Glycaemic effects of non-statin lipid-lowering therapies

Since the publication of the JUPITER trial, attention has been focused on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic links between lipid metabolism and glycemic control raise the prospect of a broader diabetogenic effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor class available evidence does not support a major glycaemic effect with the results of large scale trials awaited although preliminary genetic data does suggest a link. In contrast, there is clear evidence of a diabetogenic effect for the now outdated but well-studied niacin. For ezetimibe and fibrates, evidence is scarce but currently broadly unconcerning. For now, the glycemic effects of lipid-lowering therapies should have a limited influence on clinical decision-making. Further study in this topical area is needed

The ets-Related Transcription Factor GABP Directs Bidirectional Transcription

Approximately 10% of genes in the human genome are distributed such that their transcription start sites are located less than 1 kb apart on opposite strands. These divergent gene pairs have a single intergenic segment of DNA, which in some cases appears to share regulatory elements, but it is unclear whether these regions represent functional bidirectional promoters or two overlapping promoters. A recent study showed that divergent promoters are enriched for consensus binding sequences of a small group of transcription factors, including the ubiquitous ets-family transcription factor GA-binding protein (GABP). Here we show that GABP binds to more than 80% of divergent promoters in at least one cell type. Furthermore, we demonstrate that GABP binding is correlated and associated with bidirectional transcriptional activity in a luciferase transfection assay. In addition, we find that the addition of a strict consensus GABP site into a set of promoters that normally function in only one direction significantly increases activity in the opposite direction in 67% of cases. Our findings demonstrate that GABP regulates the majority of divergent promoters and suggest that bidirectional transcriptional activity is mediated through GABP binding and transactivation at both divergent and nondivergent promoters

Visual Estimation of Fingertip Pressure on Diverse Surfaces using Easily Captured Data

People often use their hands to make contact with the world and apply pressure. Machine perception of this important human activity could be widely applied. Prior research has shown that deep models can estimate hand pressure based on a single RGB image. Yet, evaluations have been limited to controlled settings, since performance relies on training data with high-resolution pressure measurements that are difficult to obtain. We present a novel approach that enables diverse data to be captured with only an RGB camera and a cooperative participant. Our key insight is that people can be prompted to perform actions that correspond with categorical labels describing contact pressure (contact labels), and that the resulting weakly labeled data can be used to train models that perform well under varied conditions. We demonstrate the effectiveness of our approach by training on a novel dataset with 51 participants making fingertip contact with instrumented and uninstrumented objects. Our network, ContactLabelNet, dramatically outperforms prior work, performs well under diverse conditions, and matched or exceeded the performance of human annotators

Discovery of Nanoscale Electric Field-Induced Phase Transitions in ZrO\u3csub\u3e2\u3c/sub\u3e

The emergence of ferroelectric and antiferroelectric properties in the semiconductor industry’s most prominent high-k dielectrics, HfO2 and ZrO2, is leading to technology developments unanticipated a decade ago. Yet the failure to clearly distinguish ferroelectric from antiferroelectric behavior is impeding progress. Band-excitation piezoresponse force microscopy and molecular dynamics are used to elucidate the nanoscale electric field-induced phase transitions present in ZrO2-based antiferroelectrics. Antiferroelectric ZrO2 is clearly distinguished from a closely resembling pinched La-doped HfO2 ferroelectric. Crystalline grains in the range of 3 – 20 nm are imaged independently undergoing reversible electric field induced phase transitions. The electrically accessible nanoscale phase transitions discovered in this study open up an unprecedented paradigm for the development of new nanoelectronic devices

Status quo and sector readiness for (bio)plastic food and beverage packaging in the 4IR

