gebhart/patrepeval huggingface dataset:
Radiosensitization of Mammalian Cells in Vitro by Nitroacridines (1990)

The nitroacridine nitracrine (1-NC) is a DNA intercalator and a hypoxia-selective, electron-affinic radiosensitizer. Sensitization of Chinese hamster fibroblast cultures at 0 degrees C by the nitro positional isomers of 1-NC has now been compared to help establish structure-activity relationships. The des-nitro analog (E(1) at pH 7 = -899 mV) did not sensitize, suggesting that an electron-affinic chromophore is required. All the nitroacridines (E(1) range -376 to -257 mV) sensitized hypoxic cells with a maximum sensitizer enhancement ratio of about 1.7, but with a 200-fold range in potency. When mean intracellular drug concentrations were compared, 2-, 3-, and 4-NC had potencies which were similar, independent of E(1), and no greater than predicted for non-DNA binding nitroheterocycles. Sensitization by these three isomers occurred at intracellular concentrations likely to saturate the potential intercalation sites on DNA. A large fraction of the radical sites sensitized by O2 are apparently inaccessible to these drugs. It is suggested that sensitization results from electron transfer from migrating transient charge carriers of low reduction potential to immobile bound intercalators. An additional sensitizing mechanism may be available to 1-NC, which was 20 times more potent, a potency not accounted for by E(1), cell uptake, or DNA binding affinity. The dissociation kinetics of the DNA-drug complex was faster for 1-NC than for the other isomers. The higher potency of 1-NC may reflect a short mean residence time (less than 1 ms) in its intercalation site, allowing significant mobility on the DNA within the lifetime of relatively stable radiation-induced target radicals.
Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, multiplex FISH and comparative genomic hybridization (2002)

To identify genes that are involved in breast cancer, suppression subtractive hybridization (SSH) was utilized to construct a breast cancer subtracted library. Differential screening of the library isolated 28 genes which by Northern analysis were highly expressed in the breast cancer cell line MDA-MB-231 compared to the normal breast cell line MCF12A. Sequence analysis revealed that 15 clones coded for previously described genes such as SNAP43, Cyr61, Thymosin beta4, tra1, elongation factor 1alpha, BSF-2/IL6, BiP, and GDP/GTP exchange protein. The remaining 13 clones did not match sequences in GenBank/EMBL database, indicating that they may be novel genes. SNAP43, a subunit of the TBP-TAF complex, was expressed 20-fold higher in MDA-MB-231 compared to MCF12A and several breast cancer cell lines, implying that SNAP43 may be involved in tumorigenesis of a specific subset of breast cancers. Amplification of SNAP43 was not found by Southern analysis. However, genetic alterations of MDA-MB-231 included a deletion of chromosome 14 with a reciprocal translocation t(6;14) and two additional translocations [t(12;14) and t(14;15)] as determined by fluorescent in situ hybridization (FISH) with YAC 823G8 located at chromosome 14q23 which contained SNAP43. Because of the numerous alterations observed by FISH in MDA-MB-231, we further explored the genetic abnormalities in this breast cancer cell line using multiplex FISH (M-FISH) and comparative genomic hybridization (CGH). These cells were replete with numerous complex structural rearrangements and had DNA copy-number imbalances involving multiple chromosomes including gains on chromosomes 2p, 2q31-q32, 3p14-pter, 5q, 6p, 7q36-qter, 11, 14q21-q24, 17p11.2-pter, 17q21-qter, 19, 20, Xp11-q13 and losses on chromosomes 4pter-q32, 8p, 9p21-p24, 10q26-qter, 16p13-pter, 18q12-qter, 22, Xp11.3-p22.1, Xq13-qter. In summary, SSH revealed a number of genes that were either novel or previously not associated with breast cancer. In addition, we found that breast cancer cells abounded with abnormalities as observed by M-FISH and CGH. Together, these results may facilitate defining the genetic alterations associated with breast cancer progression.
Amino acid sequence of a specific antigenic peptide of protein B23. (1986)

