<p>Biovitrumis is one of the larger biopharma companies in Euprope and conducts research in different niche areas. One of the interested areas for Biovitrum is Exocrine Pancreatic insufficiency. Biovitrum has a candidate drug (product D) in early development process for treatment of. Exocrine Pancreatic Insufficiency.</p><p>The Drug development is a long, complicated and costly process. Therefore, it is very important for managers to know the commercial value of a future drug. The purpose of this report is to develop a model for evaluation of candidate drug in early development phase and analysis of market potential for product D for treatment of Chronic pancreatitis. Chronic pancreatitis is disease within sub group of Exocrine Pancreatic Insufficiency.</p><p>The deductive reasoning approach and quantitative data is used in this report. Only secondary data is collected for this study. The sources of secondary data are research papers, Google Pub-Med database and consultant companies.</p><p>A new model is developed for evaluation of candidate drug .This model can analyse the market potential, unmet medical need, and calculate net present values. This study shows that there is unmet medical need in chronic pancreatitis. The result also shows that product D has comparative advantages over present products in the market and future competitors. The product D can full fill the unmet medical need for treatment of Chronic pancreatitis</p>

<p>Autism is a pervasive developmental disorder (PDD) that&rsquo / s incidence is approximately 1 in 158. It is four times more prevalent in males than females and is believed to be caused by both genetic and environmental factors. Research indicates that several genes are involved in autism and it is believed that these genes act together to produce autism. Many genes implicated in this disorder are involved with brain structure formation and brain functioning. Studies have identified the reelin (RELN) gene as necessary for proper formation of brain, which indicates that RELN abnormalities could contribute to the aetiology of several neurogenetic diseases such as schizophrenia, bipolar and autism. The aims of the study were (i) to genotype two SNPs (exonic rs3622691 and intronic rs736707) in the RELN gene using Taqman&reg / SNP Genotyping assays to detect association with autism in three distinct South African (SA) ethnic groups (Black, Caucasian and Mixed), and (ii) to detect candidate genes that are over and under-expressed in the samples taken from a SA Caucasian autistic group and compare those with samples taken from a healthy Caucasian group using cDNA microarray. The Taqman&reg / study indicated significant association for the intronic SNP, rs736707, with a p-value of 0.0009 in the total SA group. More so, the Mixed group displayed the highest significance amongst the ethnic groups, with a p-value of 0.00014. The microarray study yielded 21 genes with 95% significance in the Caucasian sample group. Most genes were hypothetical proteins and formed part of the FAM90A family. The LOC83459 showed the highest level of expression in the autistic samples, while the BTNL8 gene was shown to be highly suppressed in the control samples.</p>

Biovitrumis is one of the larger biopharma companies in Euprope and conducts research in different niche areas. One of the interested areas for Biovitrum is Exocrine Pancreatic insufficiency. Biovitrum has a candidate drug (product D) in early development process for treatment of. Exocrine Pancreatic Insufficiency. The Drug development is a long, complicated and costly process. Therefore, it is very important for managers to know the commercial value of a future drug. The purpose of this report is to develop a model for evaluation of candidate drug in early development phase and analysis of market potential for product D for treatment of Chronic pancreatitis. Chronic pancreatitis is disease within sub group of Exocrine Pancreatic Insufficiency. The deductive reasoning approach and quantitative data is used in this report. Only secondary data is collected for this study. The sources of secondary data are research papers, Google Pub-Med database and consultant companies. A new model is developed for evaluation of candidate drug .This model can analyse the market potential, unmet medical need, and calculate net present values. This study shows that there is unmet medical need in chronic pancreatitis. The result also shows that product D has comparative advantages over present products in the market and future competitors. The product D can full fill the unmet medical need for treatment of Chronic pancreatitis

