gebhart/patrepeval huggingface dataset:
Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment (2007)

Changes in the genes encoding sensory receptor proteins are an essential step in the evolution of new sensory capacities. In primates, trichromatic color vision evolved after changes in X chromosome-linked photopigment genes. To model this process, we studied knock-in mice that expressed a human long-wavelength-sensitive (L) cone photopigment in the form of an X-linked polymorphism. Behavioral tests demonstrated that heterozygous females, whose retinas contained both native mouse pigments and human L pigment, showed enhanced long-wavelength sensitivity and acquired a new capacity for chromatic discrimination. An inherent plasticity in the mammalian visual system thus permits the emergence of a new dimension of sensory experience based solely on gene-driven changes in receptor organization.
The type I BMP receptor BmprIB is essential for female reproductive function (2001)

Maintenance of female reproductive competence depends on the actions of several hormones and signaling factors. Recent reports suggest roles for bone morphogenetic proteins (BMPs) in early stages of folliculogenesis. A role for the type I BMP receptor BmprIB as a regulator of ovulation rates in sheep has been described recently, but little is known about the roles of BMP signaling pathways in other aspects of reproductive function. We report here that BMPRIB is essential for multiple aspects of female fertility. Mice deficient in BmprIB exhibit irregular estrous cycles and an impaired pseudopregnancy response. BmprIB mutants produce oocytes that can be fertilized in vitro, but defects in cumulus expansion prevent fertilization in vivo. This defect is associated with decreased levels of aromatase production in granulosa cells. Unexpectedly, levels of mRNA for cyclooxygenase 2, an enzyme required for cumulus expansion, are increased. BmprIB mutants also exhibit a failure in endometrial gland formation. The expression of BmprIB in uterine linings suggests that these defects are a direct consequence of loss of BMP signaling in this tissue. In summary, these studies demonstrate the importance of BMP signaling pathways for estrus cyclicity, estradiol biosynthesis, and cumulus cell expansion in vivo and reveal sites of action for BMP signaling pathways in reproductive tissues.
Axial Chirality Control of Gold(biphep) Complexes by Chiral Anions: Application to Asymmetric Catalysis (2009)

The axial chirality of tropos gold–biphep (biphep=bis(phosphanyl)biphenyl) complexes, which is controlled by a chiral anion such as (S)-2 (=X*−), is imprinted and memorized even after the dissociation of chiral anion. An enantiopure complex thus obtained efficiently function as an atropos asymmetric catalyst in an intramolecular hydroamination. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Copper-Mediated Fluorination of Aryl Iodides (2012)

The synthesis of aryl fluorides has been studied intensively because of the importance of aryl fluorides in pharmaceuticals, agrochemicals, and materials. The stability, reactivity, and biological properties of aryl fluorides can be distinct from those of the corresponding arenes. Methods for the synthesis of aryl fluorides, however, are limited. We report the conversion of a diverse set of aryl iodides to the corresponding aryl fluorides. This reaction occurs with a cationic copper reagent and silver fluoride. Preliminary results suggest this reaction is enabled by a facile reductive elimination from a cationic arylcopper(III) fluoride.
Four‐Parameter white blood cell differential counting based on light scattering measurements (1988)

Measurement of the depolarized orthogonal light scattering in flow cytometry enables one to discriminate human eosinophilic granulocytes from neutrophilic granulocytes. We use this method to perform a four-parameter differential white blood cell analysis. A simple flow cytometer was built equipped with a 5-mW helium neon laser that measures simultaneously four light scattering parameters. Lymphocytes, monocytes, and granulocytes were identified by simultaneously measuring the light scattering intensity at angles between 1.0 degrees and 2.6 degrees and angles between 3.0 degrees and 11.0 degrees. Eosinophilic granulocytes were distinguished from neutrophilic granulocytes by simultaneous measurement of the orthogonal and depolarized orthogonal light scattering. Comparison of a white blood cell differentiation of 45 donors obtained by the Technicon H-6000 and our instrument revealed good correlations. The correlation coefficients (r2) found were: 0.99 for lymphocytes, 0.76 for monocytes, 0.99 for neutrophilic granulocytes, and 0.98 for eosinophilic granulocytes. The results demonstrate that reliable white blood cell differentiation of the four most clinically relevant leukocytes can be obtained by measurement of light scattering properties of unstained leukocytes.
Impaired Peripheral Endothelial Microvascular Responsiveness in Alzheimer's Disease (2007)

The results support our hypothesis that endothelial alterations can be detected early in the course of the disease. We suggest that this simple skin test could potentially be applied as diagnostic adjunct in patients with mild cognitive symptoms or those with early clinical evidence of AD.
The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. (1995)

