gebhart/patrepeval huggingface dataset:
Liposomes as nanomedical devices (2015)

Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the "first-generation" liposomes, and liposome-based drugs on the market and in clinical trials.
Magnetoencephalography—theory, instrumentation, and applications to noninvasive studies of the working human brain (1993)

Magnetoencephalography (MEG) is a noninvasive technique for investigating neuronal activity in the living human brain. The time resolution of the method is better than 1 ms and the spatial discrimination is, under favorable circumstances, 2-3 mm for sources in the cerebral cortex. In MEG studies, the weak 10 fT-1 pT magnetic fields produced by electric currents flowing in neurons are measured with multichannel SQUID (superconducting quantum interference device) gradiometers. The sites in the cerebral cortex that are activated by a stimulus can be found from the detected magnetic-field distribution, provided that appropriate assumptions about the source render the solution of the inverse problem unique. Many interesting properties of the working human brain can be studied, including spontaneous activity and signal processing following external stimuli. For clinical purposes, determination of the locations of epileptic foci is of interest. The authors begin with a general introduction and a short discussion of the neural basis of MEG. The mathematical theory of the method is then explained in detail, followed by a thorough description of MEG instrumentation, data analysis, and practical construction of multi-SQUID devices. Finally, several MEG experiments performed in the authors' laboratory are described, covering studies of evoked responses and of spontaneous activity in both healthy and diseased brains. Many MEG studies by other groups are discussed briefly as well.
SF 36 health survey questionnaire: II. Responsiveness to changes in health status in four common clinical conditions. (1994)

These results provide the first evidence of the responsiveness of the SF 36 questionnaire to changes in perceived health status in a patient population in the United Kingdom.
Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy (2019)

Extensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed in independent cohorts and across different laboratories. In these previous studies, glucocorticoids and age were two major confounding variables. In this new study, using SomaScan technology and focusing on a subset of young DMD patients who were not yet treated with glucocorticoids, we identified 108 elevated and 70 decreased proteins in DMD relative to age matched healthy controls (p value < 0.05 after adjusting for multiple testing). The majority of the elevated proteins were muscle centric followed by cell adhesion, extracellular matrix proteins and a few pro-inflammatory proteins. The majority of decreased proteins were of cell adhesion, however, some had to do with cell differentiation and growth factors. Subsequent treatment of this group of DMD patients with glucocorticoids affected two major groups of pharmacodynamic biomarkers. The first group consisted of 80 serum proteins that were not associated with DMD and either decreased or increased following treatment with glucocorticoids, and therefore were reflective of a broader effect of glucocorticoids. The second group consisted of 17 serum proteins that were associated with DMD and these tended to normalize under treatment, thus reflecting physiologic effects of glucocorticoid treatment in DMD. In summary, we have identified a variety of circulating protein biomarkers that reflect the complex nature of DMD pathogenesis and response to glucocorticoids.
A Psychophysiological Exploration of Sexual Arousal Patterns in Females and Males (1977)

ABSTRACT Fifty‐nine female and 39 male undergraduates completed 3 sessions of a psychophysiological study on sexual arousal. Subjects were assigned to one of six experimental groups. Subjects within each group were exposed to a series of four audio‐tapes, and were asked to fantasize before and after the tape series. Tapes varied in their erotic and romantic content, and two sex role dimensions were also varied across tapes. Dependent measures included scaled subjective reports, genital pulse amplitude and blood volume responses, heart rate, and finger pulse amplitude. Erotic contents were significantly more sexually arousing than nonerotic contents for both sexes. Romantic content did not significantly enhance the facilitation of sexual arousal. Nontraditional sex roles were significantly more arousing for females, with a similar nonsignificant trend for males. There were significant correlations between genital pulse amplitude and subjective reports of arousal; however, for females the genital blood volume measure showed less reliable agreement with subjective report. Genital pulse amplitude was the most reliable and precise indicator of arousal and accounted for the most variance across conditions. No significant changes occurred on the heart rate and finger pulse amplitude measures. Although subjects were able to become aroused by fantasy alone, listening to erotic tapes did not facilitate their ability to be sexually aroused during fantasy.
Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. (1996)

The tyrosine kinases Flt4, Flt1, and Flk1 (or KDR) constitute a family of endothelial cell-specific receptors with seven immunoglobulin-like domains and a split kinase domain. Flt1 and Flk1 have been shown to play key roles in vascular development; these two receptors bind and are activated by vascular endothelial growth factor (VEGF). No ligand has been identified for Flt4, whose expression becomes restricted during development to the lymphatic endothelium. We have identified cDNA clones from a human glioma cell line that encode a secreted protein with 32% amino acid identity to VEGF. This protein, designated VEGF-related protein (VRP), specifically binds to the extracellular domain of Flt4, stimulates the tyrosine phosphorylation of Flt4 expressed in mammalian cells, and promotes the mitogenesis of human lung endothelial cells. VRP fails to bind appreciably to the extracellular domain of Flt1 or Flk1. The protein contains a C-terminal, cysteine-rich region of about 180 amino acids that is not found in VEGF. A 2.4-kb VRP mRNA is found in several human tissues including adult heart, placenta, ovary, and small intestine and in fetal lung and kidney.
On the characterization and spinning of an organic‐purified lignin toward the manufacture of low‐cost carbon fiber (2011)

