gebhart/patrepeval huggingface dataset:
Inhibition of p53 degradation by Mdm2 acetylation (2004)

Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and proteasomal degradation of the p53 tumor suppressor protein. Acetylation of p53 regulates p53's transcriptional activity and inhibits Mdm2-mediated p53 ubiquitination and degradation. We now report that Mdm2 is also a target for acetylation. Mdm2 is acetylated in vitro by CREB-binding protein (CBP) and to a lesser extent by p300, but not by p300/CPB-associated factor. Acetylation occurs primarily within the RING finger domain of Mdm2. In vivo acetylation of Mdm2 was detected easily with CBP but not p300. Efficient in vivo acetylation required the preservation of the RING finger. An Mdm2 mutant (K466/467Q) mimicking acetylation is impaired in its ability to promote p53 ubiquitination, as well as Mdm2 autoubiquitination. Moreover, K466/467Q is defective in promoting p53 degradation in living cells. We thus suggest that acetyltransferases may modulate cellular p53 activity not only by modifying p53, but also by inactivating Mdm2.
Photovoltaic cells fabricated by electrophoretic deposition of CdSe nanocrystals (2008)

Electrophoretic deposition was used to deposit CdSe nanocrystals on TiO2 for use in photovoltaic cells. The deposition current underwent a simple exponential decay, consistent with the current being comprised of charge transfer from charged nanocrystals to the electrodes. Rutherford backscattering spectroscopy showed the composition of the deposited films depended on the polarity of the electrode on which the film formed. A solar cell constructed using electrophoretic deposition exhibited a photovoltaic response from the region in which nanocrystals were deposited, with an efficiency of ∼10−6%. The low efficiency was primarily due to the planar geometry employed for the TiO2 subsrate.
An 8½-Year Clinical Experience with Surgery for Atrial Fibrillation (1996)

The Maze procedure is an effective treatment for medically refractory atrial fibrillation in properly selected patients.
Enhanced Antitumor Activity of an Anti-5T4 Antibody–Drug Conjugate in Combination with PI3K/mTOR inhibitors or Taxanes (2015)

Our results provide a biologic rationale for combining 5T4-ADC with either PI3K/mTOR pathway inhibitors or taxanes and suggest that mechanisms underlying the synergy may be attributed to cellular effects of the auristatin payload.
A Two-Dimensional Superscalar Processor Architecture (2009)

This paper proposes a new processor architecture optimized for execution of sequential instruction streams. The architecture, called Grid Alu Processor (GAP), comprises an in order superscalar pipeline front-end enhanced by a configuration unit able to dynamically issue dependent and independent standard machine instructions simultaneously to the Arithmetic Logic Units (ALUs) organized in a two-dimensional array. In contrast to well-known coarse-grained reconfigurable architectures no special synthesis tools are required and no configuration overhead occurs. Simulations of the GAP show a maximum Instructions Per Cycle (IPC) speedup of about 2.56 compared to the results of an equivalently configured SimpleScalar processor simulator.
Self-Assembling Nucleic Acid Delivery Vehicles via Linear, Water-Soluble, Cyclodextrin-Containing Polymers (2004)

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.
New compressed tablet rapidly disintegrating in saliva in the mouth using crystalline cellulose and a disintegrant. (1995)

We formulated a new compressed tablet which is rapidly disintegrated and dissolved in the mouth without the need to drink water. The crushing strength increased with increasing compression force and maximum values (8-18 kgf) for the formulations comprising crystalline cellulose and low-substituted hydroxypropylcellulose (L-HPC) were obtained at the compression force of 300 kgf. Rapid disintegration (within 30 s) was obtained in vitro using various compounding ratios of crystalline cellulose to L-HPC. Tablets prepared with crystalline cellulose and L-HPC rapidly disintegrated in saliva (small amount of water) in the mouth of humans.
Role of Telomerase in Cell Senescence and Oncogenesis (2000)

The ends of linear chromosomes are capped by specialized nucleoprotein structures termed telomeres. Telomeres comprise tracts of noncoding hexanucleotide repeat sequences that, in combination with specific proteins, protect against degradation, rearrangement, and chromosomal fusion events. Due to the polarity of conventional DNA synthesis, a net loss of telomeric sequences occurs at each cell division. It has been proposed that this cumulative telomeric erosion is a limiting factor in replicative capacity and elicits a signal for the onset of cellular senescence. To proliferate beyond the senescent checkpoint, cells must restore telomere length. This can be achieved by telomerase, an enzyme with reverse-transcriptase activity. This enzyme is absent in differentiated somatic tissues, but telomerase reactivation has been detected in most tumors. Much investigative effort is focusing on telomere dynamics with a view to possible manipulation of cellular proliferative potential. In this article, we review the role of telomeres and telomerase in senescence and tumor progression, and we discuss the potential use of telomerase in diagnosis and treatment.
Cationization of protein antigens. I. Alteration of immunogenic properties. (1987)