The origin of myofibroblasts in stromal reaction has been a subject of controversy. To address this question definitively, we developed techniques for purification and characterization of major stromal cell types. We defined a panel of markers that could, in combination, unequivocally distinguish these cell types by immunocytochemistry, iso-electric focusing, immunoblotting, and two-dimensional gel electrophoresis. We then devised an assay to recapitulate in culture, within two weeks of incubation, critical aspects of the microenvironment in vivo including the typical tissue histology and stromal reaction. When confronted with tumor cells in this assay, fibroblasts readily converted into a graded pattern of myogenic differentiation, strongest in the immediate vicinity of tumor cells. Vascular smooth muscle cells (VSMC), in contrast, did not change appreciably and remained coordinately smooth muscle differentiated. Midcapillary pericytes showed only a slight propensity for myogenic differentiation. Analysis of ten primary tumors implicated converted fibroblasts (10/10), vascular smooth muscle cells (4/10), and pericytes (1/10) in the stromal reaction. Tumor cells were shown to specifically denude the venules both in culture and in vivo, explaining the VSMC phenotype in the stroma. The establishment of this assay and clarification of the origin of these cells pave the way for further analysis of the mechanisms of conversion, and of the consequence of such heterogeneity for diagnosis and treatment.
Control Mechanisms of Glycolysis in Ehrlich Ascites Tumor Cells (1965)

Studies on the rate-limiting factors of glycolysis in Ehrlich ascites tumor cells have indicated that orthophosphate is the major rate-limiting factor for glycolysis (l-5). Pi presumably influences the rate of glyceraldehyde 3-phosphate dehydrogenase, the only glycolytic enzyme known to require Pi. However, recent reports have indicated that Pi may have other important effects on glycolytic systems. Thus, in cell-free systems, Passonneau and Lowry (6) as well as Mansour (7) showed that Pi may activate P-fructokinase by counteracting the inhibitory effect of high ATP concentrations. Rose, Warms, and O’Connell (8, 9) have reported that Pi may partially relieve the glucose-6-P inhibition of hexokinase in red blood cells. In the light of these observations intact ascites tumor cells were re-examined in order to define more precisely the site of action of Pi in the control of intracellular glycolysis. In addition, other factors which influence the rate of glycolysis, such as the availability of glucose, have been analyzed. The data to be reported in this communication revealed that the availability of glucose restricted aerobic but not anaerobic glycolysis at glucose concentrations below 1.2 mM. The primary effect of Pi appeared to be mediated through its influence on P-fructokinase, although hexokinase and glyceraldehyde-3-P dehydrogenase were also affected. A preliminary report has appeared (10).
Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection (1996)

Recent data implicates a role for the CD40-CD40 ligand (CD40L) pathway in graft rejection. One potential mechanism is direct costimulation of T cells through CD40L. Alternatively, the ability of CD40 stimulation to induce CD80 (B7-1) and CD86 (B7-2) expression on antigen-presenting cells (APCs) has led to the hypothesis that the role of CD40-CD40L interactions in transplant rejection might be indirect, i.e., to promote the costimulatory capacity of APCs. Here, we have used a murine vascularized cardiac allograft model to test this hypothesis. Treatment of the recipients with donor splenocytes and a single dose of anti-CD40L mAb induces long-term graft survival (> 100 days) in all animals. This is associated with marked inhibition of intragraft Th1 cytokine [interferon gamma and interleukin (IL) 2] and IL-12 expression with reciprocal up-regulation of Th2 cytokines (IL-4 and IL-10). In untreated allograft recipients, CD86 is strongly expressed on endothelial cells and infiltrating mononuclear cells of the graft within 24 hr. In contrast, CD80 expression is not seen until 72 hr after engraftment. Anti-CD40L mAb has no detectable effect on CD86 up-regulation, but almost completely abolishes induction of CD80. However, animals treated with anti-CD80 mAb or with a mutated form of CTLA4Ig (which does not bind to CD86) rejected their cardiac allografts, indicating that blockade of CD80 alone does not mediate the graft-prolonging effects of anti-CD40L mAb. These data support the notion that the role of CD40-CD40L in transplant rejection is not solely to promote CD80 or CD86 expression, but rather that this pathway can directly and independently costimulate T cells. These data also suggest that long-term graft survival can be achieved without blockade of either T cell receptor-mediated signals or CD28-CD86 engagement.
Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L) (2005)

