975 resultados para Vestibular fold
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Despite promising benefits and advantages, there are reports of failures and low realisation of benefits in Enterprise System (ES) initiatives. Among the research on the factors that influence ES success, there is a dearth of studies on the knowledge implications of multiple end-user groups using the same ES application. An ES facilitates the work of several user groups, ranging from strategic management, management, to operational staff, all using the same system for multiple objectives. Given the fundamental characteristics of ES – integration of modules, business process views, and aspects of information transparency – it is necessary that all frequent end-users share a reasonable amount of common knowledge and integrate their knowledge to yield new knowledge. Recent literature on ES implementation highlights the importance of Knowledge Integration (KI) for implementation success. Unfortunately, the importance of KI is often overlooked and little about the role of KI in ES success is known. Many organisations do not achieve the potential benefits from their ES investment because they do not consider the need or their ability to integrate their employees’ knowledge. This study is designed to improve our understanding of the influence of KI among ES end-users on operational ES success. The three objectives of the study are: (I) to identify and validate the antecedents of KI effectiveness, (II) to investigate the impact of KI effectiveness on the goodness of individuals’ ES-knowledge base, and (III) to examine the impact of the goodness of individuals’ ES-knowledge base on the operational ES success. For this purpose, we employ the KI factors identified by Grant (1996) and an IS-impact measurement model from the work of Gable et al. (2008) to examine ES success. The study derives its findings from data gathered from six Malaysian companies in order to obtain the three-fold goal of this thesis as outlined above. The relationships between the antecedents of KI effectiveness and its consequences are tested using 188 responses to a survey representing the views of management and operational employment cohorts. Using statistical methods, we confirm three antecedents of KI effectiveness and the consequences of the antecedents on ES success are validated. The findings demonstrate a statistically positive impact of KI effectiveness of ES success, with KI effectiveness contributing to almost one-third of ES success. This research makes a number of contributions to the understanding of the influence of KI on ES success. First, based on the empirical work using a complete nomological net model, the role of KI effectiveness on ES success is evidenced. Second, the model provides a theoretical lens for a more comprehensive understanding of the impact of KI on the level of ES success. Third, restructuring the dimensions of the knowledge-based theory to fit the context of ES extends its applicability and generalisability to contemporary Information Systems. Fourth, the study develops and validates measures for the antecedents of KI effectiveness. Fifth, the study demonstrates the statistically significant positive influence of the goodness of KI on ES success. From a practical viewpoint, this study emphasises the importance of KI effectiveness as a direct antecedent of ES success. Practical lessons can be drawn from the work done in this study to empirically identify the critical factors among the antecedents of KI effectiveness that should be given attention.
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Recent algorithms for monocular motion capture (MoCap) estimate weak-perspective camera matrices between images using a small subset of approximately-rigid points on the human body (i.e. the torso and hip). A problem with this approach, however, is that these points are often close to coplanar, causing canonical linear factorisation algorithms for rigid structure from motion (SFM) to become extremely sensitive to noise. In this paper, we propose an alternative solution to weak-perspective SFM based on a convex relaxation of graph rigidity. We demonstrate the success of our algorithm on both synthetic and real world data, allowing for much improved solutions to marker less MoCap problems on human bodies. Finally, we propose an approach to solve the two-fold ambiguity over bone direction using a k-nearest neighbour kernel density estimator.
