gebhart/patrepeval huggingface dataset:
The diversity of small eukaryotic phytoplankton (≤3 μm) in marine ecosystems (2008)

Small cells dominate photosynthetic biomass and primary production in many marine ecosystems. Traditionally, picoplankton refers to cells < or =2 microm. Here we extend the size range of the organisms considered to 3 microm, a threshold often used operationally in field studies. While the prokaryotic component of picophytoplankton is dominated by two genera, Prochlorococcus and Synechococcus, the eukaryotic fraction is much more diverse. Since the discovery of the ubiquitous Micromonas pusilla in the early 1950s, just over 70 species that can be <3 microm have been described. In fact, most algal classes contain such species. Less than a decade ago, culture-independent approaches (in particular, cloning and sequencing, denaturing gradient gel electrophoresis, FISH) have demonstrated that the diversity of eukaryotic picoplankton is much more extensive than could be assumed from described taxa alone. These approaches revealed the importance of certain classes such as the Prasinophyceae but also unearthed novel divisions such as the recently described picobiliphytes. In the last couple of years, the first genomes of photosynthetic picoplankton have become available, providing key information on their physiological capabilities. In this paper, we discuss the range of methods that can be used to assess small phytoplankton diversity, present the species described to date, review the existing molecular data obtained on field populations, and end up by looking at the promises offered by genomics.
The Hedgehog Signaling Pathway in Cancer (2006)

The Hedgehog (Hh) pathway is a signaling cascade that directs patterning in most animals and is crucial for proper development. At the molecular level, Hh ligands drive cell proliferation in some cell types while causing others to undergo differentiation. Hh signaling is most active during embryogenesis, and aberrant reactivation of the pathway in adult tissue can lead to the development of cancer. A comprehensive understanding of Hh signaling during development will undoubtedly shed light into the mechanism of Hh in cancer progression and identify potential targets for therapeutic intervention.
Dermal Stem Cells Can Differentiate Down an Endothelial Lineage (2012)

In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle.
Modeling Surface Discharge Effects of Atmospheric RF on Gas Flow Control (2005)

Abstract : The advantages of plasma actuators for flow control are being increasingly recognized in the literature in all speed regimes encountered in aerospace applications. Recent experiments with suitably configured atmospheric RF discharges have demonstrated particularly striking effects by reducing or eliminating separation in low-speed flows. In this paper, a finite-element multi-fluid formulation is developed and utilized to model the RF induced plasma dynamics of an asymmetric electrode configuration. Partially ionized helium gas flow is considered over two electrodes, one exposed and one embedded in a thin dielectric material. The exposed electrode is powered with an RF potential and the embedded electrode is considered grounded. In a previous work, the derived electric field for a discharge between two insulated electrodes was coupled to a simple phenomenological model for the transverse velocity in a one-dimensional situation that predicted the anticipated hump in the near wall profile. Here the model is modified for the surface barrier discharge, extended to two-dimensions and applied to a realistic configuration comprised of a flush-mounted surface electrode and a corresponding streamwise displaced electrode embedded in the dielectric. The results extract features of the plasma-wall interaction on the neutral flow field with a self-consistent approach. The computed solutions for the evolution of electric field, space charge distribution and neutral gas densities are presented. The effect of the electric force due to surface discharge on the working gas flow is also demonstrated.
Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain (2005)

Recently, it was reported that anesthetizing infant rats for 6 h with a combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused widespread apoptotic neurodegeneration in the developing brain, followed by lifelong cognitive deficits. It has also been reported that ketamine triggers neuroapoptosis in the infant rat brain if administered repeatedly over a period of 9 h. The question arises whether less extreme exposure to anesthetic drugs can also trigger neuroapoptosis in the developing brain. To address this question we administered ketamine, midazolam or ketamine plus midazolam subcutaneously at various doses to infant mice and evaluated the rate of neuroapoptosis in various brain regions following either saline or these various drug treatments. Each drug was administered as a single one-time injection in a dose range that would be considered subanesthetic, and the brains were evaluated by unbiased stereology methods 5 h following drug treatment. Neuroapoptosis was detected by immunohistochemical staining for activated caspase-3. It was found that either ketamine or midazolam caused a dose-dependent, statistically significant increase in the rate of neuroapoptosis, and the two drugs combined caused a greater increase than either drug alone. The apoptotic nature of the neurodegenerative reaction was confirmed by electron microscopy. We conclude that relatively mild exposure to ketamine, midazolam or a combination of these drugs can trigger apoptotic neurodegeneration in the developing mouse brain.
Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. (1994)

