiffness and thickening of the condylar osteochondral interface. In recent years, such therapies as intraarticular platelet-rich plasma (PRP), hyaluronic acid (HA), and mesenchymal stem cell-based treatment (MSCs) have shown promising results with respect to the regeneration of joint structures or the protection against further damage in TMJ OA. Nevertheless, PRP and MSCs are more frequently associated with cartilage and/or bone repair than HA. According to recent findings, the latter could enhance the restorative potential of other therapies (PRP, MSCs) when used in combination, rather than repair TMJ structures by itself. TMJ OA is a complex disease in which degenerative changes in the cartilage and bone develop through intricate mechanisms. The regenerative potential of such therapies as PRP, MSCs, and HA regarding the cartilage and subchondral bone (alone or in various combinations) in TMJ OA remains a matter of further research, with studies sometimes obtaining discrepant results.