Interleukin-15 and [alpha](1,3)galactosyl-expressing vaccine combination therapy for melanoma

The hyperacute immune response observed in humans after xenotransplantation is mainly induced by the alpha(1,3)Galactosyl (alphaGal) epitopes expressed on xenografts and the pre-existing anti-alphaGal antibodies that recognize these epitopes. Based on this hyperacute rejection, we hypothesized that human cancer cells genetically modified to express the alphaGal epitope could provide a new anti-cancer vaccine. This hypothesis was previously studied using the alpha1,3-galactosyltransferase knockout (alphaGT KO) mouse model and B16 melanoma cells genetically modified to express alphaGal epitopes (B16alphaGal). In this model, the B16alphaGal vaccine showed efficacy in treating pre-existing subcutaneous and pulmonary alphaGal-negative B16 melanomas in mice. Furthermore, adoptively transferred lymphocytes from mice vaccinated with the B16alphaGal vaccine elicited a therapeutic response in mice bearing pulmonary tumors. In an attempt to increase the efficacy of the B16alphaGal vaccine, in the present study, IL-15-expressing vaccine cells (B16IL-15) were administered to mice in combination with the B16aGal vaccine with or without B16N/V vaccine cells (irradiated B16F0 melanoma cells). As documented in literature, IL-15 stimulates the proliferation and maintenance of memory CD8+ T cells. We exploited these effects of IL-15 in preventive and therapeutic experiments, wherein B16 tumors were implanted either subcutaneously or intravenously in alphaGT KO mice. In all the efficacy studies, the combination therapy showed efficacy in vaccinated mice versus control mice receiving no vaccination. In three out of five in vivo experiments, mice receiving the combination therapy were more effectively treated for B16 melanomas compared to mice receiving B16alphaGal vaccine (with or without B16N/V vaccine). Moreover, long-term memory CD8+ T cells adoptively transferred from mice receiving the combination therapy successfully treated mice with pulmonary B16 melanomas. In vivo 5,6-carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeling experiments demonstrated that mice receiving the combination therapy developed CD8 + T cells which proliferated to a greater degree than CD8+ T cells from mice vaccinated with B16alphaGal plus B16N/V vaccine. In conclusion, the results obtained in this study using the described murine system demonstrate a trend supporting the hypothesis that a combined therapy of B16alphaGal plus B16IL-15 vaccines provides a potential improved treatment outcome compared to the B16alphaGal vaccine alone

Big data fusion to estimate urban fuel consumption: A case study of Riyadh

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this recordFalling oil revenues and rapid urbanization are putting a strain on the budgets of oil-producing nations, which often subsidize domestic fuel consumption. A direct way to decrease the impact of subsidies is to reduce fuel consumption by reducing congestion and car trips. As fuel consumption models have started to incorporate data sources from ubiquitous sensing devices, the opportunity is to develop comprehensive models at urban scale leveraging sources such as Global Positioning System (GPS) data and Call Detail Records. This paper combines these big data sets in a novel method to model fuel consumption within a city and estimate how it may change in different scenarios. To do so a fuel consumption model was calibrated for use on any car fleet fuel economy distribution and applied in Riyadh, Saudi Arabia. The model proposed, based on speed profiles, was then used to test the effects on fuel consumption of reducing flow, both randomly and by targeting the most fuelinefficient trips in the city. The estimates considerably improve baseline methods based on average speeds, showing the benefits of the information added by the GPS data fusion. The presented method can be adapted to also measure emissions. The results constitute a clear application of data analysis tools to help decision makers compare policies aimed at achieving economic and environmental goals.MIT Energy Solutions InitiativeCenter for Complex Engineering Systems, King Abdulaziz City for Science and TechnologyRoyal SocietyBritish AcademyAcademy of Medical Science

Raman spectra of copper, cobalt, and nickel complexes of nicotinic acid: Equilibrium studies

This article summarizes the protonation and complexation equilibrium constants of nicotinic acid (NA) using different analytical techniques and software’s. Additionally, Raman, IR, and NMR spectra were done for nicotinic acid ligand and for its solid complexes with copper(II), cobalt(II) and nickel(II) metal ions.               KEY WORDS: Nicotinic acid, Potentiometry, Spectrometry, Equilibrium constants Bull. Chem. Soc. Ethiop. 2018, 32(3), 459-467.DOI: https://dx.doi.org/10.4314/bcse.v32i3.

Bioactivities of holmium(III) and gadolinium(III) complexes of thymoquinone

Chemotherapeutic agents which are the main stay in cancer treatment are toxic with numerous contrary side effects. A number of chemical, physical, and computational techniques were applied to synthesize and elucidate the structural and functional characterization of the new designed bioligands and their metal complexes. Besides, several biological techniques for developing therapeutics and diagnostics agents of these new designed materials were used. The trivalent holmium(III) and gadolinium(III) metal complexes of thymoquinone (TQ) were synthesized. Toxicities and other bioactivites were undertaken with existing drug combinations and more effective tumor models will be established. The molecular structures of TQ-metal complexes were elucidated based on particular spectral approaches. The NF-kB (nuclear factor kappa-light-chain enhancer of activated B Cells) luciferase, elastase release, superoxide anion (O2•−) generation, and DPPH (1,1-diphenyl-2-picryl hydrazyl) free-radical scavenging activities of TQ and its synthesized complexes were elucidated and discussed. The core research is to use coordination and organometallic chemistry to design new bioligands and binary, ternary, mixed ligand, multi metal multi ligand complexes pursing a bio target continuously with structure-activity relationships (SARS).                     KEY WORDS: Thymoquinone, Holmium, Gadolinium, Bioactivities   Bull. Chem. Soc. Ethiop. 2021, 35(1), 87-96. DOI: https://dx.doi.org/10.4314/bcse.v35i1.

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Consumer Adoption of Self-Service Technologies in the Context of the Jordanian Banking Industry: Examining the Moderating Role of Channel Types

YesThis study aimed to examine the key factors predicting Jordanian consumers’ intentions and usage of three types of self-service banking technologies. This study also sought to test if the impacts of these main predictors could be moderated by channel type. This study proposed a conceptual model by integrating factors from the unified theory of acceptance and use of technology (UTAUT), along with perceived risk. The required data were collected from a convenience sample of Jordanian banking customers using a survey questionnaire. The statistical results strongly support the significant influence of performance expectancy, social influence, and perceived risk on customer intentions for the three types of SSTs examined. The results of the X2 differences test also indicate that there are significant differences in the influence of the main predictors due to the moderating effect of channel type. One of the key contributions of this study is that three types of SSTs were tested in a single study, which had not been done before, leading to the identification of the factors common to all three types, as well as the salient factors unique to each type

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

Background: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion

Cancer recurrence times from a branching process model

As cancer advances, cells often spread from the primary tumor to other parts of the body and form metastases. This is the main cause of cancer related mortality. Here we investigate a conceptually simple model of metastasis formation where metastatic lesions are initiated at a rate which depends on the size of the primary tumor. The evolution of each metastasis is described as an independent branching process. We assume that the primary tumor is resected at a given size and study the earliest time at which any metastasis reaches a minimal detectable size. The parameters of our model are estimated independently for breast, colorectal, headneck, lung and prostate cancers. We use these estimates to compare predictions from our model with values reported in clinical literature. For some cancer types, we find a remarkably wide range of resection sizes such that metastases are very likely to be present, but none of them are detectable. Our model predicts that only very early resections can prevent recurrence, and that small delays in the time of surgery can significantly increase the recurrence probability.Comment: 26 pages, 9 figures, 4 table

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially