**4. Conclusion**

350 Mechanical Engineering

the mechanism. Because of the critical dynamical pressure the mechanism is deformed and the flow is interrupted. In this case the current position guarantees the closure of the pipe. Low-pressure on the compliant part of the valve makes the flow possible again. The next Figure 10 b shows that the effect of the critical pressure yields to a deformation of the monostable mechanism, so the pipe is completely closed. If the pressure falls under the critical level, the original position is recaptured and the flow rate is reconstituted. The last example in Figure 10 c illustrates a valve installed in a pipe with two outputs. Output B is disabled, as soon as the critical pressure is reached. Decreasing the pressure enables this

Situations with bifurcation of structures are avoided systematically in engineering. The following theoretical analyses reveal some opportunities to apply this behaviour profitably

The best known examples for the loss of stability under static loads are the Eulerian cases of stability. For loads under the critical level, the equilibrium is determinate, whereas at the critical level of loads, bifurcations in the solutions occur to state equations. The solutions are no longer bijective, one load situation may lead to more than one possible geometric configurations of the system. Such structures are shown in Figure 11. Herein, the load is generated by the attraction force of the filaments e.g. SMA-wires or by the low-pressure in cavities. If the wires are uniformly pulled or the cavities possess the same low-pressure, the classical Euler stability problem (bifurcation) is regarded as replacing the named

The following statement explains how the bifurcation effect can be used profitably. The response of a systematically designed system with bifurcation behaviour (deformation or displacement in several directions) on external (e.g. temperature change) or on user-defined conditions leads to one preferred direction. The deformation direction is selected "autonomously" whereas the drive regime for each process always remains the same. The sensory and control effort are minimised enormously. The control of the system is partly

Fig. 11. Structures among the influence of an axial load which is generated by the attraction force of the filaments or Shape-Memory-Alloy-wires (a) and by the low-pressure in cavities

Figure 12 exemplifies this phenomenon in the case of a half-cycle shaped bending beam subject to loading by a single force with constant direction (conservative force) but with a

**3.4 Instable deformation behaviour of compliant mechanisms: Bifurcation**

rotationally drive configuration by an axial acting force.

adopted by "intelligent" mechanics.

output.

(b, c)

to a technical system.

The introduced classification which considers the deformation of compliant mechanisms is supposed to forward their development and to facilitate their implementation in rigid body systems or the functional expanded substitution of individual parts of the rigid body. The meaningful application of compliant mechanisms especially of such structures with instable static behaviour offers a great development potential. The role of the sensor system can be partly or completely adopted by "intelligent" mechanics. With the application of compliant mechanisms and structural elements, which show an instable static behaviour and therefore segue from one state to another depending on external conditions, elementary characteristics of the system can change (Risto et al., 2008; Linß et al., 2008; Risto et al., 2010; Griebel et al., 2010). Hence such systems will autonomously and directly adapt to the working conditions.

In relation with functional dominating compliant characteristics many application-oriented tasks, for example gripping-fingers with particular characteristics, medical structural elements and systems are conceivable.


**6. Findings**

**Table 1** shows the thirteen sessions observed with a breakdown of theory or practical. The comments in column two have been extracted from the full observation feedback as they show aspects of signature pedagogy. Column three shows the analysis of the comment in the light of Shulman's [1] dimensions of signature pedagogy, these being surface/deep/implicit. All lessons observed showed deep or implicit dimensions of signature pedagogy in practice, these being references to specific professional learning or moral or value judgements.

#### **Table 1.**

*To show the observation data analysed in terms of the way that vocational teachers use signature pedagogies in practice.*

#### **7. Discussion**

Interestingly the strongest lessons showing aspects of an implicit structure for a signature pedagogy came from the plumbing and construction teams. This was seen as implicit due to the references concerning health and safety and craftmanship. There were three lessons observed in this department, two theory-based lessons and one practical. Clearly the issue of dealing with a potential gas hazard can be considered as a moral judgement as did the comment made about being a master craftsman. In these instances, the teachers were drawing on their own experience as master craftsman to highlight the professional aspects of their trades. The comment regarding a 'hairdressing pace' was seen in a practical session in which the teacher was getting the learners to work at a pace appropriate to a real hairdressing salon even though they were still training. A point worth making here is that both gas and hairdressing involve working directly with customers and that in both health and safety is vital to a professional approach.

