Influence of adhesive non-linearities on the performance and optimal length of adhesive bonded joints

An analytical study for the static strength of adhesive lap joints is presented. The earlier solutions of Volkersen [i], DeBruyne[2] and others were limited to linear adhesives. The influence of adhesive non-linearity was first considered by Grimes' et al[3] and Dickson et al [4]. Recently Hart-Smith[5] successfully introduced elastic-plastic behaviour of the adhesive. In the present study the problem is formulated for general non-linear adhesive behaviour and an efficient numerical algorithm is written for the solution. Bilinear and trilinear models for the nonlinearity yield closed form analytical solutions.

Molecular genetics of tooth agenesis

Congenital missing of teeth, tooth agenesis or hypodontia, is one of the most common developmental anomalies in man. The common forms in which one or a few teeth are absent, may cause occlusal or cosmetic harm, while severe forms which are relatively rare always require clinical attention to support and maintain the dental function. Observation of tooth agenesis is also important for diagnosis of malformation syndromes. Some external factors may cause developmental defects and agenesis in dentition. However, the role of inheritance in the etiology of tooth agenesis is well established by twin and family studies. Studies on familial tooth agenesis as well as mouse null mutants have also identified several genetic factors. However, these explain syndromic or rare dominant forms of tooth agenesis, whereas the genes and defects responsible for the majority of cases of tooth agenesis, especially the common and less severe forms, are largely unknown. In this study it was shown, that a dominant nonsense mutation in PAX9 was responsible for severe tooth agenesis (oligodontia) in a Finnish family. In a study of tooth agenesis associated with Wolf-Hirschhorn syndrome, it was shown that severe tooth agenesis was present if the causative deletion in 4p spanned the MSX1 locus. It was concluded that severe tooth agenesis was caused by haploinsufficiency of these transcription factors. A summary of the phenotypes associated with known defects in MSX1 and PAX9 showed that, despite similarities, they were significantly different, suggesting that the genes, in addition to known interactions, also have independent roles during the development of human dentition. The original aim of this work was to identify gene defects that underlie the common incisor and premolar hypodontia. After excluding several candidate genes, a genome-wide search was conducted in seven Finnish families in which this phenotype was inherited in an autosomal dominant manner. A promising locus for second premolar agenesis was identified in chromosome 18 in one family and this finding was supported by results from other families. The results also implied the existence of other loci both for second premolar agenesis and for incisor agenesis. On the other hand the results did not lend support for comprehensive involvement of the most obvious candidate genes in the etiology of incisor and premolar hypodontia. Rather, they suggest remarkable genetic heterogeneity of tooth agenesis. The available evidence suggests that quantitative defects during tooth development predispose to a failure to overcome a developmental threshold and to agenesis. The results of the study increase the understanding of the etiology and heredity of tooth agenesis. Further studies may lead to identification of novel genes that affect the development of teeth.

