gebhart/patrepeval huggingface dataset:
Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells. (2005)

Histone deacetylases (HDACs) represent a large family of enzymes identified as key regulators of nucleosomal histone acetylation, a major epigenetic event that controls eukaryotic gene transcription. Inappropriate deacetylation mediated by HDACs has been associated with profound alterations in cellular biology. We have thus hypothesized that an altered HDAC expression may favor cancer development/progression. To test this possibility, we have sought to screen the expression profiles of several class I and class II HDACs (HDAC1-8) in DU-145, PC-3 and LNCaP human prostate cancer cell lines as well as in matched malignant and non-malignant prostate tissues by use of real time RT-PCR, immunoblot and immunohistochemistry. All HDAC transcripts tested were detected at various levels in all prostate cancer cell lines and tissue samples analyzed. In prostate tissues, the abundance of HDAC1 protein, which was exclusively expressed in the cell nucleus, was similar in normal and malignant epithelial cells, but was usually lower in stromal cells. Unexpectedly, HDAC8, another class I HDAC, was not detected in epithelial cells but was uniquely expressed in the cytoplasm of stromal cells. HDAC5, a class II HDAC involved in myogenesis, was not detected in the tissues. Altogether, our findings indicate that epithelial and stromal cells exhibit distinct class I HDAC expression profiles, and the abundance of HDAC1 is not altered in human prostate cancer. In addition, our observations are the first to demonstrate the prominently cytosolic distribution of a class I HDAC, HDAC8.
Factors that Influence Stability of Recombinant Adenoviral Preparations for Human Gene Therapy (1998)

This report identifies formulation and processing factors that influence stability of viral preparations such as selection of appropriate buffer systems, cryoprotectants, and cooling rates. Adenovirus type 5 containing the lacZ marker gene was suspended in combinations of trehalose, sorbitol, sucrose, mannitol, glycine, CaCl2, and gelatin. X-gal stains of 293 cells were used to determine the lac-forming units (lfu)/ml of each preparation before and after treatments. Phosphate-buffered solutions (except those containing sucrose or trehalose) demonstrated a drop of 3 pH units upon freezing regardless of cryoprotectant used. Tris-buffered solutions demonstrated a variation in pH which was dependent upon chosen cryoprotectant, with 1 M trehalose exhibiting no change and a 5% mannitol/10 mM CaCl2 combination showing a 3-unit drop in pH. 4-[2-Hydroxyethyl]-1-piperazine ethanesulfonic acid (HEPES)-buffered solutions showed little change in initial pH when frozen regardless of cryoprotectant chosen. In solution, adenovirus was not affected by incubation for 24 hr in buffers ranging from pH 4 to 8. However, when the solutions were frozen, the number of remaining infectious virions was dependent upon the final pH of the suspending medium. Cryoprotectant solutions that significantly maintained viral stability during a single freeze--thaw cycle were 0.5 M sucrose, 0.5 M trehalose, and 10% sorbitol/0.4% gelatin. Long-term stability studies were performed at 4 degrees C with lyophilized sorbital/gelatin and sucrose preparations. Both formulations provided adequate stability for the adenovirus, with 2.6 and 5.6 x 10(11) lfu/ml detected 150 days after drying, respectively.
Stimulation of Microglial Metabotropic Glutamate Receptor mGlu2 Triggers Tumor Necrosis Factor α-Induced Neurotoxicity in Concert with Microglial-Derived Fas Ligand (2005)

Activated microglia may be detrimental to neuronal survival in a number of neurodegenerative diseases. Thus, strategies that reduce microglial neurotoxicity may have therapeutic benefit. Stimulation of group II metabotropic glutamate (mGlu) receptors on rat primary microglia with the specific group II agonist 2 S ,2′ R ,3′ R -2-(2′,3′-dicarboxy-cyclopropyl)glycine for 24 h induced microglial activation and resulted in a neurotoxic microglial phenotype. These effects were attributable to preferential mGlu2 stimulation, because N -acetyl- l -aspartyl- l -glutamate, a specific mGlu3 agonist, did not induce microglial activation or neurotoxicity. Stimulation of microglial mGlu2 but not mGlu3 induced caspase-3 activation in cerebellar granule neurons in culture, using microglial-conditioned media as well as cocultures. Stimulation of microglial mGlu2 induced tumor necrosis factor-α (TNFα) release, which contributed to microglial neurotoxicity mediated via neuronal TNF receptor 1 and caspase-3 activation. Stimulation of microglial group I or III mGlu receptors did not induce TNFα release. TNFα was only neurotoxic in the presence of microglia or microglial-conditioned medium. The toxicity of TNFα could be prevented by coexposure of neurons to conditioned medium from microglia stimulated by the specific group III agonist l -2-amino-4-phosphono-butyric acid. The neurotoxicity of TNFα derived from mGlu2-stimulated microglia was potentiated by microglial-derived Fas ligand (FasL), the death receptor ligand. FasL was constitutively expressed in microglia and shed after mGlu2 stimulation. Our data suggest that selective and inverse modulation of microglial mGlu2 and mGlu3 may prove a therapeutic target in neuroinflammatory diseases such as Alzheimer's disease and multiple sclerosis.
Zinc‐ and sequence‐dependent binding to nucleic acids by the N‐terminal zinc finger of the HIV‐1 nucleocapsid protein: NMR structure of the complex with the Psi‐site analog, dACGCC (1993)

Abstract The nucleic acid interactive properties of a synthetic peptide with sequence of the N‐terminal CCHC zinc finger (CCHC = Cys‐X 2 ‐Cys‐X 4 ‐His‐X 4 ‐Cys; × = variable amino acid) of the human immunodeficiency virus (HIV) nucleocapsid protein, Zn(HIV1‐F1), have been studied by 1 H NMR spectroscopy. Titration of Zn(HIV1‐F1) with oligodeoxyribonucleic acids containing different nucleotide sequences reveals, for the first time, sequence‐dependent binding that requires the presence of at least one guanosine residue for tight complex formation. The dynamics of complex formation are sensitive to the nature of the residues adjacent to guanosine, with residues on the 3′ side of guanosine having the largest influence. An oligodeoxyribonucleotide with sequence corresponding to a portion of the HIV‐1 psi‐packaging signal, d(ACGCC), forms a relatively tight complex with Zn(HIV1‐F1) ( K d = 5 × 10 −6 M). Two‐dimensional nuclear Overhauser effect (NOESY) data indicate that the bound nucleic acid exists predominantly in a single‐stranded, A‐helical conformation, and the presence of more than a dozen intermolecular NOE cross peaks enabled three‐dimensional modeling of the complex. The nucleic acid binds within a hydrophobic cleft on the peptide surface. This hydrophobic cleft is defined by the side chains of residues Val 1 , Phe 4 , Ile 12 , and Ala 13 . Backbone amide protons of Phe 4 and Ala 13 and the backbone carbonyl oxygen of Lys 2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively. In addition, the positively charged side chain of Arg 14 is ideally positioned for electrostatic interactions with the phosphodiester backbone of the nucleic acid. The structural findings provide a rationalization for the general conservation of these hydrophobic and basic residues in CCHC zinc fingers, and are consistent with site‐directed mutagenesis results that implicate these residues as direct participants in viral genome recognition.
Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial (2011)

Cancer Research UK (CRUK/03/005).
Ambient RF Energy Scavenging: GSM and WLAN Power Density Measurements (2008)

To assess the feasibility of ambient RF energy scavenging, a survey of expected power density levels distant from GSM-900 and GSM-1800 base stations has been conducted and power density measurements have been performed in a WLAN environment. It appears that for distances ranging from 25 m to 100 m from a GSM base station, power density levels ranging from 0.1 mW/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> to 3.0 mW/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> may be expected. First measurements in a WLAN environment indicate even lower power density values, making GSM and WLAN unlikely to produce enough ambient RF energy for wirelessly powering miniature sensors. A single GSM telephone however has proven to deliver enough energy for wirelessly powering small applications on moderate distances.
Optical Systems with Resolving Powers Exceeding the Classical Limit II (1967)

