gebhart/patrepeval huggingface dataset:
17β-Estradiol Regulation of Human Endothelial Cell Basal Nitric Oxide Release, Independent of Cytosolic Ca 2+ Mobilization (1997)

Estradiol retards the development of atherosclerosis. Animal models have suggested that NO may be a critical effector molecule in this cardiovascular protection. In this study, female human umbilical vein endothelial cells (HUVECs) were propagated in phenol red-free gonadal hormone-free medium and pretreated with 17 beta-estradiol (E2). Reduced NO2- and NO3- (NOx) concentration, determined by chemiluminescence, demonstrated a rapid increase in basal HUVEC NO release in response to physiological concentrations of E2. The estrogen receptor (ER) antagonist ICI 164,384 inhibited the augmented NO release, demonstrating an ER-mediated component of this response. Because endothelial NO synthase (eNOS) activity is largely regulated by cytosolic Ca2+, relative [Ca2+]i in response to E2 was determined in a fluorometric assay. E2 did not promote HUVEC Ca2+ fluxes. Furthermore, eNOS activity in E2-pretreated endothelial whole-cell lysates was not dependent on additional Ca2+. Despite involving the ER, this is a nongenomic effect E2, as demonstrated by maintained responses in transcriptionally inhibited cells and by the rapidly (10 minutes) of cGMP formation in an NO bioassay. We demonstrate, for the first time, that independent of cytosolic Ca2+ mobilization, there is augmentation of eNOS activity with a resultant increase in HUVEC basal NO release in response to short-term estradiol exposure. Implications for the cardiovascular protective role of estrogen are discussed.
A construction of standardized near infrared hyper-spectral teeth database: a first step in the development of reliable diagnostic tool for quantification and early detection of caries (2011)

Dental caries is a disease characterized by demineralization of enamel crystals leading to the penetration of bacteria into the dentin and pulp. If left untreated, the disease can lead to pain, infection and tooth loss. Early detection of enamel demineralization resulting in increased enamel porosity, commonly known as white spots, is a difficult diagnostic task. Several papers reported on near infrared (NIR) spectroscopy to be a potentially useful noninvasive spectroscopic technique for early detection of caries lesions. However, the conducted studies were mostly qualitative and did not include the critical assessment of the spectral variability of the sound and carious dental tissues and influence of the water content. Such assessment is essential for development and validation of reliable qualitative and especially quantitative diagnostic tools based on NIR spectroscopy. In order to characterize the described spectral variability, a standardized diffuse reflectance hyper-spectral database was constructed by imaging 12 extracted human teeth with natural lesions of various degrees in the spectral range from 900 to 1700 nm with spectral resolution of 10 nm. Additionally, all the teeth were imaged by digital color camera. The influence of water content on the acquired spectra was characterized by monitoring the teeth during the drying process. The images were assessed by an expert, thereby obtaining the gold standard. By analyzing the acquired spectra we were able to accurately model the spectral variability of the sound dental tissues and identify the advantages and limitations of NIR hyper-spectral imaging.
Neutrophils play a critical role in the pathogenesis of experimental cerebral malaria (2000)

The role of neutrophils in experimental cerebral malaria (ECM) is not well understood. In this study we used a MoAb, RB6-8C5, to deplete the peripheral neutrophils of ECM-susceptible CBA/NSlc mice 24 h before Plasmodium berghei ANKA (PbA) infection. We found that early neutrophil depletion prevented the development of ECM and dramatically decreased the sequestration of monocytes and microhaemorrhage in the brain. The depletion of neutrophils also down-regulated tumour necrosis factor-alpha, interferon-gamma and IL-2 mRNAs and abrogated IL-12p40 mRNA expression in the brain as examined by competitive reverse transcriptase-polymerase chain reaction. Although depletion of neutrophils decreased the expression of Th1 cytokines in both spleen and brain, our results did not show the shift of a Th1 to a Th2 immune response since there was no obvious augmentation of expression of Th2 cytokine mRNAs (IL-4 and IL-10). We conclude that neutrophils play a role in the pathogenesis of ECM via enhancement of the expression of Th1 cytokines in the brain.
Determination of plasma tissue factor antigen and its clinical significance (1994)

