Developmental dynamics of cardiac progenitors and their role in congenital heart defects

Cardiac progenitors are the fundamental building blocks of the heart and play a central role in the pathogenesis of congenital heart defects. Recent single-cell RNA sequencing studies have revealed that the cell populations in both developing and mature heart are more diverse than previously recognized. In particular, there has been a great interest in characterizing the transcriptional signatures of human cardiac progenitor populations and building a roadmap of the early heart lineages. This thesis work is a part of an ongoing effort to map the early human heart progenitors, their developmental dynamics and their role in the pathogenesis of congenital heart defects at a single-cell resolution. In paper I, we present a single-cell characterization of in vitro cardiac differentiation of human embryonic stem cells to beating cardiomyocytes and other populations. We used single-cell RNA sequencing data integration to compare the in vitro-derived cardiac cells to human embryonic heart, studied the developmental dynamics of cardiac progenitors by building a differentiation roadmap, and investigated the effect of loss of ISL1 transcription factor on the differentiation process. In paper II, we mapped the genetic landscape of non-syndromic Tetralogy of Fallot, a form of complex congenital heart defect, in a cohort of 146 patient-parent trios. We intersected the identified disease-associated genes with single-cell RNA sequencing analysis of in vivo and in vitro human cardiac development generated by us and other laboratories. Interestingly, we could pinpoint cardiac progenitors as a cellular hotspot in cardiac disease pathogenesis. Paper III introduces a novel cardiac progenitor marked by LGR5, which exists both in the human embryonic heart in vivo and the human embryonic stem cell cardiac differentiation system in vitro. The LGR5+ cono-ventricular progenitor population originates from the ISL1+ progenitor pool and populates the cardiac outflow tract, a cardiac region often affected in congenital heart defects. Taken together, these studies support the importance of cardiac progenitors in the pathogenesis of cardiac abnormalities and explore their developmental dynamics at a singlecell level

Exploring the Role of Syntactic Information on User Behavior in Online Social Platforms

The proliferation of information technologies, applications and online services has changed the way users access information. In particular, an increasing amount of users engage with online social platforms on a daily basis where they are exposed to a continuous stream of information. A great deal of this information is available through numbers and numbers as self-representative visualisations such as likes, views, shares, endorsements and diggs, which sparked an interest in its role in influencing users. This study thus explores the role of syntactic information on user behaviour in online social platforms. The investigation introduces a taxonomy based on four categories (push, pull, personal, and public) as a possible departure point for discussion. The results suggested that users are particularly interested and motivated by personally attributed syntactical information and claim to dismiss the equivalent of public information. Nevertheless, it became clear that public syntactic information was still unconsciously processed and applied as a measure or benchmark on the online social content

Resistance is Utile

The declining access to public service is a concern for most rural areas in Sweden. This study aims to understand how civil society organize in order to maintain public service with the example of the occupation of Sollefteå Hospital. The protest opposes the closure of acute health care wards, most notably the maternity ward. I examine how the resistance is an expression of conflicting descriptions of reality. The neolib-eral discourse within the medical field constructs a logic, where highly centralised, cost-effective health care is the most rational and where efficiency is estimated on explicit and measurable goals. With the Foucauldian concepts of discourse, biopower and governmentality, I argue that within this discourse the identity of the citizens that are to be governed and disciplined is constructed. Thereto the responsibility for ac-cessing health care is put on the individual. For the expecting rural mothers this takes form in self-regulating injunctions, such taking classes in car-births or simply leaving the rural area, during late pregnancy or for good. By organizing resistance, the civil society is condemning the rational of the discourse as well as it’s depicting of them-selves and the rural which is perceived as a place of lack of modernity and economic hardship. This thesis suggests that by framing their actions and creating a collective identity based on the cultural heritage of ‘Red Ådalen’; a shared memory and previ-ous forms of resistance are used as a tool to regain access to health care. The findings also suggest that the usage of cooperative strategies and a repertoire connected to the cultural heritage of ‘Red Ådalen’, has gained recognition and legitimacy from the public, although being a subversive and by principle an illegal action

