FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism

A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function

Prefrontal control of familiarity and recollection in working memory

Left inferior frontal gyrus (IFG) is a critical neural substrate for the resolution of proactive interference (PI) in working memory. We hypothesized that left IFG achieves this by controlling the influence of familiarity- versus recollection-based information about memory probes. Consistent with this idea, we observed evidence for an early (200 msec)-peaking signal corresponding to memory probe familiarity and a late (500 msec)-resolving signal corresponding to full accrual of trial-related contextual ("recollection-based") information. Next, we applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time locked to these mnemonic signals, to left IFG and to a control region. Only early rTMS of left IFG produced a modulation of the false alarm rate for high-PI probes. Additionally, the magnitude of this effect was predicted by individual differences in susceptibility to PI. These results suggest that left IFG-based control may bias the influence of familiarity- and recollection-based signals on recognition decisions

Amifostine (wr-2721), A Cytoprotective Agent During High-dose Cyclophosphamide Treatment Of Non-hodgkin's Lymphomas: A Phase Ii Study.

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.33791-

Oscillator neural network model with distributed native frequencies

We study associative memory of an oscillator neural network with distributed native frequencies. The model is based on the use of the Hebb learning rule with random patterns ($\xi_i^{\mu}=\pm 1$), and the distribution function of native frequencies is assumed to be symmetric with respect to its average. Although the system with an extensive number of stored patterns is not allowed to get entirely synchronized, long time behaviors of the macroscopic order parameters describing partial synchronization phenomena can be obtained by discarding the contribution from the desynchronized part of the system. The oscillator network is shown to work as associative memory accompanied by synchronized oscillations. A phase diagram representing properties of memory retrieval is presented in terms of the parameters characterizing the native frequency distribution. Our analytical calculations based on the self-consistent signal-to-noise analysis are shown to be in excellent agreement with numerical simulations, confirming the validity of our theoretical treatment.Comment: 9 pages, revtex, 6 postscript figures, to be published in J. Phys.

A critique of Paulo Freire’s perspective on human nature to inform the construction of theoretical underpinnings for research

From Crossref via Jisc Publications RouterHistory: epub 2020-04-20, issued 2020-04-20Article version: VoRKate Sanders - ORCID 0000-0003-3516-7030 https://orcid.org/0000-0003-3516-7030This article presents a critique of Paulo Freire's philosophical perspective on human nature in the context of a doctoral research study to explore “muchness” or nurses’ subjective experience of well‐being; and demonstrates how this critique has informed the refinement of the theoretical principles used to inform research methodology and methods. Engaging in philosophical groundwork is essential for research coherence and integrity. Through this groundwork, largely informed by Freire's critical pedagogy and his ideas on humanization, I recognized the need to clarify my understanding of the concepts of persons and personhood and how this related to Freire's use of the term human beings. This clarification process is essential to ensure congruence between the theoretical principles that I draw from his work and my beliefs about persons, personhood and person‐centredness. The article begins with a brief introduction to the research, followed by an overview of Freire's philosophical perspectives, and subsequently, the critique process is presented and discussed. This process involved engaging with the vast literature and debates about what it means to be a person, to make sense of the often complex and contradictory arguments. Eventually, three headings emerged that helped me to frame my evolving understanding: Our species: human beings ; The kind that we are: human nature ; and This person that I am: personhood. Through this process of exploration, I recognized that Freire's perspective on human nature (a) foregrounded cognitive rationality, which presented itself as a limitation when considering my ontological beliefs and the focus of my research, leading me to draw on the work of Mark Johnson and his ideas about embodiment to help me to further develop my theoretical principles; (b) focused on the “collective” rather than individuals, which is a shortcoming in relation to person‐centred research that acknowledges the uniqueness of participants.21pubpub

