gebhart/patrepeval huggingface dataset:
The epithelial/carcinoma antigen EGP‐1, recognized by monoclonal antibody RS7–3G11, is phosphorylated on serine 303 (1995)

RS7-3G11 is a murine monoclonal antibody (MAb) raised against human non-small-cell lung carcinoma, and is under clinical evaluation. The epithelial/carcinoma antigen EGP-1, defined by RS7-3G11, was isolated and purified to homogeneity from a cervical carcinoma cell line, ME180. EGP-1 is a glycoprotein with an average molecular mass of 47.8 kDa. Metabolic labeling of the antigen with 32P-orthophosphate and subsequent immunoprecipitation with RS7-3G11 showed that it is a phosphoprotein. Phosphoamino acid analysis of the in vivo phosphorylated EGP-1 revealed that the phosphorylation is on serine. In vitro analysis with purified antigen demonstrated that protein kinase C, and not protein kinase A, is involved in phosphorylating the antigen in vitro. In vitro analysis indicated a stoichiometry of phosphorylation of 0.54 mole of phosphate per mole of EGP-1. Phosphoamino acid analysis and phosphopeptide mapping of the antigen phosphorylated in vitro by protein kinase C showed that phosphorylation occurred on a serine residue, specifically on serine 303, located in the cytoplasmic domain of EGP-1. Treatment of ME180 cells with phorbol ester increased the phosphorylation of EGP-1. The biological function of EGP-1 remains to be elucidated. In this report we elucidate an involvement of protein kinase C in phosphorylating EGP-1, which may signify a role for this antigen in signal transduction across the cell membrane.
Peptide nucleic acids (PNA) derived from N-(N-methylaminoethyl)glycine. Synthesis, hybridization and structural properties (1999)

Backbone N-methylated peptide nucleic acids (PNAs) containing the four nucleobases adenine, cytosine, guanine and thymine were synthesized via solid phase peptide oligomerization. The oligomers bind to their complementary target with a thermal stability that is 1.5–4.5°C lower per '‘N-methyl nucleobase unit’' [dependent on the number and position(s) of the N-methyl] than that of unmodified PNA. However, even fully N-methyl modified PNAs bind as efficiently to DNA or RNA targets as DNA itself. Furthermore, the hybridization efficiency per N-methyl unit in a PNA decreased with increasing N-methyl content, and the effect was more pronounced when the N-methyl backbone units are present in the Hoogsteen versus the Watson–Crick strand in (PNA)2-DNA triplexes. Interestingly, CD spectral analyses indicate that 30% (3 out of ten) substitution with N-methyl nucleobases did not alter the structure of PNA-DNA (or RNA) duplexes or (PNA)2-DNA triplexes, and likewise CD spectroscopy and X-ray crystallography showed no major structural differences between N-methylated (30%) and unmodified PNA-PNA duplexes. However, PNA-DNA duplexes as well as triplexes adopted a different conformation when formed with all-N-methyl PNAs.
SNR Walls for Signal Detection (2008)

This paper considers the detection of the presence/absence of signals in uncertain low SNR environments. Small modeling uncertainties are unavoidable in any practical system and so robustness to them is a fundamental performance metric. The impact of these modeling uncertainties can be quantified by the position of the "SNR wall" below which a detector will fail to be robust, no matter how long it can observe the channel. We propose simple mathematical models for the uncertainty in the noise and fading processes. These are used to show what aspects of the model lead to SNR walls for differing levels of knowledge of the signal to be detected. These results have implications for wireless spectrum regulators. The context is opportunistically sharing spectrum with primary users that must be detected in order to avoid causing harmful interference on a channel. Ideally, a secondary system would be able to detect primaries robustly without having to know much about their signaling strategies. We argue that the tension between primary and secondary users is captured by the technical question of computing the optimal tradeoff between the primary user's capacity and the secondary user's sensing robustness as quantified by the SNR wall. This is an open problem, but we compute this tradeoff for some simple detectors.
Metabolic Sites of Action of Fluridone in Isolated Mesophyll Cells (1979)