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The rapid economic development and social changes in Malaysia recently have led to many psychosocial problems in young people, such as drug addiction, child sexual abuse and mental illness. The Malaysian government is beginning to focus more attention on its social welfare and human service needs in order to alleviate these psychosocial problems. Although counselling is accepted and widespread in Malaysia, the practice of family therapy is not as accepted as it is still a widely held belief that family problems need to be kept within the family. However, changes are imminent and thus the theoretical basis of family therapy needs to be culturally relevant. Bowen‟s Family Systems Theory (BFST) is already one of the major theories taught to tertiary counselling students in Malaysian universities. The main tenet of Bowen‟s theory is that the family as a system may be unstable unless each member of the family is well differentiated. High differentiation levels in the family allow a person to both leave the family‟s boundaries in search of uniqueness and to continually return to the family fold in order to establish a more mature sense of belonging. The difficulty, however, is that while Bowen has claimed that his theory is universal nearly all of the research confirming the theory has been conducted in the United States of America. The only known study outside America, however, did show that Bowen‟s theory applied to a Filipino population but, one of the theory‟s propositions that differentiation is intergenerational was not supported in this non-American sample. The American sample that was compared to the Malay sample was taken from Skowron and Friedlander‟s (1998) study. One hundred and twenty-seven faculty staff in an American university completed the Differentiation of Self Inventory (DSI) to measure level of differentiation of self. This thesis therefore, set out to determine whether Bowen‟s theory applied to another non-American sample, the Malaysian community. The research also investigated if the intergenerational effect was present in the Malaysian sample as well as explored the role of socio-economic status on Bowen‟s theory of differentiation and gender effect. Three hundred and seventy-four families completed four measures to examine these research questions: the Differentiation of Self Inventory (DSI), the Family Inventory of Life Event (FILE), the Depression Anxiety and Stress Scale (DASS) and the Connor-Davidson Resilience Scale (CD-RISC). The results of the study showed that differentiation of self is a valid construct for the Malay population. However, all four subscales of the Differentiation of Self Inventory (DSI); emotional reactivity (ER), emotional cut-off (EC), fusion with other (FO) and I position (IP), showed significant differences compared to the American sample from Skowron and Friedlander‟s (1998) study. The Malay sample scored higher in emotional reaction (ER), fusion with other (FO), but lower on emotional cut-off (EC) and I position (IP) than the American sample. The intergenerational effect was found in the Malay population as the parent‟s level of differentiation correlated with their children‟s level of differentiation. It was found that stress as measured by the Family Inventory of Life Event (FILE) and as measured by the Depression Anxiety and Stress Scale (DASS) were not correlated with the level of differentiation of self in parents. However, gender had a significant effect in predicting the level of differentiation among parents in Malay population with females scores higher on emotional reactivity (ER) and fusion with other (FO) than males. An additional finding was that resilience can be predicted from the level of differentiation of self in children in the Malay sample. There was also a positive correlation between the level of differentiation of self in parents and resilience in their children. Findings from this study indicate that the concept of differentiation of self is applicable to a Malay sample; however, the implementation of the theory should be applied with cultural sensitivity.
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Membranes prepared from a protein, fibroin, isolated from domesticated silkworm (Bombyx mori) silk, support the cultivation of human limbal epithelial (HLE) cells and thus display significant potential as biomaterials for ocular surface reconstruction. We presently extend this promising avenue of research by directly comparing the attachment, morphology and phenotype of primary HLE cell cultures grown on fibroin to that observed on donor amniotic membrane (AM), the current clinical standard substrate for HLE transplantation. Fibroin membranes measuring 6.3 ± 0.5 μm (mean ± sd) in thickness and permeable to FITC dextran of a molecular weight up to 70 kDa, were used. Attachment of HLE cells to fibroin was similar to that supported by tissue culture plastic but approximately 6-fold less than that observed on AM. Nevertheless, epithelia constructed from HLE on fibroin maintained evidence of corneal phenotype (K3/K12 expression) and displayed a comparable number and distribution of ΔNp63+ progenitor cells to that seen in cultures grown on AM. These results support the suitability of membranes constructed from Bombyx mori silk fibroin as substrata for HLE cultivation and encourage progression to studies of efficacy in preclinical models.
