CaMKK2 Knockout Bone Marrow Cells Collected/Processed in Low Oxygen (Physioxia) Suggests CaMKK2 as a Hematopoietic Stem to Progenitor Differentiation Fate Determinant

Little is known about a regulatory role of CaMKK2 for hematopoietic stem (HSC) and progenitor (HPC) cell function. To assess this, we used Camkk2−/− and wild type (WT) control mouse bone marrow (BM) cells. BM cells were collected/processed and compared under hypoxia (3% oxygen; physioxia) vs. ambient air (~21% oxygen). Subjecting cells collected to ambient air, even for a few minutes, causes a stress that we termed Extra Physiological Shock/Stress (EPHOSS) that causes differentiation of HSCs and HPCs. We consider physioxia collection/processing a more relevant way to assess HSC/HPC numbers and function, as the cells remain in an oxygen tension closer physiologic conditions. Camkk2−/− cells collected/processed at 3% oxygen had positive and negative effects respectively on HSCs (by engraftment using competitive transplantation with congenic donor and competitor cells and lethally irradiated congenic recipient mice), and HPCs (by colony forming assays of CFU-GM, BFU-E, and CFU-GEMM) compared to WT cells processed in ambient air. Thus, with cells collected/processed under physioxia, and therefore never exposed and naïve to ambient air conditions, CaMKK2 not only appears to act as an HSC to HPC differentiation fate determinant, but as we found for other intracellular mediators, the Camkk−/− mouse BM cells were relatively resistant to effects of EPHOSS. This information is of potential use for modulation of WT BM HSCs and HPCs for future clinical advantage. Graphical Abstract: [Figure not available: see fulltext.]

Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition

PTPN11 encodes the Shp2 non-receptor protein-tyrosine phosphatase implicated in several signaling pathways. Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms. Here we report that Shp2 mutations occur in human acute myeloid leukemia (AML) at a rate of 6.6% (6/91) in the ECOG E1900 data set. We examined the role of mutated Shp2 in leukemias harboring MLL translocations, which co-occur in human AML. The hyperactive Shp2E76K mutant, commonly observed in leukemia patients, significantly accelerated MLL-AF9-mediated leukemogenesis in vivo. Shp2E76K increased leukemic stem cell frequency and affords MLL-AF9 leukemic cells IL3 cytokine hypersensitivity. As Shp2 is reported to regulate anti-apoptotic genes, we investigated Bcl2, Bcl-xL and Mcl1 expression in MLL-AF9 leukemic cells with and without Shp2E76K. Although the Bcl2 family of genes was upregulated in Shp2E76K cells, Mcl1 showed the highest upregulation in MLL-AF9 cells in response to Shp2E76K. Indeed, expression of Mcl1 in MLL-AF9 cells phenocopies expression of Shp2E76K, suggesting Shp2 mutations cooperate through activation of anti-apoptotic genes. Finally, we show Shp2E76K mutations reduce sensitivity of AML cells to small-molecule-mediated Mcl1 inhibition, suggesting reduced efficacy of drugs targeting MCL1 in patients with hyperactive Shp2