A specific antigenic peptide was obtained from protein B23 (Mr/pI = 37,000/5.1) after 30 min of digestion with staphylococcal V8 protease (10 micrograms/ml/mg protein B23). The antigenic peptide was purified by DEAE-cellulose chromatography and high pressure liquid chromatography on a reverse-phase C18 column. The antigenic peptide contains 14.7 and 18.7 mol% of glutamic acid and lysine, respectively. Amino acid sequence analysis showed that the peptide has 68 amino acids and is located on the carboxyl-terminal sequence of protein B23. The sequence is Ser-Phe-Lys-Lys-Gln-Glu-Lys-Thr-Pro-Lys-Thr-Pro- Lys-Gly-Pro-Ser-Ser-Val-Glu-Asp-Ile-Lys-Ala-Lys-Met-Gln-Ala-Ser-Ile-Glu- Lys-Gly- Gly-Ser-Leu-Pro-Lys-Val-Glu-Ala-Lys-Phe-Ile-Asn-Tyr-Val-Lys-Asn-Cys-Phe- Arg-Met- Thr-Asp-Gln-Glu-Ala-Ile-Gln-Asp-Leu-Trp-Gln-Trp-Arg-Lys-Ser-Leu-Cooh. Extensive digestion of the antigenic peptide with V8 protease, trypsin, or chymotrypsin results in loss of the antigenic activity. Three cloned cDNAs (hpB1, hpB2, and hpB7) which code for the 82 amino acids at the COOH terminus of protein B23 and the 3' non-translating sequence were identified and characterized. All three clones have identical nucleotide sequences coding for the antigenic portion of the protein (68 amino acids at the COOH terminus), the stop codon, and the 3' non-translated region. However, mutation of 6 nucleotide bases of one clone (hpB2) caused changes in 4 amino acids in the sequence just preceding the immunoreactive region. The result suggests the presence of at least 2 immunologically similar but distinct proteins which are both recognized by the anti-B23 antibody.
A33scFv Green fluorescent protein, a recombinant single-chain fusion protein for tumor targeting (2007)

Chemical conjugates of monoclonal antibodies with fluorophores or enzymes have long been used for diagnostic purposes and experimental therapeutic approaches. Recombinant technology allows for the design and expression of tailored genuine fusion proteins, providing defined molecules as to size, molar ratios of the functional components and stability. The production of functional protein, however, is often limited or impossible due to refolding and solubility problems. Here, we report on the production of a soluble recombinant fusion construct, A33scFv-green fluorescent protein (A33scFv::GFP) in Pichia pastoris. A33scFv is a single-chain antibody recognizing the A33 antigen, which is expressed by approximately 95% of colorectal carcinomas and has become a focus of pre-clinical and clinical investigation. The fusion partner GFP was selected both as an experimental tool for functional studies of the A33 antigen and as a potential diagnostic for colon cancer detection and therapy planning. Pichia pastoris yeast strains were transformed with A33scFv::GFP cDNA under the methanol-inducible AOX1 promotor. The construct was properly expressed and secreted into culture supernatants as a soluble protein, which was bifunctional without additional renaturation or solubilization steps. The crude protein solution was purified by affinity chromatography. Surface plasmon resonance, flow cytometry and fluorescence microscopy on sections of normal and cancerous colon tissue revealed specific binding and the applicability of this fusion protein for diagnostic purposes. In addition, the biodistribution of A33scFv::GFP was analyzed in mice bearing A33-positive tumor xenografts, confirming specific tumor targeting.
Involvement of substance P and neurokinin-1 receptors in the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint (1995)

