Understanding Optical Music Recognition

For over 50 years, researchers have been trying to teach computers to read music notation, referred to as Optical Music Recognition (OMR). However, this field is still difficult to access for new researchers, especially those without a significant musical background: Few introductory materials are available, and, furthermore, the field has struggled with defining itself and building a shared terminology. In this work, we address these shortcomings by (1) providing a robust definition of OMR and its relationship to related fields, (2) analyzing how OMR inverts the music encoding process to recover the musical notation and the musical semantics from documents, and (3) proposing a taxonomy of OMR, with most notably a novel taxonomy of applications. Additionally, we discuss how deep learning affects modern OMR research, as opposed to the traditional pipeline. Based on this work, the reader should be able to attain a basic understanding of OMR: its objectives, its inherent structure, its relationship to other fields, the state of the art, and the research opportunities it affords

A membrane reformer with permeate side combustion for CO2 capture: Modeling and design

AbstractThe design of a pre-combustion natural gas fired power plant is presented, which makes use of a membrane assisted reformer with permeate side combustion. A detailed reactor model has been made with which the impact of the air distribution pattern is assessed. The results demonstrate that a flat air distribution pattern is sufficient for avoiding hot spots in the reactor. A system assessment shows that the concept is competitive with conventional membrane reformers in terms of system efficiency, and offers a more compact design

Charge Detection Mass Spectrometry Reveals Conformational Heterogeneity in Megadalton-Sized Monoclonal Antibody Aggregates

Aggregation of protein-based therapeutics can occur during development, production, or storage and can lead to loss of efficacy and potential toxicity. Native mass spectrometry of a covalently linked pentameric monoclonal antibody complex with a mass of ∼800 kDa reveals several distinct conformations, smaller complexes, and abundant higher-order aggregates of the pentameric species. Charge detection mass spectrometry (CDMS) reveals individual oligomers up to the pentamer mAb trimer (15 individual mAb molecules; ∼2.4 MDa) whereas intermediate aggregates composed of 6-9 mAb molecules and aggregates larger than the pentameric dimer (1.6 MDa) were not detected/resolved by standard mass spectrometry, size exclusion chromatography (SEC), capillary electrophoresis (CE-SDS), or by mass photometry. Conventional quadrupole time-of-flight mass spectrometry (QTOF MS), mass photometry, SEC, and CE-SDS did not resolve partially or more fully unfolded conformations of each oligomer that were readily identified using CDMS by their significantly higher extents of charging. Trends in the charge-state distributions of individual oligomers provides detailed insight into how the structures of compact and elongated mAb aggregates change as a function of aggregate size. These results demonstrate the advantages of CDMS for obtaining accurate masses and information about the conformations of large antibody aggregates despite extensive overlapping m/z values. These results open up the ability to investigate structural changes that occur in small, soluble oligomers during the earliest stages of aggregation for antibodies or other proteins

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis

Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU)

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment

Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU)

Trehalose-6-phosphate-mediated toxicity determines essentiality of OtsB2 in Mycobacterium tuberculosis in vitro and in mice

Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2. We found that otsB2 is essential for growth of M. tuberculosis in vitro as well as for the acute infection phase in mice following aerosol infection. By contrast, otsB2 is not essential for the chronic infection phase in mice, highlighting the substantial remodelling of trehalose metabolism during infection by M. tuberculosis. Blocking OtsB2 resulted in the accumulation of its substrate T6P, which appears to be toxic, leading to the self-poisoning of cells. Accordingly, blocking T6P production in a ΔotsA mutant abrogated otsB2 essentiality. T6P accumulation elicited a global upregulation of more than 800 genes, which might result from an increase in RNA stability implied by the enhanced neutralization of toxins exhibiting ribonuclease activity. Surprisingly, overlap with the stress response caused by the accumulation of another toxic sugar phosphate molecule, maltose-1-phosphate, was minimal. A genome-wide screen for synthetic lethal interactions with otsA identified numerous genes, revealing additional potential drug targets synergistic with OtsB2 suitable for combination therapies that would minimize the emergence of resistance to OtsB2 inhibitors

Gravitational Reference Sensor Front-End Electronics Simulator for LISA

At the ETH Zurich we are developing a modular simulator that provides a realistic simulation of the Front End Electronics (FEE) for LISA Gravitational Reference Sensor (GRS). It is based on the GRS FEE-simulator already implemented for LISA Pathfinder. It considers, in particular, the non-linearity and the critical details of hardware, such as the non-linear multiplicative noise caused by voltage reference instability, test mass charging and detailed actuation and sensing algorithms. We present the simulation modules, considering the above-mentioned features. Based on the ETH GRS FEE-simulator for LISA Pathfinder we aim to develop a modular simulator that provides a realistic simulation of GRS FEE for LISA

GRS vs. OMS Calibration in LISA Pathfinder Data Analysis

On board LISA Pathfinder spacecraft the test mass displacement along the main measurement axis is sensed in two different ways: optically and electrostatically. We have monitored the relative calibration between the two measurements during the mission science phase. The trend sensitivity of the relative calibration has been computed for different physical parameters, such as temperature, magnetic field, test mass bias voltage and current

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

High–Valent Metal–Oxo and –Hydroxo Porphyrinoid Complexes: Structural and Mechanistic Studies

The heme cofactor, which consists of an iron-bound porphyrin, is at the active site of many enzymes and facilitates several critical transformations in biology. Heme enzymes utilize common intermediates (such as metal-oxo and –hydroxo species) derived from dioxygen in their mechanistic cycles. The development of synthetic analogs of these intermediates allow for structure-function correlations to be made, and provides systems in which bond-making and bond-breaking events that occur at the metal to be studied in well-controlled environments. This dissertation features structural and reactivity studies on various metal(V)-oxo porphyrinoid complexes, as well as on novel metal(IV)-hydroxo complexes. An overview to high-valent iron-oxo and iron-hydroxo species found in heme enzymes, as well as a background on the synthetic metalloporphyrinoid analogues using Fe, Mn, and Re complexes are provided in Chapter 1. Valence tautomerism in high-valent metalloporphyrinoid complexes is also briefly discussed. In Chapter 2, the O-atom transfer (OAT) reactivity of a MnV(O) complex, MnV(O)(TBP8Cz) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3-) was compared with its valence tautomer, a MnIV(O) π-radical-cation complex, stabilized by addition of Lewis acids (LA) (LA = ZnII, B(C6F5)3, H+). The MnIV(O)(π-radical-cation) derivatives exhibit dramatically inhibited OAT rates with the triarylphosphine (PAr3) substrates as compared to the MnV(O) tautomer, contrasting the previously observed rate increase of H-atom transfer (HAT) for MnIV(O-LA)(TBP8Cz•+) with phenols. Chapter 3 describes the isolation of an ReV(O)(TBP8Cz) complex, an isoelectronic analogue to MnV(O)(TBP8Cz). The reactivity of this complex involves one of the meso-N atoms of the corrolazine ligand. One-electron oxidation of this ReV(O) complex leads to the formation of ReV(O)(TBP8Cz•+), which is reactive towards H-atom donors. These experiments demonstrate that the meso-N atom of corrolazine π-radical cation complexes can also serve as a site for H-atom transfer reactions. The direct observation of the oxygen rebound step in transition metal-catalyzed C-H hydroxylation reactions is featured in Chapter 4. Key to this study is the synthesis of the first example of an FeIV(OH) model complex, stabilized in a corrole scaffold. Mechanistic analysis of the reaction of this complex, FeIV(OH)(ttppc) (ttppc = tris(2,4,6-triphenyl)phenyl), with a series of para-substituted trityl radicals led to the conclusion that the oxygen rebound occurs in a concerted fashion, as opposed to a stepwise electron transfer/carbocation transfer mechanism. In Chapter 5, assessment of the electronic structures of formally FeIV corroles, FeIV(OH)(ttppc) and FeIV(Cl)(ttppc), was carried out with Fe K- and L2,3-edge spectroscopies. These experiments, along with density functional theory calculations, suggest that these complexes are best described as FeIII corrole π-radical cation complexes. These findings demonstrate that a pure FeIV state is not necessary for radical rebound reactivity in synthetic models of heme enzymes. Chapter 6 describes the isolation and structural characterization of Mn corrole complexes in three oxidation states: MnV(O)(ttppc), MnIV(OH)(ttppc), and MnIII(OH2)(ttppc). These complexes constitute the different forms of metalloporphyrinoid species over the course of an H-atom transfer reaction to a high-valent metal-oxo species. The H-atom transfer reactivity of the MnV(O) and MnIV(OH) complexes were compared and placed in the context of the mechanism of H-atom abstraction by other metal-oxo complexes. MnIV(OH)(ttppc) was shown to cleave phenolic O-H bonds with much faster rates than MnV(O)(ttppc), supporting a mechanism in which MnIV(OH)(ttppc) is a steady-state intermediate during H-atom abstraction with MnV(O)(ttppc). Further study of these reactions, including the measurement of a deuterium kinetic isotope effect (KIE), provides insight into the mechanism of HAT. The H-atom transfer reactivity of FeIV(OH)(ttppc) towards substituted phenol derivatives is presented in Chapter 7. These reactions are shown in the context of substrate desaturation, which occurs as an alternative to substrate hydroxylation. Rapid H-atom transfer kinetics are observed, in contrast to the slower rebound kinetics seen under similar conditions. Analysis of the HAT reaction leads to a concerted H-atom transfer mechanism for FeIV(OH)(ttppc). In Chapter 8 the synthesis and characterization of a diiron µ-oxo-dimer and an FeIV(OH) species in a dichlorophenyl-substituted corrole scaffold is presented. The µ-oxo dimer [FeIV(tdcc)]2(O) (tdcc = tris(2,6-dichlorophenyl)corrole) was isolated by addition of excess OH‑ to FeIV(Cl)(tdcc), and was characterized by X-ray crystallography. Controlled, stoichiometric addition of OH‑ to FeIV(Cl)(tdcc) led to the in situ formation of FeIV(OH)(tdcc), which could be characterized by paramagnetic 1H NMR. This work led to some insights on the requirements for stabilizing and isolating Fe(OH) units in corroles