104 research outputs found
"Psychic Degenerate": Why G. Was Interned
Abstract
This chapter explains how homosexuality was pathologised: to do this, it traces the origins of the "effeminate male" stereotype, explaining how the socio-cultural concept of degeneration was extended to include "sexual inversion". Through the doctors' words, G.'s biography starts to take shape and it becomes clear how it matched the "degenerate" and "effeminate pederast" stereotypical description
Combinatorial Clustering of Residue Position Subsets Predicts Inhibitor Affinity across the Human Kinome
The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell. Because
of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity
among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and
physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity.
The Combinatorial Clustering Of Residue Position Subsets (CCORPS) method, introduced here, provides a semi-supervised
learning approach for identifying structural features that are correlated with a given set of annotation labels. Here, CCORPS is
applied to the problem of identifying structural features of the kinase ATP binding site that are informative of inhibitor
binding. CCORPS is demonstrated to make perfect or near-perfect predictions for the binding affinity profile of 8 of the 38
kinase inhibitors studied, while only having overall poor predictive ability for 1 of the 38 compounds. Additionally, CCORPS is
shown to identify shared structural features across phylogenetically diverse groups of kinases that are correlated with
binding affinity for particular inhibitors; such instances of structural similarity among phylogenetically diverse kinases are
also shown to not be rare among kinases. Finally, these function-specific structural features may serve as potential starting
points for the development of highly specific kinase inhibitors
Identifying Compound-Target Associations by Combining Bioactivity Profile Similarity Search and Public Databases Mining
Molecular target identification is of central importance to drug discovery. Here, we developed a computational approach, named bioactivity profile similarity search (BASS), for associating targets to small molecules by using the known target annotations of related compounds from public databases. To evaluate BASS, a bioactivity profile database was constructed using 4296 compounds that were commonly tested in the US National Cancer Institute 60 human tumor cell line anticancer drug screen (NCI-60). Each compound was used as a query to search against the entire bioactivity profile database, and reference compounds with similar bioactivity profiles above a threshold of 0.75 were considered as neighbor compounds of the query. Potential targets were subsequently linked to the identified neighbor compounds by using the known targets o
Advances in structure elucidation of small molecules using mass spectrometry
The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules
INPH and parkinsonism: A positive shunt response with a negative tap test
IntroductionThe aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery. Materials and methodsThis is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P-). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery. ResultsA total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P-. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P- on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P- for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P- significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299). ConclusionPatients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS
Characterization of urinary stones using Raman and Fourier transform infrared spectroscopy compared to a chemical colorimetric method
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