gebhart/patrepeval huggingface dataset:
Characterization of Microbial Communities Found in the Human Vagina by Analysis of Terminal Restriction Fragment Length Polymorphisms of 16S rRNA Genes (2005)

To define and monitor the structure of microbial communities found in the human vagina, a cultivation-independent approach based on analyses of terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes was developed and validated. Sixteen bacterial strains commonly found in the human vagina were used to construct model communities that were subsequently used to develop efficient means for the isolation of genomic DNA and an optimal strategy for T-RFLP analyses. The various genera in the model community could best be resolved by digesting amplicons made using bacterial primers 8f and 926r with HaeIII; fewer strains could be resolved using other primer-enzyme combinations, and no combination successfully distinguished certain species of the same genus. To demonstrate the utility of the approach, samples from five women that had been collected over a 2-month period were analyzed. Differences and similarities among the vaginal microbial communities of the women were readily apparent. The T-RFLP data suggest that the communities of three women were dominated by a single phylotype, most likely species of Lactobacillus. In contrast, the communities of two other women included numerically abundant populations that differed from Lactobacillus strains whose 16S rRNA genes had been previously determined. The T-RFLP profiles of samples from all the women were largely invariant over time, indicating that the kinds and abundances of the numerically dominant populations were relatively stable throughout two menstrual cycles. These findings show that T-RFLP of 16S rRNA genes can be used to compare vaginal microbial communities and gain information about the numerically dominant populations that are present.
CYP17 Inhibitors for Prostate Cancer Treatment – An Update (2008)

It is almost 70 years since the discovery by Huggins et al. that androgens are essential for prostate cancer (PC) growth and progression, and there has been about 30 years experience using ketoconazole for PC therapy. Since then we have come a long way in learning about the disease and developing new strategies to approach it, among which is cytochrome 17alpha-hydroxylase-C(17,20)-lyase (CYP17) inhibition. This review focuses on the efforts to find prospective CYP17 inhibitors, both steroidal and nonsteroidal, in the absence of a 3D structure of the enzyme. It covers almost 4 decades of literature with highlights on the most significant achievements in this area, providing insight into PC pathophysiology, management and treatment options.
Discriminant Analysis of Raman Spectra for Body Fluid Identification for Forensic Purposes (2010)

Detection and identification of blood, semen and saliva stains, the most common body fluids encountered at a crime scene, are very important aspects of forensic science today. This study targets the development of a nondestructive, confirmatory method for body fluid identification based on Raman spectroscopy coupled with advanced statistical analysis. Dry traces of blood, semen and saliva obtained from multiple donors were probed using a confocal Raman microscope with a 785-nm excitation wavelength under controlled laboratory conditions. Results demonstrated the capability of Raman spectroscopy to identify an unknown substance to be semen, blood or saliva with high confidence.
Functional Modulation of the Glucocorticoid Receptor and Suppression of NF-κB-dependent Transcription by Ursodeoxycholic Acid (2001)

Ursodeoxycholic acid (UDCA) is the current mainstay of treatment for various liver diseases including primary biliary cirrhosis. UDCA acts as a bile secretagogue, cytoprotective agent, immunomodulator, and inhibitor of cellular apoptosis. Despite this cumulative evidence of the cytoprotective and immunosuppressive effects of UDCA, both the target molecule and pathway of UDCA action remain unknown. We previously described that, in the absence of glucocorticoid ligand, UDCA activates the glucocorticoid receptor (GR) into DNA binding species but does not elicit its transactivational function in a transient transfection assay. Here we further studied the molecular mechanism of UDCA action and revealed that the ligand binding domain of the GR is responsible for UDCA-dependent nuclear translocation of the GR. Indeed, we demonstrated that UDCA acts on the distinct region of the ligand binding domain when compared with the classical GR agonist dexamethasone, resulting in loss of coactivator recruitment and differential regulation of gene expression by the GR. Our data clearly indicated that UDCA, at least in part via activation of the GR, suppresses NF-kappaB-dependent transcription through the intervention of GR-p65 interaction. Together with the established clinical safety of UDCA, we may propose that UDCA could be a prototypical compound for development of a novel and selective GR modifier.
Stabilization and Release of Enzymes from Silk Films (2010)

