Pulsed plasma chemical functionalization of solid surfaces

Pulsed plasma polymerization provides a highly efficient, single step, solventless method of surface functionalization. These surfaces can then be further derivatlzed for particular applications. The motivation underlying this work is to utilise this technique for a variety of applications to improve on existing methods of surface treatment. This approach is substrate independent and not hindered by geometry and in most cases the number of reactions stages required reach the desired product can be noticeably reduced. Applications for surface coatings produced in this research cover a wide area for example a single step method of manufacturing a thermally responsive coating for cell culture has been developed. Previous preparative methods have required three of more steps to produce the desired surface which comprises poly(n-isopropylacrylamide) and although attempts have been made employing plasma polymerization, the depositions were carried out under continuous wave conditions, resulting in Irreversible adsorption of proteins at temperatures above that of the lower critical solution temperature. A significant increase in structural retention and a lesser degree of cross-linking resulting from the use of pulsed conditions in this work has eliminated this major drawback. The versatility of pulsed plasma chemical functionalization has also been exemplified by the surface immobilization of various Initiating groups that can be further deployed to grow polymer brushes from the surface by a variety of well-established methods including atom transfer radical polymerization. This method has found to be suitable for a wide range of substrates such as silicon, polytetrafluoretylene and polystyrene beads. The formation of block copolymers and microscopic polymeric arrays has also been possible. Plasma polymer coatings generated from nitrogen-containing precursors have allowed the surface attachment of a Palladium catalyst, which in turn facilitates the electrode less deposition of transition metals. Previously, catalysts could not be adhered to a substrate In less than four or five individual steps. The approach adopted here achieved the desired results in just two reaction stages

Costs of Illness in the 1993 Waterborne Cryptosporidium Outbreak, Milwaukee, Wisconsin

To assess the total medical costs and productivity losses associated with the 1993 waterborne outbreak of cryptosporidiosis in Milwaukee, Wisconsin, including the average cost per person with mild, moderate, and severe illness, we conducted a retrospective cost-of-illness analysis using data from 11 hospitals in the greater Milwaukee area and epidemiologic data collected during the outbreak. The total cost of outbreak-associated illness was $96.2 million:$31.7 million in medical costs and $64.6 million in productivity losses. The average total costs for persons with mild, moderate, and severe illness were$116, $475, and$7,808, respectively. The potentially high cost of waterborne disease outbreaks should be considered in economic decisions regarding the safety of public drinking water supplies

Interobserver Reliability in the Interpretation of Computed Tomographic Scans of Stroke Patients

Interobserver Reliability in Interpretation of Computed Tomographic Images Was Studied by Six Senior Neurologists Who Independently Evaluated on a Standardized Stroke Data Bank Form the Brain Lesions of 17 Patients. the Results Analyzed with K Statistics Yielded Moderate to Substantial Agreement on Most Items of Interest Including the Stroke Pathology and Anatomy. in General, the Levels of Agreement Were as High as Previously Reported for the Diagnosis of the Mechanism of the Stroke, and Much Higher Than on Many Stroke History Items and Items of Neurologic Examination. Excellent Agreement Was Obtained for the Detection of Infarcts and Intracerebral Hemorrhage, and Substantial Agreement Was Obtained on Whether the Computed Tomographic Images Were Normal or Indicative of Small Deep Infarcts, Superficial and Deep Infarcts, and Aneurysms. the Level of Agreement on Anatomy of the Lesions Was Best for the Frontal, Parietal, and Temporal Lobes, Putamen, Cerebellum, and Subarachnoid Space. Implications for Clinical Research and Diagnosis Are Discussed. © 1987 American Medical Association All Rights Reserved

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

The IceCube Data Acquisition System: Signal Capture, Digitization, and Timestamping

IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs), detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved.Comment: 42 pages, 20 figures, submitted to Nuclear Instruments and Methods

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation

All-flavor constraints on nonstandard neutrino interactions and generalized matter potential with three years of IceCube DeepCore data

We report constraints on nonstandard neutrino interactions (NSI) from the observation of atmospheric neutrinos with IceCube, limiting all individual coupling strengths from a single dataset. Furthermore, IceCube is the first experiment to constrain flavor-violating and nonuniversal couplings simultaneously. Hypothetical NSI are generically expected to arise due to the exchange of a new heavy mediator particle. Neutrinos propagating in matter scatter off fermions in the forward direction with negligible momentum transfer. Hence the study of the matter effect on neutrinos propagating in the Earth is sensitive to NSI independently of the energy scale of new physics. We present constraints on NSI obtained with an all-flavor event sample of atmospheric neutrinos based on three years of IceCube DeepCore data. The analysis uses neutrinos arriving from all directions, with reconstructed energies between 5.6 GeV and 100 GeV. We report constraints on the individual NSI coupling strengths considered singly, allowing for complex phases in the case of flavor-violating couplings. This demonstrates that IceCube is sensitive to the full NSI flavor structure at a level competitive with limits from the global analysis of all other experiments. In addition, we investigate a generalized matter potential, whose overall scale and flavor structure are also constrained

Search for Quantum Gravity Using Astrophysical Neutrino Flavour with IceCube

Along their long propagation from production to detection, neutrino states undergo quantum interference which converts their types, or flavours. High-energy astrophysical neutrinos, first observed by the IceCube Neutrino Observatory, are known to propagate unperturbed over a billion light years in vacuum. These neutrinos act as the largest quantum interferometer and are sensitive to the smallest effects in vacuum due to new physics. Quantum gravity (QG) aims to describe gravity in a quantum mechanical framework, unifying matter, forces and space-time. QG effects are expected to appear at the ultra-high-energy scale known as the Planck energy, $E_{P}\equiv 1.22\times 10^{19}$~giga-electronvolts (GeV). Such a high-energy universe would have existed only right after the Big Bang and it is inaccessible by human technologies. On the other hand, it is speculated that the effects of QG may exist in our low-energy vacuum, but are suppressed by the Planck energy as $E_{P}^{-1}$ ($\sim 10^{-19}$~GeV$^{-1}$), $E_{P}^{-2}$ ($\sim 10^{-38}$~GeV$^{-2}$), or its higher powers. The coupling of particles to these effects is too small to measure in kinematic observables, but the phase shift of neutrino waves could cause observable flavour conversions. Here, we report the first result of neutrino interferometry~\cite{Aartsen:2017ibm} using astrophysical neutrino flavours to search for new space-time structure. We did not find any evidence of anomalous flavour conversion in IceCube astrophysical neutrino flavour data. We place the most stringent limits of any known technologies, down to $10^{-42}$~GeV$^{-2}$, on the dimension-six operators that parameterize the space-time defects for preferred astrophysical production scenarios. For the first time, we unambiguously reach the signal region of quantum-gravity-motivated physics.Comment: The main text is 7 pages with 3 figures and 1 table. The Appendix includes 5 pages with 3 figure

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale νμ_{μ} Disappearance at IceCube

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter εμτ. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of −0.0041≤εμτ≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date

Validation of Human Telomere Length Multi-Ancestry Meta-Analysis Association Signals Identifies POP5 and KBTBD6 as Human Telomere Length Regulation Genes

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation