gebhart/patrepeval huggingface dataset:
Preparation of RNA from Tissues and Cells (1999)

Most procedures for isolating RNA from eukaryotic cells involve lysing and denaturing cells to liberate total nucleic acids. Additional steps are then required to remove DNA. The first basic protocol describes hot phenol extraction of RNA; the method eliminates or minimizes DNA contamination by the shearing of DNA. The second basic protocol allows rapid preparation of total cytoplasmic RNA by using a nonionic detergent to lyse the plasma membrane, leaving the nuclei intact. The nuclei and hence the bulk of the cellular DNA are then removed with a simple brief centrifugation. A guanidinium thiocyanate protocol describes the separation of RNA from other cellular macromolecules in a guanidinium lysate using a CsCl step gradient. A protocol is also provided for isolation of poly(A(+)) mRNAs from total RNA.
Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection (1982)

Monoclonal antibodies specific for the five major glycoproteins of herpes simplex virus type 1 (HSV-1) were tested for their capacity to mediate immunity to ocular HSV-1 infection. The specificity of the immunoglobulin made by each monoclone was determined by immunoprecipitation of [14C]glucosamine-labeled polypeptides from detergent-solubilized HSV-1-infected cells. Of the five monoclonal antibodies studied, two immunoprecipitated glycoproteins gA/B, one immunoprecipitated glycoprotein gC, one immunoprecipitated glycoprotein gD, and one immunoprecipitated glycoprotein gE. All five were effective in passively transferring immunity to mice when they were given 4 to 24 h after HSV-1 infection on an abraded cornea. Four of the monoclonal antibodies were also evaluated for their capacity to neutralize HSV-1 and to promote complement-mediated cell lysis and antibody-dependent cellular cytotoxicity. It was found that none of these in vitro assays correlated with the protective activity of the antibodies in vivo. In fact, one of the monoclonal antibodies was unreactive in all three immunological reactions, even though it was highly effective in promoting recovery from HSV-1 induced ocular disease in vivo. The results suggest that antibodies can interact in vivo with virus-specific glycoproteins gA/B, gC, gD, and gE to initiate recovery from HSV-1-induced ocular disease, and that the therapeutic effectiveness of a specific monoclonal antibody does not correlate with its immunological reactivity in vitro.
Determination of size distribution from small-angle scattering data for systems with effective hard-sphere interactions (1994)

Methods for the free-form determination of size distributions for systems with hard-sphere interactions are described. An approximation, called the local monodisperse approximation, is introduced. Model calculations show that this approximation gives relatively small errors even at relatively high polydispersities and large volume fractions. The size distributions are determined by least-squares methods with smoothness and non-negativity constraints. The local monodisperse approximation leads to normal equations that are linear in the amplitude of the size distribution. This is used when solving the least-squares problem: only the two effective parameters describing the interference effects are treated as nonlinear parameters in an external optimization routine. The parameters describing the size distribution are determined by a linear least-squares method. The size distribution is also determined using the nonlinear equations from the calculation of the scattering intensity in the Percus–Yevick approximation. For this, a nonlinear least-squares routine with a smoothness constraint and a non-negativity constraint is used. Both approaches are tested by analysis of simulated examples calculated by the analytical expressions in the Percus–Yevick approximation. Finally, the methods are applied to two sets of experimental data from silica particles and from δ′ precipitates in an Al–Li alloy. For the simulated examples, good agreement is found with the input distributions. For the experimental examples, the results agree with the expected and known properties of the samples.
Television computer games: a 'new look' in performance testing. (1982)

Work at the Naval Biodynamics Laboratory aims at developing a battery of performance evaluation tests for environmental research (PETER). Because repeated-measures designs are virtually universal in environmental studies, the paradigm focuses on stabilisation with practice; thus far, over 50 tasks have been studied. The present report describes how five computerized video games fare as performance tests. The tasks were performed for 3 weeks each, in the same order, by the same subjects. The results show that four out of the five games meet all criteria satisfactorily and one does not, a favorable showing for the video games in comparison with conventional tests of either the paper-and-pencil or apparatus types. In terms of availability, equipment reliability, expense, and other practical considerations, the video games have many advantages. It is concluded that video games have considerable promise for performance testing and other applied contexts.
Procalcitonin Guidance of Antibiotic Therapy in Community-acquired Pneumonia (2006)

Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.
Site‐Specific Control of Distances between Gold Nanoparticles Using Phosphorothioate Anchors on DNA and a Short Bifunctional Molecular Fastener (2007)

Going for double gold: Precise control of the positions of and distances between gold nanoparticles (AuNP; gold spheres in picture) is achieved by linking the AuNPs to phosphorothioate-modified DNA (green and red helices) with a bifunctional fastener. The distance between AuNPs is controlled simply by changing the position of the modifications on the DNA template. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z702569_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CRM1 As a New Therapeutic Target For Non-Hodgkin Lymphoma (2013)

Abstract Background The nuclear export protein chromosomal region maintenance 1 (CRM1) may play a role in human neoplasia and serve as a novel target for cancer treatment. Investigators recently developed orally bioavailable selective inhibitors of nuclear export (SINEs) that irreversibly bind to CRM1 and block its function. Our objective was to evaluate the therapeutic efficacy of the novel SINEs KPT-185 and KPT-276 against NHL in vitro and in vivo and elucidate the mechanism of CRM1 inhibitor-mediated antitumor activity. Methods Cell viability, apoptosis and cell cycle were evaluated in 8 B and T cell lymphoma cell lines (Jeko-1, Mino, Granta519, Sp53, RL, Hut102, Hut78 and Jurkat) which were treated with KPT-185; Primary tumor cells from 5 patients and normal human lymphocytes from 2 healthy volunteers were treated directly with KPT-185. Tumor suppressor proteins were detected by western blot to explore the possible mechanisms of KPT-185 inducing lymphoma cells growth inhibition and apoptosis. BALB/c nude mice bearing Jeko-1 tumors were treated orally with KPT-276 (similar structure to KPT-185, but improved animal pharmacokinetics) to examine the efficacy and side-effects of KPT-276. Results KPT-185 displayed potent antiproliferative properties at submicromolar concentrations (half-maximal inhibitory concentrations, 60-120 nM) and induced cell-cycle arrest and apoptosis in NHL cell lines and normal lymphocytes. The antitumor activity mainly consisted of regulating cell growth and apoptosis mechanisms by inducing caspase cleavage and downregulating the expression of antiapoptotic proteins such as CRM1, nuclear factor-kB, and survivin. Furthermore, oral administration of KPT-276 significantly suppressed tumor growth and prolonged survival in mice with NHL xenografts without any major toxic effects (P &lt; 0.001). Analysis of tumor remnants in the mice demonstrated that KPT-276 trapped the antiapoptoic protein survivin within the nuclei of NHL cells. Conclusions We observed the biologic and pharmacologic activity of CRM1-inhibiting SINEs in NHL cells, primary NHL tumor samples, and a murine NHL xenograft model. SINE CRM1 inhibitors inhibited growth of lymphoma cells both in vitro and in vivo. The antitumor activity of the SINEs resulted primarily from induction of caspase activity and downregulation of expression of antiapoptoic proteins such as survivin and NF-kB. The preclinical in vitro and in vivo results reported herein support further study of CRM1-inhibiting SINEs as novel therapeutics for NHL. Disclosures: No relevant conflicts of interest to declare.
Clinical outcome and predictors of disease evolution in patients with incomplete lupus erythematosus (2000)

To determine the outcome and identify risk factors for evolution into systemic lupus erythematosus (SLE) in a population of incomplete lupus erythematosus (ILE) patients, we studied the clinical and serologic manifestations in a cohort of 87 ILE patients. ILE patients had at least one but less than four of the American College of Rheumatology (ACR) classification criteria of SLE and did not present distinctive clinical features or meet classification criteria of other connective tissue diseases. The patients that remained with ILE were compared with patients that evolved into SLE and with a cohort of 94 SLE patients. The mean disease duration and follow up of ILE patients were 4.4 +/- 4.1 and 2.2 +/- 2.4 years respectively. Eight patients evolved into SLE, but none presented major organ damage. At baseline, patients that remained with ILE were less likely to have photosensitivity, elevated anti-dsDNA and decreased C3 complement than patients that evolved into SLE. At the end of the study, malar rash and oral ulcerations were also less frequent in the ILE group. Compared with all SLE cases, ILE patients were less likely to have photosensitivity, malar rash, oral ulcers, Raynaud's phenomenon, arthritis, low C3, low C4, positive anti-dsDNA, anti-Sm, anti-RNP, anti-Ro and anti-La antibodies at baseline. Hazard analyses showed that malar rash, oral ulcers, elevated anti-dsDNA and decreased C4 were associated with SLE occurrence. In conclusion, this study suggests that ILE represents a mild spectrum of lupus in which mucocutaneous and serological abnormalities are associated with progression into SLE.
A Randomized, Pharmacokinetic and Pharmacodynamic, Cross-Over Study of Duodenal Or Jejunal Administration Compared To Nasogastric Administration of Omeprazole Suspension in Patients at Risk for Stress Ulcers (2001)

In critically ill surgical patients, pharmacokinetic parameters and subsequent pH control after the administration of SOS are similar by the jejunal, nasogastric, or duodenal route. SOS suspension offers an alternative acid control measure when patients are unable to take oral medications, yet have an enteral tube in place.
Increased Intrathecal Chemokine Receptor CCR2 Expression in Multiple Sclerosis (2007)

Expression of CCR2, CXCR3 and CCR4 on CD4 + T or CD8 + T cells in blood and cerebrospinal fluid (CSF) for multiple sclerosis (MS) was measured by 3-color flow cytometry, and compared to blood from healthy controls and CSF from patients with other inflammatory neurological diseases (INDs). CD4 + CXCR3 + /CD4 + CCR4 + ratio (representing Th1/Th2 balance) was higher in both CSF and blood of MS patients than those of IND patients or healthy controls. Percentage of CCR2-positive T cells was significantly higher in CSF from MS patients. Increased CCR2 expression on T cells in CSF and Th1/Th2 imbalance may reflect the pathological processes involved in MS.
Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases (2005)

Liver tissue engineering using hepatocyte transplantation has been proposed as an alternative to whole-organ transplantation or liver-directed gene therapy to correct various types of hepatic insufficiency. Hepatocytes are not sustained when transplanted under the kidney capsule of syngeneic mice. However, when we transplanted hepatocytes with the extracellular matrix components extracted from Engelbreth-Holm-Swarm cells, hepatocytes survived for at least 140 days and formed small liver tissues. Liver engineering in hemophilia A mice reconstituted 5% to 10% of normal clotting activity, enough to reduce the bleeding time and have a therapeutic benefit. Conversely, the subcutaneous space did not support the persistent survival of hepatocytes with Engelbreth-Holm-Swarm gel matrix. We hypothesized that establishing a local vascular network at the transplantation site would reduce graft loss. To test this idea, we provided a potent angiogenic agent before hepatocyte transplantation into the subcutaneous space. With this procedure, persistent survival was achieved for the length of the experiment (120 days). To establish that these engineered liver tissues also retained their native regeneration potential in vivo, we induced two different modes of proliferative stimulus to the naive liver and confirmed that hepatocytes within the extrahepatic tissues regenerated with activity similar to that of naive liver. In conclusion, our studies indicate that liver tissues can be engineered and maintained at extrahepatic sites, retain their capacity for regeneration in vivo, and used to successfully treat genetic disorders.
Intersubband absorption in strained InxGa1−xAs/Al0.4Ga0.6As (0≤x≤0.15) multiquantum wells (1989)

We report, for the first time, temperature-dependent intersubband absorption data in doped pseudomorphic InxGa1−xAs/Al0.4Ga0.6As (0≤x≤0.15) multiquantum wells. In this composition range the absorption resonance varies in the range 6–7 μm for 50 Å wells, which agrees extremely well with theoretical calculations.
Intracellular Redistribution of Nucleolin upon Interaction with the CD3ε Chain of the T Cell Receptor Complex (2001)

