gebhart/patrepeval huggingface dataset:
Functional neuronal ionotropic glutamate receptors are expressed in the non-neuronal cell line MIN6. (1994)

We report that a non-neuronal cell line, MIN6, derived from insulin-secreting pancreatic beta-cells, naturally expresses functional ionotropic glutamate receptors. Electrophysiological recordings show that kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and N-methyl-D-aspartate (NMDA) depolarize single MIN6 cells and evoke inward ionic currents. These agents also increase the intracellular calcium concentration in MIN6 cells. Furthermore, insulin secretion from MIN6 cells is stimulated by kainate, AMPA, and NMDA. The presence of AMPA/kainate and NMDA receptor subtypes is confirmed by reverse transcriptase-polymerase chain reaction. These results demonstrate that ionotropic glutamate receptors with properties similar to those in neuronal cells are expressed in a non-neuronal cell line, MIN6. Thus, MIN6 provides a useful and valuable model system for biochemical, pharmacological, and physiological studies of ionotropic glutamate receptors.
Identifying differences in protein expression levels by spectral counting and feature selection (2008)

Spectral counting is a strategy to quantify relative protein concentrations in pre-digested protein mixtures analyzed by liquid chromatography online with tandem mass spectrometry. In the present study, we used combinations of normalization and statistical (feature selection) methods on spectral counting data to verify whether we could pinpoint which and how many proteins were differentially expressed when comparing complex protein mixtures. These combinations were evaluated on real, but controlled, experiments (yeast lysates were spiked with protein markers at different concentrations to simulate differences), which were therefore verifiable. The following normalization methods were applied: total signal, Z-normalization, hybrid normalization, and log preprocessing. The feature selection methods were: the Golub index, the Student t-test, a strategy based on the weighting used in a forward-support vector machine (SVM-F) model, and SVM recursive feature elimination. The results showed that Z-normalization combined with SVM-F correctly identified which and how many protein markers were added to the yeast lysates for all different concentrations. The software we used is available at http://pcarvalho.com/patternlab.
The efficacy of topical drugs in treatment of noninflammatory acne vulgaris. (2010)

Treatment of Acne Vulgaris still remains as an actual problem. The purpose of the research was to study the curing process and side effects of topical drugs - Diacneal and Skinoren in patients with non-inflammatory acne vulgaris. The results of the research has confirmed the swift and stable treating effect of both preparations, that expressed in decrease in number and size of comedonal and papulo-comedonal formations, actually without side effects. Thus, in spite of divergence of either chemical composition or mechanism of action, both, Diacneal and Skinoren, may be recommended as a very good choice for monotherapy of non-inflammatory acne vulgaris.
Docosahexaenoic Acid (DHA), not Leucine, May Protect HepG2 Cells from Palmitate‐Induced Non‐Alcoholic Fatty Liver Disease (2017)

Non‐alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States, affecting 70 million adults and ~3% of young children. NAFLD is characterized by an accumulation of fat in the liver cells that is not caused by alcohol. NAFLD is closely associated with obesity and insulin resistance, which are precursors for development of type 2 diabetes. Recent data suggests that the PPARs (PPARα and PPARγ may be connected to the development and progression of NAFLD, which make them potential biomarkers for treating and diagnosing NAFLD. Currently, there are several approaches to treating NAFLD, including nutrition therapy and specific food recommendations. Diets high in protein, high in the branched‐chain amino acid leucine, and diets high in polyunsaturated fatty acids, such as DHA, have been linked with weight reduction and improved insulin resistance. However, neither has been evaluated as a treatment for NAFLD. Therefore, the objective of this study was to analyze the ability of leucine and DHA to act either synergistically or alone to reduce markers of NAFLD using HepG2 cells treated with palmitate as an in vitro model. HepG2 cells (80% confluent) received one of 6 treatments for 48 hours: control, vector control, 0.75 mM palmitate, 5 mM leucine + palmitate, 0.1 mM DHA + palmitate, or leucine + DHA + palmitate. Lipid deposition and markers of energy metabolism were measured. Data was analyzed using one‐way ANOVA with P &lt; 0.05 indicating significance. There was no effect of leucine on cellular lipid deposition. However, cells treated with DHA had significantly less lipid deposition compared to cells treated with palmitate or palmitate + leucine. Palmitate increased Tfam expression compared to controls, however, there was no further effect of leucine. Palmitate + DHA and palmitate + leucine + DHA significantly increased Tfam expression compared to control, palmitate and palmitate + leucine. Palmitate significantly lowered PGC1a and PPARg expression, however treatment with DHA further decreased PGC1α and PPARγ compared to controls and palmitate, alone. Preliminary data shows no treatment effect on SIRT1 or mTOR phosphorylation. Taken together, these data suggest that DHA, not leucine, has the potential to reduce markers of NAFLD in HepG2 cells. Support or Funding Information Arkansas Biosciences Institute. University of Arkansas State Undergraduate Research Fellowship.
Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity (1992)