The dbl oncogene product contains a 238-amino acid domain, which is shared by an expanding family of growth regulatory proteins. These include the Saccharomyces cerevisiae cell division cycle protein, CDC24, the breakpoint cluster region protein, the ect2 and vav oncogene products, and the brain GDP-releasing factor for Ras. Previous studies have provided evidence that oncogenic Dbl or an associated protein stimulates GDP dissociation from the human species (Hs) homolog of CDC42. We show here that Dbl specifically complexes with the GDP-bound forms of CDC42Hs and RhoA, but not Rac1 or TC10, and that this specificity correlates with the ability of Dbl to act as a GDP-releasing factor. Small deletions throughout the Dbl domain, which inactivate transformation, eliminated the ability of Dbl to stimulate GDP dissociation, whereas deletions outside of this domain did not impair either function. Finally, the Dbl domain itself, when expressed and purified as a recombinant protein, was shown to stimulate GDP dissociation from purified, recombinant CDC42Hs. These findings establish that a minimal unit on Dbl that is critical to its transforming function directly regulates GDP-GTP exchange activity.
Structural and functional aspects of the blood-brain barrier (2003)

All organisms with a complex nervous system have a well-developed blood-central nervous system barrier. In the vertebrates the central nervous system (CNS) lies behind the protective blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). In all mammals the BBB is formed at the level of the cerebral capillary endothelial cells and the BCSFB by the choroid plexus epithelium.
MDM4 expression as an indicator of TP53 reactivation by combined targeting of MDM2 and MDM4 in cancer cells without TP53 mutation (2014)

MDM2 and MDM4, a structurally related MDM2 homolog, negatively regulates expression and functions of TP53 tumor suppressor gene. To explore the precise expression patterns and function of MDM2 and MDM4 in wild-type (wt) TP53 cancer cells, we analyzed 11 various cancer cell lines with wt TP53. All cell lines exhibited deregulated expression of MDM2 and MDM4, and were divided into two distinct types; the one expressing high levels of MDM4 and another expressing low levels of MDM4. The low MDM4 type expressed higher MDM2 levels than the high MDM4 type. In cells with high MDM4 expression, knockdown of MDM4 or MDM2 reactivated TP53, and simultaneous knockdown of MDM2 and MDM4 synergistically reactivated TP53. In contrast, in cells with low MDM4 expression, knockdown of only MDM2 reactivated TP53. These results suggest that both MDM2 and MDM4 are closely involved in TP53 inactivation in cancer cells with high MDM4 expression, whereas only MDM2, and not MDM4, is a regulator of TP53 in cells with low MDM4 expression. MDM4 expression in wt TP53-tumors is a potential indicator for TP53 reactivation cancer therapy by simultaneous targeting of MDM4 and MDM2. Specific knockdown of MDM2 and MDM4 might be applicable for TP53 restoration therapy.
The Poisson distribution and beyond: methods for microfluidic droplet production and single cell encapsulation (2015)

There is a recognized and growing need for rapid and efficient cell assays, where the size of microfluidic devices lend themselves to the manipulation of cellular populations down to the single cell level. An exceptional way to analyze cells independently is to encapsulate them within aqueous droplets surrounded by an immiscible fluid, so that reagents and reaction products are contained within a controlled microenvironment. Most cell encapsulation work has focused on the development and use of passive methods, where droplets are produced continuously at high rates by pumping fluids from external pressure-driven reservoirs through defined microfluidic geometries. With limited exceptions, the number of cells encapsulated per droplet in these systems is dictated by Poisson statistics, reducing the proportion of droplets that contain the desired number of cells and thus the effective rate at which single cells can be encapsulated. Nevertheless, a number of recently developed actively-controlled droplet production methods present an alternative route to the production of droplets at similar rates and with the potential to improve the efficiency of single-cell encapsulation. In this critical review, we examine both passive and active methods for droplet production and explore how these can be used to deterministically and non-deterministically encapsulate cells.
Determination of haplotypes at structurally complex regions using emulsion haplotype fusion PCR (2012)

This study has demonstrated a novel use for emulsion haplotype fusion PCR in addressing the issue of reconstructing structural haplotypes at multiallelic copy variable regions, using the DEFA1A3 locus as an example.
PPP Over AAL5 (1998)