T cell activation through the antigen receptor (TCR) involves the cytoplasmic tails of the CD3 subunits CD3gamma, CD3delta, CD3epsilon, and CD3zeta. Whereas the biological significance of the cytoplasmic tails of these molecules is suggested, in part, by their evolutionarily conserved sequences, their interactions with signal transduction molecules are not completely understood. We used affinity chromatography columns of glutathione S-transferase fused to the CD3epsilon cytoplasmic tail to isolate proteins that specifically interact with this subunit. In this way, we identified the shuttling protein nucleolin as a specific CD3epsilon-interacting molecule. Using competition studies and affinity chromatography on peptide columns, we were able to identify a central proline-rich sequence as the nucleolin-interacting sequence in CD3epsilon. Transfection in COS cells of wild type CD3epsilon, but not of nonbinding mutants of CD3epsilon, resulted in redistribution of nucleolin from the nucleus and nucleoli to the cytoplasm. This property was transferred to a CD8 protein chimera by appending the cytoplasmic tail of CD3epsilon. We also found that nucleolin associated with the TCR complex. This association was increased upon TCR engagement, suggesting that the CD3epsilon/nucleolin interaction may have a role in T cell activation.
Gutted adenoviral vector growth using E1/E2b/E3‐deleted helper viruses (2002)

These new packaging cell lines and helper viruses offer several significant advantages for gutted Ad vector production. They allow gutted virus amplification using a reduced number of passages, which should reduce the chances of selecting rearranged products. Furthermore, the residual helper contamination in gutted vector preparations should be less able to elicit immunological reactions upon delivery to tissues, since E2b-deleted vectors display a profound reduction in viral gene expression.
VirR, a response regulator critical for Listeria monocytogenes virulence (2005)

Signature-tagged mutagenesis (STM) was used to identify new genes involved in the virulence of the Gram-positive intracellular pathogen Listeria monocytogenes. One of the mutants isolated by this technique had the transposon inserted in virR, a gene encoding a putative response regulator of a two-component system. Deletion of virR severely decreased virulence in mice as well as invasion in cell-culture experiments. Using a transcriptomic approach, we identified 12 genes regulated by VirR, including the dlt-operon, previously reported to be important for L. monocytogenes virulence. However, a strain lacking dltA, was not as impaired in virulence as the DeltavirR strain, suggesting a role in virulence for other members of the vir regulon. Another VirR-regulated gene is homologous to mprF, which encodes a protein that modifies membrane phosphatidyl glycerol with l-lysine and that is involved in resistance to human defensins in Staphylococcus aureus. VirR thus appears to control virulence by a global regulation of surface components modifications. These modifications may affect interactions with host cells, including components of the innate immune system. Surprisingly, although controlling the same set of genes as VirR, the putative cognate histidine kinase of VirR, VirS, encoded by a gene located three genes downstream of virR, was shown not to be essential for virulence. By monitoring the activity of VirR with a GFP reporter construct, we showed that VirR can be activated independently of VirS, for example through a mechanism involving variations in the level of intracellular acetyl phosphate. In silico analysis of the VirR-regulated promoters revealed a VirR DNA-binding consensus site and specific interaction between purified VirR protein and this consensus sequence was demonstrated by gel mobility shift assays. This study identifies a second key virulence regulon in L. monocytogenes, after the prfA regulon.
Ultra Wideband Indoor Positioning Technologies: Analysis and Recent Advances (2016)

