gebhart/patrepeval huggingface dataset:
A human interleukin 3 analog with increased biological and binding activities. (1992)

Human interleukin 3 (IL-3) variants generated by site-directed mutagenesis were analyzed in multiple biological and binding assays to identify residues critical for IL-3 activity. Two mutants carrying substitutions in the predicted hydrophilic region within the first alpha-helix, [Ala21,Leu22]IL-3 and [Ala21,Leu22,Ala25]IL-3 showed loss of biological activity and high-affinity binding. Mutants in a second predicted hydrophilic region, [Ala44,Leu45,Ala46]IL-3 and [Ala44,Ala46]IL-3, however, showed similar biological and binding activities to wild-type IL-3. Mutations in a C-terminal hydrophilic region that overlaps the fourth predicted alpha-helix led to either loss or gain of function. IL-3 analogs [Glu104,Asp105]-, [Leu108]-, [Asn108]-, [Thr108]-, and [Ala101,Leu108]IL-3 were less active than wild-type IL-3, whereas [Ala101]IL-3 and [Val116]IL-3 were 2- to 3-fold more potent. Significantly, the double mutant [Ala101,Val116]IL-3 exhibited a 15-fold greater potency than native IL-3. Receptor binding studies showed that [Ala101,Val116]IL-3 exhibited increased binding to the high- and low-affinity receptors of monocytes. These results show the generation of an IL-3 analog with increased biological and binding activities and support a model where the C terminus of IL-3 interacts with the alpha chain of the IL-3 receptor, making this region a useful focus for the development of more potent IL-3 agonists or antagonists.
Bridged Nucleic Acids (BNAs) as Molecular Tools (2015)

There has been a growing interest in developing chemically modified nucleotides for diagnostics or therapeutics. Among the list of the artificial nucleotides, bridged nucleic acids (BNAs) appear to be most promising nucleic acid analogs to date in view of the usage for applications. Here we briefly introduced the modified nucleotides and the applications of the new generation BNAs. For the possible applications, BNAs can be used for antisense, antigene, aptamer development, and real-time clamp technology. Eventually, BNAs may play a pivotal role in a new type of disease diagnostics and therapeutics in the foreseeable future.
DNA Probes: Background Applications Procedures (1993)

Preface - Molecular Hybridization Technology - Sample Preparation - Synthesis of DNA and DNA Analogs - Radioactive Labeling Procedures - Non-Radioactive Labeling Procedures - Hybridization Procedures and Detection Formats - Amplification Systems - In Situ Analysis - Molecular Cloning and Screening - Detection of Retroviruses - Diagnosis of Genetic Orders - Cancer Diagnosis - Bacterial Detection - Microbiological Analysis of Foods - Environmental Monitoring - Forensic Analysis - Appendix - Index
Sulphide tolerance and adaptation in the California killifish, Fundulus parvipinnis, a salt marsh resident (1993)

Hydrogen sulphide is a toxicant naturally produced in hypoxic marine sediments, hydrocarbon and brine seeps and hydrothermal vents. The California killifish, a salt marsh resident, is remarkably tolerant of sulphide. The 50% lethal concentration is 700 μM total sulphide in 96 h, and 5 mM in 8 h (determined in flow‐through, oxygenated sea water). Killifish exposed to sulphide produce thiosulphate which accumulates in the blood. The cytochrome c oxidase (a major site of toxicity) of the killifish is 50% inhibited by &lt;1 μM sulphide. Killifish liver mitochondria are poisoned by 50–75 μM sulphide but can oxidize 10–20 μM sulphide to thiosulphate. Sulphide causes sulphhaemoglobin formation (and impairment of oxygen transport) at 1–5 mM in vitro and to a small extent at 2 mM in vivo . Killifish blood neither catalyses sulphide oxidation significantly nor binds sulphide at environmental (low) sulphide concentrations. Exposure to 200 μM and 700 μM sulphide over several days causes significant increases in lactate concentrations, indicating shift to anaerobic glycolysis. However, individuals with the most lactate die. In terms of diffusible H 2 S, the killifish can withstand concentrations two to three orders of magnitude greater than would poison cytochrome c oxidase. The high sulphide tolerance of the killifish, particularly of concentrations typical of salt marshes, can be explained chiefly by mitochondrial sulphide oxidation. Sulphide tolerance and mitochondrial sulphide oxidation in the killifish have a constitutive basis, i.e. do not diminish in fish held in the laboratory in sulphide‐free water for 1–2 months, and are improved by prior acclimation.
Practical fiber-optic Bragg grating strain gauge system (1993)