A significant challenge remains to protect protein drugs from inactivation during production, storage, and use. In the present study, the stabilization and release of horseradish peroxidase (HRP) in silk films was investigated. Water-insoluble silk films were prepared under mild aqueous conditions, maintaining the activity of the entrapped enzyme. Depending on film processing and post-processing conditions, HRP retained more than 90% of the initial activity at 4 degrees C, room temperature and 37 degrees C over two months. The stability of protein drugs in silk films is attributed to intermolecular interactions between the silk and the enzymes, based on Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The unique structural feature of silk molecules, periodic hydrophobic-hydrophilic domains, enabled strong interactions with proteins. The entrapped protein was present in two states, untrapped active and trapped inactive forms. The ratio between the two forms varied according to processing conditions. Proteolytic degradation and dissolution of the silk films resulted in the release of the bound enzyme which was otherwise not released by diffusion; enzyme recovered full activity upon release. There was a linear relationship between silk degradation/dissolution and the release of entrapped enzyme. Modifying the secondary structure of the silk matrix and the interactions with the non-crystalline domains resulted in control of the film degradation or dissolution rate, and therefore the release rate of the entrapped enzyme. Based on the above results, silk materials are an intriguing carrier for proteins in terms of both retention of activity and controllable release kinetics from the films.
Comparison of correction techniques for simultaneous201Tl/99mTc myocardial perfusion SPECT imaging: a dog study (2000)

We compared two correction methods for simultaneous 201Tl/99mTc dual-isotope single-photon emission computed tomography (SPECT). Both approaches use the information from the third energy window placed between the photopeak windows of the 201Tl and 99mTc. The first approach, described by Moore et al, corrects only for the contribution of the 99mTc to the 201Tl primary 70 keV window. We developed the three-window transformation dual isotope correction method, which is a simultaneous cross-talk correction. The two correction methods were compared in a simultaneous 201Tl/99mTc sestamibi cardiac dog study. Three separate acquisitions were performed in this dog study: two single-isotope and one dual-isotope acquisition. The 201Tl single-isotope images were used as references. The total number of counts, and the contrast between the left ventricular cavity (LVC) and the myocardium, were used in 70 keV short axis slices as parameters for evaluating the results of the dual-isotope correction methods. Three consecutive short-axis slices were used to calculate averaged contrast and the averaged total number of counts. The total number of the counts was 667000+/-500 and 414500+/-400 counts for the dual isotope (201Tl+/-99mTc) and single-isotope (201Tl-only) 70 keV images, respectively. The corrected dual-isotope images had 514700+/-700 and 368000+/-600 counts for Moore's correction and our approach, respectively. Moore's method improved contrast in the dual isotope 70 keV image to 0.14+/-0.03 from 0.11+/-0.02, which was the value in the 70 keV non-corrected dual-isotope image. Our method improved the same contrast to 0.22+/-0.03. The contrast in the 201Tl single-isotope 70 keV image was 0.28+/-0.02. Both methods improved the 70 keV dual-isotope images. However, our approach provided slightly better images than Moore's correction when compared with 201Tl-only 70 keV images.
Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments (1999)

Myofibrillogenesis in situ was investigated by confocal microscopy of immunofluorescently labelled whole mount preparations of early embryonic chicken heart rudiments. The time-course of incorporation of several components into myofibrils was compared in triple-stained specimens, taken around the time when beating starts. All sarcomeric proteins investigated so far were already expressed before the first contractions and myofibril assembly happened within a few hours. No typical stress fibre-like structures or premyofibrils, structures observed in cultured cardiomyocytes, could be detected during myofibrillogenesis in the heart. Sarcomeric proteins like (&agr;)-actinin, titin and actin were found in a defined localisation pattern even in cardiomyocytes that did not yet contain myofibrils, making up dense body-like structures. As soon as the heart started to beat, all myofibrillar proteins were already located at their exact position in the sarcomere. The maturation of the sarcomeres was characterised by a short delay in the establishment of the pattern for M-line epitopes of titin with respect to Z-disk epitopes and the incorporation of the M-line component myomesin, which preceded that of myosin binding protein-C. Thus dense body-like structures, made up of titin, (&agr;)-actinin and actin filaments serve as the first organised complexes also during myofibrillogenesis in situ and titin functions as a ruler for sarcomere assembly as soon as its C termini have become localised. We suggest that assembly of thin and thick filament occurs independently during myofibrillogenesis in situ and that myomesin might be important for integrating thick filaments with the M-line end of titin.
Use of Mass Spectrometry To Rapidly Characterize the Heterogeneity of Bovine α-Lactalbumin (1999)