To investigate the clinical significance of determination of plasma tissue factor (TF) antigen, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for plasma TF, using two different monoclonal antibodies against TF apoprotein, 6B4 (catching antibody) and 5G9 (detecting antibody), and tetramethyl benzidine/H2O2 as substrates. Titration curves of recombinant human TF in buffer containing Triton X-100 were linear within the range from 50 to 2000 pg/ml. The total assay time was 3 h. Ultracentrifugation and immunoblot analysis indicated that human plasma and urine contained 50,000 g sedimentable and non-sedimentable forms of TF, both of which were detected by our ELISA method. Plasma and urine concentrations of TF in healthy subjects and patients with various diseases were measured by the ELISA method. In healthy subjects, plasma and urinary TF levels were found to be 149 +/- 72 pg/ml (n = 30) and 175 +/- 60 pg TF/urine creatinine mg (n = 95), respectively. TF was increased in plasma of patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, vasculitis associated with collagen diseases, diabetic microangiopathy and chronic renal failure receiving haemodialysis, but not in the plasma of endotoxaemic patients without DIC. The plasma TF/serum creatinine ratio did not show a positive correlation. Measurement of TF antigen in plasma may be useful for evaluating the endothelial damage and cell destruction in TF-containing tissues.
[Experimental study of MAT1 gene silencing mediated by siRNA in pancreatic cancer]. (2007)

MAT1 gene silencing mediated by siRNA significantly suppresses the growth of pancreatic cancer cells in vitro, and significantly achieves an anti-tumor effect on the subcutaneously transplanted pancreatic tumor in vivo.
Functional Roles for the Cytoplasmic Domain of the Type III Transforming Growth Factor β Receptor in Regulating Transforming Growth Factor β Signaling (2001)

Transforming growth factor beta (TGF-beta) signals through three high affinity cell surface receptors, TGF-beta type I, type II, and type III receptors. The type III receptor, also known as betaglycan, binds to the type II receptor and is thought to act solely by "presenting" the TGF-beta ligand to the type II receptor. The short cytoplasmic domain of the type III receptor is thought to have no role in TGF-beta signaling because deletion of this domain has no effect on association with the type II receptor, or with the presentation role of the type III receptor. Here we demonstrate that the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor and the ability of the type II receptor to autophosphorylate. This interaction results in the phosphorylation of the cytoplasmic domain of the type III receptor by the type II receptor. The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor but is unable to enhance TGF-beta2 signaling, determining that the cytoplasmic domain is essential for some functions of the type III receptor. The type III receptor functions by selectively binding the autophosphorylated type II receptor via its cytoplasmic domain, thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex. These studies, for the first time, elucidate important functional roles of the cytoplasmic domain of the type III receptor and demonstrate that these roles are essential for regulating TGF-beta signaling.
Pharmacokinetics, Biodistribution, Stability and Toxicity of a Cell-Penetrating Peptide−Morpholino Oligomer Conjugate (2007)

This study demonstrates that conjugation of CPP to PMO enhances the PMO pharmacokinetic profile, tissue uptake, and subsequent retention. Therefore, when dosed at < or = 15 mg/kg, CPP is a promising transporter for enhancing PMO delivery in therapeutic settings.
Nerve growth factor expression and innervation of the painful intervertebral disc (2002)

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.
Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer (2015)

We provide proof of principle that analyses of xenopatients (avatar) and liquid biopsies allow the identification of drug resistance mechanisms in parallel with clinical treatment of an individual patient. We describe for the first time that p.G595R and p.G667C TRKA mutations drive acquired resistance to entrectinib in colorectal cancers carrying NTRK1 rearrangements.
Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture. (1988)

We investigated the effects of B cell stimulatory factor 2/interleukin 6 (BSF-2/IL-6) on the development of murine hemopoietic progenitors using serum-containing culture and serum-free culture. In serum-containing culture, BSF-2 mainly supported multipotential blast cell colonies from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice. In serum-free culture, no colony growth was seen in the presence of BSF-2. Addition of BSF-2 to the serum-free culture containing IL-3 resulted in a significant increase in the number of colonies formed from multipotential progenitors in spleen cells and bone marrow cells of 5-FU-treated mice, whereas no effects were seen on the number of single or oligolineage colonies formed by the spleen cells of normal mice. These results suggested that BSF-2 and IL-3 act synergistically on the multipotential progenitors but not on the maturer progenitors. When BSF-2 was added to a culture containing low concentrations of IL-3 (1 U/ml, 4 U/ml), which had little effect on colony formation, the number of total colonies formed by the spleen cells and bone marrow cells of 5-FU-treated mice increased significantly. The combination of BSF-2 and 40 U/ml of IL-3 resulted in a significant enlargement of GMM colonies. Thus, BSF-2 appears to enhance the sensitivity of multipotential hemopoietic progenitors to IL-3.
The estimated prevalence and incidence of late stage age related macular degeneration in the UK (2012)