The lessons which were deemed to show deep structures rather than implicit ones were because they did not touch on the moral aspects of the craft but rather were aspects of specific knowledge relating to that subject. Here there were several references to the real world of work and being a professional. Here as well the teachers were modelling good practice as in for example, the hairdressing teacher who was demonstrating techniques in a professional way so as to enable students to observe a professional person in action. This resonates with Claxton's [6] ideas of habits of mind where teamworking, creativity and communication are important skills required for that profession.

To some degree it can be argued that in Engineering there were elements of habits of mind as the reference to the need for 'equation' does highlight the need for students in this discipline to be able to visualise or 'move from abstract to concrete' as Lucas and Hanson [5] indicate as being an EHoM for this subject. Finally, it is clear from all the observations undertaken that there were deep structures of teachers using signature pedagogies as part of professional vocational learning.


**5.6 Influence of phase shifts / strain compensation**

336 Recent Trends in Processing and Degradation of Aluminium Alloys

curves follow a common progression and only some slight lifetime-decreasing effects are

The typically start-stop-operation of a motor vehicle as well as the alternating fired and nonfired operation causes dwell times. To study this effect out-of-phase TMF tests with four different dwell times at the particular maximum temperatures were conducted (8, 24, 144

Whereas with the alloy AlCuBiPb, a higher dwell time always causes a lifetime decreasing effect. This is not the case with the alloy AlSi7MgCu0.5, as figure 6 (left) shows, where the strain values are scaled between the minimum and maximum in this range. The TMF strainlife curve for the dwell time of *tD3*=144 s is quite steep for higher strain values (and therefore temperatures). A point of intersection of the curves for the lower dwell times (8 s and 24 s) is visible at about 1000 cycles. This phenomenon is explained with pronounced softening effects in the first few cycles that occur due to the high aging tendency at the high dwell time and temperature level. The capacious over-aging at this level can mainly be seen in the highly plastic parts, what results in an upward movement of the total strain-life curve. For that reason the high over-aging at the dwell time of 144 s shows that a high mechanical strain amplitude can be endured for a longer time compared to the smaller dwell times. If the maximum temperatures are low, this effect turns around at the dimensioning level for cylinder heads (about 5000 cycles) and a lifetime decreasing effect is visible with a higher

Two extreme LCF tests were conducted at the mean value for the TMF maximum temperatures. A LCF test series at a constant higher temperature of 250°C and one tested at room temperature, but pre-aged at 250°C for 500 hours. Figure 6 (right) shows that these two LCF strain-life curves span the TMF range for all dwell times of the materials investigated, if the mechanical strain (and not the thermal strain) is considered. The comparison of the LCF hysteresis loops at 250°C with comparable mechanically strained TMF hysteresis loops for all dwell times also shows a good accordance. Moreover the cyclic deformation behaviour according to Ramberg-Osgood shows the best accordance of the LCF-250°C curve with the TMF curves. This investigation shows that the macroscopic

behaviour is comparable if the aging status is similar (Riedler et al., 2004).

 **AlSi7MgCu0.5 TMF-OP - LCF**

**TMF tD1**

1,E+01

1,E-01 1,E+00 1,E+01 1,E+02 **Strain** ε **mecha,t at Nf/2 [‰]**

 **LCF - T=25°C / 250°C / 25°C - pre-aged 500h at 250°C, TMF-OP - tD = 8 / 24 / 144 s Stress-strain curves acc. Ramberg-Osgood**

 **AlCuBiPb, R=-1**

1,E+02

**Stress** σ**a at N f/2 [N/mm 2**

Fig. 6. Influence of TMF dwell-time and LCF-pre-aging and constant elevated temperature

on the lifetime (on the left) and on the cyclic deformation behaviour (on the right)

**]**

1,E+03

LCF 25°C LCF pre-aged LCF 250°C OP-TMF tD=8s OP-TMF tD=24s OP-TMF tD=144s

**LCF 25°C / preaged 500 h at 250°C**

1,E+02 1,E+03 1,E+04 **Number of cycles to failure Nf [-]**

ascertainable at pulsating executed TMF test series.

**5.5 Influence of dwell-time**

and 864 s).

dwell time.

