Miracle-dz/UniFAR-FTUs huggingface dataset:
Resort Destinations: Evolution, Management and Development

Destinations and resorts are key building blocks in the development and operation of the global tourism system. Their viability, sustainability and long term management are critical to a healthy global tourism system. While much has been written on aspects of destinations and resorts, including their development, management, sustainability, marketing, history and so forth major gaps remain. The aim of this book is to examine some of these gaps with a specific emphasis on future sustainability in its broadest sense in a rapidly changing world where the future will be redefined in ways that are not yet obvious but which must be speculated on and planned for. Climate change and the enormous cost of providing food and shelter for a future global population that according to the UN is likely to be 50% higher in 2050 than today will present enormous challenges to the global political system and strain global markets to provide the basics of life. The most recent news on the climate front is that the IPCC's (2007) forecast of sea level changes are significantly underestimated and that a rise of 1 meter of more is now more likely than not. This has significant implications for coastal tourism and the 50% of the global population who live in coastal zones. The reordering of global markets in the wake of the Global Financial Crisis may see a fundamental shift from neo-liberal free market economics to a more regulated global economy. All of these forces and many more discussed in this book will create a new world in which tourism will continue to thrive but within constraints that take into account the impact of climate change and the need to achieve a new level of sustainability that recognizes there are limits to growth. Destinations will need to adapt to these new realities. It is my hope that tins book goes at least some way to contributing to the debate we need to have on how the gathering storm of climate change and declining global sustainability will be confronted at the destination level.
Comment on “Next‐Generation Ice Core Technology Reveals True Minimum Natural Levels of Lead (Pb) in the Atmosphere: Insights From the Black Death” by More et al.

Over the past four decades numerous studies of lake sediment, marine sediment, and peat from sites in close proximity to mining or metallurgical centers and in remote locations have detailed local and regional histories of lead (Pb) pollution in Europe. Contrary to More et al.'s (2017, https://doi.org/10.1002/2017GH000064) claim that “previous assumptions about preindustrial “natural” background lead levels in the atmosphere have been misleading,” these studies have clearly shown that true natural background conditions occurred more than 2,500 or even 3,500 years ago, and Pb pollution has proceeded uninterrupted since. The implications of this have been discussed within the context of environmental policy, for example, European Water Framework Directive. Though these records reflect a common European narrative of mining, metallurgy, and pollution, each reflects a combination of local and regional events, leading to differences in the timing and intensity of changes in each Pb record. No one record—ice or otherwise—fully represents the three millennia Pb pollution history in Europe. While the resolution of the ice record is impressive, there are questions about its interpretation. First, the authors discount local and regional Pb sources, whereas there is a close connection between the mining history in an area 40 km from the glacier and changes in a nearby lake Pb record; second, significant changes in ice chemistry cooccurring with the lowest Pb values are overlooked. A sharp increase in Ca/Fe ratios occurs precisely with the steepest Pb declines during the Black Death and mid‐1400s, suggesting additional processes influencing the Pb record.
Autistic Intensity in Relations to the Demographic Variables of Parents

Autism is a developmental disorder that is marked by profound deficits in social, language, and cognitive abilities. The manifestations of autism vary considerably among children and within an individual child over time. There is no single behavior that is always typical of autism and no behavior that would automatically exclude an individual child from a diagnosis of autism, even though there are strong commonalities, especially in social deficits. In general terms, children within the autistic spectrum display a highly unusual pattern of deficits and skills. Children with autistic characteristics may be classified as having autism spectrum disorder, also known as pervasive developmental disorder (PDD). Pervasive developmental disorder includes several differentiated disorders, including autistic disorder, but all are characterized by “severe and pervasive impairment in several areas of development: reciprocal social interaction skills, communication skills, or the presence of stereotyped behavior, interests, and activities” [1].
Targeting RAS Driven Human Cancer Cells with Antibodies to Upregulated and 1 Essential Cell-Surface Proteins 2 3