These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments.
BIOCHEMICAL TAXONOMY AND MOLECULAR PHYLOGENY OF THE GENUS CHLORELLA SENSU LATO (CHLOROPHYTA) (1999)

A multimethod approach was used to characterize unicellular green algae that were traditionally assigned to the genus Chlorella Beijerinck and to resolve their phylogenetic relationships within the Chlorophyta. Biochemical, physiological, and ultrastructural characters, together with molecular data such as DNA base composition and DNA hybridization values, were compared with a molecular phylogeny based on complete 18S rRNA sequences. Our results show that Chlorella taxa are dispersed over two classes of chlorophytes, the Trebouxiophyceae and the Chlorophyceae. We propose that only four species should be kept in the genus Chlorella (Chlorophyta, Trebouxiophyceae): C. vulgaris Beijerinck, C. lobophora Andreyeva, C. sorokiniana Shih. et Krauss, and C. kessleri Fott et Nováková. Common characteristics of these taxa are glucosamine as a dominant cell wall component and the presence of a double thylakoid bisecting the pyrenoid matrix. Norspermine, norspermidine, and secondary carotenoids are never produced. Other “Chlorella” species belong to different taxa within the Trebouxiophyceae ( “C.” protothecoides = Auxenochlorella protothecoides [Krüger] Kalina et Punčochářová, “C.” ellipsoidea, “C.” mirabilis, “C.” saccharophila, and “C.” luteoviridis ) and Chlorophyceae ( “C.” zofingiensis and “C.” homosphaera = Mychonastes homosphaera Kalina et Punčochářová). The latter taxa can easily be recognized by the production of secondary carotenoids under nitrogen‐deficient conditions.
Biphasic alterations in gastrointestinal transit following endotoxaemia in mice (2001)

Lipopolysaccharide (LPS)-induced alterations of gastrointestinal transit were studied in mice using activated charcoal. LPS (10 mg kg-1) induced biphasic alterations of intestinal transit. Increase (acceleration phase) and delay (lag phase) in gastrointestinal transit were observed at 90 and 480 min after LPS injection, respectively. LPS administration induced significant increases in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and nitrate levels in blood serum with maximal levels observed at 1.5, 4, and 8 h after LPS administration, respectively. The effects of recombinant human lzactoferrin (rhLF) on LPS- induced alteration of gastrointestinal transit, and production of TNF-alpha, IL-1beta and nitrate were also studied. Animals were pretreated with rhLF 24 hours before intraperitoneal administration of LPS. RhLF significantly increased gastrointestinal transit during the lag phase. In addition, rhLF decreased the level of TNF-alpha in endotoxaemic animals. The levels of IL-1beta and nitrate were not significantly changed by rhLF. In conclusion, the effect of LPS on gastrointestinal transit is biphasic and the mechanism controlling the second phase most likely depends on TNF-alpha production, while the first phase most likely does not depend on TNF-alpha. On the other hand, it may be regulated by IL-1beta and nitric oxide production.
Helicobacter pylori: an invading microorganism? A review (2003)

In this review we evaluate the pros and cons of Helicobacter pylori invasion of epithelial cells as part of the natural history of H. pylori infection. H. pylori is generally considered an extracellular microorganism. However, a growing body of evidence supports the controversial hypothesis that at least a subset of H. pylori microorganisms has an intracellular (intraepithelial) location. Most significant is the fact that H. pylori invades cultured epithelial cells with invasion frequencies similar to Yersinia enterocolitica and better than Shigella flexneri; furthermore, studies of invasion mechanisms suggest that H. pylori invasion of and survival within epithelial cells is not merely a passive event, but requires active participation of the microorganism. Although many studies of human gastric biopsy specimens have failed to demonstrate any intracellular H. pylori, some studies have revealed a minor fraction of H. pylori inside gastric epithelial cells, with possible linkage to peptic ulceration and epithelial cell damage. In conclusion, these data encourage further research to establish whether intracellular H. pylori does play a role in H. pylori colonization of the human stomach and in peptic ulcer pathogenesis.
High-refractive-index composite materials for terahertz waveguides: trade-off between index contrast and absorption loss (2011)

