BREATHE to Understand

BREATHE is an acronym for Breathe, Reflect, Empathize, Accept, Thank, Hearten, Engage. The addition of Understand allows for a holistic approach to living a healthy and balanced life both inside and outside the classroom. This paper took form as a result of my personal, spiritual journey, as well as my teaching practice. I noticed that the majority of my students enjoyed experiential activities that included time and space for self-reflection, relaxation and meditation. I began looking for books, seminars, and workshops that explored these areas. Deepak Chopra, Jonathan Kabat-Zinn, Dan Siegel, Eckhart Tolle, et al. offer insights into the benefits of meditation and mindfulness as a vehicle for improved quality of life. His Holiness the Dalai Lama describes compassion as a basic human value that is separate from religious practices and beliefs. The positive effects of gratitude on a person’s well-being have been studied by Dr. Robert Emmons and others. In addition, Charles A. Curran writes about the importance of understanding and its connection to our sense of belonging. SIT Graduate Institute’s focus on reflective teaching practices is another piece of the puzzle that creates a holistic approach to life-long learning. Each chapter includes practical activities for EFL teachers to use in the classroom. The goal of this paper is to provide a framework for EFL teachers, students and anyone interested in lifelong learning to incorporate activities that enable all of us to BREATHE to Understand as a part of our daily lives

Domestic bliss : how a group of white South Africans understand their relationships with the domestic workers who helped to raise them.

In the dearth of literature regarding domestic workers in general, there is a notable absence of the relationships formed between domestic workers and their employers’ children. Nine young white adults who self-identified themselves as having a close relationship with their families’ domestic workers for a minimum of ten years, were interviewed on the nature of this closeness and what it means in the context of the family and in South Africa. These participants shared the significance of their domestic workers in their lives, highlighting their integration into the family structure. These women often filled in for absent parents or mediated conflicted parent-child interactions, serving as a unique support system for the participants. However, contradictory evidence was also apparent as the boundaries between domestic workers and the participants’ families were described. Issues of race and social difference were cloaked in a silence perceived to be an aspect of concealing the uncomfortable elements of whiteness and the implicit understandings of the institution of domestic work. When these matters were addressed, the interviewees were often ambivalent about their own role in maintaining this norm. Exploring the less than perfect parts of the relationship with these caregivers seemed to threaten the very foundations of the relationship. The findings in this report support the argument that having multiple caregivers is optimal for children’s development but when the third caregiver is a black domestic worker the benefits of this arrangement are complicated by racial, social and class constructions. Moreover, constructions of the ideal Western family create friction in allowing a non-relative to be fully integrated into the family

Sustainable Finance in Southeast Asia

This chapter provides an overview of sustainable finance policies and frameworks that have been established in Southeast Asian countries and at the regional level, reviews developments in sustainable financial markets across the region, contextualises the challenges in scaling up sustainable finance and investment, and discusses the opportunities and actions that could be undertaken both individually and collectively. It provides recommendations for ASEAN countries to further align finance with sustainability objectives

SubTuning: Efficient Finetuning for Multi-Task Learning

Finetuning a pretrained model has become a standard approach for training neural networks on novel tasks, resulting in fast convergence and improved performance. In this work, we study an alternative finetuning method, where instead of finetuning all the weights of the network, we only train a carefully chosen subset of layers, keeping the rest of the weights frozen at their initial (pretrained) values. We demonstrate that \emph{subset finetuning} (or SubTuning) often achieves accuracy comparable to full finetuning of the model, and even surpasses the performance of full finetuning when training data is scarce. Therefore, SubTuning allows deploying new tasks at minimal computational cost, while enjoying the benefits of finetuning the entire model. This yields a simple and effective method for multi-task learning, where different tasks do not interfere with one another, and yet share most of the resources at inference time. We demonstrate the efficiency of SubTuning across multiple tasks, using different network architectures and pretraining methods

Loss of Liver Kinase B1 (LKB1) in Beta Cells Enhances Glucose-stimulated Insulin Secretion Despite Profound Mitochondrial Defects

The tumor suppressor liver kinase B1 (LKB1) is an important regulator of pancreatic β cell biology. LKB1-dependent phosphorylation of distinct AMPK (adenosine monophosphate-activated protein kinase) family members determines proper β cell polarity and restricts β cell size, total β cell mass, and glucose-stimulated insulin secretion (GSIS). However, the full spectrum of LKB1 effects and the mechanisms involved in the secretory phenotype remain incompletely understood. We report here that in the absence of LKB1 in β cells, GSIS is dramatically and persistently improved. The enhancement is seen both in vivo and in vitro and cannot be explained by altered cell polarity, increased β cell number, or increased insulin content. Increased secretion does require membrane depolarization and calcium influx but appears to rely mostly on a distal step in the secretion pathway. Surprisingly, enhanced GSIS is seen despite profound defects in mitochondrial structure and function in LKB1-deficient β cells, expected to greatly diminish insulin secretion via the classic triggering pathway. Thus LKB1 is essential for mitochondrial homeostasis in β cells and in parallel is a powerful negative regulator of insulin secretion. This study shows that β cells can be manipulated to enhance GSIS to supra-normal levels even in the face of defective mitochondria and without deterioration over months

mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes.

Pancreatic beta cells (β-cells) differentiate during fetal life, but only postnatally acquire the capacity for glucose-stimulated insulin secretion (GSIS). How this happens is not clear. In exploring what molecular mechanisms drive the maturation of β-cell function, we found that the control of cellular signaling in β-cells fundamentally switched from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK), and that this was critical for functional maturation. Moreover, AMPK was activated by the dietary transition taking place during weaning, and this in turn inhibited mTORC1 activity to drive the adult β-cell phenotype. While forcing constitutive mTORC1 signaling in adult β-cells relegated them to a functionally immature phenotype with characteristic transcriptional and metabolic profiles, engineering the switch from mTORC1 to AMPK signaling was sufficient to promote β-cell mitochondrial biogenesis, a shift to oxidative metabolism, and functional maturation. We also found that type 2 diabetes, a condition marked by both mitochondrial degeneration and dysregulated GSIS, was associated with a remarkable reversion of the normal AMPK-dependent adult β-cell signature to a more neonatal one characterized by mTORC1 activation. Manipulating the way in which cellular nutrient signaling pathways regulate β-cell metabolism may thus offer new targets to improve β-cell function in diabetes

LKB1 and AMPK differentially regulate pancreatic β-cell identity.

Fully differentiated pancreatic β cells are essential for normal glucose homeostasis in mammals. Dedifferentiation of these cells has been suggested to occur in type 2 diabetes, impairing insulin production. Since chronic fuel excess ("glucotoxicity") is implicated in this process, we sought here to identify the potential roles in β-cell identity of the tumor suppressor liver kinase B1 (LKB1/STK11) and the downstream fuel-sensitive kinase, AMP-activated protein kinase (AMPK). Highly β-cell-restricted deletion of each kinase in mice, using an Ins1-controlled Cre, was therefore followed by physiological, morphometric, and massive parallel sequencing analysis. Loss of LKB1 strikingly (2.0-12-fold, E<0.01) increased the expression of subsets of hepatic (Alb, Iyd, Elovl2) and neuronal (Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamate signaling. These changes were partially recapitulated by the loss of AMPK, which also up-regulated β-cell "disallowed" genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8- to 3.4-fold (E<0.01). Correspondingly, targeted promoters were enriched for neuronal (Zfp206; P=1.3×10(-33)) and hypoxia-regulated (HIF1; P=2.5×10(-16)) transcription factors. In summary, LKB1 and AMPK, through only partly overlapping mechanisms, maintain β-cell identity by suppressing alternate pathways leading to neuronal, hepatic, and other characteristics. Selective targeting of these enzymes may provide a new approach to maintaining β-cell function in some forms of diabetes.-Kone, M., Pullen, T. J., Sun, G., Ibberson, M., Martinez-Sanchez, A., Sayers, S., Nguyen-Tu, M.-S., Kantor, C., Swisa, A., Dor, Y., Gorman, T., Ferrer, J., Thorens, B., Reimann, F., Gribble, F., McGinty, J. A., Chen, L., French, P. M., Birzele, F., Hildebrandt, T., Uphues, I., Rutter, G. A. LKB1 and AMPK differentially regulate pancreatic β-cell identity

Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets

It has been well established that excessive levels of glucose and palmitate lower glucose-stimulated insulin secretion (GSIS) by pancreatic beta cells. This beta cell 'glucolipotoxicity' is possibly mediated by mitochondrial dysfunction, but involvement of bioenergetic failure in the pathological mechanism is subject of ongoing debate. We show here that increased palmitate levels impair GSIS before altering mitochondrial function. We demonstrate that GSIS defects arise from increased insulin release under basal conditions in addition to decreased insulin secretion under glucose-stimulatory conditions. Real-time respiratory analysis of intact mouse pancreatic islets reveals that mitochondrial ATP synthesis is not involved in the mechanism by which basal insulin is elevated. Equally, mitochondrial lipid oxidation and production of reactive oxygen species do not contribute to increased basal insulin secretion. Palmitate does not affect KCl-induced insulin release at a basal or stimulatory glucose level, but elevated basal insulin release is attenuated by palmitoleate and associates with increased intracellular calcium. These findings deepen our understanding of beta cell glucolipotoxicity and reveal that palmitate-induced GSIS impairment is disconnected from mitochondrial dysfunction, a notion that is important when targeting beta cells for the treatment of diabetes and when assessing islet function in human transplants