The steroid sulphates: studies on the conjugated sulphates of mare's pregnancy urine

The original purpose of this work was to determine the constitution of an organic half -ester of sulphuric acid isolated from mare's pregnancy urine by Schachter and Marrian in Toronto in 1938.Two new organic sulphates, one of which may be identical with that of Schachter, have been isolated and studied. The scope of the work has been widened, so that it now represents some initial stages in a general study of the conjugates of horse urine. Some incidental work on the pure chemistry of organic sulphates has also been done.PART 1 of this Thesis outlines the previous work on the organic sulphates of mare's pregnancy urine (Schachter and Marrian, 1936, 1938; Schachter, Ph.D. Thesis, 1939; Butenandt and I-Iofstetter, 1939) .PART 2 describes the sources and collection of urine, the extraction of the sulphates and the early stages in their purification. These methods have been developed from those of Schachter.PART 3 describes the isolation and study of a sulphate (2 sulphate) which may be identical with that of Schachter and Marrian. This sulphate on acid hydrolysis yields a compound of the probable formula C₂₁H₃₂O₂ (Compound Z) which is apparently not identical with any substance previously obtained from mare's pregnancy urine. Z appears to be a 3-ß-hydroxy steroid and may contain an αß-unsaturated ketonic group. Comparison of Z and Δ¹⁶ allopregnene-3 (ß)-ol-20-one indicates that these substances are probably identical, although the evidence is insufficient for proof.PART 4 describes the isolation and study of another sulphate (Y sulphate). This on acid hydrolysis yields Compound Y, probable formula C₂₁H₃₂O₂. Y is a saturated dihydroxy compound, probably a 3(ß)-hydroxy steroid. The properties of Y and its derivatives closely resemble those of ' uranediol' and its derivatives (Marker et al., 1938f), but no direct comparison has yet been possible.PART 5 of this Thesis describes miscellaneous experiments on mare's urine, conjugates, incidental to the study of Z and Y, which may be useful if a thorough study of horse-urine steroids is undertaken.The great drawback throughout the work has been lack of material. Probably more time has been spent in looking for urine than in working it up. So far as the primary purpose of the work is concerned, lack of material has prevented a complete study of Compounds Z and Y. In the wider field, few definite results have been obtained; it has rarely been possible to study a number of batches of urine in the same way, and so to obtain results of quantitative significance. Again,while many different methods of extraction and separation have been tried at different times (Part 2, section 6), controls have rarely been carried out, and this part of the work must be considered a very sporadic reconnaisance The author begs anyone who reads this thesis to bear these facts constantly in mind

Microhydration of protonated 5-hydroxyindole revealed by infrared spectroscopy

Controlled microsolvation of protonated aromatic biomolecules with water is fundamental to understand proton transfer reactions in aqueous environments. We measured infrared photodissociation (IRPD) spectra of mass-selected microhydrates of protonated 5-hydroxyindole (5HIH+–Wn, W = H2O, n = 1–3) in the OH and NH stretch ranges (2700–3800 cm−1), which are sensitive to the spectroscopic characteristics of interior solvation, water network formation, and proton transfer to solvent. Analysis of the IRPD spectra by dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ) reveals the coexistence of C3- and C4-protonated carbenium ions, 5HIH+(C3) and 5HIH+(C4), as well as the O-protonated oxonium ion, 5HIH+(O). Monohydrated 5HIH+–W2/3 clusters are formed by hydrogen-bonding (H-bonding) of the first water to the most acidic functional group, namely, the NH group in the case of 5HIH+(C3), the OH group for 5HIH+(C4), and the OH2 group for 5HIH+(O). The latter benefits from its twofold degeneracy and the outstandingly high binding energy of D0 ∼ 100 kJ mol−1. Larger 5HIH+–W2/3 clusters preferably grow (i) by H-bonding of the second water to the remaining vacant functional group and and/or (ii) by formation of W2 water chains at the respective most acidic functional group. Our IRPD spectra of 5HIH+–Wn do not indicate any proton transfer to the solvent up to n = 3, in line with the proton affinities of 5HI and Wn. Comparison of 5HIH+–Wn to neutral 5HI–W and cationic 5HI+–Wn clusters elucidates the impact of different charge states on the topology of the initial solvation shell. Furthermore, to access the influence of the size of the arene ion and a second functional group, we draw a comparison to microhydration of protonated phenol.TU Berlin, Open-Access-Mittel - 201

Gathering Our Medicine: Strengthening and Healing Relationships Between Indigenous Youth and their Kinship Circle