A fiber-optic strain gauge system for use in structural monitoring and smart-structure applications is described. The strain gauge uses a fiber-optic Bragg grating sensor to measure strain and a passive, wavelength demodulation system to determine the wavelength of the narrow-band, backreflected spectrum from the grating sensor. The fiber-optic strain gauge system permits the measurement of both static and dynamic strains with a noise-limited resolution of 0.44 microstrain/√Hz, a measurement dynamic range of 27.8 dB, and a bandwidth of 250 Hz.
Automatic registration of aerial imagery with untextured 3D LiDAR models (2008)

A fast 3D model reconstruction methodology is desirable in many applications such as urban planning, training, and simulations. In this paper, we develop an automated algorithm for texture mapping oblique aerial images onto a 3D model generated from airborne light detection and ranging (LiDAR) data. Our proposed system consists of two steps. In the first step, we combine vanishing points and global positioning system aided inertial system readings to roughly estimate the extrinsic parameters of a calibrated camera. In the second step, we refine the coarse estimate of the first step by applying a series of processing steps. Specifically, We extract 2D corners corresponding to orthogonal 3D structural corners as features from both images and the untextured 3D LiDAR model. The correspondence between an image and the 3D model is then performed using Hough transform and generalized M-estimator sample consensus. The resulting 2D corner matches are used in Lowepsilas algorithm to refine camera parameters obtained earlier. Our system achieves 91% correct pose recovery rate for 90 images over the downtown Berkeley area, and overall 61% accuracy rate for 358 images over the residential, downtown and campus portions of the city of Berkeley.
Ring Closure Reactions of Chalcones Using Microwave Technology (1999)

Abstract The synthesis of heterocyclic compounds containing pyrimidine, pyrazoline, isoxazoline and cyclohexenone ring from chalcone derivatives containing anisole and 3′4′-methylenedioxy phenyl ring under ‘dry conditions’ using microwaves and by conventional methods are described.
Regioselective Friedel—Crafts Alkylation of Anilines and Amino‐Substituted Heteroarenes with Hexafluoroacetone Sesquihydrate. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Coherent aperture-synthesis, wide-field, high-resolution holographic microscopy of biological tissue (2010)

We show for the first time, to our knowledge, high-resolution wide-field images of biological samples recorded using coherent aperture-synthesis Fourier holography. To achieve this, we combined off-axis plane-wave polarized illumination with an axial sample rotation and polarization-sensitive collection of backscattered light. We synthesized 180 Fourier holograms using an efficient postdetection phase-matching correlation scheme. The result was an annular spatial frequency-space synthetic aperture (NA=0.93) with an effective area 25 times larger than that due to a single hologram. A high-resolution high-contrast microscopic reconstruction of biological tissue was computed over a sample area of 9 mm(2) from holograms acquired at 34 mm working distance.
Discovery of Small-Molecule Inhibitors of Bcl-2 through Structure-Based Computer Screening (2001)