We have shown that a cationized form of bovine serum albumin (BSA) produced by substituting anionic side chain carboxylic groups with aminoethylamide groups possesses unique immunologic properties. The two forms of antigen, native (nBSA) and cationized (cBSA), cross-react at the level of the B cell, as evidenced by the ability of antibody raised against one form to react with the other and by inhibition assays using ELISA. T cell cross-reactivity was also observed in proliferation assays, but the amount of cBSA required for stimulation was 500 times less than the amount of native protein needed. In vivo, cBSA produced responses which, at their optimal levels, were at least double the response to nBSA and which showed a different kinetic pattern, peaking later and lasting longer than the response to the native molecule. Moreover, antibodies were produced in response to administration of cBSA but not nBSA when given i.v. in saline, without an adjuvant. Although a mechanism for these phenomena is not yet clear, we speculate that the cBSA may have a greater affinity for antigen-presenting cells or for the T cell receptor, or that the altered structure may enhance recognition of the molecule by APC and/or helper T cells.
Identification of Potent Non-Peptide Somatostatin Antagonists with sst3 Selectivity (2001)

Using a solution-phase parallel synthesis strategy, a series of non-peptide somatostatin analogues were prepared, and their binding affinities to the five human somatostatin receptor subtypes (sst(1-5)) were determined. Imidazolyl derivatives 2 were found to bind with moderate affinity but with high selectivity to the sst(3) receptor subtype. Further modifications of these structures led to a more potent class of ligands, the tetrahydro-beta-carboline derivatives 4. Among these, compounds 4k (BN81644) and 4n (BN81674) bind selectively and with high affinity to the sst(3) receptor subtype (K(i) = 0.64 and 0.92 nM, respectively). Furthermore, 4k and 4n reverse the inhibition of cyclic AMP accumulation induced by 1 nM somatostatin via sst(3) receptors, with IC(50) = 2.7 and 0.84 nM, respectively. The most potent compound 4n was shown to be a competitive antagonist of human sst(3) receptors by increasing the EC(50) of SRIF-14-mediated inhibition of cAMP accumulation with a K(B) of 2.8 nM (where K(B) is the concentration of antagonist that shifts the agonist dose-response 2-fold). These new derivatives are, to our knowledge, the first potent and highly selective non-peptide human sst(3) antagonists known and, as such, are useful tools for investigating the physiological role of sst(3) receptors.
Length and Base Composition of PCR-Amplified Nucleic Acids Using Mass Measurements from Electrospray Ionization Mass Spectrometry (1997)

A generally applicable algorithm has been developed to allow base composition of polymerase chain reaction (PCR) products to be determined from mass spectrometrically measured molecular weights and the complementary nature of DNA. Mass measurements of arbitrary precision for single-stranded DNA species are compatible with an increasingly large number of possible base compositions as molecular weight increases. For example, the number of base compositions that are consistent with a molecular weight of 35,000 is approximately 6000, based on a mass measurement precision of 0.01%. However, given the low misincorporation rate of standard DNA polymerases, mass measurement of both of the complementary single strands produced in the PCR reduces the number of possibilities to less than 100 at 0.01% mass precision, and base composition is uniquely defined at 0.001% mass precision. Taking into account the low misincorporation rate of standard DNA polymerases and the fact that the final PCR product also contains primers of known sequence (generally 15-20-mer in size, which flank the targeted region), this reduces the number of possible base combinations to only approximately 3 at MW = 35,000. In addition, the number of base pairs (i.e., length of the DNA molecule) is uniquely defined. We show that the use of modified bases in PCR or post-PCR modification chemistry allows unique solutions for the base composition of the PCR product with only modest mass measurement precision.
Towards monitoring real-time cellular response using an integrated microfluidics-matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion mobility-mass spectrometry platform (2010)

The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental set-up and control parameters and online desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signalling pathways.
Perfect optics with imperfect components (2015)

Many advanced optical functions, including spatial mode converters, linear optics quantum computing gates, and arbitrary linear optical processors for communications and other applications could be implemented using meshes of Mach–Zehnder interferometers in technologies such as silicon photonics, but performance is limited by beam splitters that deviate from the ideal 50∶50 split. We propose a new architecture and a novel self-adjustment approach that automatically compensate for imperfect fabricated split ratios anywhere from 85∶15 to 15∶85. The entire mesh can be both optimized and programmed after initial fabrication, with progressive algorithms, without calculations or calibration, and even using only sources and detectors external to the mesh. Hence, one universal field-programmable linear array optical element could be mass fabricated, with broad process tolerances, and then configured automatically for a wide range of complex and precise linear optical functions.
ChemInform Abstract: Antiinflammatory Activity of Substituted 6‐Hydroxypyrimido[2,1‐f]purine‐2,4,8(1H,3H,9H)‐triones. (1986)