Long held beliefs about “right” responses to human suffering that underpin the dominant mental health paradigm are Eurocentric and marginalize Indigenous worldviews, including definitions of wellness and beliefs about the aims of healing. Also to be noted is the fact that the mental health field has evolved to the exclusion of Indigenous ontologies and epistemologies resulting in ongoing subjugation and ethno-stress. Approaches characterized by superficial and reductionistic interpretations of symptoms further obfuscate understanding by the non-expert resulting in the ongoing disempowerment of Indigenous peoples, in particular, parents. For all these reasons, I contend that the dominant mental health paradigm is problematic for Indigenous peoples.  I propose an alternative way of seeing and responding to the impacts of intergenerational trauma, Gathering Our Medicine (GOM), that offers a more ethical response to the escalating mental health crisis that exists within Indigenous communities and families. GOM has an entry point to healing that invites questioning the very presuppositions that underlie long held and unquestioned beliefs about healing, wellness, and mental health. In this presentation, a concretely outlined protocol for healing was proposed entitled The Four Circles of Healing. Lessons learned through the creation and implementation of this community-based program, GOM, were also shared.

Average partial effect estimation using double machine learning

Single-parameter summaries of variable effects are desirable for ease of interpretation, but linear models, which would deliver these, may fit poorly to the data. A modern approach is to estimate the average partial effect -- the average slope of the regression function with respect to the predictor of interest -- using a doubly robust semiparametric procedure. Most existing work has focused on specific forms of nuisance function estimators. We extend the scope to arbitrary plug-in nuisance function estimation, allowing for the use of modern machine learning methods which in particular may deliver non-differentiable regression function estimates. Our procedure involves resmoothing a user-chosen first-stage regression estimator to produce a differentiable version, and modelling the conditional distribution of the predictors through a location-scale model. We show that our proposals lead to a semiparametric efficient estimator under relatively weak assumptions. Our theory makes use of a new result on the sub-Gaussianity of Lipschitz score functions that may be of independent interest. We demonstrate the attractive numerical performance of our approach in a variety of settings including ones with misspecification.Comment: 61 pages, 4 figure

Adventures in Semantic Publishing: Exemplar Semantic Enhancements of a Research Article

Scientific innovation depends on finding, integrating, and re-using the products of previous research. Here we explore how recent developments in Web technology, particularly those related to the publication of data and metadata, might assist that process by providing semantic enhancements to journal articles within the mainstream process of scholarly journal publishing. We exemplify this by describing semantic enhancements we have made to a recent biomedical research article taken from PLoS Neglected Tropical Diseases, providing enrichment to its content and increased access to datasets within it. These semantic enhancements include provision of live DOIs and hyperlinks; semantic markup of textual terms, with links to relevant third-party information resources; interactive figures; a re-orderable reference list; a document summary containing a study summary, a tag cloud, and a citation analysis; and two novel types of semantic enrichment: the first, a Supporting Claims Tooltip to permit “Citations in Context”, and the second, Tag Trees that bring together semantically related terms. In addition, we have published downloadable spreadsheets containing data from within tables and figures, have enriched these with provenance information, and have demonstrated various types of data fusion (mashups) with results from other research articles and with Google Maps. We have also published machine-readable RDF metadata both about the article and about the references it cites, for which we developed a Citation Typing Ontology, CiTO (http://purl.org/net/cito/). The enhanced article, which is available at http://dx.doi.org/10.1371/journal.pntd.0000228.x001, presents a compelling existence proof of the possibilities of semantic publication. We hope the showcase of examples and ideas it contains, described in this paper, will excite the imaginations of researchers and publishers, stimulating them to explore the possibilities of semantic publishing for their own research articles, and thereby break down present barriers to the discovery and re-use of information within traditional modes of scholarly communication

The Research Object Suite of Ontologies: Sharing and Exchanging Research Data and Methods on the Open Web

Research in life sciences is increasingly being conducted in a digital and online environment. In particular, life scientists have been pioneers in embracing new computational tools to conduct their investigations. To support the sharing of digital objects produced during such research investigations, we have witnessed in the last few years the emergence of specialized repositories, e.g., DataVerse and FigShare. Such repositories provide users with the means to share and publish datasets that were used or generated in research investigations. While these repositories have proven their usefulness, interpreting and reusing evidence for most research results is a challenging task. Additional contextual descriptions are needed to understand how those results were generated and/or the circumstances under which they were concluded. Because of this, scientists are calling for models that go beyond the publication of datasets to systematically capture the life cycle of scientific investigations and provide a single entry point to access the information about the hypothesis investigated, the datasets used, the experiments carried out, the results of the experiments, the people involved in the research, etc. In this paper we present the Research Object (RO) suite of ontologies, which provide a structured container to encapsulate research data and methods along with essential metadata descriptions. Research Objects are portable units that enable the sharing, preservation, interpretation and reuse of research investigation results. The ontologies we present have been designed in the light of requirements that we gathered from life scientists. They have been built upon existing popular vocabularies to facilitate interoperability. Furthermore, we have developed tools to support the creation and sharing of Research Objects, thereby promoting and facilitating their adoption.Comment: 20 page

Interacting with robots as performers and producers of music

Is it really so strange to think about a robot as something, or perhaps someone that can produce music, as a performer or even as a composer? What happens when robots perform on stage to live audiences, and when they are perceived as intelligent? In this abstract we start to unpack and explicate some of the issues that emerge when the fields of music technology and robotics come together. The aim of this piece of writing is to prompt the Digital Music Research community to engage in debate, in order develop this emerging field of research

Diastereo-specific conformational properties of neutral, protonated and radical cation forms of (1R,2S)-cis- and (1R,2R)-trans-amino-indanol by gas phase spectroscopy

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Chirality effects on the intramolecular interactions strongly depend on the charge and protonation states. Here, the influence of chirality on the structure of the neutral, protonated, and radical cation forms of (1R,2S)-cis- and (1R,2R)-trans-1-amino-2-indanol diastereomers, prototypical molecules with two chiral centers, is investigated in a molecular beam by laser spectroscopy coupled with quantum chemical calculations. The neutral systems are structurally characterised by double resonance IR-UV spectroscopy, while IR-induced dissociation spectroscopy is employed for the charged molecules. The sterical constraints due to the cyclic nature of the molecule emphasise the chirality effects, which manifest themselves by the formation of an intramolecular hydrogen bond in neutral or protonated (1R,2S)-cis-amino-indanol. In contrast, this interaction is not possible in (1R,2R)-trans-amino-indanol. In the protonated species, chirality also influences the spectroscopic probes in the NH/OH stretch range by fine-tuning subtle effects such as the hyperconjugation between the sigma(OH) orbital and sigma* orbitals localised on the alicyclic ring. The radical cation undergoes opening of the alicyclic ring, which results in an ionisation-induced loss of the chirality effects.EC/FP7/600209/EU/International Post-Doc Initiative of the Technische Universität Berlin/IPODIEC/FP7/312284/EU/Coordinated Access to Lightsources to Promote Standards and Optimization/CALIPS

Risk factors for low back pain outcome: Does it matter when they are measured?

Background: The early identification of factors that increase risk of poor recovery from acute low back pain (LBP) is critical to prevent the transition to chronicity. Although most studies of risk factors for poor outcome in LBP tend to investigate the condition once it is already persistent, there is evidence to suggest that this differs from risk factors measured during the early-acute stage. This study aimed to identify early risk factors for poor outcome in the short- and long-term in individuals with acute LBP, and to compare this with factors identified at 3 months in the same cohort. Methods: One hundred and thirty-three individuals were recruited within 2 weeks of an acute LBP episode and completed questionnaires related to their sociodemographic, psychological, clinical and history/treatment status at baseline and 3 months later, and their pain-level fortnightly for 12 months. Results: Of the 133 participants recruited, follow-up data were provided by 120 at 3 months, 97 at 6 months, 85 at 9 months and 94 at 12 months. Linear regression identified various factors at baseline (acute phase) and 3 months later that predicted short- and long-term outcome (pain level, change in pain). Key findings were that: (1) depressive symptoms at baseline most consistently predicted worse outcome; (2) psychological factors in general at 3 months were more predictive of outcome than when measured at baseline; (3) early health care utilization predicted better outcome, whereas use of pain medication later (3 months) predicted worse outcome; and (4) sex and BMI predicted outcome inconsistently over 12-months. Conclusions: The results highlight the multidimensional nature of risk factors for poor outcome in LBP and the need to consider time variation in these factors

Effect of types and anatomical arrangement of painful stimuli on conditioned pain modulation

Reduced pain perception during painful stimulation to another body region (ie, conditioned pain modulation [CPM]) is considered important for pain modulation and development of pain disorders. The various methods used to study CPM limit comparison of findings. We investigated the influence of key methodologic variations on CPM and the properties of CPM when the back is used for the test stimulus or the conditioning stimulus (CS). Two different test stimuli (pressure pain threshold and pain response to suprathreshold heat [Pain-45, ie, pain rated at 45 on a 0–100 numeric rating scale]) were assessed before and during application of a noxious or non-noxious (sham) CS. Eight blocks of trials varied the anatomic location (back and forearms) and arrangement (body side) of the stimuli. Pressure pain threshold (as the test stimulus) increased during application of noxious, but not non-noxious, CS when stimuli were applied to opposite body sides or heterotopic sites on one body side. Inconsistent with pain-induced CPM, Pain-45 decreased during both noxious and non-noxious CS. These findings indicate that 1) pressure pain threshold can be more confidently interpreted with respect to CPM evoked by a painful stimulus than Pain-45, 2) the back and forearm are equally effective as sites for stimuli, and 3) stimuli arrangement does not influence CPM, except for identical anatomic regions on the same body side