19 20 While there have been tremendous efforts to target oncogenic RAS signaling 21 from inside the cell, little effort has focused on the cell-surface. Here, we used 22 quantitative surface proteomics to reveal a signature of proteins that are 23 upregulated on cells transformed with KRASG12V, and driven by MAPK pathway 24 signaling. We next generated a toolkit of recombinant antibodies to seven of these 25 RAS induced proteins. We found that five of these proteins are broadly distributed 26 on cancer cell lines harboring RAS mutations. In parallel, a cell-surface CRISPRi 27 screen identified integrin and Wnt signaling proteins as critical to RAS transformed 28 cells. We show that antibodies targeting CDCP1, a protein common to our 29 proteomics and CRISPRi datasets, can be leveraged to deliver cytotoxic and 30 immunotherapeutic payloads to RAS transformed cancer cells and report for RAS 31 signaling status in vivo. Taken together, this work presents a technological platform 32 for attacking RAS from outside the cell. 33 34 Introduction: 35 36 RAS is a family of three ubiquitously expressed small GTPases found in all 37 animal cell types. RAS is localized to the intracellular leaflet of the cell membrane 38 where it serves as a major communication hub that relays extracellular growth 39 factor-dependent signaling to as many as a dozen different intracellular signaling 40 pathways, including the classically studied MAPK and PI3K pathways (Downward, 41 2003). Collectively, these pathways induce dramatic changes to cells including 42 transcriptional reprogramming, promotion of cell survival, suppression of 43 apoptosis, metabolic rewiring, promotion of proliferation, and increased cell 44 invasiveness (Pylayeva-Gupta et al., 2011). Many of these phenotypes are well45 known hallmarks of cancer survival (Hanahan and Weinberg, 2011). Thus, it is not 46 surprising that nearly one third of all human malignancies have been found to be 47 driven by mutational activation of one of the three RAS isoforms: KRAS, NRAS and 48 HRAS (Roberts and Der, 2007). Hence oncogenic RAS has been an important focus of 49 the cancer biology and drug discovery communities for several decades (Ledford, 5
Landmark-Based Robot Localization Using a Stereo Camera System

This paper proposes the method of 2D localization using a stereo camera system. The navigating space of robot with landmarks for robot localization is an indoor environment. Therefore, the main task is that features of landmarks that are unchanged in scales and directions are determined from the left and right images. The algorithm of the Scale-Invariance Feature Transform (SIFT) is applied for transformation of all features of the landmark image to multi-dimensional vectors. Moreover, the pixel locations of the detected landmarks on the left and right images are transformed to distances using the geometric projections. The coordinates of each detected landmark and the distances to the robot are finally combined using Euclid distance equations for estimating the robot location. Results are shown to illustrate the effectiveness of the proposed stereo camera system with the consuming time and the low cost, but it still satisfies the localization task.
Long noncoding RNA HOXD-AS1 in various cancers: a meta-analysis and TCGA data review

Background and aims: HOXD antisense growth-associated long noncoding RNA (HOXD-AS1) was reported to be upregulated in various cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and glioma. Here, we conducted a meta-analysis and The Cancer Genome Atlas data review to investigate the clinicopathologic and prognostic value of HOXD-AS1 in patients with malignant tumors. Materials and methods: Systematic literatures were searched from PubMed, Medline, Cochrane Library, Web of Science, EMBASE database, Ovid, Chinese CNKI, and the Chinese WanFang database. The role of HOXD-AS1 in cancers was evaluated by pooled ORs and HRs with 95% CIs. The Cancer Genome Atlas dataset was used to explore the prognostic value of HOXD-AS1 in various cancers. Results: Fifteen studies with 1,678 patients were included in this meta-analysis. The results indicated that HOXD-AS1 was associated with tumor size, differentiation, lymph node metastasis, and TNM stage. Moreover, the high HOXD-AS1 expression indicated a poor overall survival (OS) rate and can be an independent predictive factor for OS. The TCGA dataset, which included 9,502 cancer patients, showed that the expression of HOXD-AS1 was related to poor OS and disease-free survival. We also analyzed the prognostic role in different kinds of cancers such as digestive cancers, female reproductive system cancers, respiratory system cancers, and urinary system cancers. Conclusion: This study demonstrated that HOXD-AS1 was closely correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage, and an increased HOXD-AS1 expression could be a reliable prognostic biomarker in human cancers. However, more studies are needed to confirm this conclusion.
Reversed paired-gRNA plasmid cloning strategy for e�cient genome editing in Escherichia coli.