Abstract A Kraft hardwood lignin (HWL) and an organic‐purified hardwood lignin (HWL‐OP) were evaluated as potential precursors for the production of low‐cost carbon fibers. It was found that the unpurified HWL exhibited poor spinnability while the HWL‐OP exhibited excellent spinnability characteristics. Fibers of various diameters were obtained from the HWL‐OP. Thermostabilization studies showed that oxidative stabilization can only be used to convert HWL‐OP‐based fibers into carbon fibers if extremely low heating rates are applied. Carbonized lignin‐based fibers had tensile strength of 0.51 GPa and tensile modulus of 28.6 GPa. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Shade avoidance responses are mediated by the ATHB-2 HD-Zip protein, a negative regulator of gene expression (1999)

The ATHB-2 gene encoding an homeodomain-leucine zipper protein is rapidly and strongly induced by changes in the ratio of red to far-red light which naturally occur during the daytime under the canopy and induce in many plants the shade avoidance response. Here, we show that elevated ATHB-2 levels inhibit cotyledon expansion by restricting cell elongation in the cotyledon-length and -width direction. We also show that elevated ATHB-2 levels enhance longitudinal cell expansion in the hypocotyl. Interestingly, we found that ATHB-2-induced, as well as shade-induced, elongation of the hypocotyl is dependent on the auxin transport system. In the root and hypocotyl, elevated ATHB-2 levels also inhibit specific cell proliferation such as secondary growth of the vascular system and lateral root formation. Consistent with the key role of auxin in these processes, we found that auxin is able to rescue the ATHB-2 lateral root phenotype. We also show that reduced levels of ATHB-2 result in reciprocal phenotypes. Moreover, we demonstrate that ATHB-2 functions as a negative regulator of gene expression in a transient assay. Remarkably, the expression in transgenic plants of a derivative of ATHB-2 with the same DNA binding specificity but opposite regulatory properties results in a shift in the orientation of hypocotyl cell expansion toward radial expansion, and in an increase in hypocotyl secondary cell proliferation. A model of ATHB-2 function in the regulation of shade-induced growth responses is proposed.
Probiotic administration alters the gut flora and attenuates colitis in mice administered dextran sodium sulfate (2008)

Prior administration of probiotic bacteria reduced mucosal inflammation and damage in DSS-induced colitis. DSS colitis was associated with significant changes in the fecal anaerobic bacterial flora and these changes were modulated by administration of probiotic bacteria.
The Inhibitory Effect of IL-1β on IL-6-Induced α2-Macroglobulin Expression Is Due to Activation of NF-κB (2001)

The cross-talk between the signal transduction of simultaneous acting cytokines largely determines the final impact of cytokines on their target genes. Both NF-kappaB and STAT3 are transcription factors well known to be activated by many stimuli and to mediate transcriptional activation by binding to specific enhancer sequences. In this study, it is analyzed how IL-1beta inhibits IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. It is shown that IL-1beta prevents STAT3 binding to the two STAT3-responsive sites within the alpha(2)-macroglobulin promoter by association of IL-1beta-activated NF-kappaB to this region. The observation that inhibition of IL-6-induced transcriptional activation of this promoter by IL-1beta is reversed by cotransfection with I-kappaBalpha provides evidence that NF-kappaB activation by IL-1beta is responsible for inhibition of IL-6-mediated trans activation of the alpha(2)-macroglobulin gene. Accordingly, cotransfection of the NF-kappaB subunits p50 or p65 themselves inhibited activation of the alpha(2)-macroglobulin promoter by IL-6. Introduction of point mutations in each of the two NF-kappaB sites overlapping the two STAT3 binding sites within the alpha(2)-macroglobulin promoter provides evidence that each of these two sites counteracts transcriptional activation via STAT3. Most interestingly, at least one functional NF-kappaB consensus site is essential for the IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. Additional data are provided indicating that the activation of NF-kappaB by IL-1beta is also responsible for the inhibition of other IL-6-inducible genes, such as the alpha(1)-antichymotrypsin gene as well as the suppressor of cytokine signaling 3 gene, suggesting a more general relevance of this mechanism for transcriptional regulation.
Systemic and Renal‐Specific Sympathoinhibition in Obesity Hypertension (2011)

