An investigation of genetic variation in complex disorders of the pituitary gland

Congenital hypopituitarism can be triggered by environmental insults, such as viral infections, vascular or degenerative damage and exposure to alcohol and drugs. Genetic mutations have been identified in genes responsible for pituitary development and function, however, only up to 10% of patients affected by hypopituitarism have recognised mutations in known genes. Clinical phenotypes may arise from gene dosage imbalance, but routine cytogenetic and molecular techniques can be insufficiently sensitive to detect chromosome rearrangements that are either submicroscopic in size or limited to a specific genomic locus or both. In the present study, ten patients with a complex pathology of the pituitary gland of unknown aetiology were clinically pre-selected according to a criteria checklist, to undergo a genome-wide screening of copy number changes with high-resolution 250K SNP array. Genomic sequencing of three candidate genes, BARX2, OTX2 and BMP4, was carried out in larger cohorts of selected patients. Three pathogenic genomic imbalances, chromosome 6q terminal duplication, chromosome 11q terminal deletion, and an interstitial deletion of chromosome 22q were detected in two patients, and the breakpoints were defined at high resolution. A submicroscopic rearrangement in the chromosome region 1p36.33 was found in a patient presenting with the association of hypopituitarism and tetralogy of Fallot. Two CNVs were found at the location of the breakpoints of a cytogenetically visible translocation between chromosomes 11q and 22q in one patient. One region of genomic imbalance, identified in one patient, contained the whole length of the ENG gene. A novel amino acid change was identified in BARX2 in a patient with isolated hypopituitarism. A novel nonsense mutation was found in OTX2 in a patient with pathology of the pituitary gland associated wth severe eye defects. These findings contribute to the understanding of the genetic bases of congenital hypopituitarism

Design of an Intrinsically Motivating AR Experience for Environmental Awareness

Augmented Reality seems a promising tool to provide engaging and effective educational experiences, thanks to its potentiality in stimulating intrinsic motivation, that could influence the learning process and the attitude of the users towards behaviours. This paper presents the Resized Plastic Augmented Reality learning experience, designed on the basis of Dunleavy's framework to provide a systemic overview of the microplastics issue to allow users to understand its mechanisms, educate them about their role in the system and help them to connect this information to their everyday actions

Augmented Reality to Engage Visitors of Science Museums through Interactive Experiences

In the last years, interactive exhibitions based on digital technologies have become widely common, thanks to their flexibility and effectiveness in engaging visitors and creating memorable experiences. One of the topics in which digital technologies can be particularly effective is the communication of abstract concepts that are difficult for the human mind to imagine. An emblematic example is the astronomy discipline, which requires us to imagine and understand phenomena far away from our everyday life. In this paper, the authors present a research project, MARSS, in which digital technologies are used effectively to enhance the Users' Experience of the Museo Astronomico di Brera located in Milan. Specifically, the MARSS project aims at designing and developing a new digital journey inside the museum to allow different categories of visitors to enjoy the exhibition in an engaging and interactive way. The paper presents the design and development phases of the experience and its evaluation with users. The results of the evaluation indicate that the digital interactive experience is appreciated by users and is successful in translating the content of high scientific value into more engaging and easily understandable elements

Accuracy and Reliability of Dosing Equations to Individualize Theophylline Treatment of Apnea of Prematurity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90103/1/j.1875-9114.1995.tb04360.x.pd

Ligands of Therapeutic Utility for the Liver X Receptors.

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain

The digital whomanities project. Best practices for digital pedagogy in the pandemic era

This paper aims to enter the ongoing debate about the critical issues of digital pedagogy through the presentation of Digital WHOmanities, a series of online conferences and workshops held at the University of Bologna. Distance learning has become one of the most discussed topics in educational institutions during the spread of Covid-19, revealing a discrepancy between the rapid development of technology and the ability of learning environments to adapt to this turn. In view of this ongoing debate, Digital WHOmanities tried to define the complex and multifaceted figure of the digital humanist and to provide a methodological framework that could foster further online academic initiatives. Specifically, the accurate organization of timing and contents and the adoption of synchronous and asynchronous approaches have highlighted the effectiveness of flexible digital didactics