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Action learning / research is a broad field of research with deep roots in the 20th century. Unlike futures studies, which is more content oriented (i.e., the futures of health, peace futures, global futures), action learning / research is process and methodology oriented – addressing the manner in which research is done, rather than what is researched. At its core it is collaborative learning for social change. This is particularly important because, in this age of heterogenous changes and multi-fold social challenges, we need to be able to bridge learning about our futures with action and innovation in the present, in a way that is effective and accessible for lay communities and organisations, not just experts. [Introduction]
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At the international level, the higher education sector is currently being subjected to increased calls for public accountability and the current move by the OECD to rank universities based on the quality of their teaching and learning outcomes. At the national level, Australian universities and their teaching staff face numerous challenges including financial restrictions, increasing student numbers and the reality of an increasingly diverse student population. The Australian higher education response to these competing policy and accreditation demands focuses on precise explicit systems and procedures which are inflexible and conservative and which ignore the fact that assessment is the single biggest influence on how students approach their learning. By seriously neglecting the quality of student learning outcomes, assessment tasks are often failing to engage students or reflect the tasks students will face in the world of practice. Innovative assessment design, which includes new paradigms of student engagement and learning and pedagogically based technologies have the capacity to provide some measure of relief from these internal and external tensions by significantly enhancing the learning experience for an increasingly time-poor population of students. That is, the assessment process has the ability to deliver program objectives and active learning through a knowledge transfer process which increases student participation and engagement. This social constructivist view highlights the importance of peer review in assisting students to participate and collaborate as equal members of a community of scholars with both their peers and academic staff members. As a result of increasing the student’s desire to learn, peer review leads to more confident, independent and reflective learners who also become more skilled at making independent judgements of their own and others' work. Within this context, in Case Study One of this project, a summative, peer-assessed, weekly, assessment task was introduced in the first “serious” accounting subject offered as part of an undergraduate degree. The positive outcomes achieved included: student failure rates declined 15%; tutorial participation increased fourfold; tutorial engagement increased six-fold; and there was a 100% student-based approval rating for the retention of the assessment task. However, in stark contrast to the positive student response, staff issues related to the loss of research time associated with the administration of the peer-review process threatened its survival. This paper contributes to the core conference topics of new trends and experiences in undergraduate assessment education and in terms of innovative, on-line, learning and teaching practices, by elaborating the Case Study Two “solution” generated to this dilemma. At the heart of the resolution is an e-Learning, peer-review process conducted in conjunction with the University of Melbourne which seeks to both create a virtual sense of belonging and to efficiently and effectively meet academic learning objectives with minimum staff involvement. In outlining the significant level of success achieved, student-based qualitative and quantitative data will be highlighted along with staff views in a comparative analysis of the advantages and disadvantages to both students and staff of the staff-led, peer review process versus its on-line counterpart.
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Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor and (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.
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This paper reports on a unique study of a large, random sample of business start-ups that were identified prior to the actual, commercial launch of the ventures. The purpose of this paper is two-fold. First, to present frequencies on the involvement of the Swedish population in the small business sector (particularly in start-ups of firms) and to compare these with estimates from Norway and the USA, which are based on studies using a similar research design. The authors also discuss the possible reasons for the differences that emerge between countries. Second, the characteristics of nascent entrepreneurs (i.e. individuals trying to start an independent business) are analysed and compared for sub-groups within the sample and with characteristics of business founders as they appear in theoretical accounts or retrospective empirical studies of surviving all firms. In order to get a representative sample from the working age population, respondents (n = 30,427) were randomly selected and interviewed by telephone. It was found that 2.0% of the Swedish population at the time of the interview were trying to start an independent business. Sweden had a significantly lower prevalence rate of nascent entrepreneurs compared to Norway and the USA. Nascent entrepreneurs were then compared to a control group of people not trying to start a business. The results confirmed findings from previous studies of business founders pointing to the importance of role models and the impression of self-employment obtained through these, employment status, age, education and experience. Marital status, the number of children in the household, and length of employment experience were unrelated to the probability of becoming a nascent entrepreneur. The gender of the respondent was the strongest distinguishing factor. Importantly, the results suggest that while one has a reasonably good understanding of the characteristics associated with men going into business for themselves, the type of variables investigated here have very limited ability to predict nascent entrepreneur status for women.