Time- and concentration-course studies were conducted to determine the metabolic sites of action of fluridone {1-methyl-3-phenyl-5-[3-(trifluoromethyl)phenyl]-4(1 H )-pyridinone} in isolated mesophyll cells of cotton ( Gossypium hirsutum L. ‘Acala SJ-1′) and red kidney bean ( Phaseolus vulgaris L.). Cotton is resistant and bean is susceptible to fluridone. The herbicide was not metabolized in cells of either species during the 2-h incubation period. At the highest concentration (10 -4 M) and longest incubation time (2 h), fluridone inhibited photosynthesis, RNA synthesis, and protein synthesis 59, 56, and 32%, respectively in bean and 24, 21, and 14% in cotton. Lipid synthesis and dark respiration were only slightly affected. The lowest concentration and the shortest incubation period that inhibited photosynthesis, RNA synthesis, and protein synthesis in bean did not have any significant effect in cotton. The difference in responses may contribute to the selectivity of the herbicide. Although photosynthesis appeared to be the primary site of action, RNA synthesis was also markedly inhibited. These inhibitions and the somewhat lower inhibition of protein synthesis may ultimately contribute to the herbicidal action of fluridone in the intact plant.
Dietary fat and reduced levels of TGFβ1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions (2000)

Transforming growth factor-(beta) (TGF(beta)) has a wide range of activities on vascular cells and inflammatory cells, suggesting it may have different functions during various stages of atherogenesis. We report that mice heterozygous for the deletion of the tgfb1 gene (tgfb1(+/-) mice) have reduced levels of TGF(beta)1 in the artery wall until at least 8 weeks of age. On a normal mouse chow diet, the vascular endothelium of tgfb1(+/-) mice is indistinguishable from wild-type littermates, assessed by morphology and intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. In contrast, levels of the smooth muscle isoforms of actin and myosin in medial smooth muscle cells of tgfb1(+/-) mice are significantly reduced. Following feeding a cholesterol-enriched diet for 12 weeks, high levels of ICAM-1 and VCAM-1 were detected in the vascular endothelial cells of tgfb1(+/-) mice, but not wild-type mice. Furthermore, marked deposition of lipid into the artery wall was only observed in the tgfb1(+/-) mice on the cholesterol-enriched diet. These vascular lipid lesions were accompanied by local invasion of macrophages. We conclude that deletion of a single allele of the tgfb1 gene results in a reduced level of TGFbeta1 antigen in the aorta together with reduced smooth muscle cell differentiation, whereas the addition of a high fat dietary challenge is required to activate the vascular endothelium and to promote the formation of fatty streaks resembling early atherosclerosis in humans.
Bilayer graphene: gap tunability and edge properties (2008)

Bilayer graphene { two coupled single graphene layers stacked as in graphite { provides the only known semiconductor with a gap that can be tuned externally through electric fleld efiect. Here we use a tight binding approach to study how the gap changes with the applied electric fleld. Within a parallel plate capacitor model and taking into account screening of the external fleld, we describe real back gated and/or chemically doped bilayer devices. We show that a gap between zero and midinfrared energies can be induced and externally tuned in these devices, making bilayer graphene very appealing from the point of view of applications. However, applications to nanotechnology require careful treatment of the efiect of sample boundaries. This being particularly true in graphene, where the presence of edge states at zero energy { the Fermi level of the undoped system { has been extensively reported. Here we show that also bilayer graphene supports surface states localized at zigzag edges. The presence of two layers, however, allows for a new type of edge state which shows an enhanced penetration into the bulk and gives rise to band crossing phenomenon inside the gap of the biased bilayer system.
Functional borders, genetic fine structure, and distance requirements of cis elements mediating light responsiveness of the parsley chalcone synthase promoter. (1990)

The genetic fine structure of cis-acting sequences previously shown to be necessary for light-regulated expression in the promoter of the parsley (Petroselinum crispum) chalcone synthase gene was analyzed. Site-directed mutations and changes in spacing between cis elements were measured in transient expression assays in parsley protoplasts. Clustered point mutations allowed assignment of functional borders. Single-base substitutions within a highly conserved cis element (box II/G box) defined a critical core of seven bases, 5'-ACGTGGC-3'. It is functionally equivalent to a second sequence-related element (box III), which could replace box II in an orientation-dependent manner. The activity of box II required the presence of another juxtaposed element (box I) at a defined distance. No distance requirement was observed between the two large separable promoter regions known to independently confer light-regulated expression. These data support our hypothesis that a cis-acting sequence that is present in a limited number of diversely regulated plant genes gains its functional capacity and specificity by combinatorial diversity involving flanking partner elements.
Characterization of Clones of HIV‐1 Infected HuT 78 Cells Defective in gag Gene Processing and of SIV Clones Producing Large Amounts of Envelope Glycoprotein (1990)