Single-use plastics emanating from the food and beverage industry are polluting the environment, and there is increasing public pressure to find ‘green’ solutions to plastic pollution. The introduction of more bio-based and biodegradable plastics (possibly manufactured by disruptive technologies), increased plastic recycling, and enhanced degradation of plastics (micro, meso, and macro) in the environment can holisticallycontribute to solving the problem for future generations. In order to inform future research, it is imperative that robust background data and information are available. This review provides details about the volumes and categories of food and beverage packaging manufactured and recycled, and available data (qualitative and quantitative) on environmental plastic pollution in South Africa, and to a lesser extent, in Europe andglobally. In addition, current and future trends and technologies for recycling, enhanced degradation, and manufacturing of plastics are discussed, with an emphasis on the manufacture of bioplastics. Significance: Plastic pollution needs to be tackled through a holistic combination of reduced use, enhanced recycling efforts, public education about littering, replacement of selected conventional plastics by degradable alternatives, and enhanced degradation of plastics in the environment

Micronutrients and respiratory infections: the biological rationale and current state of clinical evaluation

A range of nutrients has been studied or proposed for use in preventing respiratory tract infections and reducing their severity. This article gives a narrative review of the existing literature, biological rationales and current state of clinical evaluation for micronutrient therapies. The importance of vitamin A, the B vitamins, vitamin C, vitamin D, eicosapentaenoic acid, vitamin E, selenium, zinc and a range of combination therapies are discussed, looking at their effects on reducing rates of infection, reducing severity of infection and improved recovery from infection. Further discussion regarding the level of evidence required for nutritional interventions is included

On the communication cost of entanglement transformations

We study the amount of communication needed for two parties to transform some given joint pure state into another one, either exactly or with some fidelity. Specifically, we present a method to lower bound this communication cost even when the amount of entanglement does not increase. Moreover, the bound applies even if the initial state is supplemented with unlimited entanglement in the form of EPR pairs, and the communication is allowed to be quantum mechanical. We then apply the method to the determination of the communication cost of asymptotic entanglement concentration and dilution. While concentration is known to require no communication whatsoever, the best known protocol for dilution, discovered by Lo and Popescu [Phys. Rev. Lett. 83(7):1459--1462, 1999], requires a number of bits to be exchanged which is of the order of the square root of the number of EPR pairs. Here we prove a matching lower bound of the same asymptotic order, demonstrating the optimality of the Lo-Popescu protocol up to a constant factor and establishing the existence of a fundamental asymmetry between the concentration and dilution tasks. We also discuss states for which the minimal communication cost is proportional to their entanglement, such as the states recently introduced in the context of ``embezzling entanglement'' [W. van Dam and P. Hayden, quant-ph/0201041].Comment: 9 pages, 1 figure. Added a reference and some further explanations. In v3 some arguments are given in more detai

Pharmacological and Physiological Characterization of the Tremulous Jaw Movement Model of Parkinsonian Tremor: Potential Insights into the Pathophysiology of Tremor

Tremor is a cardinal symptom of parkinsonism, occurring early on in the disease course and affecting more than 70% of patients. Parkinsonian resting tremor occurs in a frequency range of 3–7 Hz and can be resistant to available pharmacotherapy. Despite its prevalence, and the significant decrease in quality of life associated with it, the pathophysiology of parkinsonian tremor is poorly understood. The tremulous jaw movement (TJM) model is an extensively validated rodent model of tremor. TJMs are induced by conditions that also lead to parkinsonism in humans (i.e., striatal DA depletion, DA antagonism, and cholinomimetic activity) and reversed by several antiparkinsonian drugs (i.e., DA precursors, DA agonists, anticholinergics, and adenosine A2A antagonists). TJMs occur in the same 3–7 Hz frequency range seen in parkinsonian resting tremor, a range distinct from that of dyskinesia (1–2 Hz), and postural tremor (8–14 Hz). Overall, these drug-induced TJMs share many characteristics with human parkinsonian tremor, but do not closely resemble tardive dyskinesia. The current review discusses recent advances in the validation of the TJM model, and illustrates how this model is being used to develop novel therapeutic strategies, both surgical and pharmacological, for the treatment of parkinsonian resting tremor

Functional analysis of transcription factor binding sites in human promoters

BACKGROUND: The binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1. RESULTS: In each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif. CONCLUSIONS: The genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions