fundamental challenge
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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda Henwood ◽  
João Guerreiro ◽  
Aleksandar Matic ◽  
Paul Dolan

AbstractIt is widely assumed that the longer we spend in happier activities the happier we will be. In an intensive study of momentary happiness, we show that, in fact, longer time spent in happier activities does not lead to higher levels of reported happiness overall. This finding is replicated with different samples (student and diverse, multi-national panel), measures and methods of analysis. We explore different explanations for this seemingly paradoxical finding, providing fresh insight into the factors that do and do not affect the relationship between how happy we report feeling as a function of how long it lasts. This work calls into question the assumption that spending more time doing what we like will show up in making us happier, presenting a fundamental challenge to the validity of current tools used to measure happiness.


2022 ◽  
Vol 65 (1) ◽  
pp. 50-54
Author(s):  
Patrick Thomson

The fundamental challenge of software engineering is one of complexity.


Author(s):  
Jamie Levine Daniel ◽  
Fredrik Andersson

The question of when a new nonprofit is founded has not been pursued with sufficient precision. Specifically, a fundamental challenge facing any nonprofit researcher planning to detect, isolate, and analyze new nonprofits is that nonprofit founding is a process, not a discrete event. This study uses administrative data that includes three different founding indicators from more than 4,000 arts organizations, supplemented with survey data from 242 organizations, to illustrate some of the problems inherent in treating the founding process as one discrete event. It also elevates the voices of founders to demonstrate their conceptualization of the concept and offer insights into the multidimensionality of founding.  


Author(s):  
Benlin Sun ◽  
Lei Hou ◽  
Binbin Sun ◽  
Yu Han ◽  
Yunqing Zou ◽  
...  

The fabrication of tissue-engineered vascular grafts to replace damaged vessels is a promising therapy for cardiovascular diseases. Endothelial remodeling in the lumen of TEVGs is critical for successful revascularization. However, the construction of well-functioning TEVGs remains a fundamental challenge. Herein, chiral hybrid scaffolds were prepared by electrospinning using D/L-phenylalanine based gelators [D(L)PHEG] and poly-ε-caprolactone (PCL). The chirality of scaffolds significantly affected the endothelial remodeling progress of TEVGs. Compared with L-phenylalanine based gelators/poly-ε-caprolactone (L/PCL) and PCL, D-phenylalanine based gelators/poly-ε-caprolactone (D/PCL) scaffolds enhanced cell adhesion, and proliferation and upregulated the expression of fibronectin-1, and vinculin. These results suggests that chiral hybrid scaffolds can promote endothelial remodeling of TEVGs by upregulating adhesion-associated protein levels. This study offers an innovative strategy for endothelial remodeling of TEVGs by fabricating chiral hybrid scaffolds, and provides new insight for the treatment of cardiovascular diseases.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5791
Author(s):  
Elisabetta Catalani ◽  
Matteo Giovarelli ◽  
Silvia Zecchini ◽  
Cristiana Perrotta ◽  
Davide Cervia

Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.


2021 ◽  
pp. 149-159
Author(s):  
Ariel Santos ◽  
Davin T. Combs ◽  
Yasser Ajabnoor ◽  
Cameron Onks

In acute care surgery, regional trauma centers and the American College of Surgeons Committee of Trauma (COT) have worked to address the fundamental challenge of patient stabilization at remote referring facilities, followed by timely patient transfers. However, limitations with patient transport still exist because of adverse weather and lack of emergency vehicles or logistics for emergent transport, demanding ongoing patient care at the originating site. Integration of telemedicine protocols in regional trauma systems has been shown to be effective in facilitating appropriate and timely patient transfers and helps improve the efficacy of resuscitative care in critical-access facilities. Telemedicine has also been shown to be an effective means of service delivery for preoperative, operative and postoperative consultations, reducing time and cost barriers for patients living in remote areas and improving adherence to treatment plans. This increased continuity of care promotes positive outcomes and reduces preventable hospital admissions. Telemedicine also plays a role in surgical education, preceptorship, and mentorship, as well as continuing medical education and multidisciplinary conferences.