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Regulatory sequences with endosperm specificity are essential for foreign gene expression in the desired tissue for both grain quality improvement and molecular pharming. In this study, promoters of seed storage α-kafirin genes coupled with signal sequence (ss) were isolated from Sorghum bicolor L. Moench genomic DNA by PCR. The α-kafirin promoter (α-kaf) contains endosperm specificity-determining motifs, prolamin-box, the O2-box 1, CATC, and TATA boxes required for α-kafirin gene expression in sorghum seeds. The constructs pMB-Ubi-gfp and pMB-kaf-gfp were microprojectile bombarded into various sorghum and sweet corn explants. GFP expression was detected on all explants using the Ubi promoter but only in seeds for the α-kaf promoter. This shows that the α-kaf promoter isolated was functional and demonstrated seed-specific GFP expression. The constructs pMB-Ubi-ss-gfp and pMB-kaf-ss-gfp were also bombarded into the same explants. Detection of GFP expression showed that the signal peptide (SP)::GFP fusion can assemble and fold properly, preserving the fluorescent properties of GFP.
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Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus (EBV) and ecologically linked to Plasmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific BL incidence and standardized incidence ratios using data collected from 1997 through 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 500 patients, median age was 6 years (inter-quartile range 5-8) and male-to-female ratio was 1.8:1. Among those known, most presented with abdominal (56%, M: F 1.4:1) vs. only facial tumors (35%, M: F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p<0.001) and more frequently in female children (68% vs. 50%; OR 2.2, 95% CI 1.5-3.5). The age-standardized incidence was 2.4 per 100,000, being 0.6 in 1-4 year olds, 4.1 in 5-9 year olds and 2.8 in 10-14 year olds and varied 3-4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. While districts close to Lacor were also more urbanized, the incidence was higher in the nearby perirural areas. We highlight high BL incidence and geographic variation in neighboring districts in northern Uganda. While distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation has shifted away from facial to mostly abdominal. Keywords: Africa, cancer, malaria, Epstein-Barr virus, clustering, epidemiology
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Purpose Serum levels of the inflammatory markers YKL-40 and IL-6 are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma (HL), a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis HL. Experimental Design We analyzed Danish and Swedish patients with incident HL (N=470) and population controls from Denmark (N= 245 for YKL-40; N= 348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analysed by linear regression, adjusting for age and sex. Results Serum levels of YKL-40 and IL-6 were increased in HL patients compared to controls (YKL-40: 3.6-fold, IL-6: 8.3-fold; both p<0.0001). In samples from pre-treatment HL patients (N=176), levels were correlated with more advanced stages (ptrend 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms, but levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment onset had significantly lower levels than pre-treatment patients, but even >6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased, compared to controls. In patients who died (N=12), pre-treatment levels for both YKL-40 and IL-6 were higher than in survivors, although not statistically significantly. Conclusions Serum YKL-40 and IL-6 levels were increased in untreated HL patients and those with more advanced stages but did not differ significantly by HL histology. Following treatment, serum levels were significantly lower.
