Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing

Mosquitoes containing gene drive systems are being developed as complementary tools to prevent transmission of malaria and other mosquito-borne diseases. As with any new tool, decision makers and other stakeholders will need to balance risks (safety) and benefits (efficacy) when considering the rationale for testing and deploying gene drive-modified mosquito products. Developers will benefit from standards for judging whether an investigational gene drive product meets acceptability criteria for advancing to field trials. Such standards may be formalized as preferred product characteristics and target product profiles, which describe the desired attributes of the product category and of a particular product, respectively. This report summarizes discussions from two scientific workshops aimed at identifying efficacy and safety characteristics that must be minimally met for an investigational gene drive-modified mosquito product to be deemed viable to move from contained testing to field release and the data that will be needed to support an application for first field release

Ensemble Sales Forecasting Study in Semiconductor Industry

Sales forecasting plays a prominent role in business planning and business strategy. The value and importance of advance information is a cornerstone of planning activity, and a well-set forecast goal can guide sale-force more efficiently. In this paper CPU sales forecasting of Intel Corporation, a multinational semiconductor industry, was considered. Past sale, future booking, exchange rates, Gross domestic product (GDP) forecasting, seasonality and other indicators were innovatively incorporated into the quantitative modeling. Benefit from the recent advances in computation power and software development, millions of models built upon multiple regressions, time series analysis, random forest and boosting tree were executed in parallel. The models with smaller validation errors were selected to form the ensemble model. To better capture the distinct characteristics, forecasting models were implemented at lead time and lines of business level. The moving windows validation process automatically selected the models which closely represent current market condition. The weekly cadence forecasting schema allowed the model to response effectively to market fluctuation. Generic variable importance analysis was also developed to increase the model interpretability. Rather than assuming fixed distribution, this non-parametric permutation variable importance analysis provided a general framework across methods to evaluate the variable importance. This variable importance framework can further extend to classification problem by modifying the mean absolute percentage error(MAPE) into misclassify error. Please find the demo code at : https://github.com/qx0731/ensemble_forecast_methodsComment: 14 pages, Industrial Conference on Data Mining 2017 (ICDM 2017

Osteoarthritis of the hip in children at the Lome´ Teaching Hospital

Objectives The aim of this study was to describe the epidemiological and therapeutic aspects of osteoarthritis of the hip in children, analyze the outcome, and describe the techniques for its diagnosis in a hospital with poor working conditions.Materials and methods This was a retrospective study including children in the age group of 0–15 years, who were managed for osteoarthritis at the Pediatric Surgery Department of the Lome´ Teaching Hospital (Togo) between July 2000 and June 2008. The data were collated from patients’ records and analyzed for epidemiology, clinical features, treatment, and outcome of osteoarthritis.Results A total of 30 children were included in this study, of whom 17 (24.4%) were girls and 13 (43.3%) were boys. Their mean age was 4 years (range: 1–15 years). Children in the age range of 0–6 years accounted for 73.33% of patients included. Fifteen patients were of the homozygous sickle cell genotype (SS). Treatment included antibiotic therapy and immobilization of the joint. The outcome was excellent in eight AA patients (26.67%); good in three (10%), including one SS, one AS, and one SC; and fair in 19 patients (63.33%), including 14 SS, four AS, and one SC. The average duration of hospital stay was 18 days (range: 2–35 days).Conclusion Sickle cell disease (SS genotype) is the predominant cause of osteoarthritis in children presenting to the Pediatric Surgery Department of the Lome´ Teaching Hospital. Early diagnosis and appropriate treatment are necessary for a complete cure.Keywords: child, hip, osteoarthritis, sickle cell, Tog

The role of fatty acid desaturases in epidermal metabolism

The lipid composition of skin is important to a variety of functions served by this organ. Therefore, skin expresses multiple enzymes that synthesize and metabolize lipids. An important class of lipid metabolism enzymes expressed in skin is the lipid desaturases. Various isoforms of stearoyl-CoA desaturase, a delta-9 desaturase, as well as a delta-6 desaturase alter the lipid composition of the skin, thereby affecting skin barrier homeostasis and consequently, whole body energy balance. This review will focus on the role of fatty acid desaturases in maintaining epidermal metabolism

