Distribution of microelements in human articular cartilage : initial report

The aim of this study was evaluation of distribution microelements in human articular cartilage and to determine factors influencing it. The following elements were taken under consideration: Mg, Ca, Zn, Fe, Pb. Their concentration was assessed in the articular cartilage harvested from the loaded an unloaded area of human femoral heads. Initial results indicate that mechanical loadings are one of the important factors influencing distribution of microelements in human articular cartilage

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway(1,2). Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis

Immunohistochemistry on a Panel of Emery-Dreifuss Muscular Dystrophy Samples Reveals Nuclear Envelope Proteins as Inconsistent Markers for Pathology

Reports of aberrant distribution for some nuclear envelope proteins in cells expressing a few Emery–Dreifuss muscular dystrophy mutations raised the possibility that such protein redistribution could underlie pathology and/or be diagnostic. However, this disorder is linked to 8 different genes encoding nuclear envelope proteins, raising the question of whether a particular protein is most relevant. Therefore, myoblast/fibroblast cultures from biopsy and tissue sections from a panel of nine Emery–Dreifuss muscular dystrophy patients (4 male, 5 female) including those carrying emerin and FHL1 (X-linked) and several lamin A (autosomal dominant) mutations were stained for the proteins linked to the disorder. As tissue-specific nuclear envelope proteins have been postulated to mediate the tissue-specific pathologies of different nuclear envelopathies, patient samples were also stained for several muscle-specific nuclear membrane proteins. Although linked proteins nesprin 1 and SUN2 and muscle-specific proteins NET5/Samp1 and Tmem214 yielded aberrant distributions in individual patient cells, none exhibited defects through the larger patient panel. Muscle-specific Tmem38A normally appeared in both the nuclear envelope and sarcoplasmic reticulum, but most patient samples exhibited a moderate redistribution favouring the sarcoplasmic reticulum. The absence of striking uniform defects in nuclear envelope protein distribution indicates that such staining will be unavailing for general diagnostics, though it remains possible that specific mutations exhibiting protein distribution defects might reflect a particular clinical variant. These findings further argue that multiple pathways can lead to the generally similar pathologies of this disorder while at the same time the different cellular phenotypes observed possibly may help explain the considerable clinical variation of EDMD

Frankenstein's robot manipulator

The goal of this project was to design, build, program, upgrade, and remotely control an existing industrial-grade robotic manipulator on a budget that was equal to a graduate student's salary. Inverse kinematic equations were developed to model the CRS arm using Denavit-Hartenberg convention. After converting these equations into a system of Python code, the equations were verified via graphical simulation. The CRS arm's obsolete motor driver box was completely removed and replaced with cutting-edge, low-cost microcontrollers. The wiring, mechanics, and controls for the five degrees of freedom (DOF) were reverse engineered based on very limited datasheets, including the arm's motors, brakes, encoder pin-outs, gripper, and fixed global reference frame movement. The microcontrollers were then programmed in C/C++ to allow a user to control every electrical and mechanical aspect of the arm. The kinematic equations were implemented on a Python server, which commands how each joint in the robotic arm must move to reach a desired point in space. The user interface was developed in conjunction with Evan Boldt to allow for remote control of the robotic arm and monitoring through webcams, which includes twisting and tilting a tablet

PROBLEMS IN THE IMPLEMENTATION OF THE CIVIL BUDGET ON THE EXAMPLE OF THE CITY OF KRAKÓW IN 2016 AND 2018.

Przedmiotem niniejszej pracy było wskazanie problemów pojawiających się podczas realizacji wygranych projektów w ramach Budżetu Obywatelskiego na przykładzie Miasta Krakowa w latach 2016 i 2018 oraz ukazanie nieprawidłowości pojawiających się podczas realizacji projektów. Wiedza teoretyczna została opartao autorów takich jak: G. Prawelska-Skrzypek, M. Trocki i wielu innych. Wiedza teoretyczna oraz wyniki badań zostały uporządkowane zgodnie z logiką.W pierwszej kolejności zaprezentowane zostały pojęcia związane z rodzajami projektów oraz cyklem życia projektu wraz z typami projektów w sektorze publicznymi i ich charakterystyką. Następnie został przedstawiony proces realizacji inicjatyw budżetu obywatelskiego w latach 2016 i 2018 ze wskazaniem występujących projektów. Do przeprowadzenia niniejszej pracy zostały wykorzystane dwie metody badawcze. Pierwszą z nich jest wywiad pogłębiony z dwiema ważnymi osobami, którymi są przedstawiciel Urzędu Miasta Krakowa oraz jeden z twórców projektu “Skrzydła Krakowa”, który prosił o zachowanie anonimowości podczas przeprowadzanego wywiadu. Kolejną metodą była analiza danych zastanych, która opierała się głównie na analizie raportów ewaluacyjnych z lat 2016 i 2018. Wyniki badań wykazały, że większość osób dostrzegało problemy podczas realizacji projektów oraz wskazywały rozwiązania, które mogły zostać wykorzystane w przyszłości.The subject of this work was to identify the problems that arose during the implementation of the winning projects under the Civic Budget on the example of the City of Krakow in 2016 and 2018. The work aimed to show the irregularities that occurred during the implementation of projects. The theoretical knowledge was based on authors such as G. Prawelska-Skrzypek, M. Trocki and many others.The theoretical knowledge and research results have been organized according to logic. First, the concepts related to the types of projects and the project life cycle were presented along with the types of projects in the public sector and their characteristics. Then, the process of implementing the civic budget initiatives in 2016 and 2018 was presented, with an indication of the existing projects.Two research methods were used to carry out this work. The first is an in-depth interview with two important people, who are a representative of the Krakow City Hall and one of the creators of the "Wings of Krakow" project, who asked for anonymity during the interview. Another method was the analysis of existing data, which was based mainly on the analysis of evaluation reports from 2016 and 2018. The results of the research showed that most people saw problems during the implementation of projects and indicated solutions that could be used in the future