2021 ◽  
Vol 1 (1) ◽  
pp. 1-11
Author(s):  
Jennifer Switzer ◽  
Barath Raghavan

Coping with the intermittency of renewable power is a fundamental challenge, with load shifting and grid-scale storage as key responses. We propose Information Batteries (IB), in which energy is stored in the form of information---specifically, the results of completed computational tasks. Information Batteries thus provide storage through speculative load shifting, anticipating computation that will be performed in the future. We take a distributed systems perspective, and evaluate the extent to which an IB storage system can be made practical through augmentation of compiler toolchains, key-value stores, and other important elements in modern hyper-scale compute. In particular, we implement one specific IB prototype by augmenting the Rust compiler to enable transparent function-level precomputation and caching. We evaluate the overheads this imposes, along with macro-level job prediction and power prediction. We also evaluate the space of operation for an IB system, to identify the best case efficiency of any IB system for a given power and compute regime.


Development ◽  
2021 ◽  
Vol 148 (20) ◽  
Author(s):  
Carla Mulas ◽  
Agathe Chaigne ◽  
Austin Smith ◽  
Kevin J. Chalut

ABSTRACT A fundamental challenge when studying biological systems is the description of cell state dynamics. During transitions between cell states, a multitude of parameters may change – from the promoters that are active, to the RNAs and proteins that are expressed and modified. Cells can also adopt different shapes, alter their motility and change their reliance on cell-cell junctions or adhesion. These parameters are integral to how a cell behaves and collectively define the state a cell is in. Yet, technical challenges prevent us from measuring all of these parameters simultaneously and dynamically. How, then, can we comprehend cell state transitions using finite descriptions? The recent Company of Biologists virtual workshop entitled ‘Cell State Transitions: Approaches, Experimental Systems and Models’ attempted to address this question. Here, we summarise some of the main points that emerged during the workshop's themed discussions. We also present examples of cell state transitions and describe models and systems that are pushing forward our understanding of how cells rewire their state.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Oliver R. Maguire ◽  
Iris B. A. Smokers ◽  
Wilhelm T. S. Huck

AbstractThe incorporation of orthophosphate from scarce geochemical sources into the organic compounds essential for life under mild conditions is a fundamental challenge for prebiotic chemistry. Here we report a prebiotic system capable of overcoming this challenge by taking inspiration from extant life’s recycling of orthophosphate via its conversion into kinetically stable thermodynamically activated (KSTA) nucleotide triphosphates (e.g. ATP). We separate the activation of orthophosphate from its transfer to organic compounds by, crucially, first accumulating a KSTA phosphoramidate. We use cyanate to activate orthophosphate in aqueous solution under mild conditions and then react it with imidazole to accumulate the KSTA imidazole phosphate. In a paste, imidazole phosphate phosphorylates all the essential building blocks of life. Integration of this chemistry into a wet/dry cycle enables the continuous recycling of orthophosphate and the accretion of phosphorylated compounds. This system functions even at low reagent concentrations due to solutes concentrating during evaporation. Our system demonstrates a general strategy for how to maximise the usage of scarce resources based upon cycles which accumulate and then release activated intermediates.


Biometrika ◽  
2021 ◽  
Author(s):  
Yuqian Zhang ◽  
Jelena Bradic

Abstract A fundamental challenge in semi-supervised learning lies in the observed data’s disproportional size when compared with the size of the data collected with missing outcomes. An implicit understanding is that the dataset with missing outcomes, being significantly larger, ought to improve estimation and inference. However, it is unclear to what extent this is correct. We illustrate one clear benefit: root-n inference of the outcome’s mean is possible while only requiring a consistent estimation of the outcome, possibly at a rate slower than root-n. This is achieved by a novel k-fold cross-fitted, double robust estimator. We discuss both linear and nonlinear outcomes. Such an estimator is particularly suited for models that naturally do not admit root-n consistency, such as high-dimensional, nonparametric, or semiparametric models. We apply our methods to the heterogeneous treatment effects.


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