Cuando los miembros de una sociedad tienen que tomar una decisión sobre un conjunto de alternativas suelen usar ciertas reglas que tratan de alcanzar un acuerdo entre sus diferentes intereses. Estas reglas se suelen denominar mecanismos de votación, procedimientos de elección social o, simplemente, elecciones. Las reglas de votación definen escenarios en los que los miembros de la sociedad interaccionan y tratan de obtener el mejor resultado de acuerdo con sus preferencias. Esta tesis doctoral está dedicada al estudio de los incentivos estratégicos de los participantes (votantes y candidatos) en procesos de elección social.Nuestro análisis se centra en modelos generales en los que se admite que el resultado de la elección consista en un conjunto de alternativas. Aunque resulta natural suponer que sólo una alternativa será finalmente elegida, existen múltiples situaciones en las que este supuesto es sumamente restrictivo. Por ejemplo, podríamos considerar la elección como una etapa intermedia en el proceso de decisión. El objeto del proceso electoral sería reducir el número de alternativas entre las que la sociedad tendría que escoger. Con esta interpretación, nos centraríamos en situaciones en los que existe cierto grado de incertidumbre sobre la resolución final de la elección social.En esta tesis seguimos dos importantes ramas de la literatura de la teoría de la elección social, el estudio de reglas decisión social no manipulables y el análisis de los problemas de candidatura estratégica.En primer lugar, siguiendo el trabajo seminal de Dutta, Jackson y Le Breton (Econometrica, 2001) estudiamos los incentivos de los candidatos para entrar o abandonar la lucha electoral con la intención de afectar al resultado de la elección. Si los candidatos comparan conjuntos de candidatos de forma consistente con los postulados de la teoría de la utilidad esperada, cualquier regla de decisión unánime y no dictatorial provee a algún candidato con incentivos a abandonar su candidatura. Sin embargo, si los candidatos comparan los resultados de la elección de acuerdo con métodos menos sofisticados, sí que se pueden obtener resultados positivos.Seguidamente, pasamos a analizar los incentivos estratégicos de los candidatos en un entorno complementario: en el que el resultado de la elección es explícitamente probabilístico. En esta situación podemos caracterizar la familia de reglas de votación que nunca incentivan la salida de ningún candidato. Sorprendentemente, aunque la familia de dictadores aleatorios juega un papel central dentro de la caracterización, podemos probar que reglas de decisión más flexibles también satisfacen los requerimientos de estabilidad en las candidaturas.Finalmente, nos centramos en la posibilidad de construir reglas de decisión no manipulables cuando los votantes comparan conjuntos de alternativas de acuerdo con actitudes extremas ante el riesgo. En este contexto, analizamos la compatibilidad entre la condición de no manipulabilidad y otras condiciones de regularidad que han sido propuestas en la literatura como por ejemplo, Resolución Residual. Además, también presentamos los requerimientos en las preferencias de los votantes sobre conjuntos de alternativas que reducen la posibilidad de reglas de decisión no manipulables a reglas dictatoriales. / When a society has to make a choice from an array of alternatives, it usually relies on certain rules that try to reconcile the opposite interest of the members of the society. These rules define environments in which the agents interact and try to obtain the best outcome according to their preferences. This work is devoted to the study of the strategic incentives of the participants in the social decision processes.We analyse general frameworks in which the outcome of the social choice process can be multivalued. Even when it seems natural to assume that the result of an election as a singleton, there are many situation in which our assumption should not be precluded. For instance, we can consider the social decision process as an interim stage that narrows the social agenda. Another possibility is to consider the set of the possible equilibria that could eventually arise in the voting procedure as the outcome of the election.Our study focuses on two important branches of the literature, the study of strategy-proof social choice correspondences and the analysis of strategic candidacy in multivalued voting procedures.First, we study the possibility of constructing non-manipulable social choice correspondences when the voters have strict attitudes towards risk. We analyse the trade-off between strategy-proofness and some regularity conditions proposed in the literature like Residual Resoluteness. Moreover, we introduce necessary conditions for strategy-proof and onto social choice correspondences. We also present the requirements in voters' preferences over sets of alternatives that reduce the possibility of strategy-proof correspondences to dictatorial ones.Second, we study the incentives of candidates to enter or to exit elections in order to affect strategically the outcome of a voting correspondence. We show that, if candidates form their preferences over sets according to Expected Utility Theory and Bayesian Updating, every unanimous and non dictatorial voting correspondence violates candidate stability, at least a candidate has incentives to leave the ballot at one profile of preferences. We also analyse the implications of using other extension criteria to define candidate stability that open the door to positive results.Finally, we analyse the strategic incentives of the candidates to withdraw the election in probabilistic environments. We characterise the family of unanimous and candidate stable probabilistic voting procedures when the candidates are expected utility maximisers. Surprisingly, we show that there are rules that are not probabilistic combinations of single-valued candidate stable voting procedures (random dictatorships) that do not provide incentives to the candidates to withdraw the election.