1,E+00

**LCF 250°C**

**TMF tD3**

**TMF tD2**

εref,min

**Strain amplitude** ε

 **mecha,t at N f/2**

**[‰]**

1,E+01

εref,max

In order to investigate the influence of stiffness and phase shifts, different TMF conditions were tested. Besides the ideal OP-TMF situation (ε*t,mech*=ε*th*, *KTM*=1.0), two overcompensated conditions of the thermal strain (*KTM*=1.5 and 2.0), a 75% compliance (*KTM*=0.75, which is near to the real circumstances in cylinder heads) and an ideal in-phase-TMF situation (*KTM*=-1.0) were tested.

When the local strains are taken into account at rigid clamped specimens, all OP-TMF results can be drawn together in a common strain vs. cycles to failure diagram. Because of creep damage at higher temperatures the IP-TMF lifetime is shorter than the OP-TMF lifetime, as figure 10 shows.


**F ´atima Matos Silva**

Fatima Matos Silva earned her Ph.D. from the University of Granada in 2008. Since 1988, she ´ has been developing her professional activity at the Portucalense University (Porto, Portugal) as a researcher, professor, and coordinator of cycles of studies, integrating several advisory bodies into the institution. She has directed and collaborated on diversified research projects, both nationally and internationally, and is currently an integrated member of the REMIT and CITCEM - FCT R&D units. She has directed multiple archaeological excavations, conducted environmental and heritage impact studies, and researched spatial planning, sustainable development, and universal accessibility to cultural heritage, particularly for the Santiago Way, among others. In addition, she has organised bibliographic editions, scientific and cultural events, exhibitions, and museological programs, among other cultural actions. The author of several books, she also has published (individually and in partnership) more than 80 articles and book chapters on diverse heritage themes. Her expertise lies in the field of the Humanities and Social Sciences, with a focus on archaeology; cultural heritage; preventive conservation; heritage management, spatial planning, and sustainable development; impacts and threats to cultural heritage; heritage interpretation and enhancement; museology; universal accessibility; accessibility of heritage; cultural tourism; religious and accessible tourism; and pilgrimages.


**3. Results and Discussions**

### *3.1. Film Quality Characterization*

As shown in Figure 4a, the full width half maximum (FWHM) of the 2*θ*/*θ* scans of the 200 nm *Al*0.7*Sc*0.3*N* films grown on Pt and Mo surfaces were 0.36◦ and 0.50◦ , respectively. The FWHM of the *ω*-rocking curve of *Al*0.7*Sc*0.3*N* (0002) peak is below 2.5◦ on Pt samples, and approximately 3◦ on Mo samples. The absence of other peaks near the *Al*0.7*Sc*0.3*N* (0002) peak indicates that the film has a good c-axis orientation [20]. The diffraction peak of the sample on the Pt surface is stronger and has a better grain orientation [21].  These AOGs lead to a partial or total loss of the c-axis texture in the surface layer of the films. Since the polarization direction of AlScN is along the c-axis, it can be assumed that the ferroelectric properties of the Mo sample will be worse than those of the Pt sample, which will be further verified in the later measurement.

**Figure 4.** (**a**) X-ray diffraction 2*θ*/*θ* scan *Al*0.7*Sc*0.3*N* on (**a**) Pt and (**b**) Mo. The peak of *Al*0.7*Sc*0.3*N* (0002) on the Pt sample is stronger than that of the Mo sample. SEM image of *Al*0.7*Sc*0.3*N* grown on: (**b**) Pt with a good crystal orientation; (**c**) Mo with a large number of abnormal grains.


*2.2.2 EGFR gene copy number*

*Advances in the Molecular Understanding of Colorectal Cancer*

*2.2.1 Skin toxicity*

**2.2 Future predictive biomarkers for anti-EGFR therapy**

for anti-EGFR therapy efficacy in patients with mCRC.