The natural activation of the baroreflex has been shown to chronically suppress renal sympathetic nerve activity (RSNA) and promote sodium excretion. Therefore, we compared the relative antihypertensive effects of bilateral electrical stimulation of the carotid baroreflex to bilateral renal denervation (DNX) in dogs with obesity hypertension. After control measurements, the diet was supplemented with beef fat for 4 weeks until body weight increased to ~ 150% of control. There were increases in mean arterial pressure (MAP) from 100±3 to 116±1 mmHg and heart rate (HR) from 84±4 to 121±5 bpm. Subsequently, baroreflex activation reduced blood pressure to control levels within 24 hours. Moreover, this antihypertensive response was sustained for the 7 days of stimulation (day 7, MAP= 100±3 mmHg). HR decreased substantially, falling to 99±3 bpm on day 7. Both MAP and HR returned to pre-stimulation hypertensive levels during the recovery period. Next, the dogs were subjected to DNX. Within 48 hours, MAP fell to normotensive levels, whereas HR remained elevated. Fourteen days after DNX, MAP and HR were 100±3 mmHg 119±5 bpm, respectively. These results emphasize the critical role of increased sympathetic activity in the pathogenesis of obesity hypertension and suggest that sustained suppression of RSNA may be the essential response mediating the long-term blood pressure lowering effects of baroreflex activation. In addition, by improving autonomic control of cardiac function, a clear advantage of baroreflex activation over renal denervation is that the former may diminish the likelihood of adverse cardiac events.
Allosteric Modulation of the Calcium-Sensing Receptor (2007)

The calcium (Ca(2+))-sensing receptor (CaR) belongs to family C of the G-protein coupled receptors (GPCRs). The receptor is activated by physiological levels of Ca(2+) (and Mg(2+)) and positively modulated by a range of proteinogenic L-alpha-amino acids. Recently, several synthetic allosteric modulators of the receptor have been developed, which either act as positive modulators (termed calcimimetics) or negative modulators (termed calcilytics). These ligands do not activate the wild-type receptor directly, but rather shift the concentration-response curves of Ca(2+) to the left or right, respectively. Like other family C GPCRs, the CaR contains a large amino-terminal domain and a 7-transmembrane domain. Whereas the endogenous ligands for the receptor, Ca(2+), Mg(2+) and the L-alpha-amino acids, bind to the amino-terminal domain, most if not all of the synthetic modulators published so far bind to the 7-transmembrane domain. The most prominent physiological function of the CaR is to maintain the extracellular Ca(2+) level in a very tight range via control of secretion of parathyroid hormone (PTH). Influence on e.g. secretion of calcitonin from thyroid C-cells and direct action on the tubule of the kidney also contribute to the control of the extracellular Ca(2+) level. This control over PTH and Ca(2+) levels is partially lost in patients suffering from primary and secondary hyperparathyroidism. The perspectives in CaR as a therapeutic target have been underlined by the recent approval of the calcimimetic cinacalcet for the treatment of certain forms of primary and secondary hyperparathyroidism. Cinacalcet is the first clinically administered allosteric modulator acting on a GPCR, and thus the compound constitutes an important proof-of-concept for future development of allosteric modulators on other GPCR drug targets.
Videoendoscopic evaluation of the mare's uterus: I. Findings in normal fertile mares (1992)

The new generation of videoendoscopes uses an electronic, instead of an optical, system for image transmission. Advantages over conventional fibre-optic endoscopes include increased image quality, handling robustness and direct display of the image on a TV monitor for multiple simultaneous viewing. In the present study, hysteroscopy was performed on 14 normal fertile Welsh Pony and Thoroughbred mares at various times during the annual and ovarian breeding cycles. Oestrus was characterised by an oedematous, relaxed cervix lying on the floor of the vagina, diffuse oedema of the endometrium and the occasional accumulation of small amounts of clear secretions in the uterine lumen. In dioestrus, the cervix appeared tight and pale and was located in the centre of the vaginal fornix. The endometrium appeared thinner due to the reduction in interstitial fluid, which allowed the underlying blood vessels to become visible, but it still had a glistening surface as a result of endometrial gland secretions. The appearance of the uterotubal papillae reflected the changes in the cervix, being relaxed, pinkish and oedematous during oestrus but remaining pale, tight and erect in dioestrus (between Days 7 and 12 after ovulation). A flexible polythene cannula was passed into the uterine lumen through the working channel of the endoscope for directed collection of uterine fluid for cytological and bacteriological examinations. Site-directed biopsies of the endometrium were taken, with flexible forceps inserted through the working channel of the endoscope, or with rigid forceps passed through the cervix alongside the endoscope. Both methods enabled accurate visual selection of the sampling area but the rigid forceps were preferred due to the larger size of the piece of endometrium recovered.
Combined reflection and transmission microscope for telemedicine applications in field settings (2011)

