gebhart/patrepeval huggingface dataset:
Minireview: Constitutively Active G Protein-Coupled Receptors: Potential Mechanisms of Receptor Activation (1997)

Mutations of G protein-coupled receptors can increase their constitutive (agonist-independent) activity. Some of these mutations have been artificially introduced by site-directed mutagenesis, others occur spontaneously in human diseases. The analysis of the constitutively active G protein-coupled receptors has provided important informations about the molecular mechanisms underlying receptor activation and drug action.
Detection of Cell-Affecting Agents with a Silicon Biosensor (1989)

Cellular metabolism is affected by many factors in a cell's environment. Given a sufficiently sensitive method for measuring cellular metabolic rates, it should be possible to detect a wide variety of chemical and physical stimuli. A biosensor has been constructed in which living cells are confined to a flow chamber in which a potentiometric sensor continually measures the rate of production of acidic metabolites. Exploratory studies demonstrate several applications of the device in basic science and technology.
Localizer: fast, accurate, open-source, and modular software package for superresolution microscopy (2012)

We present Localizer, a freely available and open source software package that implements the computational data processing inherent to several types of superresolution fluorescence imaging, such as localization (PALM/STORM/GSDIM) and fluctuation imaging (SOFI/pcSOFI). Localizer delivers high accuracy and performance and comes with a fully featured and easy-to-use graphical user interface but is also designed to be integrated in higher-level analysis environments. Due to its modular design, Localizer can be readily extended with new algorithms as they become available, while maintaining the same interface and performance. We provide front-ends for running Localizer from Igor Pro, Matlab, or as a stand-alone program. We show that Localizer performs favorably when compared with two existing superresolution packages, and to our knowledge is the only freely available implementation of SOFI/pcSOFI microscopy. By dramatically improving the analysis performance and ensuring the easy addition of current and future enhancements, Localizer strongly improves the usability of superresolution imaging in a variety of biomedical studies.
Caprine beta-mannosidosis. Abnormal thyroid structure and function in a lysosomal storage disease. (1990)

Deficient activity of the lysosomal enzyme beta-mannosidase leads to widespread tissue accumulation of oligosaccharides in caprine beta-mannosidosis, an autosomal recessive neurovisceral storage disease. Severe thyroid morphologic abnormalities found in a previous light microscopic survey of tissues from neonatal affected goats suggested the possibility of impairment of function. Since considerable evidence indicates that thyroid hormone plays an important role in regulation of myelination, thyroid hormone deficiency, if present during central nervous system development, could be a factor in the hypomyelination seen in affected animals. Thus, this study was designed to characterize thyroid structure and function in beta-mannosidosis. To investigate developmental aspects of structural abnormalities, thyroids from six pairs of affected and control animals ranging in age from 96/150 days gestation to 3 days postnatal were analyzed by light and electron microscopy. Major findings in thyroids from affected animals, as early as 96/150 days gestation, included follicle irregularities and pronounced presence of lysosomal storage vacuoles in all cell types, particularly in follicular cells. The degree of cytoplasmic vacuolation increased with advancing age. To assess thyroid function, thyroid hormone concentrations were determined in six age-matched, neonatal pairs of affected and control goats. Significantly decreased thyroid hormone concentrations were present in affected animals. It is hypothesized that thyroid hormone deficiency plays a role in the pathogenesis of hypomyelination in affected animals. This study comprises, to our knowledge, both the most complete description of developmental abnormalities and the first report of abnormal function in an endocrine organ in a lysosomal storage disease. Further, this report suggests that systemic perturbations induced by a genetically determined deficiency of a lysosomal hydrolase could be a factor in the pathogenesis of central nervous system lesions.
Effects of different expression and posttranslational modifications of myosin light chains on contractility of skinned human cardiac fibers (1992)