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Proteasomes can exist in several different molecular forms in mammalian cells. The core 20S proteasome, containing the proteolytic sites, binds regulatory complexes at the ends of its cylindrical structure. Together with two 19S ATPase regulatory complexes it forms the 26S proteasome, which is involved in ubiquitin-dependent proteolysis. The 20S proteasome can also bind 11S regulatory complexes (REG, PA28) which play a role in antigen processing, as do the three variable c-interferoninducible catalytic b-subunits (e.g. LMP7). In the present study, we have investigated the subcellular distribution of the different forms of proteasomes using subunit speci®c antibodies. Both 20S proteasomes and their 19S regulatory complexes are found in nuclear, cytosolic and microsomal preparations isolated from rat liver. LMP7 was enriched approximately two-fold compared with core a-type proteasome subunits in the microsomal preparations. 20S proteasomes were more abundant than 26S proteasomes, both in liver and cultured cell lines. Interestingly, some signi®cant differences were observed in the distribution of different subunits of the 19S regulatory complexes. S12, and to a lesser extent p45, were found to be relatively enriched in nuclear fractions from rat liver, and immuno¯uorescent labelling of cultured cells with anti-p45 antibodies showed stronger labelling in the nucleus than in the cytoplasm. The REG was found to be localized predominantly in the cytoplasm. Three- to six-fold increases in the level of REG were observed following cinterferon treatment of cultured cells but c-interferon had no obvious effect on its subcellular distribution. These results demonstrate that different regulatory complexes and subpopulations of proteasomes have different distributions within mammalian cells and, therefore, that the distribution is more complex than has been reported for yeast proteasomes.
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Purpose: To study the effect of the size of the surface-coated polycaprolactone (PCL) microparticle carriers on the aerosolization and dispersion of Salbutamol Sulfate (SS) from Dry Powder Inhaler (DPI) formulations. Methods: The microparticles were fabricated using an emulsion technique in four different sizes (25, 48, 104 and 150 μm) and later coated with Magnesium stearate (MgSt) and leucine. They were characterized by laser diffraction and SEM. The Fine Particle Fraction (FPF) of SS from powder mixtures was determined by a Twin Stage Impinger (TSI). Results: As the carrier size increased from 25 μm to 150 μm, the FPF of the SS delivered by the coated PCL particles increased approximately four fold. A linear relationship was found between the FPF and Volume mean Diameter (VMD) of the particles over this range. Conclusions: The dispersion behaviour of SS from PCL carriers was dependent on the inherent size of the carriers and the increased FPF of SS with increased carrier size probably reflects the higher mechanical forces produced due to the carrier-carrier collisions or collisions between the carrier particles and the internal walls of the inhaler during aerosolization.
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Public health decision making is critically dependant on accurate, timely and reliable information. There is a widespread belief that most of the national and sub-national health information systems fail in providing much needed information support for evidence based health planning and interventions. This situation is more acute in developing nations where resources are either stagnant or decreasing, coupled with the situations of demographic transition and double burden of diseases. Literature abounds with publications, which provide information on misguided health interventions in developing nations, leading to failure and waste of resources. Health information system failure is widely blamed for this situation. Nevertheless, there is a dearth of comprehensive evaluations of existing national or sub-national health information systems, especially in the region of South-East Asia. This study makes an attempt to bridge this knowledge gap by evaluating a regional health information system in Sri Lanka. It explores the strengths and weaknesses of the current health information system and related causative factors in a decentralised health system and then proposes strategic recommendations for reform measures. A mix methodological and phased approach was adopted to reach the objectives. An initial self administered questionnaire survey was conducted among health managers to study their perceptions in relation to the regional health information system and its management support. The survey findings were used to establish the presence of health information system failure in the region and also as a precursor to the more in-depth case study which was followed. The sources of data for the case study were literature review, document analysis and key stake holder interviews. Health information system resources, health indicators, data sources, data management, data quality, and information dissemination were the six major components investigated. The study findings reveal that accurate, timely and reliable health information is unavailable and therefore evidence based health planning is lacking in the studied health region. Strengths and weaknesses of the current health information system were identified and strategic recommendations were formulated accordingly. It is anticipated that this research will make a significant and multi-fold contribution for health information management in developing countries. First, it will attempt to bridge an existing knowledge gap by presenting the findings of a comprehensive case study to reveal the strengths and weaknesses of a decentralised health information system in a developing country. Second, it will enrich the literature by providing an assessment tool and a research method for the evaluation of regional health information systems. Third, it will make a rewarding practical contribution by presenting valuable guidelines for improving health information systems in regional Sri Lanka.
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An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.