Determination of Tool Profile for the Milling of Three Screw Pump Rotor

partially_open2The rotors of three screw pumps are commonly machined using shaped milling cutters. The determination of the exact shape of the cutter is very important, since a high precision in the machining is required to obtain a high volumetric efficiency of the pump. This paper describes a method to determine the theoretical shape of the cutter, starting from the characteristic parameters of the pump. The rotors are modeled in space by helicoids. Then, the contact line between the tool and the workpiece is determined and this allows us to define the exact cutter profile, with a suitable reference system transformation.MIMMI G.; PENNACCHI P.Mimmi, Giovanni; Pennacchi, PAOLO EMILIO LINO MARI

Deviations Induced by Tool Sharpening in the Profile of Three Screw Pump Rotors

Three screw pumps represent an important family of positive displacement rotary pumps. They are quite easy to construct, even if the use of a shaped milling cutter for the rotor machining can cause some problems when the tool is not new. In fact the sharpening of the tool modifies the total geometry of the milling cutter by reducing its diameter. The shape of the single cutter does not change, but the cutter radial position is shifted towards the tool center. This causes deviations in the profile cut and the screws consequently need a long breaking in. In this paper the problem is analyzed from a quantitative point of view, using a method that allows us to determine the machining error as a function of the tool geometry variation. Moreover some alternative solutions to this problem are suggested

Non Undercutting Conditions in Internal Gears

Many contributions regarding internal gear theory exist in literature. They mainly consider the problem of undercutting by means of analytical methods applied to specific and limited cases. The present paper deals with a general method showing the analytical condition for avoiding undercutting by the use of the concept of the limit curve. In particular the analytical determination of the limit curve allows the designer to obtain significant graphical representations of the design limits

Pre-shaping motion input for a rotating flexible link

The interest in the design of manipulators for space operations with a light structure has grown meaningfully in comparison with rigid manipulators, even if these flexible manipulators are unavoidably characterized by a not negligible structural flexibility. This paper deals with the first phase of a project financed by a grant from the Italian Space Agency (ASI) which is concerned with the setting up of an open loop control for a planar manipulator with flexible linkages. In this phase, the project is subdivided into two parts: on one hand, different command inputs have been proposed for point to point operations; on the other hand, dynamic simulations have been carried out by using a multibody model with flexible parts, in order to evaluate the residual vibrations due to the selected command input at the end of the motion. These command inputs will be applied to the actual manipulator, which is already available, in a future phase of the project. The command inputs, which are described here, are based on both the convolution of special impulse inputs suitably chosen on the basis of the system natural frequencies and the reduction of impulsive inertia forces by means of a suitable algorithm proposed here and derived from cam design. The simulations are carried out by commercial software for the study of multibody systems and custom programs for the command input implementation. The results obtained for the residual vibrations are compared to those obtained by conventional command inputs in the simulations on the same model

Analytical Model of a Particular Type of Positive Displacement Blower

Many papers exist in literature which deal with the twin screw compressor; this usually has two different rotors, a male and a female, and is commonly used to produce compressed gas for industrial uses. However, a different type of positive displacement rotary compressor with two screws is sometimes used; one of its typical applications is in car engine supercharging. Present paper deals with the latter type, which is defined as a two screw blower. This blower has two identical helical rotors, each with three lobes. The kinematics and the geometry of the rotors are analysed here, and a complete mathematical model for the rotor is defined. Moreover different possible shapes of the rotors, depending on the design parameters, are analysed and the limitations in the choice of the design parameters are presented. Finally an analysis of the theoretical specific slipping of the rotors is presented, showing which zones of the profile are the most stressed. This model will be useful for further studies on rotor pressure loads and blower dynamics

Violence in African Elections: Between Democracy and Big Man Politics

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