Investigation on the Aha-Experience as an Indicator of Correct Solutions in Functional Analysis in Engineering Design

The functional analysis of technical systems is an important part of the design process. To further improve the design process, especially the functional analysis, it must not be viewed as a monodisciplinary process. To this end, cognitive factors such as the aha-experience must also be included in studies of analysis processes to a greater extent. This paper investigates the relationship between the occurrence of aha-experiences and the correctness of solutions in the analysis of a technical system. An aha-experience is a strong feeling of subjective certainty that accompanies the cognitive process of suddenly finding a previously unknown solution. For this purpose, a study on the functional analysis was evaluated. The results show that many identified subfunctions of the system under investigation were identified with an aha-experience and that these subfunctions are more often correct. The results also suggest that aha-experiences occur more often among students than among experienced design engineers. Especially among students, a positive relation of aha-experiences on the correctness of the identified subfunction can be seen. This offers potential for further investigations to make aha-experiences useful in design methods

Early virological response may predict treatment response in sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center “real-life” cohort

Background: The combination of sofosbuvir (SOF), ribavirin (RBV) and peg-interferon-alfa-2a (peg-IFN-alfa-2a) as well as the combination of SOF and RBV for the treatment of patients infected with hepatitis c virus (HCV) has improved rates of sustained virological response (SVR) considerably in recent trials. However, there is only limited data concerning the efficacy and safety in a “real-life” cohort. Methods: We analyzed a cohort of 119 patients with chronic HCV infection treated at four investigational sites in Germany. All patients received either a combination treatment of SOF, RBV and peg-IFN-alfa-2a or SOF and RBV. Results: The rates of SVR at 12 weeks after end of treatment (SVR 12) were as follows: Among 76 patients with genotype 1 infection the SVR 12 rate was 74 % (n = 56), among 14 patients with genotype 2 infection the SVR 12 rate was 79 % (n = 11), among 24 patients with genotype 3 infection the SVR 12 rate was 92 % (n = 22) and among 5 patients with genotype 4 infection the SVR 12 rate was 80 % (n = 4). Of all 26 patients with a relapse in our cohort, 69 % (n = 18) of these patients presented with liver cirrhosis and 58 % (n = 15) were treatment experienced. Notably, the level of HCV-RNA after 4 weeks of treatment was a significant predictor of treatment response in genotype 1 patients. Patients with HCV-RNA levels ≥ 12 IU ml-1 after 4 weeks of treatment achieved SVR 12 only in 30 % (n = 17/56, p < 0.0001) of cases and treatment response was even lower with SVR 12 of 25 % (n = 5/20, p = 0.0016) in the subgroup of patients with cirrhosis. Conclusion: We observed a high rate of SVR 12 with SOF-based treatment regimes, however probably due to the high number of patients with liver cirrhosis and prior treatment experience, treatment response rates were lower than in previously published trials. In genotype 1 patients the analysis of early virological response may predict treatment response in SOF-based combination therapies

Near-real time oculodynamic MRI: a feasibility study for evaluation of diplopia in comparison with clinical testing

Objective: To demonstrate feasibility of near-real-time oculodynamic magnetic resonance imaging (od-MRI) in depicting extraocular muscles and correlate quantitatively the motion degree in comparison with clinical testing in patients with diplopia. Methods: In 30 od-MRIs eye movements were tracked in the horizontal and sagittal plane using a a TrueFISP sequence with high temporal resolution. Three physicians graded the visibility of extraocular muscles by a qualitative scale. In 12 cases, the maximal monocular excursions in the horizontal and vertical direction of both eyes were measured in od-MRIs and a clinical test and correlated by the Pearson test. Results: The medial and lateral rectus muscles were visible in the axial plane in 93% of the cases. The oblique, superior and inferior rectus muscles were overall only in 14% visible. Horizontal (p = 0,015) and vertical (p = 0,029) movements of the right eye and vertical movement of the left eye (p = 0,026) measured by od-MRI correlated positively to the clinical measurements. Conclusions: Od-MRI is a feasible technique. Visualization of the horizontal/vertical rectus muscles is better than for the superior/inferior oblique muscle. Od-MRI correlates well with clinical testing and may reproduce the extent of eye bulb motility and extraocular muscle structural or functional deteriorations. Key Points • Oculodynamic MRI technique helps clinicians to assess eye bulb motility disorders • MRI evaluation of eye movement provides functional information in cases of diplopia • Oculodynamic MRI reproduces excursion of extraocular muscles with good correlation with clinical testing • Dynamic MRI sequence supplements static orbital protocol for evaluation of motility disorder

Culturing of Melanocytes from the Equine Hair Follicle Outer Root Sheath

Hair follicles harbor a heterogeneous regenerative cell pool and represent a putative low-to-non-invasively available source of stem cells. We previously reported a technology for culturing human melanocytes from the hair follicle outer root sheath (ORS) for autologous pigmentation of tissue engineered skin equivalents. This study translated the ORS technology to horses. We de-veloped a culture of equine melanocytes from the ORS (eMORS) from equine forelock hair follicles cultured by means of an analogue human hair follicle-based in vitro methodology. The procedure was adjusted to equine physiology by addition of equine serum to the culture medium. The hair follicles were isolated by macerating forelock skin rests, enzymatically digested and subjected to air-medium-interface cultivation method. The procedure resulted in differentiated equine melanocytes, which exhibited typical morphology, presence of melanosomes, expression of cytoskeleton proteins vimentin, α-SMA, Sox2, S100ß and tyrosinase as well as tyrosinase activity followed by production of melanin. According to all assessed parameters, eMORS could be ranked as partially melanotic melanocytes. The results of the study offer an experimental base for further insight into hair follicle biology in equine and for comparative studies of hair follicles across different species

The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells

The Effect of High-Variability Training on the Perception and Production of French Stops by German Native Speakers

We investigated the effect of high-variability training (HVT) on the production and perception of French bilabial voiced and voiceless stops by German native speakers. Stop consonants in the two languages differ with respect to several articulatory and acoustic features. German learners of French (Experiment Group) trained the perception of word-initial bilabial stops spoken by six French native speakers using identification tests, whereas subjects of a Control Group did not perform a training. Additional perception and production tests of French words including bilabial, alveolar, and velar stops in all word positions were performed to capture the impact of HVT. Subjects were found to be quite good at distinguishing voiced and voiceless stops. However, voiceless stops received lower correctness scores than voiced ones and subjects of the Experiment group were able to further increase their scores after training. Results for production are mirror-inverted showing that subjects of the Experiment Group successfully produced longer negative VOT values but did not show an improvement for voiceless stops