In the human ventricle two isoforms of the phosphorylatable myosin light chain (MPLC) are expressed. These two forms are designated with increasing acidity as LC-2 and LC-2*. In the normal human heart the relation between LC-2/LC-2*-expression is 70/30, suggesting the existence of three different myosin isoenzymes (MPLC-polymorphism) in the normal human ventricle. Both ventricular MPLC-isoforms are monophosphorylated, the LC-2 being higher phosphorylated than the LC-2*. In some patients with heart failure both MPLC isoforms were found to be completely dephosphorylated. In the human atrium a MPLC isoform is expressed which is different from the ventricular MPLC isoforms. The atrial MPLC isoform is mono- and diphosphorylated. Mono-phosphorylation of both the ventricular MPLC isoforms and the atrial MPLC isoform increased responsiveness as well as sensitivity of isometric tension generation of skinned fibers to Ca2+. Part of this effect could be explained by changing the cross-bridge-cycling rate: MPLC increased fapp, the rate-constant for the transition of cross-bridges from the non-force into the force-generating state, thus increasing the amount of force-generating cross-bridge states at a given [Ca2+]. Monophosphorylation of the MPLC isoforms did not change maximal shortening velocity.
The coding sequence of Duffy blood group gene in humans and simians: restriction fragment length polymorphism, antibody and malarial parasite specificities, and expression in nonerythroid tissues in Duffy- negative individuals (1995)

The coding and untranslated flanking sequences of Duffy gene (FY) in humans and simians are in a single exon. The difference between the two codominant alleles, FY*A and FY*B, is a single change at nucleotide 306: guanidine is in FY*A and adenine is in FY*B. This produces a codon change that subsequently modifies the amino acid at position 43 of gpFy, the major subunit of the Duffy blood group protein complex. The glycine at this position in antigen Fya exchanges with aspartic acid in antigen Fyb. The guanidine at nucleotide 306 creates an additional Ban I restriction site in FY*A. Ban I digestion of DNA-PCR amplified products of FY*B and FY*A yields three and four fragments, respectively. Restriction fragment length polymorphism (RFLP) studies show that Fy(a+b-) and Fy(a-b+) whites are FY homozygous, that most Fy(a-b-) blacks have FY*B, and most Fy(a+b-) blacks are FY*A/FY*B heterozygous. In the black population a silent FY*B is very common, but a silent FY*A has not been found yet. On RNA blot analysis, the gpFy cDNA clone detected mRNA in the lung, spleen, and colon but not in the bone marrow of Duffy-negative individuals. Therefore, there is no null phenotype in Fy(a-b-) blacks. The gpFy homology between human and chimpanzee is 99% with a single residue change at position 116 (valine to isoleucine), whereas a 94% homology is found in squirrel and rhesus monkeys, and there is a 93% homology in aotus monkey when compared with humans. The N-terminal exocellular domain of simian gpFy helps to identify a set of amino acids critical for antibody and malarial parasite specificities.
Characterization and functional analysis of adult human bone marrow cell subsets in relation to B-lymphoid development (1993)

To study the frontiers between pluripotent stem cells and committed progenitors and to further define the B-cell pathway in adult bone marrow (BM), CD34+ subpopulations and CD34- B-lineage cells were analyzed by multiparameter flow cytometry, studied by light and electron microscopy, and in short-term and long-term cultures (LTC). While the total CD34+ cells represent 4.9% +/- 0.8 of BM mononuclear cells within the lymphoid-blast window, 73.8 +/- 3.5%, 14.4 +/- 1.8% and 8.8 +/- 2.9% of them were CD34+ CD10- CD19-, CD34+ CD10+ CD19+, and CD34+ CD10+ CD19-, respectively. CD34+ CD10+ CD19+ cells represent a smal homogeneous TdT4 c micro-blast population. Although expressing CD38 and high level of HLA-DR antigens, like myeloid committed progenitors, they did not generate LTC, myeloid, and T lymphoid colonies suggesting that the CD34+ CD10+ CD19+ population represents exclusively B lymphoid committed progenitors. By contrast, all myeloid progenitors and LTC-initiating cells were found in the CD34+ CD10- CD19- cell fraction. This fraction appeared more heterogeneous and contained CD38- HLA-DRlow small cells, larger blasts, and promonocyte-like cells exhibiting small peroxidase-positive granules. Interestingly, CD10 was also present on CD34+ CD19- cells. This population mainly coexpressed CD33 and gave rise to macrophagic colonies.
Particle-Mediated Gene Transfer of Granulocyte-Macrophage Colony-Stimulating Factor cDNA to Tumor Cells: Implications for a Clinically Relevant Tumor Vaccine (1996)