Abstract Die Synthese der im Titel genannten Verbindungen (III) durch Kondensation der 8‐Aminopurine (I) mit den Malonsäureestern (II) bzw. durch spezifische 7‐Alky ie‐ rung der Tricyclen (IV) wird beschrieben.
Heat Pumps Using Organometallic Liquid Absorbents (1998)

Abstract A family of new organometallic liquid absorbents have been invented and are being developed for heat pump and cryocooler applications. Both hydrogen absorbing “HySorb liquids” and nitrogen absorbing “NiSorb liquids” have been synthesized in the laboratory and their properties are being measured. Previous research has shown that some organometallic substances can absorb large amounts of hydrogen — up to several weight percent, but all of the previously reported materials are solids. The only reversible hydrogen or nitrogen absorbing organometallic materials known that are liquids are the HySorb and NiSorb liquids. These liquid absorbents are environmentally clean, have 1–13 wt.% gas uptake capacity and have ΔH/cp up to 15 times higher than that of ammonia/water or lithium bromide/water, so more compact, higher power density heat pumps are possible. These liquids are also non-corrosive, compatible with oils and may be readily pumped through conventional heat exchangers, absorbers and desorbers. Compressor driven and heat driven heat pumps and cryocoolers are described. Analysis of the NiSorb heat pump indicates that high efficiencies are possible.
Investigation of stretching behaviour induced by the selective 5‐HT6 receptor antagonist, Ro 04–6790, in rats (1999)

1. The present study examined the effects of the selective 5-HT6 receptor antagonist 4-amino-N-(2, 6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) on locomotor activity and unconditioned behaviour in male Sprague Dawley rats (230-300 g). 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing. The latter behaviour was most pronounced between 30 and 90 min following the administration of Ro 04-6790. 3. Detailed analysis of the stretching and yawning behaviour showed that Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p.) dose-dependently induced stretching. The number of stretches observed following treatment with either Ro 04-6790 (10 mg kg(-1) i.p.) or Ro-04-6790 (30 mg kg(-1), i.p.) was significantly greater than that observed in saline-treated rats. The yawning behaviour, however, was not dose-dependent nor was the number of yawns in any of the drug treated groups significantly greater than in those treated with saline. 4. Pretreatment (30 min) with the non-selective muscarinic antagonists scopolamine (0.1, 0.3 or 1 mg kg(-1), i.p.) and atropine (0.3, 1 or 3 mg kg(-1), s.c.) but not methylatropine (1, 3 or 10 mg kg(-1), s.c) significantly inhibited stretching induced by Ro 04-6790 (30 mg kg(-1), i.p.). 5. The dopamine D2-like receptor antagonist, haloperidol (0.03, 0.1 or 0.3 mg kg(-1), s.c.) given at the same time as Ro 04-6790 (30 mg kg(-1), i.p.) had no effect on the stretching induced by the 5-HT6 antagonist. 6. These data suggest that systemic injection of the 5-HT6 antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT6 receptor blockade. There is no evidence for dopamine D2-like receptor involvement in this behaviour.
Microbial Conversion with Cofactor Regeneration using Genetically Engineered Bacteria (2001)

In the synthesis of fine chemicals, biotransformations have been recognized as useful methods and applied for large-scale manufacturing. Especially, the recent development of recombinant DNA technology has greatly expanded the whole microbial cell processes for manufacturing fine chemicals. The whole-cell approaches have been applied not only to single conversion process but also to biotransformations requiring cofactor regeneration, such as reductions with NADH or NADPH and phosphorylations with ATP. The whole microbial cell conversion process with cofactor regeneration enables the production of complicated compounds, such as sugar nucleotides and oligosaccharides, on an industrial scale. 1 Introduction 2 NAD(P)H Regeneration 3 ATP Regeneration 4 NTP Regeneration System 5 Conclusion
A Rapid Non-Culture-Based Assay for Clinical Monitoring of Phenotypic Resistance of Human Immunodeficiency Virus Type 1 to Lamivudine (3TC) (1999)