Providing Self-Aware Systems with Reflexivity

We propose a new type of self-aware systems inspired by ideas from higher-order theories of consciousness. First, we discussed the crucial distinction between introspection and reflexion. Then, we focus on computational reflexion as a mechanism by which a computer program can inspect its own code at every stage of the computation. Finally, we provide a formal definition and a proof-of-concept implementation of computational reflexion, viewed as an enriched form of program interpretation and a way to dynamically "augment" a computational process.Comment: 12 pages plus bibliography, appendices with code description, code of the proof-of-concept implementation, and examples of executio

Democratic Teacher Education Practices

[Living reference work entry] This entry provides an insight into the turbulent and recently disappointing events in the history of Design and Technology (D&T) teacher education in England over the last 150 years. It is a complex journey that needs to include a review of the generic history of teacher education in England, the differing educational needs of children, the changing role of D&T as a school curriculum subject, the requirements for an appropriately trained workforce to meet the economic needs of the country, and how various government educational initiatives and interventions (Gillard 2018) have affected how teachers in general and D&T teachers in particular have been and still are trained today. All these factors are inseparably intertwined. Therefore, this entry discusses them all together in chronological date order

On the reciprocal interaction between believing and feeling: an adaptive agent modelling perspective

An agent’s beliefs usually depend on informational or cognitive factors such as observation or received communication or reasoning, but also affective factors may play a role. In this paper, by adopting neurological theories on the role of emotions and feelings, an agent model is introduced incorporating the interaction between cognitive and affective factors in believing. The model describes how the strength of a belief may not only depend on information obtained, but also on the emotional responses on the belief. For feeling emotions a recursive body loop between preparations for emotional responses and feelings is assumed. The model introduces a second feedback loop for the interaction between feeling and belief. The strength of a belief and of the feeling both result from the converging dynamic pattern modelled by the combination of the two loops. For some specific cases it is described, for example, how for certain personal characteristics an optimistic world view is generated in the agent’s beliefs, or, for other characteristics, a pessimistic world view. Moreover, the paper shows how such affective effects on beliefs can emerge and become stronger over time due to experiences obtained. It is shown how based on Hebbian learning a connection from feeling to belief can develop. As these connections affect the strenghts of future beliefs, in this way an effect of judgment ‘by experience built up in the past’ or ‘by gut feeling’ can be obtained. Some example simulation results and a mathematical analysis of the equilibria are presented

2.4 Magnetic resonance imaging, ultrasonography and conventional radiography in the assessment of bone erosions in juvenile idiopathic arthritis

OBJECTIVE: To compare magnetic resonance imaging (MRI), conventional radiography, and ultrasonography in identifying bone erosions in patients with juvenile idiopathic arthritis (JIA), and to determine the validity and reliability of an MRI scale in detecting and grading joint damage. METHODS: In 26 JIA patients, the clinically more affected wrist was studied with MRI, radiography, and ultrasonography, coupled with standard clinical assessment and biochemical analysis. MR images were assessed independently by 2 readers according to an apposite devised scoring system. RESULTS: Of 26 patients, 25 (96.1%) had 1 or more erosions as detected by MRI, whereas conventional radiography and ultrasonography revealed erosions in 13 (50%) of 26 and 12 (50%) of 24 patients, respectively. The ability of MRI to detect erosive changes was significantly higher with respect to conventional radiography (P = 0.002 with Bonferroni correction [P(B)]) and ultrasonography (P(B) = 0.0002) in the group of patients with <3 years' disease duration. Ultrasonography and conventional radiography were of equivalent value for the detection of destructive changes. Wrist MRI score correlated highly with radiographic erosion score (r(s) = 0.82) and with wrist limited range of motion score (r(s) = 0.69). The interreader intraclass correlation coefficient (ICC) for MRI score was excellent (0.97); intrareader ICCs were good for both investigators (0.97 and 0.79). CONCLUSION: MRI seems to be a powerful tool to detect early structural damage in JIA. The proposed MRI scale for bone erosions appears promising in terms of reliability and construct validity. The pathophysiologic meaning and the prognostic value of bone erosions revealed only by MRI remain to be established in longitudinal studies