Dermatological toxicities such as papulopustular rash (acneiform eruption), erythema, and skin fissures are common side effects of treatment with anti-EGFR antibodies, as EGFR is involved in the normal development and physiology of the epidermis [54]. Both undifferentiated and proliferating keratinocytes in the basal and suprabasal layers of the epidermis express EGFR, and keratinocytes depend on EGFR to regulate proliferation, differentiation, migration, and survival [55]. The emergence of skin toxicity has therefore been investigated as an on-target marker

Subset analyses of outcomes by skin toxicity severity suggest that improvements in outcome are associated with a higher grade of severity for patients treated with either panitumumab or cetuximab. For example, in the CRYSTAL trial of cetuximab as a first-line therapy, PFS was 11.3 months compared with 5.4 months in patients with G3 and G0-1 skin reactions, respectively [56]. Similarly, the randomized phase III EPIC study of cetuximab plus irinotecan *vs* irinotecan after fluoropyrimidine and oxaliplatin failure in patients with EGFR-expressing mCRC observed a median PFS of 15.6 months for patients who developed G3-4 rash compared to 5.8 months for those with no rash [57]. In the PRIME study of panitumumab plus FOLFOX4 (first line) and 20050181 study of panitumumab plus FOLFIRI (second line) the addition of a targeted agent even appeared detrimental for outcomes in patients with G0-1 skin toxicity as compared to the control arms [58, 59]. Better outcomes in patients with higher-grade skin toxicity were further noted for both arms in a randomized trial of cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer [60]. A meta-analysis by Petrelli *et al* of 14 studies including a total of 3833 patients, found that the occurrence of skin toxicity was a predictive factor for survival (HR 0.51; 95% CI 0.40–0.64) and progression (HR 0.58; 95% CI 0.49–0.68). However, 12 of the studies included patients with either *KRAS* wild-type or mutated

tumors, and data on skin toxicity by *KRAS* mutation status remains limited.

Analysis of skin toxicity in the randomized phase III ASPECCT study of panitumumab *vs* cetuximab in chemorefractory wild-type *KRAS* exon 2 mCRC observed improved outcomes in patients with higher grade of severity for both antibodies, although patients with higher-grade skin toxicity had longer median duration of treatment [61]. Two retrospective trial analyses (PRIME and AIO CRC-0104 [cetuximab with CAPOX or CAPIRI, first-line]) suggest that the relationship between skin toxicity and outcome may not only apply to patients with wild-type *RAS* tumors, but perhaps also to patients mutant *RAS* tumors [62, 63]. A recent meta-analysis of skin toxicity identified seven and five studies that reported information on PFS and OS stratified by *KRAS* mutation status, respectively [64]. Improved clinical outcome in the presence of higher grade severity was observed for both patients with wildtype *KRAS* tumors and those with mutant *KRAS* tumors (PFS for wild-type *KRAS*, HR = 0.60, 95% CI (0.51, 0.70); mutant *KRAS*, HR = 0.60, 95% CI (0.45, 0.80), OS for wild-type *KRAS*, HR = 0.54, 95% CI (0.46, 0.65), mutant *KRAS*, HR = 0.64, 95% CI (0.50, 0.81), P < 0.001]. However, only mCRC patients with wild-type *KRAS* tumors who suffered grade 2+ skin toxicity derived absolute benefit from anti-EGFR treatment additional to best BSC or chemotherapy (PFS HR = 0.58, 95% CI (0.41,

These data raise the question whether wild-type *RAS* patients receiving anti-EGFR therapy who do not develop skin toxicity should receive a dose escalation to induce skin toxicity or whether treatment should be discontinued. Further prospective data are needed to establish the clinical value of skin toxicity as a predictive biomarker.

**114**

0.82), OS HR = 0.73, 95% CI (0.61, 0.88)).

*EGFR* is localized on chromosome 7p11.2 which exhibits DNA copy number gain in approximately 35% of colorectal cancers [65]. Based on this observation, *EGFR* gene copy number has been investigated as a predictive biomarker for anti-EGFR therapy in multiple *post hoc* analyses. Study results have been aggregated in three meta-analyses [66-68], which broadly concurred in identifying gain of *EGFR* gene copy number as associated with improved outcomes among patients receiving cetuximab or panitumumab treatment. This association was found to be retained in subgroup analyses for patients with *KRAS* wild-type tumors, with one metaanalysis suggesting that this difference was not present in patients with *KRAS* mutated tumors [69]. However, the methodologies and criteria used for scoring increased EGFR gene copy number were highly inconsistent across different studies, and more research is required to clarify the predictive potential of this biomarker.