Excessive activation of NMDA receptors is thought to mediate the calcium-dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity.
Characterization and Dynamics of Aggresome Formation by a Cytosolic Gfp-Chimera✪ (1999)

Formation of a novel structure, the aggresome, has been proposed to represent a general cellular response to the presence of misfolded proteins (Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883-1898; Wigley, W.C., R.P. Fabunmi, M.G. Lee, C.R. Marino, S. Muallem, G.N. DeMartino, and P.J. Thomas. 1999. J. Cell Biol. 145:481-490). To test the generality of this finding and characterize aspects of aggresome composition and its formation, we investigated the effects of overexpressing a cytosolic protein chimera (GFP-250) in cells. Overexpression of GFP-250 caused formation of aggresomes and was paralleled by the redistribution of the intermediate filament protein vimentin as well as by the recruitment of the proteasome, and the Hsp70 and the chaperonin systems of chaperones. Interestingly, GFP-250 within the aggresome appeared not to be ubiquitinated. In vivo time-lapse analysis of aggresome dynamics showed that small aggregates form within the periphery of the cell and travel on microtubules to the MTOC region where they remain as distinct but closely apposed particulate structures. Overexpression of p50/dynamitin, which causes the dissociation of the dynactin complex, significantly inhibited the formation of aggresomes, suggesting that the minus-end-directed motor activities of cytoplasmic dynein are required for aggresome formation. Perinuclear aggresomes interfered with correct Golgi localization and disrupted the normal astral distribution of microtubules. However, ER-to-Golgi protein transport occurred normally in aggresome containing cells. Our results suggest that aggresomes can be formed by soluble, nonubiquitinated proteins as well as by integral transmembrane ubiquitinated ones, supporting the hypothesis that aggresome formation might be a general cellular response to the presence of misfolded proteins.
NCBI GEO: mining millions of expression profiles--database and tools (2004)

The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest fully public repository for high-throughput molecular abundance data, primarily gene expression data. The database has a flexible and open design that allows the submission, storage and retrieval of many data types. These data include microarray-based experiments measuring the abundance of mRNA, genomic DNA and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. GEO currently holds over 30,000 submissions representing approximately half a billion individual molecular abundance measurements, for over 100 organisms. Here, we describe recent database developments that facilitate effective mining and visualization of these data. Features are provided to examine data from both experiment- and gene-centric perspectives using user-friendly Web-based interfaces accessible to those without computational or microarray-related analytical expertise. The GEO database is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo.
Immunohistochemical expression of RBP2 and LSD1 in papillary thyroid carcinoma. (2013)

Both LSD1 and RBP2 are well related with the occurrence and malignant transformation of papillary thyroid carcinoma. Though the positive expression of both LSD1 and RBP2 can be used to estimate the potentiality of thyroid carcinoma and help for the adjuvant treatment, LSD1 is a more sensitive molecular marker than RBP2 on thyroid cancer diagnosis.
Time-Domain Fluorescence Molecular Tomography Based on Generalized Pulse Spectrum Technique (2006)

Based on previously developed the generalized pulse spectrum technique, we propose an algorithm of time-domain Fluorescence Molecular Tomography for simultaneous reconstruction of both the fluorescence yield and lifetime and validate the methodology with simulated data
A novel antimicrobial peptide from the loach, Misgurnus anguillicaudatus (1997)

A novel antimicrobial peptide, named misgurin, was isolated and characterized from the loach (mudfish), Misgurnus anguillicaudatus. The 21-amino-acid peptide with a molecular mass of 2502 Da was purified to homogeneity using a heparin-affinity column and C18 reverse-phase and gel-permeation high-performance liquid chromatography. The complete amino acid sequence of misgurin, which was determined by an automated amino acid sequencer, was Arg-Gln-Arg-Val-Glu-Glu-Leu-Ser-Lys-Phe-Ser-Lys-Lys-Gly-Ala-Ala-Ala-Arg- Arg-Arg-Lys. Misgurin is a strongly basic peptide which has 5 arginine and 4 lysine residues. Comparison of the amino acid sequence with those of other known antimicrobial peptides revealed that misgurin was a novel antimicrobial peptide. Misgurin showed a strong antimicrobial activity in vitro against a broad spectrum of microorganisms without significant hemolytic activity and was about 6 times more potent than magainin 2. Scanning electron microscopy confirmed that the peptide caused damage to the cell membrane by a pore-forming mechanism similar to that of magainin 2. This damage occurred at the minimal inhibition concentration (MIC), but at higher concentration than MIC it lysed the cell.
Information flow inference for ML (2002)