The fundamental invariant of an optical system is the number N of degrees of freedom of the message it can transmit. The spatial bandwidth of the system can be increased over the classical limit by reducing one of the other constituent factors of N. As examples of this invariance theorem N=const. established in Part I of this series [ J. Opt. Soc. Am.56, 1463 ( 1966)], we discuss (a) a system whose spatial-bandwidth increase is achieved by a proportional reduction of its temporal bandwidth, and (b) the airborne synthetic-aperture, terrain-mapping radar, whose spatial resolution comes from exploitation of the temporal degrees of freedom of the received signal. The increase of the spatial bandwidth beyond the classical limit is, however, limited by the appearance of evanescent waves.The number of degrees of freedom of the object wave field stored in a hologram is discussed. The storage capacity of the photographic plate, which is proportional to its size times its spatial cutoff frequency, is fully exploited only by single-sideband Fraunhofer but not by single-sideband Fresnel holograms.
A Liver-Specific Enhancer in the Core Promoter Region of Human Hepatitis B Virus (1989)

An 88-base pair fragment in the core promoter of the human hepatitis B virus (HBV) contains a functional promoter and a strong liver-specific enhancer. This enhancer functions in human hepatoma cells, where it is much more active than the previously described HBV enhancer in stimulating expression of the linked bacterial chloramphenicol acetyltransferase gene expressed from heterologous promoters. Studies of the role of this enhancer-promoter in HBV may help to clarify mechanisms of gene expression in cells infected with HBV and the role of the virus in the pathogenesis of hepatitis and hepatocellular carcinoma.
Oxidation in rheumatoid arthritis. (2004)

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as important intracellular signaling molecules that amplify the synovial inflammatory-proliferative response. Repetitive cycles of hypoxia and reoxygenation associated with changes in synovial perfusion are postulated to activate hypoxia-inducible factor-1alpha and nuclear factor-kappaB, two key transcription factors that are regulated by changes in cellular oxygenation and cytokine stimulation, and that in turn orchestrate the expression of a spectrum of genes critical to the persistence of synovitis. An understanding of the complex interactions involved in these pathways might allow the development of novel therapeutic strategies for rheumatoid arthritis.
Synthesis and Biological Activities of Phosphonylalkylpurine Derivatives (1989)

Abstract Syntheses and biological activities of 2-phosphonylmethoxy-ethyl (PME) purine analogs are described.
Allopurinol-Induced Orotidinuria (1990)

Ornithine carbamoyltransferase is an X-linked mitochondrial enzyme expressed in hepatocytes and enterocytes. A deficiency of this enzyme results in central nervous system dysfunction, which may be fatal in newborn boys. Milder forms are seen in older boys and girls and in adults. Establishing the carrier status of women at risk for ornithine carbamoyltransferase deficiency is important for determining reproductive and medical risks for affected women. We report a test to establish the carrier status of women at risk for ornithine carbamoyltransferase deficiency. This test relies on the allopurinol-induced accumulation of orotidine, whose synthesis is stimulated by carbamoyl phosphate, a substrate that accumulates in ornithine carbamoyltransferase deficiency. We used anion-exchange, high-performance liquid chromatography to measure urinary orotidine and orotic acid excretion after the administration of a 300-mg oral dose of allopurinol in 25 [corrected] women who were obligate heterozygotes, 13 who were probable heterozygotes, 15 mothers of affected boys from monoplex families (families with only one affected member), 12 mothers of affected girls from monoplex families, and 21 [corrected] normal, unrelated women who were not carriers. Urinary orotidine excretion was increased 3 SD or more above the mean value for the normal women in 95.8 percent of the obligate heterozygotes, 84.6 percent of the probable heterozygotes, 73.3 percent of the mothers of affected boys in monoplex families, and 33.3 percent of the mothers of affected girls in monoplex families, thus establishing that these women were carriers of a mutant ornithine carbamoyltransferase allele. The presence of allopurinol-induced orotic aciduria was not as sensitive or specific an indicator of carrier status as the presence of orotidinuria. We conclude that measurement of urinary orotidine excretion after the administration of allopurinol is a simple and reliable test for the identification of women who are heterozygous for ornithine carbamoyltransferase deficiency.
Intent-aware long-term prediction of pedestrian motion (2016)

