gebhart/patrepeval huggingface dataset:
Inhibitors of purine nucleoside phosphorylase: effects of 9-deazapurine ribonucleosides and synthesis of 5'-deoxy-5'-iodo-9-deazainosine. (1986)

9-Deazapurine ribonucleosides constitute a new class of noncleavable purine nucleoside phosphorylase inhibitors that have at least 30-fold greater affinity for the enzyme than the corresponding C-nucleosides of the formycin B series. 9-Deazaguanosine, 9-deazainosine, and 5'-deoxy-5'-iodo-9-deazainosine competitively inhibited human erythrocytic purine nucleoside phosphorylase with Ki values of 29, 20, and 1.8 X 10(-7) M. The last compound is the most potent nucleoside inhibitor of the enzyme presently available and its synthesis is described. In contrast, 7,9-dideaza-7-thiainosine is a very weak inhibitor of the enzyme. When tested as an inhibitor of 2'-deoxyguanosine phosphorolysis in intact human erythrocytes and MOLT-3 human T-cell lymphoblastic leukemia cells, 5'-deoxy-5'-iodo-9-deazainosine was equipotent with 8-aminoguanosine (which is a precursor for 8-aminoguanine, Ki = 2 X 10(-7) M). Similarly, 5'-deoxy-5'-iodo-9-deazainosine and 8-aminoguanosine both potentiated the growth inhibition of human T-lymphocytic MOLT-3 cells by 2'-deoxyguanosine, reducing the 50% inhibitory concentration from approximately 2 X 10(-5) to approximately 2 X 10(-6) M.
The Splicing Factor U1C Represses EWS/FLI-mediated Transactivation (2000)

EWS is an RNA-binding protein involved in human tumor-specific chromosomal translocations. In approximately 85% of Ewing's sarcomas, such translocations give rise to the chimeric gene EWS/FLI. In the resulting fusion protein, the RNA binding domains from the C terminus of EWS are replaced by the DNA-binding domain of the ETS protein FLI-1. EWS/FLI can function as a transcription factor with the same DNA binding specificity as FLI-1. EWS and EWS/FLI can associate with the RNA polymerase II holoenzyme as well as with SF1, an essential splicing factor. Here we report that U1C, one of three human U1 small nuclear ribonucleoprotein-specific proteins, interacts in vitro and in vivo with both EWS and EWS/FLI. U1C interacts with other splicing factors and is important in the early stages of spliceosome formation. Importantly, co-expression of U1C represses EWS/FLI-mediated transactivation, demonstrating that this interaction can have functional ramifications. Our findings demonstrate that U1C, a well characterized splicing protein, can also function in transcriptional regulation. Furthermore, they suggest that EWS and EWS/FLI may function both in transcriptional and post-transcriptional processes.
Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase (1995)

Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides. The enzyme deactivates various antibiotics by transferring a nucleoside monophosphate group from ATP to the 4'-hydroxyl group of the drug. Detailed knowledge of the interactions between the protein and the substrates may lead to the design of aminoglycosides less susceptible to bacterial deactivation. Here we describe the structure of KNTase complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin. Crystals employed in the investigation were grown from poly(ethylene glycol) solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit. Least-squares refinement of the model at 2.5 A resolution reduced the crystallographic R factor to 16.8%. The binding pockets for both the nucleotide and the antibiotic are extensively exposed to the solvent and are composed of amino acid residues contributed by both subunits in the dimer. There are few specific interactions between the protein and the adenine ring of the nucleotide; rather the AMPCPP molecule is locked into position by extensive hydrogen bonding between the alpha-, beta-, and gamma-phosphates and protein side chains. This, in part, may explain the observation that the enzyme can utilize other nucleotides such as GTP and UTP. The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)
The Catalytic Asymmetric Total Synthesis of Elatol (2007)

Described in this report is the first total synthesis of elatol, a halogenated sesquiterpene in the chamigrene natural product family. The key disconnections in our synthetic approach include an enantioselective decarboxylative allylation to form the all-carbon quaternary stereocenter and a ring-closing olefin metathesis to concomitantly form the spirocyclic core as well as the fully substituted chlorinated olefin. This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route.
Increases in guinea pig small intestinal transepithelial resistance induced by osmotic loads are accompanied by rapid alterations in absorptive-cell tight-junction structure. (1983)