Monitoring for lamivudine (3TC) resistance is important both for the clinical management of human immunodeficiency virus type 1 (HIV-1)-infected patients treated with 3TC and for surveillance of transmission of 3TC-resistant HIV-1. We developed a novel non-culture-based assay for the rapid analysis of phenotypic resistance to 3TC of HIV-1 in plasma. The assay measures the susceptibility of HIV-1 reverse transcriptase (RT) activity to 3TC triphosphate (3TC-TP) in plasma. RT detection was done by the Amp-RT assay, an ultrasensitive PCR-based RT assay. Under our assay conditions, we found that 5 microM 3TC-TP inhibited RT activity from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance mutations (77L/116Y/151M or 62V/75I/77L/116Y/151M). Mixing experiments showed a detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV-1. To validate the assay for the detection of phenotypic resistance of HIV-1 to 3TC in plasma samples, HIV-1 RT in 30 plasma specimens collected from 15 patients before and during therapy with 3TC was tested for evidence of phenotypic resistance by the Amp-RT assay. The results were compared with those of genotypic analysis. The RT in 12 samples was found to be 3TC sensitive, while the RT in 18 samples had evidence of phenotypic resistance. All 12 samples with 3TC-sensitive RT had WT genotypes at codon 184 and were retrieved before treatment with 3TC. In contrast, all 18 specimens with 3TC-resistant RT were posttherapy samples. This assay provides a simple, rapid, and reliable method for the detection of phenotypic resistance of HIV-1 to 3TC in plasma.
Effect of DNA-binding Drugs on Early Growth Response Factor-1 and TATA Box-binding Protein Complex Formation with the Herpes Simplex Virus Latency Promoter (1996)

Adjacent binding sites for early growth response factor-1 (EGR1) and TATA box-binding protein (TBP) were identified on the herpes simplex virus latency promoter in previous work. The binding of EGR1 to the GC-rich region prevented TBP binding to the AT-rich region. With the simultaneous addition of both EGR1 and TBP, the intercalator nogalamycin prevented EGR1 complex formation, resulting in a dose-dependent increase of the TBP.DNA complex. The minor groove binder chromomycin A3 inhibited EGR1 complex formation but resulted in a smaller increase of the TBP complex. In contrast, an alkylating intercalator hedamycin strongly inhibited binding of both proteins. The ability of these GC-binding drugs to prevent EGR1.DNA complex formation was in the following order: hedamycin > nogalamycin > chromomycin A3, and the specificity was nogalamycin > chromomycin A3 > hedamycin. With transcription factor IIA (TFIIA) in the assay, TBP was able to bind the promoter whereas formation of the EGR1.DNA complex was reduced. An AT minor groove-binding drug, distamycin A, disrupted the TBP.TFIIA.DNA complex and restored the EGR1.DNA complex. We conclude that the binding motif and sequence preference of DNA-interactive drugs are manifested in their ability to inhibit the transcription factor-DNA complexes.
Site‐Selective In Situ Grown Calcium Carbonate Micromodels with Tunable Geometry, Porosity, and Wettability (2016)

Micromodels with simplified porous microfluidic systems are widely used to mimic the underground oil‐reservoir environment for multiphase flow studies, enhanced oil recovery, and reservoir network mapping. However, previous micromodels cannot replicate the length scales and geochemistry of carbonate because of their material limitations. Here a simple method is introduced to create calcium carbonate (CaCO 3 ) micromodels composed of in situ grown CaCO 3 . CaCO 3 nanoparticles/polymer composite microstructures are built in microfluidic channels by photopatterning, and CaCO 3 nanoparticles are selectively grown in situ from these microstructures by supplying Ca 2+ , CO 3 2− ions rich, supersaturated solutions. This approach enables us to fabricate synthetic CaCO 3 reservoir micromodels having dynamically tunable geometries with submicrometer pore‐length scales and controlled wettability. Using this new method, acid fracturing and an immiscible fluid displacement process are demonstrated used in real oil field applications to visualize pore‐scale fluid–carbonate interactions in real time.
Short, 12 mer fluorescently labeled methylphosphonated oligonucleotides to visualize beta-actin MRNA in vivo. (2003)

A pair of fluorescently labeled antisense ( complementary to beta-actin mRNA) or control methylphosphonated DNA 12-mers were introduced into live cells. After fixation their distribution throughout the cell was compared to the localization pattern for the pair of control oligos.The distribution of the two sets of oligos differed in that there was a distinct pool of antisense probes that were detected at elevated levels in the leading edge of fibroblast and cortical underlining. The resulting fluorescence patterns of antisense probes colocalized and were analogous to labeling pattern already described and produced by in situ hybridization. The length of each of the probe destabilized binding to mismatched sequences at physiological temperature, while the overall length of the pair gave a unique, highly sequence specific recognition of a target sequence. Simultaneous, in vivo application of multiple probes let include internal controls into the experimental setup, in order to distinguish different distributions of antisense and control probes in the same specimen.
Through-Hole Plating Without a Palladium Catalyst (1982)

SummaryAt the activation stage in the pretreatment of drilled printed circuit laminate prior to plating with electroless copper, processes based on palladium solutions, complexes or colloidal sols have been used by almost all manufacturers of printed circuit boards. Alternative catalytic processes are now available and performance in production has shown that some of these, especially those based on colloidal copper, promote more comprehensive coverage of the laminates with electroless copper and therefore produce more reliable ‘plated through-holes’. The paper compares the catalytic processes and shows the improvements that can be produced with catalysts based on non-precious metals such as copper.