Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model

Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting.

Inhibition of Thrombin in Cardiac Surgery : experiments in a porcine model

Cardiac surgery involving cardiopulmonary bypass (CPB) induces activation of inflammation and coagulation systems and is associated with ischemia-reperfusion injury (I/R injury)in various organs including the myocardium, lungs, and intestine. I/R injury is manifested as organ dysfunction. Thrombin, the key enzyme of coagulation , plays a cenral role also in inflammation and contributes to regulation of apoptosis as well. The general aim of this thesis was to evaluate the potential of thrombin inhibition in reducing the adverse effects of I/R injury in myocardium, lungs, and intestine associated with the use of CPB and cardiac surgery. Forty five pigs were used for the studies. Two randomized blinded studies were performed. Animals underwent 75 min of normothermic CPB, 60 min of aortic clamping, and 120 min of reperfusion period. Twenty animals received iv. recombinant hirudin, a selective and effective inbitor of thrombin, or placebo. In a similar setting, twenty animals received an iv-bolus (250 IU/kg) of antithrombin (AT) or placebo. An additional group of 5 animals received 500 IU/kg in an open label setting to test dose response. Generation of thrombin (TAT), coagulation status (ACT), and hemodynamics were measured. Intramucosal pH and pCO2 were measured from the luminal surface of ileum using tonometry simultaneusly with arterial gas analysis. In addition, myocardial, lung, and intestinal biopsies were taken to quantitate leukocyte infiltration (MPO), for histological evaluation, and detection of apoptosis (TUNEL, caspase 3). In conclusion, our data suggest that r-hirudin may be an effective inhibitor of reperfusion induced thrombin generation in addition to being a direct inhibitor of preformed thrombin. Overall, the results suggest that inhibition of thrombin, beyond what is needed for efficient anticoagulation by heparin, has beneficial effects on myocardial I/R injury and hemodynamics during cardiac surgery and CPB. We showed that infusion of the thrombin inhibitor r-hirudin during reperfusion was associated with attenuated post ischemia left ventricular dysfunction and decreased systemic vascular resistance. Consequently microvascular flow was improved during ischemia-reperfusion injury. Improved recovery of myocardium during the post-ischemic reperfusion period was associated with significantly less cardiomyocyte apoptosis and with a trend in anti-inflammatory effects. Thus, inhibition of reperfusion induced thrombin may offer beneficial effects by mechanisms other than direct anticoagulant effects. AT, in doses with a significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of myocardial recovery, histological inflammatory changes or post-ischemic troponin T release. Instead, AT attenuated reperfusion induced increase in pulmonary pressure after CPB. Taken the clinical significance of postoperative pulmonary hemodynamics in patients undergoing cardiopulmonary bypass, the potential positive regulatory role of AT and clinical implications needs to be studied further. Inflammatory response in the gut wall proved to be poorly associated with perturbed mucosal perfusion and the animals with the least neutrophil tissue sequestration and I/R related histological alterations tended to have the most progressive mucosal hypoperfusion. Thus, mechanisms of low-flow reperfusion injury during CPB can differ from the mechanisms seen in total ischemia reperfusion injury.

Genetic analysis of structural brain connectivity using DICCCOL models of diffusion MRI in 522 twins

Genetic and environmental factors affect white matter connectivity in the normal brain, and they also influence diseases in which brain connectivity is altered. Little is known about genetic influences on brain connectivity, despite wide variations in the brain's neural pathways. Here we applied the 'DICCCOL' framework to analyze structural connectivity, in 261 twin pairs (522 participants, mean age: 21.8 y ± 2.7SD). We encoded connectivity patterns by projecting the white matter (WM) bundles of all 'DICCCOLs' as a tracemap (TM). Next we fitted an A/C/E structural equation model to estimate additive genetic (A), common environmental (C), and unique environmental/error (E) components of the observed variations in brain connectivity. We found 44 'heritable DICCCOLs' whose connectivity was genetically influenced (α2>1%); half of them showed significant heritability (α2>20%). Our analysis of genetic influences on WM structural connectivity suggests high heritability for some WM projection patterns, yielding new targets for genome-wide association studies.