Background: Co-expression of two distinct guide RNAs (gRNAs) has been used to facilitate the application of CRISPR/Cas9 system in �elds such as large genomic deletion. The paired gRNAs are often placed adjacently in the same direction and expressed individually by two identical promoters, constituting direct repeats (DRs) which are susceptible to self-homologous recombination. As a result, the paired-gRNA plasmids cannot remain stable, which greatly prevents scalable application of the CRISPR/Cas9 system. Results: To address this limitation, different DRs-involved paired-gRNA plasmids were designed and the events of recombination were characterized. Deletion between DRs occurred with high frequencies during plasmid construction and subsequent plasmid propagation. This recombination event was RecA-independent, which agreed with the replication slippage model. To increase plasmid stability, a reversed paired-gRNA plasmids (RPGPs) cloning strategy was developed by converting DRs to the more stable invert repeats (IRs), which completely eliminated DRs-induced recombination. Using RPGPs, rapid deletion of chromosome fragments up to 100 kb with an e�ciency of 83.33% was achieved in Escherichia coli. Conclusions: The RPGPs cloning strategy serves as a general solution to avoid plasmid RecA-independent recombination. It can be adapted to applications that rely on paired gRNAs or repeated genetic parts.
Experimental Investigation on the Morphology of Interstellar Ice Analogues

Spectroscopic observations of cold and dense interstellar clouds show the presence of "dirty ice" mantles on dust grains, mainly composed by water molecules. These ices are enriched by the presence of other simple species that are either formed by surface reactions or accreted from the gas phase. While there is quite a general consensus that interstellar water ice is mainly amorphous, its morphology (porous or compact) still remains poorly known. Morphology is important due to its influence both on the catalytic efficiency of grain surfaces and on the release to the grain of the fraction of the formation energy of species, as shown by laboratory simulations of molecular hydrogen formation. Ice porosity may be identified through the weak infrared absorption features (~ 2.7 μm) showing the presence of dangling bonds on the pore surface. To our knowledge, there has been to date no detection of such absorptions in the infrared spectra of interstellar ices, perhaps suggesting that they may have a compact nature. It has been already investigated that interstellar porous ice may be compacted by the transient heating of stellar radiation and cosmic ray bombardment. In this thesis I report an experimental work, performed using FORMOLISM (the experimental apparatus at the University of Cergy-Pontoise - France), that shows relevant changes in the ice morphology following atomic hydrogen exposure. In particular, it is shown that a thin highly porous ice film is gradually changed into a more compact structure. This is probably due to the transient heating caused by the energy released to the ice during H2 formation. Such a process may also produce in the interstellar space compact amorphous ice mantles concurrently with the other envisaged processes. Moreover, I have experimentally analyzed the morphology of the just formed water ice. Analysing one of the possible mechanism of water formation (the pathway H + O2) under conditions mimicking those found in a molecular cloud, we have found that the water just synthesized has a non-porous structure. Indeed, the layers of water formed in this way show the kinetic characteristics typical of a compact (non-porous) ice, as for instance the D2 TPD peak position.
Numerical investigation of the interplay between wall geometry and friction in granular fault gouge

The influence of surface roughness is central in understanding the behavior of various types of shear zones including faults, landslides, and deformation in glacial till. All of these systems contain a non‐planar rough wall, which interacts with either a gouge zone or another wall. We use the 3‐D discrete element method (DEM) to investigate both the effect of boundary roughness and friction. Granular non‐cohesive gouge is sandwiched between rough walls with large grooves, or smooth walls composed of spherical particles that can be adjusted to control roughness. Roughness and gouge properties are scaled to laboratory friction experiments. We vary friction between the particles and the wall and monitor shear strength, height, coordination number, distribution, and orientation of particle forces, localization, and porosity distribution in the shear zone. We find that, on the first‐order, strength is controlled by particle‐particle friction and mechanical coupling of the fault zone wall to the gouge. Rough boundaries (RMS roughness > grain radius) force more shear within the gouge zone, dilating the layer and sliding more grains, which leads to large stress necessary to shear the layer. When large amplitude roughness is removed, and roughness is at the grain‐scale, the coupling, and thus the strength, is controlled by both wall and particle friction as well as fine‐scale boundary roughness. These differences are reflected in profiles of shear within the gouge zone and offset at the boundary in smooth models. From our simulations, we quantify how and why rough natural faults will have a higher overall strength.
Impact of Religious and Spiritual Activity on Risk of Dementia and Cognitive Impairment with Differences across Race/Ethnicity and Sex

Religion and spirituality (R/S) are positively associated with cognitive function and individual dementia risk factors, yet few studies have examined R/S association with dementia. Identifying possible protective factors against developing dementia is needed to decrease the rising dementia burden. We examined the frequency of religious attendance on the risk of developing a cognitive condition over time, adjusting for race/ethnicity and age in U.S. older adults ( N = 103). A higher frequency of religious attendance and a higher percentage of dementia was found among non-Hispanic Black, Hispanic, and female older adults. However, religious attendance was not associated with developing a cognitive condition over time. More research is needed to examine these associations with consideration of a bi-directional relationship between stress and R/S practices and with consideration of premature mortality. In addition, examining if R/S could delay dementia onset should be explored, especially among a large, diverse sample.
Explorer Intelligence in youth and health at age 50