Bcl-2 belongs to a growing family of proteins which regulates programmed cell death (apoptosis). Overexpression of Bcl-2 has been observed in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer. Thereby, Bcl-2 is an attractive new anti-cancer target. Herein, we describe the discovery of novel classes of small-molecule inhibitors targeted at the BH3 binding pocket in Bcl-2. The three-dimensional (3D) structure of Bcl-2 has been modeled on the basis of a high-resolution NMR solution structure of Bcl-X(L), which shares a high sequence homology with Bcl-2. A structure-based computer screening approach has been employed to search the National Cancer Institute 3D database of 206 876 organic compounds to identify potential Bcl-2 small-molecule inhibitors that bind to the BH3 binding site of Bcl-2. These potential Bcl-2 small-molecule inhibitors were first tested in an in vitro binding assay for their potency in inhibition of the binding of a Bak BH3 peptide to Bcl-2. Thirty-five potential inhibitors were tested in this binding assay, and seven of them were found to have a binding affinity (IC(50) value) from 1.6 to 14.0 microM. The anti-proliferative activity of these seven active compounds has been tested using a human myeloid leukemia cell line, HL-60, which expresses the highest level of Bcl-2 protein among all the cancer cell lines examined. Compound 6 was the most potent compound and had an IC(50) value of 4 microM in inhibition of cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Five other compounds had moderate activity in inhibition of cell growth. Compound 6 was further evaluated for its ability to induce apoptosis in cancer cells. It was found that 6 induces apoptosis in cancer cells with high Bcl-2 expression and its potency correlates with the Bcl-2 expression level in cancer cells. Furthermore, using NMR methods, we conclusively demonstrated that 6 binds to the BH3 binding site in Bcl-X(L). Our results showed that small-molecule inhibitors of Bcl-2 such as 6 modulate the biological function of Bcl-2, and induce apoptosis in cancer cells with high Bcl-2 expression, while they have little effect on cancer cells with low or undetectable levels of Bcl-2 expression. Therefore, compound 6 can be used as a valuable pharmacological tool to elucidate the function of Bcl-2 and also serves as a novel lead compound for further design and optimization. Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2.
Fine-Needle Aspiration Biopsy of the Thyroid (1984)

Cases in which thyroid nodules yielded suspicious cytologic findings on fine-needle aspiration biopsy were prospectively studied during a 3-year period. Of 1970 patients, 333 (17%) had suspicious cytologic findings; from this group, the cases of 253 patients were studied. The cytologic diagnoses were 96 (38%) H urthle cell neoplasms, 84 (33%) follicular cell neoplasms, and 73 (29%) nonspecific diagnoses. A thyroid scan was obtained in 123 of 203 (61%) patients with a solitary nodule, and the nodules were hypofunctional in 102 (83%). Malignant lesions were found in 60 (24%) of the 253 patients. Our findings are consistent with reports that 20% of patients who have a fine-needle aspiration biopsy will have suspicious cytologic findings and that of these, 20% may have a malignant lesion. Thyroid scanning will not distinguish between benign and malignant thyroid lesions that are suspicious on cytologic examination. Surgical excision of all suspicious lesions seems reasonable.
Androgen Receptor Expression in Prostate Carcinoma Cells Suppresses α6β4 Integrin-Mediated Invasive Phenotype1 (2000)

Prostate cancer cells may lose androgen-sensitivity after androgen ablation therapy, becoming highly invasive and metastatic. The biological mechanisms responsible for higher tumurogenicity of androgen-independent prostate carcinomas are not entirely known. We demonstrate that androgen receptor regulation of adhesion and invasion of prostate cancer cells through modulation of alpha6beta4 integrin expression may be one of the molecular mechanisms responsible of this phenomenon. We found that protein and gene expressions of alpha6 and beta4 subunits were strongly reduced in the androgen-sensitive cell line LNCaP respect to the androgen-independent PC3 and that transfection of PC3 cells with a full-length androgen receptor expression vector resulted in a decreased expression of alpha6beta4 integrin, reduced adhesion on laminin, and suppressed Matrigel invasion. Growth in soft agar was also suppressed in androgen receptor-positive PC3 clones. Treatment of androgen receptor positive clones with the synthetic androgen R1881 further reduced alpha6 and beta4 messenger RNA expression as well as adhesion on laminin and Matrigel invasion. Our results indicate that androgens regulate cell-extracellular matrix adhesion and invasion by modulation of integrin expression and function, thus keeping a low invasive phenotype of prostate cancer cells.
ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD (2010)

Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-beta, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug candidates for AD therapy. However, how ACAT inhibitors act in the brain has so far remained unclear. Here we show that ACAT1 is the major functional isoenzyme in the mouse brain. ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human APPswe as well as its proteolytic fragments, and ameliorates cognitive deficits. At 4 months of age, A1- causes a 32% content increase in 24-hydroxycholesterol (24SOH), the major oxysterol in the brain. It also causes a 65% protein content decrease in HMG-CoA reductase (HMGR) and a 28% decrease in sterol synthesis rate in AD mouse brains. In hippocampal neurons, A1- causes an increase in the 24SOH synthesis rate; treating hippocampal neuronal cells with 24SOH causes rapid declines in hAPP and in HMGR protein levels. A model is provided to explain our findings: in neurons, A1- causes increases in cholesterol and 24SOH contents in the endoplasmic reticulum, which cause reductions in hAPP and HMGR protein contents and lead to amelioration of amyloid pathology. Our study supports the potential of ACAT1 as a therapeutic target for treating certain forms of AD.
Functional Partitioning to Optimize End-to-End Performance on Many-core Architectures (2010)

Scaling computations on emerging massive-core supercomputers is a daunting task, which coupled with the significantly lagging system I/O capabilities exacerbates applications' end-to-end performance. The I/O bottleneck often negates potential performance benefits of assigning additional compute cores to an application. In this paper, we address this issue via a novel functional partitioning (FP) runtime environment that allocates cores to specific application tasks - checkpointing, de-duplication, and scientific data format transformation - so that the deluge of cores can be brought to bear on the entire gamut of application activities. The focus is on utilizing the extra cores to support HPC application I/O activities and also leverage solid-state disks in this context. For example, our evaluation shows that dedicating 1 core on an oct-core machine for checkpointing and its assist tasks using FP can improve overall execution time of a FLASH benchmark on 80 and 160 cores by 43.95% and 41.34%, respectively.
An immunofluorescence procedure for the detection of intracellular immunoglobulins. (1969)

This paper gives the technical details of an immunofluorescence procedure that was specially developed for the study of intracellular immunoglobulins but also proved useful for other purposes. After suspending and washing of the cells, slides are prepared with a sedimentation apparatus. The result is a preparation with a minimal background and a large number of cells in a limited area. These preparations have been found to be eminently suitable for qualitative and quantitative studies. The description of the method also deals with the testing of specificity of the conjugates and photomicrography.
Low-loss superconducting resonant circuits using vacuum-gap-based microwave components (2010)

We have produced high-quality complex microwave circuits, such as multiplexed resonators and superconducting phase qubits, using a “vacuum-gap” technology that eliminates lossy dielectric materials. We have improved our design and fabrication strategy beyond our earlier work, leading to increased yield, enabling the realization of these complex circuits. We incorporate both novel vacuum-gap wiring crossovers for gradiometric inductors and vacuum-gap capacitors (VGC) on chip to produce resonant circuits that have large internal quality factors (30 000&amp;lt;QI&amp;lt;165 000) at 50 mK, outperforming most dielectric-filled devices. Resonators with VGCs as large as 180 pF confirm single mode behavior of our lumped-element components.
miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma (2011)

These results reveal that ARTN, a known tumor metastasis-related gene, is a direct target of miR-223 and that miR-223 may have a tumor suppressor function in esophageal carcinoma and could be used in anticancer therapies.
Acetylcholine receptor aggregation at nerve-muscle contacts in mammalian cultures: induction by ventral spinal cord neurons is specific to axons (1995)

We used a novel mammalian coculture system to study ACh receptor (AChR) redistribution and synaptic structure at nerve-muscle contacts. Ventral spinal cord (VSC) neurons were plated on cultures containing extensive myotubes but few fibroblasts. Neurite-induced redistribution of AChRs occurred within 6 hr after plating neurons and was maximal between 36-48 hr. This AChR redistribution appeared in two patterns: (1) AChR density at sites directly apposed to the neurite where neurites crossed preexisting AChR patches was sharply reduced, (2) Newly aggregated AChRs formed swaths lateral to the neurite path. VSC neurons induced more AChR aggregation than hippocampal, superior cervical ganglion and dorsal root ganglion neurons. The 43 and 58 kDa postsynaptic proteins were colocalized with AChR-enriched domains in all VSC neurite-induced aggregates whereas the colocalization of laminin was variable. Electron microscopy of regions with neurite-induced AChR aggregation showed postsynaptic membrane specializations characteristic of developing synapses and, in older cultures, features of more mature synaptic structure. Thus, the coculture system is useful for studying early stages of neuromuscular junction (NMJ) formation. Neurites in these cocultures were identified as axons or dendrites by morphological criteria and by their immunoreactivity for synaptophysin and phosphorylated heavy neurofilament subunits or for microtubule associated protein 2 (MAP2), respectively. Axons showed a 10-fold higher induction of AChR aggregation than did dendrites. Thus, at least one essential signaling molecule necessary for the induction of AChR aggregation at sites of interaction with muscle appears to be expressed in a polarized fashion in developing VSC neurons.
Optimized Design of Plasmonic MSM Photodetector (2007)