Genetic programming metamodel for rotating beams

This paper investigates the use of Genetic Programming (GP) to create an approximate model for the non-linear relationship between flexural stiffness, length, mass per unit length and rotation speed associated with rotating beams and their natural frequencies. GP, a relatively new form of artificial intelligence, is derived from the Darwinian concept of evolution and genetics and it creates computer programs to solve problems by manipulating their tree structures. GP predicts the size and structural complexity of the empirical model by minimizing the mean square error at the specified points of input-output relationship dataset. This dataset is generated using a finite element model. The validity of the GP-generated model is tested by comparing the natural frequencies at training and at additional input data points. It is found that by using a non-dimensional stiffness, it is possible to get simple and accurate function approximation for the natural frequency. This function approximation model is then used to study the relationships between natural frequency and various influencing parameters for uniform and tapered beams. The relations obtained with GP model agree well with FEM results and can be used for preliminary design and structural optimization studies.

Disease burden due to Streptococcus dysgalactiae subsp equisimilis (group G and C streptococcus) is higher than that due to Streptococcus pyogenes among Mumbai school children

Streptococcus pyogenes [group A streptococcus (GAS)], a human pathogen, and Streptococcus dysgalactiae subsp. equisimilis [human group G and C streptococcus (GGS/GCS)] are evolutionarily related, share the same tissue niche in humans, exchange genetic material, share up to half of their virulence-associated genes and cause a similar spectrum of diseases. Yet, GGS/GCS is often considered as a commensal bacterium and its role in streptococcal disease burden is under-recognized. While reports of the recovery of GGS/GCS from normally sterile sites are increasing, studies describing GGS/GCS throat colonization rates relative to GAS in the same population are very few. This study was carried out in India where the burden of streptococcal diseases, including rheumatic fever and rheumatic heart disease, is high. As part of a surveillance study, throat swabs were taken from 1504 children attending 7 municipal schools in Mumbai, India, during 2006-2008. GAS and GGS/GCS were identified on the basis of beta-haemolytic activity, carbohydrate group and PYR test, and were subsequently typed. The GGS/GCS carriage rate (1166/1504, 11%) was eightfold higher than the GAS carriage (22/1504, 1.5%) rate in this population. The 166 GGS/GCS isolates collected represented 21 different emm types (molecular types), and the 22 GAS isolates represented 15 different emm types. Although the rate of pharyngitis associated with GGS/GCS is marginally lower than with GAS, high rates of throat colonization by GGS/GCS underscore its importance in the pathogenesis of pharyngitis.

Approaches for improving the safety and efficacy of adenoviral gene therapy

Cancer is a devastating disease with poor prognosis and no curative treatment, when widely metastatic. Conventional therapies, such as chemotherapy and radiotherapy, have efficacy but are not curative and systemic toxicity can be considerable. Almost all cancers are caused due to changes in the genetic material of the transformed cells. Cancer gene therapy has emerged as a new treatment option, and past decades brought new insights in developing new therapeutic drugs for curing cancer. Oncolytic viruses constitute a novel therapeutic approach given their capacity to replicate in and kill specifically tumor cells as well as reaching tumor distant metastasis. Adenoviral gene therapy has been suggested to cause liver toxicity. This study shows that new developed adenoviruses, in particular Ad5/19p-HIT, can be redirected towards kidney while adenovirus uptake by liver is minimal. Moreover, low liver transduction resulted in a favorable tumor to liver ratio of virus load. Further, we established a new immunocompetent animal model Syrian hamsters. Wild type adenovirus 5 was found to replicate in Hap-T1 hamster tumors and normal tissues. There are no antiviral drugs available to inhibit adenovirus replication. In our study, chlorpromazine and cidofovir efficiently abrogated virus replication in vitro and showed significant reduction in vivo in tumors and liver. Once safety concerns were addressed together with the new given antiviral treatment options, we further improved oncolytic adenoviruses for better tumor penetration, local amplification and host system modulation. Further, we created Ad5/3-9HIF-Δ24-VEGFR-1-Ig, oncolytic adenovirus for improved infectivity and antiangiogenic effect for treatment of renal cancer. This virus exhibited increased anti-tumor effect and specific replication in kidney cancer cells. The key player for good efficacy of oncolytic virotherapy is the host immune response. Thus, we engineered a triple targeted adenovirus Ad5/3-hTERT-E1A-hCD40L, which would lead to tumor elimination due to tumor-specific oncolysis and apoptosis together with an anti-tumor immune response prompted by the immunomodulatory molecule. In conclusion, the results presented in this thesis constitute advances in our understanding of oncolytic virotherapy by successful tumor targeting, antiviral treatment options as a safety switch in case of replication associated side-effects, and modulation of the host immune system towards tumor elimination.  