1. In anesthetized rats we studied the involvement of substance P and neurokinin-1 receptors in the generation and maintenance of hyperexcitability in spinal cord neurons, which develops in the course of an acute experimental inflammation in the knee. In all experiments one nociceptive neuron with knee input was identified, and the responses to mechanical stimuli and the receptive fields were monitored before and after induction of inflammation by the injections of kaolin and carrageenan into the knee joint. In 18 experiments either the specific antagonist at the neurokinin-1 receptor ionophoretically close to the neuron or intravenously during the injections of kaolin and carrageenan and in three periods of 15 min in the 95 min postkaolin (initial period of inflammation) to test their effects on the development of hyperexcitability. CP96,345 and CP96,344 were also administered after full development of inflammation to study their effects in hyperexcitable neurons. CP96,345 was ejected at currents that reduced or completely suppressed the effects of ionophoretically administered substance P but not those of neurokinin A, the agonist at neurokinin-2 receptors. 2. After the injections of kaolin and carrageenan into the knee joint, untreated control neurons (n = 8) developed hyperexcitability consisting of enhanced responses to noxious stimuli applied to the injected knee and the noninjected ankle, of an enhancement or induction of the responses to innocuous pressure applied to the joints and of an expansion of the receptive field. In eight neurons treated with ionophoretic administration of CP96,345 during the induction and initial period of inflammation, the development of hyperexcitability was not completely prevented but significantly attenuated. In comparison with the changes in the control neurons, the development of hyperexcitability was markedly reduced from the 2nd h up to 5 h postkaolin, but it was barely affected by CP96,345 within the 1st h postkaolin. Intravenous administration of CP96,345 in the initial period of inflammation produced a similar reduction of the development of hyperexcitability in another four neurons. The ionophoretic application of CP96,344 during and after induction of inflammation did not apparently impair the development of hyperexcitability (n = 6 neurons). 3. After development of inflammation and hyperexcitability, both the responses to innocuous and noxious pressure applied to the inflamed knee joint were reduced by the ionophoretic (n = 16 neurons) and intravenous administration (n = 9 neurons) of CP96,345 (tested 4.5-8 h postkaolin). Similarly, the responses to innocuous and noxious pressure applied to the noninflamed ankle were reduced by CP96,345 after inflammation had developed in the knee joint.(ABSTRACT TRUNCATED AT 400 WORDS)
Liquid Triarylamines: The Scope and Limitations of Piers–Rubinsztajn Conditions for Obtaining Triarylamine–Siloxane Hybrid Materials (2012)

New liquid triarylamine-siloxane hybrid materials are produced using the Piers-Rubinsztajn reaction. Under mild conditions, liquid analogues of conventional and commonly crystalline triarylamines are easily synthesized from readily available or accessible intermediates. Using a diverse selection of triarylamines, we explored the effects of siloxane group and substitution pattern on the physical properties of these materials, and we have demonstrated that relatively large molecular liquids with desirable electrochemical properties can be produced. The interactions between the strongly Lewis acidic catalyst used for this transformation, tris(pentafluorophenyl)borane (BCF), and the Lewis basic triarylamine substrates were studied. Through UV-vis-NIR and (19)F NMR spectroscopy, we have proposed that the catalyst undergoes a reversible redox reaction with the substrates to produce a charge transfer complex. The formation of this charge transfer complex is sensitive to the oxidation potential of the triarylamine and can greatly affect the kinetics of the Piers-Rubinsztajn reaction.
Tetracycline: Levels Achievable in Gingival Crevice Fluid and <i>in Vitro</i> Effect on Subgingival Organisms: Part I. Concentrations in Crevicular Fluid After Repeated Doses (1981)

The concentration of tetracycline in gingival crevice fluid and blood was determined using a sensitive bioassay after oral administration of repeated doses of tetracycline. Crevicular fluid was sampled by an intracrevicular technique from four gingival sites in each individual and blood was obtained by finger puncture. Four volunteers received doses of 250 mg of tetracycline-HCl either every 6 hours or every 12 hours and were sampled at hours 0 to 15, 21 to 36, 48 to 60 and 96 to 102. Volunteers given 250 mg every 6 hours had average crevicular fluid concentrations between 4 to 8 micrograms/ml and blood concentrations between 2 to 2.5 micrograms/ml after 48 hours. The levels in crevicular fluid and blood of volunteers who received 250 mg every 12 hours were 2 to 4 micrograms/ml and 0.3 to 1.4 micrograms/ml respectively after 48 hours. The results demonstrated that after repeated doses of tetracycline the crevicular fluid levels were typically 2 to 4 times the blood levels.
Regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by inositol. Inositol is an inhibitor of phosphatidylserine synthase activity. (1988)