Here, we describe the generation of a novel transgenic mouse model of human tauopathy. The rTg(tau(P301L))4510 mouse expresses the P301L mutation in tau (4R0N) associated with frontotemporal dementia and parkinsonism linked to chromosome 17. Transgene expression was driven by a forebrain-specific Ca(2+) calmodulin kinase II promoter system resulting in high levels of expression in the hippocampus and neocortex. Importantly, transgene expression in this model is induced via the tetracycline-operon responsive element and is suppressed after treatment with doxycycline. Continued transgene expression in rTg(tau(P301L))4510 mice results in age-dependent development of many salient characteristics of hereditary human dementia. From an early age, immunohistochemical studies demonstrated abnormal biochemical processing of tau and the presence of pathological conformation- and phosphorylation-dependent epitopes. Neurofibrillary tangle (NFT) pathology was first observed in the neocortex and progressed into the hippocampus and limbic structures with increasing age. Consistent with the formation of NFTs, immunoblots indicated an age-dependent transition of accumulating tau species from Sarkosyl soluble 55 kDa to insoluble hyperphosphorylated 64 kDa. Ultrastructural analysis revealed the presence of straight tau filaments. Furthermore, the effects of tau(P301L) expression on spatial reference memory were longitudinally tested using the Morris water maze. Compared with nontransgenic age-matched control littermates, rTg(tau(P301L))4510 mice developed significant cognitive impairments from 4 months of age. Memory deficits were accompanied by gross forebrain atrophy and a prominent loss of neurons, most strikingly in hippocampal subdivision CA1. Collectively, these data describe a novel transgenic mouse that closely mimics human tauopathy and may represent an important model for the future study of tau-related neurodegenerative disease.
Comparative Dissolution Studies on Human Enamel and Fluorapatite (1970)

Polished fluorapatite crystal surfaces were etched with lactic acid adjusted to pH4 or with ethylenediamine tetra-acetic acid (Edta) and the surfaces examined by scanning electron microscopy. The resultant acid etch patterns or pits were observed to be typical of the hexagonal system, as expected from the crystal structure of fluorapatite; however, the fluorapatite surfaces exposed to Edta at pH7 were relatively unaffected. Several different natural surfaces of fluorapatite were exposed to lactic acid and the comparative dissolution rate for each surface determined by the micro estimate of the dissolved calcium component. Observations indicated similar dissolution rates for the different surfaces examined. A relatively simple technique was employed to compare dissolution rates of human enamel and fluorapatite under static conditions. Sample granules were suspended upon porous glass filter crucibles and weight losses of the granules versus the time of dissolution were recorded for a variety of solutions. Constant rates of dissolution were obtained, fluorapatite exhibiting low values in lactic acid and EDTA solutions compared with high dissolution rates observed for enamel granules in these solutions. The rate of rate loss of enamel granules in 0.15 M Edta is higher than that in 0.25 M lactic acid. Surprisingly, the opposite was observed for fluorapatite granules.
Surface Modification of Poly(dimethylsiloxane) Microfluidic Devices by Ultraviolet Polymer Grafting (2002)

Poly(dimethylsiloxane) (PDMS)-based microfluidic devices are increasing in popularity due to their ease of fabrication and low costs. Despite this, there is a tremendous need for strategies to rapidly and easily tailor the surface properties of these devices. We demonstrate a one-step procedure to covalently link polymers to the surface of PDMS microchannels by ultraviolet graft polymerization. Acrylic acid, acrylamide, dimethylacrylamide, 2-hydroxylethyl acrylate, and poly(ethylene glycol)monomethoxyl acrylate were grafted onto PDMS to yield hydrophilic surfaces. Water droplets possessed contact angles as low as 45 degrees on the grafted surfaces. Microchannels constructed from the grafted PDMS were readily filled with aqueous solutions in contrast to devices composed of native PDMS. The grafted surfaces also displayed a substantially reduced adsorption of two test peptides compared to that of oxidized PDMS. Microchannels with grafted surfaces exhibited electroosmotic mobilities intermediate to those displayed by native and oxidized PDMS. Unlike the electroosmotic mobility of oxidized PDMS, the electroosmotic mobility of the grafted surfaces remained stable upon exposure to air. The electrophoretic resolution of two test peptides in the grafted microchannels was considerably improved compared to that in microchannels composed of oxidized PDMS. By using the appropriate monomer, it should be possible to use UV grafting to impart a variety of surface properties to PDMS microfluidics devices.
A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2 (2020)