Clinical Phenotype and Genetic Epidemiology of Schizophrenia in a Finnish Isolate

This study is part of the joint project "The Genetic Epidemiology and Molecular Genetics of schizophrenia in Finland" between the Departments of Mental Health and Alcohol Research, and Molecular Medicine at the National Public Health Institute. In the study, we utilized three nationwide health care registers: 1) the Hospital Discharge Register, 2) the Free Medication Register, and 3) the Disability Pension Register, plus the National Population Register, in order to identify all patients with schizophrenia born from 1940 to 1976 (N=33,731) in Finland, and their first degree-relatives. 658 patients with at least one parent born in a homogeneous isolate in northeastern Finland were identified, as well as 4904 familial schizophrenia patients with at least two affected siblings from the whole country. The comparison group was derived from the Health 2000 Study. We collected case records and reassessed the register diagnosis. Were contacted the isolate patients and a random sample of patients from the whole country to make diagnostic clinical interviews and to assess the negative and positive symptoms and signs of schizophrenia. In addition to these patients, we interviewed siblings who were initially healthy according to the Hospital Discharge Register. Of those with a register diagnosis of schizophrenia, schizoaffective or schizophreniform disorder, 69% received a record-based consensus diagnosis and 63% an interview-based diagnosis of schizophrenia. Patients with schizophrenia having first-degree relatives with psychotic disorder had more severe affective flattening and alogia than those who were the only affected individuals in their family. The novel findings were: 1) The prevalence of schizophrenia in the isolate was relatively high based on register (1.5%), case record (0.9-1.3%), and interview (0.7-1.2%) data. 2) Isolate patients, regardless of their familial loading for schizophrenia, had less delusions and hallucinations than the whole country familial patients, which may be related to the genetic homogeneity in the isolate. This phenotype encourages the use of endophenotypes in genetic analyses instead of diagnoses alone. 3) The absence of register diagnosis does not confirm that siblings are healthy, because 7.7% of siblings had psychotic symptoms already before the register diagnoses were identified in 1991. For genetic research, the register diagnosis should therefore be reassessed using either a structured interview or a best- estimate case note consensus diagnosis. Structured clinical interview methods need be considered also in clinical practice.

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.

Intrahepatic cholestasis of pregnancy : genetic background, epidemiology and hepatobiliary consequences