We present an optimized design for a plasmonic metal-semiconductor-metal photodetector with interdigitated electrodes with subwavelength dimensions and a single GaInNAs quantum well (QW) as an absorbing layer. The excitation of surface plasmons at the metal-semiconductor interface leads to a strong field enhancement near the metallic electrodes. This results in an increased absorption in the QW, allowing both fast electrical response of the photodetector and high quantum efficiencies. With a grating periodicity of 820 nm and electrode finger width of 460 nm a 16-fold increase in the absorption of p-polarized light in the QW is achieved in comparison to the case without electrodes.
Effects of 3,3-dipyridylmethyl-1-phenyl-2-indolinone on gamma-aminobutyric acid elicited chloride current of snail central neuron. (1997)

The effects of (1) gamma-aminobutyric acid (GABA) on the excitable membrane and (2) DPMPI (3,3-dipyridylmethyl-1-phenyl-2-indolinone) on the microperfused GABA elicited currents were investigated on central LP5 neuron of giant African snail, Achatina fulica Ferussac, with conventional voltage-clamp technique. GABA elicited an inward current of LP5 neuron by a concentration and voltage dependent manner. Muscimol, GABAA receptor agonist, did, while baclofen, GABAB receptor agonist, did not, elicit the membrane current on the neuron. The GABA elicited currents in LP5 neuron were blocked by picrotoxin, a GABAA receptor ion channel complex antagonist while the currents were not blocked by phaclofen, a GABAB receptor antagonist. The results suggested that the GABA elicited current in LP5 neuron was mainly due to activation of GABAA receptor. DPMPI increased the frequency of the spontaneously generated action potential of the neuron. In the voltage clamped neuron, DPMPI decreased the GABA elicited responses by a concentration dependent manner. DPMPI altered neither the reversal potential of GABA elicited current, nor the membrane resistance of the excitable membrane of central LP5 neuron. The results concluded that DPMPI altered the GABAA activated receptor ionic channel complex of the LP5 neuron.
Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China (2011)

Epidemiological evidence has suggested that consumption of a diet rich in cruciferous vegetables reduces the risk of several types of cancers and chronic degenerative diseases. In particular, broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can release the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases. Two broccoli sprout-derived beverages, one sulforaphane-rich (SFR) and the other glucoraphanin-rich (GRR), were evaluated for pharmacodynamic action in a crossover clinical trial design. Study participants were recruited from the farming community of He Zuo Township, Qidong, China, previously documented to have a high incidence of hepatocellular carcinoma with concomitant exposures to aflatoxin and more recently characterized with exposures to substantive levels of airborne pollutants. Fifty healthy participants were randomized into two treatment arms. The study protocol was as follows: a 5 days run-in period, a 7 days administration of beverage, a 5 days washout period and a 7 days administration of the opposite beverage. Urinary excretion of the mercapturic acids of acrolein, crotonaldehyde, ethylene oxide and benzene were measured both pre- and postinterventions using liquid chromatography tandem mass spectrometry. Statistically significant increases of 20-50% in the levels of excretion of glutathione-derived conjugates of acrolein, crotonaldehyde and benzene were seen in individuals receiving SFR, GRR or both compared with their preintervention baseline values. No significant differences were seen between the effects of SFR versus GRR. Intervention with broccoli sprouts may enhance detoxication of airborne pollutants and attenuate their associated health risks.