none

To establish the gene expression profile and cascade subsequently on avian sex-determining candidate genes, seven avian sex-determining candidate genes including DMRT1, FET1, FOXL2, LHX9, HINT1, SMC2L1 and SOX9 were analyzed at early embryogenesis. Quantitative reverse transcription PCR (Quantitative RT-PCR) technology was used to establish the gene expression profiles among these genes at four, five, six and seven days of embryos. The results of quantitative RT-PCR reveal that the DMRT1 was expressed in chicken embryos of both sexes. DMRT1 gene expressions were up-regulated at four, five and six days of chicken embryos. DMRT1 expression increased at 5-Dpc. of male embryos, however, expression was not signification different in females embryos. Gene expression of FET1, FOXL2, LHX9 and HINT1 were higher in females than in males. The SMC2L1 and SOX9 were expressed in both sexes. Also, to identify the novel sex-determination genes in early chicken subtractive embryos, cDNA libraries from male-minus-female and female-minus-male 3.5 Dpc. embryos cDNA were established. Gene annotation was carried out by data-mining in public databases, GeneBank (NCBI, USA) and TIGR gene indices (The Institute for Genome Research, USA). A total 548 of colonies in male-minus-female library and 79 sequences were annotated. However, a total of 589 of colonies in female-minus-male library and 16 sequences were annotated. Sequences were homologous to the steroid 5£\-reductase protein (SRD5A1) using BLASTx in male-minus-female subtractive library. The SRD5A1 may play a sex-differentiation role in male chicken. We need more study to know function of steroid 5£\-reductase protein in future.

Bladder cancer is a common malignancy affecting the genitourinary system. Although a large number of studies have been carried out on these areas for a long time, little is know about the molecular events which may involve in tumorigenesis. Until now, no profound immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. The purpose of this thesis is to identify a novel bladder cancer carcinogenesis related genes. Chapter 1 attempts to illustrate the background, molecular markers, chromosomal abnormalities and genetic instability related to bladder cancer. In Chapter 2, various bioinformatics methodologies were used to annotate and identify candidate genes. Twenty-one genes were identified 1.5-fold up- or down-regulated in mRNA expression from RT4, TSGH8301 and J82, three different stages of bladder cancer cell lines by microarray chips (Dr. Liu, personal communications). Another eight candidate tumor suppressor genes were preliminarily identified from suppression subtractive hybridization (SSH) cDNA library of RT4 cell line based on an isoflavones-treated minus non-treated and further subjected to quantitative RT-PCR analyses to confirm the mRNA expression level in different stages of bladder cancer cell lines. Chapter 3 studies on the ANXA10 gene with special emphasis on its cloning, protein expression, subcellular localization and the preparation of polyclonal antibody. The result suggests that ANXA10 is a cytoplasmic protein in N18 cells. Chapter 4 analyzes the CDK2AP1 gene in mRNA and protein level at different bladder cancer cell lines and various specimens. In our preliminary observations, there are lost of CDK2AP1 expressions at invasive TCCs specimens when compared to noninvasive TCCs specimens. The mechanism of the tumor-associated loss of the CDK2AP1 expression is currently not clear. In Chapter 5, bladder cancer cell lines TSGH8301, UB37, TCCSUP and J82 in SCID mice xenograft model were established for further in vivo studies.

Abstract Election to provide opportunities and pipelines for political participation, related to the development of political system and the implementation of democratic politics, the regime is peaceful, orderly transfer of tools, is also an important democratic process, which is a democratic country to maintain political legitimacy of the main Methods, but also non-democratic countries in transition towards a democratic system of government an important mechanism, and voting is the most popular political participation of citizens, the most common, is also close to the general public most likely a form of participation. The study use the visit information of Taiwan elections and democratization investigation in 2006 that relating to Kaohsiung Mayor election survey data, in order to investigate factors influencing the choice of the voters from the social psychology study ways to survey the Michigan Model in party Identification, candidate evaluation, campaign issues and other variables in the voting model of the importance. Finally, we attempt to identify influencing the choice of Kaohsiung people to vote deciding factor. This study showed that, the five social background of voters (including the gender, age, ethnic group, educational level, families income) and party Identification, candidate evaluation, campaign issues, ethnic identity, these five variables and four intermediate variables were significantly associated. Particularly, the ethnic identity is a very important effect and these four intermediary variables also have very significant influence for choice of the voters voting. Polynomial logistic regression was used to establish the simple and complete model in order to check variables and intermediary variables between the relations of voter choice. In simple model was found that party Identification, the five candidate evaluation and the three campaign issues affect the voters choice definitely, especially the party Identification, the relatively reliable in the candidate evaluation and the remedial for the Love River, the completion of Singuang Ferry Wharf in the campaign issues, but to understand that ethnic identity with regard to the voters intention was not significant affects. In complete model showed that the nine variables (including the age, ethnic group, educational level, families income and the party identification, more ability to work, to understand that the people demand, relatively reliable, the most enthusiastic service to the people, remedial for the Love River, the completion of Singuang Ferry Wharf and the incident of walking fees) affect the voting choice of the voters. In particular, age, party identification, have more ability to work, relatively reliable, remedial for the Love River, the completion of Singuang Ferry Wharf were the most important explanatory variables and have significant relevance to the election with the support of the mayor candidates. Party Identification, candidate evaluation, campaign issues, and the ethnic identity of these four variables is a pretty good model that ability to explain the voting behavior. Key words: Voting choice, Party Identification, Candidate evaluation, Campaign issues, Ethnic identity