General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac. uk providing details, and we will remove access to the work immediately and investigate your claim. a b s t r a c t a r t i c l e i n f o Background: The link between intelligence in youth and all-cause mortality in later-life is well established. To better understand this relationship, the current study examines the links between pre-morbid intelligence and a number of specific health outcomes at age 50 using the NLSY-1979 cohort. Methods: Participants were the 5793 participants in the NLSY-79 who responded to questions about health outcomes at age 50. Sixteen health outcomes were examined: two were summary measures (physical health and functional limitation), 9 were diagnosed illness conditions, 4 were self-reported conditions, and one was a measure of general health status. Linear and logistic regressions were used, as appropriate, to examine the relationship between intelligence in youth and the health outcomes. Age, sex and both childhood and adult SES, and its sub-components – income, education, & occupational prestige – are all adjusted for separately. Results & conclusion: Higher pre-morbid intelligence is linked with better physical health at age 50, and a lower risk for a number of chronic health conditions. For example, a 1 SD higher score in IQ was significantly associated with increased odds of having good, very good, or excellent health, with an odds ratio of 1.70 (C.I. 1.55–1.86). Thirteen of the illness outcomes were significantly and negatively associated with IQ in youth; the odds ratios ranged from 0.85 for diabetes/high blood sugar to 0.65 for stroke, per one standard deviation higher score in IQ. Adjustment for childhood SES led to little attenuation but adult SES partially mediated the relationship for a number of conditions. Mediation by adult SES was not consistently explained by any one of its components—income, education, and occupation status. The current findings contribute to our understanding of lower intelligence as a risk factor …
Supplemental Text for: Sky Optimization: Semantically aware image processing of skies in low-light photography

Inputs to the filter are: a 3-channel reference image I (assumed to be in YUV), the quantities to be filtered, P (in our case, the sky mask), a confidence map C, and hyperparameters: s, the downsampling factor, and `, and c, the regularization factors for the luma and chroma, respectively. The output of the filter is Y , a mask that resembles P where C is large, and adheres to the edges in I . Regarding notation, ◦ is the Hadamard product (where 1-channel images are “broadcasted” to match the dimensions of images with more channels), and · is a dot product (Hadamard product that is then summed over channels). The outer product of two images A = X ⊗ Y is defined as taking two 3-channel images X and Y and producing a 6-channel image A representing the upper-triangular portion of the outer product of each pixel of X and Y :
high feasibility of cytological specimens for detection of ROS1 fusion by reverse transcriptase Pcr in chinese patients with advanced non-small-cell lung cancer

Purpose: Our previous study demonstrated that cytological specimens can be used as alternative samples for detecting anaplastic lymphoma kinase ( ALK ) fusion with the method of reverse transcriptase PCR (RT-PCR) in patients with advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate the feasibility of cytological specimens for ROS proto-oncogene 1, receptor tyrosine kinase ( ROS1 ) fusion detection by RT-PCR in advanced NSCLC patients. Patients and methods: A total of 2,538 patients with advanced NSCLC, including 2,101 patients with cytological specimens and 437 patients with tumor tissues, were included in this study. All patients were screened for ROS1 fusion status by RT-PCR. The efficacy of crizotinib treatment was evaluated in ROS1 fusion-positive NSCLC patients. Results: Among 2,101 patients with cytological specimens, the average concentration of RNA acquired from cytological specimens was 47.68 ng/ μ L (95% CI, 43.24–52.62), which was lower than the average of 66.54 ng/ μ L (95% CI, 57.18–76.60, P = 0.001) obtained from 437 tumor tissues. Fifty-five patients harbored ROS1 fusion gene that was detected by RT-PCR, and 14 of them were treated with crizotinib. The incidence of ROS1 fusion was 1.95% (41/2,101) in 2,101 patients with cytological specimens, similar to the rate of 3.20% (14/437, P = 0.102) for the 437 patients with tumor tissue. Regarding crizotinib treatment, no statistically significant differences were observed in the objective response rate (ORR) (81.8% vs 100%, P = 0.604) between the cytological and tissue subgroups of ROS1 -positive patients. Conclusion: This study shows that cytological specimens can be utilized as alternative samples for ROS1 fusion detection by RT-PCR in advanced NSCLC patients.