Mechanisms and molecular regulation of mammalian tooth replacement

In most non-mammalian vertebrates, such as fish and reptiles, teeth are replaced continuously. However, tooth replacement in most mammals, including human, takes place only once and further renewal is apparently inhibited. It is not known how tooth replacement is genetically regulated, and little is known on the physiological mechanism and evolutionary reduction of tooth replacement in mammals. In this study I have attempted to address these questions. In a rare human condition cleidocranial dysplasia, caused by a mutation in a Runt domain transcription factor Runx2, tooth replacement is continued. Runx2 mutant mice were used to investigate the molecular mechanisms of Runx2 function. Microarray analysis from dissected embryonic day 14 Runx2 mutant and wild type dental mesenchymes revealed many downstream targets of Runx2, which were validated using in situ hybridization and tissue culture methods. Wnt signaling inhibitor Dkk1 was identified as a candidate target, and in tissue culture conditions it was shown that Dkk1 is induced by FGF4 and this induction is Runx2 dependent. These experiments demonstrated a connection between Runx2, FGF and Wnt signaling in tooth development and possibly also in tooth replacement. The role of Wnt signaling in tooth replacement was further investigated by using a transgenic mouse model where Wnt signaling mediator β-catenin is continuously stabilized in dental epithelium. This stabilization led to activated Wnt signaling and to the formation of multiple enamel knots. In vitro and transplantation experiments were performed to examine the process of extra tooth formation. We showed that new teeth were continuously generated and that new teeth form from pre-existing teeth. A morphodynamic activator-inhibitor model was used to simulate enamel knot formation. By increasing the intrinsic production rate of the activator (β-catenin), the multiple enamel knot phenotype was reproduced by computer simulations. It was thus concluded that β-catenin acts as an upstream activator of enamel knots, closely linking Wnt signaling to the regulation of tooth renewal. As mice do not normally replace teeth, we used other model animals to investigate the physiological and genetic mechanisms of tooth replacement. Sorex araneus, the common shrew was earlier reported to have non-functional tooth replacement in all antemolar tooth positions. We showed by histological and gene expression studies that there is tooth replacement only in one position, the premolar 4 and that the deciduous tooth is diminished in size and disappears during embryogenesis without becoming functional. The growth rates of deciduous and permanent premolar 4 were measured and it was shown by competence inference that the early initiation of the replacement tooth in relation to the developmental stage of the deciduous tooth led to the inhibition of deciduous tooth morphogenesis. It was concluded that the evolutionary loss of deciduous teeth may involve the early activation of replacement teeth, which in turn suppress their predecessors. Mustela putorius furo, the ferret, has a dentition that resembles that of the human as ferrets have teeth that belong to all four tooth families, and all the antemolar teeth are replaced once. To investigate the replacement mechanism, histological serial sections from different embryonic stages were analyzed. It was noticed that tooth replacement is a process which involves the growth and detachment of the dental lamina from the lingual cervical loop of the deciduous tooth. Detachment of the deciduous tooth leads to a free successional dental lamina, which grows deeper into the mesenchyme, and later buds the replacement tooth. A careful 3D analysis of serial histological sections was performed and it was shown that replacement teeth are initiated from the successional dental lamina and not from the epithelium of the deciduous tooth. The molecular regulation of tooth replacement was studied and it was shown by examination of expression patterns of candidate regulatory genes that BMP/Wnt inhibitor Sostdc1 was strongly expressed in the buccal aspect of the dental lamina, and in the intersection between the detaching deciduous tooth and the successional dental lamina, suggesting a role for Sostdc1 in the process of detachment. Shh was expressed in the enamel knot and in the inner enamel epithelium in both generations of teeth supporting the view that the morphogenesis of both generations of teeth is regulated by similar mechanisms. In summary, histological and molecular studies on different model animals and transgenic mouse models were used to investigate tooth replacement. This thesis work has significantly contributed to the knowledge on the physiological mechanisms and molecular regulation of tooth replacement and its evolutionary suppression in mammals.

Sostdc1 Plays an Essential Role in Mammalian Tooth Patterning : Insight into the Rodent Dental Evolution