Single‐cell clones of HIV‐1 (FRE‐3) or SIV/Mne infected HuT 78 cells were obtained by plating dilutions of virally infected HuT 78 cells on a monolayer of sheep choroid plexus cells in 96‐well microliter plates. Several of these clones produce HIV‐1 virus mutants that accumulate the gag precursor polyprotcin and lack a functional protease. These protease‐deficient viruses are non‐infectious and consist of aberrant “immature” virus particles as determined by electron microscopy. Several SIV mutants are also described that produce large amounts of either the envelope glycoprotein gp120 or the nucleic acid binding gag protein. These mutants are useful for the purification of these retroviral proteins, in developing assays of protease inhibitors, and in preparing SIV envelope protein vaccines.
Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine (2017)

Objective To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3 study evaluating ADAM zolmitriptan 1 mg, 1.9 mg, and 3.8 mg versus placebo. Co-primary endpoints were pain freedom and freedom from most bothersome other migraine-associated symptom 2 hours post-dose. Results Of patients treated with ADAM zolmitriptan 3.8 mg or placebo, 41.5% and 14.2%, respectively were pain-free 2 hours post-dose ( p = 0.0001) and 68.3% and 42.9% were free from their most bothersome other symptom ( p = 0.0009). Due to the fixed sequential testing methodology, formal statistical significance was not established for secondary endpoints. However, the proportion of patients who were photophobia-free, phonophobia-free, and nausea-free at 2 hours post-dose was higher in the ADAM zolmitriptan 3.8 mg group compared with placebo, as were the percentages of patients who were pain-free, and who experienced pain relief up to 48 hours post-dose. Systemic adverse events were consistent with previous triptan trials, and included dizziness, paresthesia, muscle tightness, and nausea, all of which occurred in < 5% of patients in any group. Application site reactions were generally mild and resolved within 48 hours, although erythema and bruising persisted for longer periods in some patients. Conclusion ADAM zolmitriptan 3.8 mg provides effective relief of migraine headache and associated most bothersome symptoms compared with placebo, and is well-tolerated. ClinicalTrials.gov NCT02745392.
Apoptosis in Autoimmune Diseases. (2001)

Over the past decade, our understanding of apoptosis, or programmed cell death, has increased greatly, with the identification of some of the major components of the apoptotic program and the processes regulating their activation. Although apoptosis is an intrinsic process present in all cells, it can be regulated by extrinsic factors, including growth factors, cell surface receptors, cellular stress and hormones. Apoptotis plays an important role in autoimmune diseases. Normal thyrocytes could induce apoptosis of infiltrating activated T cells and protect against attack by such cells, i.e., the normal thyroid tissues act as an immune privileged site. In Hashimoto's thyroiditis (HT), Fas-mediated apoptosis of thyrocytes in a section of tissues is due to at least two separate mechanisms, the first by infiltrating activated T cells, and the other by FasL-positive thyrocytes in a suicidal or fratricidal fashion. A common feature of autoimmune diseases such as systemic lupus erythematosus (SLE) is the breakdown of tolerance of self antigens, a consequence of which is the production of autoantibodies reactive with multiple self proteins. Evidence is accumulating that modifications of autoantigens during apoptosis lead to the development of autoantibodies by bypassing the normal mechanisms of tolerance. Tissue homeostasis is maintained through a balance between cell proliferation and apoptotic cell death. Rheumatoid arthritis (RA) is characterized by pronounced hyperplasia of the synovial tissue, cell infiltration and periarticular osteoporosis. Enhanced Bcl-2 expression and NF-kappaB nuclear translocation of synovial cells are induced by inflammatory cytokines and/or growth factors. These synovial cells become resistant toward apoptosis triggered by various stimuli. The infiltrated cells which are defect in activation-induced cell death can cause autoimmunity by allowing the survival of autoreactive T and B cells. These data suggest that apoptosis might be implicated with the pathogenesis of autoimmunity, whereas the mechanisms might be distinct in each autoimmune disease.
Snapshot imaging Mueller matrix polarimeter using polarization gratings (2012)

A snapshot imaging Mueller matrix polarimeter (SIMMP) is theoretically described and empirically demonstrated through simulation. Spatial polarization fringes are localized onto a sample by incorporating polarization gratings (PGs) into a polarization generator module. These fringes modulate the Mueller matrix (MM) components of the sample, which are subsequently isolated with PGs in an analyzer module. The MM components are amplitude modulated onto spatial carrier frequencies which, due to the PGs, maintain high visibility in spectrally broadband illumination. An interference model of the SIMMP is provided, followed by methods of reconstruction and calibration. Lastly, a numerical simulation is used to demonstrate the system's performance in the presence of noise.
Tissue engineering of a bioartificial kidney (1994)

Tissue engineering is a rapidly growing field in biotechnology. The use and packaging of synthetic materials, biologic compounds, and cellular components of specific tissues can be envisioned to replace physiologic function of diseased organs. Long-term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. The initial concepts for these devices are just beginning to be considered and developed. (c) 1994 John Wiley & Sons, Inc.
The in vivo metabolism of recombinant human erythropoietin in the rat (1989)