In some epithelia, mucosal exposure to osmotic loads produces an increase in transepithelial resistance that is presumed to relate to the collapse of the paracellular spaces. Since proximal small intestinal epithelium may transiently encounter osmotic loads during normal digestion, we examined the short-term effect of osmotic loads on resistance and on epithelial structure of mucosal sheets prepared from guinea pig jejunum using Ussing-chamber, thin-section electron-microscopic, and freeze-fracture techniques. After equilibration of mucosal sheets in chambers, mucosal buffer tonicity was increased to 600 mosM with mannitol. This resulted in a 64% increase in resistance within 20 min. Concomitantly, 600 mosM produced a decrease in tight-junction cation selectivity as judged from dilution potentials, collapse of paracellular spaces, decreased cytoplasmic electron density in 10-40% of absorptive cells, and focal absorptive-cell subjunctional lateral-membrane evaginations often associated with microfilament arrays. Freeze-fracture replicas of absorptive-cell tight junctions revealed significant increases in both strand count and depth. Preincubation with 5 micrograms/ml cytochalasin D reduced the 600 mosM resistance increase caused by 600 mosM exposure by 48% but did not prevent the collapse of paracellular spaces. Lowered temperatures that produced morphologic evidence consistent with a gel-phase transition of absorptive-cell lateral membranes prevented both the resistance response and the alterations in tight-junction structure. In conclusion, transient osmotic loads produce an increase in resistance in jejunal epithelium and alter both absorptive-cell tight-junction charge selectivity and structure. These responses, which may have physiologic implications, can be reduced by cytoskeletal inhibitors and ablated by conditions that restrict mobility of absorptive-cell lateral-membrane molecules.
Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures (2005)

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.
Freezing Resistance in Some Antarctic Fishes (1969)

Measurements of serum freezing points in three Antarctic marine fishes indicated that they do not freeze in the -1.87 degrees C seawater because their blood is isosmotic to seawater. Concentrations of sodium chloride, urea, and free amino acids in the serum accounted for only half of the freezing-point depression of the serum. A protein containing carbohydrate was isolated which accounted for 30 percent of the freezing-point depression of the serum.
Inhibiting Glycosphingolipid Synthesis Improves Glycemic Control and Insulin Sensitivity in Animal Models of Type 2 Diabetes (2007)

Previous reports have shown that glycosphingolipids can modulate the activity of the insulin receptor, and studies in transgenic mice suggest a link between altered levels of various gangliosides and the development of insulin resistance. Here, we show that an inhibitor of glycosphingolipid synthesis can improve glucose control and increase insulin sensitivity in two different diabetic animal models. In the Zucker diabetic fatty rat, the glucosylceramide synthase inhibitor (1R,2R)-nonanoic acid[2-(2',3'-dihydro-benzo [1, 4] dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]- amide-l-tartaric acid salt (Genz-123346) lowered glucose and A1C levels and improved glucose tolerance. Drug treatment also prevented the loss of pancreatic beta-cell function normally observed in the Zucker diabetic fatty rat and preserved the ability of the animals to secrete insulin. In the diet-induced obese mouse, treatment with Genz-123346 normalized A1C levels and improved glucose tolerance. Analysis of the phosphorylation state of the insulin receptor and downstream effectors showed increased insulin signaling in the muscles of the treated Zucker diabetic fatty rats and diet-induced obese mice. These results suggest that inhibiting glycosphingolipid synthesis can significantly improve insulin sensitivity and glucose homeostasis and may therefore represent a novel therapeutic approach for the treatment of type 2 diabetes.
External cavity operated angled-stripe geometry DH lasers (1980)

Complete elimination of feedback reflections from the cleaved facets of GaAs/GaAlAs double-heterostructure injection lasers has been achieved. This results in smooth amplified spontaneous emission spectra, from diodes modified by a combination of antireflection coating and angled stripe contacts, at currents greater than 2.5 times the cw threshold for unmodified lasers. The angled-stripe lasers operate in a two-mirror cavity producing smooth spectra with 1-Å (FWHM) bandwidths.
A Novel, Selective, and Efficacious Nanomolar Pyridopyrazinone Inhibitor of V600EBRAF (2010)