In recent years, indoor positioning has emerged as a critical function in many end-user applications; including military, civilian, disaster relief and peacekeeping missions. In comparison with outdoor environments, sensing location information in indoor environments requires a higher precision and is a more challenging task in part because various objects reflect and disperse signals. Ultra WideBand (UWB) is an emerging technology in the field of indoor positioning that has shown better performance compared to others. In order to set the stage for this work, we provide a survey of the state-of-the-art technologies in indoor positioning, followed by a detailed comparative analysis of UWB positioning technologies. We also provide an analysis of strengths, weaknesses, opportunities, and threats (SWOT) to analyze the present state of UWB positioning technologies. While SWOT is not a quantitative approach, it helps in assessing the real status and in revealing the potential of UWB positioning to effectively address the indoor positioning problem. Unlike previous studies, this paper presents new taxonomies, reviews some major recent advances, and argues for further exploration by the research community of this challenging problem space.
Similarities and differences in the neuronal death processes activated by 3OH‐kynurenine and quinolinic acid (2001)

3OH-Kynurenine and quinolinic acid are tryptophan metabolites able to cause, at relatively elevated concentrations, neuronal death in vitro and in vivo. In primary cultures of mixed cortical cells, the minimal concentration of these compounds leading to a significant degree of neurotoxicity decreased from 100 to 1 microM, when the exposure time was prolonged from 24 to 72 h. NMDA receptor antagonists and inhibitors of nitric oxide synthase or poly(ADP-ribose) polymerase reduced quinolinic acid, but not 3OH-kynurenine toxicity. In contrast, scavengers of free radicals, caspase inhibitors and cyclosporin preferentially reduced 3OH-kynurenine neurotoxicity. These observations suggest that quinolinic acid causes necrosis, whereas 3OH-kynurenine-exposed neurons primarily die in apoptosis. In line with this possibility, we found that ATP levels decreased more rapidly in quinolinate- than in 3OH-kynurenine-exposed cultures and that poly(ADP-ribose) polymer, the product of poly(ADP-ribose) polymerase activity, was more abundant in the nuclei of quinolinic acid than in those of 3OH-kynurenine-exposed neurons. Because minor changes in the physiological concentrations of 3OH-kynurenine and quinolinic acid may cause neuronal death, our data suggest that these metabolites play a key role in the pathogenesis of several neurological disorders.
Recombinant cyclic AMP response element binding protein (CREB) phosphorylated on Ser-133 is transcriptionally active upon its introduction into fibroblast nuclei. (1994)

To date, it has not been possible to determine whether the single phosphorylation of the cyclic AMP response element binding factor (CREB) at Ser-133 is sufficient for the transcriptional activation by cAMP-mediated pathways. Previous in vivo studies investigating this point have relied upon transfection of cyclic AMP-dependent kinase (cAPK) or its activation by treatment of cells with cell-permeable cAMP analogs. However, as numerous cellular proteins, including CREB, are substrates for activated cAPK, the possibility remains that cAPK substrates other than CREB are required for the transcriptional activity of CRE-containing promoters. To further address this, we compared the activity of recombinant CREB phosphorylated on Ser-133 in both cell-free transcription assays and in vivo after introduction of the same preparations into fibroblasts by microinjection. The activity of phosphorylated CREB, nonphosphorylated CREB, and a mutant form of CREB, containing Ala substituted for Ser at position 133, was found to be nearly identical in cell-free in vitro transcription assays. In contrast, we found that only the phosphorylated CREB microinjected into fibroblasts resulted in the stimulation of expression of CRE-regulated genes. These results suggest that phosphorylation of CREB on Ser-133 directly stimulates its ability to transactivate gene expression in intact cells.
The role of histone deacetylases (HDACs) in human cancer (2007)

The balance of histone acetylation and deacetylation is an epigenetic layer with a critical role in the regulation of gene expression. Histone acetylation induced by histone acetyl transferases (HATs) is associated with gene transcription, while histone hypoacetylation induced by histone deacetylase (HDAC) activity is associated with gene silencing. Altered expression and mutations of genes that encode HDACs have been linked to tumor development since they both induce the aberrant transcription of key genes regulating important cellular functions such as cell proliferation, cell-cycle regulation and apoptosis. Thus, HDACs are among the most promising therapeutic targets for cancer treatment, and they have inspired researchers to study and develop HDAC inhibitors.
Synthesis and SAR of a New Series of COX-2-Selective Inhibitors:  Pyrazolo[1,5-a]pyrimidines (2001)

The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series.