Time to transform the way we travel?: A conceptual framework for slow tourism and travel research

Slow food movement gave rise to subsequent movements including Cittáslow and slow tourism. This emphasises a steady state mindful approach to travel and consumption patterns. With consideration for pressing issues like overtourism, mass tourism and the onslaught of the COVID-19 pandemic, it is pertinent to discuss viable alternatives to a fast-paced life and travel that we consider normal. One such alternative is slow tourism that accentuates sustainable tourism practices as well as tourism at a reduced pace. It endorses mindfulness in travelling and discovering destinations in a responsible manner. Furthermore, slow travel aims to promote tourists\u27 consumption-oriented enjoyment of experience through slow-paced and low carbon emission travel patterns. An in-depth scientometric review coupled with a critical qualitative review highlights the state-of-the-art of slow tourism and travel research, offers an integrative multilevel and multistage framework, and proposes future research avenues drawing on the gaps within the slow tourism and travel research

Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy

The introduction of targeted therapy is the biggest success in the treatment of cancer in the past few decades. However, heterogeneous cancer is characterized by diverse molecular alterations as well as multiple clinical profiles. Specific genetic mutations in cancer therapy targets may increase drug sensitivity, or more frequently result in therapeutic resistance. In the past 3 years, several novel targeted therapies have been approved for cancer treatment, including drugs with new targets (i.e., anti-PD1/PDL1 therapies and CDK4/6 inhibitors), mutation targeting drugs (i.e., the EGFR T790M targeting osimertinib), drugs with multiple targets (i.e., the EGFR/HER2 dual inhibitor neratinib) and drug combinations (i.e., encorafenib/binimetinib and dabrafenib/trametinib). In this perspective, we focus on the most up-to-date knowledge of targeted therapy and describe how genetic mutations influence the sensitivity of targeted therapy, highlighting the challenges faced within this era of precision medicine. Moreover, the strategies that deal with mutation-driven resistance are further discussed. Advances in these areas would allow for more targeted and effective therapeutic options for cancer patients

Subordinate Actors’ Institutional Maintenance in Response to Coercive Reforms

Institutional work research shows how actors purposively create, maintain, and disrupt institutions. Failed or unintended consequences of institutional maintenance remain relatively unexplored, for two reasons. First, the role of coercive disruption actors (e.g., a state) has not been fully explored. Second, existing literature takes scant account of power and disregards the resistance tactics of subordinate actors. Drawing on a longitudinal case study of a migrant workers’ union in China, we show how subordinate actors were first able to maintain institutional arrangements followed by a maintenance failure under the disruption work performed by the authoritarian state. This study extends the institutional maintenance literature in two ways. First, subordinate actors can sustain institutions insofar as they collectively deploy superficial deference and hidden forms of resistance. Second, maintenance work is vulnerable in the sense that it is contingent on the systems of domination and the level of pressure exerted by the disruption actors

A generalized analytical model of gain bandwidth for design of optical parametric amplifiers

An analytical model is derived for calculating the maximum gain bandwidth of optical parametric amplifiers (OPA). The model relates in an explicit but simple way the gain bandwidth to the key design parameters of an optical parametric amplifier. It can be used as a tool to obtain the design parameters of an OPA capable of achieving the maximal gain bandwidth. The model is especially useful to design of long wavelength (>6μm)optical parametric amplifiers which have small difference between the center wavelengths of pump and signal.Agency for Science, Technology and Research (A*STAR)We acknowledge the financial support from SERC, Singapore (Grant No. 1426500050, and 1426500051) from the Agency for Science, Technology and Research (A*STAR), Singapore

1,4-Diazabicyclo[2.2.2]octane-Promoted Aminotrifluoromethylthiolation of α,β-Unsaturated Carbonyl Compounds: <i>N-</i>Trifluoromethylthio-4-nitrophthalimide Acts as Both the Nitrogen and SCF₃ Sources

A novel difunctionalization reaction is described. It uses <i>N</i>-trifluoromethylthio-4-nitrophthalimide as the reagent, which serves as both the nitrogen and SCF₃ sources. In the presence of DABCO (1,4-diazabicyclo[2.2.2]­octane), the nitrogen and SCF₃ groups can be incorporated into α,β-unsaturated carbonyl compounds easily and give versatile β-amino ketones and esters in good yields. This difunctionalization reaction features mild reaction conditions, high atom-economy, and efficient access to α-SCF₃ amino acids

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer

Abstract Background The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Methods Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Results Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Conclusions Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage

Desulfovibrio fairfieldensis-Derived Outer Membrane Vesicles Damage Epithelial Barrier and Induce Inflammation and Pyroptosis in Macrophages

Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-M&phi;) and activated various inflammatory factors secretion, including interferon-&gamma; (IFN-&gamma;), tumor necrosis factor (TNF-&alpha;), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1&beta; and caused pyroptosis in THP-1-M&phi; cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation

<i>Desulfovibrio fairfieldensis</i>-Derived Outer Membrane Vesicles Damage Epithelial Barrier and Induce Inflammation and Pyroptosis in Macrophages

Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-Mφ) and activated various inflammatory factors secretion, including interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1β and caused pyroptosis in THP-1-Mφ cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation

Volatile Compound Abundance Correlations Provide a New Insight into Odor Balances in Sauce-Aroma Baijiu

Sauce-aroma Baijiu (SAB) is one of the most famous Baijius in China; SAB has more than 500 aroma compounds in it. However, the key aroma compound in SAB flavor remains unclear. Volatiles play an important role in SAB aroma and are highly correlated to SAB quality. In the present study, 63 volatile compounds were quantified among 66 SAB samples using gas chromatography with flame ionization detector (GC-FID). The authors analyzed odor contributions and volatile compound correlations in two quality groups of SAB samples. Moreover, an odor activity value (OAV) ratio-based random forest classifier was used to explain the volatile compound relationship differentiations between the two quality groups. Our results proved higher quality SABs had richer aromas and indicated a set of fruity-like ethyl valerate, green- and malt-like isobutyraldehyde and malt-like 3-methylbutyraldehyde and sweet-like furfural, had closer co-abundance correlations in higher quality SABs. These results indicated that the aroma and contributions of volatile compounds in SABs should be analyzed not only with compound odor activity values, but also the correlations between different aroma compounds