The addition of inositol to the growth medium of Saccharomyces cerevisiae resulted in rapid changes in the rates of phospholipid biosynthesis. The partitioning of the phospholipid intermediate CDP-diacylglycerol was shifted to phosphatidylinositol at the expense of phosphatidylserine and its derivatives phosphatidylethanolamine and phosphatidylcholine. Serine at 133-fold greater concentrations than that of inositol shifted the partitioning of CDP-diacylglycerol to phosphatidylserine at the expense of phosphatidylinositol but to a much lesser degree. Kinetic experiments with pure phosphatidylserine synthase and phosphatidylinositol synthase indicated that the partitioning of CDP-diacylglycerol between phosphatidylserine and phosphatidylinositol was not governed by the affinities both enzymes have for their common substrate CDP-diacylglycerol. Instead, the main regulation of phosphatidylinositol and phosphatidylserine synthesis was through the exogenous supply of inositol. The Km of inositol (0.21 mM) for phosphatidylinositol synthase was 9-fold higher than cytosolic concentration of inositol (24 microM). The Km of serine (0.83 mM) for phosphatidylserine synthase was 3-fold below the cytosolic concentration of serine (2.6 mM). Therefore, inositol supplementation resulted in a dramatic increase in the rate of phosphatidylinositol synthesis, whereas serine supplementation resulted in little affect on the rate of phosphatidylserine synthesis. Inositol also contributed to the regulation of phosphatidylinositol and phosphatidylserine synthesis by having a direct affect on phosphatidylserine synthase activity. Kinetic experiments with pure phosphatidylserine synthase showed that inositol was a noncompetitive inhibitor of the enzyme with a Ki of 65 microM.
ε‐Caprolactamium Hydrogen Sulfate: An Ionic Liquid Used for Decades in the Large‐Scale Production of ε‐Caprolactam (2008)

An iconic liquid: Investigation of the mechanism of the Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam (1) in sulfuric acid or oleum has led to the conclusion that the manufacturing process for ε-caprolactam is in fact the largest-scale industrial technology that has been using an ionic liquid, caprolactamium hydrogen sulfate (2), as the reaction medium for decades.
Hydroxycitric Acid Inhibits Renal Calcium Oxalate Deposition by Reducing Oxidative Stress and Inflammation (2020)

HCA inhibits renal injury and calcium oxalate crystal deposition in the glyoxylate-induced mouse model through antioxidation and anti-inflammation.
Heat Stress, Plant‐Available Soil Moisture, and Corn Yields in Iowa: A Short‐ and Long‐Term View (1990)

The weather of the 1980s has been very dramatic relative to crop production in a large part of the USA, providing both excellent and stressful years. Because of this, and also because of general concerns and predictions of more stressful times in years to come, a study was conducted to identify weather factors that (i) significantly affect corn ( Zea mays L.) production in Iowa, and (ii) were available in long‐term weather records. Regression analyses identified heat stress and plant‐available soil moisture as the two most important weather‐related variables affecting corn yields in central Iowa. Heat stress was defined as the monthly or seasonal accumulation of the number of degrees each day when maximum temperatures exceeded 86 °F (30 °C). The regression model used included terms representing technology (time), heat stress in July and August, 1 July plant‐available soil moisture in the top 5 ft of soil, and an interaction term between the last two variables. The model accounted for 90% of the variation in corn yield between 1954 and 1988. Time trend accounted for 62% of the yield variation and weather factors were 28%. When 1 July plant‐available soil moisture was below normal (approximately 7 in.), heat stress in July and August caused greater yield reductions than when plant‐available soil moisture was above normal. To compare our present climate with previous years, a seasonal heat‐stress variable was computed for 1900–1988. This revealed periods of both benign (1958–1975) and hostile (1900–1957) characteristics relative to expected and realized corn yields. Runs of stressful days each season showed similar patterns of season‐to‐season variability. The 1 July plant‐available soil moisture trends for central Iowa clearly show that the benign period mentioned was also one of adequate levels of crop growing season soil moisture. It is not possible to predict future weather, but this work identifies two variables (heat stress and 1 July plant‐available soil moisture) that, over a long period of time, reveal considerable interannual variability. The late 1950s, the 1960s, and the early 1970s were very favorable for corn production in central Iowa, as well as in other parts of the Midwest. These data show this to be an unusual and benign time period when compared to other time periods of this century. The ups and downs of the 1908s may be closer to our expected weather.
Patisiran, an RNAi Therapeutic for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis (2018)

Hereditary transthyretin-mediated amyloidosis is a rapidly progressive, heterogeneous disease caused by the accumulation of misfolded transthyretin protein as amyloid fibrils at multiple sites, and is characterized by peripheral sensorimotor neuropathy, autonomic neuropathy and/or cardiomyopathy. Current treatment options have limited efficacy and often do not prevent disease progression. Patisiran is a novel RNA interference therapeutic that specifically reduces production of both wild-type and mutant transthyretin protein. In Phase II, III and long-term extension studies in patients with hereditary transthyretin-mediated amyloidosis, patisiran has consistently slowed or improved progression of neuropathy. In addition, the Phase III trial demonstrated significant improvements in quality of life measures and indicators of cardiomyopathy. Here, we highlight efficacy and safety data from the patisiran clinical trial programme.
A Review of Learning Behavior in Horses and its Application in Horse Training (1990)