Intrahepatic cholestasis of pregnancy (ICP) is the most common cholestatic liver disease during pregnancy. The reported incidence varies from 0.4 to 15% of full-term pregnancies. The etiology is heterogeneous but familial clustering is known to occur. Here we have studied the genetic background, epidemiology, and long-term hepatobiliary consequences of ICP. In a register-based nation-wide study (n=1 080 310) the incidence of ICP was 0.94% during 1987-2004. A slightly higher incidence, 1.3%, was found in a hospital-based series (n=5304) among women attending the University Hospital of Helsinki in 1992-1993. Of these 16% (11/69) were familial and showed a higher (92%) recurrence rate than the sporadic (40%) cases. In the register-based epidemiological study, advanced maternal age and, to a lesser degree, parity were identified as new risk factors for ICP. The risk was 3-fold higher in women >39 years of age compared to women <30 years. Multiple pregnancy also associated with an elevated risk. In a genetic study we found no association of ICP with the genes regulating bile salt transport (ABCB4, ABCB11 and ATP8B1). The livers of postmenopausal women with a history of ICP tolerated well the short-term exposure to oral and transdermal estradiol, although the doses used were higher than those in routine clinical use. The response of serum levels of sex hormone-binding globulin (SHBG) to oral estradiol was slightly reduced in the ICP group. Transdermal estradiol had no effect on C-reactive protein (CRP) or SHBG. A number of liver and biliary diseases were found to be associated with ICP. Women with a history of ICP showed elevated risks for non-alcoholic liver cirrhosis (8.2 CI 1.9-36), cholelithiasis and cholecystitis (3.7 CI 3.2-4.2), hepatitis C (3.5 CI 1.6-7.6) and non-alcoholic pancreatitis (3.2 CI 1.7-5.7). In conclusion, ICP complicates around 1% of all full-term pregnancies in Finland and its incidence has remained unchanged since 1987. It is familial in 16% of cases with a higher recurrence rate. Although the cause remains unknown, several risk factors, namely advanced maternal age, parity and multiple pregnancies, can be identified. Both oral and transdermal regimens of postmenopausal hormone therapy (HT) are safe for women with a history of ICP when liver function is considered. Some ICP patients are at risk of other liver and biliary diseases and, contrary to what has been thought, a follow-up is warranted.

Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Finland

In recent reports, adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have had a better outcome with pediatric treatment than with adult protocols. ALL can be classified into biologic subgroups according to immunophenotype and cytogenetics, with different clinical characteristics and outcome. The proportions of the subgroups are different in children and adults. ALL subtypes in AYA patients are less well characterized. In this study, the treatment and outcome of ALL in AYA patients aged 10-25 years in Finland on pediatric and adult protocols was retrospectively analyzed. In total, 245 patients were included. The proportions of biologic subgroups in different age groups were determined. Patients with initially normal or failed karyotype were examined with oligonucleotide microarray-based comparative genomic hybridization (aCGH). Also deletions and instability of chromosome 9p were screened in ALL patients. In addition, patients with other hematologic malignancies were screened for 9p instability. aCGH data were also used to determine a gene set that classifies AYA patients at diagnosis according to their risk of relapse. Receiver operating characteristic analysis was used to assess the value of the set of genes as prognostic classifiers. The 5-year event-free survival of AYA patients treated with pediatric or adult protocols was 67% and 60% (p=0.30), respectively. White blood cell count larger than 100x109/l was associated with poor prognosis. Patients treated with pediatric protocols and assigned to an intermediate-risk group fared significantly better than those of the pediatric high-risk or adult treatment groups. Deletions of 9p were detected in 46% of AYA ALL patients. The chromosomal region 9p21.3 was always affected, and the CDKN2A gene was always deleted. In about 15% of AYA patients, the 9p21.3 deletion was smaller than 200 kb in size, and therefore, probably undetectable with conventional methods. Deletion of 9p was the most common aberration of AYA ALL patients with initially normal karyotype. Instability of 9p, defined as multiple separate areas of copy number loss or homozygous loss within a larger heterozygous area in 9p, was detected in 19% (n=27) of ALL patients. This abnormality was restricted to ALL; none of the patients with other hematologic malignancies had the aberration. The prognostic model identification procedure resulted in a model of four genes: BAK1, CDKN2B, GSTM1, and MT1F. The copy number profile combinations of these genes differentiated between AYA ALL patients at diagnosis depending on their risk of relapse. Deletions of CDKN2B and BAK1 in combination with amplification of GSTM1 and MT1F were associated with a higher probability of relapse. Unlike all previous studies, we found that the outcome of AYA patients with ALL treated using pediatric or adult therapeutic protocols was comparable. The success of adult ALL therapy emphasizes the benefit of referral of patients to academic centers and adherence to research protocols. 9p deletions and instability are common features of ALL and may act together with oncogene-activating translocations in leukemogenesis. New and more sensitive methods of molecular cytogenetics can reveal previously cryptic genetic aberrations with an important role in leukemic development and prognosis and that may be potential targets of therapy. aCGH also provides a viable approach for model design aiming at evaluation of risk of relapse in ALL.