Stability in a long length NbTi CICC

A crucial issue for a superconducting coil in order to be safely used in the magnetic system of a fusion reactor is stability against all foreseen disturbances. To simulate the fusion machine conditions, including off-normal events, e.g. plasma disruptions, the energy deposition has to be spread over a "long length" cable in conduit conductor (CICC) and a background magnetic field is needed. We have therefore designed and built an experiment consisting of an instrumented NbTi test module inserted in a pair of co-axial pulsed copper coils. A 0.6 m diameter superconducting coil provides a background magnetic field up to 3 T. Calibration of the energy inductively coupled between the pulsed coils and the module has been obtained measuring the system temperature increase just after the pulse by means of thermometers positioned along the conductor. Stability vs. operating current I/sub op/ has been examined for different helium temperatures and different background magnetic fields. The finite element code Gandalf for the stability and quenching transients analysis in forced flow cooled superconducting coils has been run to check the matching with the experimental results. (3 refs)

OS MÚLTIPLOS SABERES NA FORMAÇÃO JURÍDICA: UM RELATO DE EXPERIÊNCIA DA MUDANÇA NA MATRIZ CURRICULAR DO CURSO DE DIREITO DA UniEVANGELICA EM ANÁPOLIS, GOIÁS.

Este artigo é resultado de uma ampla discussão acadêmica, vivenciada pelo colegiado do Curso de Direito no Centro Universitário de Anápolis e que os professores/autores fizeram questão de registrar. Também, representa asocialização de experiências do Núcleo Docente Estruturante (NDE) no sentido de construir um projeto pedagógico que supere os entraves do conservadorismo rumo a uma formação integral, humanista e interdisciplinar. Nossa intenção não é apresentar um novo modelo curricular, mas apresentar as nossas experiências coletivas em pensar um curso de Direito que leve em consideração a multiplicidadede olhares necessários à formação do estudante de direito. Nesse sentido, não esperamos, com esse relato, apresentar um modelo acabado, longe disso. Muito mais, registrar a nossa experiência na construção coletiva de um projeto de curso e os nossos argumentos na defesa dessa proposta apresentada

Smith-Magenis sindrome and growth hormone deficiency

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome including physical and neurobehavioural features. The disease is commonly associated with a ca. 3.7 Mb interstitial deletion of chromosome 17p11.2, while a 1.1 Mb critical region has been identified, containing about 20 genes expressed in multiple tissues. Haploinsufficiency of one of them, RAI1, seems to be responsible for the neurobehavioural, craniofacial and otolaryngological features of the syndrome, but not for short stature, commonly seen in SMS patients with chromosome deletion, implying the role of other genes in the 17p11.2 region. Growth failure is a final result of several different mechanisms involving decreased growth hormone (GH) production, reduced tissue response to GH, or impaired activity of epistatic factors. To our knowledge, the association of GH deficiency with SMS has never been reported and rarely investigated, despite the very short stature of SMS patients. We describe a girl with a full SMS phenotype and a typical 3.7 Mb deletion of 17p11.2 who also has GH deficiency. After starting replacement therapy, growth has significantly improved, her stature being now above both the 10th percentile and her genetic target. CONCLUSION: we suggest that an investigation of both growth hormone secretion and function is carried out in patients with Smith-Magenis syndrome and 17p11.2 deletion

Super-heavy fermion material as metallic refrigerant for adiabatic demagnetization cooling

Low-temperature refrigeration is of crucial importance in fundamental research of condensed matter physics, as the investigations of fascinating quantum phenomena, such as superconductivity, superfluidity and quantum criticality, often require refrigeration down to very low temperatures. Currently, cryogenic refrigerators with $^3$He gas are widely used for cooling below 1 Kelvin. However, usage of the gas is being increasingly difficult due to the current world-wide shortage. Therefore, it is important to consider alternative methods of refrigeration. Here, we show that a new type of refrigerant, super-heavy electron metal, YbCo$_2$Zn$_{20}$, can be used for adiabatic demagnetization refrigeration, which does not require 3He gas. A number of advantages includes much better metallic thermal conductivity compared to the conventional insulating refrigerants. We also demonstrate that the cooling performance is optimized in Yb$_{1-x}$Sc$_x$Co$_2$Zn$_{20}$ by partial Sc substitution with $x\sim$0.19. The substitution induces chemical pressure which drives the materials close to a zero-field quantum critical point. This leads to an additional enhancement of the magnetocaloric effect in low fields and low temperatures enabling final temperatures well below 100 mK. Such performance has up to now been restricted to insulators. Since nearly a century the same principle of using local magnetic moments has been applied for adiabatic demagnetization cooling. This study opens new possibilities of using itinerant magnetic moments for the cryogen-free refrigeration