This thesis work focuses on the role of TGF-beta family antagonists during the development of mouse dentition. Tooth develops through an interaction between the dental epithelium and underlying neural crest derived mesenchyme. The reciprocal signaling between these tissues is mediated by soluble signaling molecules and the balance between activatory and inhibitory signals appears to be essential for the pattern formation. We showed the importance of Sostdc1 in the regulation of tooth shape and number. The absence of Sostdc1 altered the molar cusp patterning and led to supernumerary tooth formation both in the molar and incisor region. We showed that initially, Sostdc1 expression is in the mesenchyme, suggesting that dental mesenchyme may limit supernumerary tooth induction. We tested this in wild-type incisors by minimizing the amount of mesenchymal tissue surrounding the incisor tooth germs prior to culture in vitro. The cultured teeth phenocopied the extra incisor phenotype of the Sostdc1-deficient mice. Furthermore, we showed that minimizing the amount of dental mesenchyme in cultured Sostdc1-deficient incisors caused the formation of additional de novo incisors that resembled the successional incisor development resulting from activated Wnt signaling. Sostdc1 seemed to be able to inhibit both mesenchymal BMP4 and epithelial canonical Wnt signaling, which thus allows Sostdc1 to restrict the enamel knot size and regulate the tooth shape and number. Our work emphasizes the dual role for the tooth mesenchyme as a suppressor as well as an activator during tooth development. We found that the placode, forming the thick mouse incisor, is prone to disintegration during initiation of tooth development. The balance between two mesenchymal TGF-beta family signals, BMP4 and Activin is essential in this regulation. The inhibition of BMP4 or increase in Activin signaling led to the splitting of the large incisor placode into two smaller placodes resulting in thin incisors. These two signals appeared to have different effects on tooth epithelium and the analysis of the double null mutant mice lacking Sostdc1 and Follistatin indicated that these TGF-beta inhibitors regulate the mutual balance of BMP and Activin in vivo. In addition, this work provides an alternative explanation for the issue of incisor identity published in Science by Tucker et al. in 1998 and proposes that the molar like morphology that can be obtained by inhibiting BMP signaling is due to partial splitting of the incisor placodes and not due to change in tooth identity from the incisor to the molar. This thesis work presents possible molecular mechanisms that may have modified the mouse dental pattern during evolution leading to the typical rodent dentition of modern mouse. The rodent dentition is specialized for gnawing and consists of two large continuously growing incisors and toothless diastema region separating the molars and incisors. The ancestors of rodents had higher number of more slender incisors together with canines and premolars. Additionally, murine rodents, which include the mouse, have lost their ability for tooth replacement. This work has revealed that the inhibitory molecules appear to play a role in the tooth number suppression by delineating the spatial and temporal action of the inductive signals. The results suggest that Sostdc1 plays an essential role in several stages of tooth development through the regulation of both the BMP and Wnt pathway. The work shows a dormant sequential tooth forming potential present in wild type mouse incisor region and gives a new perspective on tooth suppression by dental mesenchyme. It reveals as well a novel mechanism to create a large mouse incisor through the regulation of mesenchymal balance between inductive and inhibitory signals.

When and why threats go undetected: Impacts of event rate and shift length on threat detection accuracy during airport baggage screening

Objective: We aimed to assess the impact of task demands and individual characteristics on threat detection in baggage screeners. Background: Airport security staff work under time constraints to ensure optimal threat detection. Understanding the impact of individual characteristics and task demands on performance is vital to ensure accurate threat detection. Method: We examined threat detection in baggage screeners as a function of event rate (i.e., number of bags per minute) and time on task across 4 months. We measured performance in terms of the accuracy of detection of Fictitious Threat Items (FTIs) randomly superimposed on X-ray images of real passenger bags. Results: Analyses of the percentage of correct FTI identifications (hits) show that longer shifts with high baggage throughput result in worse threat detection. Importantly, these significant performance decrements emerge within the first 10 min of these busy screening shifts only. Conclusion: Longer shift lengths, especially when combined with high baggage throughput, increase the likelihood that threats go undetected. Application: Shorter shift rotations, although perhaps difficult to implement during busy screening periods, would ensure more consistently high vigilance in baggage screeners and, therefore, optimal threat detection and passenger safety.

A multiple nucleotide length polymorphism (MNLP) mediates androgen regulation of IRX4 in prostate cancer

Androgens and the androgen receptor (AR) play a crucial role in the initiation and progression of prostate cancer (PCa), regulating the expression of many PCa risk-associated genes. Iroquois Homeobox 4 (IRX4) has been recently identified with PCa risk and overexpressed in PCa. We observed a down-regulation of IRX4 expression in the cells undergoing epithelial to mesenchymal transition, suggesting its potential role in PCa progression and aim to delineate the androgenmediated regulation of IRX4 in PCa.

Direct estimate of transport length scales in semiconducting polymers

A method for determining the electron/hole transport length scale of model semiconducting polymer systems by scanning a narrow-light probe beam over the nonoverlapping anode/cathode region in asymmetric sandwich device structures is presented (see figure). Electron versus hole collection efficacy, and disorder and spatial anisotropy in the electrical transport parameters can be estimated.

Neck length and mean arterial pressure in the sauropod dinosaurs

How blood was able to reach the heads of the long-necked sauropod dinosaurs has long been a matter of debate and several hypotheses have been presented. For example, it has been proposed that sauropods had exceptionally large hearts, multiple ‘normal’ sized hearts spaced at regular intervals up the neck or held their necks horizontal, or that the siphon effect was in operation. By means of an experimental model, we demonstrate that the siphon principle is able to explain how blood was able to adequately perfuse the sauropod brain. The return venous circulation may have been protected from complete collapse by a structure akin to the vertebral venous plexus. We derive an equation relating neck height and mean arterial pressure, which indicates that with a mean arterial pressure similar to that of the giraffe, the maximum safe vertical distance between heart and head would have been about 12 m. A hypothesis is presented that the maximum neck length in the fossil record is due to the siphon height limit. The equation indicates that to migrate over high ground, sauropods would have had to either significantly increase their mean arterial pressure or keep their necks below a certain height dependent on altitude.