We fabricate polymer compounds from titania-doped polyethylene and characterize their linear optical properties by terahertz time domain spectroscopy. We show that the high concentration of dopants not only enhances the refractive index of the composite material, but it also can dramatically raise its absorption coefficient. We demonstrate that the optimal design of photonic bandgap fibers based on lossy composites depends on finding a compromise between the high-refractive-index (hRI) contrast and corresponding material losses. Finally, fabrication and transmission measurements for the hRI contrast hollow-core Bragg fiber are reported and compared with simulations.
Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy (2011)

Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.
High‐throughput discovery of functional disordered regions (2018)

Abstract Partially or fully intrinsically disordered proteins are widespread in eukaryotic proteomes and play important biological functions. With the recognition that well defined protein structure is not a fundamental requirement for function come novel challenges, such as assigning function to disordered regions. In their recent work, Babu and colleagues (Ravarani et al, 2018) took on this challenge by developing IDR‐Screen, a robust high‐throughput approach for identifying functions of disordered regions.
Endocrine and ovarian responses to exogenous estradiol-17β in 6-month-old heifers previously immunized against growth hormone-releasing factor (1995)

We hypothesized that estradiol-17 beta (E2) was capable of stimulating an LH surge in 6-mo-old heifers immunized against growth hormone-releasing factor (GRFi). To test this hypothesis Angus x Simmental heifers were immunized against GRF (n = 11) or human serum albumin (HSAi) (n = 6) at 113 d of age. Heifers were injected i.m. with 500 micrograms of E2 at 172 d of age. To characterize the LH response, samples were collected at frequent intervals for 1 h before and 32 h after E2. To assess ovarian responses, real-time ultrasonography was performed from d 9 to 20, and serum progesterone was evaluated from d 6 to 25 after E2, then weekly for 13 wk. Exogenous E2 stimulated (P < .001) LH surges, preceded by negative E2 feedback that decreased serum LH, in all GRFi and HSAi heifers. During the negative feedback period, serum LH was greater (P < .001), and the change in LH from before to after E2 was lower (P < .05), in GRFi than in HSAi heifers. Puberty occurred in 7/17 heifers within 66 d after receiving E2. We conclude that GRFi does not impair the release of an E2-induced LH surge, but it does decrease hypothalamo-hypophyseal sensitivity to the inhibitory effect of E2.
Modeling the acoustic radiation force in microfluidic chambers (2008)

A procedure is demonstrated to quantitatively evaluate the acoustic radiation forces in microfluidic particle manipulation chambers. Typical estimates of the acoustic pressure and the acoustic radiation force are based on an analytical solution for a simple one-dimensional standing wave pattern. The complexities of a typical microfluidic channel limit the usefulness of this approach. By leveraging finite elements, and a generalized equation for the acoustic radiation force, channel designs can be investigated in two and three dimensions. Calculations and experimental observations in this report and the literature, confirm these claims.
An Enhanced Monomeric Blue Fluorescent Protein with the High Chemical Stability of the Chromophore (2011)

Commonly used monomeric blue fluorescent proteins suffer from moderate brightness. The brightest of them, mTagBFP, has a notably low chemical stability over time. Prolonged incubation of mTagBFP leads to its transition from a blue fluorescent state with absorbance at 401 nm to a non-fluorescent state with absorbance at 330 nm. Here, we have determined the chemical structure of the degraded product of the blue mTagBFP-like chromophore. On the basis of mTagBFP we have developed an improved variant, named mTagBFP2. mTagBFP2 exhibits 2-fold greater chemical stability and substantially higher brightness in live cells than mTagBFP. mTagBFP2 is also 1.2-fold and 1.7-fold more photostable than mTagBFP in widefield and confocal microscopy setups, respectively. mTagBFP2 maintains all other beneficial properties of the parental mTagBFP including the high pH stability and fast chromophore formation. The enhanced photostability and chromophore chemical stability of mTagBFP2 make it a superior protein tag. mTagBFP2 performs well in the numerous protein fusions and surpasses mTagBFP as a donor in Förster resonance energy transfer with several green fluorescent protein acceptors.