This paper presents a type-based information flow analysis for a call-by-value λ-calculus equipped with references, exceptions and let-polymorphism, which we refer to as Core ML. The type system is constraint-based and has decidable type inference. Its non-interference proof is reasonably lightweight, thanks to the use of a number of orthogonal techniques. First, a syntactic segregation between values and expressions allows a lighter formulation of the type system. Second, non-interference is reduced to subject reduction for a non-standard language extension. Lastly, a semi-syntactic approach to type soundness allows dealing with constraint-based polymorphism separately.
A Novel Cytoplasmic Tail MXXXL Motif Mediates the Internalization of Prostate-specific Membrane Antigen (2003)

Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostate cancer and in tumor-associated neovasculature. In this study, we report that PSMA is internalized via a clathrin-dependent endocytic mechanism and that internalization of PSMA is mediated by the five N-terminal amino acids (MWNLL) present in its cytoplasmic tail. Deletion of the cytoplasmic tail abolished PSMA internalization. Mutagenesis of N-terminal amino acid residues at position 2, 3, or 4 to alanine did not affect internalization of PSMA, whereas mutation of amino acid residues 1 or 5 to alanine strongly inhibited internalization. Using a chimeric protein composed of Tac antigen, the alpha-chain of interleukin 2-receptor, fused to the first five amino acids of PSMA (Tac-MWNLL), we found that this sequence is sufficient for PSMA internalization. In addition, inclusion of additional alanines into the MWNLL sequence either in the Tac chimera or the full-length PSMA strongly inhibited internalization. From these results, we suggest that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization. We also show that dominant negative micro2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalization of PSMA mediated by the MXXXL motif.
Biochemical pharmacology in medical oncology. (1981)

In this patient series, doxorubicin and cycloleucine at a dose of 300 mg/kg both show response rates in the treatment of advanced soft tissue sarcomas of about 15%. Lower doses of cycloleucine (200 mg/kg) yielded less toxicity but were less effective against the sarcomas (6% response rate, three of 51 patients). There were no complete responses with cycloleucine and there were three with doxorubicin. Survival times for patients receiving doxorubicin were significantly longer than those of patients receiving cycloleucine at doses of 300 mg/kg (P less than 0.001) or 200 mg/kg (P = 0.02). The estimated survival times were 29 weeks for doxorubicin and 21 (300 mg/kg) and 18 (200 mg/kg) weeks for cycloleucine. Toxic effects due to cycloleucine were excessive, with severe thrombocytopenia and central nervous system depression being the most prominent.
Differentiation and identification of the two catalytic metal binding sites in bovine lens leucine aminopeptidase by x-ray crystallography. (1993)

The tightly binding and readily exchanging metal binding sites in the active site of bovine lens leucine aminopeptidase (blLAP; EC 3.4.11.1) have been differentiated and identified by x-ray crystallography. In native blLAP,Zn2+ occupies both binding sites. In solution, site 1 readily exchanges Zn2+ for other divalent cations, including Mg2+. The Zn2+ in site 2 is unavailable for metal exchange under conditions which allow exchange at site 1. The Zn2+/Mg2+ metal hybrid of blLAP (Mg-blLAP) was prepared in solution and crystallized. X-ray diffraction data to 2.9-A resolution were collected at -150 degrees C from single crystals of Mg-blLAP and native blLAP. Comparisons of omit maps calculated from the Mg-blLAP data with analogous maps calculated from the native blLAP data show electron density in one of the metal binding sites in Mg-blLAP which is much weaker than the electron density in the other binding site. Since there are fewer electrons associated with Mg2+ than with Zn2+, the difference in electron density between the two metal binding sites is consistent with occupancy of the weaker electron density site by Mg2+ and identifies this metal binding site as site 1, defined as the readily exchanging site. The present identification of the metal binding sites reverses the previous presumptive assignment of the metal binding sites which was based on the structure of native blLAP [Burley, S. K., David, P. R., Sweet, R. M., Taylor, A. & Lipscomb, W. N. (1992) J. Mol. Biol. 224, 113-140]. According to the residue-numbering convention of native blLAP, the new assignment of the metal binding sites identifies the readily exchanging site 1 with Zn-488, which is within interaction distance of one side-chain carboxylate oxygen from each of Asp-255, Asp-332, and Glu-334 and the main-chain carbonyl oxygen of Asp-332. The more tightly binding site 2 is identified with Zn-489, which is within interaction distance of one side-chain carboxylate oxygen from each of Asp-255, Asp-273, and Glu-334 and the side-chain amine nitrogen of Lys-250.
Adaptive coded modulation over slow frequency-selective fading channels (2003)