This document describes the use of ATM Adaptation Layer 5 (AAL5) for
framing PPP encapsulated packets. [STANDARDS-TRACK]
Antigen‐binding site anatomy and somatic mutations in antibodies that recognize different types of antigens (2012)

The number of antibody structures co-crystallized with their respective antigens has increased rapidly in the last few years, thus offering a formidable source of information to gain insight into the structure-function relationships of this family of proteins. We have analyzed here 140 unique middle-resolution to high-resolution (<3 Å) antibody structures, including 55 in complex with proteins, 39 with peptides, and 46 with haptens. We determined (i) length variations of the hypervariable loops, (ii) number of contacts with antigen, (iii) solvent accessible area buried upon binding, (iv) location and frequency of antigen contacting residues, (v) type of residues interacting with antigens, and (vi) putative somatic mutations. Except for somatic mutations, distinctive profiles were identified for all the variables analyzed. Compared with contacts, somatic mutations occurred with less abundance at any given position and extended beyond the regions in contact, with no clear difference among antibodies that recognize different types of antigens. This observation is consistent with the fact that although antigen recognition accomplished by shape and physicochemical complementarity is selective in nature, the somatic mutation process is stochastic and selection for mutations leading to improved affinity is not directly related to contact residues. Thus, the knowledge emerging from this study enhances our understanding of the structure-function relationship in antibodies while providing valuable guidance to design libraries for antibody discovery and optimization.
Tropoelastin Incorporation into a Dermal Regeneration Template Promotes Wound Angiogenesis (2014)

Severe burn injury results in substantial skin loss and cannot be treated by autografts. The Integra Dermal Regeneration Template (IDRT) is the leading synthetic skin substitute because it allows for wound bed regeneration and wound healing. However, all substitutes suffer from slow blood vessel ingrowth and would benefit considerably from enhanced vascularization to nurture tissue repair. It is shown here that by incorporating the human elastic protein tropoelastin into a dermal regeneration template (TDRT) we can promote angiogenesis in wound healing. In small and large animal models comprising mice and pigs, the hybrid TDRT biomaterial and IDRT show similar contraction to autografts and decrease wound contraction compared to open wounds. In mice, TDRT accelerates early stage angiogenesis by 2 weeks, as evidenced by increased angiogenesis fluorescent radiant efficiency in live animal imaging and the expression of endothelial cell adhesion marker CD146. In the pig, a full thickness wound repair model confirms increased numbers of blood vessels in the regenerating areas of the dermis closest to the hypodermis and immediately below the epidermis at 2 weeks post-surgery. It is concluded that including tropoelastin in a dermal regeneration template has the potential to promote wound repair through enhanced vascularization.
Randomized, Single-Blind, Placebo-Controlled Studyof Topical Application of the Immune Response ModulatorResiquimod in HealthyAdults (2003)

Resiquimod is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent inducer of alpha interferon (IFN-alpha) and other cytokines. The effects of multiple applications of resiquimod gel were assessed in a randomized, single-blind, dose-ranging, placebo-controlled study with 41 healthy subjects. Over a 3-week period, 1-g doses of resiquimod or vehicle gel (3:1 randomization) were applied to a 50-cm2 area of the upper arm according to the following regimens: 0.25% applied for 8 h two times per week, 0.05% applied for 8 h two times per week, 0.05% applied for 8 h three times per week, and 0.01% applied for 24 h three times per week. Skin biopsy specimens were obtained prior to the application of the first dose and after the completion of application of the last dose. Dosing with 0.01 and 0.05% resiquimod was well tolerated, but that with 0.25% was not; a dose-response relationship for local adverse effects was observed. The level of systemic exposure during multiple topical dosings was <1% of the applied dose. A significant increase in responders after completion of application of the last dose was observed for serum IFN and the interleukin-1 (IL-1) receptor antagonist (P<0.01, Fisher's exact test). Increased levels of mRNA for IL-6, IL-8, IFN-alpha, and Mx (an IFN-alpha-inducible protein) were seen in posttreatment biopsy specimens from the group receiving 0.25% resiquimod compared to the levels seen in specimens from the group receiving vehicle only (P<0.01, Wilcoxon rank sum test). A dose-response-related increase in CD3-positive cells consistent with T-lymphocyte infiltration and a decrease in CD1a-positive cells, consistent with emigration of Langerhans' cells, were observed in treated skin. This study suggests that resiquimod is a potent topically active immune response modifier that significantly enhances the cutaneous immune response.
Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation (2006)

Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.
Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin (1991)

<h3>Objective.</h3> —To determine the efficacy of short-term administration of a synthetic analogue of α-melanotropin, [<i>N</i>le<sup>4</sup>D-Phe<sup>7</sup>] (NDP)—α-melanocyte-stimulating hormone (MSH), in darkening (tanning) human skin. <h3>Design.</h3> —Randomized, placebo-controlled, double-blind clinical trial. <h3>Setting.</h3> —Clinical research unit of a university medical center. <h3>Subjects.</h3> —Twenty-eight healthy white men with a history of either poor tanning (skin type I or II) or good tanning (skin type III or IV) recruited from advertisements and paid to participate in the study. <h3>Methods.</h3> —Each subject received 10 subcutaneous injections of either a purified NDP preparation or saline over 12 days. They were followed up for 7 weeks after therapy was completed. All subjects used a high-potency sunscreen during the the trial. <h3>Main Outcome Measure.</h3> —Skin darkening was quantified by serial chromaticity measurements prior to, during, and after therapy. <h3>Results.</h3> —A significant parabolic curve of skin darkening activity was noted in subjects with skin type I or II (<i>P</i>,.001) and with skin type III or IV (<i>P</i>&lt;&lt;.001) who were given NDP. No darkening occurred in the subjects who were given a placebo. Peak changes were seen 1 to 3 weeks after therapy was completed. <h3>Conclusion.</h3> —Human skin darkens as a response to a synthetic melanotropin given by subcutaneous injection. Skin tanning appears possible without potentially harmful exposure to ultraviolet radiation. (<i>JAMA</i>. 1991;266:2730-2736)
Growth of Sesbania rostrata (Brem) with stem nodules under controlled conditions (1992)

ABSTRACT A series of experiments was carried out in an attempt to produce nodulated plants of Sesbania rostrata with qualities more closely resembling those in the wild than has been achieved to date. When groups of five plants were grown in a controlled climate chamber in pipes containing ∼12dm 3 modified Jensen's medium with 6mol m −3 nitrate, the daily growth in height reached 5 cm and at 30 d the plants were ∼40cm high. At this time, the stems were inoculated with Azorhizobium caulinodans ORS 571 and the medium replaced with Jensen's medium without nitrate. In the subsequent 19‐d period ∼300 nodules (representing &gt;50% of the potential infection sites) developed on each stem. The nodules increased linearly in size over this time to ∼15mg. Specific acetylene reduction activity, ARA ((μmol C 2 H 4 mg −1 h −1 ) rose to 45 between days 5 and 10 after inoculation and plateaued; total ARA rose to ∼200 μmol C 2 H 4 plant −1 h −1 . Under the conditions described the plants grew vigorously, and reproducibly uniform yields of nodules with high ARA activities were obtained. As outlined, the procedure offers a standard system in which, within a 2‐week period after inoculation, individual strains of bacteria can be quantitatively compared in their ability to induce nodulation and N 2 ‐fixation. Physiological and biochemical aspects of the nodulated system can be much more readily approached than with plants producing only root nodules. The inhibitory effects of stem nodules induced by wild type and two mutant strains of Azorhizobium on the development and activity of root nodules are described.
Neural and Photochemical Mechanisms of Visual Adaptation in the Rat (1963)

The effects of light adaptation on the increment threshold, rhodopsin content, and dark adaptation have been studied in the rat eye over a wide range of intensities. The electroretinogram threshold was used as a measure of eye sensitivity. With adapting intensities greater than 1.5 log units above the absolute ERG threshold, the increment threshold rises linearly with increasing adapting intensity. With 5 minutes of light adaptation, the rhodopsin content of the eye is not measurably reduced until the adapting intensity is greater than 5 log units above the ERG threshold. Dark adaptation is rapid (i.e., completed in 5 to 10 minutes) until the eye is adapted to lights strong enough to bleach a measurable fraction of the rhodopsin. After brighter light adaptations, dark adaptation consists of two parts, an initial rapid phase followed by a slow component. The extent of slow adaptation depends on the fraction of rhodopsin bleached. If all the rhodopsin in the eye is bleached, the slow fall of threshold extends over 5 log units and takes 2 to 3 hours to complete. The fall of ERG threshold during the slow phase of adaptation occurs in parallel with the regeneration of rhodopsin. The slow component of dark adaptation is related to the bleaching and resynthesis of rhodopsin; the fast component of adaptation is considered to be neural adaptation.