SISTEMA WEB DE APOYO A LA DOCENCIA, AL APRENDIZAJE Y A LA GESTIÓN DE DATOS ACADÉMICOS DE ASIGNATURAS UNIVERSITARIAS

 RESUMEN En este artículo se propone un modelo jerárquico de roles de usuario para el diseño de sistemas Web que permite un diseño estructurado de la interfaz de usuario, una mejor adaptabilidad al perfil del usuario y la simplificación de la especificación de tareas del sistema. Dicho modelo ha sido aplicado al desarrollo de un sistema Web, denominado Tutor, que da soporte a la docencia, al aprendizaje y a la gestión de datos académicos (de alumnos, profesores, titulaciones, etc.) relacionados con asignaturas de la Universidad de Granada. El equipo de desarrollo ha estado formado por profesores, estudiantes y técnicos de los servicios de informática y redes de comunicaciones de dicha universidad, por lo que desde el principio se ha tenido presente la finalidad pedagógica de cada utilidad a la hora de incluirla en el sistema. El sistema implementado ofrece una serie de servicios electrónicos, siendo algunos de ellos de acceso libre, mientras que otros son de acceso restringido sólo a usuarios registrados en el sistema (cuando se requiere proteger la privacidad de los datos). La principal finalidad de nuestro sistema consiste en lograr algunos de los objetivos establecidos en el contexto del Espacio Europeo de Educación Superior, que fija y unifica los criterios de calidad que deben cumplir los estudios superiores en los estados miembros.  PALABRAS CLAVESSistema Web de Apoyo a la DocenciaSistema Web de Soporte al AprendizajeTecnologías de la Información y la Comunicación (TIC)Aplicadas a la EducaciónInnovación Docente  ABSTRACT In this paper, we propose a hierarchical model of user roles to be applied in the development of Web-based applications. The model facilitates a structured design of user interfaces, a better adaptability to user profiles and the simplification of the specification of system tasks. This model has been applied to the development of a Web-based system, called Tutor, that provides support for teaching and learning some subjects taught at the University of Granada, and for the management of academic data (of students, teachers, degrees, etc.) related with these subjects. The development team is made up of teachers, students and technicians of computer science and communication network services belonging to this university. For that reason, we have always had in mind the pedagogic purpose of each utility included in the system. The implemented system offers a series of electronic services, some of them are free access, while others are restricted access only to users registered in the system (when data privacy protection is required). The main aim of our system is to achieve some of the objectives established in the context of the European Space of Higher Education, which sets and unifies quality criteria that the higher studies within its member states must satisfy.  KEYWORDSWeb-Based Teaching-Support SystemWeb-Based Learning-Support SystemInformation and Communication Technologies Appliedto EducationTeaching Innovation

SISTEMA WEB DE APOYO A LA DOCENCIA, AL APRENDIZAJE Y A LA GESTIÓN DE DATOS ACADÉMICOS DE ASIGNATURAS UNIVERSITARIAS

 RESUMEN En este artículo se propone un modelo jerárquico de roles de usuario para el diseño de sistemas Web que permite un diseño estructurado de la interfaz de usuario, una mejor adaptabilidad al perfil del usuario y la simplificación de la especificación de tareas del sistema. Dicho modelo ha sido aplicado al desarrollo de un sistema Web, denominado Tutor, que da soporte a la docencia, al aprendizaje y a la gestión de datos académicos (de alumnos, profesores, titulaciones, etc.) relacionados con asignaturas de la Universidad de Granada. El equipo de desarrollo ha estado formado por profesores, estudiantes y técnicos de los servicios de informática y redes de comunicaciones de dicha universidad, por lo que desde el principio se ha tenido presente la finalidad pedagógica de cada utilidad a la hora de incluirla en el sistema. El sistema implementado ofrece una serie de servicios electrónicos, siendo algunos de ellos de acceso libre, mientras que otros son de acceso restringido sólo a usuarios registrados en el sistema (cuando se requiere proteger la privacidad de los datos). La principal finalidad de nuestro sistema consiste en lograr algunos de los objetivos establecidos en el contexto del Espacio Europeo de Educación Superior, que fija y unifica los criterios de calidad que deben cumplir los estudios superiores en los estados miembros.  PALABRAS CLAVESSistema Web de Apoyo a la DocenciaSistema Web de Soporte al AprendizajeTecnologías de la Información y la Comunicación (TIC)Aplicadas a la EducaciónInnovación Docente  ABSTRACT In this paper, we propose a hierarchical model of user roles to be applied in the development of Web-based applications. The model facilitates a structured design of user interfaces, a better adaptability to user profiles and the simplification of the specification of system tasks. This model has been applied to the development of a Web-based system, called Tutor, that provides support for teaching and learning some subjects taught at the University of Granada, and for the management of academic data (of students, teachers, degrees, etc.) related with these subjects. The development team is made up of teachers, students and technicians of computer science and communication network services belonging to this university. For that reason, we have always had in mind the pedagogic purpose of each utility included in the system. The implemented system offers a series of electronic services, some of them are free access, while others are restricted access only to users registered in the system (when data privacy protection is required). The main aim of our system is to achieve some of the objectives established in the context of the European Space of Higher Education, which sets and unifies quality criteria that the higher studies within its member states must satisfy.  KEYWORDSWeb-Based Teaching-Support SystemWeb-Based Learning-Support SystemInformation and Communication Technologies Appliedto EducationTeaching Innovation