Despite various levels of preventive measures, in 2020, many countries have suffered severely from the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Using a model, we show that population heterogeneity can affect disease-induced immunity considerably because the proportion of infected individuals in groups with the highest contact rates is greater than that in groups with low contact rates. We estimate that if <i>R</i> <sub>0</sub> = 2.5 in an age-structured community with mixing rates fitted to social activity, then the disease-induced herd immunity level can be ~43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity rather than as an exact value or even a best estimate.
Intramural Delivery of Recombinant Apolipoprotein A-I Milano /Phospholipid Complex (ETC-216) Inhibits In-Stent Stenosis in Porcine Coronary Arteries (2003)

A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.
Review Article Techniques for Bioavailability Enhancement of BCS Class II Drugs: A Review (2013)

Traditionally, nearly 40% of the new chemical entities (NCEs) identified by pharmaceutical industry screening programmes have failed to be developed because of poor water-solubility, which makes their formulation difficult or even impossible. The solubility issues complicating the delivery of these new drugs also affect the delivery of many existing drugs. The various traditional and novel techniques that that can be used for solubility enhancement of BCS Class II drugs are briefly discussed in this article. The Traditional techniques that has been discussed in this article includes use of co-solvents, Hydrotropy, micronization, change in dielectric constant of solvent, amorphous forms, chemical modification of drug, use of surfactants, inclusion complex or clathrates, alteration of pH of solvent, use of hydrates or solvates, use of soluble prodrugs, application of ultrasonic waves, functional polymer technology, controlled precipitation technology, evaporative precipitation in aqueous solution, use of precipitation inhibitors, solvent deposition, precipitation, selective adsorption on insoluble carriers. Novel drug delivery technologies developed in recent years for solubility enhancement of insoluble drugs are size reduction technologies, lipid based delivery system, micellar technologies, porous microparticle technology. Solid Dispersion Technique and various types of solid dispersion systems has also been explained briefly.
Newly synthesized acetylcholine receptors are located in the Golgi apparatus. (1978)

Chick skeletal muscle cells in tissue culture were fixed and treated with saponin to allow [125I]alpha-bungarotoxin access into the cells while preserving ultrastructure. The kinetics of binding of iodinated alpha-bungarotoxin to intracellular acetylcholine (ACh) receptors and to surface A Ch receptors were comparable. About half of the intracellular ACh receptors are newly synthesized and in the pathway leading to incorporation into the plasma membrane. Correlated electron microscope autoradiographic and kinetic studies of this receptor population suggest that a substantial fraction of the newly synthesized ACh receptors are located in the Golgi apparatus, where they reside for approx. 2 h.
Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells (2004)

Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread distribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the arylsulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and prevented the development of motor conduction impairment, learning and coordination deficits, and neuropathological abnormalities typical of the disease. Remarkably, ex vivo gene therapy had a significantly higher therapeutic impact than WT HSC transplantation, indicating a critical role for enzyme overexpression in the HSC progeny. These results indicate that transplantation of LV-transduced autologous HSCs represents a potentially efficacious therapeutic strategy for MLD and possibly other neurodegenerative disorders.
Protection against β‐amyloid peptide toxicity in vivo with long‐term administration of ferulic acid (2001)

1. beta-Amyloid peptide (A beta), a 39 -- 43 amino acid peptide, is believed to induce oxidative stress and inflammation in the brain, which are postulated to play important roles in the pathogenesis of Alzheimer's disease. Ferulic acid is an antioxidant and anti-inflammatory agent derived from plants; therefore, the potential protective activity of ferulic acid against A beta toxicity in vivo was examined. 2. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%). After 4 weeks, A beta 1-42 (410 pmol) was administered via intracerebroventricular injection. 3. Injection of control mice with A beta 1-42 impaired performance on the passive avoidance test (35% decrease in step-through latency), the Y-maze test (19% decrease in alternation behaviour), and the water maze test (32% decrease in percentage time in platform-quadrant). In contrast, mice treated with ferulic acid prior to A beta 1-42 administration were protected from these changes (9% decrease in step-through latency; no decrease in alternation behaviour; 14% decrease in percentage time in platform-quadrant). A beta 1-42 induced 31% decrease in acetylcholine level in the cortex, which was tended to be ameliorated by ferulic acid. 4. In addition, A beta 1-42 increased immunoreactivities of the astrocyte marker glial fibrillary acidic protein (GFAP) and interleukin-1 beta (IL-1 beta) in the hippocampus, effects also suppressed by pretreatment with ferulic acid. 5. Administration of ferulic acid per se unexpectedly induced a transient and slight increase in GFAP and IL-1 beta immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. A slight (8%) decrease in alternation behaviour was observed on day 14. 6. These results demonstrate that long-term administration of ferulic acid induces resistance to A beta 1-42 toxicity in the brain, and suggest that ferulic acid may be a useful chemopreventive agent against Alzheimer's disease.