Conversion detection for improved online ad selection

Online ads sometimes continue unchanged even after the ad had resulted in a conversion, e.g., after a user has purchased the advertised product. Many users find such continued presence of the ad annoying. Also, not refreshing the ad with a different product represents lost revenue for the website publisher and the ad network. This disclosure describes techniques to detect if the user has purchased a given product by analyzing, with user consent and permission, user data such as emails and other data. Upon detecting conversion, display of ads relating to the product or similar products is discontinued

Facial Onset Sensory and Motor Neuronopathy: A Case Series and Literature Review

Introduction: Facial Onset Sensory and Motor Neuronopathy (FOSMN) typically presents with paresthesias in the trigeminal nerve distribution and weakness that progresses rostro-caudally. Objective: To present two new cases of FOSMN, summarize the current literature, and address areas for future study. Methods: Observational data was collected from two patients with FOSMN from our institution. A literature review of FOSMN was completed using PubMed. Results: We identified 100 cases of FOSMN, including our two new cases. 93% presented with facial paresthesias. 97% had bulbar symptoms. Five had family history of ALS. Abnormal Blink reflex was most common on EMG/NCS. CSF was typically normal, but a rare severe case showed elevated protein. Mutations included: TARDBP, OPMD, D90A-SOD1, CHCHD10, VCP, and SQSTM1. Neuropathological studies showed neurodegenerative changes without inflammation. Some cases have reported transient stabilization or improvement to immunomodulatory therapy. Case Reports: A 72-year-old man presented with right-sided trigeminal paresthesias that progressed in a rostro-caudal fashion, dysphagia, and hand weakness. He died 4-5 years after symptom onset. A 69-year-old man presented with left-sided jaw paresthesias, dysphagia and dysarthria. He was trialed on IVIG for 1.5 years without improvement and died 2.6 years after symptom onset. Conclusion: FOSMN is a rare disorder with a unique clinical and electrophysiological phenotype. The pathophysiology has been associated with neurodegeneration and multiple gene mutations have correlated to FOSMN. Some reports suggest transient response to immunomodulatory therapy, though prospective studies are lacking. CSF protein elevation may be seen in severe disease. Future studies will help further elucidate the approach to diagnosis, treatment, and prognostic counseling (biomarkers). &nbsp

Apoptosis Initiation and Angiogenesis Inhibition: Melanoma Targets for Nanosecond Pulsed Electric Fields

Many effective anti-cancer strategies target apoptosis and angiogenesis mechanisms. Applications of non-ionizing, nanosecond pulsed electric fields (nsPEFs) induce apoptosis in vitro and eliminate cancer in vivo; however in vivo mechanisms require closer analysis. These studies investigate nsPEF-induced apoptosis and anti-angiogenesis examined by fluorescent microscopy, immunoblots, and morphology. Six hours after treatment with one hundred 300 ns pulses at 40 kV/cm, cells transiently expressed active caspases indicating that caspase-mediated mechanisms. Three hours after treatment transient peaks in Histone 2AX phosphorylation coincided with terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and pyknotic nuclei, suggesting caspase-independent mechanisms on nuclei/DNA. Large DNA fragments, but not 180 bp fragmentation ladders, were observed, suggesting incomplete apoptosis. Nevertheless, tumor weight and volume decreased and tumors disappeared. One week after treatment, vessel numbers, vascular endothelial growth factor (VEGF), platelet derived endothelial cell growth factor (PD-ECGF), CD31, CD35 and CD105 were decreased, indicating anti-angiogenesis. The nsPEFs activate multiple melanoma therapeutic targets, which is consistent with successes of nsPEF applications for tumor treatment in vivo as a new cancer therapeutic modality

Simulations of Intracellular Calcium Release Dynamics in Response to a High-Intensity, Ultrashort Electric Pulse

Numerical simulations for electrically induced, intracellular calcium release from the endoplasmic reticulum are reported. A two-step model is used for self-consistency. Distributed electrical circuit representation coupled with the Smoluchowski equation yields the ER membrane nanoporation for calcium outflow based on a numerical simulation. This is combined with the continuum Li-Rinzel model and drift diffusion for calcium dynamics. Our results are shown to be in agreement with reported calcium release data. A modest increase (rough doubling) of the cellular calcium is predicted in the absence of extra-cellular calcium. In particular, the applied field of 15 kV/cm with 60 ns pulse duration makes for a strong comparison. No oscillations are predicted and the net recovery period of about 5 min are both in agreement with published experimental results. A quantitative explanation for the lack of such oscillatory behavior, based on the density dependent calcium fluxes, is also provided