Oncogenic BRAF is a critical driver of proliferation and survival and is thus a validated therapeutic target in cancer. We have developed a potent inhibitor, termed 1t (CCT239065), of the mutant protein kinase, (V600E)BRAF. 1t inhibits signaling downstream of (V600E)BRAF in cancer cells, blocking DNA synthesis, and inhibiting proliferation. Importantly, we show that 1t is considerably more selective for mutated BRAF cancer cell lines compared with wild-type BRAF lines. The inhibitor is well tolerated in mice and exhibits excellent oral bioavailability (F = 71%). Suppression of (V600E)BRAF-mediated signaling in human tumor xenografts was observed following oral administration of a single dose of 1t. As expected, the growth rate in vivo of a wild-type BRAF human tumor xenograft model is unaffected by inhibitor 1t. In contrast, 1t elicits significant therapeutic responses in mutant BRAF-driven human melanoma xenografts.
Heart Regeneration in Zebrafish (2002)

Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration.
Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics (2009)

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.
Normalized and differential convolution (2002)

It is shown how false operator responses due to missing or uncertain data can be significantly reduced or eliminated. It is shown how operators having a higher degree of selectivity and higher tolerance against noise can be constructed using simple combinations of appropriately chosen convolutions. The theory is based on linear operations and is general in that it allows for both data and operators to be scalars, vectors or tensors of higher order. Three new methods are represented: normalized convolution, differential convolution and normalized differential convolution. All three methods are examples of the power of the signal/certainty-philosophy, i.e., the separation of both data and operator into a signal part and a certainty part. Missing data are handled simply by setting the certainty to zero. In the case of uncertain data, an estimate of the certainty must accompany the data. Localization or windowing of operators is done using an applicability function, the operator equivalent to certainty, not by changing the actual operator coefficients. Spatially or temporally limited operators are handled by setting the applicability function to zero outside the window.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Unpredictable Stereochemical Preferences for Mu Opioid Receptor Activity in an Exhaustively Stereodiversified Library of 1,4-Enediols (2003)

Using olefin cross-metathesis, we synthesized a novel stereodiversified library of compounds 3 containing a trans-1,4-enediol. Screening this library for mu opioid receptor (MOR) affinity identified multiple high-affinity ligands and revealed that the stereochemical configuration varied widely among those ligands having the highest affinity. It was not possible to predict the configurations of the most active compounds 3 on the basis of the configuration of endomorphin-2, a known MOR peptide ligand, validating the diversity-based approach to ligand discovery.
Generalized implicit functions for computer graphics (1991)

We describe a method of generalizing implicit functions by use of modal deformations and displacement maps. Modal deformations, also known as free vibration modes, are used to describe the overall shape of a solid, while displacement maps provide local and fine surface detail by offsetting the surface of the solid along its surface normals. The advantage of this approach to geometric description is that collision detection and dynamic simulation become simple and inexpensive even for complex shapes. In addition, we outline an efficient method for fitting such models to three dimensional point data.
Effects of oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms (2007)

The aim of this study was to evaluate the effect of oregano essential oil, carvacrol and thymol on biofilm-grown Staphylococcus aureus and Staphylococcus epidermidis strains, as well as the effects of the oils on biofilm formation. For most of the S. aureus (n=6) and S. epidermidis (n=6) strains tested, the biofilm inhibitory concentration (0.125-0.500 %, v/v, for oregano, and 0.031-0.125 %, v/v, for carvacrol and thymol) and biofilm eradication concentration (0.25-1.0 %, v/v, for oregano and 0.125-0.500 %, v/v, for carvacrol and thymol) values were twofold or fourfold greater than the concentration required to inhibit planktonic growth. Subinhibitory concentrations of the oils attenuated biofilm formation of S. aureus and S. epidermidis strains on polystyrene microtitre plates.
Electron driven chemistry in microreactors (2009)