We consider adaptive coded modulation for systems using QPSK/8PSK/16QAM constellations with a decision-feedback equalizer for slow frequency-selective fading channels. We investigate several potential channel-quality metrics that could be used to choose the correct coding and modulation scheme. We then present a threshold-adaptive algorithm that is especially useful for channels with a wide range of multipath profiles.
<title>Focal plane array readout integrated circuit with per-pixel analog-to-digital and digital-to-analog conversion</title> (2000)

A pixel array readout integrated circuit (ROIC) containing per-pixel analog-to-digital conversion (ADC) and digital-to- analog conversion (DAC) for infrared detectors is presented with design and test result details. Fabricated in a standard 0.35 micron, 3.3 volt CMOS technology. the prototype consists of a linear array of 64 pixels, containing over 100 transistors per 30 by 30 micron pixel. The 8-bit per-pixel ADC is a Nyquist-rate single-slope design consisting of a three stage comparator and an 8 bit memory. This fully pixel- parallel ADC architecture operates in full-frame 'snapshot' mode and can reach over 1,000 frames per second. Each pixel also contains cascoded current source, globally biased to subtract an identical, fixed amount of current from each pixel in order to remove a common background signal by 'charge skimming.' It operates over more than 3 decades of current cancellation (approximately 10 pA to &gt; 10 nA). As well, each pixel contains a 4 to 6+ bit current-mode DAC, intended to trim-out pixel-to-pixel variations in background current. It consists of 16 unit-cells of switched cascoded current sources per pixel, organized as two separately biased weights and controlled by a 16-bit per-pixel memory. The DAC operates over more than 4 decades of current cancellation (&lt; 10 pA to approximately equals 100 nA) per least significant bit (LSB).
Isolation and characterization of microplasminogen. A low molecular weight form of plasminogen. (1988)

A functionally active human microplasminogen without kringle structures was produced by incubation of plasminogen with urokinase-free plasmin at an alkaline pH. The microplasminogen was purified by affinity chromatography on lysine- and soybean trypsin inhibitor-Sepharose and by chromofocusing. Human plasminogen is specifically cleaved at Arg529-Lys530 by plasmin to form microplasminogen, which consists of a single polypeptide of 261 residues from the COOH-terminal portion of native plasminogen. It has an Mr of 28,617, calculated from the sequence, which is consistent with the molecular weight determined by sodium dodecyl sulfate gel electrophoresis. Microplasminogen is a slightly basic protein and is eluted from a chromofocusing column at pH 8.3. It can be activated by urokinase and streptokinase to a catalytically active microplasmin. The specific amidolytic activity of microplasmin is about three times higher than Lys77-plasmin on a weight basis and is about the same on a molar basis. The activation of microplasminogen by streptokinase is slower than that of either Glu-plasminogen or Lys77-plasminogen. On the other hand, the activation of microplasminogen by urokinase is faster than that of either of the latter. The Arg560-Val561 bond is cleaved during activation of both microplasminogen and native plasminogen.
Filtering for increased power for microarray data analysis (2009)

The case studies show that both detection call and variance filtering are viable methods of filtering which can increase the number of differentially expressed genes identified. The simulation study demonstrates that when paired with a false discovery rate method, filtering by variance can increase power while still controlling the false discovery rate. Filtering out 50% of probe sets seems reasonable as long as the majority of genes are not expected to be differentially expressed.
Total Chemical Synthesis of the Integral Membrane Protein Influenza A Virus M2:  Role of Its C-Terminal Domain in Tetramer Assembly (1999)

The M2 protein from influenza A virus is a 97-residue homotetrameric membrane protein that functions as a proton channel. To determine the features required for the assembly of this protein into its native tetrameric state, the protein was prepared by total synthesis using native chemical ligation of unprotected peptide segments. Circular dichroism spectroscopy of synthetic M2 protein in dodecylphosphocholine (DPC) micelles indicated that approximately 40 residues were in an alpha-helical secondary structure. The tetramerization of the full-length protein was compared to that of a 25-residue transmembrane (TM) fragment. Analytical ultracentrifugation demonstrated that both the peptide and the full-length protein in DPC micelles existed in a monomer-tetramer equilibrium. Comparison of the association constants for the two sequences showed the free energy of tetramerization of the full-length protein was more favorable by approximately 7 kcal/mol. Partial proteolysis of DPC-solubilized M2 was used as a further probe of the structure of the full-length protein. A 15-20-residue segment C-terminal to the membrane-spanning region was found to be highly resistant to digestion by chymotrypsin and trypsin. This region, which we have modeled as an extension of the TM helices, may help to stabilize the tetrameric assembly.