Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

We recently identified the secreted protein IGFBP7 as a factor required for an activated BRAF oncogene to induce senescence or apoptosis in primary human cells. In human melanomas containing an activating BRAF mutation (BRAF-positive melanomas), IGFBP7 is epigenetically silenced, which seems to be a critical step in melanoma genesis. Restoration of IGFBP7 function by the addition of recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAF-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses the growth of BRAF-positive primary tumors in xenografted mice. Here we further evaluate the role of IGFBP7 in the treatment of BRAF-positive melanoma and other malignancies. We find that in human metastatic melanoma samples IGFBP7 is epigenetically silenced and at an even higher frequency than that found in primary melanomas. Using a murine experimental metastasis assay, we show that systemic administration of rIGFBP7 markedly suppresses the growth of metastatic disease and prolongs survival. An analysis of the NCI60 panel of human cancer cell lines reveals that in addition to melanoma, IGFBP7 induces apoptosis in several other cancer types, in particular colorectal cancer cell lines. In general, IGFBP7 induces apoptosis in human cancer cell lines that have an activating mutation in BRAF or RAS, and that are sensitive to chemical inhibition of BRAF-MEK-ERK signaling. Significantly, systemically administered rIGFBP7 blocks the growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts. The results presented here, in conjunction with those from previous studies, justify the further development of IGFBP7 as an anticancer agent

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

GEN Z'S PERCEPTION OF ORGANIZATIONAL ALIGNMENT AND ITS IMPACT ON EMPLOYEE ENGAGEMENT

<p>As members of Generation Z (Gen Z) become integral parts of the contemporary workforce, characterized by their tech-savvy nature, they bring distinct perspectives and expectations to the workplace. This paper aims to comprehensively explore the factors influencing Gen Z's engagement in the workplace and elucidate the correlation of these factors with overall employee engagement. The foundation of this research lies in a thorough literature review, which informs the development of hypotheses. Leveraging insights from existing research papers, this study employs MS Excel for data analysis, utilizing statistical tools such as correlation coefficient and regression. The findings reveal a positive correlation between identified factors and both organizational performance and employee engagement among Gen Z. Notably, career development and rewards and recognitions emerge as pivotal factors. The paper underscores the necessity for policy adaptations to accommodate the unique expectations of this emerging workforce. Failure to address these evolving dynamics may impede companies' ability to effectively attract, retain, and engage Gen Z in the evolving workplace landscape</p&gt

High-pressure studies of GaAs-AlxGa1-xAs quantum wells at 300 and 80 K using photoreflectance spectroscopy

URL:http://link.aps.org/doi/10.1103/PhysRevB.38.9790 DOI:10.1103/PhysRevB.38.9790A detailed photoreflectance study of a GaAs-Al0.3Ga0.7As multiple quantum well of well width 260 Å is carried out at 300 and 80 K. The pressure dependence of a large number of quantized states is observed. The sublinearity of pressure dependence increases with increasing quantum number. A model calculation that includes the pressure dependence of electron effective mass accurately describes the data. Transitions associated with L and X band extrema are observed and their pressure coefficients deduced.This work was supported by the U.S. Department of Energy under Contract No. DE-AC02-84ER45048 and by the U.S. Army under Contract No. DAAL03-86-K0083

Temperature dependence of the quantized states in a GaAs-Ga1-xAlxAs superlattice

URL:http://link.aps.org/doi/10.1103/PhysRevB.37.1035 DOI:10.1103/PhysRevB.37.1035A detailed study of the photoreflectance spectra of a GaAs-Al0.3Ga0.7As superlattice as a function of temperature has revealed the temperature coefficients of the quantum- well transitions associated with the direct Γ conduction band (CB) of GaAs and the staggered transitions from the X-CB of AlxGa1-xAs to the valence band of GaAs. The data have been fitted to Varshni's equation. We have also observed the evolution of the excitonic transitions, especially for lower quantized states, as the temperature is decreased yielding the binding energies.This work ws supported by the u.S. Department of Energy under Contract No. DE-AC0284ER45048. The work by one of us (M.C.) was supported in part by the Alfred P. Sloan Foundation

Research in Tourism and Hospitality Management

The tourism and hospitality industry makes a significant contribution to a nation’s economy. It also plays a vital role in the geographical, cultural and political advancement of the region and is one of the fastest growing sectors of the globe. According to the latest research by World Travel & Tourism Council (WTTC), the sector is on a speedy recovery phase from the devastating impact of the COVID-19 pandemic and is projected to contribute $8.6 trillion to global GDP in 2022. In the contemporary times, which entails a change in consumer expectations and behaviour in the post-pandemic era on one hand and the impact of Industry 4.0 technologies on the other, the tourism and hospitality industry is all set to embrace the transformation required for the Hospitality 4.0 revolution. This edited volume is being published for the benefit of researchers, academicians, and Industry stakeholders in the field of tourism and hospitality. It contains sixteen different chapters covering a wide range of topics on tourism and hospitality management. This book explores the emerging trends in tourism and hospitality management and covers a wide range of research in the areas of consumer behaviour, human resource management practices, sustainable tourism, marketing strategies, the impact of social media, eco-friendly practices, factors influencing job satisfaction of employees, employee motivation, the impact of COVID -19 on Tourism and hospitality and so on