This research explores whether ¡§party identification, candidate orientation, ethnic identification and issue orientation,¡¨ the four intermediate variables of election, are correlated to the results of Taipei mayor elections in 2002 and 2006. The data in this research are mainly based on the interview broadly carried out to collect facts for ¡§the study on democratization through election¡¨ executed by Professors Huang Chi and Huang Siu-Twen in 2002 and 2005. It is with these data that this research compares the voting behavior of the voters in the two mayor elections in an attempt to find out the deviation of election for further studies. Each individual voter has of his own a variety of social backgrounds which inevitably form to some extent a connection with each of the four intermediate variables. In examination of the connection just mentioned, it is obvious that of all the voter¡¦s backgrounds the place of birth is probably the most potential and influential, and has a significant connection with each of the four factors. However, an evaluation of the connection between the voting preference and the four factors indicates that the four factors are apparently convincing in justification of the results of the second Taipei mayor election in 2006. In addition, a detailed analysis of the connections between voter¡¦s social backgrounds and his voting preference shows that the voter¡¦s place of birth plays an important role in making his voting preference. Other social backgrounds except the voter¡¦s educational level are slightly related to the voting preference in the Taipei mayor election in 2006. Based on the analysis mentioned above, it is understood that there are many variables which will influence the voting preference. Of all the intermediate variables, however, the four factors of party identification candidate orientation ethnic identification and issue orientation are perhaps most crucial and decisive. By means of the analysis and evaluation of the four factors functioning in the recent elections, it is discovered that the people here in Taiwan are relatively better educated and have made a tremendous progress in democracy. It seems that Taiwan has already developed into a nation of two-party politics.

The acknowledgement of the existence of stress changes in the reservoir due to production from a propped-open fracture has resulted in the development of a new concept: oriented or altered-stress refracturing. By initiating a secondary fracture perpendicular to the initial fracture, refracturing makes it possible to access higher pressurized regions of the reservoir, thus improving the productivity of the well. The redistribution of stresses around a fractured vertical well has two sources: (a) opening of propped fracture (mechanical effects) and (b) production or injection of fluids in the reservoir (poroelastic effects). The coupling of both phenomena is numerically modeled to quantify the extent and timing of stress reorientation around fractured production wells. Guidelines and type-curves are established that allow an operator to choose the timing of the refracture operation in the life of the well, and evaluate the potential increase in well production after refracturing. The selection of candidate wells for refracturing is often very difficult based on the information available at the surface. We propose a systematic methodology, based on dimensionless groups, that allows a field engineer to evaluate a well's potential for refracturing from an analysis of field production data and other reservoir data commonly available. This analysis confirms the crucial role played by stress reorientation in the success of refracturing operations. Another topic of interest is the multi-stage fracturing of horizontal wells. The opening of a propped transverse fracture causes a reorientation of stresses in its neighborhood, which in turn affects the direction of propagation of subsequent fractures. This phenomenon, often referred to as stress shadowing, can negatively impact the efficiency of each fracturing stage. By calculating the trajectory of multiple transverse fractures, we offer some insight on the completion designs that will (a) minimize fracture spacing without compromising the efficiency of each fracturing stage and (b) effectively stimulate natural fractures in the vicinity of the created fracture. In addition, a novel detection method of mechanical interference between multiple transverse fractures is established, based on net fracturing pressure data measured in the field, to calculate the optimum fracture spacing for a specific well. / text