From a bovine whey protein fraction the nonglycosylated and glycosylated alpha-lactalbumin fractions were isolated by gel-permeation chromatography followed by reversed-phase high-performance liquid chromatography. Both fractions were studied by electrospray-ionization mass spectrometry (ESI-MS). For the nonglycosylated fraction, a mass of 14 178 Da was found, which was in accordance with the known amino acid sequence of the protein. The glycosylated fraction appeared to be a mixture of components with mass values ranging from ca. 15 840 to 16 690 Da. Given the published carbohydrate composition of the whole glyco-alpha-lactalbumin fraction, these masses could be matched to those of 14 differently glycosylated forms of alpha-lactalbumin. Further support for these forms was obtained from the results of a separate mass spectrometric analysis of the mixture of oligosaccharides released from the protein by treatment with peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase F. ESI-MS was found to be a powerful tool to gain insight into the composition of the complex mixture of glycoforms of alpha-lactalbumin without the need of further purification of these forms or of the oligosaccharides released thereof.
Interleukin-8 gene expression in human bronchial epithelial cells. (1991)

The capacity of cells of the human bronchial epithelium to express the gene for interleukin-8 (IL-8) was evaluated in bronchial epithelium derived cell lines, HS-24 and BET-1A, using tumor necrosis factor-alpha (TNF) as a model inflammatory stimulus. As in other epithelium, TNF markedly increased the level of the 1.8-kilobase IL-8 mRNA transcripts in both bronchial epithelial cell lines. In HS-24 cells, nuclear run-on analyses showed the IL-8 gene transcription rate was dramatically increased, more than 30-fold, after TNF stimulation. The half-life of IL-8 mRNA transcripts in these cells was approximately 40 min and did not change after TNF stimulation, suggesting that TNF up-regulated IL-8 gene expression mainly at the transcriptional level. DNase I hypersensitivity site mapping of chromatin DNA in resting HS-24 cells demonstrated two hypersensitivity sites within 400 base pairs (bp) 5' to exon I and one site within exon I. However, after TNF stimulation, the exon I hypersensitivity site disappeared and a new site approximately 120 bp 5' to exon I emerged. Consistent with these observations, transfection studies with HS-24 cells using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene demonstrated potent promoter activity in a 174-bp segment (-130 to +44 relative to the transcription start site), which also exhibited a response to TNF, while a segment from -112 to +44 showed very low promoter activity and no response to TNF. Thus, human bronchial epithelial cells can express the IL-8 gene, with expression in response to the inflammatory mediator TNF regulated mainly at the transcriptional level, and with elements within the 5'-flanking region of the gene that are directly or indirectly modulated by the TNF signal.
Building with feeling (2006)

‘We mould our buildings, and then our buildings mould us’ is a truism attributed to Winston Churchill. We are in the process of renewing much of the UK healthcare estate. Conventional mindsets associated with the design of healthcare buildings have been process centred and construction centred rather then patient-experience centred. There is an opportunity to match the move towards a patient-centred NHS with a more patient-perspective-centred design mindset amongst those involved in commissioning and delivering the new healthcare estate, regardless of scale. This could enable virtuous circles of improvement to emerge, adding value for both the individual and the state, and capitalizing on recent international research into the therapeutic impact of well-directed design. Valuable issues for the individual such as intimacy, trust, compassion and empathy have been considered conventionally outside the realm of building. However, on closer examination such issues have a fundamental relationship to stress, well-being and healing and have direct environmental components and therefore fall within the remit of design. Therefore their consideration can influence building design if our mindset is open to them early enough. Underpinning this approach is an understanding of the nature of stress in the context of the patient experience. Copyright © 2006 John Wiley & Sons, Ltd.
Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study) (2010)

Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
Oxypropylation of lignins and characterization of the ensuing polyols (2007)

Four lignin samples (Alcell, Indulin AT, Curan 27-11P and Sarkanda) were converted into liquid polyols by a chain extension reaction with propylene oxide (oxypropylation). The reaction was carried out in a batch reactor using potassium hydroxide (KOH) as a catalyst. The oxypropylation process was first optimized with Alcell lignin by modifying the lignin/propylene oxide ratio (L/PO, w/v) and catalyst content (C/(C+L), % w/w). L/PO ratios of 10/90, 20/80, 30/70 and 40/60, and catalyst contents from 2 to 5% were used. Based on the studied formulations, and considering the polyol requirements for polyurethane foam synthesis (a hydroxyl number (IOH) between 300 and 800 and a viscosity below 300 Pa.s), three formulations were chosen and applied for the oxypropylation the other lignin samples: 20/80/5, 30/70/2 and 35/65/2. The produced polyols were characterized. Their IOH and viscosity were found to be in the range of those typical of commercial polyols employed in polyurethane preparation.
Characterisation of a 3-hydroxypropionic acid-inducible system from Pseudomonas putida for orthogonal gene expression control in Escherichia coli and Cupriavidus necator (2017)