Guessing based on length functions

Close relationships between guessing functions and length functions are established. Good length functions lead to good guessing functions. In particular, guessing in the increasing order of Lempel-Ziv lengths has certain universality properties for finite-state sources. As an application, these results show that hiding the parameters of the key-stream generating source in a private key crypto-system may not enhance the privacy of the system, the privacy level being measured by the difficulty in brute-force guessing of the key stream.

Morbid obesity in total hip arthroplasty: Redefining outcomes for operative time, length of stay, and readmission

Background The incidence of obesity amongst patients presenting for elective Total Hip Arthroplasty (THA) has increased in the last decade and the relationship between obesity and the need for joint replacement has been demonstrated. This study evaluates the effects of morbid obesity on outcomes following primary THA by comparing short-term outcomes in THA between a morbidly obese (BMI ≥40) and a normal weight (BMI 18.5 - <25) cohort at our institution between January 2003 and December 2010. Methods Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission and length of readmission were compared. Results Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (p=0.002). Post-operatively there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI ≥40 compared with 2.7% (p= 0.005) as well as a 5.1 fold increase in surgery related readmitted bed days - 0.32 bed days per patient for normal weight compared with 1.64 per patient for the morbidly obese (p=0.026). Conclusion Morbidly obese patients present a technical challenge and likely this and the resultant complications are underestimated. More work needs to be performed in order to enable suitable allocation of resources.

Effect of Chain Length of Alcohol on the Lipase-Catalyzed Esterification of Propionic Acid in Supercritical Carbon Dioxide

The esterification of propionic acid was investigated using three different alcohols, namely, isopropyl alcohol, isobutyl alcohol, and isoamyl alcohol. The variation of conversion with time for the synthesis of isoamyl propionate was investigated in the presence of five enzymes. Novozym 435 showed the highest activity, and this was used as the enzyme for investigating the various parameters that influence the esterification reaction. The Ping-Pong Bi-Bi model with inhibition by both acid and alcohol was used to model the experimental data and determine the kinetics of the esterification reaction.

High-Throughput Flexible Constraint Length Viterbi Decoders on De Bruijn, Shuffle-Exchange and Butterfly Connected Architectures

Flexible constraint length channel decoders are required for software defined radios. This paper presents a novel scalable scheme for realizing flexible constraint length Viterbi decoders on a de Bruijn interconnection network. Architectures for flexible decoders using the flattened butterfly and shuffle-exchange networks are also described. It is shown that these networks provide favourable substrates for realizing flexible convolutional decoders. Synthesis results for the three networks are provided and a comparison is performed. An architecture based on a 2D-mesh, which is a topology having a nominally lesser silicon area requirement, is also considered as a fourth point for comparison. It is found that of all the networks considered, the de Bruijn network offers the best tradeoff in terms of area versus throughput.

The Line Spectral Frequency Model of a Finite-Length Sequence

The line spectral frequency (LSF) of a causal finite length sequence is a frequency at which the spectrum of the sequence annihilates or the magnitude spectrum has a spectral null. A causal finite-length sequencewith (L + 1) samples having exactly L-LSFs, is referred as an Annihilating (AH) sequence. Using some spectral properties of finite-length sequences, and some model parameters, we develop spectral decomposition structures, which are used to translate any finite-length sequence to an equivalent set of AH-sequences defined by LSFs and some complex constants. This alternate representation format of any finite-length sequence is referred as its LSF-Model. For a finite-length sequence, one can obtain multiple LSF-Models by varying the model parameters. The LSF-Model, in time domain can be used to synthesize any arbitrary causal finite-length sequence in terms of its characteristic AH-sequences. In the frequency domain, the LSF-Model can be used to obtain the spectral samples of the sequence as a linear combination of spectra of its characteristic AH-sequences. We also summarize the utility of the LSF-Model in practical discrete signal processing systems.