Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

Alterations in mitochondrial function are an important control variable in the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), while also noted by increased de novo lipogenesis (DNL) and hepatic insulin resistance. We hypothesized that the organization and function of a mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. We addressed this question using a transgenic mouse model with increased hepatic insulin resistance and DNL due to constitutively active human SREBP-1c. The abundance of ETC complex subunits and components of key metabolic pathways are regulated in the liver of these animals. Further omics approaches combined with functional assays in isolated liver mitochondria and primary hepatocytes revealed that the SREBP-1c-forced fatty liver induced a substrate limitation for oxidative phosphorylation, inducing enhanced complex II activity. The observed increased expression of mitochondrial genes may have indicated a counteraction. In conclusion, a shift of available substrates directed toward activated DNL results in increased electron flows, mainly through complex II, to compensate for the increased energy demand of the cell. The reorganization of key compounds in energy metabolism observed in the SREBP-1c animal model might explain the initial increase in mitochondrial function observed in the early stages of human MAFLD.     

Inhibition of FLT3: A Prototype for Molecular Targeted Therapy in Acute Myeloid Leukemia

Modern therapy of acute myeloid leukemia (AML) began in 1973 with the first report of the successful combination of daunorubicin and cytarabine, which led to complete remission in approximately 45% of patients. Accurate AML diagnosis was dependent on morphology, aided initially only by cytochemistry. Unlike acute lymphoblastic leukemia (ALL), immunophenotyping offered little in the diagnosis of AML, at least during the 1970s and 1980s. The advent of reliable cytogenetics changed the entire prognostic outlook of AML. With karyotypic analysis, different groups of AML could be classified and stratified for various therapies. Unique mutational profiling was a major advance in further categorizing AML patients, aided by the immunophenotypic identification of antigenic markers on the cells. All these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease (MRD)—became crucial for the management of AML patients. The efficacy of MRD has rapidly progressed in the past decade, from a specificity of 10⁻³ with immunophenotyping to 10⁻⁴ with polymerase chain reaction (PCR), which is only appropriate for some patients with AML, and finally to 10⁻⁵ or even 10⁻⁶ cells with the extraordinary sensitivity of next-generation sequencing (NGS). All of these advances have promoted the concept of personalized medicine, which has led to the advent of targeted agents that can accurately be used for specific diagnostic subtypes. Responses can be predicted and measured accurately. Such targeted agents have now become a cornerstone in the management of AML, increasing efficacy and dramatically reducing toxicity. The focus of this review is on one of the most well-studied targeted agents in AML: the FMS-like tyrosine kinase 3 (FLT3) inhibitors, which have impacted the prognostication and therapeutics of AML. This review selectively discusses the FLT3 inhibitors in detail, as a model for the other burgeoning targeted agents that have already been approved, as well as those that are currently in development.     

Designing on-site: Facilitating participatory contextual architecture with mobile phones

Some movements within modern architecture particularly emphasise the importance of matching buildings to their surroundings. However, practicing such “contextual architecture” is highly challenging and typically not something the future inhabitants of a building are well equipped for participating in. This paper explores the potentials of using mobile phone technology for facilitating such client participation in the parts of an architecture process that take place on the building site. For this we introduce ArchiLens, a mobile system for interactive on-site 3D visualisation of houses, and findings from a field study with 40 participants in the process of building or modifying their home. The study showed that using the system helped evoke people’s imagination of the look and feel of their future house, and envision it in context. This enabled them to participate more closely in the design process on-site by iteratively reviewing design alternatives and exploring, for example, other placements and materials.     

Hide-n-Sense: Preserving Privacy Efficiently in Wireless mHealth

As healthcare in many countries faces an aging population and rising costs, mobile sensing technologies promise a new opportunity. Using mobile health (mHealth) sensing, which uses medical sensors to collect data about the patients, and mobile phones to act as a gateway between sensors and electronic health record systems, caregivers can continuously monitor the patients and deliver better care. Furthermore, individuals can become better engaged in monitoring and managing their own health. Although some work on mHealth sensing has addressed security, achieving strong privacy for low-power sensors remains a challenge. We make three contributions. First, we propose an mHealth sensing protocol that provides strong security and privacy properties at the link layer, with low energy overhead, suitable for low-power sensors. The protocol uses three novel techniques: adaptive security, to dynamically modify transmission overhead; MAC striping, to make forgery difficult even for small-sized Message Authentication Codes; and asymmetric resource requirements, in recognition of the limited resources in tiny mHealth sensors. Second, we demonstrate its feasibility by implementing a prototype on a Chronos wrist device, and evaluating it experimentally. Third, we provide a security, privacy, and energy analysis of our system.     

Enviro-Friendly Synthesis of Silver Nanoparticles Using Berberis lycium Leaf Extract and Their Antibacterial Efficacy

In the present study,an enviro-friendly synthesis of silver nanoparticles from Berberis lycium Royle leaf extract and their antibacterial efficacy against five pathogenic bacteria were investigated.This biosynthesis technique is proved to be advantageous over physical and chemical methods as no toxic chemicals are used.The structural and morphological characterization was made by UV-visible spectroscopy,scanning electron microscopy,and transmission electron microscopy.The synthesized nanoparticles were oval,rectangular,and spherical in shape,size ranges from 8 to 100 nm and exhibited an absorption peak at 458 nm.The biosynthesized silver nanoparticles have shown good antibacterial effect toward tested bacteria.It is believed that these biosynthesized silver nanoparticles can play a vital role in nano-based products in future.     

The economics of visual disamenity reductions of offshore wind farms—Review and suggestions from an emerging field

The offshore wind power generation market is currently experiencing large growth rates on a global scale and investments exceeding several billion euro are being made. From a welfare economic point of view there is a non-trivial economic trade-off between offshore wind generation costs and the visual impacts from offshore wind farms. Offshore wind farms close to the shore generate cheaper electricity, but also cause higher levels of visual impacts compared to locations at larger distances. In the present paper we carry out a review of the stated preference studies that have elicited the demand for visual disamenity reduction from offshore wind farms. The review has three objectives: (a) to present the results of the different surveys; (b) to explore the more technical parts of the different surveys; and (c) to present the frontiers in the assessment of the demand for visual disamenity reductions associated with offshore wind farm locations. The paper is based on the results from five different studies. The review indicates that locations of offshore wind farms which are close to the shore generate significant welfare losses and that these can be reduced by locating the wind farms at more distant locations. The results also show that the welfare economic costs vary in terms of a range of socio demographic characteristics, experience with wind turbines and recreational activities. Finally, the review suggests that the welfare impacts related to the spatial distribution of the wind farms, intergenerational effects and experience with wind turbines are potential areas that would be beneficial to explore in future studies.