3-hydroxypropionic acid (3-HP) is an important platform chemical used as a precursor for production of added-value compounds such as acrylic acid. Metabolically engineered yeast, Escherichia coli, cyanobacteria and other microorganisms have been developed for the biosynthesis of 3-HP. Attempts to overproduce this compound in recombinant Pseudomonas denitrificans revealed that 3-HP is consumed by this microorganism using the catabolic enzymes encoded by genes hpdH, hbdH and mmsA. 3-HP-inducible systems controlling the expression of these genes have been predicted in proteobacteria and actinobacteria. In this study, we identify and characterise 3-HP-inducible promoters and their corresponding LysR-type transcriptional regulators from Pseudomonas putida KT2440. A newly-developed modular reporter system proved possible to demonstrate that PpMmsR/P <sub>mmsA</sub> and PpHpdR/P <sub>hpdH</sub> are orthogonal and highly inducible by 3-HP in E. coli (12.3- and 23.3-fold, respectively) and Cupriavidus necator (51.5- and 516.6-fold, respectively). Bioinformatics and mutagenesis analyses revealed a conserved 40-nucleotide sequence in the hpdH promoter, which plays a key role in HpdR-mediated transcription activation. We investigate the kinetics and dynamics of the PpHpdR/P <sub>hpdH</sub> switchable system in response to 3-HP and show that it is also induced by both enantiomers of 3-hydroxybutyrate. These findings pave the way for use of the 3-HP-inducible system in synthetic biology and biotechnology applications.
Anticipatory and Stimulus-Evoked Blood Oxygenation Level-Dependent Modulations Related to Spatial Attention Reflect a Common Additive Signal (2009)

Covert attention is associated with prestimulus blood oxygenation level-dependent (BOLD) modulations in visual cortex. In some situations, this preparatory activity can predict how well human subjects will perceive upcoming visual objects. Preparatory activity may mediate this behavioral effect by affecting the stimulus-evoked response, but the relationship between preparatory and stimulus-evoked BOLD modulations is unclear. Here, we examine this relationship by comparing the effects of spatial attention on anticipatory and stimulus-evoked signals and by measuring the trial-to-trial correlation between prestimulus and poststimulus modulations. We find that in extrastriate visual cortex (V4), modulations related to spatial attention are relatively large, extend from prestimulus through the peak of the evoked response, and are slightly larger in the evoked response compared with the prestimulus response. In striate cortex (V1), the frontal eye fields (FEF), and the intraparietal sulcus (IPS), modulations related to spatial attention are relatively small, are confined primarily to the prestimulus period, and are slightly larger in preparatory versus stimulus-evoked activity. Importantly, across visual cortex, the attentional biases (activity for attended versus unattended locations) in preparatory and evoked activity are more positively correlated, trial-by-trial, than would be expected on the basis of activity measured in subjects at rest. We argue that this pattern of results suggests that the same mechanisms underlie preparatory and stimulus-evoked BOLD modulations related to spatial attention and that incoming sensory signals add to preexistent biases in preparatory activity to generate the stimulus-evoked response.
ADMISSION ANGIOPOIETIN LEVELS IN CHILDREN WITH SEPTIC SHOCK (2007)

Angiopoietin (angpt) 1 and angpt-2 are circulating proteins first ascribed opposing roles in embryonic angiogenesis. Both bind the tyrosine kinase with immunoglobulin-like loop and epidermal growth factor homology domains (Tie) 2 receptor on endothelial cells, but angpt-1 is a Tie-2 agonist, whereas angpt-2 antagonizes Tie-2 signaling. In the developed vasculature, angpt-1 protects against vascular leak, whereas angpt-2 promotes increased vascular permeability. Because alterations in vascular permeability are common in septic shock, we obtained plasma from critically ill children within 24 h of diagnosis of the systemic inflammatory response syndrome (SIRS, n = 20), sepsis (n = 20), or septic shock (n = 61), as well as 15 healthy controls. Plasma levels of angpt-1 and angpt-2 were measured via a commercially available enzyme-linked immunosorbent assay. Plasma angpt-2 levels were significantly elevated in children with septic shock when compared with healthy children, as well as critically ill children with either SIRS or sepsis, and circulating angpt-2 levels seemed to correlate with disease severity and outcome. In addition, plasma angpt-1 levels were significantly decreased in critically ill children with septic shock compared with critically ill children with either SIRS or sepsis. Given the contrasting effects of angpt-2 and angpt-1 on the vascular endothelium, these two factors may play an important role in the pathophysiology of septic shock in children, and further studies are warranted.