We present a method to predict long-term motion of pedestrians, modeling their behavior as jump-Markov processes with their goal a hidden variable. Assuming approximately rational behavior, and incorporating environmental constraints and biases, including time-varying ones imposed by traffic lights, we model intent as a policy in a Markov decision process framework. We infer pedestrian state using a Rao-Blackwellized filter, and intent by planning according to a stochastic policy, reflecting individual preferences in aiming at the same goal.
The nuclear location signal (1985)

A short sequence of predominantly basic amino acids Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val from SV40 Large T is responsible for the normal nuclear location of the protein. Alteration of Lys-128 to each of six different residues other than Arg renders Large T cytoplasmic, whereas single amino acid changes in the surrounding region impair but do not prevent nuclear accumulation. When transposed to the amino terminus of cytoplasmic Large T species, or Escherichia coli beta-galactosidase or of chicken muscle pyruvate kinase, the sequence around Lys-128 of Large T is able to direct the recipient protein to the nucleus. This demonstrates that these amino acids can be sufficient for nuclear location and can act as a nuclear location signal. A computer search of over 2500 proteins reveals that some other nuclear proteins (for example, BK virus Large T, SV40 VP2 and adenovirus 72kDa DNA binding protein) contain very similar basic tracts, but so too do some presumed non-nuclear proteins (for example, poliovirus VP3). We suggest that the related sequence acts as the nuclear location signal in the other nuclear proteins but that the sequence does not function in all cases, perhaps because it is not accessible. A similar, but shorter or less basic sequence, was detected in a number of other nuclear proteins, for example, polyoma virus Large T, SV40 VP1 and several histones. However, such sequences were also found in many other proteins. Perhaps the shorter basic sequences can also act as nuclear location signals, but to be functional they need to be exposed (for example, at the amino terminus of the protein as in SV40 VP1) or to be present in multiple copies.
Fat (fat) and Tubby (tub): Two Autosomal Recessive Mutations Causing Obesity Syndromes in the Mouse (1990)

This report describes the development of obesity syndromes in mice caused by two autosomal recessive mutations, fat (fat), located on chromosome 8, and tubby (tub), located on chromosome 7. Both mutations cause slowly developing but ultimately severe obesity conditions. Although hyperinsulinemia, hyperactivity of the beta cell of the islets of Langerhans, and beta-cell degranulation are consistent features, these obesity syndromes do not progress to severe diabetes. The many different single-gene mutations in the mouse that produce obesity-diabetes syndromes of varying degrees of severity make the mutant mouse a powerful tool for analyzing the number and nature of the primary defects than can cause obesity states.
Intramuscular β2-agonist administration enhances early regeneration and functional repair in rat skeletal muscle after myotoxic injury (2008)

Systemic administration of beta(2)-adrenoceptor agonists (beta(2)-agonists) can improve skeletal muscle regeneration after injury. However, therapeutic application of beta(2)-agonists for muscle injury has been limited by detrimental cardiovascular side effects. Intramuscular administration may obviate some of these side effects. To test this hypothesis, the right extensor digitorum longus (EDL) muscle from rats was injected with bupivacaine hydrochloride to cause complete muscle fiber degeneration. Five days after injury, half of the injured muscles received an intramuscular injection of formoterol (100 mug). Muscle function was assessed at 7, 10, and 14 days after injury. A single intramuscular injection of formoterol increased muscle mass and force-producing capacity at day 7 by 17 and 91%, respectively, but this effect was transient because these values were not different from control levels at day 10. A second intramuscular injection of formoterol at day 7 prolonged the increase in muscle mass and force-producing capacity. Importantly, single or multiple intramuscular injections of formoterol did not elicit cardiac hypertrophy. To characterize any potential cardiovascular effects of intramuscular formoterol administration, we instrumented a separate group of rats with indwelling radio telemeters. Following an intramuscular injection of formoterol, heart rate increased by 18%, whereas systolic and diastolic blood pressure decreased by 31 and 44%, respectively. These results indicate that intramuscular injection can enhance functional muscle recovery after injury without causing cardiac hypertrophy. Therefore, if the transient cardiovascular effects associated with intramuscular formoterol administration can be minimized, this form of treatment may have significant therapeutic potential for muscle-wasting conditions.
Heuristics in real user interfaces (1993)

It is the conventional wisdom in user interface design that direct manipulation is best and that interfaces should be predictable. This tends to argue against having a system “guess” or use heuristics or other AI approaches. However, an increasing number of today's successful software products do use heuristics in their interfaces. The heuristics are used to help guide the user and to perform tasks that would be too difficult to specify by conventional direct manipulation approaches. We believe that user interface designers will increasingly need to consider using heuristic techniques in their interfaces. This panel discusses a number of today's successful products using heuristics and the important HCI design issues such as feedback.
ACAPELLA, a capillary-based submicroliter automated sample preparation system for genome analysis (1999)

The Genomation Laboratory in the Electrical Engineering Department at the University of Washington has been developing an automated, high-throughput submicroliter-scale reaction preparation system for use in molecular biology, especially as part of the Human Genome Project and other high-throughput DNA sequencing endeavors. Small glass capillaries enable the preparation, handling and monitoring of one-microliter reaction volumes. The Genomation Laboratory, with corporate partners Orca Photonic Systems, Inc. and Engineering Arts, has developed modules for aspiration, dispensing, mixing, transport and rapid thermal treatment of biological samples contained in glass capillaries. The "ACAPELLA 1K" is the first integration of these modules, designed to process 1000 samples in an 8-hour day. It has served as a test bed for the technologies as well as for performing biological experiments in conjunction with the University of Washington Genome Center. The Genomation Laboratory is presently developing the next-stage "ACAPELLA 5K" system based on the results of the ACAPELLA 1K system.
Characterization and modeling of silicon-on-insulator field effect transistors (1999)

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1999.
Effectiveness of the Leukotriene Receptor Antagonist Zafirlukast for Mild-to-Moderate Asthma (1997)

A daily regimen of zafirlukast added to as-needed inhaled beta-agonists is more effective than beta-agonists alone in treating mild-to-moderate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further impetus to use regular "preventive" therapy in patients with mild-to-moderate asthma.
Evaluation of a Modular Strategy for the Construction of Novel Polydactyl Zinc Finger DNA-Binding Proteins (2003)

In previous studies, we have developed a technology for the rapid construction of novel DNA-binding proteins with the potential to recognize any unique site in a given genome. This technology relies on the modular assembly of modified zinc finger DNA-binding domains, each of which recognizes a three bp subsite of DNA. A complete set of 64 domains would provide comprehensive recognition of any desired DNA sequence, and new proteins could be assembled by any laboratory in a matter of hours. However, a critical parameter for this approach is the extent to which each domain functions as an independent, modular unit, without influence or dependence on its neighboring domains. We therefore examined the detailed binding behavior of several modularly assembled polydactyl zinc finger proteins. We first demonstrated that 80 modularly assembled 3-finger proteins can recognize their DNA target with very high specificity using a multitarget ELISA-based specificity assay. A more detailed analysis of DNA binding specificity for eight 3-finger proteins and two 6-finger proteins was performed using a target site selection assay. Results showed that the specificity of these proteins was as good or better than that of zinc finger proteins constructed using methods that allow for interdependency. In some cases, near perfect specificity was achieved. Complications due to target site overlap were found to be restricted to only one particular amino acid interaction (involving an aspartate in position 2 of the alpha-helix) that occurs in a minority of cases. As this is the first report of target site selection for designed, well characterized 6-finger proteins, unique insights are discussed concerning the relationship of protein length and specificity. These results have important implications for the design of proteins that can recognize extended DNA sequences, as well as provide insights into the general rules of recognition for naturally occurring zinc finger proteins.