Nitrogen fixation and transfer in open ocean diatom–cyanobacterial symbioses

Many diatoms that inhabit low-nutrient waters of the open ocean live in close association with cyanobacteria. Some of these associations are believed to be mutualistic, where N2-fixing cyanobacterial symbionts provide N for the diatoms. Rates of N2 fixation by symbiotic cyanobacteria and the N transfer to their diatom partners were measured using a high-resolution nanometer scale secondary ion mass spectrometry approach in natural populations. Cell-specific rates of N2 fixation (1.15–71.5 fmol N per cell h−1) were similar amongst the symbioses and rapid transfer (within 30 min) of fixed N was also measured. Similar growth rates for the diatoms and their symbionts were determined and the symbiotic growth rates were higher than those estimated for free-living cells. The N2 fixation rates estimated for Richelia and Calothrix symbionts were 171–420 times higher when the cells were symbiotic compared with the rates estimated for the cells living freely. When combined, the latter two results suggest that the diatom partners influence the growth and metabolism of their cyanobacterial symbionts. We estimated that Richelia fix 81–744% more N than needed for their own growth and up to 97.3% of the fixed N is transferred to the diatom partners. This study provides new information on the mechanisms controlling N input into the open ocean by symbiotic microorganisms, which are widespread and important for oceanic primary production. Further, this is the first demonstration of N transfer from an N2 fixer to a unicellular partner. These symbioses are important models for molecular regulation and nutrient exchange in symbiotic systems

Transformer substation of STLmb-6 type with a remote control system

Dotychczas układy sterowania w stacjach są realizowane za pomocą dużych sterowników. Zastosowanie w stacji transformatorowej STLmb-6 silnikowego napędu rozłączników oraz modułów sterownika I/O pozwoliło zbudować układ z możliwością rozbudowy, który pozwala sterować stacją za pośrednictwem dowolnego medium. Moduły analogowe umożliwiają odczytywanie, rejestrowanie i gromadzenie mierzonych wartości, a zastosowany interfejs Ethernet - monitoring i sterowanie stacją przy pomocy istniejącej w obiekcie sieci komputerowej. Taki system pozwala optymalnie zmieniać istniejący układ.Up to now substation control systems have been realised with the use of large controllers. Motor-driven load interrupters and I/O modules applied to a transformer substation make it possible to develop an expandable system that can control a substation via any medium. Analog modules read, record and store the measured values and the applied Ethernet interface enable monitoring and controlling a station by means of the facility computer network. Such a system allows optimal modification of the existing system

Medium voltage distribution board with the use of a new electrical energy measuring system

W artykule przedstawiono nowe rozwiązanie rozdzielnicy stało-powietrznej średniego napięcia typu RSL, w której pomiar energii elektrycznej oparto na przekładnikach prądowo-napięciowych współpracujących z elektronicznym wzmacniaczem sygnału. Układ pomiarowy jest obecnie na etapie badań naukowo-technicznych.The article presents a new medium voltage RSL distribution board in which the measurement of electrical energy was based on current-voltage transformers co-operating with an electronic signal amplifier. The measuring system is currently at the stage of tests