Abstract We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.
Inelastic Electron Tunneling Spectroscopy of an Alkanedithiol Self-Assembled Monolayer (2004)

Inelastic electron tunneling spectroscopy (IETS) of an alkanedithiol self-assembled monolayer (SAM) is investigated using a nanometer-scale device. The IETS spectrum of the octanedithiol device clearly shows vibrational signatures of an octanedithiolate, −SC8 H16S−, bonded to gold electrodes. The pronounced IETS peaks correspond to vibrational modes perpendicular to the junction interface, which include the stretching modes of Au−S (at 33 mV) and C−C (at 133 mV) and the wagging mode of CH2 (at 158 mV). The observed peak intensities and peak widths are in good agreement with theoretical predictions.
Ethanolic fermentation of xylose with Saccharomyces cerevisiae harboring the Thermus thermophilus xylA gene, which expresses an active xylose (glucose) isomerase (1996)

The Thermus thermophilus xylA gene encoding xylose (glucose) isomerase was cloned and expressed in Saccharomyces cerevisiae under the control of the yeast PGK1 promoter. The recombinant xylose isomerase showed the highest activity at 85 degrees C with a specific activity of 1.0 U mg-1. A new functional metabolic pathway in S. cerevisiae with ethanol formation during oxygen-limited xylose fermentation was demonstrated. Xylitol and acetic acid were also formed during the fermentation.
Sewage Reflects the Microbiomes of Human Populations (2015)

The gut microbiota serves important functions in healthy humans. Numerous projects aim to define a healthy gut microbiome and its association with health states. However, financial considerations and privacy concerns limit the number of individuals who can be screened. By analyzing sewage from 71 cities, we demonstrate that geographically distributed U.S. populations share a small set of bacteria whose members represent various common community states within U.S. adults. Cities were differentiated by their sewage bacterial communities, and the community structures were good predictors of a city's estimated level of obesity. Our approach demonstrates the use of sewage as a means to sample the fecal microbiota from millions of people and its potential to elucidate microbiome patterns associated with human demographics.
Stimulation of yeast adenylyl cyclase activity by lysophospholipids and fatty acids. Implications for the regulation of Ras/effector function by lipids. (1994)

A reconstituted system containing membranes prepared from various Saccharomyces cerevisiae strains (CYR1 ras1 ras2) and a recombinant RAS2 protein was used to evaluate the effect of lipids on adenylyl cyclase activity. Incubation of wild-type membranes with lysophosphatidylinositol, lysophosphatidylserine, or lysophosphatidylcholine stimulated adenylyl cyclase activity in the absence and presence of RAS between 2-10-fold depending upon the individual lipid. Unsaturated fatty acids preferentially increased activity 2-3-fold in the presence of RAS. Other phospholipids as well as several detergents had only marginal effects on adenylyl cyclase activity. Lipids had no effect on either the binding or hydrolysis of GTP by RAS. LysoPI decreased both the Km for ATP and the amount of RAS required for enzyme activation. Four catalytically active deletion mutants of the CYR1 protein including one containing only the C-terminal 417 amino acids were similarly responsive to lysoPI when compared to the wild-type enzyme. These data suggest that lysophospholipids and fatty acids, metabolites of the mitogenically responsive enzyme phospholipase A2, may represent a novel mechanism for modulating the activity of downstream effector molecules and their interaction with Ras proteins.
The Role of Wnt Signaling in Physiological and Pathological Angiogenesis (2010)

Early stages of vascular development include endothelial cell differentiation in a network of arteries, veins, and lymphatics. Subsequently, to respond to the specific needs of the organs, endothelial cells acquire specialized properties such as permeability control, expression of specific transcellular transport systems, membrane adhesive molecules, and others. Endothelial cell differentiation depends on communication between the surrounding tissues, which is mediated by growth and differentiation factors able to activate specific gene expression programs. Recent reports underline the important role of the Wnt system in vascular morphogenesis in the embryo and in organ-specific endothelial differentiation. Wnt signaling regulates fundamental aspects of development, including cell fate specification, proliferation, and survival, and may use different receptors and signaling pathways. Both loss- and gain-of-function experiments of members of the Wnt signaling pathway were found to cause marked alterations of vascular development and endothelial cell specification. Furthermore, altered Wnt signaling in the endothelium may contribute to pathological conditions such as retinopathies, pulmonary arterial hypertension, stroke, and others. Continued progress in this field holds the potential to identify novel therapeutics for the treatment of these diseases.