The necessity for prolonged tissue culture manipulations limits the clinical application of many form of gene therapy in patients with malignancies. We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA in a plasmid expression vector could be effectively introduced into resting tumor cells, without the need for tissue culture propagation prior to or following transfection, and that efficient expression of transgenic GM-CSF by the transfected tumor cells would confer an effective immune response against tumors. GM-CSF cDNA in expression vectors was coated onto gold particles and accelerated with a gene gun device into mouse and human tumor cells. Human tumor tissue transfected within 4 hr of surgery produced significant levels of transgenic human GM-CSF protein in vitro. Human GM-CSF was readily detectable in serum and at the injection site following subcutaneous implantation of these transfected tumor cells into nude mice. Transfected and irradiated murine B16 melanoma cells produced > or = 100 ng/ml murine GM-CSF/10(6) cells per 24 hr in vitro for at least 10 days. The antitumor efficacy of this nonviral approach was tested using irradiated B16 tumor cells that were transfected with mGM-CSF cDNA and injected into mice as tumor "vaccine". Subsequent challenge of these mice with nonirradiated, nontransfected B16 tumor cells showed that 58% of the animals wer protected from the tumor by the prior vaccine treatment. In contrast, only 2% of control animals were protected by prior treatment with irradiated B16 cells transfected with the vector containing the luciferase gene. These results suggest that particle-mediated transfection of fresh tumor explants with cytokine cDNA is an effective and clinically attractive approach for cancer therapy.
Note on the Use of Weibull Statistics to Characterize Wind-Speed Data (1978)

A hybrid density function is given for describing wind-speed distributions having nonzero probability of “calm.” A Weibull probability graph paper designed specifically for plotting wind-speed distributions is used to determine distribution parameters to within a few percent of values obtained by the maximum likelihood technique. Data from the National Weather Service are used to demonstrate the use of the hybrid density function and the Weibull graph paper.
Analgesia for amniocentesis or chorionic villus sampling (2011)

In general, women who undergo amniocentesis could be informed that pain during procedure is minor and that there is currently insufficient evidence to support the use of local anaesthetics, leg rubbing or subfreezing the needle for pain reduction during procedure.
Direct detection of low-frequency NMR using a dc SQUID (1986)

A system has been developed to directly observe NMR free induction signals at very low frequencies. We use a nonresonant pickup arrangement with a commercial dc SQUID to monitor the precessing magnetization in a 0.5–50-kHz range of Larmor frequencies. A relocking interval for the SQUID’s flux locked loop presently sets our pulse recovery around 20–30 μs throughout this frequency range. The noise for this system is less than 1.5 times that recorded for the SQUID with shorted input terminals.
Kolmogorov complexity estimates for detection of viruses in biologically inspired security systems: A comparison with traditional approaches (2003)

Abstract This article presents results in two mutually complementary areas: distributed immunological information assurance and a new signature‐matching technique based on Kolmogorov Complexity. This article introduces a distributed model for security based on biological paradigms of epidemiology and immunology. In this model each node in the network has an immune system that identifies and destroys pathogens in the incoming network traffic as well as files resident on the node. The network nodes present a collective defense to the pathogens by working symbiotically and sharing pathogen information with each other. Each node compiles a list of pathogens that are perceived as threats by using information provided from all the nodes in the network. The signatures for these pathogens are incorporated into the detector population of the immune systems to increase the probability of detection. Critical to the success of this system is the detection scheme, which should not only be accurate but also efficient. Three separate schemes for detecting pathogens are examined, namely, contiguous string matching, Hamming distance, and Kolmogorov Complexity. This work provides a model of the system and examines the efficiency of different detection schemes. A simulation model is built to study the sensitivity of model parameters, such as signature length, sampling rate, and network topology, to detection of pathogens. © 2004 Wiley Periodicals, Inc. Complexity 9: 54–73, 2004
EGFRvIII–Stat5 Signaling Enhances Glioblastoma Cell Migration and Survival (2018)