A novel cell immunoassay to measure survival of motor neurons protein in blood cells

BACKGROUND: The motor neuron degenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN) gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples. METHODS: We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody. RESULTS: SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity. CONCLUSION: SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials

Autoregulation of the Escherichia coli melR promoter: repression involves four molecules of MelR

The Escherichia coli MelR protein is a transcription activator that autoregulates its own promoter by repressing transcription initiation. Optimal repression requires MelR binding to a site that overlaps the melR transcription start point and to upstream sites. In this work, we have investigated the different determinants needed for optimal repression and their spatial requirements. We show that repression requires a complex involving four DNA-bound MelR molecules, and that the global CRP regulator plays little or no role

Woody plants optimise stomatal behaviour relative to hydraulic risk

Stomatal response to environmental conditions forms the backbone of all ecosystem and carbon cycle models, but is largely based on empirical relationships. Evolutionary theories of stomatal behaviour are critical for guarding against prediction errors of empirical models under future climates. Longstanding theory holds that stomata maximise fitness by acting to maintain constant marginal water use efficiency over a given time horizon, but a recent evolutionary theory proposes that stomata instead maximise carbon gain minus carbon costs/risk of hydraulic damage. Using data from 34 species that span global forest biomes, we find that the recent carbon‐maximisation optimisation theory is widely supported, revealing that the evolution of stomatal regulation has not been primarily driven by attainment of constant marginal water use efficiency. Optimal control of stomata to manage hydraulic risk is likely to have significant consequences for ecosystem fluxes during drought, which is critical given projected intensification of the global hydrological cycle.W.R.L.A. acknowledges funding for this research from NSF 1714972 and from the USDA National Institute of Food and Agriculture, Agricultural and Food Research Initiative Competitive Programme, Ecosystem Services and Agro-Ecosystem Management, grant no. 2017-05521. We thank T. Brodribb and one anonymous reviewer for their insightful reviews, B. Medlyn and Y.S. Lin for sharing data and R. Norby for providing Vcmax data for several species. We appreciate the assistance from Marion Feifel in collecting data of leaf photosynthetic parameters of five European tree species. S.L. acknowledges financial support from the China Scholarship Council (CSC). VRD acknowledges funding from a Ram on y Cajal fellowship (RYC-2012-10970). B.T.W. was supported by the Next Generation Ecosystem Experiments-Tropics, funded by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research. DJC acknowledges funding from the National Science Centre, Poland (NN309 713340)

Bioelectric Effects of Intense Nanosecond Pulses

Electrical models for biological cells predict that reducing the duration of applied electrical pulses to values below the charging time of the outer cell membrane (which is on the order of 100 ns for mammalian cells) causes a strong increase in the probability of electric field interactions with intracellular structures due to displacement currents. For electric field amplitudes exceeding MV/m, such pulses are also expected to allow access to the cell interior through conduction currents flowing through the permeabilized plasma membrane. In both cases, limiting the duration of the electrical pulses to nanoseconds ensures only nonthermal interactions of the electric field with subcellular structures. This intracellular access allows the manipulation of cell functions. Experimental studies, in which human cells were exposed to pulsed electric fields of up to 300 kY/cm amplitude with durations as short as 3 ns, have confirmed this hypothesis and have shown that it is possible to selectively alter the behavior and/or survival of cells. Observed nanosecond pulsed effects at moderate electric fields include intracellular release of calcium and enhanced gene expression, which could have long term implications on cell behavior and function. At increased electric fields, the application of nanosecond pulses induces a type of programmed cell death, apoptosis, in biological cells. Cell survival studies with 10 ns pulses have shown that the viability of the cells scales inversely with the electrical energy density, which is similar to the ‘dose’ effect caused by ionizing radiation. On the other hand, there is experimental evidence that, for pulses of varying durations, the onset of a range of observed biological effects is determined by the electrical charge that is transferred to the cell membrane during pulsing. This leads to an empirical similarity law for nanosecond pulse effects, with the product of electric field intensity, pulse duration, and the square root of the number of pulses as the similarity parameter. The similarity law allows one not only to predict cell viability based on pulse parameters, but has also been shown to be applicable for inducing platelet aggregation, an effect which is triggered by internal calcium release. Applications for nanosecond pulse effects cover a wide range: from a rather simple use as preventing biofouling in cooling water systems, to advanced medical applications, such as gene therapy and tumor treatment. Results of this continuing research are leading to the development of wound healing and skin cancer treatments, which are discussed in some detail