A Historical Approach to Children s Physics Education : Modelling of DC-circuit Phenomena in a Small Group

This three-phase design research describes the modelling processes for DC-circuit phenomena. The first phase presents an analysis of the development of the DC-circuit historical models in the context of constructing Volta s pile at the turn of the 18th century. The second phase involves the designing of a teaching experiment for comprehensive school third graders. Among other considerations, the design work utilises the results of the first phase and research literature of pupils mental models for DC-circuit phenomena. The third phase of the research was concerned with the realisation of the planned teaching experiment. The aim of this phase was to study the development of the external representations of DC-circuit phenomena in a small group of third graders. The aim of the study has been to search for new ways to guide pupils to learn DC-circuit phenomena while emphasing understanding at the qualitative level. Thus, electricity, which has been perceived as a difficult and abstract subject, could be learnt more comprehensively. Especially, the research of younger pupils learning of electricity concepts has not been of great interest at the international level, although DC-circuit phenomena are also taught in the lower classes of comprehensive schools. The results of this study are important, because there has tended to be more teaching of natural sciences in the lower classes of comprehensive schools, and attempts are being made to develop this trend in Finland. In the theoretical part of the research an Experimental-centred representation approach, which emphasises the role of experimentalism in the development of pupil s representations, is created. According to this approach learning at the qualitative level consists of empirical operations like experimenting, observations, perception, and prequantification of nature phenomena, and modelling operations like explaining and reasoning. Besides planning teaching, the new approach can be used as an analysis tool in describing both historical modelling and the development of pupils representations. In the first phase of the study, the research question was: How did the historical models of DC-circuit phenomena develop in Volta s time? The analysis uncovered three qualitative historical models associated with the historical concept formation process. The models include conceptions of the electric circuit as a scene in the DC-circuit phenomena, the comparative electric-current phenomenon as a cause of different observable effect phenomena, and the strength of the battery as a cause of the electric-current phenomenon. These models describe the concept formation process and its phases in Volta s time. The models are portrayed in the analysis using fragments of the models, where observation-based fragments and theoretical fragements are distinguished from each other. The results emphasise the significance of the qualitative concept formation and the meaning of language in the historical modelling of DC-circuit phenomena. For this reason these viewpoints are stressed in planning the teaching experiment in the second phase of the research. In addition, the design process utilised the experimentation behind the historical models of DC-circuit phenomena In the third phase of the study the research question is as follows: How will the small group s external representations of DC-circuit phenomena develop during the teaching experiment? The main question is divided into the following two sub questions: What kind of talk exists in the small group s learning? What kinds of external representations for DC-circuit phenomena exist in the small group discourse during the teaching experiment? The analysis revealed that the teaching experiment of the small group succeeded in its aim to activate talk in the small group. The designed connection cards proved especially successful in activating talk. The connection cards are cards that represent the components of the electric circuit. In the teaching experiment the pupils constructed different connections with the connection cards and discussed, what kinds of DC-circuit phenomena would take place in the corresponding real connections. The talk of the small group was analysed by comparing two situations, firstly, when the small group discussed using connections made with the connection cards and secondly with the same connections using real components. According to the results the talk of the small group included more higher-order thinking when using the connection cards than with similar real components. In order to answer the second sub question concerning the small group s external representations that appeared in the talk during the teaching experiment; student talk was visualised by the fragment maps which incorporate the electric circuit, the electric current and the source voltage. The fragment maps represent the gradual development of the external representations of DC-circuit phenomena in the small group during the teaching experiment. The results of the study challenge the results of previous research into the abstractness and difficulty of electricity concepts. According to this research, the external representations of DC-circuit phenomena clearly developed in the small group of third graders. Furthermore, the fragment maps uncover that although the theoretical explanations of DC-circuit phenomena, which have been obtained as results of typical mental model studies, remain undeveloped, learning at the qualitative level of understanding does take place.