Glioblastoma multiforme (GBM) is the most common brain malignancies in adults. Most GBM patients succumb to the disease less than 1 year after diagnosis due to the highly invasive nature of the tumor, which prevents complete surgical resection and gives rise to tumor recurrence. The invasive phenotype also confers radioresistant and chemoresistant properties to the tumor cells; therefore, there is a critical need to develop new therapeutics that target drivers of GBM invasion. Amplification of EGFR is observed in over 50% of GBM tumors, of which half concurrently overexpress the variant EGFRvIII, and expression of both receptors confers a worse prognosis. EGFR and EGFRvIII cooperate to promote tumor progression and invasion, in part, through activation of the Stat signaling pathway. Here, it is reported that EGFRvIII activates Stat5 and GBM invasion by inducing the expression of a previously established mediator of glioma cell invasion and survival: fibroblast growth factor-inducible 14 (Fn14). EGFRvIII-mediated induction of Fn14 expression is Stat5 dependent and requires activation of Src, whereas EGFR regulation of Fn14 is dependent upon Src-MEK/ERK-Stat3 activation. Notably, treatment of EGFRvIII-expressing GBM cells with the FDA-approved Stat5 inhibitor pimozide blocked Stat5 phosphorylation, Fn14 expression, and cell migration and survival. Because EGFR inhibitors display limited therapeutic efficacy in GBM patients, the EGFRvIII-Stat5-Fn14 signaling pathway represents a node of vulnerability in the invasive GBM cell populations.<b>Implications:</b> Targeting critical effectors in the EGFRvIII-Stat5-Fn14 pathway may limit GBM tumor dispersion, mitigate therapeutic resistance, and increase survival. <i>Mol Cancer Res; 16(7); 1185-95. ©2018 AACR</i>.
Reconstruction of seismic data using adaptive regularization (2002)

In seismic data processing, we often need to interpolate/extrapolate missing spatial locations in a domain of interest. The reconstruction problem can be posed as an inverse problem where from inadequate and incomplete data one attempts to recover the complete band-limited seismic wavefield. However, the problem is often ill posed due to factors such as inaccurate knowledge of bandwidth and noise. In this case, regularization can be used to help to obtain a unique and stable solution. In this paper, we formulate band-limited data reconstruction as a minimum norm least squares type problem where an adaptive DFT-weighted norm regularization term is used to constrain solutions. In particular, the regularization term is updated iteratively through using the modified periodogram of the estimated data. The technique allows for adaptive incorporation of prior knowledge of the data such as the spectrum support and the shape of the spectrum. The adaptive regularization can be accelerated using FFTs and an iterative solver like preconditioned conjugate gradient algorithm. Examples on synthetic and real seismic data illustrate improvement of the new method over damped least squares estimation.
Rapid Identification of Highly Active and Selective Substrates for Stromelysin and Matrilysin Using Bacteriophage Peptide Display Libraries (1995)

The discovery of useful peptide substrates for proteases that recognize many amino acids in their active sites is often a slow process due to the lack of initial substrate data and the expense of analyzing large numbers of peptide substrates. To overcome these obstacles, we have made use of bacteriophage peptide display libraries. We prepared a random hexamer library in the fd-derived vector fAFF-1 and included a "tether" sequence that could be recognized by monoclonal antibodies. We chose the matrix metalloproteinases stromelysin and matrilysin as the targets for our studies, as they are known to require at least 6 amino acids in a peptide substrate for cleavage. The phage library was treated in solution with protease and cleaved phage separated from uncleaved phage using a mixture of tether-binding monoclonal antibodies and Protein A-bearing cells followed by precipitation. Clones were screened by the use of a rapid screening assay that identified phage encoding peptide sequences susceptible to cleavage by the enzymes. The nucleotide sequence of the random hexamer region of 43 such clones was determined for stromelysin and 23 for matrilysin. Synthetic peptides were prepared whose sequences were based on some of the positive clones, as well as consensus sequences built from the positive clones. Many of the peptides have kcat/KM values as good or better than those of previously reported substrates, and in fact, we were able to produce stromelysin and matrilysin substrates that are both the most active and smallest reported to date. In addition, the phage data predicted selectivity in the P2 and P'1 positions of the two enzymes that were supported by the kinetic analysis of the peptides. This work demonstrates that the phage selection techniques enable the rapid identification of highly active and selective protease substrates without making any a priori assumptions about the specificity or the "physiological substrate" of the protease under study.
Improved Somatic Mutagenesis in Zebrafish Using Transcription Activator-Like Effector Nucleases (TALENs) (2012)