We demonstrate a field-portable upright and inverted microscope that can image specimens in both reflection and transmission modes. This compact and cost-effective dual-mode microscope weighs only ∼135 grams (<4.8 ounces) and utilizes a simple light emitting diode (LED) to illuminate the sample of interest using a beam-splitter cube that is positioned above the object plane. This LED illumination is then partially reflected from the sample to be collected by two lenses, creating a reflection image of the specimen onto an opto-electronic sensor-array that is positioned above the beam-splitter cube. In addition to this, the illumination beam is also partially transmitted through the same specimen, which then casts lensfree in-line holograms of the same objects onto a second opto-electronic sensor-array that is positioned underneath the beam-splitter cube. By rapid digital reconstruction of the acquired lensfree holograms, transmission images (both phase and amplitude) of the same specimen are also created. We tested the performance of this field-portable microscope by imaging various micro-particles, blood smears as well as a histopathology slide corresponding to skin tissue. Being compact, light-weight and cost-effective, this combined reflection and transmission microscope might especially be useful for telemedicine applications in resource limited settings.
Functional Characterization of Desaturases Involved in the Formation of the Terminal Double Bond of an Unusual 16:3Δ9, 12, 15 Fatty Acid Isolated from Sorghum bicolor Root Hairs (2006)

Sorgoleone, produced in root hair cells of sorghum (Sorghum bicolor), is likely responsible for much of the allelopathic properties of sorghum root exudates against broadleaf and grass weeds. Previous studies suggest that the biosynthetic pathway of this compound initiates with the synthesis of an unusual 16:3 fatty acid possessing a terminal double bond. The corresponding fatty acyl-CoA serves as a starter unit for polyketide synthases, resulting in the formation of 5-pentadecatrienyl resorcinol. This resorcinolic intermediate is then methylated by an S-adenosylmethionine-dependent O-methyltransferase and subsequently dihydroxylated, yielding the reduced (hydroquinone) form of sorgoleone. To characterize the corresponding enzymes responsible for the biosynthesis of the 16:3 fatty acyl-CoA precursor, we identified and cloned three putative fatty acid desaturases, designated SbDES1, SbDES2, and SbDES3, from an expressed sequence tag (EST) data base prepared from isolated root hairs. Quantitative real-time RT-PCR analyses revealed that these three genes were preferentially expressed in sorghum root hairs where the 16:2 and 16:3 fatty acids were exclusively localized. Heterologous expression of the cDNAs in Saccharomyces cerevisiae revealed that recombinant SbDES2 converted palmitoleic acid (16:1Delta(9)) to hexadecadienoic acid (16:2Delta(9,12)), and that recombinant SbDES3 was capable of converting hexadecadienoic acid into hexadecatrienoic acid (16:3Delta(9,12,15)). Unlike other desaturases reported to date, the double bond introduced by SbDES3 occurred between carbons 15 and 16 resulting in a terminal double bond aliphatic chain. Collectively, the present results strongly suggest that these fatty acid desaturases represent key enzymes involved in the biosynthesis of the allelochemical sorgoleone.
Sequence Motifs and Proteolytic Cleavage of the Collagen-Like Glycoprotein BclA Required for Its Attachment to the Exosporium of Bacillus anthracis (2009)

Bacillus anthracis spores are enclosed by an exosporium comprised of a basal layer and an external hair-like nap. The filaments of the nap are composed of trimers of the collagen-like glycoprotein BclA. The attachment of essentially all BclA trimers to the exosporium requires the basal layer protein BxpB, and both proteins are included in stable high-molecular-mass exosporium complexes. BclA contains a proteolytically processed 38-residue amino-terminal domain (NTD) that is essential for basal-layer attachment. In this report, we identify three NTD submotifs (SM1a, SM1b, and SM2, located within residues 21 to 33) that are important for BclA attachment and demonstrate that residue A20, the amino-terminal residue of processed BclA, is not required for attachment. We show that the shortest NTD of BclA-or of a recombinant protein-sufficient for high-level basal-layer attachment is a 10-residue motif consisting of an initiating methionine, an apparently arbitrary second residue, SM1a or SM1b, and SM2. We also demonstrate that cleavage of the BclA NTD is necessary for efficient attachment to the basal layer and that the site of cleavage is somewhat flexible, at least in certain mutant NTDs. Finally, we propose a mechanism for BclA attachment and discuss the possibility that analogous mechanisms are involved in the attachment of many different collagen-like proteins of B. anthracis and closely related Bacillus species.
Cost-Effectiveness of Pneumococcal Conjugate Vaccine (2006)

IPD herd effects in the nonvaccinated population substantially reduce the cost, and substantially improve the cost-effectiveness, of PCV. The cost-effectiveness of PCV in actual use has been more favorable than predicted by estimates created before the vaccine was licensed.