This thesis describes the development of novel process windows by the combination of atmospheric pressure plasmas with microreaction technology. In the first chapter, recent literature on microreactor technology and non-equilibirum microplasma chemistry is discussed. The focus is on microplasmas in confined microchannels for the purpose of chemical synthesis and environmental applications. Study of oxidative conversion of propane using dielectric barrier discharge in a microreactor is described. This generates a cold microplasma at atmospheric pressure and ambient temperature. Surprisingly, large amounts of products with molecular weight higher than propane, such as, C4 and C4+ were mainly observed due to C-C bond formation, in contrast to what is usually observed for this reaction when it is carried out under thermal activation, which leads to cracking products. Development of a plasma catalytic reactor based on a dielectric barrier discharge for oxidative cracking of hexane with Li/MgO based catalysts is reported. The effect of temperature, oxygen concentration, helium flow, and MgO support, and the role of Li/MgO catalysts on the conversion of hexane, and on the selectivity and yield of olefin formation are described. Direct synthesis of liquid oxygenates from partial oxidation of methane is demonstrated in a multi-phase flow, non-equilibrium plasma microreactor near 0oC at atmospheric pressure. A method for liquid-water injection into the microreactor was introduced in order to remove incomplete oxidation products such as methanol, which prevents further oxidation with excited species originating from the microplasma. In the sixth chapter, development of an in-situ CVD method for the growth of CNFs on Ni/alumina and nickel thin film catalyst coated inside a closed channel fused silica microreactor is described. Synthesis, characterization and atmospheric pressure field emission operation of tungsten oxide W18O49 nanorods is discussed. Atmospheric pressure field emission measurements in air showed a turn-on field of 3.3 V/μm, and a stable and reproducible emission current density of 28 mA/cm2. Carbon nanofibers (CNFs) and tungsten oxide nanorods have been incorporated in a continuous flow microplasma reactor to increase the reactivity and efficiency of the barrier discharge at atmospheric pressure.
Variable development in anthers of partially male-sterile soybeans (1982)

Journal Article Variable development in anthers of partially male-sterile soybeans Get access David M. Stelly, David M. Stelly Department of Horticulture, University of WisconsinMadison, WI 53706; and research geneticist, ARS, USDA. Department of Agronomy, Iowa State UniversityAmes, IA 50011 Search for other works by this author on: Oxford Academic PubMed Google Scholar Reid G. Palmer Reid G. Palmer Department of Horticulture, University of WisconsinMadison, WI 53706; and research geneticist, ARS, USDA. Department of Agronomy, Iowa State UniversityAmes, IA 50011 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 73, Issue 2, March 1982, Pages 101–108, https://doi.org/10.1093/oxfordjournals.jhered.a109589 Published: 01 March 1982
Intermediate-range order in glasses and liquids (1988)

Many glasses and liquids exhibit a first sharp diffraction peak that is evidence for intermediate-range order caused by regularities in the packing of structural units. These tend to cluster around particular values of the wavevector when scaled by the nearest-neighbour distance or the mean inter-atomic spacing. The first sharp diffraction peak is distinguished from the pre-peak in binary metallic glasses, which occurs at higher wavevectors when scaled in this way.
Reconstruction of Mandibular Defects Using Autografts Combined With Demineralized Bone Matrix and Cancellous Allograft (2007)

Facial bone defects can be managed by a variety of means, such as inlay or onlay applied nonvascularized bone grafts, local pedicled/distal free osteocutaneous/osseous flaps or distraction osteogenesis. Although each method has its own advantages and drawbacks, the indications of using these methods may overlap in certain clinical situations. The use of nonvascularized bone grafts, conceptually and technically simple method, relies on creeping substitution of applied graft with regenerating new bone. However, using vascularized osteocutaneous free flaps provide not only plenty of bony tissue for reconstruction, but also soft tissue coverage over the reconstructed bony segment. Furthermore, bone healing in vascularized osteocutaneous free flaps resembles as the physiologic fracture healing. In selected cases with enough soft tissue coverage over the defective bony segment, on the other hand, using larger nonvascularized bone grafts with osteoinductive growth factors may decrease the risk of graft failure while avoiding the drawbacks of the free tissue transfer. Here we present our results of three cases with facial bone defects, to which nonvascularized iliac bone grafts and demineralized bone matrix with cancellous allograft (Orthoblast II) as a source of BMP were used together for mandibular reconstruction.