Shrinking wings for ultrasonic pitch production: hyperintense ultra-short-wavelength calls in a new genus of neotropical katydids (Orthoptera: tettigoniidae)

This article reports the discovery of a new genus and three species of predaceous katydid (Insecta: Orthoptera) from Colombia and Ecuador in which males produce the highest frequency ultrasonic calling songs so far recorded from an arthropod. Male katydids sing by rubbing their wings together to attract distant females. Their song frequencies usually range from audio (5 kHz) to low ultrasonic (30 kHz). However, males of Supersonus spp. call females at 115 kHz, 125 kHz, and 150 kHz. Exceeding the human hearing range (50 Hz–20 kHz) by an order of magnitude, these insects also emit their ultrasound at unusually elevated sound pressure levels (SPL). In all three species these calls exceed 110 dB SPL rms re 20 µPa (at 15 cm). Males of Supersonus spp. have unusually reduced forewings (<0.5 mm2). Only the right wing radiates appreciable sound, the left bears the file and does not show a particular resonance. In contrast to most katydids, males of Supersonus spp. position and move their wings during sound production so that the concave aspect of the right wing, underlain by the insect dorsum, forms a contained cavity with sharp resonance. The observed high SPL at extreme carrier frequencies can be explained by wing anatomy, a resonant cavity with a membrane, and cuticle deformation

Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

<p>Abstract</p> <p>Background</p> <p>The identification and characterization of several interferon (IFN)-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5) that blocks a unique late stage of the HIV-1 life cycle.</p> <p>Results</p> <p>HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV) Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus.</p> <p>Conclusions</p> <p>HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.</p

Awe and Wonder in Scientific Practice: Implications for the Relationship Between Science and Religion

This paper examines the role of awe and wonder in scientific practice. Drawing on evidence from psychological research and the writings of scientists and science communicators, I argue that awe and wonder play a crucial role in scientific discovery. They focus our attention on the natural world, encourage open-mindedness, diminish the self (particularly feelings of self-importance), help to accord value to the objects that are being studied, and provide a mode of understanding in the absence of full knowledge. I will flesh out implications of the role of awe and wonder in scientific discovery for debates on the relationship between science and religion. Abraham Heschel argued that awe and wonder are religious emotions because they reduce our feelings of self-importance, and thereby help to cultivate the proper reverent attitude towards God. Yet metaphysical naturalists such as Richard Dawkins insist that awe and wonder need not lead to any theistic commitments for scientists. The awe some scientists experience can be regarded as a form of non-theistic spirituality, which is neither a reductive naturalism nor theism. I will attempt to resolve the tension between these views by identifying some common ground

Flow through a circular tube with a permeable Navier slip boundary

For Newtonian fluid flow in a right circular tube, with a linear Navier slip boundary, we show that a second flow field arises which is different to conventional Poiseuille flow in the sense that the corresponding pressure is quadratic in its dependence on the length along the tube, rather than a linear dependence which applies for conventional Poiseuille flow. However, assuming that the quadratic pressure is determined, say from known experimental data, then the new solution only exists for a precisely prescribed permeability along the boundary. While this cannot occur for conventional pipe flow, for fluid flow through carbon nanotubes embedded in a porous matrix, it may well be an entirely realistic possibility, and could well explain some of the high flow rates which have been reported in the literature. Alternatively, if the radial boundary flow is prescribed, then the new flow field exists only for a given quadratic pressure. Our primary purpose here is to demonstrate the existence of a new pipe flow field for a permeable Navier slip boundary and to present a numerical solution and two approximate analytical solutions. The maximum flow rate possible for the new solution is precisely twice that for the conventional Poiseuille flow, which occurs for constant inward directed flow across the boundary

Messina: A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease

BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package