Dentre as substâncias químicas secretadas pelas plantas, contra os insetos herbívoros, os inibidores de peptidases são de grande interesse. A atenção dada a esses inibidores deve-se ao fato, de eles serem uma boa alternativa no controle de insetos praga, uma vez que não causam danos ao meio ambiente. Contudo, muitas espécies de insetos são capazes de escapar dos efeitos negativos dos inibidores de peptidases das plantas, via diferentes mecanismos adaptativos. Devido a esse fato, é importante compreender os mecanismos desenvolvidos pelos insetos para burlar os efeitos dos inibidores de peptidases das plantas. Diante desse panorama, este trabalho teve como objetivo estudar o mecanismo adaptativo das serina endopeptidases de Spodoptera frugiperda aos inibidores de endopeptidases de soja. Foram realizadas análises do transcriptoma dos intestinos das lagartas mantidas em exposição crônica ao inibidor. Para averiguar os efeitos causados devido à exposição crônica ao inibidor, foram realizadas comparações da expressão relativa, dos genes de tripsinas e quimotripsinas, de intestinos de lagartas de sexto instar. Contudo, para entender o efeito da exposição aguda ao inibidor, lagartas de S. frugiperda foram criadas em dieta artificial controle até o primeiro dia do sexto instar, após esse período elas foram transferidas para dieta artificial acrescida com 0,5 % dos inibidores de endopeptidases de soja, durante 48 horas. Para verificar a ocorrência de um possível controle epigenético na expressão dos genes, as lagartas foram conduzidas até a fase adulta e os adultos, de cada tratamento, foram acasalados entre si, constituindo uma segunda geração. Dados de expressão relativa foram obtidos, de indivíduos da primeira e segunda geração, e foram então comparados. Foram identificados 14 possíveis genes de quimotripsinas e nove possíveis genes de tripsinas. Os genes de tripsina foram divididos em dois grupos distintos em relação a sua sensibilidade aos inibidores de endopepetidases de soja e expressão relativa. Houve uma resposta diferenciada na ativação dos genes de serina endopeptidases de S. frugiperda, a qual dividiu os genes em dois grupos, os responsivos e os não responsivos ao inibidor. A exposição aguda ao inibidor ativou um pequeno grupo de genes, enquanto que a exposição crônica promoveu uma maior amplitude de expressão gênica, sugerindo mecanismos temporalmente regulados. Por último, evidências indicam, pela primeira vez, a possível ocorrência de um mecanismo epigenético, na resposta das enzimas digestivas aos inibidores de serina endopeptidases de soja. / Among the chemicals secreted by plants against insect herbivores, peptidase inhibitors (PIs) are of great interest. The attention given to PIs is due to the fact that they are a good alternative to control insect pests since they do not cause damage to human health and the environment. However, many species of insects are able to escape the negative effects of PIs plants via different adaptive mechanisms. Because of this, it is important to understand the mechanisms developed by insects to circumvent the effects of PIs plants. Against this background, this research aimed to study the adaptive mechanism of serine endopeptidases Spodoptera frugiperda to soybean endopeptidase inhibitors. For this purpose, larvae of S. frugiperda were reared on artificial diet and control artificial diet plus 0.5% of endopeptidase inhibitors of soybean. We conducted a transcriptome midgut of worms maintained in chronic ingestion of the inhibitor. The relative expression of the genes, trypsin and chymotrypsin, was also compared the midgut of sixth instar larvae kept in these diets. In another experiment, the larvae were conducted to moth, then the treatments were mated forming a second generation. Relative expression data were obtained for individuals of the first and second generation, and then compared. Identified 14 genes with potential of chymotrypsin and 9 trypsin like genes. The trypsin gene were divided into two groups for both their sensitivity to PI soybean endopeptidase, and for their relative expression pattern. There was a differentiated response on the genes activation of S. frugiperda serina endopeptidases. The genes were clustered in 2 groups, the responsive ones and the non responsive to the inhibitor. The acute exposition to the inhibitor activated a small group of genes and the chronic exposition affected several genes, indicating the existence of temporal regulated mechanism. Besides, there is a possible occurance of an epigenetic mechanism, which is related to the digestive serina endopeptidases inhibitors of soybean.

Limited knowledge of the neuromechanical response to use of an ankle foot orthosis-footwear combination (AFO-FC) has created a lack of consensus in understanding orthotic motion control as a therapeutic treatment. Lack of consensus may hinder the clinician’s ability to target the motion control needs of persons with movement impairment (e.g., peripheral nerve injury, stroke, etc.). Some evidence suggests a proportional relationship between joint motion and neuromuscular activity based on the notion that use of lower limb orthoses that constrain joint motion may invoke motor slacking and decreasing levels of muscle activity. Use of AFO-FCs likely alters the biomechanical and neuromuscular output as the central control system gradually forms new movement patterns. If there is proportional relationship between muscle activation and joint motion, then it could be examined by quantifying joint motion and subsequent neuromuscular output. Considering principles of neuromechanical adjustment, my general hypothesis examines whether orthotic control of lower limb motion alters neuromuscular output in proportion to the biomechanical output as a representation of the limb’s dynamics are updated by the neural control system. The rationale for this approach is that reference knowledge of the neuromechanical response is needed to inform clinicians about how a person responds to walking with motion controlling devices such as ankle foot orthoses combined with footwear. In the first line of research, I hypothesize that a newly developed AFO which maximizes leverage and stiffness will constrain the talocrural joint and alter joint kinematics and ground reaction force patterns. To answer the hypothesis, I sampled kinematics and kinetics of healthy subjects’ treadmill walking using an AFO-FC in a STOP condition and confirmed that the AFO substantially limited the range of talocrural plantarflexion and dorsiflexion motion to 3.7° and in a FREE condition maintained talocrural motion to 24.2° compared to 27.7° in a CONTROL (no AFO) condition. A follow up controlled static loading study sampled kinematics of matched healthy subjects limbs and cadaveric limbs in the AFO STOP and FREE conditions. Findings revealed healthy and cadaveric limbs in the AFO STOP condition substantially limited their limb segment motion similar to matched healthy subjects walking in the STOP condition and in the AFO FREE condition healthy and cadaveric limbs maintained similar limb segment motion to matched healthy subjects walking in the FREE condition. In a second line of research, I hypothesize that flexibility of a newly developed footwear system will allow normal walking kinetics due to the shape and flexibility of the footwear. To answer the hypothesis, I utilized a curved-flexible footwear system integrated with an AFO in a STOP condition and sampled kinematics and kinetics of healthy subjects during treadmill walking. Results revealed subjects elicited similar cadence, stance and swing duration and effective leg-ankle-foot roll over radius compared to walking in the curved-flexible footwear integrated with the AFO in a FREE condition and a CONTROL (no AFO) condition. To validate rollover dynamics of the curved-flexible footwear system, a follow up study of healthy subjects’ treadmill walking in newly developed flat-rigid footwear system integrated with the AFO in a STOP condition revealed interrupted leg-ankle-foot rollover compared to walking in curved-flexible footwear in STOP, FREE and CONTROL conditions. In a third line of research, I hypothesize that use of an AFO that limits talocrural motion in a STOP condition will proportionally reduce activation of Tibialis Anterior, Soleus, Medial and Lateral Gastrocnemii muscles compared to a FREE and CONTROL condition due to alterations in length dependent representation of the limb’s dynamics undergoing updates to the central control system that modify the pattern of motor output. To answer the question, the same subjects and AFO-footwear presented in the first two lines of research were used in a treadmill walking protocol in STOP, FREE, and CONTROL conditions. Findings revealed the same subjects and ipsilateral AFO-footwear system presented in Aim 1 exhibited an immediate yet moderate 30% decline in EMG activity of ipsilateral Soleus (SOL), Medial Gastrocnemius (MG) and Lateral Gastrocnemius (LG) muscles in the STOP condition compared to the CONTROL condition. The reduction in EMG activity in ipsilateral SOL, MG and LG muscles continued to gradually decline during 15 minutes of treadmill walking. On the contralateral leg, there was an immediate yet small increase of 1% to 14% in EMG activity in SOL, MG, LG muscles above baseline. After 10 minutes of walking, the EMG activity in contralateral SOL, MG and LG declined to a baseline level similar to the EMG activity in the contralateral CONTROL condition. These collective findings provide compelling evidence that the moderate 30% reduction in muscle activation exhibited by subjects as they experience substantial (85%) constraint of total talocrural motion in the AFO STOP condition is not proportionally equivalent. Further, the immediate decrease in muscle activation may be due to a reactive feedback mechanism whereas the continued decline may in part be explained by a feedforward mechanism. The clinical relevance of these findings suggests that short term use of orthotic constraint of talocrural motion in healthy subjects does not substantially reduce muscle activation. These preliminary findings could be used to inform the development of orthoses and footwear as therapeutic motion control treatments in the development of motor rehabilitation protocols.

The explosion of information and information technology has led many firms to evolve a dispersed product development process with people and organizations spread throughout the world. To coordinate such dispersed processes managers attempt to establish a culture that implicitly rewards product development teams based on their ability to perform against a set of strategic metrics such as customer satisfaction, time to market, defect reduction, or platform reuse. Many papers have focused on selecting the right metrics and establishing the culture. In this paper we focus on a practical method to fine-tune a firm's relative emphasis on the metrics that they have chosen. In particular, we seek to advise a firm whether to increase or decrease their emphasis on each metric such that the change in emphasis improves profits. Using a thermostat analogy we apply an adaptive control feedback mechanism in which we estimate the incremental improvements in priorities that will increase profits. Iterations of adaptive control seek to maximize profits even if the environment is changing. We demonstrate the metric thermostat’s use in an application to a firm with over $20 billion in revenue. In developing the metric thermostat we recognize that there are hundreds of detailed actions, such as the use of the house of quality and the use of robust design, among which the product development team must choose. We also recognize that they will act in their own best interests to choose the actions that maximize their own implicit rewards as determined by the metrics. Management need not observe or dictate these detailed actions, but rather control the process by establishing the culture that sets the implicit weights on the metrics. The thermostat works by changing those implicit weights. We define the problem, introduce the adaptive control mechanism, modify “agency” theory to deal with incremental changes about an operating point, and derive methods that are practical and robust in light of the data that firms have available. Our methods include statistical estimation and internal surveys. The mathematics identify the critical few parameters that need be determined and highlight how to estimate them. Both the measures and the estimation are illustrated in our initial application to a large officeequipment firm. The metrics thermostat suggests that this firm has about the right emphasis on timeto- market, but has overshot on platform reuse and has lost its focus on customer satisfaction. We describe how the firm reacted to the recommendations and changed its organization. We describe additional ongoing applications with the US Air Force, the US Navy, and a major automobile and truck manufacturer. / This research was funded by the Center for Innovation in Product Development (CIPD) and the International Center for Research on the Management of Technology (ICRMOT), M.I.T.

摘 要 本研究主要是藉由探討台灣企業在面臨「轉型升級壓力」而必須做經營策略調整時，經由本研究所建構的理論模型與實際個案間的檢證研究突顯出「企業學習能力」在企業轉型升級與策略選擇過程中的關鍵地位。 本研究以創造台灣最高經濟產值貢獻的資訊科技(IT)產業之個案廠商為對象，探究其「企業學習能力」對「企業轉型升級策略」選擇的影響，以及「目標產業的知識特質」、「企業學習能力」、「企業轉型升級壓力」三者間的關聯性。本論文的研究方法是以對個案的資料文件做深度探究的內容分析法為主，選取國內具代表地位的二家資訊硬體大廠為研究對象，嘗試對其「企業學習能力」與「企業轉型決策過程」作系統性的探索。 本研究歸納分析所得到的研究發現如下： 【研究發現一】取得「企業學習能力」的實證觀察指標。 【研究發現二】「企業轉型升級壓力」的大小會影響「企業轉型升級策略選擇」。壓力愈小時，企業選擇「攻勢」之轉型升級的機會就愈大；反之，則企業選擇「守勢」之退守退出的機會就愈大。 【研究發現三】「企業學習能力」的強弱會影響「企業轉型升級策略的選擇」。企業學習能力愈強時，則企業選擇「攻勢」之轉型升級的機會就愈大；反之，則企業選擇「守勢」之退守退出的機會就愈大。 【研究發現四】「企業學習壓力數學關係式」的發現實證了「企業學習能力」與「目標產業知識特質」和「企業轉型升級壓力」之間，存有簡單的「數學關聯」。 【研究發現五】「企業轉型升級策略選擇」的決策關係式。 因此，本研究認為企業在做轉型升級的決策時，千萬不要忽略企業本身的「學習能力」是否能承載「目標產業的知識特質」？建議企業宜在所欲朝向轉型升級之「目標產業的知識特質」下，考量企業本身的「學習能力」強弱，評估本身「企業轉型升級壓力」的大小，最終對「企業轉型升級策略」做出合乎自身最佳利益的理性選擇。此外，本研究亦建議企業或可藉由參考「企業學習能力系統-SOFA模型」來規劃建構或是強化自身的「企業學習能力」，以因應未來無窮的變局與挑戰！ / Abstract This research is conducted by exploration and explanation between theoretical model and case studies to prove the key role of the enterprise’s learning ability (ELA) in the procedure of the enterprise’s transformation and the option of strategy. The researcher selected cases from information technology industry which contributed most to Taiwan economic growth in recent years to explain the influence of ELA on selecting the strategy of transformation and to explore the relevance among the characteristics of objective industrial knowledge, ELA and the pressure of enterprise transformation. This thesis applied content analysis to explore the documents from two big enterprises of information hardware , trying to systematically study their learning ability and to find out how they make a decision of transformation. According to the analyses of these two cases, the study has got the following conclusions： 1.The collection of empirical indexes of enterprise learning ability (ELA). 2.The pressure of enterprise transformation will influence the option of transformation strategy. The smaller the pressure is , the bigger the chance for the enterprise choosing aggressive way to transform would be. On the contrary, the bigger the presser is , the bigger the chance for the enterprise choosing conservative way to withdraw would be. 3.The performance of ELA will influence the option of enterprise transformation strategy. The stronger the ELA is , the bigger the chance for the enterprise choosing aggressive way to transform would be. On the contrary, the weaker the ELA is , the bigger the chance for the enterprise choosing conservative way to withdraw would be. 4.The formula of enterprise learning pressure proves the existence of simple mathematical relevance among ELA, the characteristics of objective industrial knowledge and the pressure of enterprise transformation. 5.The decision-making formula of the option of enterprise transformation strategy. As a result , this research indicates that an enterprise making transformation decision should never neglect the fact whether its ELA could undertake the characteristics of objective industrial knowledge or not . This research suggests that enterprises facing transformation pressure from the characteristics of objective industrial knowledge had better take their learning ability into consideration , and finally make a rational choice of transformation strategy to meet their best needs. In addition , this research recommends that enterprises might use “Enterprise Learning Ability System (ELAS)” i.e. “SOFA model” to construct or strengthen their learning ability in order to cope with countless challenge in the future.