Selective dissemination of XML documents based on genetically learned user model and Support Vector Machines

Extensible Markup Language ( XML) has emerged as a medium for interoperability over the Internet. As the number of documents published in the form of XML is increasing, there is a need for selective dissemination of XML documents based on user interests. In the proposed technique, a combination of Adaptive Genetic Algorithms and multi class Support Vector Machine ( SVM) is used to learn a user model. Based on the feedback from the users, the system automatically adapts to the user's preference and interests. The user model and a similarity metric are used for selective dissemination of a continuous stream of XML documents. Experimental evaluations performed over a wide range of XML documents, indicate that the proposed approach significantly improves the performance of the selective dissemination task, with respect to accuracy and efficiency.

Is the mental wellbeing of young Australians best represented by a single, multidimensional or bifactor model?

Internationally there is a growing interest in the mental wellbeing of young people. However, it is unclear whether mental wellbeing is best conceptualized as a general wellbeing factor or a multidimensional construct. This paper investigated whether mental wellbeing, measured by the Mental Health Continuum-Short Form (MHC-SF), is best represented by: (1) a single-factor general model; (2) a three-factor multidimensional model or (3) a combination of both (bifactor model). 2,220 young Australians aged between 16 and 25 years completed an online survey including the MHC-SF and a range of other wellbeing and mental ill-health measures. Exploratory factor analysis supported a bifactor solution, comprised of a general wellbeing factor, and specific group factors of psychological, social and emotional wellbeing. Confirmatory factor analysis indicated that the bifactor model had a better fit than competing single and three-factor models. The MHC-SF total score was more strongly associated with other wellbeing and mental ill-health measures than the social, emotional or psychological subscale scores. Findings indicate that the mental wellbeing of young people is best conceptualized as an overarching latent construct (general wellbeing) to which emotional, social and psychological domains contribute. The MHC-SF total score is a valid and reliable measure of this general wellbeing factor.

A model based factorization approach for dense 3D recovery from monocular video

Feature track matrix factorization based methods have been attractive solutions to the Structure-front-motion (Sfnl) problem. Group motion of the feature points is analyzed to get the 3D information. It is well known that the factorization formulations give rise to rank deficient system of equations. Even when enough constraints exist, the extracted models are sparse due the unavailability of pixel level tracks. Pixel level tracking of 3D surfaces is a difficult problem, particularly when the surface has very little texture as in a human face. Only sparsely located feature points can be tracked and tracking error arc inevitable along rotating lose texture surfaces. However, the 3D models of an object class lie in a subspace of the set of all possible 3D models. We propose a novel solution to the Structure-from-motion problem which utilizes the high-resolution 3D obtained from range scanner to compute a basis for this desired subspace. Adding subspace constraints during factorization also facilitates removal of tracking noise which causes distortions outside the subspace. We demonstrate the effectiveness of our formulation by extracting dense 3D structure of a human face and comparing it with a well known Structure-front-motion algorithm due to Brand.

Synthetic and conformational studies on dehydroalanine-containing model peptides

Three model dipeptides containing a dehydroalanine residue (Ala) at the C-terminal, Boc-X-Ala-NHCH3 [X = Ala, Val, and Phe,] have been synthesized and their solution conformations investigated by 1H-NMR, IR, and CD spectroscopy. NMR studies on these peptides in CDCl3 clearly indicate that the NH group of dehydroalanine is involved in an intramolecular hydrogen bond. This conclusion is supported by IR studies also. Nuclear Overhauser effect (NOE) studies are also accommodative of an inverse -turn-type of conformation that is characterised by conformational angles of -70° and +70° around the X residue, and a C[stack i+1 ]H-Ni+2H interproton distance of 2.5 Å. It appears that unlike dehydrophenylalanine or dehydroleucine, which tend to stabilize -turn type of structures occupying the i + 2 position of the turn, dehydroalanine favors the formation of an inverse -turn, centered at the proceeding L-residue in such solvents as CDCl3 and (CD3)2SO. A comparison of solution conformation of Boc Val-Ala-NHCH3 with the corresponding saturated analogue, Boc-Val-Ala-NHCH3, is also presented and shows that dehydroalanine is responsible for inducing the turn structure. It may be possible to design peptides with different preferred conformations using the suitable dehydroamino acid.