Zinc Finger Nucleases (ZFNs) made by Context-Dependent Assembly (CoDA) and Transcription Activator-Like Effector Nucleases (TALENs) provide robust and user-friendly technologies for efficiently inactivating genes in zebrafish. These designer nucleases bind to and cleave DNA at particular target sites, inducing error-prone repair that can result in insertion or deletion mutations. Here, we assess the relative efficiencies of these technologies for inducing somatic DNA mutations in mosaic zebrafish. We find that TALENs exhibited a higher success rate for obtaining active nucleases capable of inducing mutations than compared with CoDA ZFNs. For example, all six TALENs tested induced DNA mutations at genomic target sites while only a subset of CoDA ZFNs exhibited detectable rates of mutagenesis. TALENs also exhibited higher mutation rates than CoDA ZFNs that had not been pre-screened using a bacterial two-hybrid assay, with DNA mutation rates ranging from 20%-76.8% compared to 1.1%-3.3%. Furthermore, the broader targeting range of TALENs enabled us to induce mutations at the methionine translation start site, sequences that were not targetable using the CoDA ZFN platform. TALENs exhibited similar toxicity to CoDA ZFNs, with >50% of injected animals surviving to 3 days of life. Taken together, our results suggest that TALEN technology provides a robust alternative to CoDA ZFNs for inducing targeted gene-inactivation in zebrafish, making it a preferred technology for creating targeted knockout mutants in zebrafish.
Chemical Oxidation of Dibenzothiophene with a Directly Combined Amphiphilic Catalyst for Deep Desulfurization (2006)

A combined amphiphilic catalyst of octadecyltrimethylammonium bromide (STAB) and phosphotungstic acid was formed directly in a reaction system. Deep desulfurization of dibenzothiophene (DBT) with high selectivity was achieved using the combined amphiphilic catalyst with hydrogen peroxide (H2O2) as the oxidant at 50 °C under atmospheric pressure. The optimum molar ratio between STAB and phosphotungstic acid in DBT oxidation has been determined, and the highest reaction rate was obtained when the molar ratio between STAB and phosphotungstic acid approached 1, not 3 as has been reported in some literature, whereas superfluous STAB beyond this ratio caused resistance for mass transfer of products and reagents at the interface. The influence of reaction temperature, catalyst concentration, H2O2/DBT ratio, and mixing conditions on the oxidation of DBT was examined in detail. An increase in the reaction temperature from 40 °C to 70 °C led to a remarkable increase in the reaction rate. A complete DBT conversion with a DBT concentration of 3000 ppm could be shortened to 10 min as the temperature was elevated to 70 °C. The reaction rate of DBT was improved when the H2O2/DBT ratio was increased. Complete sulfur removal from a 3000 ppm dibenzothiophene mixture was achieved within 20 min at 50 °C. This oxidation process showed high selectivity toward DBT, and the enhancement of DBT oxidation was illustrated when investigated in the presence of 2-methylnaphthalene.
Versatile Photosensitizers for Photodynamic Therapy at Infrared Excitation (2007)

A new type of photosensitizers used in photodynamic therapy, which is based on photon upconverting nanoparticles, is reported. These photosensitizers are excitable with infrared irradiation and have several times larger tissue penetration depth than the currently available ones. They are brought close to the target cancer cells through antigen−antibody interaction with good specificity and versatility. The design is also flexible in that various photosensitive molecules can be potentially adopted into the design. Results from in vitro experiments demonstrate their promise of becoming the next generation photodynamic therapy drugs.
ModBase, a database of annotated comparative protein structure models and associated resources (2013)

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