A literature review of the equine learning research conducted in the past 20 yr revealed that the purpose of most of the studies was to determine whether horses respond to learning situations in the same way that other animals do
Steroid receptor coactivator-1 (SRC-1) mediates the development of sex-specific brain morphology and behavior (2000)

Steroid hormone action during brain development exerts profound effects on reproductive physiology and behavior that last into adulthood. A variety of in vitro studies indicate that steroid receptors require nuclear receptor coactivators for efficient transcriptional activity. To determine the functional significance of the nuclear receptor coactivator SRC-1 in developing brain, we investigated the consequence of reducing SRC-1 protein during sexual differentiation of the brain. We report that reducing SRC-1 protein interferes with the defeminizing actions of estrogen in neonatal rat brain. Our data indicate that SRC-1 protein expression is critically involved in the hormone-dependent development of normal male reproductive behavior and brain morphology.
Interactive free viewpoint video streaming using prioritized network coding (2013)

In free viewpoint applications, the images are captured by an array of cameras that acquire a scene of interest from different perspectives. Any intermediate viewpoint not included in the camera array can be virtually synthesized by the decoder, at a quality that depends on the distance between the virtual view and the camera views available at decoder. Hence, it is beneficial for any user to receive camera views that are close to each other for synthesis. This is however not always feasible in bandwidth-limited overlay networks, where every node may ask for different camera views. In this work, we propose an optimized delivery strategy for free viewpoint streaming over overlay networks. We introduce the concept of layered quality-of-experience (QoE), which describes the level of interactivity offered to clients. Based on these levels of QoE, camera views are organized into layered subsets. These subsets are then delivered to clients through a prioritized network coding streaming scheme, which accommodates for the network and clients heterogeneity and effectively exploit the resources of the overlay network. Simulation results show that, in a scenario with limited bandwidth or channel reliability, the proposed method outperforms baseline network coding approaches, where the different levels of QoE are not taken into account in the delivery strategy optimization.
The Role of Base Flipping in Damage Recognition and Catalysis by T4 Endonuclease V (1997)

The process of moving a DNA base extrahelical (base flipping) has been shown in the co-crystal structure of a UV-induced pyrimidine dimer-specific glycosylase, T4 endonuclease V, with its substrate DNA. Compared with other enzymes known to use base flipping, endonuclease V is unique in that it moves the base opposite the target site extrahelical, rather than moving the target base itself. Utilizing substrate analogs and catalytically inactive mutants of T4 endonuclease V, this study investigates the discrete steps involved in damage recognition by this DNA repair enzyme. Specifically, fluorescence spectroscopy analysis shows that fluorescence changes attributable to base flipping are specific for only the base directly opposite either abasic site analogs or the 5'-thymine of a pyrimidine dimer, and no changes are detected if the 2-aminopurine is moved opposite the 3'-thymine of the pyrimidine dimer. Interestingly, base flipping is not detectable with every specific binding event suggesting that damage recognition can be achieved without base flipping. Thus, base flipping does not add to the stability of the specific enzyme-DNA complex but rather induces a conformational change to facilitate catalysis at the appropriate target site. When used in conjunction with structural information, these types of analyses can yield detailed mechanistic models and critical amino acid residues for extrahelical base movement as a mode of damage recognition.
Synthesis of alkylaminoethanethiolsulfuric acids substituted with heterocyclic moieties (1966)

Abstract Several alkylaminoethanethiolsulfurie acids substituted with heterocyclic moieties have been synthesized to determine their effectiveness as radiation protection agents. These compounds are represented by the structure R(CH 2 ) 3 NH(CH 2 ) 2 S 2 O 3 H, where R is 8‐quinoly‐oxy (V), 8‐quinaldyloxy (IX), 5‐quinolyloxy (XII), 4‐pyridyl (XVI), and 4‐pyridylmethyl (XXIII). The diheterocyclic‐substituted compound, 2‐[bis‐(2‐phenyl‐1, 2, 3, 2 H ‐triazol‐4‐ylmethyl)amino]ethanethiolsulfuric acid (XIV) was also synthesized.